Sample records for factor-bb rhpdgf-bb combined

  1. Treatment of periodontal intrabony defects using β-TCP alone or in combination with rhPDGF-BB: a randomized controlled clinical and radiographic study.

    PubMed

    Maroo, Sneha; Murthy, K Raja V

    2014-01-01

    The need to increase the predictability of periodontal regeneration has encouraged clinicians and researchers to employ cell-stimulating proteins in combination with osteoconductive scaffolds, based on the principles of tissue engineering. The purpose of this clinical and radiographic study was to compare the regenerative potential of the combination of β-tricalcium phosphate (β-TCP) and recombinant human platelet-derived growth factor BB (rhPDGF-BB) in the grafting of intraosseous defects with the established technique of bone grafting with (β-TCP alone. A total of 30 sites from 15 patients with infrabony defects in two different quadrants were selected, and the sites were randomly divided into test sites (rhPDGF + β-TCP) and control sites (β-TCP alone) using a split-mouth design. Clinical parameters, including probing pocket depth, clinical attachment level, and gingival recession, were recorded at baseline, 6 months, and 9 months. Radiographic evaluation was carried out to evaluate defect fill, change in alveolar crest height, and percentage of defect fill at baseline, 6 months, and 9 months. Both the experimental groups showed statistically significant reduction in probing pocket depth and gain in clinical attachment level. On intergroup comparison, sites treated with rhPDGF + β-TCP demonstrated a significantly greater pocket depth reduction (P < .05) and greater gain in clinical attachment level (P < .01). Mean percentage defect fill was significantly greater in test sites as compared with control sites at 6 and 9 months (P < .01). rhPDGF + β-TCP-treated sites demonstrated a significant gain in mean alveolar crest height at 6 and 9 months (P < .05), while β-TCP-treated sites demonstrated crestal resorption. Both groups demonstrated potential in enhancing periodontal regeneration; however, on comparison between the two groups, the results obtained by rhPDGF + β-TCP were significantly better with respect to both clinical and radiographic parameters.

  2. Specificity of EIA immunoassay for complement factor Bb testing.

    PubMed

    Pavlov, Igor Y; De Forest, Nikol; Delgado, Julio C

    2011-01-01

    During the alternative complement pathway activation, factor B is cleaved in two fragments, Ba and Bb. Concentration of those fragments is about 2 logs lower than of factor B present in the blood, which makes fragment detection challenging because of potential cross-reactivity. Lack of information on Bb assay cross-reactivity stimulated the authors to investigate this issue. We ran 109 healthy donor EDTA plasmas and 80 sera samples with both factor B immunodiffusion (The Binding Site) and Quidel Bb EIA assays. During the study it was shown that physiological concentrations of gently purified factor B demonstrated approximately 0.15% cross-reactivity in the Quidel Bb EIA assay. We also observed that Bb concentration in serum is higher than in plasma due to complement activation during clot formation which let us use sera as samples representing complement activated state. Our study demonstrated that despite the potential 0.15% cross-reactivity between endogenous factor B and cleaved Bb molecule, measuring plasma concentrations of factor Bb is adequate to evaluate the activation of the alternative complement pathway.

  3. Covalently immobilized platelet-derived growth factor-BB promotes angiogenesis in biomimetic poly(ethylene glycol) hydrogels

    PubMed Central

    Saik, Jennifer E.; Gould, Daniel J.; Watkins, Emily M.; Dickinson, Mary E.; West, Jennifer L.

    2011-01-01

    The field of tissue engineering is severely limited by a lack of microvascularization in tissue engineered constructs. Biomimetic poly(ethylene glycol) hydrogels containing covalently immobilized platelet-derived growth factor BB (PDGF-BB) were developed to promote angiogenesis. Poly(ethylene glycol) hydrogels resist protein absorption and subsequent non-specific cell adhesion, thus providing a “blank slate”, which can be modified through the incorporation of cell adhesive ligands and growth factors. PDGF-BB is a key angiogenic protein able to support neovessel stabilization by inducing functional anastomoses and recruiting pericytes. Due to the widespread effects of PDGF in the body and a half-life of only 30 min in circulating blood, immobilization of PDGF-BB may be necessary. In this work bioactive, covalently immobilized PDGF-BB was shown to induce tubulogenesis on two-dimensional modified surfaces, migration in three-dimensional (3D) degradable hydrogels and angiogenesis in a mouse cornea micro-pocket angiogenesis assay. Covalently immobilized PDGF-BB was also used in combination with covalently immobilized fibroblast growth factor-2, which led to significantly increased endothelial cell migration in 3D degradable hydrogels compared with the presentation of each factor alone. When a co-culture of endothelial cells and mouse pericyte precursor 10T1/2 cells was seeded onto modified surfaces tubule formation was independent of surface modifications with covalently immobilized growth factors. Furthermore, the combination of soluble PDGF-BB and immobilized PDGF-BB induced a more robust vascular response compared with soluble PDGF-BB alone when implanted into an in vivo mouse cornea micropocket angiogenesis assay. Based on these results, we believe bioactive hydrogels can be tailored to improve the formation of functional microvasculature for tissue engineering. PMID:20801242

  4. Platelet-Derived Growth Factor BB Influences Muscle Regeneration in Duchenne Muscle Dystrophy.

    PubMed

    Piñol-Jurado, Patricia; Gallardo, Eduard; de Luna, Noemi; Suárez-Calvet, Xavier; Sánchez-Riera, Carles; Fernández-Simón, Esther; Gomis, Clara; Illa, Isabel; Díaz-Manera, Jordi

    2017-08-01

    Duchenne muscular dystrophy (DMD) is characterized by a progressive loss of muscle fibers, and their substitution by fibrotic and adipose tissue. Many factors contribute to this process, but the molecular pathways related to regeneration and degeneration of muscle are not completely known. Platelet-derived growth factor (PDGF)-BB belongs to a family of growth factors that regulate proliferation, migration, and differentiation of mesenchymal cells. The role of PDGF-BB in muscle regeneration in humans has not been studied. We analyzed the expression of PDGF-BB in muscle biopsy samples from controls and patients with DMD. We performed in vitro experiments to understand the effects of PDGF-BB on myoblasts involved in the pathophysiology of muscular dystrophies and confirmed our results in vivo by treating the mdx murine model of DMD with repeated i.m. injections of PDGF-BB. We observed that regenerating and necrotic muscle fibers in muscle biopsy samples from DMD patients expressed PDGF-BB. In vitro, PDGF-BB attracted myoblasts and activated their proliferation. Analysis of muscles from the animals treated with PDGF-BB showed an increased population of satellite cells and an increase in the number of regenerative fibers, with a reduction in inflammatory infiltrates, compared with those in vehicle-treated mice. Based on our results, PDGF-BB may play a protective role in muscular dystrophies by enhancing muscle regeneration through activation of satellite cell proliferation and migration. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  5. Low plasma PDGF-BB levels are associated with estradiol in postmenopausal osteoporosis: PDGF-BB mediated by estradiol in women.

    PubMed

    Tang, Lanhua; Xia, Zhuying; Luo, Zhongwei; Long, Haitao; Zhu, Yong; Zhao, Shushan

    2017-08-01

    Objective This study aimed to investigate the association between low plasma Platelet-derived growth factor-BB (PDGF-BB) levels and oestradiol in Postmenopausal osteoporosis (PMOP). Methods This prospective study measured plasma PDGF-BB and oestradiol levels in outpatients who were admitted to our hospital. Participants were screened and then allocated to three groups: normal young women, postmenopausal control, and PMOP. Additionally, Sprague-Dawley rats underwent either sham surgery or bilateral ovariectomy (OVX), and were divided into the following groups: sham, OVX, OVX + oestradiol, and OVX + PDGF-BB. Plasma oestradiol and PDGF-BB levels were measured using commercially available ELISA kits. Results A total of 121 participants, including 69 normal young women, 28 patients with primary PMOP, and 24 age-matched postmenopausal women were enrolled. Plasma oestradiol and PDGF-BB levels were lower in postmenopausal women, especially in PMOP ( P < 0.01). Pearson correlations analysis showed that PDGF-BB levels were positively correlated with oestradiol levels and inversely correlated with age ( P < 0.01). The OVX rat model showed that oestradiol replacement increased plasma PDGF-BB levels, while PDGF-BB systematic treatment had no effect on plasma oestradiol levels. Conclusions Plasma PDGF-BB levels are maintained by oestrogen in normal young women and play a major role in PMOP.

  6. Platelet-Derived Growth Factor-BB Lessens Light-Induced Rod Photoreceptor Damage in Mice.

    PubMed

    Takahashi, Kei; Shimazawa, Masamitsu; Izawa, Hiroshi; Inoue, Yuki; Kuse, Yoshiki; Hara, Hideaki

    2017-12-01

    Platelet-derived growth factor (PDGF)-BB is known to have neuroprotective effects against various neurodegenerative disorders. The purpose of this study was to determine whether PDGF-BB can be neuroprotective against light-induced photoreceptor damage in mice. Mice were exposed to 8000-lux luminance for 3 hours to induce phototoxicity. Two hours before light exposure, the experimental mice were injected with PDGF-BB intravitreally, and the control mice were injected with phosphate-buffered saline. The light-exposed PDGF-BB-injected mice and saline-injected mice were evaluated electroretinographically and histologically. The site and expression levels of PDGFR-β and PDGF-BB were determined by immunostaining and Western blotting, respectively. The effect of PDGF-BB on light-induced cone and rod photoreceptor damage was also evaluated in vitro in 661W cells, a murine cone photoreceptor cell line, and in primary retinal cell cultures. An intravitreal injection of PDGF-BB significantly reduced the decrease in the amplitudes of the electroretinograms (ERGs) and the thinning of the outer nuclear layer (ONL) induced by the light exposure. It also reduced the number of TUNEL-positive cells in the ONL. PDGFR-β was expressed in the rod outer segments (OSs) but not the cone OSs. The levels of PDGF-BB and PDGFR-β were decreased after light irradiation. In addition, PDGF-BB had protective effects against light-induced damage to cells of rod photoreceptors but had no effect on the 661W cells in vitro. These findings indicate that PDGF-BB reduces the degree of light-induced retinal damage by activating PDGFR-β in rod photoreceptors. These findings suggest that PDGF-BB could play a role in the prevention of degeneration in eyes susceptible to phototoxicity.

  7. Syndecan-4 enhances PDGF-BB activity in diabetic wound healing.

    PubMed

    Das, Subhamoy; Majid, Marjan; Baker, Aaron B

    2016-09-15

    Non-healing ulcers are a common consequence of long-term diabetes and severe peripheral vascular disease. These non-healing wounds are a major source of morbidity in patients with diabetes and place a heavy financial burden on the healthcare system. Growth factor therapies are an attractive strategy for enhancing wound closure in non-healing wounds but have only achieved mixed results in clinical trials. Platelet derived growth factor-BB (PDGF-BB) is the only currently approved growth factor therapy for non-healing wounds. However, PDGF-BB therapy is not effective in many patients and requires high doses that increase the potential for side effects. In this work, we demonstrate that syndecan-4 delivered in a proteoliposomal formulation enhances PDGF-BB activity in diabetic wound healing. In particular, syndecan-4 proteoliposomes enhance the migration of keratinocytes derived from patients with diabetes. In addition, syndecan-4 proteoliposomes sensitize keratinocytes to PDGF-BB stimulation, enhancing the intracellular signaling response to PDGF-BB. We further demonstrated that co-therapy with syndecan-4 proteoliposomes enhanced wound closure in diabetic, hyperlipidemic ob/ob mice. Wounds treated with both syndecan-4 proteoliposomes and PDGF-BB had increased re-epithelization and angiogenesis in comparison to wounds treated with PDGF-BB alone. Moreover, the wounds treated with syndecan-4 proteoliposomes and PDGF-BB also had increased M2 macrophages and reduced M1 macrophages, suggesting syndecan-4 delivery induces immunomodulation within the healing wounds. Together our findings support that syndecan-4 proteoliposomes markedly improve PDGF-BB efficacy for wound healing and may be useful in enhancing treatments for non-healing wounds. Non-healing wounds are major healthcare issue for patients with diabetes and peripheral vascular disease. Growth factor therapies have potential for healing chronic wounds but have not been effective for many patients. PDGF-BB is

  8. Application of platelet derived growth factor-BB and diabetic wound healing: the relationship with oxidative events.

    PubMed

    Gökşen, Sibel; Balabanlı, Barbaros; Coşkun-Cevher, Şule

    2017-05-01

    The reasons that cause delay in wound healing in diabetes are a decrease in the level of growth factors secretion, an increase in the destruction of growth factors and in oxidative stress. Platelet derived growth factor (PDGF) is one of the important growth factors that play a role in all phases of wound healing. This study investigates time-dependent effects of topically PDGF-BB administration on oxidative events on the healing of dorsolateral-excisional wounds in diabetic rats. Forty-two female Wistar-albino rats with streptozotocin-induced diabetes were divided into four groups: control group, untreated group, chitosan-treated group, chitosan + PDGF-BB-treated group. Two identical full-thickness excisional skin wounds were made under anaesthesia in all rats except for the control group. In the PDGF-BB-treated and chitosan-treated groups, the wounds were treated topically PDGF-BB (7 ng/mL, single daily dose) and blank chitosan gel (equal amount) after wounding, respectively. After these administrations, on day 3 and day 7 of wound healing, rats were sacrificed. Thiobarbituric acid reactive substances, glutathione, nitric oxide, ascorbic acid levels, and superoxide dismutase activity in wound tissues were spectrophotometrically measured. PDGF-BB administration significantly increased TBARS levels and non-enzymatic antioxidant levels in early phase of diabetic wound healing. PDGF-BB dramatically reduced NO x levels on day 3 and sharply increased NO x levels on day 7 of wound healing. Consequently, PDGF-BB administration can be effective on oxidative balance in the early phase of diabetic wound healing.

  9. Portable aptamer biosensor of platelet-derived growth factor-BB using a personal glucose meter with triply amplified.

    PubMed

    Hong, Lu; Zhou, Fu; Shi, Dongmin; Zhang, Xiaojun; Wang, Guangfeng

    2017-09-15

    Sensitive and rapid detection of platelet-derived growth factor BB (PDGF-BB), a cancer-related protein, could help early diagnosis, treatment, and prognosis of cancers. Although some methods have been developed to detect PDGF-BB, few can provide quantitative results using an affordable and portable device that is suitable for home use or field application. In this work, we report the first use of a portable kind of personal glucose meter (PGM) combining a catalytic and molecular beacon (CAMB) system with a cation exchange reaction (CX reaction) for ultrasensitive PDGF-BB assay. It realized the amplification of the detection in three ways, including greater aptamer payload on nanoparticles, CX reaction releasing thousands of Zn 2+ and the cycle by the catalyzing cleavage of 8-17 DNAzyme. In the process, with the addition of PDGF-BB into the aptasensor, the specific recognition between aptamer and protein was initiated resulting in the combination of ZnS NNC for further CX reaction to release thousands of Zn 2+ , which could cleave the substrate DNA in the CAMB system realizing multiple cycle. The cleaved DNA fragment was designed with invertase-labeled could convert sucrose into glucose which could be detected and quantified by PGM accompanying with the change of color of the control window from yellow to green. The enhanced signal of the PGM has a relationship with the concentration of PDGF-BB in the range of 3.16×10 -16 M to 3.16×10 -12 M, and the detection limit is 0.11fM. Moreover, the catalytic and cleavage activities of 8-17 DNAzyme can be achieved in solution; thus, no enzyme immobilization is needed for detection. The triply amplified strategy showed high selectivity, stability, and applicability for detecting the desired protein. Copyright © 2017. Published by Elsevier B.V.

  10. The autophagy-related genes BbATG1 and BbATG8 have different functions in differentiation, stress resistance and virulence of mycopathogen Beauveria bassiana

    PubMed Central

    Ying, Sheng-Hua; Liu, Jing; Chu, Xin-Ling; Xie, Xue-Qin; Feng, Ming-Guang

    2016-01-01

    Autophagy-related proteins play significantly different roles in eukaryotes. In the entomopathogenic fungus Beauveria bassiana, autophagy is associated with fungal growth and development. BbATG1 (a serine/threonine protein kinase) and BbATG8 (a ubiquitin-like protein) have similar roles in autophagy, but different roles in other processes. Disruption mutants of BbATG1 and BbATG8 had impaired conidial germination under starvation stress. The mutant ΔBbATG8 exhibited enhanced sensitivity to oxidative stress, while a ΔBbATG1 mutant did not. BbATG1 and BbATG8 showed different roles in spore differentiation. The blastospore yield was reduced by 70% and 92% in ΔBbATG1 and ΔBbATG8 mutants, respectively, and the double mutant had a reduction of 95%. Conidial yield was reduced by approximately 90% and 50% in ΔBbATG1 and ΔBbATG8 mutants, respectively. A double mutant had a reduction similar to ΔBbATG1. Additionally, both BbATG1 and BbATG8 affected the levels of conidial protein BbCP15p required for conidiation. The virulence of each autophagy-deficient mutant was considerably weakened as indicated in topical and intrahemocoel injection assays, and showed a greater reduction in topical infection. However, BbATG1 and BbATG8 had different effects on fungal virulence. Our data indicate that these autophagy-related proteins have different functions in fungal stress response, asexual development and virulence. PMID:27197558

  11. Regulation of human bone sialoprotein gene transcription by platelet-derived growth factor-BB.

    PubMed

    Mezawa, Masaru; Araki, Shouta; Takai, Hideki; Sasaki, Yoko; Wang, Shuang; Li, Xinyue; Kim, Dong-Soon; Nakayama, Youhei; Ogata, Yorimasa

    2009-04-15

    Platelet-derived growth factor (PDGF) is produced by mesenchymal cells and released by platelets following aggregation and is synthesized by osteoblasts. In bone, PDGF stimulates proliferation and differentiation of osteoblasts. PDGF also increases bone resorption, most likely by increasing the number of osteoclasts. Bone sialoprotein (BSP) is thought to function in the initial mineralization of bone, selectively expressed by differentiated osteoblast. To determine the molecular mechanisms PDGF regulation of human BSP gene transcription, we have analyzed the effects of PDGF-BB on osteoblast-like Saos2 and ROS17/2.8 cells. PDGF-BB (5 ng/ml) increased BSP mRNA and protein levels at 12 h in Saos2 cells, and induced BSP mRNA expression at 3 h, reached maximal at 12 h in ROS17/2.8 cells. Transient transfection analyses were performed using chimeric constructs of the human BSP gene promoter linked to a luciferase reporter gene. Treatment of Saos2 cells with PDGF-BB (5 ng/ml, 12 h) increased luciferase activities of all constructs between -184LUC to -2672LUC including the human BSP gene promoter. Effects of PDGF-BB abrogated in constructs included 2 bp mutations in the two cAMP response elements (CRE1 and CRE2), activator protein 1(3) (AP1(3)) and shear stress response element 1 (SSRE1). Luciferase activities induced by PDGF-BB were blocked by protein kinase A inhibitor H89 and tyrosine kinase inhibitor herbimycin A. Gel mobility shift analyses showed that PDGF-BB increased binding of CRE1, CRE2, AP1(3) and SSRE1 elements. CRE1- and CRE2-protein complexes were supershifted by CREB1 and phospho-CREB1 antibodies. Notably, AP1(3)-protein complexes were supershifted by c-Fos and JunD, and disrupted by CREB1, phospho-CREB1, c-Jun and Fra2 antibodies. These studies, therefore, demonstrate that PDGF-BB stimulates human BSP transcription by targeting the CRE1, CRE2, AP1(3) and SSRE1 elements in the human BSP gene promoter.

  12. Management of BB shot wounds to the heart.

    PubMed

    Thompson, E C; Block, E F; Mancini, M C

    1996-01-01

    The aim of this study was to review our experience with BB shot injuries to the heart. This is a retrospective chart review. Three patients were found to have BB injuries to the heart. All patients were stable upon presentation. Echocardiography localized the BB pellets to the muscular septum. All patients were treated with nonoperative therapy. There was not mortality. One patient developed an interventricular conduction delay that resolved before discharge. Nonoperative management of stable patients who present with BB wounds to the heart is safe and effective if the BB is intramuscular. An echocardiogram should be used to localize the pellets and evaluate the pericardium.

  13. Combination CTLA-4 Blockade and 4-1BB Activation Enhances Tumor Rejection by Increasing T-Cell Infiltration, Proliferation, and Cytokine Production

    PubMed Central

    Curran, Michael A.; Kim, Myoungjoo; Montalvo, Welby; Al-Shamkhani, Aymen; Allison, James P.

    2011-01-01

    Background The co-inhibitory receptor Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) attenuates immune responses and prevent autoimmunity, however, tumors exploit this pathway to evade the host T-cell response. The T-cell co-stimulatory receptor 4-1BB is transiently upregulated on T-cells following activation and increases their proliferation and inflammatory cytokine production when engaged. Antibodies which block CTLA-4 or which activate 4-1BB can promote the rejection of some murine tumors, but fail to cure poorly immunogenic tumors like B16 melanoma as single agents. Methodology/Principal Findings We find that combining αCTLA-4 and α4-1BB antibodies in the context of a Flt3-ligand, but not a GM-CSF, based B16 melanoma vaccine promoted synergistic levels of tumor rejection. 4-1BB activation elicited strong infiltration of CD8+ T-cells into the tumor and drove the proliferation of these cells, while CTLA-4 blockade did the same for CD4+ effector T-cells. Anti-4-1BB also depressed regulatory T-cell infiltration of tumors. 4-1BB activation strongly stimulated inflammatory cytokine production in the vaccine and tumor draining lymph nodes and in the tumor itself. The addition of CTLA-4 blockade further increased IFN-γ production from CD4+ effector T-cells in the vaccine draining node and the tumor. Anti 4-1BB treatment, with or without CTLA-4 blockade, induced approximately 75% of CD8+ and 45% of CD4+ effector T-cells in the tumor to express the killer cell lectin-like receptor G1 (KLRG1). Tumors treated with combination antibody therapy showed 1.7-fold greater infiltration by these KLRG1+CD4+ effector T-cells than did those treated with α4-1BB alone. Conclusions/Significance This study shows that combining T-cell co-inhibitory blockade with αCTLA-4 and active co-stimulation with α4-1BB promotes rejection of B16 melanoma in the context of a suitable vaccine. In addition, we identify KLRG1 as a useful marker for monitoring the anti-tumor immune response elicited by

  14. The effect of controlled release of PDGF-BB from heparin-conjugated electrospun PCL/gelatin scaffolds on cellular bioactivity and infiltration

    PubMed Central

    Lee, Jongman; Yoo, James J.; Atala, Anthony; Lee, Sang Jin

    2013-01-01

    Heparin-conjugated electrospun poly(ε-caprolactone) (PCL)/gelatin scaffolds were developed to provide controlled release of platelet-derived growth factor-BB (PDGF-BB) and allow prolonged bioactivity of this molecule. A mixture of PCL and gelatin was electrospun into three different morphologies. Next, heparin molecules were conjugated to the reactive surface of the scaffolds. This heparin-conjugated scaffold allowed the immobilization of PDGF-BB via electrostatic interaction. In vitro PDGF-BB release profiles indicated that passive physical adsorption of PDGF-BB to non-heparinized scaffolds resulted in an initial burst release of PDGF-BB within 5 days, which then leveled off. However, electrostatic interaction between PDGF-BB and the heparin-conjugated scaffolds gave rise to a sustained release of PDGF-BB over the course of 20 days without an initial burst. Moreover, PDGF-BB that was strongly bound to the heparin-conjugated scaffolds enhanced smooth muscle cell (SMC) proliferation. In addition, scaffolds composed of 3.0 µm diameter fibers that were immobilized with PDGF-BB accelerated SMC infiltration into the scaffold when compared to scaffolds composed of smaller diameter fibers or scaffolds that did not release PDGF-BB. We concluded that the combination of the large pore structure in the scaffolds and the heparin-mediated delivery of PDGF-BB provided the most effective cellular interactions through synergistic physical and chemical cues. PMID:22770570

  15. 4-1BB Aptamer-Based Immunomodulation Enhances the Therapeutic Index of Radiation Therapy in Murine Tumor Models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Benaduce, Ana Paula; Brenneman, Randall; Schrand, Brett

    Purpose: To report a novel strategy using oligonucleotide aptamers to 4-1BB as an alternate method for costimulation, and show that combinatorial therapy with radiation improves the therapeutic ratio over equivalent monoclonal antibodies. Methods and Materials: Subcutaneous 4T1 (mouse mammary carcinoma) tumors were established (approximately 100 mm{sup 3}), and a radiation therapy (RT) dose/fractionation schedule that optimally synergizes with 4-1BB monoclonal antibody (mAb) was identified. Comparable tumor control and animal survival was observed when either 4-1BB antibody or aptamer were combined with RT using models of breast cancer and melanoma (4T1 and B16-F10). Off-target CD8{sup +} T-cell toxicity was evaluated by quantification ofmore » CD8{sup +} T cells in livers and spleens of treated animals. Results: When combined with 4-1BB mAb, significant differences in tumor control were observed by varying RT dose and fractionation schedules. Optimal synergy between RT and 4-1BB mAb was observed at 5 Gy × 6. Testing 4-1BB mAb and aptamer independently using the optimal RT (5 Gy × 6 for 4T1/Balb/c and 12 Gy × 1 for B16/C57BL6J mouse models) revealed equivalent tumor control using 4-1BB aptamer and 4-1BB mAb. 4-1BB mAb, but not 4-1BB aptamer-treated animals, exhibited increased lymphocytic liver infiltrates and increased splenic and liver CD8{sup +} T cells. Conclusions: Radiation therapy synergizes with 4-1BB mAb, and this effect is dependent on RT dose and fractionation. Tumor control by 4-1BB aptamer is equivalent to 4-1BB mAb when combined with optimal RT dose, without eliciting off-target liver and spleen CD8{sup +} expansion. 4-1BB aptamer-based costimulation affords a comparable and less toxic strategy to augment RT-mediated tumor control.« less

  16. Prospective Randomized Controlled Trial of Hindfoot and Ankle Fusions Treated With rhPDGF-BB in Combination With a β-TCP-Collagen Matrix.

    PubMed

    Daniels, Timothy R; Younger, Alastair S E; Penner, Murray J; Wing, Kevin J; Le, Ian L D; Russell, Iain S; Lalonde, Karl-André; Evangelista, Peter T; Quiton, Jovelyn D; Glazebrook, Mark; DiGiovanni, Christopher W

    2015-07-01

    Ankle and hindfoot arthrodesis is often supplemented with autograft to promote bony union. Autograft harvest can lead to increased perioperative morbidity. Purified recombinant human platelet-derived growth factor BB homodimer (rhPDGF-BB) has stimulated bone formation in mandibular defects and hindfoot fusion. This randomized controlled trial evaluated the efficacy and safety of rhPDGF-BB combined with an injectable, osteoconductive beta-tricalcium phosphate (β-TCP)-collagen matrix versus autograft in ankle and hindfoot fusions. Seventy-five patients requiring ankle or hindfoot fusion were randomized 5:1 for rhPDGF-BB/β-TCP-collagen (treatment, n = 63) or autograft (control, n = 12). Prospective analysis included 142 autograft control subjects from another clinical trial with identical study protocols. Standardized operative and postoperative protocols were used. Patients underwent standard internal fixation augmented with autograft or 0.3 mg/mL rhPDGF-BB/β-TCP-collagen. Radiologic, clinical, and quality-of-life outcomes were assessed over 52 weeks. Primary outcome was joint fusion (50% or more osseous bridging on computed tomography) at 24 weeks. Secondary outcomes included radiographs, clinical healing status, visual analog scale pain score, American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scale score, Foot Function Index score, and Short Form-12 score. Noninferiority P values were calculated. Complete fusion of all involved joints at 24 weeks as indicated by computed tomography was achieved in 53 of 63 (84%) rhPDGF-BB/β-TCP-collagen-treated patients and 100 of 154 (65%) autograft-treated patients (P < .001). Mean time to fusion was 14.3 ± 8.9 weeks for rhPDGF-BB/β-TCP-collagen patients versus 19.7 ± 11.5 weeks for autograft patients (P < .01). Clinical success at 52 weeks was achieved in 57 of 63 (91%) rhPDGF-BB/β-TCP-collagen patients and 120 of 154 (78%) autograft patients (P < .001). Safety-related outcomes were equivalent. Autograft controls

  17. Biological responses to PDGF-BB versus PDGF-DD in human mesangial cells.

    PubMed

    van Roeyen, C R C; Ostendorf, T; Denecke, B; Bokemeyer, D; Behrmann, I; Strutz, F; Lichenstein, H S; LaRochelle, W J; Pena, C E; Chaudhuri, A; Floege, J

    2006-04-01

    Platelet-derived growth factor (PDGF)-BB and PDGF-DD mediate mesangial cell proliferation in vitro and in vivo. While PDGF-BB is a ligand for the PDGF alpha- and beta-receptor chains, PDGF-DD binds more selectively to the beta-chain, suggesting potential differences in the biological activities. Signal transduction and regulation of gene expression induced by PDGF-BB and -DD were compared in primary human mesangial cells (HMCs), which expressed PDGF alpha- and beta-receptor subunits. The growth factor concentrations used were chosen based on their equipotency in inducing HMCs proliferation and binding to the betabeta-receptor. Both growth factors, albeit at different concentrations induced phosphorylation and activation of extracellular signal-regulated kinase 1 (ERK1) and ERK2. In addition, PDGFs led to the phosphorylation and activation of signal transducers and activators of transcription 1 (STAT1) and STAT3. HMCs proliferation induced by either PDGF-BB or -DD could be blocked by signal transduction inhibitors of the mitogen-activated protein kinase-, Janus kinase (JAK)/STAT-, or phosphatidyl-inositol 3-kinase pathways. Using a gene chip array and subsequent verification by real-time reverse transcriptase (RT)-polymerase chain reaction, we found that in HMC genes for matrix metalloproteinase 13 (MMP-13) and MMP-14 and, to a low extent, cytochrome B5 and cathepsin L were exclusively regulated by PDGF-BB, whereas no exclusive gene regulation was detected by PDGF-DD. However, at the protein level, both MMP-13 and -14 were equally induced by PDGF-BB and -DD. PDGF-BB and -DD effect similar biological responses in HMCs albeit at different potencies. Rare apparently differential gene regulation did not result in different protein expression, suggesting that in HMCs both PDGFs exert their biological activity almost exclusively via the PDGF beta-receptor.

  18. Phloretin Inhibits Platelet-derived Growth Factor-BB-induced Rat Aortic Smooth Muscle Cell Proliferation, Migration, and Neointimal Formation After Carotid Injury.

    PubMed

    Wang, Dong; Wang, Qingjie; Yan, Gaoliang; Qiao, Yong; Tang, Chengchun

    2015-05-01

    Abnormal vascular smooth muscle cell proliferation and migration are key factors in many cardiovascular diseases. Here, we investigated the effects of phloretin on platelet-derived growth factor homodimer (PDGF-BB)-induced rat aortic smooth muscle cell (RASMC) proliferation, migration, and neointimal formation after carotid injury. Phloretin significantly inhibited the PDGF-BB-stimulated RASMC proliferation in a concentration-dependent manner (10-100 μM). Also, PDGF-BB-stimulated RASMC migration was inhibited by phloretin at 50 μM. Pretreating RASMC with phloretin dose-dependently inhibited PDGF-BB-induced Akt and p38 mitogen-activated protein kinases activation. Furthermore, phloretin increased p27 and decreased cyclin-dependent kinase 2, CDK4 expression, and p-Rb activation in PDGF-BB-stimulated RASMC in a concentration-dependent manner (10-50 μM). PDGF-BB-induced cell adhesion molecules and matrix metalloproteinase-9 expression were blocked by phloretin at 50 μM. Preincubation with phloretin dose-dependently reduced the intracellular reactive oxygen species production. In vivo study showed that phloretin (20 mg/kg) significantly reduced neointimal formation 14 days after carotid injury in rats. Thus, phloretin may have potential as a treatment against atherosclerosis and restenosis after vascular injury.

  19. Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

    PubMed Central

    Chen, Zhuo; Liu, Suixin; Cai, Ying; Xie, Kangling; Zhang, Wenliang; Dong, Lei; Liu, Yuan; Zheng, Fan; Dun, Yaoshan; Li, Ning

    2016-01-01

    Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus, has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF-BB-induced upregulation of cell cycle-related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF-BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis. PMID:27588108

  20. Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells.

    PubMed

    Chen, Zhuo; Liu, Suixin; Cai, Ying; Xie, Kangling; Zhang, Wenliang; Dong, Lei; Liu, Yuan; Zheng, Fan; Dun, Yaoshan; Li, Ning

    2016-09-01

    Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) has been implicated in intimal hyperplasia, atherosclerosis and restenosis following percutaneous coronary intervention. Formononetin, a phytoestrogen extracted from the root of Astragalus membranaceus , has been widely used in Chinese tradition medicine due to its protective effects against certain symptoms of cancer, hypertension, inflammation, hypoxia-induced cytotoxicity and ovariectomy-induced bone loss. However, the effect of formononetin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs, as well as the underlying molecular mechanism, remains largely unclear. In the present study, treatment with formononetin significantly inhibited PDGF-BB-induced proliferation and migration of human VSMCs. Investigation into the underlying molecular mechanism revealed that the administration of formononetin suppressed PDGF-BB-stimulated switch of VSMCs to a proliferative phenotype. Furthermore, treatment with formononetin inhibited the PDGF-BB-induced upregulation of cell cycle-related proteins, matrix metalloproteinase (MMP2) and MMP9. In addition, the that administration of formononetin inhibited the phosphorylation of AKT induced by PDGF-BB in VSMCs. The present results suggest that formononetin has a suppressive effect on PDGF-BB-stimulated VSMCs proliferation and migration, which may occur partly via the inhibition of AKT signaling pathway. Therefore, formononetin may be useful for the treatment of intimal hyperplasia, atherosclerosis and restenosis.

  1. Cordyceps sinensis polysaccharide inhibits PDGF-BB-induced inflammation and ROS production in human mesangial cells.

    PubMed

    Wang, Ying; Wang, Yan; Liu, Dan; Wang, Wang; Zhao, Huan; Wang, Min; Yin, Hongping

    2015-07-10

    CPS-F, a polysaccharide derived from Cordyceps sinensis, is a potential anti-inflammatory and anti-oxidative agent. We demonstrated that CPS-F not only inhibits platelet-derived growth factor BB (PDGF-BB)-induced intracellular reactive oxygen species (ROS) generation, and up-regulation of tumor necrosis factor-α (TNF-α), TNF-α receptor 1 (TNFR1), and monocyte chemotactic protein-1 (MCP-1), but also acts synergistically in combination with MAPK/ERK inhibitor U0126 and PI3K/Akt inhibitor LY294002. Additionally, up-regulation of pro-inflammatory factors was reversed by use of a combination of CPS-F and NADPH oxidase (NOX) inhibitor diphenyleneiodonium chloride (DPI) or silencing of NOX1. Furthermore, CPS-F prevents the PDGF receptor β (PDGFRβ) promoter activity induced by PDGF-BB in transfected cells and ameliorates increased levels of TNF-α, TNFR1, and MCP-1 when PDGFRβ is silenced, thereby suggesting that CPS-F possesses a bidirectional regulatory function. Our findings suggest CPS-F may exert its therapeutic effect for the treatment of glomerulonephritis related to human mesangial cells (HMCs) through the ERK1/2/Akt pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Growth factors in porcine full and partial thickness burn repair. Differing targets and effects of keratinocyte growth factor, platelet-derived growth factor-BB, epidermal growth factor, and neu differentiation factor.

    PubMed Central

    Danilenko, D. M.; Ring, B. D.; Tarpley, J. E.; Morris, B.; Van, G. Y.; Morawiecki, A.; Callahan, W.; Goldenberg, M.; Hershenson, S.; Pierce, G. F.

    1995-01-01

    The topical application of recombinant growth factors such as epidermal growth factor, platelet-derived growth factor-BB homodimer (rPDGF-BB), keratinocyte growth factor (rKGF), and neu differentiation factor has resulted in significant acceleration of healing in several animal models of wound repair. In this study, we established highly reproducible and quantifiable full and deep partial thickness porcine burn models in which burns were escharectomized 4 or 5 days postburn and covered with an occlusive dressing to replicate the standard treatment in human burn patients. We then applied these growth factors to assess their efficacy on several parameters of wound repair: extracellular matrix and granulation tissue production, percent reepithelialization, and new epithelial area. In full thickness burns, only rPDGF-BB and the combination of rPDGF-BB and rKGF induced significant changes in burn repair. rPDGF-BB induced marked extracellular matrix and granulation tissue production (P = 0.013) such that the burn defect was filled within several days of escharectomy, but had no effect on new epithelial area or reepithelialization. The combination of rPDGF-BB and rKGF in full thickness burns resulted in a highly significant increase in extracellular matrix and granulation tissue area (P = 0.0009) and a significant increase in new epithelial area (P = 0.007), but had no effect on reepithelialization. In deep partial thickness burns, rKGF induced the most consistent changes. Daily application of rKGF induced a highly significant increase in new epithelial area (P < 0.0001) but induced only a modest increase in reepithelialization (83.7% rKGF-treated versus 70.2% control; P = 0.016) 12 days postburn. rKGF also doubled the number of fully reepithelialized burns (P = 0.02) at 13 days postburn, at least partially because of marked stimulation of both epidermal and follicular proliferation as assessed by proliferating cell nuclear antigen expression. In situ hybridization for

  3. Differences in acid tolerance between Bifidobacterium breve BB8 and its acid-resistant derivative B. breve BB8dpH, revealed by RNA-sequencing and physiological analysis.

    PubMed

    Yang, Xu; Hang, Xiaomin; Tan, Jing; Yang, Hong

    2015-06-01

    Bifidobacteria are common inhabitants of the human gastrointestinal tract, and their application has increased dramatically in recent years due to their health-promoting effects. The ability of bifidobacteria to tolerate acidic environments is particularly important for their function as probiotics because they encounter such environments in food products and during passage through the gastrointestinal tract. In this study, we generated a derivative, Bifidobacterium breve BB8dpH, which displayed a stable, acid-resistant phenotype. To investigate the possible reasons for the higher acid tolerance of B. breve BB8dpH, as compared with its parental strain B. breve BB8, a combined transcriptome and physiological approach was used to characterize differences between the two strains. An analysis of the transcriptome by RNA-sequencing indicated that the expression of 121 genes was increased by more than 2-fold, while the expression of 146 genes was reduced more than 2-fold, in B. breve BB8dpH. Validation of the RNA-sequencing data using real-time quantitative PCR analysis demonstrated that the RNA-sequencing results were highly reliable. The comparison analysis, based on differentially expressed genes, suggested that the acid tolerance of B. breve BB8dpH was enhanced by regulating the expression of genes involved in carbohydrate transport and metabolism, energy production, synthesis of cell envelope components (peptidoglycan and exopolysaccharide), synthesis and transport of glutamate and glutamine, and histidine synthesis. Furthermore, an analysis of physiological data showed that B. breve BB8dpH displayed higher production of exopolysaccharide and lower H(+)-ATPase activity than B. breve BB8. The results presented here will improve our understanding of acid tolerance in bifidobacteria, and they will lead to the development of new strategies to enhance the acid tolerance of bifidobacterial strains. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. 4-1BB regulates NKG2D costimulation in human cord blood CD8+ T cells.

    PubMed

    Kim, Young-June; Han, Myung-Kwan; Broxmeyer, Hal E

    2008-02-01

    Ligation of NKG2D, a potent costimulatory receptor, can be either beneficial or detrimental to CD8(+) cytotoxic T cell (CTL) responses. Factors for these diverse NKG2D effects remain elusive. In this study, we demonstrate that 4-1BB, another costimulatory receptor, is an essential regulator of NKG2D in CD8(+) T cells. Costimulation of NKG2D caused down-modulation of NKG2D, but induced 4-1BB expression on the cell surface, even in the presence of TGF-beta1, which inhibits 4-1BB expression. Resulting NKG2D(-)4-1BB(+) cells were activated but still in an immature state with low cytotoxic activity. However, subsequent 4-1BB costimulation induced cytotoxic activity and restored down-modulated NKG2D. The cytotoxic activity and NKG2D expression induced by 4-1BB on NKG2D(+)4-1BB(+) cells were refractory to TGF-beta1 down-modulation. Such 4-1BB effects were enhanced by IL-12. In contrast, in the presence of IL-4, 4-1BB effects were abolished because IL-4 down-modulated NKG2D and 4-1BB expression in cooperation with TGF-beta1, generating another CD8(+) T-cell type lacking both NKG2D and 4-1BB. These NKG2D(-)4-1BB(-) cells were inert and unable to gain cytotoxic activity. Our results suggest that 4-1BB plays a critical role in protecting NKG2D from TGF-beta1-mediated down-modulation. Co-expression of NKG2D and 4-1BB may represent an important biomarker for defining competency of tumor infiltrating CD8(+) T cells.

  5. Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson's disease patients.

    PubMed

    Paul, Gesine; Zachrisson, Olof; Varrone, Andrea; Almqvist, Per; Jerling, Markus; Lind, Göran; Rehncrona, Stig; Linderoth, Bengt; Bjartmarz, Hjalmar; Shafer, Lisa L; Coffey, Robert; Svensson, Mikael; Mercer, Katarina Jansson; Forsberg, Anton; Halldin, Christer; Svenningsson, Per; Widner, Håkan; Frisén, Jonas; Pålhagen, Sven; Haegerstrand, Anders

    2015-03-02

    BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson's disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 μg rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD. TRIAL REGISTRATION. Clinical Trials.gov NCT00866502. FUNDING. Newron Sweden AB (former NeuroNova AB) and Swedish Governmental Agency for Innovation Systems (VINNOVA).

  6. PDGF-BB Does Not Accelerate Healing in Diabetic Mice with Splinted Skin Wounds

    PubMed Central

    Shah, Nihar M.; Teixeira, Leandro; Motta, Monica J.; Covert, Jill; Dubielzig, Richard; Schurr, Michael; Isseroff, Roslyn Rivkah; Abbott, Nicholas L.; McAnulty, Jonathan; Murphy, Christopher J.

    2014-01-01

    Topical application of platelet-derived growth factor-BB (PDGF-BB) is considered to accelerate tissue repair of impaired chronic wounds. However, the vast literature is plagued with conflicting reports of its efficacy in animal models and this is often influenced by a wide array of experimental variables making it difficult to compare the results across the studies. To mitigate the confounding variables that influence the efficacy of topically applied PDGF-BB, we used a controlled full thickness splinted excisional wound model in db/db mice (type 2 diabetic mouse model) for our investigations. A carefully-defined silicone-splinted wound model, with reduced wound contraction, controlled splint and bandage maintenance, allowing for healing primarily by reepithelialization was employed. Two splinted 8 mm dorsal full thickness wounds were made in db/db mice. Wounds were topically treated once daily with either 3 µg PDGF-BB in 30 µl of 5% PEG-PBS vehicle or an equal volume of vehicle for 10 days. Body weights, wound contraction, wound closure, reepithelialization, collagen content, and wound bed inflammation were evaluated clinically and histopathologically. The bioactivity of PDGF-BB was confirmed by in vitro proliferation assay. PDGF-BB, although bioactive in vitro, failed to accelerate wound healing in vivo in the db/db mice using the splinted wound model. Considering that the predominant mechanism of wound healing in humans is by re-epeithelialization, the most appropriate model for evaluating therapeutics is one that uses splints to prevent excessive wound contraction. Here, we report that PDGF-BB does not promote wound closure by re-epithelialization in a murine splinted wound model. Our results highlight that the effects of cytoactive factors reported in vivo ought to be carefully interpreted with critical consideration of the wound model used. PMID:25121729

  7. Human buccal plate extraction socket regeneration with recombinant human platelet-derived growth factor BB or enamel matrix derivative.

    PubMed

    Nevins, Marc L; Camelo, Marcelo; Schupbach, Peter; Nevins, Myron; Kim, Soo-Woo; Kim, David M

    2011-01-01

    The objective of this study was to assess the osseous healing of buccal plate extraction socket defects. There were four cohorts: group A (mineral collagen bone substitute [MCBS] scaffold alone), group B (MCBS with recombinant human platelet-derived growth factor BB [rhPDGF-BB; 0.3 mg/mL]), group C (MCBS with enamel matrix derivative [EMD]), and group D (combination of EMD with bone ceramic). The primary outcome of bone quality was evaluated using light microscopy, backscatter scanning electron microscopy, and histomorphometrics. Reentry surgery provided an opportunity for clinical observation of the healed ridge morphology. Sixteen patients with buccal wall extraction socket defects were randomized into four treatment groups of equal size. Grafting was provided at the time of extraction with advancement of the buccal flap for primary closure. A trephine core biopsy of the implant site preparation was performed after 5 months for implant placement. Histologic examination identified new bone healing around the biomaterial scaffolds. Statistically significant differences in new bone formation were not observed among the treatment groups. There was a histomorphometric trend toward more new bone for the rhPDGF-BB-treated group (group B). This group had the most favorable ridge morphology for optimal implant placement.

  8. Sustained functional improvement by hepatocyte growth factor-like small molecule BB3 after focal cerebral ischemia in rats and mice

    PubMed Central

    Chaparro, Rafael E; Izutsu, Miwa; Sasaki, Toshihiro; Sheng, Huaxin; Zheng, Yi; Sadeghian, Homa; Qin, Tao; von Bornstadt, Daniel; Herisson, Fanny; Duan, Bin; Li, Jing-Song; Jiang, Kai; Pearlstein, Molly; Pearlstein, Robert D; Smith, David E; Goldberg, Itzhak D; Ayata, Cenk; Warner, David S

    2015-01-01

    Hepatocyte growth factor (HGF), efficacious in preclinical models of acute central nervous system injury, is burdened by administration of full-length proteins. A multiinstitutional consortium investigated the efficacy of BB3, a small molecule with HGF-like activity that crosses the blood–brain barrier in rodent focal ischemic stroke using Stroke Therapy Academic Industry Roundtable (STAIR) and Good Laboratory Practice guidelines. In rats, BB3, begun 6 hours after temporary middle cerebral artery occlusion (tMCAO) reperfusion, or permanent middle cerebral artery occlusion (pMCAO) onset, and continued for 14 days consistently improved long-term neurologic function independent of sex, age, or laboratory. BB3 had little effect on cerebral infarct size and no effect on blood pressure. BB3 increased HGF receptor c-Met phosphorylation and synaptophysin expression in penumbral tissue consistent with a neurorestorative mechanism from HGF-like activity. In mouse tMCAO, BB3 starting 10 minutes after reperfusion and continued for 14 days improved neurologic function that persisted for 8 weeks in some, but not all measures. Study in animals with comorbidities and those exposed to common stroke drugs are the next steps to complete preclinical assessment. These data, generated in independent, masked, and rigorously controlled settings, are the first to suggest that the HGF pathway can potentially be harnessed by BB3 for neurologic benefit after ischemic stroke. PMID:25712497

  9. Rotavirus shedding following administration of RV3-BB human neonatal rotavirus vaccine.

    PubMed

    Cowley, Daniel; Boniface, Karen; Bogdanovic-Sakran, Nada; Kirkwood, Carl D; Bines, Julie E

    2017-08-03

    The RV3-BB human neonatal rotavirus vaccine aims to provide protection from severe rotavirus disease from birth. A phase IIa safety and immunogenicity trial was undertaken in Dunedin, New Zealand between January 2012 and April 2014. Healthy, full-term (≥ 36 weeks gestation) babies, who were 0-5 d old were randomly assigned (1:1:1) to receive 3 doses of oral RV3-BB vaccine with the first dose given at 0-5 d after birth (neonatal schedule), or the first dose given at about 8 weeks after birth (infant schedule), or to receive placebo (placebo schedule). Vaccine take (serum immune response or stool shedding of vaccine virus after any dose) was detected after 3 doses of RV3-BB vaccine in >90% of participants when the first dose was administered in the neonatal and infant schedules. The aim of the current study was to characterize RV3-BB shedding and virus replication following administration of RV3-BB in a neonatal and infant vaccination schedule. Shedding was defined as detection of rotavirus by VP6 reverse transcription polymerase chain reaction (RT-PCR) in stool on days 3-7 after administration of RV3-BB. Shedding of rotavirus was highest following vaccination at 8 weeks of age in both neonatal and infant schedules (19/30 and 17/27, respectively). Rotavirus was detected in stool on days 3-7, after at least one dose of RV3-BB, in 70% (21/30) of neonate, 78% (21/27) of infant and 3% (1/32) placebo participants. In participants who shed RV3-BB, rotavirus was detectable in stool on day 1 following RV3-BB administration and remained positive until day 4-5 after administration. The distinct pattern of RV3-BB stool viral load demonstrated using a NSP3 quantitative qRT-PCR in participants who shed RV3-BB, suggests that detection of RV3-BB at day 3-7 was the result of replication rather than passage through the gastrointestinal tract.

  10. Influence of calcareous soil on Cry3Bb1 expression and efficacy in the field.

    PubMed

    Wangila, David S; Valencia J, Arnubio; Wang, Haichuan; Siegfried, Blair D; Meinke, Lance J

    2017-06-01

    Greater than expected injury by western corn rootworm (WCR) (Diabrotica virgifera virgifera LeConte) to Cry3Bb1 expressing maize hybrids (Zea mays L.) has been reported in southwestern Nebraska. Affected areas of some fields are often associated with high pH calcareous soils where maize growth is poor and iron chlorosis is common. As part of a comprehensive study to understand potential causes of unexpected injury, experiments were conducted during 2013 and 2014 to ascertain whether the calcareous soil conditions and associated poor maize growth negatively affect the expression of Cry3Bb1. Quantitative determination of Cry3Bb1 protein expression levels in root tissues was carried out on plants at V5-V6 growth stage using the enzyme-linked immunosorbent assay. Cry3Bb1 and non-Bt near isoline maize hybrids were artificially infested with Cry3Bb1-susceptible WCR eggs to measure survival and efficacy of Cry3Bb1 maize in calcareous and non-calcareous soils. Results showed that there was not a significant difference in expression of Cry3Bb1 protein between plants from calcareous and non-calcareous soils (18.9-21.2 µg/g fresh weight). Western corn rootworm survival was about sevenfold greater from the non-Bt isoline than Cry3Bb1 maize indicating that Cry3Bb1 performed as expected when infested with a Cry3Bb1 susceptible rootworm population. When survival from calcareous and non-calcareous soils was compared, no significant differences were observed in each soil. A significant positive correlation between soil pH and expression of Cry3Bb1 protein in roots was detected from samples collected in 2014 but not in 2013. No such correlation was found between soil pH and survival of WCR. Results suggest that Cry3Bb1 expression levels were sufficient to provide adequate root protection against WCR regardless of soil environment, indicating that lowered Cry3Bb1 expression is not a contributing factor to the greater than expected WCR injury observed in some southwestern Nebraska

  11. In vitro comparison of the efficacy of TGF-β1 and PDGF-BB in combination with freeze-dried bone allografts for induction of osteogenic differentiation in MG-63 osteoblast-like cells.

    PubMed

    Vahabi, Surena; Torshabi, Maryam; Esmaeil Nejad, Azadeh

    2016-12-01

    Predictable regeneration of alveolar bone defects has always been a challenge in implant dentistry. Bone allografts are widely used bone substitutes with controversial osteoinductive activity. This in vitro study aimed to assess the osteogenic potential of some commercially available freeze-dried bone allografts supplemented with human recombinant platelet-derived growth factor-BB and transforming growth factor beta-1. Cell viability, mineralization, and osteogenic gene expression of MG-63 osteoblast-like cells were compared among the allograft alone, allograft/platelet-derived growth factor-BB, allograft/transforming growth factor beta-1, and allograft/platelet-derived growth factor-BB/transforming growth factor beta-1 groups. The methyl thiazol tetrazolium assay, real-time quantitative reverse transcription polymerase chain reaction and alizarin red staining were performed, respectively, for assessment of cell viability, differentiation, and mineralization at 24-72 h post treatment. The allograft with greater cytotoxic effect on MG-63 cells caused the lowest differentiation among the groups. In comparison with allograft alone, allograft/transforming growth factor beta-1, and allograft/transforming growth factor beta-1/platelet-derived growth factor-BB caused significant upregulation of bone sialoprotein and osteocalcin osteogenic mid-late marker genes, and resulted in significantly higher amounts of calcified nodules especially in mineralized non-cytotoxic allograft group. Supplementation of platelet-derived growth factor-BB alone in 5 ng/mL concentration had no significant effect on differentiation or mineralization markers. According to the results, transforming growth factor beta-1 acts synergistically with bone allografts to enhance the osteogenic differentiation potential. Therefore, this combination may be useful for rapid transformation of undifferentiated cells into bone-forming cells for bone regeneration. However, platelet-derived growth factor-BB

  12. Growth and adhesion to HT-29 cells inhibition of Gram-negatives by Bifidobacterium longum BB536 e Lactobacillus rhamnosus HN001 alone and in combination.

    PubMed

    Inturri, R; Stivala, A; Furneri, P M; Blandino, G

    2016-12-01

    The aim of this study was to test the inhibitory effect of supernatants of broth cultures of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001, both individually and in combination, against Gram-negative strains (uropathogens, enteropathogens and a reference strain). Moreover, in vitro protection of B. longum BB536 and L. rhamnosus HN001, both individually and in combination, against pathogen adhesion to HT-29 cell line, was investigated. The inhibitory activity was performed by the agar diffusion test and in vitro antagonistic activity against pathogen adhesion to human epithelial intestinal HT-29 cells was performed using standardized culture techniques. The study showed that B. longum BB536 and L. rhamnosus HN001, individually and in combination have inhibitory activity against the majority of the Gram negative strains tested. Furthermore, the results showed that both probiotic strains have a good capacity to inhibit pathogenic adhesion to HT-29 cells. Moreover, the ability of B. longum BB536 and L. rhamnosus HN001 to inhibit pathogenic adhesion increased when they were used in combination. The combination of B. longum BB536 and L. rhamnosus HN001 showed inhibitory activity against Gram-negatives and an improved ability to reduce their adhesion properties and to compete with them. The simultaneous presence of the two-probiotic strains could promote competitive mechanisms able to reduce the adhesion properties of pathogen strains and have an important ecological role within the highly competitive environment of the human gut.

  13. Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease.

    PubMed

    Padel, Thomas; Özen, Ilknur; Boix, Jordi; Barbariga, Marco; Gaceb, Abderahim; Roth, Michaela; Paul, Gesine

    2016-10-01

    Parkinson's disease (PD) is a neurodegenerative disease where the degeneration of the nigrostriatal pathway leads to specific motor deficits. There is an unmet medical need for regenerative treatments that stop or reverse disease progression. Several growth factors have been investigated in clinical trials to restore the dopaminergic nigrostriatal pathway damaged in PD. Platelet-derived growth factor-BB (PDGF-BB), a molecule that recruits pericytes to stabilize microvessels, was recently investigated in a phase-1 clinical trial, showing a dose-dependent increase in dopamine transporter binding in the putamen of PD patients. Interestingly, evidence is accumulating that PD is paralleled by microvascular changes, however, whether PDGF-BB modifies pericytes in PD is not known. Using a pericyte reporter mouse strain, we investigate the functional and restorative effect of PDGF-BB in a partial 6-hydroxydopamine medial forebrain bundle lesion mouse model of PD, and whether this restorative effect is accompanied by changes in pericyte features. We demonstrate that a 2-week treatment with PDGF-BB leads to behavioural recovery using several behavioural tests, and partially restores the nigrostriatal pathway. Interestingly, we find that pericytes are activated in the striatum of PD lesioned mice and that these changes are reversed by PDGF-BB treatment. The modulation of brain pericytes may contribute to the PDGF-BB-induced neurorestorative effects, PDGF-BB allowing for vascular stabilization in PD. Pericytes might be a new cell target of interest for future regenerative therapies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. 40 CFR Appendix A to Subpart Bb of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart BB

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... additional requirements. 63.7(f) Alternative Test Method Yes. 63.7(g) Data Analysis Yes. 63.7(h) Waiver of....8(g)(1) Data Reduction Yes. 63.8(g)(2) No Subpart BB does not require COMS or CEMS. 63.8(g)(3... Data Reports No Subpart BB does not require COMS. 63.10(f) Recordkeeping/Reporting Waiver Yes. 63.11(a...

  15. Safety and tolerability of intracerebroventricular PDGF-BB in Parkinson’s disease patients

    PubMed Central

    Paul, Gesine; Zachrisson, Olof; Varrone, Andrea; Almqvist, Per; Jerling, Markus; Lind, Göran; Rehncrona, Stig; Linderoth, Bengt; Bjartmarz, Hjalmar; Shafer, Lisa L.; Coffey, Robert; Svensson, Mikael; Mercer, Katarina Jansson; Forsberg, Anton; Halldin, Christer; Svenningsson, Per; Widner, Håkan; Frisén, Jonas; Pålhagen, Sven; Haegerstrand, Anders

    2015-01-01

    BACKGROUND. Recombinant human PDGF-BB (rhPDGF-BB) reduces Parkinsonian symptoms and increases dopamine transporter (DAT) binding in several animal models of Parkinson’s disease (PD). Effects of rhPDGF-BB are the result of proliferation of ventricular wall progenitor cells and reversed by blocking mitosis. Based on these restorative effects, we assessed the safety and tolerability of intracerebroventricular (i.c.v.) rhPDGF-BB administration in individuals with PD. METHODS. We conducted a double-blind, randomized, placebo-controlled phase I/IIa study at two clinical centers in Sweden. Twelve patients with moderate PD received rhPDGF-BB via an implanted drug infusion pump and an investigational i.c.v. catheter. Patients were assigned to a dose cohort (0.2, 1.5, or 5 μg rhPDGF-BB per day) and then randomized to active treatment or placebo (3:1) for a 12-day treatment period. The primary objective was to assess safety and tolerability of i.c.v.-delivered rhPDGF-BB. Secondary outcome assessments included several clinical rating scales and changes in DAT binding. The follow-up period was 85 days. RESULTS. All patients completed the study. There were no unresolved adverse events. Serious adverse events occurred in three patients; however, these were unrelated to rhPDGF-BB administration. Secondary outcome parameters did not show dose-dependent changes in clinical rating scales, but there was a positive effect on DAT binding in the right putamen. CONCLUSION. At all doses tested, i.c.v. administration of rhPDGF-BB was well tolerated. Results support further clinical development of rhPDGF-BB for patients with PD. TRIAL REGISTRATION. Clinical Trials.gov NCT00866502. FUNDING. Newron Sweden AB (former NeuroNova AB) and Swedish Governmental Agency for Innovation Systems (VINNOVA). PMID:25689258

  16. Evaluation of Recombinant Human FGF-2 and PDGF-BB in Periodontal Regeneration: A Systematic Review and Meta-Analysis.

    PubMed

    Li, Feifei; Yu, Fanyuan; Xu, Xin; Li, Chunjie; Huang, Dingming; Zhou, Xuedong; Ye, Ling; Zheng, Liwei

    2017-03-06

    The prognosis for successful treatment of periodontal diseases is generally poor. Current therapeutic strategies often fail to regenerate infected periodontium. Recently an alternative strategy has been developed that combines conventional treatment with the application of recombinant human growth factors (rhGFs). But ambiguities in existed studies on the clinical efficacy of rhGFs do not permit either the identification of the specific growth factors effective for therapeutic interventions or the optimal concentration of them. Neither is it known whether the same rhGF can stimulate regeneration of both soft tissue and bone, or whether different patient populations call for differential use of the growth factors. In order to explore these issues, a meta-analysis was carried out. Particular attention was given to the therapeutic impact of fibroblast growth factor 2(FGF-2) and platelet derived growth factor BB (PDGF-BB). Our findings indicate that 0.3% rhFGF-2 and 0.3 mg/ml rhPDGF-BB show a greater capacity for periodontal regeneration than other concentrations and superiority to control groups with statistical significance. In the case of patients suffering only from gingival recession, however, the application of rhPDGF-BB produces no significant regenerative advantage. The findings of this study can potentially endow clinicians with guidelines for the appropriate application of these two rhGFs.

  17. The Tick-Over Theory Revisited: Formation and Regulation of the Soluble Alternative Complement C3 Convertase (C3(H2O)Bb)

    PubMed Central

    Bexborn, Fredrik; Andersson, Per Ola; Chen, Hui; Nilsson, Bo; Ekdahl, Kristina N.

    2009-01-01

    The molecular interactions between the components of the C3 convertase of the alternative pathway (AP) of complement and its regulators, in both surface-bound and fluid-phase form, are still incompletely understood. The fact that the AP convertase is labile makes studies difficult to perform. According to the so called tick-over theory, hydrolyzed C3, called C3(H2O), forms the initial convertase in fluid phase together with factor B. In the present study, we have applied western blot analysis and ELISA together with fluorescence resonance energy transfer (FRET) to study the formation of the fluid-phase AP convertases C3(H2O)Bb and C3bBb and their regulation by factor H and factor I at specific time points and, with FRET, in real time. In our hands, factor B showed a higher affinity for C3(H2O) than for C3b, although in both cases it was readily activated to Bb. However, the convertase activity of C3bBb was approximately twice that of C3(H2O)Bb, as monitored by the generation of C3a. But in contrast, the C3(H2O)Bb convertase was more resistant to inactivation by factor H and factor I than was the C3bBb convertase. Under conditions that totally inactivated C3bBb, C3(H2O)Bb still retained approximately 25% of its initial activity. PMID:18096230

  18. The tick-over theory revisited: formation and regulation of the soluble alternative complement C3 convertase (C3(H2O)Bb).

    PubMed

    Bexborn, Fredrik; Andersson, Per Ola; Chen, Hui; Nilsson, Bo; Ekdahl, Kristina N

    2008-04-01

    The molecular interactions between the components of the C3 convertase of the alternative pathway (AP) of complement and its regulators, in both surface-bound and fluid-phase form, are still incompletely understood. The fact that the AP convertase is labile makes studies difficult to perform. According to the so called tick-over theory, hydrolyzed C3, called C3(H(2)O), forms the initial convertase in fluid phase together with factor B. In the present study, we have applied western blot analysis and ELISA together with fluorescence resonance energy transfer (FRET) to study the formation of the fluid-phase AP convertases C3(H(2)O)Bb and C3bBb and their regulation by factor H and factor I at specific time points and, with FRET, in real time. In our hands, factor B showed a higher affinity for C3(H(2)O) than for C3b, although in both cases it was readily activated to Bb. However, the convertase activity of C3bBb was approximately twice that of C3(H(2)O)Bb, as monitored by the generation of C3a. But in contrast, the C3(H(2)O)Bb convertase was more resistant to inactivation by factor H and factor I than was the C3bBb convertase. Under conditions that totally inactivated C3bBb, C3(H(2)O)Bb still retained approximately 25% of its initial activity.

  19. B.B. Contracting & Remodeling Information Sheet

    EPA Pesticide Factsheets

    B.B. Contracting & Remodeling (the Company) is located in St. Louis, Missouri. The settlement involves renovation activities conducted at property constructed prior to 1978, located in St. Louis, Missouri.

  20. COMPLEMENT ACTIVATION FRAGMENT Bb IN EARLY PREGNANCY AND SPONTANEOUS PRETERM BIRTH

    PubMed Central

    LYNCH, ANNE M.; GIBBS, RONALD S.; MURPHY, JAMES R.; BYERS, TIM; NEVILLE, MARGARET C.; GICLAS, PATRICIA C.; SALMON, JANE E.; VAN HECKE, TRISHA M; MICHAEL HOLERS, V.

    2008-01-01

    Objective To determine if an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks gestation or SPTB between 34 and 37 weeks gestation (late SPTB). Study Design Prospective study of 784 women enrolled at < 20 weeks gestation. Results Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks gestation and 25 (3.2%) a SPTB between 34 and 37 weeks gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks gestation as compared with women who had levels of Bb in the lower three quartiles (95% CI 1.5 to 14, P = 0.003). There was no association between Bb and late SPTB (RR= 0.8, 95% CI = 0.3 to 2). Conclusions A significant relationship was found between an elevated Bb in early pregnancy and SPTB < 34 weeks gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition. PMID:18928972

  1. A pancreatic venular defect in the BB/Wor rat.

    PubMed Central

    Majno, G.; Joris, I.; Handler, E. S.; Desemone, J.; Mordes, J. P.; Rossini, A. A.

    1987-01-01

    BB rats develop spontaneous autoimmune diabetes mellitus characterized morphologically by insulitis, an inflammatory lymphocytic infiltration of the islets of Langerhans. To investigate the role of the vascular endothelium of the pancreas in this destructive process, the authors injected diabetes-prone (DP) and diabetes-resistant (DR) BB/Wor rats as well as other nondiabetic strains of rats with Monastral blue B, a colloidal pigment that identifies leaky microvasculature. They found evidence of a venular defect limited to the pancreas that is specific to the BB rat. Light- and electron-microscopic evidence suggests that this defect is due to a population of trapped (marginating) intravascular monocytes, which may be activated by the colloidal pigment and release vasoactive mediators. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3618725

  2. Simple and efficient generation of virus-specific T cells for adoptive therapy using anti-4-1BB antibody.

    PubMed

    Imahashi, Nobuhiko; Nishida, Tetsuya; Goto, Tatsunori; Terakura, Seitaro; Watanabe, Keisuke; Hanajiri, Ryo; Sakemura, Reona; Imai, Misa; Kiyoi, Hitoshi; Naoe, Tomoki; Murata, Makoto

    2015-01-01

    Although recent studies of virus-specific T-cell (VST) therapy for viral infections after allogeneic hematopoietic stem cell transplantation have shown promising results, simple and less time-intensive and labor-intensive methods are required to generate VSTs for the wider application of VST therapy. We investigated the efficacy of anti-CD28 and anti-4-1BB antibodies, which can provide T cells with costimulatory signals similar in strength to those of antigen-presenting cells, in generating VSTs. When peripheral blood mononuclear cells were stimulated with viral peptides together with isotype control, anti-CD28, or anti-4-1BB antibodies, anti-4-1BB antibodies yielded the highest numbers of VSTs, which were on an average 7.9 times higher than those generated with isotype control antibody. The combination of anti-CD28 and anti-4-1BB antibodies did not result in increased numbers of VSTs compared with anti-4-1BB antibody alone. Importantly, the positive effect of anti-4-1BB antibody was observed regardless of the epitopes of the VSTs. In contrast, the capacity of dendritic cells (DCs) to generate VSTs differed considerably depending on the epitopes of the VSTs. Furthermore, the numbers of VSTs generated with DCs were at most similar to those generated with the anti-4-1BB antibody. Generation of VSTs with anti-4-1BB antibody did not result in excessive differentiation or deteriorated function of the generated VSTs compared with those generated with control antibody or DCs. In conclusion, VSTs can be generated rapidly and efficiently by simply stimulating peripheral blood mononuclear cells with viral peptide and anti-4-1BB antibody without using antigen-presenting cells. We propose using anti-4-1BB antibody as a novel strategy to generate VSTs for adoptive therapy.

  3. Complement activation fragment Bb in early pregnancy and spontaneous preterm birth.

    PubMed

    Lynch, Anne M; Gibbs, Ronald S; Murphy, James R; Byers, Tim; Neville, Margaret C; Giclas, Patricia C; Salmon, Jane E; Van Hecke, Trisha M; Holers, V Michael

    2008-10-01

    The objective of this study was to determine whether an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks' gestation or SPTB between 34 and 37 weeks' gestation (late SPTB). This was a prospective study of 784 women enrolled at less than 20 weeks' gestation. Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks' gestation and 25 (3.2%) a SPTB between 34 and 37 weeks' gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks' gestation as compared with women who had levels of Bb in the lower 3 quartiles (95% confidence interval [CI] 1.5-14, P = .003). There was no association between Bb and late SPTB (relative risk 0.8, 95% CI 0.3-2). A significant relationship was found between an elevated Bb in early pregnancy and SPTB less than 34 weeks' gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition.

  4. Crystal structure of the human 4-1BB/4-1BBL complex.

    PubMed

    Gilbreth, Ryan N; Oganesyan, Vaheh Y; Amdouni, Hamza; Novarra, Shabazz; Grinberg, Luba; Barnes, Arnita; Baca, Manuel

    2018-05-02

    4-1BBL is a member of the TNF superfamily and is the ligand for the TNFRsuperfamily receptor, 4-1BB. 4-1BB plays an immunomodulatory role in T cells and NK cells and agonists of this receptor have garnered strong attention as potentialimmunotherapy agents. Broadly speaking, the structural features of TNF superfamilymembers, their receptors and ligand/receptor complexes are similar. However, apublished crystal structure of human 4-1BBL suggests that it may be unique in thisregard, exhibiting a three-bladed propeller-like trimer assembly that is distinctly different from that observed in other family members. This unusual structure also suggests that the human 4-1BB/4-1BBL complex may be structurally unique within the TNF/TNFR superfamily, but to date no structural data have been reported. Here we report the crystal structure of the human 4-1BB/4-1BBL complex at 2.4 Å resolution. In this structure, 4-1BBL does not adopt the unusual trimer assembly previously reported, but instead forms a canonical bell-shaped trimer typical of other TNF superfamily members. The structure of 4-1BB is also largely canonical as is the 4-1BB/4-1BBL complex. Mutational data support the 4-1BBL structure reported here as being biologically relevant, suggesting that the previously reported structure is not. Together, the data presented here offer insight into structure/function relationships in the 4-1BB/4-1BBL system and improve our structural understanding of the TNF/TNFR superfamily more broadly. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Immunization with a Borrelia burgdorferi BB0172-Derived Peptide Protects Mice against Lyme Disease

    PubMed Central

    Small, Christina M.; Ajithdoss, Dharani K.; Rodrigues Hoffmann, Aline; Mwangi, Waithaka; Esteve-Gassent, Maria D.

    2014-01-01

    Lyme disease is the most prevalent arthropod borne disease in the US and it is caused by the bacterial spirochete Borrelia burgdorferi (Bb), which is acquired through the bite of an infected Ixodes tick. Vaccine development efforts focused on the von Willebrand factor A domain of the borrelial protein BB0172 from which four peptides (A, B, C and D) were synthesized and conjugated to Keyhole Limpet Hemocyanin, formulated in Titer Max® adjuvant and used to immunize C3H/HeN mice subcutaneously at days 0, 14 and 21. Sera were collected to evaluate antibody responses and some mice were sacrificed for histopathology to evaluate vaccine safety. Twenty-eight days post-priming, protection was evaluated by needle inoculation of half the mice in each group with 103 Bb/mouse, whereas the rest were challenged with 105Bb/mouse. Eight weeks post-priming, another four groups of similarly immunized mice were challenged using infected ticks. In both experiments, twenty-one days post-challenge, the mice were sacrificed to determine antibody responses, bacterial burdens and conduct histopathology. Results showed that only mice immunized with peptide B were protected against challenge with Bb. In addition, compared to the other the treatment groups, peptide B-immunized mice showed very limited inflammation in the heart and joint tissues. Peptide B-specific antibody titers peaked at 8 weeks post-priming and surprisingly, the anti-peptide B antibodies did not cross-react with Bb lysates. These findings strongly suggest that peptide B is a promising candidate for the development of a new DIVA vaccine (Differentiate between Infected and Vaccinated Animals) for protection against Lyme disease. PMID:24505447

  6. Control of Human Endometrial Stromal Cell Motility by PDGF-BB, HB-EGF and Trophoblast-Secreted Factors

    PubMed Central

    Schwenke, Maren; Knöfler, Martin; Velicky, Philipp; Weimar, Charlotte H. E.; Kruse, Michelle; Samalecos, Annemarie; Wolf, Anja; Macklon, Nick S.; Bamberger, Ana-Maria; Gellersen, Birgit

    2013-01-01

    Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of

  7. Synergistic effects of FGF-2 and PDGF-BB on angiogenesis and muscle regeneration in rabbit hindlimb ischemia model.

    PubMed

    Li, Jie; Wei, Yuquan; Liu, Kang; Yuan, Chuang; Tang, Yajuan; Quan, Qingli; Chen, Ping; Wang, Wei; Hu, Huozhen; Yang, Li

    2010-07-01

    Combinatorial strategy has been used in therapeutic angiogenesis in animal models of peripheral arterial disease (PAD) and coronary artery disease for decades. Previous studies have shown that basic fibroblast growth factor (FGF-2) and platelet-derived growth factor BB (PDGF-BB) proteins together establish functional and stable vascular networks on mouse corneal and also in animal model of hindlimb ischemia. However, the short half life of protein by single injection is not sufficient to achieve effective dosage, repeated and prolonged injection causes systemic toxicity. Here we study the synergistic effects of FGF-2 and PDGF-BB by intramuscular injection of naked plasmid DNA on therapeutic angiogenesis in rabbit model of hindlimb ischemia. We found that transient delivery of FGF-2 and PDGF-BB naked DNA together resulted in greater increases in capillary growth, collateral formation and popliteal blood flow compared with control and single gene delivery. Our data provided novel evidence of beneficial effects of DNA-based FGF-2 and PDFG-BB on muscle repair after ischemic injury. These findings reveal an alternative therapeutic approach in the treatment of ischemic diseases and even in muscular disorders. Copyright 2010. Published by Elsevier Inc.

  8. A highly sensitive and selective aptasensor based on graphene oxide fluorescence resonance energy transfer for the rapid determination of oncoprotein PDGF-BB.

    PubMed

    Liang, Junfei; Wei, Ran; He, Shuai; Liu, Yikan; Guo, Lin; Li, Lidong

    2013-03-21

    Oncoprotein platelet derived growth factor-BB (PDGF-BB) is one of the most critical growth factors that regulates tumor growth and division. In this work, a highly sensitive and selective fluorescence resonance energy transfer (FRET) aptasensor for PDGF-BB detection based on the assembly of dye-labeled aptamer and graphene oxide (GO) is developed for the first time. Due to the non-covalent assembly between aptamer and GO, fluorescence quenching of the dye takes place because of FRET. In the presence of PDGF-BB, the binding between aptamer and PDGF-BB will disturb the interaction between aptamer and GO, and release the dye-labeled aptamer from the GO surface, resulting in restoration of the fluorophore fluorescence. Because of the high fluorescence quenching efficiency, unique structure, and electronic properties of GO, the GO aptasensor exhibits extraordinarily high sensitivity. We also demonstrate that two highly related molecular variants of PDGF (AA, AB) can be distinguished from PDGF-BB, which indicates the aptasensor has excellent selectivity. Such an aptasensor opens a rapid, selective and sensitive route for the detection of PDGF-BB and provides a promising strategy for other cancer-related proteins detections.

  9. Effects of PDGF-BB delivery from heparinized collagen sutures on the healing of lacerated chicken flexor tendon in vivo.

    PubMed

    Younesi, Mousa; Knapik, Derrick M; Cumsky, Jameson; Donmez, Baris Ozgur; He, Ping; Islam, Anowarul; Learn, Greg; McClellan, Philip; Bohl, Michael; Gillespie, Robert J; Akkus, Ozan

    2017-11-01

    Flexor tendon lacerations are traditionally repaired by using non-absorbable monofilament sutures. Recent investigations have explored to improve the healing process by growth factor delivery from the sutures. However, it is difficult to conjugate growth factors to nylon or other synthetic sutures. This study explores the performance of a novel electrochemically aligned collagen suture in a flexor tendon repair model with and without platelet derived growth factor following complete tendon laceration in vivo. Collagen suture was fabricated via electrochemical alignment process. Heparin was covalently bound to electrochemically aligned collagen sutures (ELAS) to facilitate affinity bound delivery of platelet-derived growth factor-BB (PDGF-BB). Complete laceration of the flexor digitorum profundus in the third digit of the foot was performed in 36 skeletally mature White Leghorn chickens. The left foot was used as the positive control. Animals were randomly divided into three groups: control specimens treated with standard nylon suture (n=12), specimens repaired with heparinated ELAS suture without PDGF-BB (n=12) and specimens repaired with heparinated ELAS suture with affinity bound PDGF-BB (n=12). Specimens were harvested at either 4weeks or 12weeks following tendon repair. Differences between groups were evaluated by the degree of gross tendon excursion, failure load/stress, stiffness/modulus, absorbed energy at failure, elongation/strain at failure. Quantitative histological scoring was performed to assess cellularity and vascularity. Closed flexion angle measurements demonstrated no significant differences in tendon excursion between the study groups at 4 or 12weeks. Biomechanical testing showed that the group treated with PDGF-BB bound heparinated ELAS suture had significantly higher stiffness and failure load (p<0.05) at 12-weeks relative to both heparinated ELAS suture and nylon suture. Similarly, the group treated with PDGF-BB bound suture had significantly

  10. Effect of Photobiomodulation on Transforming Growth Factor-β1, Platelet-Derived Growth Factor-BB, and Interleukin-8 Release in Palatal Wounds After Free Gingival Graft Harvesting: A Randomized Clinical Study

    PubMed Central

    Lutfioğlu, Muge; Aydogdu, Ahmet; Saygun, N. Isil; Serdar, Muhittin A.

    2016-01-01

    Abstract Objective: This study evaluated the impact of photobiomodulation (PBM) on the healing of the donor palatal area following free gingival graft (FGG) harvesting by examining changes in transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-BB, and interleukin (IL)-8 levels in palatal wound fluid (PWF). Material and methods: Thirty patients were selected and randomly assigned to receive PBM (laser group) or PBM sham (sham group) in the palatine area after FGG harvesting. A neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (1064 nm) was applied to the test sites immediately after surgery and every 24 h thereafter for 4 days. PWF was collected on Days 7 and 12, and PWF TGF-β1, PDGF-BB, and IL-8 levels were analyzed by enzyme-linked immunosorbent assays (ELISA). Results: PWF TGF-β1, PDGF-BB, and IL-8 levels were significantly lower on Day 12 than on Day 7 for both groups. PWF TGF-β1, PDGF-BB, and IL-8 levels of the laser group were significantly higher than those of sham group on Day 7 (p < 0.05). PWF TGF-β1 levels were also significantly higher in laser group than in the sham group on Day 12; however, differences in PDGF-BB and IL-8 levels between groups on Day 12 were statistically nonsignificant. Conclusions: Observed increases in PWF TGF-β1, PDGF-BB, and IL-8 levels suggest that PBM may accelerate wound healing by stimulating production of selected mediators. PMID:27088277

  11. Program BB for calculation of PEP corrector strengths for beam-bump excitation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kheifets, S.

    Excitation of a beam-bump (BB) can be effectively used for a number of goals. Since BB is sensitive only to perturbations of elements which are located inside it, errors and their consequencies spaced separately can be singled out and studied one by one. This technique in principle can be used to study the uniformity of the quadrupole distribution around the ring, the beam stays clear size of the machine at different locations, the polarity and probably even the strength of sextupole magnets, alignments of different monitors, etc. It can be used also to increase the beam cross section if thatmore » appears to be desirable. Design of PEP correctors does not allow to use them for excitation of a halfwave BB. The minimum number of correctors which can be used in this situation is three. The situation for horizontal plane is aggravated still more since most of horizontal correctors are hooked in pairs. The presence of sextupole magnets interlacing the correctors makes it necessary to use iterative procedure to find the corrector strengths for BB, since a perturbed orbit is influenced by a field of a sextupole magnet which in turn depends on the perturbed orbit value in the sextupole. Since the strength of sextupoles are rather small as the first guess of corrector strengths for iterative procedure can be taken the linear solution neglecting sextupoles. This paper describes the program BB itself, and some results of calculations with BB for PEP. 3 refs., 4 figs., 6 tabs.« less

  12. Multimodal Broadband Vibrational Sum Frequency Generation (MM-BB-V-SFG) Spectrometer and Microscope.

    PubMed

    Lee, Christopher M; Kafle, Kabindra; Huang, Shixin; Kim, Seong H

    2016-01-14

    A broadband sum frequency generation (BB-SFG) spectrometer with multimodal (MM) capabilities was constructed, which could be routinely reconfigured for tabletop experiments in reflection, transmission, and total internal reflection (TIR) geometries, as well as microscopic imaging. The system was constructed using a Ti:sapphire amplifier (800 nm, pulse width = 85 fs, repetition rate = 2 kHz), an optical parameter amplification (OPA) system for production of broadband IR pulses tunable between 1000 and 4000 cm(-1), and two Fabry-Pérot etalons arranged in series for production of narrowband 800 nm pulses. The key feature allowing the MM operation was the nearly collinear alignment of the visible (fixed, 800 nm) and infrared (tunable, 1000-4000 cm(-1)) pulses which were spatially separated. Physical insights discussed in this paper include the comparison of spectral bandwidth produced with 40 and 85 fs pump beams, the improvement of spectral resolution using etalons, the SFG probe volume in bulk analysis, the normalization of SFG signals, the stitching of multiple spectral segments, and the operation in different modes for air/liquid and adsorbate/solid interfaces, bulk samples, as well as spectral imaging combined with principle component analysis (PCA). The SFG spectral features obtained with the MM-BB-SFG system were compared with those obtained with picosecond-scanning-SFG system and high-resolution BB-SFG system (HR-BB-SFG) for dimethyl sulfoxide, α-pinene, and various samples containing cellulose (purified commercial products, Cladophora cell wall, cotton and flax fibers, and onion epidermis cell wall).

  13. High temperature blackbody BB2000/40 for calibration of radiation thermometers and thermocouple

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ogarev, S. A.; Khlevnoy, B. B.; Samoylov, M. L.

    2013-09-11

    The cavity-type high temperature blackbody (HTBB) models of BB3200/3500 series are the most spread among metrological institutes worldwide as sources for radiometry and radiation thermometry, due to their ultra high working temperatures, high emissivity and stability. The materials of radiating cavities are graphite, pyrolytic graphite (PG) and their combination. The paper describes BB2000/40 blackbody with graphite-tube cavity that was developed for calibration of radiation thermometers at SCEI (Singapore). The peculiarity of BB2000/40 is a possibility to use it, besides calibration of pyrometers, as an instrument for thermocouples calibration. Operating within the temperature range from 900 °C to 2000 °C, themore » blackbody has a wide cavity opening of 40 mm. Emissivity of the cavity, with PG heater rings replaced partly by graphite elements, was estimated as 0.998 ± 0.0015 in the spectral range from 350 nm to 2000 nm. The uniformity along the cavity axis, accounting for 10 °C, was measured using a B-type thermocouple at 1500 °C. The BB2000/40, if necessary, can be easily modified, by replacing the graphite radiator with a set of PG rings, to be able to reach temperatures as high as 3200 °C. The HTBB utilizes an optical feedback system which allows temperature stabilization within 0.1 °C. This rear-view feedback allows the whole HTBB aperture to be used for measurements.« less

  14. Selection of single chain antibody fragments binding to the extracellular domain of 4-1BB receptor by phage display technology.

    PubMed

    Bagheri, Salman; Yousefi, Mehdi; Safaie Qamsari, Elmira; Riazi-Rad, Farhad; Abolhassani, Mohsen; Younesi, Vahid; Dorostkar, Ruhollah; Movassaghpour, Ali Akbar; Sharifzadeh, Zahra

    2017-03-01

    The 4-1BB is a surface glycoprotein that pertains to the tumor necrosis factor-receptor family. There is compelling evidence suggesting important roles for 4-1BB in the immune response, including cell activation and proliferation and also cytokine induction. Because of encouraging results of different agonistic monoclonal antibodies against 4-1BB in the treatment of cancer, infectious, and autoimmune diseases, 4-1BB has been suggested as an attractive target for immunotherapy. In this study, single chain variable fragment phage display libraries, Tomlinson I+J, were screened against specific synthetic oligopeptides (peptides I and II) designed from 4-1BB extracellular domain. Five rounds of panning led to selection of four 4-1BB specific single chain variable fragments (PI.12, PI.42, PII.16, and PII.29) which showed specific reaction to relevant peptides in phage enzyme-linked immunosorbent assay. The selected clones were successfully expressed in Escherichia coli Rosetta-gami 2, and their expression was confirmed by western blot analysis. Enzyme-linked immunosorbent assay experiments indicated that these antibodies were able to specifically recognize 4-1BB without any cross-reactivity with other antigens. Flow cytometry analysis demonstrated an acceptable specific binding of the single chain variable fragments to 4-1BB expressed on CCRF-CEM cells, while no binding was observed with an irrelevant antibody. Anti-4-1BB single chain variable fragments enhanced surface CD69 expression and interleukin-2 production in stimulated CCRF-CEM cells which confirmed the agonistic effect of the selected single chain variable fragments. The data from this study have provided a rationale for further experiments involving the biological functions of anti-4-1BB single chain variable fragments in future studies.

  15. Platelet-Derived Growth Factor-BB Protects Mesenchymal Stem Cells (MSCs) Derived From Immune Thrombocytopenia Patients Against Apoptosis and Senescence and Maintains MSC-Mediated Immunosuppression

    PubMed Central

    Zhang, Jia-min; Feng, Fei-er; Wang, Qian-ming; Zhu, Xiao-lu; Fu, Hai-xia; Xu, Lan-ping; Liu, Kai-yan

    2016-01-01

    Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Mesenchymal stem cells (MSCs) from ITP patients (MSC-ITP) do not exhibit conventional proliferative abilities and thus exhibit defects in immunoregulation, suggesting that MSC impairment might be a mechanism involved in ITP. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types. Moreover, PDGF promotes MSC proliferation. The aim of the present study was to analyze the effects of PDGF-BB on MSC-ITP. We showed that MSC-ITP expanded more slowly and appeared flattened and larger. MSC-ITP exhibited increased apoptosis and senescence compared with controls. Both the intrinsic and extrinsic pathways account for the enhanced apoptosis. P53 and p21 expression were upregulated in MSC-ITP, but inhibition of p53 with pifithrin-α markedly inhibited apoptosis and senescence. Furthermore, MSCs from ITP patients showed a lower capacity for inhibiting the proliferation of activated T cells inducing regulatory T cells (Tregs) and suppressing the synthesis of anti-glycoprotein (GP)IIb-IIIa antibodies. PDGF-BB treatment significantly decreased the expression of p53 and p21 and increased survivin expression in MSC-ITP. In addition, the apoptotic rate and number of senescent cells in ITP MSCs were reduced. Their impaired ability for inhibiting activated T cells, inducing Tregs, and suppressing the synthesis of anti-GPIIb-IIIa antibodies was restored after PDGF-BB treatment. In conclusion, we have demonstrated that PDGF-BB protects MSCs derived from ITP patients against apoptosis, senescence, and immunomodulatory defects. This protective effect of PDGF-BB is likely mediated via the p53/p21 pathway, thus potentially providing a new therapeutic approach for ITP. Significance Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Platelet-derived growth factor (PDGF) improves growth and survival in various

  16. An Investigation of Hierachical Protein Recruitment to the Inhibitory Platelet Receptor, G6B-b

    PubMed Central

    Coxon, Carmen H.; Sadler, Amanda J.; Huo, Jiandong; Campbell, R. Duncan

    2012-01-01

    Platelet activation is regulated by both positive and negative signals. G6B-b is an inhibitory platelet receptor with an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif (ITSM). The molecular basis of inhibition by G6B-b is currently unknown but thought to involve the SH2 domain-containing tyrosine phosphatase SHP-1. Here we show that G6B-b also associates with SHP-2, as well as SHP-1, in human platelets. Using a number of biochemical approaches, we found these interactions to be direct and that the tandem SH2 domains of SHP-2 demonstrated a binding affinity for G6B-b 100-fold higher than that of SHP-1. It was also observed that while SHP-1 has an absolute requirement for phosphorylation at both motifs to bind, SHP-2 can associate with G6B-b when only one motif is phosphorylated, with the N-terminal SH2 domain and the ITIM being most important for the interaction. A number of other previously unreported SH2 domain-containing proteins, including Syk and PLCγ2, also demonstrated specificity for G6B-b phosphomotifs and may serve to explain the observation that G6B-b remains inhibitory in the absence of both SHP-1 and SHP-2. In addition, the presence of dual phosphorylated G6B-b in washed human platelets can reduce the EC50 for both CRP and collagen. PMID:23185356

  17. Effects of Non-Collagenous Proteins, TGF-β1, and PDGF-BB on Viability and Proliferation of Dental Pulp Stem Cells

    PubMed Central

    Tabatabaei, Fahimeh Sadat

    2016-01-01

    ABSTRACT Objectives The dentin matrix servers as a reservoir of growth factors, sequestered during dentinogenesis. The aim of this study was to assess the viability and proliferation of dental pulp stem cells in the presence of dentin matrix-derived non-collagenous proteins and two growth factors; platelet-derived growth factor BB and transforming growth factor beta 1. Material and Methods The dental pulp cells were isolated and cultured. The dentin proteins were extracted and purified. The MTT assay was performed for assessment of cell viability and proliferation in the presence of different concentrations of dentin proteins and growth factors during 24 - 72 h post-treatment. Results The cells treated with 250 ng/mL dentin proteins had the best viability and proliferation ability in comparison with other concentrations (P < 0.05). The MTT assay demonstrated that cells cultured with 5 ng/mL platelet-derived growth factor BB had the highest viability at each time point as compared to other groups (P < 0.05). However, in presence of platelet-derived growth factor BB alone and in combination with transforming growth factor beta 1 and dentin proteins (10 ng/mL), significant higher viability was seen at all time points (P < 0.05). The least viability and proliferation at each growth factor concentration was seen in cells treated with combination of transforming growth factor beta 1 and dentin proteins at 72 h (P < 0.05). Conclusions The results indicated that the triple combination of growth factors and matrix-derived non-collagenous proteins (especially at 10 ng/mL concentration) has mitogenic effect on dental pulp stem cells. PMID:27099698

  18. Alternative complement pathway activation fragment Bb in early pregnancy as a predictor of preeclampsia

    PubMed Central

    Lynch, Anne M.; Murphy, James R.; Byers, Tim; Gibbs, Ronald S.; Neville, Margaret C.; Giclas, Patricia C.; Salmon, Jane E.; Holers, V. Michael

    2008-01-01

    OBJECTIVE Preeclampsia is a multisystem disease classically defined on the basis of hypertension and proteinuria. As shown in animal studies, complement activation is associated with inflammation in the placenta and adverse pregnancy outcomes. The association between complement activation in humans and adverse pregnancy outcomes is unclear. The purpose of this study was to determine whether elevated levels of the activation fragment Bb in early pregnancy are predictive of preeclampsia. STUDY DESIGN This prospective study of 701 women was conducted in Denver, CO. A single plasma sample was obtained from each woman before 20 weeks’ gestation. The cohort was followed up throughout pregnancy for the development of preeclampsia. Analysis included multivariate logistic regression to adjust for established risk factors for preeclampsia. RESULTS Preeclampsia developed in 4.6% of the cohort. Women with elevated Bb (90th or greater percentile) were substantially more likely to develop preeclampsia than women who had levels less than the 90th percentile (unadjusted relative risk [RR], 3.3, 95% confidence interval [CI] 1.6 to 7, P = .0009). Other significant risk factors for preeclampsia included nulliparity (RR, 2.1, 95% CI, 1–4), a high body mass index (P = .006 for trend), and maternal medical (preexisting maternal hypertension, type 1 diabetes, systemic lupus erythematosus) disease (RR, 4.4, 95% CI, 2–10). Significant risk factors among multiparous women included a history of hypertension in a previous pregnancy (RR, 5, 95% CI, 1.6 to 16) and a change of paternity (RR, 5.1, 95% CI, 1.6 to 15). Adjustment for risk factors did not attenuate the association between an elevated Bb and preeclampsia (adjusted odds ratio [OR], 3.8, 95% CI, 1.6 to 9, P = .002) in the cohort. After removing women with plasma obtained before 10 weeks, the adjusted OR of Bb in the top decile for preeclampsia was 6.1 (95% CI 2.2, 17, P = .0005). CONCLUSION The complement activation product Bb in

  19. PDGF-BB induces vascular smooth muscle cell expression of high molecular weight FGF-2, which accumulates in the nucleus.

    PubMed

    Pintucci, Giuseppe; Yu, Pey-Jen; Saponara, Fiorella; Kadian-Dodov, Daniella L; Galloway, Aubrey C; Mignatti, Paolo

    2005-08-15

    Basic fibroblast growth factor (FGF-2) and platelet-derived growth factor (PDGF) are implicated in vascular remodeling secondary to injury. Both growth factors control vascular endothelial and smooth muscle cell proliferation, migration, and survival through overlapping intracellular signaling pathways. In vascular smooth muscle cells PDGF-BB induces FGF-2 expression. However, the effect of PDGF on the different forms of FGF-2 has not been elucidated. Here, we report that treatment of vascular aortic smooth muscle cells with PDGF-BB rapidly induces expression of 20.5 and 21 kDa, high molecular weight (HMW) FGF-2 that accumulates in the nucleus and nucleolus. Conversely, PDGF treatment has little or no effect on 18 kDa, low-molecular weight FGF-2 expression. PDGF-BB-induced upregulation of HMW FGF-2 expression is controlled by sustained activation of extracellular signal-regulated kinase (ERK)-1/2 and is abolished by actinomycin D. These data describe a novel interaction between PDGF-BB and FGF-2, and indicate that the nuclear forms of FGF-2 may mediate the effect of PDGF activity on vascular smooth muscle cells.

  20. Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine.

    PubMed

    Danchin, M; Kirkwood, C D; Lee, K J; Bishop, R F; Watts, E; Justice, F A; Clifford, V; Cowley, D; Buttery, J P; Bines, J E

    2013-05-28

    RV3 is a human neonatal rotavirus strain (G3P[6]) that has been associated with asymptomatic neonatal infection and replicates well in the infant gut. RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth. A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3×10(6)FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort). Vaccine take was defined as seroconversion (a 3-fold increase in serum anti-rotavirus IgA or serum neutralising antibody (SNA) from baseline at day 28 post-dose) or evidence of RV3-BB viral replication in the faeces by RT-PCR analysis 3-6 days post-vaccination. RV3-BB presence was confirmed by sequence analysis. The RV3-BB vaccine was well tolerated in all participants, with no pattern of adverse events shown to be associated with the study vaccine. In the infant cohort, vaccine take was demonstrated in 8/9 infants following a single dose of vaccine compared with 2/7 placebo recipients. In the infant vaccine group, 5/9 infants exhibited either IgA or SNA seroconversion and 7/9 infants had evidence of RV3-BB replication on days 3-6, compared with 2/7 infants who seroconverted and 0/10 infants with evidence of replication in the placebo group. Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant. A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Human neutrophil peptides and complement factor Bb in pathogenesis of acquired thrombotic thrombocytopenic purpura.

    PubMed

    Cao, Wenjing; Pham, Huy P; Williams, Lance A; McDaniel, Jenny; Siniard, Rance C; Lorenz, Robin G; Marques, Marisa B; Zheng, X Long

    2016-11-01

    Acquired thrombotic thrombocytopenic purpura is primarily caused by the deficiency of plasma ADAMTS13 activity resulting from autoantibodies against ADAMTS13. However, ADAMTS13 deficiency alone is often not sufficient to cause acute thrombotic thrombocytopenic purpura. Infections or systemic inflammation may precede acute bursts of the disease, but the underlying mechanisms are not fully understood. Herein, 52 patients with acquired autoimmune thrombotic thrombocytopenic purpura and 30 blood donor controls were recruited for the study. The plasma levels of human neutrophil peptides 1-3 and complement activation fragments (i.e. Bb, iC3b, C4d, and sC5b-9) were determined by enzyme-linked immunosorbent assays. Univariate analyses were performed to determine the correlation between each biomarker and clinical outcomes. We found that the plasma levels of human neutrophil peptides 1-3 and Bb in patients with acute thrombotic thrombocytopenic purpura were significantly higher than those in the control (P<0.0001). The plasma levels of HNP1-3 correlated with the levels of plasma complement fragment Bb (rho=0.48, P=0.0004) and serum lactate dehydrogenase (rho=0.28, P=0.04); in addition, the plasma levels of Bb correlated with iC3b (rho=0.55, P<0.0001), sC5b-9 (rho=0.63, P<0.0001), serum creatinine (rho=0.42, p=0.0011), and lactate dehydrogenase (rho=0.40, P=0.0034), respectively. Moreover, the plasma levels of iC3b and sC5b-9 were correlated (rho=0.72, P<0.0001), despite no statistically significant difference of the two markers between thrombotic thrombocytopenic purpura patients and the control. We conclude that innate immunity, i.e. neutrophil and complement activation via the alternative pathway, may play a role in the pathogenesis of acute autoimmune thrombotic thrombocytopenic purpura, and a therapy targeted at these pathways may be considered in a subset of these patients. Copyright© Ferrata Storti Foundation.

  2. Abnormal TNF-alpha production in diabetes-prone BB rats: enhanced TNF-alpha expression and defective PGE2 feedback inhibition.

    PubMed Central

    Rothe, H; Ongören, C; Martin, S; Rösen, P; Kolb, H

    1994-01-01

    Upon stimulation with lipopolysaccharide (LPS), peritoneal macrophages from diabetes-prone Bio-Breeding (BB) rats secrete more tumour necrosis factor-alpha (TNF-alpha) than macrophages from diabetes-resistant BB or normal Wistar rats. Enhanced transcription was demonstrated by Northern blot analysis and at the single cell level by mRNA: RNA hybridization. Cytofluorometry analysis showed 2-4 times more plasma membrane and total cell-associated TNF-alpha in macrophages of diabetes-prone BB rats. The analysis of fluorescence intensity showed a single peak, and TNF-alpha mRNA was found in > 90% of macrophages. These findings exclude TNF hypersecretion as being due to an abnormal subfraction of cells. TNF-alpha gene hyperexpression in diabetes-prone BB rats was not due to mutations in the regulatory regions of the promoter, which could be shown by cloning and sequencing of the TNF-alpha promoter in the three rat strains. When searching for other regulatory defects we found the production of prostaglandin E2 (PGE2) in response to LPS to be up to 10 times lower in macrophages from diabetes-prone BB rats than from Wistar rats. Furthermore, BB rats macrophages required significantly higher concentrations of PGE2 for suppression of TNF-alpha secretion. We conclude that abnormal TNF-alpha production in macrophages from diabetes-prone BB rats is due to enhanced gene transcription and translation and that this is associated with defective PGE2 feedback inhibition. Images Figure 1 Figure 2 PMID:8206514

  3. King's Health Partners' Prostate Cancer Biobank (KHP PCaBB).

    PubMed

    Saifuddin, S R; Devlies, W; Santaolalla, A; Cahill, F; George, G; Enting, D; Rudman, S; Cathcart, P; Challacombe, B; Dasgupta, P; Galustian, C; Chandra, A; Chowdhury, S; Gillett, C; Van Hemelrijck, M

    2017-11-22

    The KHP PCaBB was established in 2013 and recruits donors from the Urology or Oncology Departments at Guy's Hospital in London (UK). Prostate cancer patients may be approached to give their consent for biobanking at any point in their treatment pathway, which allows residual material from their earlier diagnosis to be transferred and used by the Biobank. Currently, patients are specifically asked to donate samples of blood and surplus prostate tissue as well as permitting access to their clinical and pathological data that continues to be added throughout the course of their disease. Between 2013 and 2015, 549 prostate cancer patients gave their consent to the biobank and, the tissue repository collected 489 blood samples, 120 frozen prostate tissue samples and 1064 formalin fixed paraffin embedded diagnostic blocks.Prostate cancer has become a chronic disease in a large proportion of men, with many men receiving multiple subsequent treatments, and their treatment trajectory often spanning over decades. Therefore, this resource aims to provide an ideal research platform to explore potential variations in treatment response as well as disease markers in the different risk categories for prostate cancer.A recent audit of the KHP PCaBB revealed that between 2013 and 2015, 1796 patients were diagnosed with prostate cancer at King's Health Partners (KHP), out of which 549 (30.6%) gave their consent to KHP PCaBB. Comparisons between demographic and clinical characteristics of patients who had consented compared to the total patient population revealed that the KHP PCaBB is demographically representative of the total prostate cancer patient population seen in Guy's and St Thomas' NHS Foundation Trust (GSTT). We observed no differences in distribution of ethnicity (p = 0.507) and socioeconomic status (p = 0.097). Some differences were observed in clinical characteristics, specifically with treatment type - which differed significantly between the patients who had

  4. Human neonatal rotavirus vaccine (RV3-BB) targets rotavirus from birth

    PubMed Central

    Thobari, Jarir At; Satria, Cahya Dewi; Handley, Amanda; Watts, Emma; Cowley, Daniel; Nirwati, Hera; Ackland, James; Standish, Jane; Justice, Frances; Byars, Gabrielle; Lee, Katherine J.; Barnes, Graeme L.; Bachtiar, Novilia S.; Icanervilia, Ajeng Viska; Boniface, Karen; Bogdanovic-Sakran, Nada; Pavlic, Daniel; Bishop, Ruth F.; Kirkwood, Carl D.; Buttery, Jim P.; Soenarto, Yati

    2018-01-01

    Background A birth dose strategy using a neonatal rotavirus vaccine to target early prevention of rotavirus disease may address remaining barriers to global vaccine implementation. Methods We conducted a randomized, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) to prevent rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB administered in a neonatal schedule at 0-5 days, 8 and 14 weeks or infant schedule at 8, 14 and 18 weeks, or placebo. Laboratory-confirmed rotavirus gastroenteritis was graded using a modified Vesikari score. The primary analysis was efficacy against severe rotavirus gastroenteritis from two weeks after all doses to 18 months in the combined vaccine group (neonatal and infant schedule) compared with placebo. Results Vaccine efficacy against severe rotavirus gastroenteritis to 18 months was 63% in the combined vaccine group (95% CI 34, 80; p<0.001), 75% in the neonatal vaccine group (95% confidence interval [CI] 44, 91; p<0.001) and 51% in the infant vaccine group (95% CI 7, 76; p=0.03) in the per protocol analysis, with similar results in the intention-to-treat analysis. Vaccine efficacy to 12 months was 94% in the neonatal vaccine group (95%CI 56, 99; p=0.006). Vaccine take occurred in 78/83 (94%) in the neonatal vaccine group and 83/84 (99%) in the infant vaccine group. The vaccine was well tolerated, with similar incidence of adverse events in vaccine and placebo recipients. Conclusion RV3-BB was efficacious, immunogenic and well-tolerated when administered in a neonatal or infant schedule in Indonesia. PMID:29466164

  5. A biolayer interferometry-based enzyme-linked aptamer sorbent assay for real-time and highly sensitive detection of PDGF-BB.

    PubMed

    Gao, Shunxiang; Zheng, Xin; Wu, Jihong

    2018-04-15

    Accurate, fast and sensitive detection of disease-specific protein biomarkers, especially in blood, urine, or other bodily fluids, is an important approach to achieve early disease diagnosis. Platelet-derived growth factor-BB (PDGF-BB), a widely used biomarker, is involved in a substantial number of serious diseases, such as hepatic fibrosis, atherosclerosis, age-related macular degeneration and diabetic eye disease and is often over-expressed in human malignant tumors. Therefore, the development of sensitive and specific detection methods for PDGF-BB is of great importance for the early diagnosis of disease and assessments of patient recovery. In the current study, a biolayer interferometry-based enzyme-linked aptamer sorbent assay (BLI-ELASA) was successfully established for rapid (20-25min), high-throughput (8 or 16 samples) and real-time monitoring of PDGF-BB in clinical samples. The method exhibited a broad detection range from 0.5 to 1000ng/mL of PDGF-BB (good linear range from 0.5 to 10ng/mL), with a low detection limit of 0.08ng/mL. Moreover, BLI-ELASA was applied to the detection of PDGF-BB in spiked serum and urine samples and showed a high degree of selectivity for PDGF-BB, good reproducibility, and stability. We believe that the methodology in this work can be easily adapted to detect other biomolecules in clinical samples, including viruses, pathogens and toxins, in a rapid, sensitive, high-throughput and real-time manner. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Horizontal Guided Bone Regeneration in the Esthetic Area with rhPDGF-BB and Anorganic Bovine Bone Graft: A Case Report.

    PubMed

    Chiantella, Giovanni Carlo

    2016-01-01

    The present article describes the treatment given to a patient who underwent horizontal ridge augmentation surgery in the maxillary anterior area due to the premature loss of the maxillary central incisors. The complete dehiscence of the buccal plate was detected after elevation of mucoperiosteal flaps. The lesion was overfilled with deproteinized bovine xenograft particles combined with recombinant human platelet-derived growth factor BB (rhPDGF-BB) and covered with a porcine collagen barrier hydrated with the same growth factor. The soft tissues healed with no adverse complications. After 12 months, reentry surgery was carried out to place endosseous implants. Complete bone regeneration with the presence of bone-like tissue was observed. Cross-sectional computed tomography scan images confirmed integration of the bone graft and reconstruction of the lost hard tissue volume. The implants were inserted in an optimal three-dimensional position, thus facilitating esthetic restoration. Two years after insertion of final crowns, cone beam computed tomography scans displayed the stability of regenerated hard tissues around the implants. Controlled clinical studies are necessary to determine the benefit of hydrating bovine bone particles and collagen barriers with rhPDGF-BB for predictable bone regeneration of horizontal lesions.

  7. Effects of ischemic preconditioning on PDGF-BB expression in the gerbil hippocampal CA1 region following transient cerebral ischemia

    PubMed Central

    Lee, Jae-Chul; Kim, Yang Hee; Lee, Tae-Kyeong; Kim, In Hye; Cho, Jeong Hwi; Cho, Geum-Sil; Shin, Bich-Na; Park, Joon Ha; Ahn, Ji Hyeon; Shin, Myoung Cheol; Cho, Jun Hwi; Kang, Il Jun; Won, Moo-Ho; Seo, Jeong Yeol

    2017-01-01

    Ischemic preconditioning (IPC) is induced by exposure to brief durations of transient ischemia, which results in ischemic tolerance to a subsequent longer or lethal period of ischemia. In the present study, the effects of IPC (2 min of transient cerebral ischemia) were examined on immunoreactivity of platelet-derived growth factor (PDGF)-BB and on neuroprotection in the gerbil hippocampal CA1 region following lethal transient cerebral ischemia (LTCI; 5 min of transient cerebral ischemia). IPC was subjected to a 2-min sublethal ischemia and a LTCI was given 5-min transient ischemia. The animals in all of the groups were given recovery times of 1, 2 and 5 days and change in PDGF-BB immunoreactivity was examined as was the neuronal damage/death in the hippocampus induced by LTCI. LTCI induced a significant loss of pyramidal neurons in the hippocampal CA1 region 5 days after LTCI, and significantly decreased PDGF-BB immunoreactivity in the CA1 pyramidal neurons from day 1 after LTCI. Conversely, IPC effectively protected the CA1 pyramidal neurons from LTCI and increased PDGF-BB immunoreactivity in the CA1 pyramidal neurons post-LTCI. In conclusion, the results demonstrated that LTCI significantly altered PDGF-BB immunoreactivity in pyramidal neurons in the hippocampal CA1 region, whereas IPC increased the immunoreactivity. These findings indicated that PDGF-BB may be associated with IPC-mediated neuroprotection. PMID:28627606

  8. Mechanisms involved in synergistic anticancer immunity of anti-4-1BB and anti-CD4 therapy.

    PubMed

    Choi, Beom K; Kim, Young H; Kang, Woo J; Lee, Sun K; Kim, Kwang H; Shin, Su M; Yokoyama, Wayne M; Kim, Tae Y; Kwon, Byoung S

    2007-09-15

    Anti-4-1BB-mediated anticancer effects were potentiated by depletion of CD4+ cells in B16F10 melanoma-bearing C57BL/6 mice. Anti-4-1BB induced the expansion and differentiation of polyclonal tumor-specific CD8+ T cells into IFN-gamma-producing CD11c+CD8+ T cells. The CD4+ cell depletion was responsible for facilitating immune cell infiltration into tumor tissues and removing some regulatory barriers such as T regulatory and indoleamine-2,3-dioxygenase (IDO)+ dendritic cells. Both monoclonal antibodies (mAb) contributed to the efficient induction of MHC class I molecules on the tumor cells in vivo. The effectors that mediated the anti-4-1BB effect were NKG2D+KLRG1+CD11c+CD8+ T cells that accumulated preferentially in the tumor tissues. Blocking NKG2D reduced the therapeutic effect by 20% to 26%, which may indicate that NKG2D contributes partially to tumor killing by the differentiated CD8+ T cells. Our results indicate that the combination of the two mAbs, agonistic anti-4-1BB and depleting anti-CD4, results in enhanced production of efficient tumor-killing CTLs, facilitation of their infiltration, and production of a susceptible tumor microenvironment.

  9. Expression of platelet-derived growth factor BB, erythropoietin and erythropoietin receptor in canine and feline osteosarcoma

    PubMed Central

    Meyer, F.R.L.; Steinborn, R.; Grausgruber, H.; Wolfesberger, B.; Walter, I.

    2015-01-01

    The discovery of expression of the erythropoietin receptor (EPO-R) on neoplastic cells has led to concerns about the safety of treating anaemic cancer patients with EPO. In addition to its endocrine function, the receptor may play a role in tumour progression through an autocrine mechanism. In this study, the expression of EPO, EPO-R and platelet-derived growth factor BB (PDGF-BB) was analysed in five feline and 13 canine osteosarcomas using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). EPO expression was positive in all tumours by IHC, but EPO mRNA was only detected in 38% of the canine and 40% of the feline samples. EPO-R was expressed in all samples by quantitative RT-PCR (RT-qPCR) and IHC. EPO-R mRNA was expressed at higher levels in all feline tumours, tumour cell lines, and kidney when compared to canine tissues. PDGF-BB expression was variable by IHC, but mRNA was detected in all samples. To assess the functionality of the EPO-R on tumour cells, the proliferation of canine and feline osteosarcoma cell lines was evaluated after EPO administration using an alamarBlue assay and Ki67 immunostaining. All primary cell lines responded to EPO treatment in at least one of the performed assays, but the effect on proliferation was very low indicating only a weak responsiveness of EPO-R. In conclusion, since EPO and its receptor are expressed by canine and feline osteosarcomas, an autocrine or paracrine tumour progression mechanism cannot be excluded, although in vitro data suggest a minimal role of EPO-R in osteosarcoma cell proliferation. PMID:26189892

  10. Platelet-Derived Growth Factor-BB Stimulates Fibronectin Gene Expression in Fibroblasts Isolated from Rat Thoracic Aorta

    DTIC Science & Technology

    1994-06-13

    MARYLAND 20814-4799 TEACHING HOSPITALS WALTER REED ARMY MEDtCA L CENTER APPROVAL SHEET NAVAL HOSPITAL. BETHESDA MALCOLM GROW AIR FORCE MEDICAL ...CENTER WILFORD HALL "IR FORCE MEDICAL CENTER Title of Dissertation: "Platelet-derived growth factor-BB stimulates fibronectin gene expression in...fascinating world of basic medical science. His dedication and pursuit of excellence in all facets of his work are standards by which I will guide my own

  11. Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage

    PubMed Central

    Yang, Lu; Chen, Xufeng; Simet, Samantha M.; Hu, Guoku; Cai, Yu; Niu, Fang; Kook, Yeonhee

    2016-01-01

    Abuse of psychostimulants, such as cocaine, has been shown to be closely associated with complications of the lung, such as pulmonary hypertension, edema, increased inflammation, and infection. However, the mechanism by which cocaine mediates impairment of alveolar epithelial barrier integrity that underlies various pulmonary complications has not been well determined. Herein, we investigate the role of cocaine in disrupting the alveolar epithelial barrier function and the associated signaling cascade. Using the combinatorial electric cell–substrate impedance sensing and FITC-dextran permeability assays, we demonstrated cocaine-mediated disruption of the alveolar epithelial barrier, as evidenced by increased epithelial monolayer permeability with a concomitant loss of the tight junction protein zonula occludens-1 (Zo-1) in both mouse primary alveolar epithelial cells and the alveolar epithelial cell line, L2 cells. To dissect the signaling pathways involved in this process, we demonstrated that cocaine-mediated induction of permeability factors, platelet-derived growth factor (PDGF-BB) and vascular endothelial growth factor, involved reactive oxygen species (ROS)-dependent induction of hypoxia-inducible factor (HIF)-1α. Interestingly, we demonstrated that ROS-dependent induction of another transcription factor, nuclear factor erythroid-2–related factor-2, that did not play a role in cocaine-mediated barrier dysfunction. Importantly, this study identifies, for the first time, that ROS/HIF-1α/PDGF-BB autocrine loop contributes to cocaine-mediated barrier disruption via amplification of oxidative stress and downstream signaling. Corroboration of these cell culture findings in vivo demonstrated increased permeability of the alveolar epithelial barrier, loss of expression of Zo-1, and a concomitantly increased expression of both HIF-1α and PDGF-BB. Pharmacological blocking of HIF-1α significantly abrogated cocaine-mediated loss of Zo-1. Understanding the

  12. Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice.

    PubMed

    Almeida-Reis, Rafael; Theodoro-Junior, Osmar A; Oliveira, Bruno T M; Oliva, Leandro V; Toledo-Arruda, Alessandra C; Bonturi, Camila R; Brito, Marlon V; Lopes, Fernanda D T Q S; Prado, Carla M; Florencio, Ariana C; Martins, Mílton A; Owen, Caroline A; Leick, Edna A; Oliva, Maria L V; Tibério, Iolanda F L C

    2017-01-01

    Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.  C57BL / 6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNF α -, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2 α , collagen, and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. Results. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNF α -positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. Conclusions. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease.

  13. Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice

    PubMed Central

    Theodoro-Junior, Osmar A.; Oliveira, Bruno T. M.; Oliva, Leandro V.; Toledo-Arruda, Alessandra C.; Bonturi, Camila R.; Brito, Marlon V.; Prado, Carla M.; Florencio, Ariana C.; Martins, Mílton A.; Owen, Caroline A.; Oliva, Maria L. V.

    2017-01-01

    Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods.  C57BL/6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNFα-, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2α, collagen, and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. Results. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNFα-positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. Conclusions. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease. PMID:28466019

  14. Safety of Bifidobacterium animalis Subsp. Lactis (B. lactis) Strain BB-12-Supplemented Yogurt in Healthy Children.

    PubMed

    Tan, Tina P; Ba, Zhaoyong; Sanders, Mary E; D'Amico, Frank J; Roberts, Robert F; Smith, Keisha H; Merenstein, Daniel J

    2017-02-01

    Probiotics are live microorganisms that may provide health benefits to the individual when consumed in sufficient quantities. For studies conducted on health or disease endpoints on probiotics in the United States, the Food and Administration has required those studies to be conducted as investigational new drugs. This phase I, double-blinded, randomized, controlled safety study represents the first requirement of this pathway. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp. lactis (B lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of children. The secondary aim was to assess the effect of BB-12-supplemented yogurt on the gut microbiota of the children. Sixty children ages 1 to 5 years were randomly assigned to consume 4 ounces of either BB-12-supplemented yogurt or nonsupplemented control yogurt daily for 10 days. The primary outcome was to assess safety and tolerability, as determined by the number of reported adverse events. A total of 186 nonserious adverse events were reported, with no significant differences between the control and BB-12 groups. No significant changes due to probiotic treatment were observed in the gut microbiota of the study cohort. BB-12-supplemented yogurt is safe and well-tolerated when consumed by healthy children. The present study will form the basis for future randomized clinical trials investigating the potential effects of BB-12-supplemented yogurt in different disease states.

  15. [Creatine kinase BB and lactate in the cerebrospinal fluid of neonates and infants with perinatal injuries of the CNS].

    PubMed

    Alatyrtsev, V V; Iakunin, Iu A; Burkova, A S; Podkopaev, V N; Afonina, L G

    1989-01-01

    A study was made of the content of creatine kinase-BB (CK-BB) and lactate in cerebrospinal fluid (CSF) of 202 neonates and infants with perinatal CNS injuries. The relationship was found between the rise of the CK-BB content and the gravity of perinatal CNS injuries. The highest content of CK-BB in CSF was marked in neonates with cerebral disorders complicated by infectious and inflammatory diseases (pneumonia, sepsis). Within the first 5 days of life, the children of this group demonstrated the relationship between the content of CK-BB and lactate of CSF. The measurement of the content of CK-BB in CSF should be used for early diagnosis, assessment of the gravity and course of perinatal CNS injuries in neonates and in infants.

  16. 40 CFR Appendix A to Subpart Bb of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart BB

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants From Phosphate Fertilizers Production Plants Pt. 63, Subpart BB, App. A Appendix A...

  17. 40 CFR Appendix A to Subpart Bb of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart BB

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants From Phosphate Fertilizers Production Plants Pt. 63, Subpart BB, App. A Appendix A...

  18. 40 CFR Appendix A to Subpart Bb of... - Applicability of General Provisions (40 CFR Part 63, Subpart A) to Subpart BB

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES (CONTINUED) National Emission Standards for Hazardous Air Pollutants From Phosphate Fertilizers Production Plants Pt. 63, Subpart BB, App. A Appendix A...

  19. Expression of platelet-derived growth factor BB, erythropoietin and erythropoietin receptor in canine and feline osteosarcoma.

    PubMed

    Meyer, F R L; Steinborn, R; Grausgruber, H; Wolfesberger, B; Walter, I

    2015-10-01

    The discovery of expression of the erythropoietin receptor (EPO-R) on neoplastic cells has led to concerns about the safety of treating anaemic cancer patients with EPO. In addition to its endocrine function, the receptor may play a role in tumour progression through an autocrine mechanism. In this study, the expression of EPO, EPO-R and platelet-derived growth factor BB (PDGF-BB) was analysed in five feline and 13 canine osteosarcomas using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). EPO expression was positive in all tumours by IHC, but EPO mRNA was only detected in 38% of the canine and 40% of the feline samples. EPO-R was expressed in all samples by quantitative RT-PCR (RT-qPCR) and IHC. EPO-R mRNA was expressed at higher levels in all feline tumours, tumour cell lines, and kidney when compared to canine tissues. PDGF-BB expression was variable by IHC, but mRNA was detected in all samples. To assess the functionality of the EPO-R on tumour cells, the proliferation of canine and feline osteosarcoma cell lines was evaluated after EPO administration using an alamarBlue assay and Ki67 immunostaining. All primary cell lines responded to EPO treatment in at least one of the performed assays, but the effect on proliferation was very low indicating only a weak responsiveness of EPO-R. In conclusion, since EPO and its receptor are expressed by canine and feline osteosarcomas, an autocrine or paracrine tumour progression mechanism cannot be excluded, although in vitro data suggest a minimal role of EPO-R in osteosarcoma cell proliferation. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Vertical ridge augmentation using an equine bone and collagen block infused with recombinant human platelet-derived growth factor-BB: a randomized single-masked histologic study in non-human primates.

    PubMed

    Nevins, Myron; Al Hezaimi, Khalid; Schupbach, Peter; Karimbux, Nadeem; Kim, David M

    2012-07-01

    This study tests the effectiveness of hydroxyapatite and collagen bone blocks of equine origin (eHAC), infused with recombinant human platelet-derived growth factor-BB (rhPDGF-BB), to augment localized posterior mandibular defects in non-human primates (Papio hamadryas). Bilateral critical-sized defects simulating severe atrophy were created at the time of the posterior teeth extraction. Test and control blocks (without growth factor) were randomly grafted into the respective sites in each non-human primate. All sites exhibited vertical ridge augmentation, with physiologic hard- and soft-tissue integration of the blocks when clinical and histologic examinations were done at 4 months after the vertical ridge augmentation procedure. There was a clear, although non-significant, tendency to increased regeneration in the test sites. As in the first two preclinical studies in this series using canines, experimental eHAC blocks infused with rhPDGF-BB proved to be a predictable and technically viable method to predictably regenerate bone and soft tissue in critical-sized defects. This investigation supplies additional evidence that eHAC blocks infused with rhPDGF-BB growth factor is a predictable and technically feasible option for vertical augmentation of severely resorbed ridges.

  1. Radioimmunoassay measurement of creatine kinase bb in the serum of schizophrenic patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lerner, M.H.; Friedhoff, A.J.

    1980-03-03

    Brain type creatine kinase (BB) isoenzyme was measured using a highly sensitive and specific radioimmunoassay procedure in two schizophrenic populations. The data would indicate that in the schizophrenic populations examined there is insufficient tissue disruption to cause abnormal build-up of brain creatine kinase levels. However the possibility of a rapid removal of creatine kinase BB from the circulation exists. The elevated creatine kinase reported in acute schizophrenics is most likely not of brain origin.

  2. Role of 'B-b' knob-hole interactions in fibrin binding to adsorbed fibrinogen.

    PubMed

    Geer, C B; Tripathy, A; Schoenfisch, M H; Lord, S T; Gorkun, O V

    2007-12-01

    The formation of a fibrin clot is supported by multiple interactions, including those between polymerization knobs 'A' and 'B' exposed by thrombin cleavage and polymerization holes 'a' and 'b' present in fibrinogen and fibrin. Although structural studies have defined the 'A-a' and 'B-b' interactions in part, it has not been possible to measure the affinities of individual knob-hole interactions in the absence of the other interactions occurring in fibrin. We designed experiments to determine the affinities of knob-hole interactions, either 'A-a' alone or 'A-a' and 'B-b' together. We used surface plasmon resonance to measure binding between adsorbed fibrinogen and soluble fibrin fragments containing 'A' knobs, desA-NDSK, or both 'A' and 'B' knobs, desAB-NDSK. The desA- and desAB-NDSK fragments bound to fibrinogen with statistically similar K(d)'s of 5.8 +/- 1.1 microm and 3.7 +/- 0.7 microm (P = 0.14), respectively. This binding was specific, as we saw no significant binding of NDSK, which has no exposed knobs. Moreover, the synthetic 'A' knob peptide GPRP and synthetic 'B' knob peptides GHRP and AHRPY, inhibited the binding of desA- and/or desAB-NDSK. The peptide inhibition findings show both 'A-a' and 'B-b' interactions participate in desAB-NDSK binding to fibrinogen, indicating 'B-b' interactions can occur simultaneously with 'A-a'. Furthermore, 'A-a' interactions are much stronger than 'B-b' because the affinity of desA-NDSK was not markedly different from desAB-NDSK.

  3. BB and pellet guns--toys or deadly weapons?

    PubMed

    Harris, W; Luterman, A; Curreri, P W

    1983-07-01

    BB and pellet weapons are not included in gun control laws and are often sold as children's toys. Injuries caused by these weapons have been considered trivial unless they involve vulnerable surface organs such as the eye. The purpose of this study was to review the management of six cases of pellet or BB gun injuries that required abdominal exploration at the University of South Alabama Medical Center from January 1980 through June 1982. Five of the six patients had significant internal injuries including perforations of the stomach, jejunum, liver, and pancreas. The ballistics of pneumatic weapons are reviewed. The muzzle velocities of many of these weapons necessitate that wounds caused by these weapons be handled with the same principles as for any small-caliber, low-velocity (less than 1,200 feet/second) weapons. Public education programs are urgently needed to educate parents as to the potential danger involved in purchasing these weapons for unsupervised use as toys by children.

  4. Cry3Bb1-Resistant Western Corn Rootworm, Diabrotica virgifera virgifera (LeConte) Does Not Exhibit Cross-Resistance to DvSnf7 dsRNA.

    PubMed

    Moar, William; Khajuria, Chitvan; Pleau, Michael; Ilagan, Oliver; Chen, Mao; Jiang, Changjian; Price, Paula; McNulty, Brian; Clark, Thomas; Head, Graham

    2017-01-01

    There is a continuing need to express new insect control compounds in transgenic maize against western corn rootworm, Diabrotica virgifera virgifera (LeConte) (WCR). In this study three experiments were conducted to determine cross-resistance between the new insecticidal DvSnf7 dsRNA, and Bacillus thuringiensis (Bt) Cry3Bb1; used to control WCR since 2003, with field-evolved resistance being reported. Laboratory susceptible and Cry3Bb1-resistant WCR were evaluated against DvSnf7 dsRNA in larval diet-incorporation bioassays. Additionally, the susceptibility of seven field and one field-derived WCR populations to DvSnf7 (and Cry3Bb1) was assessed in larval diet-overlay bioassays. Finally, beetle emergence of laboratory susceptible and Cry3Bb1-resistant WCR was evaluated with maize plants in the greenhouse expressing Cry3Bb1, Cry34Ab1/Cry35Ab1, or DvSnf7 dsRNA singly, or in combination. The Cry3Bb1-resistant colony had slight but significantly (2.7-fold; P<0.05) decreased susceptibility to DvSnf7 compared to the susceptible colony, but when repeated using a field-derived WCR population selected for reduced Cry3Bb1 susceptibility, there was no significant difference (P<0.05) in DvSnf7 susceptibility compared to that same susceptible population. Additionally, this 2.7-fold difference in susceptibility falls within the range of DvSnf7 susceptibility among the seven field populations tested. Additionally, there was no correlation between susceptibility to DvSnf7 and Cry3Bb1 for all populations evaluated. In greenhouse studies, there were no significant differences (P<0.05) between beetle emergence of susceptible and Cry3Bb1-resistant colonies on DvSnf7 and Cry34Ab1/Cry35Ab1, and between DvSnf7 and MON 87411 (DvSnf7 + Cry3Bb1) for the Cry3Bb1-resistant colony. These results demonstrate no cross-resistance between DvSnf7 and Cry3Bb1 against WCR. Therefore, pyramiding DvSnf7 with Bt proteins such as Cry3Bb1 and Cry34Ab1/Cry35Ab1 will provide a valuable IRM tool against WCR

  5. Atorvastatin calcium inhibits phenotypic modulation of PDGF-BB-induced VSMCs via down-regulation the Akt signaling pathway.

    PubMed

    Chen, Shuang; Liu, Baoqin; Kong, Dehui; Li, Si; Li, Chao; Wang, Huaqin; Sun, Yingxian

    2015-01-01

    Plasticity of vascular smooth muscle cells (VSMCs) plays a central role in the onset and progression of proliferative vascular diseases. In adult tissue, VSMCs exist in a physiological contractile-quiescent phenotype, which is defined by lack of the ability of proliferation and migration, while high expression of contractile marker proteins. After injury to the vessel, VSMC shifts from a contractile phenotype to a pathological synthetic phenotype, associated with increased proliferation, migration and matrix secretion. It has been demonstrated that PDGF-BB is a critical mediator of VSMCs phenotypic switch. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methyl-glutaryl l coenzyme A (HMG-CoA) reductase, exhibits various protective effects against VSMCs. In this study, we investigated the effects of atorvastatin calcium on phenotype modulation of PDGF-BB-induced VSMCs and the related intracellular signal transduction pathways. Treatment of VSMCs with atorvastatin calcium showed dose-dependent inhibition of PDGF-BB-induced proliferation. Atorvastatin calcium co-treatment inhibited the phenotype modulation and cytoskeleton rearrangements and improved the expression of contractile phenotype marker proteins such as α-SM actin, SM22α and calponin in comparison with PDGF-BB alone stimulated VSMCs. Although Akt phosphorylation was strongly elicited by PDGF-BB, Akt activation was attenuated when PDGF-BB was co-administrated with atorvastatin calcium. In conclusion, atorvastatin calcium inhibits phenotype modulation of PDGF-BB-induced VSMCs and activation of the Akt signaling pathway, indicating that Akt might play a vital role in the modulation of phenotype.

  6. Atorvastatin Calcium Inhibits Phenotypic Modulation of PDGF-BB-Induced VSMCs via Down-Regulation the Akt Signaling Pathway

    PubMed Central

    Chen, Shuang; Liu, Baoqin; Kong, Dehui; Li, Si; Li, Chao; Wang, Huaqin; Sun, Yingxian

    2015-01-01

    Plasticity of vascular smooth muscle cells (VSMCs) plays a central role in the onset and progression of proliferative vascular diseases. In adult tissue, VSMCs exist in a physiological contractile-quiescent phenotype, which is defined by lack of the ability of proliferation and migration, while high expression of contractile marker proteins. After injury to the vessel, VSMC shifts from a contractile phenotype to a pathological synthetic phenotype, associated with increased proliferation, migration and matrix secretion. It has been demonstrated that PDGF-BB is a critical mediator of VSMCs phenotypic switch. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methyl-glutaryl l coenzyme A (HMG-CoA) reductase, exhibits various protective effects against VSMCs. In this study, we investigated the effects of atorvastatin calcium on phenotype modulation of PDGF-BB-induced VSMCs and the related intracellular signal transduction pathways. Treatment of VSMCs with atorvastatin calcium showed dose-dependent inhibition of PDGF-BB-induced proliferation. Atorvastatin calcium co-treatment inhibited the phenotype modulation and cytoskeleton rearrangements and improved the expression of contractile phenotype marker proteins such as α-SM actin, SM22α and calponin in comparison with PDGF-BB alone stimulated VSMCs. Although Akt phosphorylation was strongly elicited by PDGF-BB, Akt activation was attenuated when PDGF-BB was co-administrated with atorvastatin calcium. In conclusion, atorvastatin calcium inhibits phenotype modulation of PDGF-BB-induced VSMCs and activation of the Akt signaling pathway, indicating that Akt might play a vital role in the modulation of phenotype. PMID:25874930

  7. Effect of PDGF-BB and beta-tricalcium phosphate (β-TCP) on bone formation around dental implants: a pilot study in sheep.

    PubMed

    Choo, Tina; Marino, Victor; Bartold, P Mark

    2013-02-01

    The aim of this investigation was to examine the effect of a combination of purified recombinant human platelet-derived growth factor (rhPDGF-BB) mixed with a synthetic beta-tricalcium phosphate (β-TCP) on bone healing around dental implants with critical size circumferential defects. Three critical size circumferential defects were prepared in the ilium of six sheep. Three dental implants were placed into the centre of each defect and the 3.25 mm circumferential gap was filled with (a) blood clot alone; (b) β-TCP; (c) rhPDGF-BB (0.3 mg/ml) with β-TCP. All the defects in each group were covered with a Bio-Gide(®) resorbable barrier membrane. The sheep were sacrificed at 2 and 4 weeks and histological and histomorphometric analyses were performed to determine the percentage of new mineralized bone formation and residual β-TCP graft particles in the defects. Defects filled with rhPDGF-BB/β-TCP showed the highest rate of bone formation after 2 and 4 weeks with limited degradation of the β-TCP particles over 4 weeks. Defects filled with β-TCP showed the least bone fill after 2 and 4 weeks, and faster degradation of the β-TCP particles over 4 weeks compared with defects filled with rhPDGF-BB/β-TCP. Percentage of new mineralized bone was comparable in defects to blood clot alone and β-TCP after 4 weeks of healing, but there was a collapse in the defect area in defects with blood clot alone. In comparison, the space was maintained when β-TCP was used in defects at 4 weeks. Defects which had β-TCP alone showed an inhibition in bone healing at 2 and 4 weeks; however, the combination of rhPDGF-BB with β-TCP enhanced bone regeneration in these peri-implant bone defects at the same time intervals. © 2011 John Wiley & Sons A/S.

  8. SECTION BB, FLOOR PLAN Dyess Air Force Base, Atlas ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    SECTION B-B, FLOOR PLAN - Dyess Air Force Base, Atlas F Missle Site S-8, Launch Facility, Approximately 3 miles east of Winters, 500 feet southwest of Highway 1770, center of complex, Winters, Runnels County, TX

  9. Can the use of the Leggett-Garg inequality enhance security of the BB84 protocol?

    NASA Astrophysics Data System (ADS)

    Shenoy H., Akshata; Aravinda, S.; Srikanth, R.; Home, Dipankar

    2017-08-01

    Prima facie, there are good reasons to answer in the negative the question posed in the title: the Bennett-Brassard 1984 (BB84) protocol is provably secure subject to the assumption of trusted devices, while the Leggett-Garg-type inequality (LGI) does not seem to be readily adaptable to the device independent (DI) or semi-DI scenario. Nevertheless, interestingly, here we identify a specific device attack, which has been shown to render the standard BB84 protocol completely insecure, but against which our formulated LGI-assisted BB84 protocol (based on an appropriate form of LGI) is secure.

  10. Measurement Properties of the Smartphone-Based B-B Score in Current Shoulder Pathologies

    PubMed Central

    Pichonnaz, Claude; Duc, Cyntia; Gleeson, Nigel; Ancey, Céline; Jaccard, Hervé; Lécureux, Estelle; Farron, Alain; Jolles, Brigitte M.; Aminian, Kamiar

    2015-01-01

    This study is aimed at the determination of the measurement properties of the shoulder function B-B Score measured with a smartphone. This score measures the symmetry between sides of a power-related metric for two selected movements, with 100% representing perfect symmetry. Twenty healthy participants, 20 patients with rotator cuff conditions, 23 with fractures, 22 with capsulitis, and 23 with shoulder instabilities were measured twice across a six-month interval using the B-B Score and shoulder function questionnaires. The discriminative power, responsiveness, diagnostic power, concurrent validity, minimal detectable change (MDC), minimal clinically important improvement (MCII), and patient acceptable symptom state (PASS) were evaluated. Significant differences with the control group and significant baseline—six-month differences were found for the rotator cuff condition, fracture, and capsulitis patient groups. The B-B Score was responsive and demonstrated excellent diagnostic power, except for shoulder instability. The correlations with clinical scores were generally moderate to high, but lower for instability. The MDC was 18.1%, the MCII was 25.2%, and the PASS was 77.6. No floor effect was observed. The B-B Score demonstrated excellent measurement properties in populations with rotator cuff conditions, proximal humerus fractures, and capsulitis, and can thus be used as a routine test to evaluate those patients. PMID:26506355

  11. Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12®-supplemented yogurt in healthy children

    PubMed Central

    Tan, Tina P.; Ba, Zhaoyong; Sanders, Mary Ellen; D’Amico, Frank J.; Roberts, Robert F.; Smith, Keisha Herbin; Merenstein, Daniel J.

    2016-01-01

    Objectives Probiotics are live microorganisms that may provide health benefits to the individual when consumed in sufficient quantities. For studies conducted on health or disease endpoints on probiotics in the United States, the Food and Administration (FDA) has required those studies to be conducted as investigational new drugs. This phase I, double-blinded, randomized, controlled safety study represents the first requirement of this pathway. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12® (BB-12®)-supplemented yogurt when consumed by a generally healthy group of children. The secondary aim was to assess the effect of BB-12®-supplemented yogurt on the gut microbiota of the children. Methods Sixty children aged 1–5 years were randomly assigned to consume four ounces of either BB-12®-supplemented yogurt or non-supplemented control yogurt daily for 10 days. The primary outcome was to assess safety and tolerability, as determined by the number of reported adverse events. Results A total of 186 non-serious adverse events were reported, with no significant differences between the control and BB-12® groups. No significant changes due to probiotic treatment were observed in the gut microbiota of the study cohort. Conclusions BB-12®-supplemented yogurt is safe and well-tolerated when consumed by healthy children. This study will form the basis for future randomized clinical trials investigating the potential effects of BB-12®-supplemented yogurt in different disease states. PMID:28114246

  12. Regulation of a phenylalanine ammonia lyase (BbPAL) by calmodulin in response to environmental changes in the entomopathogenic fungus Beauveria bassiana.

    PubMed

    Kim, Jiyoung; Park, Hyesung; Han, Jae-Gu; Oh, Junsang; Choi, Hyung-Kyoon; Kim, Seong Hwan; Sung, Gi-Ho

    2015-11-01

    Phenylalanine ammonia lyase (PAL, E.C. 4.3.1.5) catalyses the deamination of L -phenylalanine to trans-cinnamic acid and ammonia, facilitating a critical step in the phenylpropanoid pathway that produces a variety of secondary metabolites. In this study, we isolated BbPAL gene in the entomopathogenic fungus Beauveria bassiana. According to multiple sequence alignment, homology modelling and in vitro PAL activity, we demonstrated that BbPAL acts as a typical PAL enzyme in B. bassiana. BbPAL interacted with calmodulin (CaM) in vitro and in vivo, indicating that BbPAL is a novel CaM-binding protein. The functional role of CaM in BbPAL action was to negatively regulate the BbPAL activity in B. bassiana. High-performance liquid chromatography analysis revealed that L -phenylalanine was reduced and trans-cinnamic acid was increased in response to the CaM inhibitor W-7. Dark conditions suppressed BbPAL activity in B. bassiana, compared with light. In addition, heat and cold stresses inhibited BbPAL activity in B. bassiana. Interestingly, these negative effects of BbPAL activity by dark, heat and cold conditions were recovered by W-7 treatment, suggesting that the inhibitory mechanism is mediated through stimulation of CaM activity. Therefore, this work suggests that BbPAL plays a role in the phenylpropanoid pathway mediated by environmental stimuli via the CaM signalling pathway. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

  13. Pretreatment with platelet derived growth factor-BB modulates the ability of costochondral resting zone chondrocytes incorporated into PLA/PGA scaffolds to form new cartilage in vivo.

    PubMed

    Lohmann, C H; Schwartz, Z; Niederauer, G G; Carnes, D L; Dean, D D; Boyan, B D

    2000-01-01

    Optimal repair of chondral defects is likely to require both a suitable population of chondrogenic cells and a biodegradable matrix to provide a space-filling structural support during the early stages of cartilage formation. This study examined the ability of chondrocytes to support cartilage formation when incorporated into biodegradable scaffolds constructed from copolymers (PLG) of polylactic acid (PLA) and polyglycolic acid (PGA) and implanted in the calf muscle of nude mice. Scaffolds were fabricated to be more hydrophilic (PLG-H) or were reinforced with 10% PGA fibers (PLG-FR), increasing the stiffness of the implant by 20-fold. Confluent primary cultures of rat costochondral resting zone chondrocytes (RC) were loaded into PLG-H foams and implanted intramuscularly. To determine if growth factor pretreatment could modulate the ability of the cells to form new cartilage, RC cells were pretreated with recombinant human platelet derived growth factor-BB IPDGF-BB) for 4 or 24 h prior to implantation. To assess whether scaffold material properties could affect the ability of chondrogenic cells to form cartilage, RC cells were also loaded into PLG-FR scaffolds. To determine if the scaffolds or treatment with PDGF-BB affected the rate of chondrogenesis, tissue at the implant site was harvested at four and eight weeks post-operatively, fixed, decalcified and embedded in paraffin. Sections were obtained along the transverse plane of the lower leg, stained with haematoxylin and eosin, and then assessed by morphometric analysis for area of cartilage, area of residual implant, and area of fibrous connective tissue formation (fibrosis). Whether or not the cartilage contained hypertrophic cells was also assessed. The amount of residual implant did not change with time in any of the implanted tissues. The area occupied by PLG-FR implants was greater than that occupied by PLG-H implants at both time points. All implants were surrounded by fibrous connective tissue, whether

  14. Randomness determines practical security of BB84 quantum key distribution.

    PubMed

    Li, Hong-Wei; Yin, Zhen-Qiang; Wang, Shuang; Qian, Yong-Jun; Chen, Wei; Guo, Guang-Can; Han, Zheng-Fu

    2015-11-10

    Unconditional security of the BB84 quantum key distribution protocol has been proved by exploiting the fundamental laws of quantum mechanics, but the practical quantum key distribution system maybe hacked by considering the imperfect state preparation and measurement respectively. Until now, different attacking schemes have been proposed by utilizing imperfect devices, but the general security analysis model against all of the practical attacking schemes has not been proposed. Here, we demonstrate that the general practical attacking schemes can be divided into the Trojan horse attack, strong randomness attack and weak randomness attack respectively. We prove security of BB84 protocol under randomness attacking models, and these results can be applied to guarantee the security of the practical quantum key distribution system.

  15. Randomness determines practical security of BB84 quantum key distribution

    NASA Astrophysics Data System (ADS)

    Li, Hong-Wei; Yin, Zhen-Qiang; Wang, Shuang; Qian, Yong-Jun; Chen, Wei; Guo, Guang-Can; Han, Zheng-Fu

    2015-11-01

    Unconditional security of the BB84 quantum key distribution protocol has been proved by exploiting the fundamental laws of quantum mechanics, but the practical quantum key distribution system maybe hacked by considering the imperfect state preparation and measurement respectively. Until now, different attacking schemes have been proposed by utilizing imperfect devices, but the general security analysis model against all of the practical attacking schemes has not been proposed. Here, we demonstrate that the general practical attacking schemes can be divided into the Trojan horse attack, strong randomness attack and weak randomness attack respectively. We prove security of BB84 protocol under randomness attacking models, and these results can be applied to guarantee the security of the practical quantum key distribution system.

  16. Randomness determines practical security of BB84 quantum key distribution

    PubMed Central

    Li, Hong-Wei; Yin, Zhen-Qiang; Wang, Shuang; Qian, Yong-Jun; Chen, Wei; Guo, Guang-Can; Han, Zheng-Fu

    2015-01-01

    Unconditional security of the BB84 quantum key distribution protocol has been proved by exploiting the fundamental laws of quantum mechanics, but the practical quantum key distribution system maybe hacked by considering the imperfect state preparation and measurement respectively. Until now, different attacking schemes have been proposed by utilizing imperfect devices, but the general security analysis model against all of the practical attacking schemes has not been proposed. Here, we demonstrate that the general practical attacking schemes can be divided into the Trojan horse attack, strong randomness attack and weak randomness attack respectively. We prove security of BB84 protocol under randomness attacking models, and these results can be applied to guarantee the security of the practical quantum key distribution system. PMID:26552359

  17. Cry3Bb1-Resistant Western Corn Rootworm, Diabrotica virgifera virgifera (LeConte) Does Not Exhibit Cross-Resistance to DvSnf7 dsRNA

    PubMed Central

    Khajuria, Chitvan; Pleau, Michael; Ilagan, Oliver; Chen, Mao; Jiang, Changjian; Price, Paula; McNulty, Brian; Clark, Thomas; Head, Graham

    2017-01-01

    Background and Methodology There is a continuing need to express new insect control compounds in transgenic maize against western corn rootworm, Diabrotica virgifera virgifera (LeConte) (WCR). In this study three experiments were conducted to determine cross-resistance between the new insecticidal DvSnf7 dsRNA, and Bacillus thuringiensis (Bt) Cry3Bb1; used to control WCR since 2003, with field-evolved resistance being reported. Laboratory susceptible and Cry3Bb1-resistant WCR were evaluated against DvSnf7 dsRNA in larval diet-incorporation bioassays. Additionally, the susceptibility of seven field and one field-derived WCR populations to DvSnf7 (and Cry3Bb1) was assessed in larval diet-overlay bioassays. Finally, beetle emergence of laboratory susceptible and Cry3Bb1-resistant WCR was evaluated with maize plants in the greenhouse expressing Cry3Bb1, Cry34Ab1/Cry35Ab1, or DvSnf7 dsRNA singly, or in combination. Principal Findings and Conclusions The Cry3Bb1-resistant colony had slight but significantly (2.7-fold; P<0.05) decreased susceptibility to DvSnf7 compared to the susceptible colony, but when repeated using a field-derived WCR population selected for reduced Cry3Bb1 susceptibility, there was no significant difference (P<0.05) in DvSnf7 susceptibility compared to that same susceptible population. Additionally, this 2.7-fold difference in susceptibility falls within the range of DvSnf7 susceptibility among the seven field populations tested. Additionally, there was no correlation between susceptibility to DvSnf7 and Cry3Bb1 for all populations evaluated. In greenhouse studies, there were no significant differences (P<0.05) between beetle emergence of susceptible and Cry3Bb1-resistant colonies on DvSnf7 and Cry34Ab1/Cry35Ab1, and between DvSnf7 and MON 87411 (DvSnf7 + Cry3Bb1) for the Cry3Bb1-resistant colony. These results demonstrate no cross-resistance between DvSnf7 and Cry3Bb1 against WCR. Therefore, pyramiding DvSnf7 with Bt proteins such as Cry3Bb1 and

  18. Baseline Field Testing of BB-2590 Lithium-Ion Batteries using an iRobot FasTac 510 Robot

    DTIC Science & Technology

    2010-09-17

    No. 21320 Baseline Field Testing of BB-2590 Lithium - Ion Batteries using an iRobot FasTac 510 Robot U.S. Army Tank...SEP 2010 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Baseline Field Testing of BB-2590 Lithium - Ion Batteries using an iRobot...COVERED (From - To) Baseline Field Testing of BB-2590 Lithium - Ion Batteries using an 4. TITLE AND SUBTITLE iRobot FasTac 510 Robot 5a. CONTRACT

  19. Bone resorption analysis of platelet-derived growth factor type BB application on collagen for bone grafts secured by titanium mesh over a pig jaw defect model

    PubMed Central

    Herford, Alan Scott; Cicciù, Marco

    2012-01-01

    Purpose: The aim of this investigation was to evaluate whether the addition of the platelet derived growth factor type BB (PDGF-BB) to a collagen matrix applied on a titanium mesh would favor healing and resorption onto the grafted bone. A histologic and radiographic study of two different groups (test and control) was performed. Designs: A surgical procedure was performed on 8 pigs to obtain 16 bilateral mandibular alveolar defects. All the defects were then reconstructed with a mixture of autogenous bovine bone using titanium mesh positioning. Two groups, with a total of 16 defects were created: The first to study collagen sponge and PDGF-BB and the second to control collagen only. The collagen matrix was positioned directly over the mesh and soft tissue was closed without tensions onto both groups without attempting to obtain primary closure. Possible exposure of the titanium mesh as well as the height and volume of the new bone was recorded. Results: New bone formation averaged about 6.68 mm in the test group studied; the control group had less regenerated bone at 4.62 mm. Conclusion: PDGF-BB addition to the collagen matrix induced a strong increase in hard and soft tissue healing and favored bone formation, reducing bone resorption even if the mesh was exposed. PMID:23833493

  20. Simple proof of security of the BB84 quantum key distribution protocol

    PubMed

    Shor; Preskill

    2000-07-10

    We prove that the 1984 protocol of Bennett and Brassard (BB84) for quantum key distribution is secure. We first give a key distribution protocol based on entanglement purification, which can be proven secure using methods from Lo and Chau's proof of security for a similar protocol. We then show that the security of this protocol implies the security of BB84. The entanglement purification based protocol uses Calderbank-Shor-Steane codes, and properties of these codes are used to remove the use of quantum computation from the Lo-Chau protocol.

  1. In vitro fibroblast migration by sustained release of PDGF-BB loaded in chitosan nanoparticles incorporated in electrospun nanofibers for wound dressing applications.

    PubMed

    Piran, Mehrdad; Vakilian, Saeid; Piran, Mehran; Mohammadi-Sangcheshmeh, Abdollah; Hosseinzadeh, Simzar; Ardeshirylajimi, Abdolreza

    2018-01-23

    Migration of fibroblasts into wound area is a critical phenomenon in wound healing process. We used an appropriate system to fabricate an electrospun bioactive scaffold with controlled release of PDGF-BB in order to induce migration of primary skin fibroblast cells. First of all, protein-loaded chitosan nanoparticles based on ionic gelation interaction between chitosan and sodium tripolyphosphate were prepared. Then polycaprolactone electrospun fibers containing chitosan nanoparticles or PDGF-BB-loaded chitosan nanoparticles were prepared. Cellular attachment and morphology of cells seeded on scaffolds with or without PDGF-BB were evaluated by using a fluorescence microscope and scanning electron microscopy. Cells were well-oriented 72 h after seeding on the scaffolds containing PDGF-BB. The mean aspect ratio of populations on scaffold containing PDGF-BB-loaded chitosan nanoparticles was significantly greater than those on the scaffold containing chitosan nanoparticles but no PDGF-BB. Furthermore, the Arp2 gene, which is involved in cell protrusion formation, showed about three times more expression at mRNA level, in cells seeding on PDGF-BB-containing scaffold compared to cells seeding on scaffold containing only chitosan nanoparticles, using Real Time PCR test. Finally, under agarose migration assay results demonstrated that cells' chemotaxic behavior was more toward scaffold containing PDGF-BB compared to the PDGF-BB alone or FBS group. In addition, in terms of distance, the cell mass could grow faster, in response to scaffold containing PDGF-BB compared to FBS or PDGF-BB alone; however, the number of migrating cells might be the same or significantly higher in the latter groups.

  2. Identification of two Th1 cell epitopes on the Babesia bovis-encoded 77-kilodalton merozoite protein (Bb-1) by use of truncated recombinant fusion proteins.

    PubMed Central

    Brown, W C; Zhao, S; Woods, V M; Tripp, C A; Tetzlaff, C L; Heussler, V T; Dobbelaere, D A; Rice-Ficht, A C

    1993-01-01

    Previous studies have demonstrated the serologic and T-cell immunogenicity for cattle of a recombinant form of the apical complex-associated 77-kDa merozite protein of Babesia bovis, designated Bb-1. The present study characterizes the immunogenic epitopes of the Bb-1 protein. A series of recombinant truncated fusion proteins spanning the majority of the Bb-1 protein were expressed in Escherichia coli, and their reactivities with bovine peripheral blood mononuclear cells and T-cell clones derived from B. bovis-immune cattle and with rabbit antibodies were determined. Lymphocytes from two immune cattle were preferentially stimulated by the N-terminal half of the Bb-1 protein (amino acids 23 to 266, termed Bb-1A), localizing the T-cell epitopes to the Bb-1A portion of the molecule. CD4+ T-cell clones derived by stimulation with the intact Bb-1 fusion protein were used to identify two T-cell epitopes in the Bb-1A protein, consisting of amino acids SVVLLSAFSGN VWANEAEVSQVVK and FSDVDKTKSTEKT (residues 23 to 46 and 82 to 94). In contrast, rabbit antiserum raised against the intact fusion protein reacted only with the C-terminal half of the protein (amino acids 267 to 499, termed Bb-1B), which contained 28 tandem repeats of the tetrapeptide PAEK or PAET. Biological assays and Northern (RNA) blot analyses for cytokines revealed that following activation with concanavalin A, T-cell clones reactive against the two Bb-1A epitopes produced interleukin-2, gamma interferon, and tumor necrosis factors beta and alpha, but not interleukin-4, suggesting that the Bb-1 antigen preferentially stimulates the Th1 subset of CD4+ T cells in cattle. The studies described here report for the first time the characterization, by cytokine production, of the Th1 subset of bovine T cells and show that, as in mice, protozoal antigens can induce Th1 cells in ruminants. This first demonstration of B. bovis-encoded Th1 cell epitopes provides a rationale for incorporation of all or part of the Bb-1

  3. bb̅ud̅ four-quark systems in the Born-Oppenheimer approximation: prospects and challenges

    NASA Astrophysics Data System (ADS)

    Peters, Antje; Bicudo, Pedro; Wagner, Marc

    2018-03-01

    We summarize previous work on b̅b̅ud four-quark systems in the Born-Oppenheimer approximation and discuss first steps towards an extension to the theoretically more challenging bb̅ud̅ system. Strategies to identify a possibly existing bb̅ud̅ bound state are discussed and first numerical results are presented.

  4. Continuous 4-1BB co-stimulatory signals for the optimal expansion of tumor-infiltrating lymphocytes for adoptive T-cell therapy.

    PubMed

    Chacon, Jessica Ann; Pilon-Thomas, Shari; Sarnaik, Amod A; Radvanyi, Laszlo G

    2013-09-01

    Co-stimulation through members of the tumor necrosis factor receptor (TNFR) family appears to be critical for the generation of T cells with optimal effector-memory properties for adoptive cell therapy. Our work suggests that continuous 4-1BB/CD137 co-stimulation is required for the expansion of T cells with an optimal therapeutic profile and that the administration of 4-1BB agonists upon adoptive cell transfer further improves antitumor T-cell functions.

  5. 78 FR 13742 - BB&T Capital Partners Mezzanine Fund II, L.P.; Notice Seeking Exemption Under Section 312 of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ... SMALL BUSINESS ADMINISTRATION [License No. 04/04-0311] BB&T Capital Partners Mezzanine Fund II, L... Interest Notice is hereby given that BB&T Capital Partners Mezzanine Fund II, L.P., 101 N. Cherry Street... Interest of the Small Business Administration (``SBA'') Rules and Regulations (13 CFR 107.730). BB&T...

  6. A First-look Atmospheric Modeling Study of the Young Directly Imaged Planet-mass Companion, ROXs 42Bb

    NASA Astrophysics Data System (ADS)

    Currie, Thayne; Burrows, Adam; Daemgen, Sebastian

    2014-06-01

    We present and analyze JKsL' photometry and our previously published H-band photometry and K-band spectroscopy for ROXs 42Bb, an object Currie et al. first reported as a young directly imaged planet-mass companion. ROXs 42Bb exhibits IR colors redder than field L dwarfs but consistent with other planet-mass companions. From the H2O-2 spectral index, we estimate a spectral type of L0 ± 1; weak detections/non-detections of the CO bandheads, Na I, and Ca I support evidence for a young, low surface gravity object primarily derived from the H2(K) index. ROXs 42Bb's photometry/K-band spectrum are inconsistent with limiting cases of dust-free atmospheres (COND) and marginally inconsistent with the AMES/DUSTY models and the BT-SETTL models. However, ROXS 42Bb data are simultaneously fit by atmosphere models incorporating several micron-sized dust grains entrained in thick clouds, although further modifications are needed to better reproduce the K-band spectral shape. ROXs 42Bb's best-estimated temperature is T eff ~ 1950-2000 K, near the low end of the empirically derived range in Currie et al. For an age of ~1-3 Myr and considering the lifetime of the protostar phase, ROXs 42Bb's luminosity of log(L/L ⊙) ~ -3.07 ± 0.07 implies a mass of 9^{+3}_{-3} MJ , making it one of the lightest planetary-mass objects yet imaged.

  7. Structure-function mapping of BbCRASP-1, the key complement factor H and FHL-1 binding protein of Borrelia burgdorferi.

    PubMed

    Cordes, Frank S; Kraiczy, Peter; Roversi, Pietro; Simon, Markus M; Brade, Volker; Jahraus, Oliver; Wallis, Russell; Goodstadt, Leo; Ponting, Chris P; Skerka, Christine; Zipfel, Peter F; Wallich, Reinhard; Lea, Susan M

    2006-05-01

    Borrelia burgdorferi, a spirochaete transmitted to human hosts during feeding of infected Ixodes ticks, is the causative agent of Lyme disease, the most frequent vector-borne disease in Eurasia and North America. Sporadically Lyme disease develops into a chronic, multisystemic disorder. Serum-resistant B. burgdorferi strains bind complement factor H (FH) and FH-like protein 1 (FHL-1) on the spirochaete surface. This binding is dependent on the expression of proteins termed complement-regulator acquiring surface proteins (CRASPs). The atomic structure of BbCRASP-1, the key FHL-1/FH-binding protein of B. burgdorferi, has recently been determined. Our analysis indicates that its protein topology apparently evolved to provide a high affinity interaction site for FH/FHL-1 and leads to an atomic-level hypothesis for the functioning of BbCRASP-1. This work demonstrates that pathogens interact with complement regulators in ways that are distinct from the mechanisms used by the host and are thus obvious targets for drug design.

  8. Dual delivery of rhPDGF-BB and bone marrow mesenchymal stromal cells expressing the BMP2 gene enhance bone formation in a critical-sized defect model.

    PubMed

    Park, Shin-Young; Kim, Kyoung-Hwa; Shin, Seung-Yun; Koo, Ki-Tae; Lee, Yong-Moo; Seol, Yang-Jo

    2013-11-01

    Bone tissue healing is a dynamic, orchestrated process that relies on multiple growth factors and cell types. Platelet-derived growth factor-BB (PDGF-BB) is released from platelets at wound sites and induces cellular migration and proliferation necessary for bone regeneration in the early healing process. Bone morphogenetic protein-2 (BMP-2), the most potent osteogenic differentiation inducer, directs new bone formation at the sites of bone defects. This study evaluated a combinatorial treatment protocol of PDGF-BB and BMP-2 on bone healing in a critical-sized defect model. To mimic the bone tissue healing process, a dual delivery approach was designed to deliver the rhPDGF-BB protein transiently during the early healing phase, whereas BMP-2 was supplied by rat bone marrow stromal cells (BMSCs) transfected with an adenoviral vector containing the BMP2 gene (AdBMP2) for prolonged release throughout the healing process. In in vitro experiments, the dual delivery of rhPDGF-BB and BMP2 significantly enhanced cell proliferation. However, the osteogenic differentiation of BMSCs was significantly suppressed even though the amount of BMP-2 secreted by the AdBMP2-transfected BMSCs was not significantly affected by the rhPDGF-BB treatment. In addition, dual delivery inhibited the mRNA expression of BMP receptor type II and Noggin in BMSCs. In in vivo experiments, critical-sized calvarial defects in rats showed enhanced bone regeneration by dual delivery of autologous AdBMP2-transfected BMSCs and rhPDGF-BB in both the amount of new bone formed and the bone mineral density. These enhancements in bone regeneration were greater than those observed in the group treated with AdBMP2-transfected BMSCs alone. In conclusion, the dual delivery of rhPDGF-BB and AdBMP2-transfected BMSCs improved the quality of the regenerated bone, possibly due to the modulation of PDGF-BB on BMP-2-induced osteogenesis.

  9. Chitosan-plasmid nanoparticle formulations for IM and SC delivery of recombinant FGF-2 and PDGF-BB or generation of antibodies.

    PubMed

    Jean, M; Smaoui, F; Lavertu, M; Méthot, S; Bouhdoud, L; Buschmann, M D; Merzouki, A

    2009-09-01

    Growth factor therapy is an emerging treatment modality that enhances tissue vascularization, promotes healing and regeneration and can treat a variety of inflammatory diseases. Both recombinant human growth factor proteins and their gene therapy are in human clinical trials to heal chronic wounds. As platelet-derived growth factor-bb (PDGF-BB) and fibroblast growth factor-2 (FGF-2) are known to induce chemotaxis, proliferation, differentiation, and matrix synthesis, we investigated a non-viral means for gene delivery of these factors using the cationic polysaccharide chitosan. Chitosan is a polymer of glucosamine and N-acetyl-glucosamine, in which the percentage of the residues that are glucosamine is called the degree of deacetylation (DDA). The purpose of this study was to express PDGF-BB and FGF-2 genes in mice using chitosan-plasmid DNA nanoparticles for the controlled delivery of genetic material in a specific, efficient, and safe manner. PDGF-BB and FGF-2 genes were amplified from human tissues by RT-PCR. To increase the secretion of FGF-2, a recombinant 4sFGF-2 was constructed bearing eight amino-acid residues of the signal peptide of FGF-4. PCR products were inserted into the expression vector pVax1 to produce recombinant plasmids pVax1-4sFGF2 and pVax1-PDGF-BB, which were then injected into BALB/C mice in the format of polyelectrolyte nanocomplexes with specific chitosans of controlled DDA and molecular weight, including 92-10, 80-10, and 80-80 (DDA-number average molecular weight or M(n) in kDa). ELISA assays on mice sera showed that recombinant FGF-2 and PDGF-BB proteins were efficiently expressed and specific antibodies to these proteins could be identified in sera of injected mice, but with levels that were clearly dependent on the specific chitosan used. We found high DDA low molecular weight chitosans to be efficient protein expressors with minimal or no generation of neutralizing antibodies, while lowering DDA resulted in greater antibody levels

  10. Human Neonatal Rotavirus Vaccine (RV3-BB) to Target Rotavirus from Birth.

    PubMed

    Bines, Julie E; At Thobari, Jarir; Satria, Cahya Dewi; Handley, Amanda; Watts, Emma; Cowley, Daniel; Nirwati, Hera; Ackland, James; Standish, Jane; Justice, Frances; Byars, Gabrielle; Lee, Katherine J; Barnes, Graeme L; Bachtiar, Novilia S; Viska Icanervilia, Ajeng; Boniface, Karen; Bogdanovic-Sakran, Nada; Pavlic, Daniel; Bishop, Ruth F; Kirkwood, Carl D; Buttery, Jim P; Soenarto, Yati

    2018-02-22

    A strategy of administering a neonatal rotavirus vaccine at birth to target early prevention of rotavirus gastroenteritis may address some of the barriers to global implementation of a rotavirus vaccine. We conducted a randomized, double-blind, placebo-controlled trial in Indonesia to evaluate the efficacy of an oral human neonatal rotavirus vaccine (RV3-BB) in preventing rotavirus gastroenteritis. Healthy newborns received three doses of RV3-BB, administered according to a neonatal schedule (0 to 5 days, 8 weeks, and 14 weeks of age) or an infant schedule (8 weeks, 14 weeks, and 18 weeks of age), or placebo. The primary analysis was conducted in the per-protocol population, which included only participants who received all four doses of vaccine or placebo within the visit windows, with secondary analyses performed in the intention-to-treat population, which included all participants who underwent randomization. Among the 1513 participants in the per-protocol population, severe rotavirus gastroenteritis occurred up to the age of 18 months in 5.6% of the participants in the placebo group (28 of 504 babies), in 1.4% in the neonatal-schedule vaccine group (7 of 498), and in 2.7% in the infant-schedule vaccine group (14 of 511). This resulted in a vaccine efficacy of 75% (95% confidence interval [CI], 44 to 91) in the neonatal-schedule group (P<0.001), 51% (95% CI, 7 to 76) in the infant-schedule group (P=0.03), and 63% (95% CI, 34 to 80) in the neonatal-schedule and infant-schedule groups combined (combined vaccine group) (P<0.001). Similar results were observed in the intention-to-treat analysis (1649 participants); the vaccine efficacy was 68% (95% CI, 35 to 86) in the neonatal-schedule group (P=0.001), 52% (95% CI, 11 to 76) in the infant-schedule group (P=0.02), and 60% (95% CI, 31 to 76) in the combined vaccine group (P<0.001). Vaccine response, as evidenced by serum immune response or shedding of RV3-BB in the stool, occurred in 78 of 83 participants (94%) in

  11. Silver halide sensitized gelatin derived from BB-640 holographic emulsion.

    PubMed

    Neipp, C; Pascual, I; Beléndez, A

    1999-03-10

    Silver halide sensitized gelatin (SHSG) is one of the most interesting techniques for the production of holographic optical elements, achieving relatively high sensitivity of photographic material with a low scattering of dichromated gelatin. Here we present experimental results for SHSG derived from the novel BB-640, a red-sensitive ultra-fine-grain emulsion from Holographic Recording Technologies (Steinau, Germany). The material is characterized before recording and after processing, and information about the thickness, absorption, and refractive-index modulation of the final holograms is obtained. The influence of the developer is analyzed, and diffraction efficiencies as great as 96.2% (after allowing for reflections) with a transmission of 1% and absorption and scatter losses of 2.8% are obtained with AAC developer. Our investigations reveal that high-quality SHSG transmission holograms may be obtained with the new BB-640 plates.

  12. PDGF-BB regulates the pulmonary vascular tone: impact of prostaglandins, calcium, MAPK- and PI3K/AKT/mTOR signalling and actin polymerisation in pulmonary veins of guinea pigs.

    PubMed

    Rieg, Annette D; Suleiman, Said; Anker, Carolin; Verjans, Eva; Rossaint, Rolf; Uhlig, Stefan; Martin, Christian

    2018-06-19

    Platelet-derived growth factor (PDGF)-BB and its receptor PDGFR are highly expressed in pulmonary hypertension (PH) and mediate proliferation. Recently, we showed that PDGF-BB contracts pulmonary veins (PVs) and that this contraction is prevented by inhibition of PDGFR-β (imatinib/SU6668). Here, we studied PDGF-BB-induced contraction and downstream-signalling in isolated perfused lungs (IPL) and precision-cut lung slices (PCLS) of guinea pigs (GPs). In IPLs, PDGF-BB was perfused after or without pre-treatment with imatinib (perfused/nebulised), the effects on the pulmonary arterial pressure (P PA ), the left atrial pressure (P LA ) and the capillary pressure (P cap ) were studied and the precapillary (R pre ) and postcapillary resistance (R post ) were calculated. Perfusate samples were analysed (ELISA) to detect the PDGF-BB-induced release of prostaglandin metabolites (TXA 2 /PGI 2 ). In PCLS, the contractile effect of PDGF-BB was evaluated in pulmonary arteries (PAs) and PVs. In PVs, PDGF-BB-induced contraction was studied after inhibition of PDGFR-α/β, L-Type Ca 2+ -channels, ROCK/PKC, prostaglandin receptors, MAP2K, p38-MAPK, PI3K-α/γ, AKT/PKB, actin polymerisation, adenyl cyclase and NO. Changes of the vascular tone were measured by videomicroscopy. In PVs, intracellular cAMP was measured by ELISA. In IPLs, PDGF-BB increased P PA , P cap and R post . In contrast, PDGF-BB had no effect if lungs were pre-treated with imatinib (perfused/nebulised). In PCLS, PDGF-BB significantly contracted PVs/PAs which was blocked by the PDGFR-β antagonist SU6668. In PVs, inhibition of actin polymerisation and inhibition of L-Type Ca 2+ -channels reduced PDGF-BB-induced contraction, whereas inhibition of ROCK/PKC had no effect. Blocking of EP 1/3 - and TP-receptors or inhibition of MAP2K-, p38-MAPK-, PI3K-α/γ- and AKT/PKB-signalling prevented PDGF-BB-induced contraction, whereas inhibition of EP 4 only slightly reduced it. Accordingly, PDGF-BB increased TXA 2 in the

  13. 40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

  14. 40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

  15. 40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

  16. 40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

  17. 40 CFR 174.518 - Bacillus thuringiensis Cry3Bb1 protein in corn; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Bacillus thuringiensis Cry3Bb1 protein... Cry3Bb1 protein in corn; exemption from the requirement of a tolerance. Residues of Bacillus thuringiensis Cry3Bb1 protein in corn are exempt from the requirement of a tolerance when used as plant-incorporated...

  18. Pseudomonas syringae Type III Effector HopBB1 Promotes Host Transcriptional Repressor Degradation to Regulate Phytohormone Responses and Virulence.

    PubMed

    Yang, Li; Teixeira, Paulo José Pereira Lima; Biswas, Surojit; Finkel, Omri M; He, Yijian; Salas-Gonzalez, Isai; English, Marie E; Epple, Petra; Mieczkowski, Piotr; Dangl, Jeffery L

    2017-02-08

    Independently evolved pathogen effectors from three branches of life (ascomycete, eubacteria, and oomycete) converge onto the Arabidopsis TCP14 transcription factor to manipulate host defense. However, the mechanistic basis for defense control via TCP14 regulation is unknown. We demonstrate that TCP14 regulates the plant immune system by transcriptionally repressing a subset of the jasmonic acid (JA) hormone signaling outputs. A previously unstudied Pseudomonas syringae (Psy) type III effector, HopBB1, interacts with TCP14 and targets it to the SCF COI1 degradation complex by connecting it to the JA signaling repressor JAZ3. Consequently, HopBB1 de-represses the TCP14-regulated subset of JA response genes and promotes pathogen virulence. Thus, HopBB1 fine-tunes host phytohormone crosstalk by precisely manipulating part of the JA regulon to avoid pleiotropic host responses while promoting pathogen proliferation. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. PDGF-BB Promotes Type I IFN-Dependent Vascular Alterations and Monocyte Recruitment in a Model of Dermal Fibrosis.

    PubMed

    Cho, John S; Fang, Terry C; Reynolds, Taylor L; Sofia, Daniel J; Hamann, Stefan; Burkly, Linda C

    2016-01-01

    Systemic sclerosis (SSc) is a chronic autoimmune disorder that can result in extensive tissue damage in the skin and, in advanced cases, internal organs. Vasculopathy, aberrant immune activation, and tissue fibrosis are three hallmarks of the disease that have been identified, with vasculopathy and aberrant immunity being amongst the earliest events. However, a mechanistic link between these processes has not been established. Here, we have identified a novel role of platelet derived growth factor-BB (PDGF-BB)/PDGFRβ activation in combination with dermal injury induced by bleomycin as a driver of early, aberrant expression of interferon stimulatory genes (ISGs) and inflammatory monocyte infiltration. Activation of PDGFRβ in combination with bleomycin-induced dermal injury resulted in increased dermal thickness, vascular density, monocyte/macrophage infiltration, and exacerbation of tissue injury. Many of these features were dependent on IFNAR-signaling, and an increase in the number of interferon-beta (IFN-β) producing monocytes cells was found in the skin lesions. Taken together, these results identify a novel link between PDGFRβ activation, and Type I IFN-driven vascular maintenance and monocyte/macrophage cell recruitment, and provide a potential explanation linking key features of SSc that were previously thought to be unrelated.

  20. Iptakalim inhibits PDGF-BB-induced human airway smooth muscle cells proliferation and migration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Wenrui; Kong, Hui; Zeng, Xiaoning

    Chronic airway diseases are characterized by airway remodeling which is attributed partly to the proliferation and migration of airway smooth muscle cells (ASMCs). ATP-sensitive potassium (K{sub ATP}) channels have been identified in ASMCs. Mount evidence has suggested that K{sub ATP} channel openers can reduce airway hyperresponsiveness and alleviate airway remodeling. Opening K{sup +} channels triggers K{sup +} efflux, which leading to membrane hyperpolarization, preventing Ca{sup 2+}entry through closing voltage-operated Ca{sup 2+} channels. Intracellular Ca{sup 2+} is the most important regulator of muscle contraction, cell proliferation and migration. K{sup +} efflux decreases Ca{sup 2+} influx, which consequently influences ASMCs proliferation andmore » migration. As a K{sub ATP} channel opener, iptakalim (Ipt) has been reported to restrain the proliferation of pulmonary arterial smooth muscle cells (PASMCs) involved in vascular remodeling, while little is known about its impact on ASMCs. The present study was designed to investigate the effects of Ipt on human ASMCs and the mechanisms underlying. Results obtained from cell counting kit-8 (CCK-8), flow cytometry and 5-ethynyl-2′-deoxyuridine (EdU) incorporation showed that Ipt significantly inhibited platelet-derived growth factor (PDGF)-BB-induced ASMCs proliferation. ASMCs migration induced by PDGF-BB was also suppressed by Ipt in transwell migration and scratch assay. Besides, the phosphorylation of Ca{sup 2+}/calmodulin-dependent kinase II (CaMKII), extracellular regulated protein kinases 1/2 (ERK1/2), protein kinase B (Akt), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) were as well alleviated by Ipt administration. Furthermore, we found that the inhibition of Ipt on the PDGF-BB-induced proliferation and migration in human ASMCs was blocked by glibenclamide (Gli), a selective K{sub ATP} channel antagonist. These findings provide a strong evidence to support that

  1. 56. Entry door (closed), BB16, basement level, building 500, looking ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    56. Entry door (closed), BB-16, basement level, building 500, looking southeast - Offutt Air Force Base, Strategic Air Command Headquarters & Command Center, Headquarters Building, 901 SAC Boulevard, Bellevue, Sarpy County, NE

  2. 1993/03 Baccalaureate and Beyond Longitudinal Study (B&B:93/03). Methodology Report. NCES 2006-166

    ERIC Educational Resources Information Center

    Wine, Jennifer S.; Cominole, Melissa B.; Wheeless, Sara; Dudley, Kristin; Franklin, Jeff

    2005-01-01

    This report describes the procedures and results of the full-scale implementation of the B&B:93/03 study. Students who earned a bachelor's degree in 1992-93 were first interviewed in 1993 and then subsequently in 1994 and 1997. This is the final follow-up interview of the B&B:93 cohort, 10 years following completion of the bachelor's…

  3. Ball Bearing (BB) Guns, Ease of Purchase and Potential for Significant Injury

    PubMed Central

    Grocock, C; McCarthy, R; Williams, DJ

    2006-01-01

    INTRODUCTION Ball bearing guns are used in the UK for war games, but they have the potential to cause severe injury if used incorrectly. MATERIALS AND METHODS A search was made for availability of these weapons, the ease of purchase and the potential for tissue damage. RESULTS These weapons are widely available on the Internet and are easy to purchase with no security checks. Once fully charged, an electric BB gun is capable of penetrating a cadaveric animal model at distances up to 5 m (1 m = 25 mm penetration, 3 m = 20 mm penetration, 5 m = 15 mm penetration). CONCLUSIONS BB guns are not toys and have a significant potential to cause injury. PMID:16834864

  4. Heightened clinical utility of smartphone versus body-worn inertial system for shoulder function B-B score.

    PubMed

    Pichonnaz, Claude; Aminian, Kamiar; Ancey, Céline; Jaccard, Hervé; Lécureux, Estelle; Duc, Cyntia; Farron, Alain; Jolles, Brigitte M; Gleeson, Nigel

    2017-01-01

    The B-B Score is a straightforward kinematic shoulder function score including only two movements (hand to the Back + lift hand as to change a Bulb) that demonstrated sound measurement properties for patients for various shoulder pathologies. However, the B-B Score results using a smartphone or a reference system have not yet been compared. Provided that the measurement properties are comparable, the use of a smartphone would offer substantial practical advantages. This study investigated the concurrent validity of a smartphone and a reference inertial system for the measurement of the kinematic shoulder function B-B Score. Sixty-five patients with shoulder conditions (with rotator cuff conditions, adhesive capsulitis and proximal humerus fracture) and 20 healthy participants were evaluated using a smartphone and a reference inertial system. Measurements were performed twice, alternating between two evaluators. The B-B Score differences between groups, differences between devices, relationship between devices, intra- and inter-evaluator reproducibility were analysed. The smartphone mean scores (SD) were 94.1 (11.1) for controls and 54.1 (18.3) for patients (P < 0.01). The difference between devices was non-significant for the control (P = 0.16) and the patient group (P = 0.81). The analysis of the relationship between devices showed 0.97 ICC, -0.6 bias and -13.2 to 12.0 limits of agreement (LOA). The smartphone intra-evaluator ICC was 0.92, the bias 1.5 and the LOA -17.4 to 20.3. The smartphone inter-evaluator ICC was 0.92, the bias 1.5 and the LOA -16.9 to 20.0. The B-B Score results measured with a smartphone were comparable to those of an inertial system. While single measurements diverged in some cases, the intra- and inter-evaluator reproducibility was excellent and was equivalent between devices. The B-B score measured with a smartphone is straightforward and as efficient as a reference inertial system measurement.

  5. Heightened clinical utility of smartphone versus body-worn inertial system for shoulder function B-B score

    PubMed Central

    Aminian, Kamiar; Ancey, Céline; Jaccard, Hervé; Lécureux, Estelle; Duc, Cyntia; Farron, Alain; Jolles, Brigitte M.; Gleeson, Nigel

    2017-01-01

    Background The B-B Score is a straightforward kinematic shoulder function score including only two movements (hand to the Back + lift hand as to change a Bulb) that demonstrated sound measurement properties for patients for various shoulder pathologies. However, the B-B Score results using a smartphone or a reference system have not yet been compared. Provided that the measurement properties are comparable, the use of a smartphone would offer substantial practical advantages. This study investigated the concurrent validity of a smartphone and a reference inertial system for the measurement of the kinematic shoulder function B-B Score. Methods Sixty-five patients with shoulder conditions (with rotator cuff conditions, adhesive capsulitis and proximal humerus fracture) and 20 healthy participants were evaluated using a smartphone and a reference inertial system. Measurements were performed twice, alternating between two evaluators. The B-B Score differences between groups, differences between devices, relationship between devices, intra- and inter-evaluator reproducibility were analysed. Results The smartphone mean scores (SD) were 94.1 (11.1) for controls and 54.1 (18.3) for patients (P < 0.01). The difference between devices was non-significant for the control (P = 0.16) and the patient group (P = 0.81). The analysis of the relationship between devices showed 0.97 ICC, −0.6 bias and −13.2 to 12.0 limits of agreement (LOA). The smartphone intra-evaluator ICC was 0.92, the bias 1.5 and the LOA −17.4 to 20.3. The smartphone inter-evaluator ICC was 0.92, the bias 1.5 and the LOA −16.9 to 20.0. Conclusions The B-B Score results measured with a smartphone were comparable to those of an inertial system. While single measurements diverged in some cases, the intra- and inter-evaluator reproducibility was excellent and was equivalent between devices. The B-B score measured with a smartphone is straightforward and as efficient as a reference inertial system

  6. Fragment Bb in Amniotic Fluid: Evidence for complement activation by the alternative pathway in women with Intra-amniotic Infection/Inflammation

    PubMed Central

    Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Tovi, Shali Mazaki; Pedro, Kusanovic Juan; Soto, Eleazar; Gotsch, Francesca; Dong, Zhong; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Mittal, Pooja; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.

    2013-01-01

    Objective Fragment Bb is an activator of the alternative pathway of the complement system. Recently, increased first trimester maternal plasma concentrations of this fragment were reported in patients destined to have a spontaneous preterm delivery before 34 weeks of gestation. The aim of this study was to determine whether the amniotic fluid (AF) concentrations of fragment Bb change with gestational age, spontaneous labor (term and preterm), and in the presence of intra-amniotic infection/ inflammation (IAI). Study design This cross-sectional study included patients in the following groups: 1) midtrimester (n=64); 2) term in spontaneous labor (n=70); 3) term not in labor (n=43); 4) spontaneous preterm labor (PTL) who delivered at term (n=76); 5) PTL without IAI who delivered preterm (n=73); 6) PTL with IAI (n=76); 7) prelabor rupture of the membranes (preterm PROM) without IAI (n=71); and 8) preterm PROM with IAI (n=71). Fragment Bb concentration in amniotic fluid was determined by an enzyme-linked immunoassay. Non-parametric statistics were used for analyses. Results 1) Fragment Bb was detected in all AF samples (n=544); 2) The median AF concentration of fragment Bb in patients at term not in labor was significantly higher than that of those in the mid-trimester [2.42 μg/mL, interquartile range (IQR) 1.78-3.22 vs. 1.64 μg/mL, IQR 1.06-3.49; p<0.001]; 3) Among patients with PTL, those with IAI had a higher median AF fragment Bb concentration than that of woman without IAI who delivered preterm (4.82 μg/mL, IQR 3.32-6.08 vs. 3.67 μg/mL, IQR 2.35-4.57; p<0.001) and than that of women with an episode of PTL who delivered at term (3.21 μg/mL, IQR 2.39-4.16; p<0.001); 4) Similarly, among patients with preterm PROM, the median AF fragment Bb concentration was higher in individuals with IAI than in those without IAI (4.24 μg/mL, IQR 2.58-5.79 vs. 2.79 μg/mL, IQR 2.09-3.89; p<0.001). 5) Among patients at term, the median AF fragment Bb concentration did not differ

  7. Section BB Hatch Coating; Framing Plan on Line C Lodging ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Section B-B Hatch Coating; Framing Plan on Line C Lodging Knees at Hatch; Elevation A-A Hull Framing; Section at Hatch Frame 36, Starboard Looking Aft; Midship Section Frame 37, Port Looking Aft - Steam Schooner WAPAMA, Kaiser Shipyard No. 3 (Shoal Point), Richmond, Contra Costa County, CA

  8. Exposure of a distinct PDCA-1+ (CD317) B cell population to agonistic anti-4-1BB (CD137) inhibits T and B cell responses both in vitro and in vivo.

    PubMed

    Vinay, Dass S; Lee, Seung J; Kim, Chang H; Oh, Ho Sik; Kwon, Byoung S

    2012-01-01

    4-1BB (CD137) is an important T cell activating molecule. Here we report that it also promotes development of a distinct B cell subpopulation co-expressing PDCA-1. 4-1BB is expressed constitutively, and its expression is increased when PDCA-1(+) B cells are activated. We found that despite a high level of surface expression of 4-1BB on PDCA-1(+) B cells, treatment of these cells with agonistic anti-4-1BB mAb stimulated the expression of only a few activation markers (B7-2, MHC II, PD-L2), cytokines (IL-12p40/p70), and chemokines (MCP-1, RANTES), as well as sTNFR1, and the immunosuppressive enzyme, IDO. Although the PDCA-1(+) B cells stimulated by anti-4-1BB expressed MHC II at high levels and took up antigens efficiently, Ig class switching was inhibited when they were pulsed with T-independent (TI) or T-dependent (TD) Ags and adoptively transferred into syngeneic recipients. Furthermore, when anti-4-1BB-treated PDCA-1(+) B cells were pulsed with OVA peptide and combined with Vα2(+)CD4(+) T cells, Ag-specific cell division was inhibited both in vitro and in vivo. Our findings suggest that the 4-1BB signal transforms PDCA-1(+) B cells into propagators of negative immune regulation, and establish an important role for 4-1BB in PDCA-1(+) B cell development and function.

  9. 32. SECTIONS AA, BB, CC, DD, AND EE WASTE CALCINATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    32. SECTIONS A-A, B-B, C-C, D-D, AND E-E WASTE CALCINATION FACILITY SHOWING RELATIONSHIPS OF DIFFERENT FLOOR LEVELS TO ONE ANOTHER. INEEL DRAWING NUMBER 200-0633-00-287-106353. FLUOR NUMBER 5775-CPP-633-A-3. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

  10. 2008/09 Baccalaureate and Beyond Longitudinal Study (B&B:08/09). Full-Scale Methodology Report. NCES 2014-041

    ERIC Educational Resources Information Center

    Wine, Jennifer; Janson, Natasha; Siegel, Peter; Bennett, Christopher

    2013-01-01

    This report documents the methodological procedures and evaluations of the 2008/09 Baccalaureate and Beyond Longitudinal Study (B&B:08/09). RTI, with the assistance of MPR, conducted B&B:08/09 for the National Center for Education Statistics (NCES) of the U.S. Department of Education. Chapter 1 describes the background, legislative…

  11. Advanced Manufacturing Process for Lower Cost Rechargeable Lithium-ion Batteries for DOD Including the BB2590

    DTIC Science & Technology

    2013-11-30

    Rechargeable Lithium-ion Batteries for DOD Including the BB2590 Contract #SP4701-10-C-0032 Submitted by LithChem Energy (Div. of Retriev...Lithium-ion Batteries for DOD Including the BB2590 5a. CONTRACT NUMBER AP4701-10-C-0032 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...automated lithium-ion bi-cell production machine to produce lower cost prismatic lithium-ion batteries for the DOD. This machine was completed and

  12. Hyaluronic acid/Chitosan nanoparticles as delivery vehicles for VEGF and PDGF-BB.

    PubMed

    Parajó, Yolanda; D'Angelo, Ivana; Welle, Alexander; Garcia-Fuentes, Marcos; Alonso, María José

    2010-11-01

    The development of a vascular network in tissue-engineered constructs is a fundamental bottleneck of bioregenerative medicine, particularly when the size of the implant exceeds a certain limit given by diffusion lengths and/or if the host tissue shows a very active metabolism. One of the approaches to achieve the vascularization of tissue constructs is generating a sustained release of proangiogenic factors from the ischemic site. This work describes the formation and characterization of hyaluronic acid-chitosan (HA/CS) nanoparticles for the delivery of two pro-angiogenic growth factors: vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF-BB). These nanoparticles were prepared by an ionic gelification technique, and different formulations were developed by encapsulating the growth factors in association with two stabilizing agents: bovine serum albumin or heparin sodium salt. These carriers were characterized with regard to their physicochemical properties, their stability in biological media, and their cytotoxicity in the C3a hepatoma cell line. The results show that nanoparticles around 200 nm can be prepared by this method. HA/CS nanoparticles were stable when incubated in EMEM cell culture medium or in water at 37°C for 24 h. Cell culture tests confirmed that HA/CS nanoparticles are not cytotoxic within the concentration range used for growth factor delivery. Moreover, HA/CS nanoparticles were able to entrap efficiently both growth factors, reaching association values of 94% and 54% for VEGF and PDGF, respectively. In vitro release studies confirm that PDGF-BB is released from HA/CS nanoparticles in a sustained manner over approximately 1 week. On the other hand, VEGF is completely released within the first 24 h.

  13. Electroluminescent TCC, C3dg and fB/Bb epitope assays for profiling complement cascade activation in vitro using an activated complement serum calibration standard.

    PubMed

    van Vuuren, B Jansen; Bergseth, G; Mollnes, T E; Shaw, A M

    2014-01-15

    Electroluminescent assays for epitopes on the complement components C3dg, terminal complement complex (TCC) and factor B/Bb (fB/Bb) have been developed with capture and detection antibodies to produce detection limits C3dg=91±9ng/mL, TCC=3±0.1ng/mL and fB=55.7±0.1ng/mL. The assay performance was assessed against a series of zymosan and heat aggregated IgG (HAIgG) in vitro activations of complement using a calibrated activated complement serum (ACS) as calibration standard. The ACS standard was stable within 20% accuracy over a 6-month period with freeze-thaw cycles as required. Differential activation of the complement cascade was observed for TCC showing a pseudo-first order formation half-life of 3.5h after activation with zymosan. The C3dg activation fragment indicates a 10% total activation for both activation agents. The kinetic-epitope analysis for fB indicates that the capture epitope is on the fB/Bb protein fragment which can then become covered by the formation of C3bBb or C3bBbP complexes during the time course of the cascade. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study

    PubMed Central

    Merenstein, Daniel J; Tan, Tina P; Molokin, Aleksey; Smith, Keisha Herbin; Roberts, Robert F; Shara, Nawar M; Mete, Mihriye; Sanders, Mary Ellen; Solano-Aguilar, Gloria

    2015-01-01

    Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of adults who were prescribed a 10-day course of antibiotics for a respiratory infection. Secondary aims were to assess the ability of BB-12 to affect the expression of whole blood immune markers associated with cell activation and inflammatory response. A phase I, double-blinded, randomized controlled study was conducted in compliance with FDA guidelines for an Investigational New Drug (IND). Forty participants were randomly assigned to consume 4 ounces of either BB-12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The primary outcome was to assess safety and tolerability, assessed by the number of reported adverse events. A total of 165 non-serious adverse events were reported, with no differences between the control and BB-12 groups. When compared to the control group, B lactis fecal levels were modestly higher in the BB-12-supplemented group. In a small subset of patients, changes in whole blood expression of genes associated with regulation and activation of immune cells were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe and well tolerated when consumed by healthy adults concurrently taking antibiotics. This study will form the basis for future randomized clinical trials investigating the potential immunomodulatory effects of BB-12-supplemented yogurt in a variety of disease states. PMID:25569274

  15. Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study.

    PubMed

    Merenstein, Daniel J; Tan, Tina P; Molokin, Aleksey; Smith, Keisha Herbin; Roberts, Robert F; Shara, Nawar M; Mete, Mihriye; Sanders, Mary Ellen; Solano-Aguilar, Gloria

    2015-01-01

    Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of adults who were prescribed a 10-day course of antibiotics for a respiratory infection. Secondary aims were to assess the ability of BB-12 to affect the expression of whole blood immune markers associated with cell activation and inflammatory response. A phase I, double-blinded, randomized controlled study was conducted in compliance with FDA guidelines for an Investigational New Drug (IND). Forty participants were randomly assigned to consume 4 ounces of either BB-12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The primary outcome was to assess safety and tolerability, assessed by the number of reported adverse events. A total of 165 non-serious adverse events were reported, with no differences between the control and BB-12 groups. When compared to the control group, B lactis fecal levels were modestly higher in the BB-12-supplemented group. In a small subset of patients, changes in whole blood expression of genes associated with regulation and activation of immune cells were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe and well tolerated when consumed by healthy adults concurrently taking antibiotics. This study will form the basis for future randomized clinical trials investigating the potential immunomodulatory effects of BB-12-supplemented yogurt in a variety of disease states.

  16. De Novo whole genome sequence of Xylella fastidiosa subsp. multiplex strain BB01 from blueberry in Georgia, USA

    USDA-ARS?s Scientific Manuscript database

    This study reports a de novo assembled draft genome sequence of Xylella fastidiosa subsp. multiplex strain BB01 causing blueberry bacterial leaf scorch in Georgia, USA. The BB01 genome is 2,517,579 bp with a G+C content of 51.8% and 2,943 open reading frames (ORFs) and 48 RNA genes....

  17. Trends in BB/pellet gun injuries in children and teenagers in the United States, 1985-99.

    PubMed

    Nguyen, M H; Annest, J L; Mercy, J A; Ryan, G W; Fingerhut, L A

    2002-09-01

    To characterize national trends in non-fatal BB/pellet gun related injury rates for persons aged 19 years or younger in relation to trends in non-fatal and fatal firearm related injury rates and discuss these trends in light of injury prevention and violence prevention efforts. The National Electronic Injury Surveillance System (NEISS) includes approximately 100 hospitals with at least six beds that provide emergency services. These hospitals comprise a stratified probability sample of all US hospitals with emergency departments. The National Vital Statistics System (NVSS) is a complete census of all death certificates filed by states and is compiled annually. National data on BB/pellet gun related injuries and injury rates were examined along with fatal and non-fatal firearm related injuries and injury rates. Non-fatal injury data for all BB/pellet gun related injury cases from 1985 through 1999, and firearm related injury cases from 1993 through 1999 were obtained from hospital emergency department records using the NEISS. Firearm related deaths from 1985 through 1999 were obtained from the NVSS. BB/pellet gun related injury rates increased from age 3 years to a peak at age 13 years and declined thereafter. In contrast, firearm related injury and death rates increased gradually until age 13 and then increased sharply until age 18 years. For persons aged 19 years and younger, BB/pellet gun related injury rates increased from the late 1980s until the early 1990s and then declined until 1999; these injury rates per 100 000 population were 24.0 in 1988, 32.8 in 1992, and 18.3 in 1999. This trend was similar to those for fatal and non-fatal firearm related injury rates per 100 000 which were 4.5 in 1985, 7.8 in 1993, and 4.3 in 1999 (fatal) and 38.6 in 1993 and 16.3 in 1999 (non-fatal). In 1999, an estimated 14 313 (95% confidence interval (CI) 12 025 to 16 601) cases with non-fatal BB/pellet gun injuries and an estimated 12 748 (95% CI 7881-17 615) cases with non

  18. Tangeretin, a citrus flavonoid, inhibits PGDF-BB-induced proliferation and migration of aortic smooth muscle cells by blocking AKT activation.

    PubMed

    Seo, Juhee; Lee, Hyun Sun; Ryoo, Sungwoo; Seo, Jee Hee; Min, Byung-Sun; Lee, Jeong-Hyung

    2011-12-30

    Tangeretin, a natural polymethoxylated flavone concentrated in the peel of citrus fruits, is known to have antiproliferative, antiinvasive, antimetastatic and antioxidant activities. However, the effect of tangeretin on vascular smooth muscle cells (VSMCs) is unknown. This study examined the effect of tangeretin on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of rat aortic smooth muscle cells (RASMCs) as well as its underlying mechanisms. Tangeretin significantly inhibited proliferation, DNA synthesis and migration of PDGF-BB-stimulated RASMCs without inducing cell death. Treatment with tangeretin-induced cell-cycle arrest in the G₀/G₁ phase was associated with down-regulation of cyclin D1 and cyclin E in addition to up-regulation of p27(kip1). We also showed that tangeretin inhibited PDGF-BB-induced phosphorylation of AKT, while it had no effect on the phosphorylation of phospholipase Cγ (PLCγ), PDGF receptor β-chain (PDGF-Rβ) and extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPKs). An in vitro kinase assay revealed that tangeretin inhibited AKT activity in a dose-dependent manner. Moreover, treatment of LY294002, a phosphoinositide 3-kinase (PI3K) inhibitor, had similar effects than that of tangeretin on the expression of p27(kip1) and cyclin D1, as well as cell migration in PDFG-BB-stimulated RASMCs. Taken together, these findings suggest that tangeretin could suppress PDGF-BB-induced proliferation and migration of RASMCs through the suppression of PI3K/AKT signaling pathway, and may be a potential candidate for preventing or treating vascular diseases, such as atherosclerosis and restenosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. The neonatal levels of TSB, NSE and CK-BB in autism spectrum disorder from Southern China.

    PubMed

    Lv, Meng-Na; Zhang, Hong; Shu, Yi; Chen, Shan; Hu, Yuan-Yuan; Zhou, Min

    2016-01-01

    Background" Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that impairs a child's ability to communicate with others. It also includes restricted repetitive behaviors, interests and activities. Symptoms manifest before the age of 3. In the previous studies, we found structural abnormalities of the temporal lobe cortex. High spine densities were most commonly found in ASD subjects with lower levels of cognitive functioning. In the present study, we retrospectively analyzed medical records in relation to the neonatal levels of total serum bilirubin (TSB), neuron-specific enolase (NSE), creatine kinase brain band isoenzyme (CK-BB), and neonatal behavior in ASD patients from Southern China. A total of 80 patients with ASD (ASD group) were screened for this retrospective study. Among them, 34 were low-functioning ASD (L-ASD group) and 46 were high-functioning ASD (H-ASD group). Identification of the ASD cases was confirmed with a Revised Autism Diagnostic Inventory. For comparison with ASD cases, 80 normal neonates (control group) were selected from the same period. Biochemical parameters, including TSB, NSE and CK-BB in the neonatal period and medical records on neonatal behavior were collected. The levels of serum TSB, NSE and CK-BB in the ASD group were significantly higher when compared with those from the control group (P < 0.01, or P < 0.05). The amounts of serum TSB, NSE and CK-BB in the L-ASD group were significantly higher when compared with those in the H-ASD group (P < 0.01, or P < 0.05). The Neonatal Behavioral Assessment Scale (NBAS) scores in the ASD group were significantly lower than that in the control group (P < 0.05). Likewise, the NBAS scores in the L-ASD group were significantly lower than that in the H-ASD group (P < 0.05). There was no association between serum TSB, NSE, CK-BB and NBAS scores (P > 0.05) in the ASD group. The neonatal levels of TSB, NSE and CK-BB in ASD from Southern China were significantly higher than

  20. The neonatal levels of TSB, NSE and CK-BB in autism spectrum disorder from Southern China

    PubMed Central

    Lv, Meng-na; Shu, Yi; Chen, Shan; Hu, Yuan-yuan; Zhou, Min

    2016-01-01

    Abstract Background" Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder that impairs a child’s ability to communicate with others. It also includes restricted repetitive behaviors, interests and activities. Symptoms manifest before the age of 3. In the previous studies, we found structural abnormalities of the temporal lobe cortex. High spine densities were most commonly found in ASD subjects with lower levels of cognitive functioning. In the present study, we retrospectively analyzed medical records in relation to the neonatal levels of total serum bilirubin (TSB), neuron-specific enolase (NSE), creatine kinase brain band isoenzyme (CK-BB), and neonatal behavior in ASD patients from Southern China. Methods: A total of 80 patients with ASD (ASD group) were screened for this retrospective study. Among them, 34 were low-functioning ASD (L-ASD group) and 46 were high-functioning ASD (H-ASD group). Identification of the ASD cases was confirmed with a Revised Autism Diagnostic Inventory. For comparison with ASD cases, 80 normal neonates (control group) were selected from the same period. Biochemical parameters, including TSB, NSE and CK-BB in the neonatal period and medical records on neonatal behavior were collected. Results: The levels of serum TSB, NSE and CK-BB in the ASD group were significantly higher when compared with those from the control group (P < 0.01, or P < 0.05). The amounts of serum TSB, NSE and CK-BB in the L-ASD group were significantly higher when compared with those in the H-ASD group (P < 0.01, or P < 0.05). The Neonatal Behavioral Assessment Scale (NBAS) scores in the ASD group were significantly lower than that in the control group (P < 0.05). Likewise, the NBAS scores in the L-ASD group were significantly lower than that in the H-ASD group (P < 0.05). There was no association between serum TSB, NSE, CK-BB and NBAS scores (P > 0.05) in the ASD group. Conclusions: The neonatal levels of TSB, NSE and CK-BB in ASD from

  1. Kapton wire arc track testing: Per test procedure KWATT BB01

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The results are presented of Kapton wire arc tracking tests performed at NASA-Johnson in 1990 using test procedure KWATT BB01. The tests were performed to gather data for use in assessing the safety of the Space Shuttle Orbiter wiring which is predominantly Kapton insulated.

  2. Security of BB84 with weak randomness and imperfect qubit encoding

    NASA Astrophysics Data System (ADS)

    Zhao, Liang-Yuan; Yin, Zhen-Qiang; Li, Hong-Wei; Chen, Wei; Fang, Xi; Han, Zheng-Fu; Huang, Wei

    2018-03-01

    The main threats for the well-known Bennett-Brassard 1984 (BB84) practical quantum key distribution (QKD) systems are that its encoding is inaccurate and measurement device may be vulnerable to particular attacks. Thus, a general physical model or security proof to tackle these loopholes simultaneously and quantitatively is highly desired. Here we give a framework on the security of BB84 when imperfect qubit encoding and vulnerability of measurement device are both considered. In our analysis, the potential attacks to measurement device are generalized by the recently proposed weak randomness model which assumes the input random numbers are partially biased depending on a hidden variable planted by an eavesdropper. And the inevitable encoding inaccuracy is also introduced here. From a fundamental view, our work reveals the potential information leakage due to encoding inaccuracy and weak randomness input. For applications, our result can be viewed as a useful tool to quantitatively evaluate the security of a practical QKD system.

  3. Search for CP violation in the decay Z→bb¯g

    NASA Astrophysics Data System (ADS)

    Wunsch, Martin; Aleph Collaboration

    1997-03-01

    About three million hadronic decays of the Z collected by ALEPH in the years 1991-1994 are used to search for anomalous CP violation beyond the Standard Model in the decay Z→bb¯g. The study is performed by analyzing angular correlations between the two quarks and the gluon in three-jet events and by measuring the differential two-jet rate. No signal of CP violation is found. For the combinations of anomalous CP violating couplings, h=h-h and hb*=√{h^Vb2+h^Ab2} limits of |h|<0.59 and h b* < 3.02 are given at 95% CL.

  4. Biomimetic hybrid porous scaffolds immobilized with platelet derived growth factor-BB promote cellularization and vascularization in tissue engineering.

    PubMed

    Murali, Ragothaman; Ponrasu, Thangavel; Cheirmadurai, Kalirajan; Thanikaivelan, Palanisamy

    2016-02-01

    Development of hybrid scaffolds with synergistic combination of growth factor is a promising approach to promote early in vivo wound repair and tissue regeneration. Here, we show the rapid wound healing in Wistar albino rats using biomimetic collagen-poly(dialdehyde) guar gum based hybrid porous scaffolds covalently immobilized with platelet derived growth factor-BB. The immobilized platelet derived growth factor in the hybrid scaffolds not only enhance the total protein, collagen, hexosamine, and uronic acid contents in the granulation tissue but also provide stronger tissues. The wound closure analysis reveal that the complete epithelialization period is 15.4 ± 0.9 days for collagen-poly(dialdehyde) guar gum-platelet derived growth factor hybrid scaffolds, whereas it is significantly higher for control, collagen, collagen- poly(dialdehyde) guar gum and povidine-iodine treated groups. Further, the histological evaluation shows that the immobilized platelet derived growth factor in the hybrid scaffolds induced a more robust cellular and vascular response in the implanted site. Hence, we demonstrate that the collagen-poly(dialdehyde) guar gum hybrid scaffolds loaded with platelet derived growth factor stimulates chemotactic effects in the implanted site to promote rapid tissue regeneration and wound repair without the assistance of antibacterial agents. © 2015 Wiley Periodicals, Inc.

  5. Uncoupling of the ITIM receptor G6b-B from the tyrosine phosphatases Shp1 and Shp2 disrupts platelet homeostasis in mice.

    PubMed

    Geer, Mitchell J; van Geffen, Johanna P; Gopalasingam, Piraveen; Vögtle, Timo; Smith, Christopher W; Heising, Silke; Kuijpers, Marijke J E; Tullemans, Bibian M E; Jarvis, Gavin E; Eble, Johannes A; Jeeves, Mark; Overduin, Michael; Heemskerk, Johan W M; Mazharian, Alexandra; Senis, Yotis A

    2018-06-11

    The immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptor G6b-B has emerged as a key regulator of platelet homeostasis. However, it remains unclear how it mediates its effects. Tyrosine phosphorylation of the ITIM and immunoreceptor tyrosine-based switch motif (ITSM) within the cytoplasmic tail of G6b-B provides a docking site for SH2 domain-containing protein-tyrosine phosphatases Shp1 and Shp2, which are also critical regulators of platelet production and function. In this study, we investigate the physiological consequences of uncoupling G6b-B from Shp1 and Shp2. To address this, we generated a transgenic mouse model expressing a mutant form of G6b-B in which tyrosine (Y) residues 212 and 238 within the ITIM and ITSM were mutated to phenylalanine (F), respectively. Mice homozygous for the mutation (G6b-B diY/F) were macrothrombocytopenic, due to a reduction in platelet production, had large clusters of megakaryocytes and myelofibrosis at sites of hematopoiesis, similar to that observed in G6b knockout (G6b KO) mice. Platelets from G6b-B diY/F mice were hypo-responsive to collagen, due to a significant reduction in expression of the immunoreceptor tyrosine-based activation motif (ITAM)-containing collagen receptor complex GPVI-FcR γ-chain, and thrombin, that could be partially rescued by co-stimulating the platelets with ADP. In contrast, platelets from G6b-B diY/F, G6b KO and megakaryocyte-specific Shp2 KO mice were hyper-responsive to antibody-mediated cross-linking of the hemi-ITAM-containing podoplanin receptor CLEC-2, suggesting that G6b-B inhibits CLEC-2-mediated platelet activation through Shp2. Findings from this study demonstrate that G6b-B must engage with Shp1 and Shp2 in order to mediate its regulatory effects on platelet homeostasis. Copyright © 2018 American Society of Hematology.

  6. Combined search for the standard model Higgs boson decaying to a bb pair using the full CDF data set.

    PubMed

    Aaltonen, T; Álvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Appel, J A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Auerbach, B; Aurisano, A; Azfar, F; Badgett, W; Bae, T; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauce, M; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Binkley, M E; Bisello, D; Bizjak, I; Bland, K R; Blumenfeld, B; Bocci, A; Bodek, A; Bortoletto, D; Boudreau, J; Boveia, A; Brigliadori, L; Bromberg, C; Brucken, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Calamba, A; Calancha, C; Camarda, S; Campanelli, M; Campbell, M; Canelli, F; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chung, W H; Chung, Y S; Ciocci, M A; Clark, A; Clarke, C; Compostella, G; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Crescioli, F; Cuevas, J; Culbertson, R; Dagenhart, D; d'Ascenzo, N; Datta, M; de Barbaro, P; Dell'Orso, M; Demortier, L; Deninno, M; Devoto, F; d'Errico, M; Di Canto, A; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Dorigo, M; Dorigo, T; Ebina, K; Elagin, A; Eppig, A; Erbacher, R; Errede, S; Ershaidat, N; Eusebi, R; Farrington, S; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Funakoshi, Y; Furic, I; Gallinaro, M; Garcia, J E; Garfinkel, A F; Garosi, P; Gerberich, H; Gerchtein, E; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Ginsburg, C M; Giokaris, N; Giromini, P; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldin, D; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Grinstein, S; Grosso-Pilcher, C; Group, R C; Guimaraes da Costa, J; Hahn, S R; Halkiadakis, E; Hamaguchi, A; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harr, R F; Hatakeyama, K; Hays, C; Heck, M; Heinrich, J; Herndon, M; Hewamanage, S; Hocker, A; Hopkins, W; Horn, D; Hou, S; Hughes, R E; Hurwitz, M; Husemann, U; Hussain, N; Hussein, M; Huston, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeans, D T; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Junk, T R; Kamon, T; Karchin, P E; Kasmi, A; Kato, Y; Ketchum, W; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kim, Y J; Kimura, N; Kirby, M; Klimenko, S; Knoepfel, K; Kondo, K; Kong, D J; Konigsberg, J; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Kruse, M; Krutelyov, V; Kuhr, T; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; LeCompte, T; Lee, E; Lee, H S; Lee, J S; Lee, S W; Leo, S; Leone, S; Lewis, J D; Limosani, A; Lin, C-J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, H; Liu, Q; Liu, T; Lockwitz, S; Loginov, A; Lucchesi, D; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; Madrak, R; Maeshima, K; Maestro, P; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Martínez, M; Mastrandrea, P; Matera, K; Mattson, M E; Mazzacane, A; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Mesropian, C; Miao, T; Mietlicki, D; Mitra, A; Miyake, H; Moed, S; Moggi, N; Mondragon, M N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mukherjee, A; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakano, I; Napier, A; Nett, J; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Noh, S Y; Norniella, O; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Ortolan, L; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pilot, J; Pitts, K; Plager, C; Pondrom, L; Poprocki, S; Potamianos, K; Prokoshin, F; Pranko, A; Ptohos, F; Punzi, G; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Rescigno, M; Riddick, T; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Ruffini, F; Ruiz, A; Russ, J; Rusu, V; Safonov, A; Sakumoto, W K; Sakurai, Y; Santi, L; Sato, K; Saveliev, V; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Seidel, S; Seiya, Y; Semenov, A; Sforza, F; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shochet, M; Shreyber-Tecker, I; Simonenko, A; Sinervo, P; Sliwa, K; Smith, J R; Snider, F D; Soha, A; Sorin, V; Song, H; Squillacioti, P; Stancari, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Sudo, Y; Sukhanov, A; Suslov, I; Takemasa, K; Takeuchi, Y; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thome, J; Thompson, G A; Thomson, E; Tipton, P; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Ukegawa, F; Uozumi, S; Varganov, A; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vila, I; Vilar, R; Vizán, J; Vogel, M; Volpi, G; Wagner, P; Wagner, R L; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Wester, W C; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Wick, F; Williams, H H; Wilson, J S; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, H; Wright, T; Wu, X; Wu, Z; Yamamoto, K; Yamato, D; Yang, T; Yang, U K; Yang, Y C; Yao, W-M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanetti, A; Zeng, Y; Zhou, C; Zucchelli, S

    2012-09-14

    We combine the results of searches for the standard model (SM) Higgs boson based on the full CDF Run II data set obtained from sqrt[s]=1.96  TeV pp collisions at the Fermilab Tevatron corresponding to an integrated luminosity of 9.45  fb(-1). The searches are conducted for Higgs bosons that are produced in association with a W or Z boson, have masses in the range 90-150  GeV/c(2), and decay into bb pairs. An excess of data is present that is inconsistent with the background prediction at the level of 2.5 standard deviations (the most significant local excess is 2.7 standard deviations).

  7. Local Application of Gelatin Hydrogel Sheets Impregnated With Platelet-Derived Growth Factor BB Promotes Tendon-to-Bone Healing After Rotator Cuff Repair in Rats.

    PubMed

    Tokunaga, Takuya; Ide, Junji; Arimura, Hitoshi; Nakamura, Takayuki; Uehara, Yusuke; Sakamoto, Hidetoshi; Mizuta, Hiroshi

    2015-08-01

    To determine whether the local application of platelet-derived growth factor BB (PDGF-BB) in hydrogel sheets would promote healing and improve histologic characteristics and biomechanical strength after rotator cuff (RC) repair in rats. To assess the effect of PDGF-BB on tendon-to-bone healing we divided 36 adult male Sprague-Dawley rats treated with bilateral surgery to repair the supraspinatus tendon at its insertion site into 3 groups: group 1 = suture-only group; group 2 = suture and gelatin hydrogel sheets impregnated with phosphate-buffered saline (PBS); and group 3 = suture and gelatin hydrogel sheets impregnated with PDGF-BB (0.5 μg). Semiquantitative histologic evaluation was carried out 2, 6, and 12 weeks later; cell proliferation was assessed 2 and 6 weeks postoperatively by immunostaining for proliferating cell nuclear antigen (PCNA), and biomechanical testing, including ultimate load to failure, stiffness, and ultimate stress to failure, was performed 12 weeks after the operation. At 2 weeks, the average percentage of PCNA-positive cells at the insertion site was significantly higher in group 3 (40.5% ± 2.4%) than in group 1 (32.1% ± 6.9%; P = .03) and group 2 (31.9% ± 3.7%; P = .02). At 2 and 6 weeks, the histologic scores were similar among the 3 groups. At 12 weeks, the histologic score was significantly higher in group 3 (10.3 ± 0.8) than in group 1 (8.5 ± 0.5; P = .002) or group 2 (8.8 ± 0.8; P = .009), whereas ultimate load to failure, stiffness, and ultimate load to stress (normal control population, 44.73 ± 9.75 N, 27.59 ± 4.32 N/mm, and 21.33 ± 4.65 N/mm(2), respectively) were significantly higher in group 3 (28.28 ± 6.28 N, 11.05 ± 2.37 N/mm, and 7.99 ± 2.13 N/mm(2), respectively) than in group 1 (10.44 ± 1.98 N, 4.74 ± 1.31 N/mm, and 3.28 ± 1.27 N/mm(2), respectively; all P < .001) or group 2 (11.85 ± 2.89 N, 5.86 ± 1.75 N/mm, and 3.31 ± 0.80 N/mm(2), respectively; all P < .001). The placement of a PDGF-BB

  8. Redirecting T Cells to Glypican-3 with 4-1BB Zeta Chimeric Antigen Receptors Results in Th1 Polarization and Potent Antitumor Activity

    PubMed Central

    Li, Wenpeng; Guo, Linjie; Rathi, Purva; Marinova, Ekaterina; Gao, Xiuhua; Wu, Meng-Feng; Liu, Hao; Dotti, Gianpietro; Gottschalk, Stephen; Metelitsa, Leonid S.; Heczey, Andras

    2017-01-01

    T cells engineered to express CD19-specific chimeric antigen receptors (CARs) have shown breakthrough clinical successes in patients with B-cell lymphoid malignancies. However, similar therapeutic efficacy of CAR T cells in solid tumors is yet to be achieved. In this study we systematically evaluated a series of CAR constructs targeting glypican-3 (GPC3), which is selectively expressed on several solid tumors. We compared GPC3-specific CARs that encoded CD3ζ (Gz) alone or with costimulatory domains derived from CD28 (G28z), 4-1BB (GBBz), or CD28 and 4-1BB (G28BBz). All GPC3-CARs rendered T cells highly cytotoxic to GPC3-positive hepatocellular carcinoma, hepatoblastoma, and malignant rhabdoid tumor cell lines in vitro. GBBz induced the preferential production of Th1 cytokines (interferon γ/granulocyte macrophage colony-stimulating factor) while G28z preferentially induced Th2 cytokines (interleukin-4/interleukin-10). Inclusion of 4-1BB in G28BBz could only partially ameliorate the Th2-polarizing effect of CD28. 4-1BB induced superior expansion of CAR T cells in vitro and in vivo. T cells expressing GPC3-CARs incorporating CD28, 4-1BB, or both induced sustained tumor regressions in two xenogeneic tumor models. Thus, GBBz CAR endows T cells with superior proliferative potential, potent antitumor activity, and a Th1-biased cytokine profile, justifying further clinical development of GBBz CAR for immunotherapy of GPC3-positive solid tumors. PMID:27530312

  9. Trends in BB/pellet gun injuries in children and teenagers in the United States, 1985–99

    PubMed Central

    Nguyen, M; Annest, J; Mercy, J; Ryan, G; Fingerhut, L

    2002-01-01

    Objective: To characterize national trends in non-fatal BB/pellet gun related injury rates for persons aged 19 years or younger in relation to trends in non-fatal and fatal firearm related injury rates and discuss these trends in light of injury prevention and violence prevention efforts. Setting: The National Electronic Injury Surveillance System (NEISS) includes approximately 100 hospitals with at least six beds that provide emergency services. These hospitals comprise a stratified probability sample of all US hospitals with emergency departments. The National Vital Statistics System (NVSS) is a complete census of all death certificates filed by states and is compiled annually. Methods: National data on BB/pellet gun related injuries and injury rates were examined along with fatal and non-fatal firearm related injuries and injury rates. Non-fatal injury data for all BB/pellet gun related injury cases from 1985 through 1999, and firearm related injury cases from 1993 through 1999 were obtained from hospital emergency department records using the NEISS. Firearm related deaths from 1985 through 1999 were obtained from the NVSS. Results: BB/pellet gun related injury rates increased from age 3 years to a peak at age 13 years and declined thereafter. In contrast, firearm related injury and death rates increased gradually until age 13 and then increased sharply until age 18 years. For persons aged 19 years and younger, BB/pellet gun related injury rates increased from the late 1980s until the early 1990s and then declined until 1999; these injury rates per 100 000 population were 24.0 in 1988, 32.8 in 1992, and 18.3 in 1999. This trend was similar to those for fatal and non-fatal firearm related injury rates per 100 000 which were 4.5 in 1985, 7.8 in 1993, and 4.3 in 1999 (fatal) and 38.6 in 1993 and 16.3 in 1999 (non-fatal). In 1999, an estimated 14 313 (95% confidence interval (CI) 12 025 to 16 601) cases with non-fatal BB/pellet gun injuries and an estimated 12 748

  10. 76 FR 55720 - BB&T Capital Partners Mezzanine Fund II, L.P.; Notice Seeking Exemption Under Section 312 of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-08

    ... SMALL BUSINESS ADMINISTRATION [License No. 04/04-0311] BB&T Capital Partners Mezzanine Fund II, L.P.; Notice Seeking Exemption Under Section 312 of the Small Business Investment Act, Conflicts of Interest Notice is hereby given that BB&T Capital Partners Mezzanine Fund II, 101 N. Cherry Street, Suite...

  11. rhPDGF-BB promotes early healing in a rat rotator cuff repair model.

    PubMed

    Kovacevic, David; Gulotta, Lawrence V; Ying, Liang; Ehteshami, John R; Deng, Xiang-Hua; Rodeo, Scott A

    2015-05-01

    Tendon-bone healing after rotator cuff repair occurs by fibrovascular scar tissue formation, which is weaker than a normal tendon-bone insertion site. Growth factors play a role in tissue formation and have the potential to augment soft tissue healing in the perioperative period. Our study aim was to determine if rhPDGF-BB delivery on a collagen scaffold can improve tendon-to-bone healing after supraspinatus tendon repair compared with no growth factor in rats as measured by (1) gross observations; (2) histologic analysis; and (3) biomechanical testing. Ninety-five male Sprague-Dawley rats underwent acute repair of the supraspinatus tendon. Rats were randomized into one of five groups: control (ie, repair only), scaffold only, and three different platelet-derived growth factor (PDGF) doses on the collagen scaffold. Animals were euthanized 5 days after surgery to assess cellular proliferation and angiogenesis. The remaining animals were analyzed at 4 weeks to assess repair site integrity by gross visualization, fibrocartilage formation with safranin-O staining, and collagen fiber organization with picrosirius red staining, and to determine the biomechanical properties (ie, load-to-failure testing) of the supraspinatus tendon-bone construct. The repaired supraspinatus tendon was in continuity with the bone in all animals. At 5 days, rhPDGF-BB delivery on a scaffold demonstrated a dose-dependent response in cellular proliferation and angiogenesis compared with the control and scaffold groups. At 28 days, with the numbers available, rhPDGF-BB had no effect on increasing fibrocartilage formation or improving collagen fiber maturity at the tendon-bone insertion site compared with controls. The control group had higher tensile loads to failure and stiffness (35.5 ± 8.8 N and 20.3 ± 4.5 N/mm) than all the groups receiving the scaffold, including the PDGF groups (scaffold: 27 ± 6.4 N, p = 0.021 and 13 ± 5.7 N/mm, p = 0.01; 30 µg/mL PDGF: 26.5 ± 7.5 N, p = 0.014 and 13

  12. Hybrid CATV/MMW/BB lightwave transmission system based on fiber-wired/fiber-wireless/fiber-VLLC integrations.

    PubMed

    Li, Chung-Yi; Lu, Hai-Han; Lu, Ting-Chieh; Chu, Chien-An; Chen, Bo-Rui; Lin, Chun-Yu; Peng, Peng-Chun

    2015-12-14

    A hybrid lightwave transmission system for cable television (CATV)/millimeter-wave (MMW)/baseband (BB) signal transmission based on fiber-wired/fiber-wireless/fiber-visible laser light communication (VLLC) integrations is proposed and demonstrated. For down-link transmission, the light is intensity-modulated with 50-550 MHz CATV signal and optically promoted from 25 GHz radio frequency (RF) signal to 10 Gbps/50 GHz and 20 Gbps/100 GHz MMW data signals based on fiber-wired and fiber-wireless integrations. Good performances of carrier-to-noise ratio (CNR), composite second-order (CSO), composite triple-beat (CTB), and bit error rate (BER) are obtained over a 40-km single-mode fiber (SMF) and a 10-m RF wireless transport. For up-link transmission, the light is successfully intensity-remodulated with 5-Gbps BB data stream based on fiber-VLLC integration. Good BER performance is achieved over a 40-km SMF and a 10-m free-space VLLC transport. Such a hybrid CATV/MMW/BB lightwave transmission system is an attractive alternative, it gives the benefits of a communication link for broader bandwidth and higher transmission rate.

  13. Glycogen phosphorylase BB in myocardial infarction.

    PubMed

    Dobric, Milan; Ostojic, Miodrag; Giga, Vojislav; Djordjevic-Dikic, Ana; Stepanovic, Jelena; Radovanovic, Nebojsa; Beleslin, Branko

    2015-01-01

    Early experimental and clinical reports on glycogen phosphorylase BB (GPBB) kinetics following myocardial ischemic injury suggested that it could be a useful diagnostic marker for early detection of acute myocardial infarction (AMI). After more than two decades of investigation, there is now overwhelming body of evidence that do not support the use of GPBB measurement in diagnosis of acute AMI in patients presenting with acute chest pain. Currently, GPBB cannot be recommended as a diagnostic marker of AMI either as a stand-alone test or as an addition to (high-sensitive) troponin testing. It should be noted that these considerations apply to the early diagnosis of AMI, not to the prognostic stratification, which is also suggested but it warrants further investigation. The aim of this review is to summarize available evidence of GPBB measurement in early diagnosis of myocardial infarction. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Blocking the 4-1BB Pathway Ameliorates Crystalline Silica-induced Lung Inflammation and Fibrosis in Mice.

    PubMed

    Li, Chao; Du, Sitong; Lu, Yiping; Lu, Xiaowei; Liu, Fangwei; Chen, Ying; Weng, Dong; Chen, Jie

    2016-01-01

    Long term pulmonary exposure to crystalline silica leads to silicosis that manifests progressive interstitial fibrosis, eventually leading to respiratory failure and death. Despite efforts to eliminate silicosis, clinical cases continue to occur in both developing and developed countries. The exact mechanisms of crystalline silica-induced pulmonary fibrosis remain elusive. Herein, we find that 4-1BB is induced in response to crystalline silica injury in lungs and that it is highly expressed during development of experimental silicosis. Therefore, we explore the role of 4-1BB pathway during crystalline silica-induced lung injury and find that a specific inhibitor blocking the pathway could effectively alleviate crystalline silica-induced lung inflammation and subsequent pulmonary fibrosis in vivo. Compared to controls, the treated mice exhibited reduced Th1 and Th17 responses. The concentrations of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF), including tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-17A following crystalline silica challenge were also reduced in inhibitor-treated mice. Although there was no significant alteration in Th2 cytokines of IL-4 and IL-13, another type of pro-fibrogenic cell, regulatory T cell (Treg) was significantly affected. In addition, one of the major participants in fibrogenesis, fibrocyte recruited less due to the blockade. Furthermore, we demonstrated the decreased fibrocyte recruitment was associated with chemokine reductions in lung. Our study discovers the 4-1BB pathway signaling enhances inflammatory response and promotes pulmonary fibrosis induced by crystalline silica. The findings here provide novel insights into the molecular events that control crystalline silica-induced lung inflammation and fibrosis through regulating Th responses and the recruitment of fibrocytes in crystalline silica-exposed lung.

  15. A newly synthesized Ligustrazine stilbene derivative inhibits PDGF-BB induced vascular smooth muscle cell phenotypic switch and proliferation via delaying cell cycle progression.

    PubMed

    Peng, Chunlian; Zhang, Siming; Liu, Haixin; Jiao, Yanxiao; Su, Guifa; Zhu, Yan

    2017-11-05

    Vascular Smooth muscle cells (VSMCs) possess remarkable phenotype plasticity that allows it to rapidly adapt to fluctuating environmental cues, including the period of development and progression of vascular diseases such as atherosclerosis and restenosis subsequent to vein grafting or coronary intervention. Although VSMC phenotypic switch is an attractive target, there is no effective drug so far. Using rat aortic VSMCs, we investigate the effects of Ligustrazine and its synthetic derivatives on platelet-derived growth factor-BB (PDGF-BB) induced proliferation and phenotypic switch by a cell image-based screening of 60 Ligustrazine stilbene derivatives. We showed that one of the Ligustrazine stilbene derivatives TMP-C 4a markedly inhibited PDGF-BB-induced VSMCs proliferation in a time and dose-dependent manner, which is more potent than Ligustrazine. Stimulation of contractile VSMCs with PDGF-BB significantly reduced the contractile marker protein α-smooth muscle actin expression and increased the synthetic marker proteins osteopontin expression. However, TMP-C 4a effectively reversed this phenotypic switch, which was accompanied by a decreased expression of Matrix metalloproteinase 2 and 9 (MMP2 and MMP9) and cell cycle related proteins, including cyclin D1 and CDK4. In conclusion, the present study showed that a new Ligustrazine stilbene derivative TMP-C 4a suppressed PDGF-induced VSMC proliferation and phenotypic switch, indicating that it has a potential to become a promising therapeutic agent for treating VSMC-related atherosclerosis and restenosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. TRPM7 channel regulates PDGF-BB-induced proliferation of hepatic stellate cells via PI3K and ERK pathways

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fang, Ling, E-mail: fangling_1984@126.com; Zhan, Shuxiang; Huang, Cheng

    2013-11-01

    TRPM7, a non-selective cation channel of the TRP channel superfamily, is implicated in diverse physiological and pathological processes including cell proliferation. Recently, TRPM7 has been reported in hepatic stellate cells (HSCs). Here, we investigated the contribution role of TRPM7 in activated HSC-T6 cell (a rat hepatic stellate cell line) proliferation. TRPM7 mRNA and protein were measured by RT-PCR and Western blot in rat model of liver fibrosis in vivo and PDGF-BB-activated HSC-T6 cells in vitro. Both mRNA and protein of TRPM7 were dramatically increased in CCl{sub 4}-treated rat livers. Stimulation of HSC-T6 cells with PDGF-BB resulted in a time-dependent increasemore » of TRPM7 mRNA and protein. However, PDGF-BB-induced HSC-T6 cell proliferation was inhibited by non-specific TRPM7 blocker 2-aminoethoxydiphenyl borate (2-APB) or synthetic siRNA targeting TRPM7, and this was accompanied by downregulation of cell cycle proteins, cyclin D1, PCNA and CDK4. Blockade of TRPM7 channels also attenuated PDGF-BB induced expression of myofibroblast markers as measured by the induction of α-SMA and Col1α1. Furthermore, the phosphorylation of ERK and AKT, associated with cell proliferation, decreased in TRPM7 deficient HSC-T6 cells. These observations suggested that TRPM7 channels contribute to perpetuated fibroblast activation and proliferation of PDGF-BB induced HSC-T6 cells via the activation of ERK and PI3K pathways. Therefore, TRPM7 may constitute a useful target for the treatment of liver fibrosis. - Highlights: • Upregulation of TRPM7 mRNA and protein in the fibrotic livers from CCl{sub 4}-treated rats. • Increasing expression of TRPM7 mRNA and protein during HSC activation. • Blockade of TRPM7 inhibited the PDGF-BB induced proliferation of HSC-T6 cells. • Blockade of TRPM7 decreased α-SMA and Col1α1 expressions in activated HSC-T6 cells. • TRPM7 up-regulation contributes to the activation of ERK and AKT pathways.« less

  17. Identification and characterization of an insect toxin protein, Bb70p, from the entomopathogenic fungus, Beauveria bassiana, using Galleria mellonella as a model system.

    PubMed

    Khan, Sehroon; Nadir, Sadia; Lihua, Guo; Xu, Jianchu; Holmes, Keith A; Dewen, Qiu

    2016-01-01

    An insect-toxic protein, Bb70p, was purified from Beauveria bassiana 70 using ammonium sulfate precipitation, ion exchange chromatography, and gel filtration. Bb70p has a high affinity for anion exchangers and 2D electrophoresis results revealed a single spot with a molecular weight of 35.5 kDa and an iso-electric point of ∼4.5. Bb70p remains active from 4 to 60°C, within a pH range of 4-10, but is more active in slightly acidic pH. A pure protein, Bb70p does not have any carbohydrate side chains. The protein caused high mortality by intra-haemocelic injection into Galleria mellonella with LD50 of 334.4 μg/g body weight and activates the phenol oxidase cascade. With a partial amino acid sequence comparison using the NCBI database, we showed no homology to known toxin proteins of entomopathogenic fungi. Thus, Bb70p appears to be an insect toxin protein, demonstrating novelty. Identification of this insect-toxic protein presents potential to enhance the virulence of B. bassiana through genetic manipulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Cordyceps sinensis polysaccharide CPS-2 protects human mesangial cells from PDGF-BB-induced proliferation through the PDGF/ERK and TGF-β1/Smad pathways.

    PubMed

    Wang, Ying; Liu, Dan; Zhao, Huan; Jiang, Huixing; Luo, Chen; Wang, Min; Yin, Hongping

    2014-02-15

    CPS-2, a Cordyceps sinensis polysaccharide, has been demonstrated to have significant therapeutic activity against chronic renal failure. However, little is known about the underlying molecular mechanism. In this study, we found that CPS-2 could inhibit PDGF-BB-induced human mesangial cells (HMCs) proliferation in a dose-dependent manner. In addition, CPS-2 notably suppressed the expression of α-SMA, PDGF receptor-beta (PDGFRβ), TGF-β1, and Smad 3 in PDGF-BB-treated HMCs. Furthermore, PDGF-BB-stimulated ERK activation was significantly inhibited by CPS-2, and this inhibitory effect was synergistically potentiated by U0126. CPS-2 could prevent the PDGFRβ promoter activity induced by PDGF-BB, and return expression of PDGFRβ, TGF-β1, and TGFβRI to normal levels while cells were under PDGFRβ and ERK silencing conditions and transfected with DN-ERK. Taken together, these findings demonstrated that CPS-2 reduces PDGF-BB-induced cell proliferation through the PDGF/ERK and TGF-β1/Smad pathways, and it may have bi-directional regulatory effects on the PDGF/ERK cellular signaling pathway. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. Consumption of Bifidobacterium animalis subsp. lactis BB-12 in yogurt reduced expression of TLR-2 on peripheral blood-derived monocytes and pro-inflammatory cytokine secretion in young adults.

    PubMed

    Meng, Huicui; Ba, Zhaoyong; Lee, Yujin; Peng, Jiayu; Lin, Junli; Fleming, Jennifer A; Furumoto, Emily J; Roberts, Robert F; Kris-Etherton, Penny M; Rogers, Connie J

    2017-03-01

    Probiotic bacteria modulate immune parameters and inflammatory outcomes. Emerging evidence demonstrates that the matrix used to deliver probiotics may influence the efficacy of probiotic interventions in vivo. The aims of the current study were to evaluate (1) the effect of one species, Bifidobacterium animalis subsp. lactis BB-12 at a dose of log10 ± 0.5 CFUs/day on immune responses in a randomized, partially blinded, 4-period crossover, free-living study, and (2) whether the immune response to BB-12 differed depending on the delivery matrix. Healthy adults (n = 30) aged 18-40 years were recruited and received four treatments in a random order: (A) yogurt smoothie alone; smoothie with BB-12 added (B) before or (C) after yogurt fermentation, or (D) BB-12 given in capsule form. At baseline and after each 4-week treatment, peripheral blood mononuclear cells (PBMCs) were isolated, and functional and phenotypic marker expression was assessed. BB-12 interacted with peripheral myeloid cells via Toll-like receptor 2 (TLR-2). The percentage of CD14 + HLA-DR + cells in peripheral blood was increased in male participants by all yogurt-containing treatments compared to baseline (p = 0.0356). Participants who consumed yogurt smoothie with BB-12 added post-fermentation had significantly lower expression of TLR-2 on CD14 + HLA-DR + cells (p = 0.0186) and reduction in TNF-α secretion from BB-12- (p = 0.0490) or LPS-stimulated (p = 0.0387) PBMCs compared to baseline. These findings not only demonstrate a potential anti-inflammatory effect of BB-12 in healthy adults, but also indicate that the delivery matrix influences the immunomodulatory properties of BB-12.

  20. Blocking the 4-1BB Pathway Ameliorates Crystalline Silica-induced Lung Inflammation and Fibrosis in Mice

    PubMed Central

    Li, Chao; Du, Sitong; Lu, Yiping; Lu, Xiaowei; Liu, Fangwei; Chen, Ying; Weng, Dong; Chen, Jie

    2016-01-01

    Long term pulmonary exposure to crystalline silica leads to silicosis that manifests progressive interstitial fibrosis, eventually leading to respiratory failure and death. Despite efforts to eliminate silicosis, clinical cases continue to occur in both developing and developed countries. The exact mechanisms of crystalline silica-induced pulmonary fibrosis remain elusive. Herein, we find that 4-1BB is induced in response to crystalline silica injury in lungs and that it is highly expressed during development of experimental silicosis. Therefore, we explore the role of 4-1BB pathway during crystalline silica-induced lung injury and find that a specific inhibitor blocking the pathway could effectively alleviate crystalline silica-induced lung inflammation and subsequent pulmonary fibrosis in vivo. Compared to controls, the treated mice exhibited reduced Th1 and Th17 responses. The concentrations of pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF), including tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-17A following crystalline silica challenge were also reduced in inhibitor-treated mice. Although there was no significant alteration in Th2 cytokines of IL-4 and IL-13, another type of pro-fibrogenic cell, regulatory T cell (Treg) was significantly affected. In addition, one of the major participants in fibrogenesis, fibrocyte recruited less due to the blockade. Furthermore, we demonstrated the decreased fibrocyte recruitment was associated with chemokine reductions in lung. Our study discovers the 4-1BB pathway signaling enhances inflammatory response and promotes pulmonary fibrosis induced by crystalline silica. The findings here provide novel insights into the molecular events that control crystalline silica-induced lung inflammation and fibrosis through regulating Th responses and the recruitment of fibrocytes in crystalline silica-exposed lung. PMID:27698940

  1. IGF-1 and PDGF-bb Suppress IL-1β-Induced Cartilage Degradation through Down-Regulation of NF-κB Signaling: Involvement of Src/PI-3K/AKT Pathway

    PubMed Central

    Mobasheri, Ali; Buhrmann, Constanze; Aldinger, Constance; Rad, Jafar Soleimani; Shakibaei, Mehdi

    2011-01-01

    Objective Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that plays a key role in the pathogenesis of osteoarthritis (OA). Growth factors (GFs) capable of antagonizing the catabolic actions of cytokines may have therapeutic potential in the treatment of OA. Herein, we investigated the potential synergistic effects of insulin-like growth factor (IGF-1) and platelet-derived growth factor (PDGF-bb) on different mechanisms participating in IL-1β-induced activation of nuclear transcription factor-κB (NF-κB) and apoptosis in chondrocytes. Methods Primary chondrocytes were treated with IL-1β to induce dedifferentiation and co-treated with either IGF-1 or/and PDGF-bb and evaluated by immunoblotting and electron microscopy. Results Pretreatment of chondrocytes with IGF-1 or/and PDGF-bb suppressed IL-1β-induced NF-κB activation via inhibition of IκB-α kinase. Inhibition of IκB-α kinase by GFs led to the suppression of IκB-α phosphorylation and degradation, p65 nuclear translocation and NF-κB-regulated gene products involved in inflammation and cartilage degradation (COX-2, MMPs) and apoptosis (caspase-3). GFs or BMS-345541 (specific inhibitor of the IKK) reversed the IL-1β-induced down-regulation of collagen type II, cartilage specific proteoglycans, β1-integrin, Shc, activated MAPKinase, Sox-9 and up-regulation of active caspase-3. Furthermore, the inhibitory effects of IGF-1 or/and PDGF-bb on IL-1β-induced NF-κB activation were sensitive to inhibitors of Src (PP1), PI-3K (wortmannin) and Akt (SH-5), suggesting that the pathway consisting of non-receptor tyrosine kinase (Src), phosphatidylinositol 3-kinase and protein kinase B must be involved in IL-1β signaling. Conclusion The results presented suggest that IGF-1 and PDGF-bb are potent inhibitors of IL-1β-mediated activation of NF-κB and apoptosis in chondrocytes, may be mediated in part through suppression of Src/PI-3K/AKT pathway, which may contribute to their anti-inflammatory effects. PMID

  2. 76 FR 13615 - B&B Manufacturing Site; Mobile, Mobile County, AL; Notice of Settlement

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-14

    ... Site; Mobile, Mobile County, AL; Notice of Settlement AGENCY: Environmental Protection Agency. ACTION... settlement for reimbursement of past response costs concerning the B&B Manufacturing Site located in Mobile, Mobile County, Alabama for publication. DATES: The Agency will consider public comments on the settlement...

  3. Classification of robust heteroclinic cycles for vector fields in {\\protect\\bb R}^3 with symmetry

    NASA Astrophysics Data System (ADS)

    Hawker, David; Ashwin, Peter

    2005-09-01

    We consider a classification of robust heteroclinic cycles in the positive octant of {\\bb R}^3 under the action of the symmetry group {{\\bb Z}_2}^3 . We introduce a coding system to represent different classes up to a topological equivalence, and produce a characterization of all types of robust heteroclinic cycle that can arise in this situation. These cycles may or may not contain the origin within the cycle. We proceed to find a connection between our problem and meandric numbers. We find a direct correlation between the number of classes of robust heteroclinic cycle that do not include the origin and the 'Mercedes-Benz' sequence of integers characterizing meanders through a 'Y-shaped' configuration. We investigate upper and lower bounds for the number of classes possible for robust cycles between n equilibria, one of which may be the origin.

  4. Combined search for the standard model Higgs boson decaying to bb using the D0 run II data set.

    PubMed

    Abazov, V M; Abbott, B; Acharya, B S; Adams, M; Adams, T; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Askew, A; Atkins, S; Augsten, K; Avila, C; Badaud, F; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Barberis, E; Baringer, P; Bartlett, J F; Bassler, U; Bazterra, V; Bean, A; Begalli, M; Bellantoni, L; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bhat, P C; Bhatia, S; Bhatnagar, V; Blazey, G; Blessing, S; Bloom, K; Boehnlein, A; Boline, D; Boos, E E; Borissov, G; Bose, T; Brandt, A; Brandt, O; Brock, R; Bross, A; Brown, D; Brown, J; Bu, X B; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Buszello, C P; Camacho-Pérez, E; Casey, B C K; Castilla-Valdez, H; Caughron, S; Chakrabarti, S; Chakraborty, D; Chan, K M; Chandra, A; Chapon, E; Chen, G; Chevalier-Théry, S; Cho, D K; Cho, S W; Choi, S; Choudhary, B; Cihangir, S; Claes, D; Clutter, J; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Croc, A; Cutts, D; Das, A; Davies, G; de Jong, S J; De La Cruz-Burelo, E; Déliot, F; Demina, R; Denisov, D; Denisov, S P; Desai, S; Deterre, C; Devaughan, K; Diehl, H T; Diesburg, M; Ding, P F; Dominguez, A; Dubey, A; Dudko, L V; Duggan, D; Duperrin, A; Dutt, S; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Evans, H; Evdokimov, A; Evdokimov, V N; Facini, G; Feng, L; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Fortner, M; Fox, H; Fuess, S; Garcia-Bellido, A; García-González, J A; García-Guerra, G A; Gavrilov, V; Gay, P; Geng, W; Gerbaudo, D; Gerber, C E; Gershtein, Y; Ginther, G; Golovanov, G; Goussiou, A; Grannis, P D; Greder, S; Greenlee, H; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guillemin, T; Gutierrez, G; Gutierrez, P; Hagopian, S; Haley, J; Han, L; Harder, K; Harel, A; Hauptman, J M; Hays, J; Head, T; Hebbeker, T; Hedin, D; Hegab, H; Heinson, A P; Heintz, U; Hensel, C; Heredia De La Cruz, I; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hoang, T; Hobbs, J D; Hoeneisen, B; Hogan, J; Hohlfeld, M; Howley, I; Hubacek, Z; Hynek, V; Iashvili, I; Ilchenko, Y; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jayasinghe, A; Jeong, M S; Jesik, R; Jiang, P; Johns, K; Johnson, E; Johnson, M; Jonckheere, A; Jonsson, P; Joshi, J; Jung, A W; Juste, A; Kaadze, K; Kajfasz, E; Karmanov, D; Kasper, P A; Katsanos, I; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y N; Kiselevich, I; Kohli, J M; Kozelov, A V; Kraus, J; Kulikov, S; Kumar, A; Kupco, A; Kurča, T; Kuzmin, V A; Lammers, S; Landsberg, G; Lebrun, P; Lee, H S; Lee, S W; Lee, W M; Lei, X; Lellouch, J; Li, D; Li, H; Li, L; Li, Q Z; Lim, J K; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, H; Liu, Y; Lobodenko, A; Lokajicek, M; Lopes de Sa, R; Lubatti, H J; Luna-Garcia, R; Lyon, A L; Maciel, A K A; Madar, R; Magaña-Villalba, R; Malik, S; Malyshev, V L; Maravin, Y; Martínez-Ortega, J; McCarthy, R; McGivern, C L; Meijer, M M; Melnitchouk, A; Menezes, D; Mercadante, P G; Merkin, M; Meyer, A; Meyer, J; Miconi, F; Mondal, N K; Mulhearn, M; Nagy, E; Naimuddin, M; Narain, M; Nayyar, R; Neal, H A; Negret, J P; Neustroev, P; Nguyen, H T; Nunnemann, T; Orduna, J; Osman, N; Osta, J; Padilla, M; Pal, A; Parashar, N; Parihar, V; Park, S K; Partridge, R; Parua, N; Patwa, A; Penning, B; Perfilov, M; Peters, Y; Petridis, K; Petrillo, G; Pétroff, P; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Popov, A V; Prewitt, M; Price, D; Prokopenko, N; Qian, J; Quadt, A; Quinn, B; Rangel, M S; Ranjan, K; Ratoff, P N; Razumov, I; Renkel, P; Ripp-Baudot, I; Rizatdinova, F; Rominsky, M; Ross, A; Royon, C; Rubinov, P; Ruchti, R; Sajot, G; Salcido, P; Sánchez-Hernández, A; Sanders, M P; Santos, A S; Savage, G; Sawyer, L; Scanlon, T; Schamberger, R D; Scheglov, Y; Schellman, H; Schlobohm, S; Schwanenberger, C; Schwienhorst, R; Sekaric, J; Severini, H; Shabalina, E; Shary, V; Shaw, S; Shchukin, A A; Shivpuri, R K; Simak, V; Skubic, P; Slattery, P; Smirnov, D; Smith, K J; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Soustruznik, K; Stark, J; Stoyanova, D A; Strauss, M; Suter, L; Svoisky, P; Takahashi, M; Titov, M; Tokmenin, V V; Tsai, Y-T; Tschann-Grimm, K; Tsybychev, D; Tuchming, B; Tully, C; Uvarov, L; Uvarov, S; Uzunyan, S; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Verdier, P; Verkheev, A Y; Vertogradov, L S; Verzocchi, M; Vesterinen, M; Vilanova, D; Vokac, P; Wahl, H D; Wang, M H L S; Wang, R-J; Warchol, J; Watts, G; Wayne, M; Weichert, J; Welty-Rieger, L; White, A; Wicke, D; Williams, M R J; Wilson, G W; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Yamada, R; Yang, S; Yang, W-C; Yasuda, T; Yatsunenko, Y A; Ye, W; Ye, Z; Yin, H; Yip, K; Youn, S W; Yu, J M; Zennamo, J; Zhao, T; Zhao, T G; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zivkovic, L

    2012-09-21

    We present the results of the combination of searches for the standard model Higgs boson produced in association with a W or Z boson and decaying into bb using the data sample collected with the D0 detector in pp collisions at √s = 1.96 TeV at the Fermilab Tevatron Collider. We derive 95% C.L. upper limits on the Higgs boson cross section relative to the standard model prediction in the mass range 100 GeV ≤ M(H) ≤ 150 GeV, and we exclude Higgs bosons with masses smaller than 102 GeV at the 95% C.L. In the mass range 120 GeV ≤ M(H) ≤145 GeV, the data exhibit an excess above the background prediction with a global significance of 1.5 standard deviations, consistent with the expectation in the presence of a standard model Higgs boson.

  5. WR 120bb and WR 120bc: a pair of WN9h stars with possibly interacting circumstellar shells

    NASA Astrophysics Data System (ADS)

    Burgemeister, S.; Gvaramadze, V. V.; Stringfellow, G. S.; Kniazev, A. Y.; Todt, H.; Hamann, W.-R.

    2013-03-01

    Two optically obscured Wolf-Rayet (WR) stars have been recently discovered by means of their infrared (IR) circumstellar shells, which show signatures of interaction with each other. Following the systematics of the WR star catalogues, these stars obtain the names WR 120bb and WR 120bc. In this paper, we present and analyse new near-IR, J-, H- and K-band spectra using the Potsdam Wolf-Rayet model atmosphere code. For that purpose, the atomic data base of the code has been extended in order to include all significant lines in the near-IR bands. The spectra of both stars are classified as WN9h. As their spectra are very similar the parameters that we obtained by the spectral analyses hardly differ. Despite their late spectral subtype, we found relatively high stellar temperatures of 63 kK. The wind composition is dominated by helium, while hydrogen is depleted to 25 per cent by mass. Because of their location in the Scutum-Centaurus Arm, WR 120bb and WR 120bc appear highly reddened, A_{K_s} ≈ 2 mag. We adopt a common distance of 5.8 kpc to both stars, which complies with the typical absolute K-band magnitude for the WN9h subtype of -6.5 mag, is consistent with their observed extinction based on comparison with other massive stars in the region, and allows for the possibility that their shells are interacting with each other. This leads to luminosities of log ({textit {L}/L}_{odot }) = 5.66 and 5.54 for WR 120bb and WR 120bc, with large uncertainties due to the adopted distance. The values of the luminosities of WR 120bb and WR 120bc imply that the immediate precursors of both stars were red supergiants (RSG). This implies in turn that the circumstellar shells associated with WR 120bb and WR 120bc were formed by interaction between the WR wind and the dense material shed during the preceding RSG phase.

  6. Evaluation of human recession defects treated with coronally advanced flaps and either purified recombinant human platelet-derived growth factor-BB with beta tricalcium phosphate or connective tissue: a histologic and microcomputed tomographic examination.

    PubMed

    McGuire, Michael K; Scheyer, Todd; Nevins, Myron; Schupbach, Peter

    2009-02-01

    The current study examined the histologic and microcomputed tomographic (micro CT) outcomes of the treatment of gingival recession defects with either a subepithelial connective tissue graft (CTG) or 0.3 mg/mL recombinant human platelet-derived growth factor (rhPDGF-BB) on a beta tricalcium phosphate (beta-TCP) matrix. Gingival recession defects were surgically created in six premolar teeth with no more than 3 mm of keratinized marginal tissue, an osseous crest 2 to 3 mm apical to the newly created gingival margin, and recession depth of at least 3 mm. The defects were left untouched for 2 months; then, four defects were grafted with rhPDGF-BB + beta-TCP + a wound healing dressing, and two defects received CTGs. A coronally advanced flap covered each grafted site. Nine months later, sections were obtained for examination. All four sites treated with rhPDGF-BB + beta-TCP showed connective tissue fibers (Sharpey fibers) perpendicularly inserting into newly formed cementum and alveolar bone. In the two sites treated with CTGs, a long junctional epithelium was seen coronal to the osseous crest and connective tissue fibers ran parallel to the adjacent root surfaces, with no evidence of insertion into cementum or bone. There was no evidence of regeneration of cementum, inserting connective tissue fibers, or supporting alveolar bone. Regeneration of the periodontium in gingival recession defects is possible through growth factor-mediated therapy.

  7. Inhibitory effect of PDGF-BB and serum-stimulated responses in vascular smooth muscle cell proliferation by hinokitiol via up-regulation of p21 and p53.

    PubMed

    Li, Jiun-Yi; Liu, Chun-Ping; Shiao, Wei-Cheng; Jayakumar, Thanasekaran; Li, Yi-Shin; Chang, Nen-Chung; Huang, Shih-Yi; Hsieh, Cheng-Ying

    2018-04-01

    Vascular smooth muscle cell (VSMC) proliferation plays a major role in the progression of vascular diseases. In the present study, we established the efficacy and the mechanisms of action of hinokitiol, a tropolone derivative found in Chamaecyparis taiwanensis , Cupressaceae, in relation to platelet-derived growth factor-BB (PDGF-BB) and serum-dependent VSMC proliferation. Primary cultured rat VSMCs were pre-treated with hinokitiol and then stimulated by PDGF-BB (10 ng/ml) or serum (10% fetal bovine serum). Cell proliferation and cytotoxicity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactose dehydrogenase assay, respectively. The degree of DNA synthesis was evaluated by BrdU-incorporation measurements and observed using confocal microscopy. Immunoblotting was utilized to determine the protein level of p-extracellular signal-regulated kinase (ERK) 1/2, p-Akt, p-phosphoinositide 3-kinase (PI3K), p-Janus kinase 2 (JAK2), p-p53, and p21 Cip1 . The promoter activity of p21 and p53 activity were measured by dual luciferase reporter assay. Treatment with hinokitiol (1-10 μM) inhibited PDGF-BB and serum-induced VSMC proliferation and DNA synthesis in a concentration-dependent manner. Cytotoxicity was not observed in hinokitiol-treated VSMCs at the studied concentrations. Pre-incubation of VSMCs with hinokitiol did not alter PDGF-BB-induced phosphorylation of ERK1/2, Akt, PI3K or JAK2. Interestingly, hinokitiol induced promoter activity of p21 and p21 protein expression in VSMCs. Furthermore, hinokitiol augmented p53 protein phosphorylation and subsequently led to enhanced p53 activity. These data suggest that the anti-proliferative effects of hinokitiol in VSMCs may be mediated by activation of p21 and p53 signaling pathways, and it may contribute to the prevention of vascular diseases associated with VSMC proliferation.

  8. Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand

    PubMed Central

    Chen, Mee-Yew; Kirkwood, Carl D.; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J.; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

    2017-01-01

    ABSTRACT Background: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Methods: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0–5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Results: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). Conclusions: The level of IgA in colostrum or breast milk and level of placental Ig

  9. Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.

    PubMed

    Chen, Mee-Yew; Kirkwood, Carl D; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

    2017-05-04

    Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or

  10. Impact of Cry3Bb1-expressing Bt maize on adults of the western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae).

    PubMed

    Meissle, Michael; Hellmich, Richard L; Romeis, Jörg

    2011-07-01

    Genetically engineered maize producing insecticidal Cry3Bb1 protein from Bacillus thuringiensis (Bt) is protected from root damage by corn rootworm larvae. An examination was made to establish whether western corn rootworm (Diabrotica virgifera virgifera) adults are affected by Cry3Bb1-expressing maize (MON88017) when feeding on above-ground tissue. In laboratory bioassays, adult D. v. virgifera were fed for 7 weeks with silk, leaves or pollen from Bt maize or the corresponding near-isoline. Male, but not female, survival was reduced in the Bt-leaf treatment compared with the control. Female weight was lower when fed Bt maize, and egg production was reduced in the Bt-silk treatment. ELISA measurements demonstrated that beetles feeding on silk were exposed to higher Cry3Bb1 concentrations than beetles collected from Bt-maize fields in the United States. In contrast to silk and pollen, feeding on leaves resulted in high mortality and low fecundity. Females feeding on pollen produced more eggs than on silk. C:N ratios indicated that silk does not provide enough nitrogen for optimal egg production. Direct effects of Cry3Bb1 on adult beetles could explain the observed effects, but varietal differences between Bt and control maize are also possible. The impact of Bt maize on adult populations, however, is likely to be limited. Copyright © 2011 Society of Chemical Industry.

  11. A recombination outside the BB deletion refines the location of the X-linked retinitis pigmentosa locus RP3

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fujita, R.; Bingham, E.; Forsythe, P.

    1996-07-01

    Genetic loci for X-linked retinitis pigmentosa (XLRP) have been mapped between Xp11.22 and Xp22.13 (RP2, RP3, RP6, and RP15). The RP3 gene, which is responsible for the predominant form of XLRP in most Caucasian populations, has been localized to Xp21.1 by linkage analysis and the map positions of chromosomal deletions associated with the disease. Previous linkage studies have suggested that RP3 is flanked by the markers DXS1110 (distal) and OTC (proximal). Patient BB was though to have RP because of a lesion at the RP3 locus, in addition to chronic granulomatous disease, Duchenne muscular dystrophy (DMD), mild mental retardation, andmore » the McLeod phenotype. This patient carried a deletion extending {approximately}3 Mb from DMD in Xp21.3 to Xp21.1, with the proximal breakpoint located {approximately}40 kb centromeric to DXS1110. The RP3 gene, therefore, is believed to reside between DXS1110 and the proximal breakpoint of the BB deletion. In order to refine the location of RP3 and to ascertain patients with RP3, we have been analyzing several XLRP families for linkage to Xp markers. Linkage analysis in an American family of 27 individuals demonstrates segregation of XLRP with markers in Xp21.1, consistent with the RP3 subtype. One affected male shows a recombination event proximal to DXS1110. Additional markers within the DXS1110-OTC interval show that the crossover is between two novel polymorphic markers, DXS8349 and M6, both of which are present in BB DNA and lie centromeric to the proximal breakpoint. This recombination places the XLRP mutation in this family outside the BB deletion and redefines the location of RP3. 22 refs., 3 figs., 2 tabs.« less

  12. Localized bone regeneration around dental implants using recombinant bone morphogenetic protein-2 and platelet-derived growth factor-BB in the canine.

    PubMed

    Thoma, Daniel S; Cha, Jae-Kook; Sapata, Vitor M; Jung, Ronald E; Hüsler, Juerg; Jung, Ui-Won

    2017-11-01

    To test whether or not one of two biological mediators (recombinant human bone morphogenetic protein-2 (rhBMP-2) and recombinant human platelet-derived growth factor (rhPDGF-BB)) is superior to the other and compared with control groups for bone regeneration around implants based on histomorphometrical outcome measures. Box-type defects (10 × 5 × 5 mm) were prepared on the buccal sides of the left and right edentulous ridge in ten mongrel dogs. Implants were placed at each site, the defects either received (i) bovine-derived particulated bone mineral (DBBM) mixed with rhBMP-2 and a collagen membrane (CM) (DBBM/BMP-2), (ii) DBBM mixed with rhPDGF-BB and CM (DBBM/PDGF), (iii) DBBM and CM (DBBM) and (iv) empty control (control). Animals were euthanized post-surgery at 8 weeks and 16 weeks. Histomorphometrical analyses were performed. The mean percentages of regenerated area within total defect area amounted to 56.95% for DBBM/BMP-2, 48.86% for DBBM/PDFG, 33.44% for DBBM and 1.59% for control at 8 weeks, and 26.79% for DBBM/BMP-2, 23.78% for DBBM/PDFG, 30.21% for DBBM and 5.07% for control at 16 weeks with no statistically significant differences between the groups (P > 0.05). The mean amount of regenerated bone was 26.97% for DBBM/BMP-2, 22.02% for DBBM/PDFG, 5.03% for DBBM and 1.25% for control at 8 weeks, and at 16 weeks, these values were lower in the two groups with biological mediators (DBBM/BMP-2 = 13.35%; DBBM/PDGF = 6.96%) and only slightly increased in group DBBM (10.68%) and the control group (4.95%) compared with 8 weeks. The first bone-to-implant contact values on the buccal side were minimal for DBBM/BMP-2 (0.57 mm) and maximal for control (3.72 mm) at 8 weeks. The use of biological mediators (rhBMP-2 and rhPDGF-BB) can increase the amount of bone regeneration at dehiscence-type defects compared with controls at 8 weeks, but not at 16 weeks due to enhanced hard tissue remodeling processes. © 2016 John Wiley & Sons A/S. Published by John

  13. Vibrational spectral signatures of crystalline cellulose using high resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS)

    DOE PAGES

    Zhang, Libing; Lu, Zhou; Velarde, Luis; ...

    2015-03-03

    Both the C–H and O–H region spectra of crystalline cellulose were studied using the sub-wavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS) for the first time. The resolution of HR-BB-SFG-VS is about 10-times better than conventional scanning SFG-VS and has the capability of measuring the intrinsic spectral lineshape and revealing many more spectral details. With HR-BB-SFG-VS, we found that in cellulose samples from different sources, including Avicel and cellulose crystals isolated from algae Valonia (Iα) and tunicates (Iβ), the spectral signatures in the O–H region were unique for the two allomorphs, i.e. Iα and Iβ, while the spectral signaturesmore » in the C–H regions varied in all samples examined. Even though the origin of the different spectral signatures of the crystalline cellulose in the O–H and C–H vibrational frequency regions are yet to be correlated to the structure of cellulose, these results lead to new spectroscopic methods and opportunities to classify and to understand the basic crystalline structures, as well as variations in polymorphism of the crystalline cellulose.« less

  14. Vibrational spectral signatures of crystalline cellulose using high resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Libing; Lu, Zhou; Velarde, Luis

    Both the C–H and O–H region spectra of crystalline cellulose were studied using the sub-wavenumber high-resolution broadband sum frequency generation vibrational spectroscopy (HR-BB-SFG-VS) for the first time. The resolution of HR-BB-SFG-VS is about 10-times better than conventional scanning SFG-VS and has the capability of measuring the intrinsic spectral lineshape and revealing many more spectral details. With HR-BB-SFG-VS, we found that in cellulose samples from different sources, including Avicel and cellulose crystals isolated from algae Valonia (Iα) and tunicates (Iβ), the spectral signatures in the O–H region were unique for the two allomorphs, i.e. Iα and Iβ, while the spectral signaturesmore » in the C–H regions varied in all samples examined. Even though the origin of the different spectral signatures of the crystalline cellulose in the O–H and C–H vibrational frequency regions are yet to be correlated to the structure of cellulose, these results lead to new spectroscopic methods and opportunities to classify and to understand the basic crystalline structures, as well as variations in polymorphism of the crystalline cellulose.« less

  15. Costimulation through the CD137/4-1BB pathway protects human melanoma tumor-infiltrating lymphocytes from activation-induced cell death and enhances antitumor effector function.

    PubMed

    Hernandez-Chacon, Jessica Ann; Li, Yufeng; Wu, Richard C; Bernatchez, Chantale; Wang, Yijun; Weber, Jeffrey S; Hwu, Patrick; Radvanyi, Laszlo G

    2011-04-01

    Adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) with high-dose interleukin-2 is a promising form of immunotherapy for stage IV melanoma having clinical response rates of 50% or more. One of the major problems preventing further success of this therapy is that the current protocols used to highly expand TIL for infusion drive CD8(+) T cells to differentiate into effector cells losing key costimulatory molecules such as CD28 and CD27. This has been associated with a lack of persistence in vivo for reasons not entirely clear. In this study, we demonstrate that while human melanoma CD8(+) TIL lost CD27 and CD28 expression during the rapid expansion for ACT, they gained expression of the alternative costimulatory molecule CD137/4-1BB, and to a lesser extent CD134/OX40. Postrapid expansion protocol (REP) TIL were found to be highly sensitive to activation-induced cell death when reactivated through the T-cell receptor with low levels of OKT3 antibody. However, coligation of 4-1BB using 2 different agonistic anti-4-1BB antibodies potently prevented activation-induced cell death of post-REP CD8(+) TIL, including those specific for melanoma antigen recognized by T cells, and facilitated even further cell expansion. This was correlated with increased levels of bcl-2 and bcl-xL together with decreased bim expression. 4-1BB costimulated post-REP TIL also expressed increased levels of the cytolytic granule proteins and exhibited enhanced cytotoxic T-cell activity against melanoma cells. Lastly, post-REP CD8(+) TIL were protected from cell death by anti-4-1BB ligation when exposed to human leukocyte antigen-matched melanoma cells. Our results indicate that 4-1BB costimulation may significantly improve TIL survival during melanoma ACT and boost antitumor cytolytic activity.

  16. Co-Stimulation through 4-1BB/CD137 Improves the Expansion and Function of CD8+ Melanoma Tumor-Infiltrating Lymphocytes for Adoptive T-Cell Therapy

    PubMed Central

    Chacon, Jessica Ann; Wu, Richard C.; Sukhumalchandra, Pariya; Molldrem, Jeffrey J.; Sarnaik, Amod; Pilon-Thomas, Shari; Weber, Jeffrey; Hwu, Patrick; Radvanyi, Laszlo

    2013-01-01

    Adoptive T-cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) can induce tumor regression in up to 50% or more of patients with unresectable metastatic melanoma. However, current methods to expand melanoma TIL, especially the “rapid expansion protocol” (REP) were not designed to enhance the generation of optimal effector-memory CD8+ T cells for infusion. One approach to this problem is to manipulate specific co-stimulatory signaling pathways to enhance CD8+ effector-memory T-cell expansion. In this study, we determined the effects of activating the TNF-R family member 4-1BB/CD137, specifically induced in activated CD8+ T cells, on the yield, phenotype, and functional activity of expanded CD8+ T cells during the REP. We found that CD8+ TIL up-regulate 4-1BB expression early during the REP after initial TCR stimulation, but neither the PBMC feeder cells in the REP or the activated TIL expressed 4-1BB ligand. However, addition of an exogenous agonistic anti-4-1BB IgG4 (BMS 663513) to the REP significantly enhanced the frequency and total yield of CD8+ T cells as well as their maintenance of CD28 and increased their anti-tumor CTL activity. Gene expression analysis found an increase in bcl-2 and survivin expression induced by 4-1BB that was associated with an enhanced survival capability of CD8+ post-REP TIL when re-cultured in the absence or presence of cytokines. Our findings suggest that adding an agonistic anti-4-1BB antibody during the time of TIL REP initiation produces a CD8+ T cell population capable of improved effector function and survival. This may greatly improve TIL persistence and anti-tumor activity in vivo after adoptive transfer into patients. PMID:23560068

  17. Homolytic Cleavage of a B-B Bond by the Cooperative Catalysis of Two Lewis Bases: Computational Design and Experimental Verification.

    PubMed

    Wang, Guoqiang; Zhang, Honglin; Zhao, Jiyang; Li, Wei; Cao, Jia; Zhu, Chengjian; Li, Shuhua

    2016-05-10

    Density functional theory (DFT) investigations revealed that 4-cyanopyridine was capable of homolytically cleaving the B-B σ bond of diborane via the cooperative coordination to the two boron atoms of the diborane to generate pyridine boryl radicals. Our experimental verification provides supportive evidence for this new B-B activation mode. With this novel activation strategy, we have experimentally realized the catalytic reduction of azo-compounds to hydrazine derivatives, deoxygenation of sulfoxides to sulfides, and reduction of quinones with B2 (pin)2 at mild conditions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Impact of inulin and okara on Lactobacillus acidophilus La-5 and Bifidobacterium animalis Bb-12 viability in a fermented soy product and probiotic survival under in vitro simulated gastrointestinal conditions.

    PubMed

    Bedani, Raquel; Rossi, Elizeu Antonio; Isay Saad, Susana Marta

    2013-06-01

    The effect of inulin and/or okara flour on Lactobacillus acidophilus La-5 and Bifidobacterium animalis Bb-12 viability in a fermented soy product (FSP) and on probiotic survival under in vitro simulated gastrointestinal conditions were investigated throughout 28 days of storage at 4 °C. Employing a 2(2) design, four FSP trials were produced from soymilk fermented with ABT-4 culture (La-5, Bb-12, and Streptococcus thermophilus): FSP (control); FSP-I (with inulin, 3 g/100 mL of soymilk); FSP-O (with okara, 5 g/100 mL); FSP-IO (with inulin + okara, ratio 3:5 g/100 mL). Probiotic viabilities ranged from 8 to 9 log cfu/g during the 28 days of storage, and inulin and/or okara flour did not affect the viability of La-5 and Bb-12. Bb-12 resistance to the artificial gastrointestinal juices was higher than for La-5, since the Bb-12 and La-5 populations decreased approximately 0.6 log cfu/g and 3.8 log cfu/g, respectively, throughout storage period. Even though the protective effect of inulin and/or okara flour on probiotic microorganisms was not significant, when compared to a fresh culture, the FSP matrix improved Bb-12 survival on day 1 of storage and may be considered a good vehicle for Bb-12 and could play an important role in probiotic protection against gastrointestinal juices. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Inhibitory effect of PDGF-BB and serum-stimulated responses in vascular smooth muscle cell proliferation by hinokitiol via up-regulation of p21 and p53

    PubMed Central

    Li, Jiun-Yi; Liu, Chun-Ping; Shiao, Wei-Cheng; Jayakumar, Thanasekaran; Li, Yi-Shin; Chang, Nen-Chung

    2018-01-01

    Introduction Vascular smooth muscle cell (VSMC) proliferation plays a major role in the progression of vascular diseases. In the present study, we established the efficacy and the mechanisms of action of hinokitiol, a tropolone derivative found in Chamaecyparis taiwanensis, Cupressaceae, in relation to platelet-derived growth factor-BB (PDGF-BB) and serum-dependent VSMC proliferation. Material and methods Primary cultured rat VSMCs were pre-treated with hinokitiol and then stimulated by PDGF-BB (10 ng/ml) or serum (10% fetal bovine serum). Cell proliferation and cytotoxicity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactose dehydrogenase assay, respectively. The degree of DNA synthesis was evaluated by BrdU-incorporation measurements and observed using confocal microscopy. Immunoblotting was utilized to determine the protein level of p-extracellular signal-regulated kinase (ERK) 1/2, p-Akt, p-phosphoinositide 3-kinase (PI3K), p-Janus kinase 2 (JAK2), p-p53, and p21Cip1. The promoter activity of p21 and p53 activity were measured by dual luciferase reporter assay. Results Treatment with hinokitiol (1–10 μM) inhibited PDGF-BB and serum-induced VSMC proliferation and DNA synthesis in a concentration-dependent manner. Cytotoxicity was not observed in hinokitiol-treated VSMCs at the studied concentrations. Pre-incubation of VSMCs with hinokitiol did not alter PDGF-BB-induced phosphorylation of ERK1/2, Akt, PI3K or JAK2. Interestingly, hinokitiol induced promoter activity of p21 and p21 protein expression in VSMCs. Furthermore, hinokitiol augmented p53 protein phosphorylation and subsequently led to enhanced p53 activity. Conclusions These data suggest that the anti-proliferative effects of hinokitiol in VSMCs may be mediated by activation of p21 and p53 signaling pathways, and it may contribute to the prevention of vascular diseases associated with VSMC proliferation. PMID:29765446

  20. Key rate for calibration robust entanglement based BB84 quantum key distribution protocol

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gittsovich, O.; Moroder, T.

    2014-12-04

    We apply the approach of verifying entanglement, which is based on the sole knowledge of the dimension of the underlying physical system to the entanglement based version of the BB84 quantum key distribution protocol. We show that the familiar one-way key rate formula holds already if one assumes the assumption that one of the parties is measuring a qubit and no further assumptions about the measurement are needed.

  1. Dual-primer self-generation SERS signal amplification assay for PDGF-BB using label-free aptamer.

    PubMed

    Ye, SuJuan; Zhai, XiaoMo; Wu, YanYing; Kuang, ShaoPing

    2016-05-15

    Highly sensitive detection of proteins, especially those associated with cancers, is essential to biomedical research as well as clinical diagnosis. In this work, a simple and novel one-two-three signal amplification surface-enhanced Raman scattering (SERS) method for the detection of protein is fabricated by using label-free aptamer and dual-primer self-generation. Platelet-derived growth factor B-chain (PDGF-BB) is selected as the model protein. The one-two-three cascade DNA amplification means one target-aptamer binding event, two hairpin DNA switches and three DNA amplification reactions. This strategy possesses some remarkable features compared to conventional signal amplification methods: (i) A smart probe including a label-free aptamer is fabricated, for suitable hybridization without hindering the affinity of the aptamer toward its target. (ii) Using the unique structure switch of the aptamer and cooperator, a one-two-three working mode is developed to amplify the SERS signal. The amplification efficiency is enhanced. Given the unique and attractive characteristics, a simple and universal strategy is designed to accomplish ultrasensitive detection of proteins. The detection limit of PDGF-BB via SERS detection is 0.42 pM, with the linear range from 1.0×10(-12)M to 10(-8)M. It is potentially universal because the aptamer can be easily designed for biomolecules whose aptamers undergo similar conformational changes. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Induction of alloantigen-specific hyporesponsiveness in human T lymphocytes by blocking interaction of CD28 with its natural ligand B7/BB1

    PubMed Central

    1993-01-01

    The specificity of T lymphocyte activation is determined by engagement of the T cell receptor (TCR) by peptide/major histocompatibility complexes expressed on the antigen-presenting cell (APC). Lacking costimulation by accessory molecules on the APC, T cell proliferation does not occur and unresponsiveness to subsequent antigenic stimulus is induced. The B7/BB1 receptor on APCs binds CD28 and CTLA-4 on T cells, and provides a costimulus for T cell proliferation. Here, we show that prolonged, specific T cell hyporesponsiveness to antigenic restimulation is achieved by blocking the interaction between CD28 and B7/BB1 in human mixed leukocyte culture (MLC). Secondary T cell proliferative responses to specific alloantigen were inhibited by addition to the primary culture of monovalent Fab fragments of anti- CD28 monoclonal antibody (mAb) 9.3, which block interaction of CD28 with B7/BB1 without activating T cells. Hypo-responsiveness was also induced in MLC by CTLA4Ig, a chimeric immunoglobulin fusion protein incorporating the extracellular domain of CTLA-4 with high binding avidity for B7/BB1. Cells previously primed could also be made hyporesponsive, if exposed to alloantigen in the presence of CTLA4Ig. Maximal hyporesponsiveness was achieved in MLC after 2 d of incubation with CTLA4Ig, and was maintained for at least 27 d after removal of CTLA4Ig. Accumulation of interleukin 2 (IL-2) and interferon gamma but not IL-4 mRNA was blocked by CTLA4Ig in T cells stimulated by alloantigen. Antigen-specific responses could be restored by addition of exogenous IL-2 at the time of the secondary stimulation. Addition to primary cultures of the intact bivalent anti-CD28 mAb 9.3, or B7/BB1+ transfected CHO cells or exogenous IL-2, abrogated induction of hyporesponsiveness by CTLA4Ig. These data indicate that interaction of CD28 with B7/BB1 during TCR engagement with antigen is required to maintain T cell competence and that blocking such interaction can result in a state of T cell

  3. Mating Success, Longevity, and Fertility of Diabrotica virgifera virgifera LeConte (Chrysomelidae: Coleoptera) in Relation to Body Size and Cry3Bb1-Resistant and Cry3Bb1-Susceptible Genotypes

    PubMed Central

    French, Bryan Wade; Hammack, Leslie; Tallamy, Douglas W.

    2015-01-01

    Insect resistance to population control methodologies is a widespread problem. The development of effective resistance management programs is often dependent on detailed knowledge regarding the biology of individual species and changes in that biology associated with resistance evolution. This study examined the reproductive behavior and biology of western corn rootworm beetles of known body size from lines resistant and susceptible to the Cry3Bb1 protein toxin expressed in transgenic Bacillus thuringiensis maize. In crosses between, and within, the resistant and susceptible genotypes, no differences occurred in mating frequency, copulation duration, courtship duration, or fertility; however, females mated with resistant males showed reduced longevity. Body size did not vary with genotype. Larger males and females were not more likely to mate than smaller males and females, but larger females laid more eggs. Moderately strong, positive correlation occurred between the body sizes of successfully mated males and females; however, weak correlation also existed for pairs that did not mate. Our study provided only limited evidence for fitness costs associated with the Cry3Bb1-resistant genotype that might reduce the persistence in populations of the resistant genotype but provided additional evidence for size-based, assortative mating, which could favor the persistence of resistant genotypes affecting body size. PMID:26569315

  4. Platelet-Derived Growth Factor Promotes Periodontal Regeneration in Localized Osseous Defects: 36-Month Extension Results From a Randomized, Controlled, Double-Masked Clinical Trial

    PubMed Central

    Nevins, Myron; Kao, Richard T.; McGuire, Michael K.; McClain, Pamela K.; Hinrichs, James E.; McAllister, Bradley S.; Reddy, Michael S.; Nevins, Marc L.; Genco, Robert J.; Lynch, Samuel E.; Giannobile, William V.

    2017-01-01

    Background Recombinant human platelet-derived growth factor (rhPDGF) is safe and effective for the treatment of periodontal defects in short-term studies up to 6 months in duration. We now provide results from a 36-month extension study of a multicenter, randomized, controlled clinical trial evaluating the effect and long-term stability of PDGF-BB treatment in patients with localized severe periodontal osseous defects. Methods A total of 135 participants were enrolled fromsix clinical centers for an extension trial. Eighty-three individuals completed the study at 36 months and were included in the analysis. The study investigated the local application of β-tricalcium phosphate scaffold matrix with or without two different dose levels of PDGF (0.3 or 1.0 mg/mL PDGF-BB) in patients possessing one localized periodontal osseous defect. Composite analysis for clinical and radiographic evidence of treatment success was defined as percentage of cases with clinical attachment level (CAL) ≥2.7mmand linear bone growth (LBG) ≥1.1 mm. Results The participants exceeding this composite outcome benchmark in the 0.3 mg/mL rhPDGF-BB group went from 62.2% at 12 months, 75.9% at 24 months, to 87.0% at 36 months compared with 39.5%, 48.3%, and 53.8%, respectively, in the scaffold control group at these same time points (P <0.05). Although there were no significant increases in CAL and LBG at 36 months among all groups, there were continued increases in CAL gain, LBG, and percentage bone fill over time, suggesting overall stability of the regenerative response. Conclusion PDGF-BB in a synthetic scaffold matrix promotes long-term stable clinical and radiographic improvements as measured by composite outcomes for CAL gain and LBG for patients possessing localized periodontal defects (ClinicalTrials.gov no. CT01530126). PMID:22612364

  5. Co-stimulation through the CD137/4-1BB pathway protects human melanoma tumor-infiltrating lymphocytes from activation-induced cell death and enhances anti-tumor effector function

    PubMed Central

    Hernandez-Chacon, Jessica Ann; Li, Yufeng; Wu, Richard C.; Bernatchez, Chantale; Wang, Yijun; Weber, Jeffrey; Hwu, Patrick; Radvanyi, Laszlo

    2011-01-01

    Adoptive T-cell therapy (ACT) using expanded tumor-infiltrating lymphocytes (TIL) with high-dose IL-2 is a promising form of immunotherapy for Stage IV melanoma having clinical response rates of 50% or more. One of the major problems preventing further success of this therapy is that the current protocols used to highly expand TIL for infusion drive CD8+ T cells to differentiate into effector cells losing key co-stimulatory molecules such as CD28 and CD27. This has been associated with a lack of persistence in vivo for reasons not entirely clear. In this study, we demonstrate that while human melanoma CD8+ TIL lost CD27 and CD28 expression during the rapid expansion for ACT, they gained expression of the alternative co-stimulatory molecule CD137/4-1BB, and to a lesser extent CD134/OX40. Post-REP TIL were found to be highly sensitive to activation-induced cell death (AICD) when re-activated through the TCR with low levels of OKT3 antibody. However, co-ligation of 4-1BB using two different agonistic anti-4-1BB antibodies potently prevented AICD of post-REP CD8+ TIL, including those specific for MART-1, and facilitated even further cell expansion. This was correlated with increased levels of bcl-2 and bcl-xL together with decreased bim expression. 4-1BB-co-stimulated post-REP TIL also expressed increased levels of the cytolytic granule proteins and exhibited enhanced CTL activity against melanoma cells. Lastly, post-REP CD8+ TIL were protected from cell death by anti-4-1BB ligation when exposed to HLA-matched melanoma cells. Our results indicate that 4-1BB co-stimulation may significantly improve TIL survival during melanoma ACT and boost anti-tumor cytolytic activity. PMID:21389874

  6. Effects of Bifidobacterium animalis subsp. lactis BB-12® on the lipid/lipoprotein profile and short chain fatty acids in healthy young adults: a randomized controlled trial.

    PubMed

    Lee, Yujin; Ba, Zhaoyong; Roberts, Robert F; Rogers, Connie J; Fleming, Jennifer A; Meng, Huicui; Furumoto, Emily J; Kris-Etherton, Penny M

    2017-06-29

    Some probiotics have hypocholesterolemic effects in animal studies, which are mediated, in part, by increases in fecal short chain fatty acids (SCFAs). Clinical trials of probiotics on lipids/lipoproteins are inconsistent. We examined the effects of Bifidobacterium animalis subsp. lactis BB-12 ® (BB-12 ® ) (3.16 × 10 9  CFUs/day) on lipids and lipoproteins and fecal excretion of SCFAs in healthy adults. In a randomized, partially blinded, 4-period, crossover study, 30 adults (11 men, 19 women) aged 18-40 years were randomly assigned to: 1) yogurt smoothie with no BB-12 ® (YS), 2) yogurt smoothie with BB-12 ® added pre-fermentation (PRE), 3) yogurt smoothie with BB-12 ® added post-fermentation (POST), 4) BB-12 ® containing capsule (CAP). We measured serum lipids/lipoproteins, glucose, insulin, C-reactive protein (CRP), and fecal SCFAs at baseline and after each treatment period. Total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides (TGs) did not differ after the PRE, POST, and CAP periods versus the YS or between treatments. Compared to baseline, fecal acetate was significantly increased after the YS (Δ = 211.89 ± 75.87 μg/g, P = 0.007) and PRE (Δ = 204.98 ± 75.70 μg/g, P = 0.009) periods. The percent increase in fecal acetate was significantly greater after the YS versus the POST period (52.2 ± 13.2% vs. 24.5 ± 13.2%, P = 0.023). Fecal total SCFAs, propionate and butyrate did not differ between treatment periods. Fecal total SCFAs were negatively associated with TC (r = -0.22, P = 0.01), LDL-C (r = -0.24, P = 0.004), age (r = -0.33, P < 0.001), and waist circumference (r = -0.25, P = 0.003). BB-12 ® supplementation did not improve lipids, lipoproteins and total and individual fecal SCFAs. Fecal SCFAs were negatively associated with TC, LDL-C, age, and waist circumference. This trial was registered at clinicaltrials.gov as NCT01399996 .

  7. The Behaviour of the Military Battery Type BB248/U Used to Start the Engine of the A.P.C.

    DTIC Science & Technology

    1979-12-01

    UNCLASS IFIED I I ABSTRACT ~ ‘The performance of the lead—acid battery used to start the diesel engine ~~~~he Armoured Personnel Carrier...vehicle engines . One factor limiting the performance of this battery system is the very low Canadian winter temperatures, especially in Northern...information on the conditions of discharge inside the vehicle. For example, the military battery type BB248/U used to start the engine of the Armoured

  8. Ultrasensitive sensing platform for platelet-derived growth factor BB detection based on layered molybdenum selenide-graphene composites and Exonuclease III assisted signal amplification.

    PubMed

    Huang, Ke-Jing; Shuai, Hong-Lei; Zhang, Ji-Zong

    2016-03-15

    A highly sensitive and ultrasensitive electrochemical aptasensor for platelet-derived growth factor BB (PDGF-BB) detection is fabricated based on layered molybdenum selenide-graphene (MoSe2-Gr) composites and Exonuclease III (Exo III)-aided signal amplification. MoSe2-Gr is prepared by a simple hydrothermal method and used as a promising sensing platform. Exo III has a specifical exo-deoxyribonuclease activity for duplex DNAs in the direction from 3' to 5' terminus, however its activity is limited on the duplex DNAs with more than 4 mismatched terminal bases at 3' ends. Herein, aptamer and complementary DNA (cDNA) sequences are designed with four thymine bases on 3' ends. In the presence of target protein, the aptamer associates with it and facilitates the formation of duplex DNA between cDNA and signal DNA. The duplex DNA then is digested by Exo III and releases cDNA, which hybridizes with signal DNA to perform a new cleavage process. Nevertheless, in the absence of target protein, the aptamer hybridizes with cDNA will inhibit the Exo III-assisted nucleotides cleavage. The signal DNA then hybridizes with capture DNA on the electrode. Subsequently, horse radish peroxidase is fixed on electrode by avidin-biotin reaction and then catalyzes hydrogen peroxide and hydroquinone to produce electrochemical response. Therefore, a bridge can be established between the concentration of target protein and the degree of the attenuation of the obtained signal, providing a quantitative measure of target protein with a broad detection range of 0.0001-1 nM and a detection limit of 20 fM. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Assessment of fitness costs in Cry3Bb1 resistant and susceptible western corn rootworm (Coleoptera:Chrysomelidae) laboratory colonies

    EPA Science Inventory

    Maize production in the United States is dominated by plants genetically modified with transgenes from Bacillus thuringiensis (Bt). Varieties of Bt maize expressing Cry3Bb endotoxins that specifically target corn rootworms (genus Diabrotica) have proven highly efficacious. Howeve...

  10. Far Ultraviolet Spectroscopic Explorer Spectroscopy of the Nova-Like Cataclysmic Variable BB Doradus

    DTIC Science & Technology

    2008-06-27

    which we have best-fit models in the parameter space, we use the infrared magnitudes J, H, and K from the Two Micron All Sky Survey ( 2MASS ) to assess the...in a high state with a visual red magnitude R ¼ 14:60 and a blue magnitude B ¼ 13:90 (whereas B 16:5 in the low state). The 2MASS IR apparent...therefore certainly larger than 300 pc, and most likely in the range of 500 pc. Since BB Dor was observed in a high state (with 2MASS ), it is likely

  11. Insights into the Effects of Complement Factor H on the Assembly and Decay of the Alternative Pathway C3 Proconvertase and C3 Convertase*

    PubMed Central

    Bettoni, Serena; Bresin, Elena; Remuzzi, Giuseppe; Noris, Marina; Donadelli, Roberta

    2016-01-01

    The activated fragment of C3 (C3b) and factor B form the C3 proconvertase (C3bB), which is cleaved by factor D to C3 convertase (C3bBb). Older studies (Conrad, D. H., Carlo, J. R., and Ruddy, S. (1978) J. Exp. Med. 147, 1792–1805; Pangburn, M. K., and Müller-Eberhard, H. J. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 2416–2420; Kazatchkine, M. D., Fearon, D. T., and Austen, K. F. (1979) J. Immunol. 122, 75–81) indicated that the complement alternative pathway regulator factor H (FH) competes with factor B for C3b binding; however, the capability of FH to prevent C3bB assembly has not been formally investigated. Moreover, in the few published studies FH did not favor C3bB dissociation. Whether FH may affect C3bBb formation from C3bB is unknown. We set up user-friendly assays based on combined microplate/Western blotting techniques that specifically detect either C3bB or C3bBb, with the aim of investigating the effect of FH on C3bB assembly and decay and C3bBb formation and decay. We document that FH does not affect C3bB assembly, indicating that FH does not efficiently compete with factor B for C3b binding. We also found that FH does not dissociate C3bB. FH showed a strong C3bBb decay-accelerating activity, as reported previously, and also exerted an apparent inhibitory effect on C3bBb formation. The latter effect was not fully attributable to a rapid FH-mediated dissociation of C3bBb complexes, because blocking decay with properdin and C3 nephritic factor did not restore C3bBb formation. FH almost completely prevented release of the smaller cleavage subunit of FB (Ba), without modifying the amount of C3bB complexes, suggesting that FH inhibits the conversion of C3bB to C3bBb. Thus, the inhibitory effect of FH on C3bBb formation is likely the sum of inhibition of C3bB conversion to C3bBb and of C3bBb decay acceleration. Further studies are required to confirm these findings in physiological cell-based settings. PMID:26903516

  12. 2008/12 Baccalaureate and Beyond Longitudinal Study (B&B:08/12). Data File Documentation. NCES 2015-141

    ERIC Educational Resources Information Center

    Cominole, Melissa; Shepherd, Bryan; Siegel, Peter

    2015-01-01

    This publication describes the methods and procedures used in the 2008/12 Baccalaureate and Beyond Longitudinal Study (B&B:08/12). These graduates, who completed the requirements for a bachelor's degree during the 2007-08 academic year, were first interviewed as part of the 2008 National Postsecondary Student Aid Study (NPSAS:08), and then…

  13. Immunological and metabolic concomitants of cyclosporin prevention of diabetes in BB rats.

    PubMed

    Yale, J F; Grose, M; Seemayer, T A; Marliss, E B

    1987-06-01

    The metabolic and immunological effects of cyclosporin given to prevent diabetes in BB rats were examined. Diabetes-prone (BBdp) and normal (BBn) BB rats received either oral cyclosporin (10 mg X kg-1 X day-1 or its vehicle from age 30-150 days. Six of 21 (29%) vehicle-treated rats became glycosuric, with hyperglycemia, weight loss, and unremitting insulin requirements, and showed destruction of islet beta-cells. Five of 24 (21%) cyclosporin-treated rats became glycosuric, but none demonstrated weight loss, all required insulin only intermittently after onset, and all showed persistence of islet beta-cells. Cyclosporin induced hypoinsulinemic glucose intolerance in BBn rats. Cyclosporin inhibited the normal rise with age of peripheral blood lymphocyte cell numbers, identified with monoclonal antibodies. OX19+ (pan-T) and W3/25+ helper T-lymphocytes were affected, and there was an increase in the large W3/13+ OX19- population characteristic of BBdp rats; in addition, this subset appeared in BBn rats. Cyclosporin also caused the appearance and/or increase in both BBdp and BBn rats of W3/25+ OX19- and OX8+ OX19- subsets. Suppressor/cytotoxic (OX8+) T-lymphocytes and Ia+ cells were less affected. The incidence of hyperglycemia and glycosuria was therefore unaltered by cyclosporin, although the diabetic syndrome was milder. BBn rats receiving cyclosporin showed glucose intolerance, suggesting that in BBdp rats, the net effects of immunosuppression on beta-cell destruction may have been counterbalanced by the direct effect on the same cells. The attenuation of diabetes in BBdp rats occurred through further immunosuppression rather than by correction of its preexisting immunodeficiency.

  14. PDGF-BB induces PRMT1 expression through ERK1/2 dependent STAT1 activation and regulates remodeling in primary human lung fibroblasts.

    PubMed

    Sun, Qingzhu; Liu, Li; Mandal, Jyotshna; Molino, Antonio; Stolz, Daiana; Tamm, Michael; Lu, Shemin; Roth, Michael

    2016-04-01

    Tissue remodeling of sub-epithelial mesenchymal cells is a major pathology occurring in chronic obstructive pulmonary disease (COPD) and asthma. Fibroblasts, as a major source of interstitial connective tissue extracellular matrix, contribute to the fibrotic and inflammatory changes in these airways diseases. Previously, we described that protein arginine methyltransferase-1 (PRMT1) participates in airway remodeling in a rat model of pulmonary inflammation. In this study we investigated the mechanism by which PDGF-BB regulates PRMT1 in primary lung fibroblasts, isolated from human lung biopsies. Fibroblasts were stimulated with PDGF-BB for up-to 48h and the regulatory and activation of signaling pathways controlling PRMT1 expression were determined. PRMT1 was localized by immuno-histochemistry in human lung tissue sections and by immunofluorescence in isolated fibroblasts. PRMT1 activity was suppressed by the pan-PRMT inhibitor AMI1. ERK1/2 mitogen activated protein kinase (MAPK) was blocked by PD98059, p38 MAPK by SB203580, and STAT1 by small interference (si) RNA treatment. The results showed that PDGF-BB significantly increased PRMT1 expression after 1h lasting over 48h, through ERK1/2 MAPK and STAT1 signaling. The inhibition of ERK1/2 MAPK or of PRMT1 activity decreased PDGF-BB induced fibroblast proliferation, COX2 production, collagen-1A1 secretion, and fibronectin production. These findings suggest that PRMT1 is a central regulator of tissue remodeling and that the signaling sequence controlling its expression in primary human lung fibroblast is PDGF-ERK-STAT1. Therefore, PRMT1 presents a novel therapeutic and diagnostic target for the control of airway wall remodeling in chronic lung diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Selection for Cry3Bb1 resistance in a genetically diverse population of nondiapausing Western Corn Rootworm (Coleoptera: Chrysomelidae)

    EPA Science Inventory

    Five short-diapause laboratory lines of western corn rootworm (Diabrotica virgifera virgifera) were selected for resistance to MON863, a variety of corn genetically modified with the Bacillus thuringiensis (Bt) transgene that expresses the Cry3Bb1 endotoxin. Three of the selecte...

  16. Assessment of fitness costs in Cry3Bb1 resistant and susceptible western corn rootworm (Coleoptera: Chrysomelidae) laboratory colonies

    USDA-ARS?s Scientific Manuscript database

    Maize production in the United States is dominated by plants genetically modified with transgenes from Bacillus thuringiensis (Bt). Varieties of Bt maize expressing Cry3Bb d endotoxins that specifically target corn rootworms (genus Diabrotica) have proven highly efficacious. However, development of ...

  17. Isolation of transcripts from Diabrotica virgifera virgifera LeConte responsive to the Bacillus thuringiensis toxin Cry3Bb1

    EPA Science Inventory

    Crystal proteins derived from Bacillus thuringiensis (Bt) have been widely used as a method of insect pest management for several decades. In recent years, a transgenic corn expressing the Cry3Bb1 toxin has been successfully used for protection against corn rootworm larvae (Genus...

  18. The fight for accretion: discovery of intermittent mass transfer in BB Doradus in the low state

    NASA Astrophysics Data System (ADS)

    Rodríguez-Gil, P.; Schmidtobreick, L.; Long, K. S.; Gänsicke, B. T.; Torres, M. A. P.; Rubio-Díez, M. M.; Santander-García, M.

    2012-05-01

    Our long-term photometric monitoring of southern nova-like cataclysmic variables with the 1.3-m Small and Moderate Aperture Research Telescope System (SMARTS) telescope found BB Doradus fading from V˜ 14.3 towards a deep low state at V˜ 19.3 in 2008 April. Here we present time-resolved optical spectroscopy of BB Dor in this faint state in 2009. The optical spectrum in quiescence is a composite of a hot white dwarf with Teff= 30 000 ± 5000 K and a M3-M4 secondary star with narrow emission lines (mainly of the Balmer series and He I) superposed. We associate these narrow profiles with an origin on the donor star. An analysis of the radial velocity curve of the Hα emission from the donor star allowed the measurement of an orbital period of 0.154 095 ± 0.000 003 d (3.698 28 ± 0.000 07 h), different from all previous estimates. We detected episodic accretion events which veiled the spectra of both stars and radically changed the line profiles within a time-scale of tens of minutes. This shows that accretion is not completely quenched in the low state. During these accretion episodes the line wings are stronger and their radial velocity curve is delayed by ˜0.2 cycle, similar to that observed in SW Sex and AM Her stars in the high state, with respect to the motion of the white dwarf. Two scenarios are proposed to explain the extra emission: impact of the material on the outer edge of a cold, remnant accretion disc, or the combined action of a moderately magnetic white dwarf (B1≲ 5 MG) and the magnetic activity of the donor star.

  19. Fixation-free rehalogenating bleached reflection holograms recorded on BB-640 plates

    NASA Astrophysics Data System (ADS)

    Neipp, C.; Pascual, I.; Beléndez, A.

    2000-08-01

    Fixation-free rehalogenating bleaching is an interesting process for the production of phase reflection holograms. The shrinkage of the emulsion is reduced in comparison with other bleaching methods (reversal bleaching or rehalogenating bleaching with a fixation step), which is particularly interesting in the case of reflection holograms. In this communication, we present experimental results for fixation-free rehalogenating bleached holograms derived from the novel BB-640 emulsion, a red-sensitive ultra-fine grain emulsion from Holographic Recording Technologies using an R-10 type bleach bath. The influence of the potassium bromide concentrations in the bleach solution on the final quality of the holograms is also studied. The concentrations of the different components of the bleach solution are adjusted to obtain the highest diffraction efficiencies. A high diffraction efficiency of 72% is obtained.

  20. Penetrating BB shot head wound in an asymptomatic 9-year-old girl: the ultimate teaching moment.

    PubMed

    Johnson, N A

    1997-01-01

    Air rifle BB injuries represent a common type of childhood accident. The purpose of this case report is to encourage all providers of pediatric care to include nonpowder firearm safety education with standard well-child anticipatory guidance. A case report is described and experience with similar injuries is discussed from cases found in a literature review using the key words "air rifle," "patient education," "pediatric," "ballistics," and "trauma." A 9-year-old girl came to the emergency department after having been accidentally shot in the head by her 7-year-old brother with a toy air rifle. The BB shot entered through the left cheek and traversed up into the soft tissue above the mandible, just medial to the internal carotid artery, and posterior to the facial nerve. Other than local pain, she was entirely asymptomatic. The cheek was repaired without complication. Conservative therapy was recommended. She and her family were given anticipatory guidance, and her course thereafter was uneventful. Firearm education is not a standard part of every well-child encounter. Injuries by all types of firearms are increasing at epidemic rates. Questioning about the accessibility of both powder- and non-powder-based weapons (ie, air rifle) and providing routine safety education should become the standard of care at all well-child encounters.

  1. The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models.

    PubMed

    Brito, Marlon V; de Oliveira, Cleide; Salu, Bruno R; Andrade, Sonia A; Malloy, Paula M D; Sato, Ana C; Vicente, Cristina P; Sampaio, Misako U; Maffei, Francisco H A; Oliva, Maria Luiza V

    2014-05-01

    The Bauhinia bauhinioides Kallikrein Inhibitor (BbKI) is a Kunitz-type serine peptidase inhibitor of plant origin that has been shown to impair the viability of some tumor cells and to feature a potent inhibitory activity against human and rat plasma kallikrein (Kiapp 2.4 nmol/L and 5.2 nmol/L, respectively). This inhibitory activity is possibly responsible for an effect on hemostasis by prolonging activated partial thromboplastin time (aPTT). Because the association between cancer and thrombosis is well established, we evaluated the possible antithrombotic activity of this protein in venous and arterial thrombosis models. Vein thrombosis was studied in the vena cava ligature model in Wistar rats, and arterial thrombosis in the photochemical induced endothelium lesion model in the carotid artery of C57 black 6 mice. BbKI at a concentration of 2.0 mg/kg reduced the venous thrombus weight by 65% in treated rats in comparison to rats in the control group. The inhibitor prolonged the time for total artery occlusion in the carotid artery model mice indicating that this potent plasma kallikrein inhibitor prevented thrombosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Using new non-invasive quick method to detect Borrelia Burgdorferi (B.B.) infection from specific parts of the heart in "seemingly normal" ECGs, and from the ECGs of Atrial Fibrillation (AF), a majority of AF ECGs are found to have: 1) Significant B.B. infection, 2) Markedly increased ANP, 3) Increased Cardiac Troponin I & 4) Markedly reduced Taurine. These 4 factors were mainly localized at infected areas of the SA node area, R-&L-Atria & pulmonary veins at the L-atrium.

    PubMed

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu

    2015-01-01

    Lyme disease is found in a majority of people we tested. Once Borrelia Burgdorferi (B.B.) spirochete enters human body, it not only causes pain by infecting joints, but it also often enters the brain and the heart. Infection of brain can be quickly detected from the pupil and infection of the heart by ECGs non-invasively. By evaluating recorded ECGs of atrial fibrillation (AF), using U.S. patented non-invasive highly sensitive electromagnetic field (EMF) resonance phenomenon between 2 identical molecules or between a molecule and its antibody, we examined 25 different AF patients' ECGs and found the majority of them suffer from various degrees of B.B. spirochete infection in SA node areas, also in the right & left atria, and pulmonary vein near and around its junction at left atrium & lesser degrees of infection at the AV node & His Bundle. When B.B. infection reaches over 224-600ng or higher at these areas, AF often appears in the majority of all AF analyzed. In order to develop AF, the 4 abnormal factors must be present simultaneously: 1) B.B. infection must be increased to 224-600ng or higher, 2) Atrial Natriuretic Peptide (ANP) must be markedly reduced from normal value of less than 4ng to over 100-400ng, 3) A significant increase of Cardiac Troponin I from normal value of less than 3ng to over 12ng and 4) Taurine must also be markedly reduced from normal value of 4-6ng to 0.25ng. These 4 changes were mainly found only at infected sites of the SA node area, both atria and between the end of the T wave & the beginning of the SA node area, which corresponds to U waves at recorded ECG. Origin of the U wave is mainly due to abnormal electrical potential of pulmonary vein at L-atrium. If all 4 factors do not occur at the infection site, no AF will develop. In seemingly normal ECGs, if using this method, one can detect invisible B.B. infection in early stages. Long before AF appears, AF can be prevented by improved treatment with Amoxicillin 500ng 3 times

  3. Genetic analysis of virulence in the Pyrenophora teres f. teres population BB25 x FGOH04Ptt021

    USDA-ARS?s Scientific Manuscript database

    Pyrenophora teres f. teres is the causal agent of net form net blotch (NFNB) of barley. In order to map the genetics of avirulence/virulence in P. teres f. teres, a fungal population was developed using P. teres f. teres isolates BB25 (Denmark) and FGOH04Ptt-21 (North Dakota, USA) due to these two i...

  4. Facile insertion of a cyclic alkyl(amino) carbene carbon into the B-B bond of diboron(4) reagents.

    PubMed

    Eichhorn, Antonius F; Kuehn, Laura; Marder, Todd B; Radius, Udo

    2017-10-24

    We report herein the room temperature insertion of the carbene carbon atom of the cyclic (alkyl)(amino) carbene cAAC Me into the B-B single bonds of the diboron(4) compounds B 2 pin 2 , B 2 cat 2 , B 2 neop 2 , and B 2 eg 2 (pin = pinacolato, cat = catecholato, neop = neopentylglycolato, eg = ethyleneglycolato).

  5. Finished Genome Sequence of Bacillus cereus Strain 03BB87, a Clinical Isolate with B. anthracis Virulence Genes

    DOE PAGES

    Johnson, Shannon L.; Minogue, Timothy D.; Teshima, Hazuki; ...

    2015-01-15

    Bacillus cereus strain 03BB87, a blood culture isolate, originated in a 56-year-old male muller operator with a fatal case of pneumonia in 2003. Here we present the finished genome sequence of that pathogen, including a 5.46-Mb chromosome and two plasmids (209 and 52 Kb, respectively).

  6. The Impact of Storage Conditions on the Stability of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis Bb12 in Human Milk.

    PubMed

    Mantziari, Anastasia; Aakko, Juhani; Kumar, Himanshu; Tölkkö, Satu; du Toit, Elloise; Salminen, Seppo; Isolauri, Erika; Rautava, Samuli

    2017-11-01

    Human milk is the optimal source of complete nutrition for neonates and it also guides the development of infant gut microbiota. Importantly, human milk can be supplemented with probiotics to complement the health benefits of breastfeeding. Storage of human milk for limited periods of time is often unavoidable, but little is known about the effect of different storage conditions (temperature) on the viability of the added probiotics. Therefore, in this study, we evaluated how different storage conditions affect the viability of two specific widely used probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis (Bb12), in human milk by culturing and quantitative polymerase chain reaction. Our results indicate that LGG and Bb12 remained stable throughout the storage period. Thus, we conclude that human milk offers an appropriate matrix for probiotic supplementation.

  7. Decomposition rates and residue-colonizing microbial communities of Bacillus thuringiensis insecticidal protein Cry3Bb-expressing (Bt) and non-Bt corn hybrids in the field.

    PubMed

    Xue, Kai; Serohijos, Raquel C; Devare, Medha; Thies, Janice E

    2011-02-01

    Despite the rapid adoption of crops expressing the insecticidal Cry protein(s) from Bacillus thuringiensis (Bt), public concern continues to mount over the potential environmental impacts. Reduced residue decomposition rates and increased tissue lignin concentrations reported for some Bt corn hybrids have been highlighted recently as they may influence soil carbon dynamics. We assessed the effects of MON863 Bt corn, producing the Cry3Bb protein against the corn rootworm complex, on these aspects and associated decomposer communities by terminal restriction fragment length polymorphism (T-RFLP) analysis. Litterbags containing cobs, roots, or stalks plus leaves from Bt and unmodified corn with (non-Bt+I) or without (non-Bt) insecticide applied were placed on the soil surface and at a 10-cm depth in field plots planted with these crop treatments. The litterbags were recovered and analyzed after 3.5, 15.5, and 25 months. No significant effect of treatment (Bt, non-Bt, and non-Bt+I) was observed on initial tissue lignin concentrations, litter decomposition rate, or bacterial decomposer communities. The effect of treatment on fungal decomposer communities was minor, with only 1 of 16 comparisons yielding separation by treatment. Environmental factors (litterbag recovery year, litterbag placement, and plot history) led to significant differences for most measured variables. Combined, these results indicate that the differences detected were driven primarily by environmental factors rather than by any differences between the corn hybrids or the use of tefluthrin. We conclude that the Cry3Bb corn tested in this study is unlikely to affect carbon residence time or turnover in soils receiving these crop residues.

  8. Selection for Cry3Bb1 resistance in a genetically diverse population of non-diapausing western corn rootworm (Coleoptera: Chrysomelidae)

    USDA-ARS?s Scientific Manuscript database

    Five short-diapause laboratory lines of western corn rootworm (Diabrotica virgifera virgifera) were selected for resistance to MON863, a variety of corn genetically modified with the Bacillus thuringiensis (Bt) transgene that expresses the Cry3Bb1 d-endotoxin. Three of the selected lines were develo...

  9. Assessment of stress tolerance acquisition in the heat-tolerant derivative strains of Bifidobacterium animalis subsp. lactis BB-12 and Lactobacillus rhamnosus GG.

    PubMed

    Aakko, J; Sánchez, B; Gueimonde, M; Salminen, S

    2014-07-01

    The purpose of this study was to investigate the heat-shock response at molecular level in Lactobacillus rhamnosus GG, Bifidobacterium animalis subsp. lactis BB-12 and their heat-tolerant derivatives and to characterize the changes that make the derivatives more robust in terms of heat stress. The study strains were exposed for 2 h to a heat-shock treatment, Bif. animalis subsp. lactis BB-12 and its derivative at 50°C and the Lact. rhamnosus GG and its derivative at 60°C. Protein synthesis before and after heat shock was examined using proteomics and RT-qPCR. The analysis revealed that the regulation of seven proteins in both strain pairs was modified as a response to heat or between the original and the derivative strain. The comparison of wild-type strains and the heat-tolerant derivatives suggests that the acquisition of heat tolerance in the Bif. animalis subsp. lactis BB-12 derivative is due to a slightly increased constitutive level of chaperones, while in Lact. rhamnosus GG derivative, the main reason seems to be a higher ability to induce the production of chaperones. This study revealed possible markers of heat tolerance in B. lactis and Lact. rhamnosus strains. This study increases our knowledge on how Lactobacillus and Bifidobacterium strains may acquire heat tolerance. These findings may be useful for improving the heat tolerance of existing probiotic strains as well as screening new heat-tolerant strains. © 2014 The Society for Applied Microbiology.

  10. MicroRNA-24 regulates vascular remodeling via inhibiting PDGF-BB pathway in diabetic rat model.

    PubMed

    Yang, Jian; Zeng, Ping; Yang, Jun; Liu, Xiaowen; Ding, Jiawang; Wang, Huibo; Chen, Lihua

    2018-06-15

    Hyperglycemia is the high risk factor of vascular remodeling induced by angioplasty, and neointimal hyperplasia is strongly implicated in the pathogenesis of vascular remodeling caused by carotid artery balloon injury. Studies have shown that MicroRNA 24 (miR-24) plays an important role in angiocardiopathy, However, the role of miR-24 is far from thorough research. In this study, we investigate whether up-regulation of miR-24 by using miR-24 recombinant adenovirus (Ad-miR-24-GFP) can inhibit PDGF-BB signaling pathway and attenuate vascular remodeling in the diabetic rat model. Male Sprague-Dawley rats (n = 60) were randomly divided into 5 groups and fed with high sugar and high fat diet (Sham, Saline, Scramble, Ad-miR-24 groups), or ordinary diet (Control group). The front four groups were treated with streptozotocin (STZ) four weeks later and the blood glucose level was closely monitored. After the successful establishment of diabetic rats, the external carotid artery was injured by pressuring balloon 1.5 after internal carotid artery ligation, then the blood vessels were harvested 14 days later and indexes were detected including the following: HE staining for the level of vascular intima thickness, immunohistochemical detection for PCNA and P27 to test the proliferative degree of vascular smooth muscle cells (VSMCs), qRT-PCR for the level of miR-24, RAS,PDGF-R, western blot for the protein levels of JNK1/2, p- JNK1/2, ERK1/2, p-ERK1/2, RAS, PDGF-R, AP-1,P27 and PCNA. Serological detection was conducted for TNF-α, IL-6, IL-8. The delivery of Ad-miR-24 into balloon injury site has significantly increased the level of miR-24. Up-regulation of miR-24 could regulate vascular remodeling effectively, lower the level of inflammatory factors, inhibit the expression of mRNA and protein levels of JNK1/2, ERK1/2, RAS, PDGF-R, AP-1, P27, PCNA. miR-24 can inhibit the expression of AP-1 via the inhibition of PDGF-BB signaling pathway, thus inhibit VSMCs proliferation

  11. Forsythoside A Inhibits BVDV Replication via TRAF2-Dependent CD28-4-1BB Signaling in Bovine PBMCs.

    PubMed

    Song, Quan-Jiang; Weng, Xiao-Gang; Cai, Dong-Jie; Zhang, Wang; Wang, Jiu-Feng

    2016-01-01

    Bovine viral diarrhea virus (BVDV), the causative agent of bovine viral diarrhea/mucosal disease (BVD/MD), is an important pathogen of cattle and other wild animals throughout the world. BVDV infection typically leads to an impaired immune response in cattle. In the present study, we investigated the effect of Forsythoside A (FTA) on BVDV infection of bovine peripheral blood mononuclear cells (PBMCs). We found that Forsythoside A could not only promote proliferation of PBMCs and T cells activation but also inhibit the replication of BVDV as well as apoptosis induced by BVDV. FTA treatment could counteract the BVDV-induced overproduction of IFN-γ to maintain the immune homeostasis in bovine PBMCs. At same time, FTA can enhance the secretion of IL-2. What's more, BVDV promotes the expression of CD28, 4-1BB and TRAF-2, which can be modulated by FTA. Our data suggest that FTA protects PBMCs from BVDV infection possibly via TRAF2-dependent CD28-4-1BB signaling, which may activate PBMCs in response to BVDV infection. Therefore, this aids in the development of an effective adjuvant for vaccines against BVDV and other specific FTA-based therapies for preventing BVDV infection.

  12. Penetrating head injuries in children due to BB and pellet guns: a poorly recognized public health risk.

    PubMed

    Kumar, Ravi; Kumar, Ramesh; Mallory, Grant W; Jacob, Jeffrey T; Daniels, David J; Wetjen, Nicholas M; Foy, Andrew B; O'Neill, Brent R; Clarke, Michelle J

    2015-10-23

    OBJECT Nonpowder guns, defined as spring- or gas-powered BB or pellet guns, can be dangerous weapons that are often marketed to children. In recent decades, advances in compressed-gas technology have led to a significant increase in the power and muzzle velocity of these weapons. The risk of intracranial injury in children due to nonpowder weapons is poorly documented. METHODS A retrospective review was conducted at 3 institutions studying children 16 years or younger who had intracranial injuries secondary to nonpowder guns. RESULTS The authors reviewed 14 cases of intracranial injury in children from 3 institutions. Eleven (79%) of the 14 children were injured by BB guns, while 3 (21%) were injured by pellet guns. In 10 (71%) children, the injury was accidental. There was 1 recognized assault, but there were no suicide attempts; in the remaining 3 patients, the intention was indeterminate. There were no mortalities among the patients in this series. Ten (71%) of the children required operative intervention, and 6 (43%) were left with permanent neurological injuries, including epilepsy, cognitive deficits, hydrocephalus, diplopia, visual field cut, and blindness. CONCLUSIONS Nonpowder guns are weapons with the ability to penetrate a child's skull and brain. Awareness should be raised among parents, children, and policy makers as to the risk posed by these weapons.

  13. Safety and immunogenicity of RV3-BB human neonatal rotavirus vaccine administered at birth or in infancy: a randomised, double-blind, placebo-controlled trial.

    PubMed

    Bines, Julie E; Danchin, Margaret; Jackson, Pamela; Handley, Amanda; Watts, Emma; Lee, Katherine J; West, Amanda; Cowley, Daniel; Chen, Mee-Yew; Barnes, Graeme L; Justice, Frances; Buttery, Jim P; Carlin, John B; Bishop, Ruth F; Taylor, Barry; Kirkwood, Carl D

    2015-12-01

    Despite the success of rotavirus vaccines, suboptimal vaccine efficacy in regions with a high burden of disease continues to present a challenge to worldwide implementation. A birth dose strategy with a vaccine developed from an asymptomatic neonatal rotavirus strain has the potential to address this challenge and provide protection from severe rotavirus disease from birth. This phase 2a randomised, double-blind, three-arm, placebo-controlled safety and immunogenicity trial was undertaken at a single centre in New Zealand between Jan 13, 2012, and April 17, 2014. Healthy, full-term (≥36 weeks gestation) babies, who weighed at least 2500 g, and were 0-5 days old at the time of randomisation were randomly assigned (1:1:1; computer-generated; telephone central allocation) according to a concealed block randomisation schedule to oral RV3-BB vaccine with the first dose given at 0-5 days after birth (neonatal schedule), to vaccine with the first dose given at about 8 weeks after birth (infant schedule), or to placebo. The primary endpoint was cumulative vaccine take (serum immune response or stool shedding of vaccine virus after any dose) after three doses. The immunogenicity analysis included all randomised participants with available outcome data. This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611001212943. 95 eligible participants were randomised, of whom 89 were included in the primary analysis. A cumulative vaccine take was detected in 27 (90%) of 30 participants in the neonatal schedule group after three doses of RV3-BB vaccine compared with four (13%) of 32 participants in the placebo group (difference in proportions 0·78, 95% CI 0·55-0·88; p<0·0001). 25 (93%) of 27 participants in the infant schedule group had a cumulative vaccine take after three doses compared with eight (25%) of 32 participants in the placebo group (difference in proportions 0·68, 0·44-0·81; p<0·0001). A serum IgA response was detected in 19

  14. Production of haploids from anther culture of banana [Musa balbisiana (BB)].

    PubMed

    Assani, A; Bakry, F; Kerbellec, F; Haïcour, R; Wenzel, G; Foroughi-Wehr, B

    2003-02-01

    We report here, for the first time, the production of haploid plants of banana Musa balbisiana (BB). Callus was induced from anthers in which the majority of the microspores were at the uninucleate stage. The frequency of callus induction was 77%. Callus proliferation usually preceded embryo formation. About 8% of the anthers developed androgenic embryos. Of the 147 plantlets obtained, 41 were haploids (n=x=11). The frequency of haploid production depended on genotypes used: 18 haploid plants were produced from genotype Pisang klutuk, 12 from Pisang batu, seven from Pisang klutuk wulung and four from Tani. The frequency of regeneration was 1.1%, which was based on the total number of anthers cultured. Diploid plants (2n=2x=22) were also observed in the regenerated plants. The haploid banana plants that were developed will be important material for the improvement of banana through breeding programmes.

  15. Assessment of Inheritance and Fitness Costs Associated with Field-Evolved Resistance to Cry3Bb1 Maize by Western Corn Rootworm.

    PubMed

    Paolino, Aubrey R; Gassmann, Aaron J

    2017-05-11

    The western corn rootworm, Diabrotica virgifera virgifera LeConte, is among the most serious insect pests of maize in North America. One strategy used to manage this pest is transgenic maize that produces one or more crystalline (Cry) toxins derived from the bacterium Bacillus thuringiensis (Bt). To delay Bt resistance by insect pests, refuges of non-Bt maize are grown in conjunction with Bt maize. Two factors influencing the success of the refuge strategy to delay resistance are the inheritance of resistance and fitness costs, with greater delays in resistance expected when inheritance of resistance is recessive and fitness costs are present. We measured inheritance and fitness costs of resistance for two strains of western corn rootworm with field-evolved resistance to Cry3Bb1 maize. Plant-based and diet-based bioassays revealed that the inheritance of resistance was non-recessive. In a greenhouse experiment, in which larvae were reared on whole maize plants in field soil, no fitness costs of resistance were detected. In a laboratory experiment, in which larvae experienced intraspecific and interspecific competition for food, a fitness cost of delayed larval development was identified, however, no other fitness costs were found. These findings of non-recessive inheritance of resistance and minimal fitness costs, highlight the potential for the rapid evolution of resistance to Cry3Bb1 maize by western corn rootworm, and may help to improve resistance management strategies for this pest.

  16. The administration of IL-12/GM-CSF and Ig-4-1BB ligand markedly decreases murine floor of mouth squamous cell cancer.

    PubMed

    Adappa, Nithin D; Sung, Chi-Kwang; Choi, Bryan; Huang, Tian-Gui; Genden, Eric M; Shin, Edward J

    2008-09-01

    To assess immune-based gene therapy in a murine floor of mouth (FOM) squamous cell carcinoma (SCC) model. In vitro and in vivo testing of immune therapy for SCC. Multiple SCC lines were infected by using advRSV-interleukin-12 (IL-12) and advCMV-interleukin-12/granulocyte macrophage colony-stimulating factor (IL-12/GM-CSF) and monitored for production of IL-12 and GM-CSF. Intratumoral injections of viral vectors were administered with systemic Ig-4-1BB ligand in an orthotopic murine FOM SCC model and followed for tumor size and survival. In vitro, all cell lines produced substantial levels of IL-12 and GM-CSF. In vivo, tumors treated with advCMV-IL-12/GM-CSF and Ig-4-1BBL showed a striking reduction in tumor volume (vs control P<0.0001) and improved median survival (38 days vs 19 days for control, P<0.0001). Combination immune-based therapies effectively improve survival in mice bearing FOM SCC over single-modality therapy.

  17. Thick phase holographic gratings recorded on BB-640 and PFG-01 silver halide materials

    NASA Astrophysics Data System (ADS)

    Neipp, Cristian; Márquez, Andrés; Pascual, Inmaculada; Beléndez, Augusto

    2003-09-01

    Photographic emulsions are still widely used to record holographic optical elements. In particular, if high diffraction efficiencies are needed, phase volume holograms are preferably recorded on these emulsions. Two particular techniques producing high-quality volume phase holograms are fixation-free rehalogenating bleaching and the use of silver-halide-sensitized gelatin. In this work we compare these two particular techniques applied to three different red-sensitive emulsions: Agfa 8E75 HD, BB-640, and Slavich PFG-01 emulsions. The differences between these emulsions determine the particular experimental conditions needed to record high-quality volume holograms on them. In this work these differences are analysed, and also their influence on the experimental procedure.

  18. Interactome analysis of transcriptional coactivator multiprotein bridging factor 1 unveils a yeast AP-1-like transcription factor involved in oxidation tolerance of mycopathogen Beauveria bassiana.

    PubMed

    Chu, Xin-Ling; Dong, Wei-Xia; Ding, Jin-Li; Feng, Ming-Guang; Ying, Sheng-Hua

    2018-02-01

    Oxidation tolerance is an important determinant to predict the virulence and biocontrol potential of Beauveria bassiana, a well-known entomopathogenic fungus. As a transcriptional coactivator, multiprotein bridging factor 1 mediates the activity of transcription factor in diverse physiological processes, and its homolog in B. bassiana (BbMBF1) contributes to fungal oxidation tolerance. In this study, the BbMBF1-interactomes under oxidative stress and normal growth condition were deciphered by mass spectrometry integrated with the immunoprecipitation. BbMBF1p factor has a broad interaction with proteins that are involved in various cellular processes, and this interaction is dynamically regulated by oxidative stress. Importantly, a B. bassiana homolog of yeast AP-1-like transcription factor (BbAP-1) was specifically associated with the BbMBF1-interactome under oxidation and significantly contributed to fungal oxidation tolerance. In addition, qPCR analysis revealed that several antioxidant genes are jointly controlled by BbAP-1 and BbMBF1. Conclusively, it is proposed that BbMBF1p protein mediates BbAP-1p factor to transcribe the downstream antioxidant genes in B. bassiana under oxidative stress. This study demonstrates for the first time a proteomic view of the MBF1-interactome in fungi, and presents an initial framework to probe the transcriptional mechanism involved in fungal response to oxidation, which will provide a new strategy to improve the biocontrol efficacy of B. bassiana.

  19. Forsythoside A Inhibits BVDV Replication via TRAF2-Dependent CD28–4-1BB Signaling in Bovine PBMCs

    PubMed Central

    Song, Quan-Jiang; Weng, Xiao-Gang; Cai, Dong-Jie; Zhang, Wang; Wang, Jiu-Feng

    2016-01-01

    Bovine viral diarrhea virus (BVDV), the causative agent of bovine viral diarrhea/mucosal disease (BVD/MD), is an important pathogen of cattle and other wild animals throughout the world. BVDV infection typically leads to an impaired immune response in cattle. In the present study, we investigated the effect of Forsythoside A (FTA) on BVDV infection of bovine peripheral blood mononuclear cells (PBMCs). We found that Forsythoside A could not only promote proliferation of PBMCs and T cells activation but also inhibit the replication of BVDV as well as apoptosis induced by BVDV. FTA treatment could counteract the BVDV-induced overproduction of IFN-γ to maintain the immune homeostasis in bovine PBMCs. At same time, FTA can enhance the secretion of IL-2. What’s more, BVDV promotes the expression of CD28, 4-1BB and TRAF-2, which can be modulated by FTA. Our data suggest that FTA protects PBMCs from BVDV infection possibly via TRAF2-dependent CD28–4-1BB signaling, which may activate PBMCs in response to BVDV infection. Therefore, this aids in the development of an effective adjuvant for vaccines against BVDV and other specific FTA-based therapies for preventing BVDV infection. PMID:27617959

  20. Influence of the addition of Lactobacillus acidophilus La-05, Bifidobacterium animalis subsp. lactis Bb-12 and inulin on the technological, physicochemical, microbiological and sensory features of creamy goat cheese.

    PubMed

    Barbosa, Ilsa C; Oliveira, Maria E G; Madruga, Marta S; Gullón, Beatriz; Pacheco, Maria T B; Gomes, Ana M P; Batista, Ana S M; Pintado, Maria M E; Souza, Evandro L; Queiroga, Rita C R E

    2016-10-12

    The effects of the addition of Lactobacillus acidophilus LA-05, Bifidobacterium animalis subsp. lactis BB-12 and inulin on the quality characteristics of creamy goat cheese during refrigerated storage were evaluated. The manufactured cheeses included the addition of starter culture (Lactococcus lactis subsp. lactis and Lactococcus lactis subsp. cremoris - R-704) (CC); starter culture, L. acidophilus LA-05 and inulin (CLA); starter culture, B. lactis BB-12 and inulin (CBB); or starter culture, L. acidophilus LA-05, B. lactis BB-12 and inulin (CLB). In the synbiotic cheeses (CLA, CBB and CLB), the counts of L. acidophilus LA-05 and B. lactis BB-12 were greater than 6log CFU g -1 , the amount of inulin was greater than 6 g per 100 g, and the firmness was reduced. The cheeses evaluated had high brightness values (L*), with a predominance of yellow (b*). CC had higher contents of proteins, lipids and minerals compared to the other cheeses. There was a decrease in the amount of short-chain fatty acids (SCFAs) and an increase of medium-chain (MCFAs) and long-chain fatty acids (LCFAs) in the synbiotic cheeses compared to CC. The amount of conjugated linoleic acid increased in CLA, CBB and CLB. The highest depth of proteolysis and the greatest changes in the release of free amino acids were found in CLB. The addition of inulin and probiotics, alone or in co-culture, did not affect the cheese acceptance. Inulin and probiotics can be used together for the production of creamy goat cheese without negatively affecting the general quality characteristics of the product, and to add value because of its synbiotic potential.

  1. Evidence for idiotypic- and antiidiotypic B-B cellular interaction with the use of cloned antiidiotypic B cell line.

    PubMed

    Bitoh, S; Fujimoto, S; Yamamoto, H

    1990-03-15

    Immunization of BALB/c mice with MOPC104E myeloma protein induces antiidiotypic B lymphocytes that have Id-specific enhancing activity on antibody production. The B-B cell interaction was restricted to both Igh and class II MHC. However, anti-Thy-1 and C-treated splenic B cells were maintained for more than 1 y in a mixture of Con A-stimulated splenocyte culture supernatant and synthetic medium. In applying the long term culture method, we have established a cloned B cell line named B19-1d, B19-1d cells are specific to MOPC104E or J558 cross-reactive Id and they express surface mu, lambda but no Ly-1. B19-1d do not spontaneously secrete Ig but produce them upon stimulation with bacterial LPS. The effect of B19-1d cell line on idiotypic antibody production was tested. Addition of only 10 to 100 B19-1d cells into dextran-immune B cell culture greatly enhanced the Id+ antidextran antibody responses. On the contrary, the antidextran antibody production was suppressed by the higher doses of B19-1d cells. The effective cooperation between dextran-immune B cells and B19-1d cloned B cells was restricted to class II MHC. The role of idiotypic- and antiidiotypic B-B cell interaction in immune regulation and repertoire generation was suggested.

  2. Multiple assays indicate varying levels of cross resistance of Cry3Bb1-selected field populations of the western corn rootworm to mCry3A, eCry3.1Ab, and Cry34/35Ab1

    USDA-ARS?s Scientific Manuscript database

    Minnesota populations of the western corn rootworm (WCR) surviving Cry3Bb1-expressing corn in the field and WCR populations assumed to be susceptible to all Bt proteins were evaluated for susceptibility to Cry3Bb1, mCry3A, eCry3.1Ab, and Cry34/35Ab1 in diet assays and three different plant-based ass...

  3. Laboratory toxicity studies demonstrate no adverse effects of Cry1Ab and Cry3Bb1 to larvae of Adalia bipunctata (Coleoptera: Coccinellidae): the importance of study design.

    PubMed

    Alvarez-Alfageme, Fernando; Bigler, Franz; Romeis, Jörg

    2011-06-01

    Scientific studies are frequently used to support policy decisions related to transgenic crops. Schmidt et al., Arch Environ Contam Toxicol 56:221-228 (2009) recently reported that Cry1Ab and Cry3Bb were toxic to larvae of Adalia bipunctata in direct feeding studies. This study was quoted, among others, to justify the ban of Bt maize (MON 810) in Germany. The study has subsequently been criticized because of methodological shortcomings that make it questionable whether the observed effects were due to direct toxicity of the two Cry proteins. We therefore conducted tritrophic studies assessing whether an effect of the two proteins on A. bipunctata could be detected under more realistic routes of exposure. Spider mites that had fed on Bt maize (events MON810 and MON88017) were used as carriers to expose young A. bipunctata larvae to high doses of biologically active Cry1Ab and Cry3Bb1. Ingestion of the two Cry proteins by A. bipunctata did not affect larval mortality, weight, or development time. These results were confirmed in a subsequent experiment in which A. bipunctata were directly fed with a sucrose solution containing dissolved purified proteins at concentrations approximately 10 times higher than measured in Bt maize-fed spider mites. Hence, our study does not provide any evidence that larvae of A. bipunctata are sensitive to Cry1Ab and Cry3Bb1 or that Bt maize expressing these proteins would adversely affect this predator. The results suggest that the apparent harmful effects of Cry1Ab and Cry3Bb1 reported by Schmidt et al., Arch Environ Contam Toxicol 56:221-228 (2009) were artifacts of poor study design and procedures. It is thus important that decision-makers evaluate the quality of individual scientific studies and do not view all as equally rigorous and relevant.

  4. 4-1BB and CD28 Signaling Plays a Synergistic Role in Redirecting Umbilical Cord Blood T Cells Against B-Cell Malignancies

    PubMed Central

    Tammana, Syam; Huang, Xin; Wong, Marianna; Milone, Michael C.; Ma, Linan; Levine, Bruce L.; June, Carl H.; Wagner, John E.; Blazar, Bruce R.

    2010-01-01

    Abstract Umbilical cord blood (UCB) T cells can be redirected to kill leukemia and lymphoma cells by engineering with a single-chain chimeric antigen receptor (CAR) and thus may have general applications in adoptive cell therapy. However, the role of costimulatory molecules in UCB T-cell activation and effector functions in context with CAR remains elusive. To investigate the effect of costimulatory molecules (4-1BB and CD28) on UCB T cells, we transduced UCB T cells with lentiviral vectors expressing Green Fluorescent Protein (GFP) and CAR for CD19 containing an intracellular domain of the CD3ζ chain and either a 4-1BB (UCB-19BBζ) or a CD28 intracellular domain (UCB-1928ζ), both (UCB-1928BBζ), or neither (UCB-19ζ). We found that UCB-19BBζ and UCB-28BBζ T cells exhibited more cytotoxicity to CD19+ leukemia and lymphoma cell lines than UCB-19ζ and UCB-1928ζ, although differences in secretion of interleukin-2 and interferon-γ by these T cells were not evident. In vivo adoptive transfer of these T cells into intraperitoneal tumor-bearing mice demonstrated that UCB-19BBζ and UCB-1928BBζ T cells mounted the most potent antitumor response. The mice adoptively transferred with UCB-1928BBζ cells survived longer than the mice with UCB-19BBζ. Moreover, UCB-1928BBζ T cells mounted a more robust antitumor response than UCB-19BBζ in a systemic tumor model. Our data suggest a synergistic role of 4-1BB and CD28 costimulation in engineering antileukemia UCB effector cells and implicate a design for redirected UCB T-cell therapy for refractory leukemia. PMID:19719389

  5. Platelet-derived growth factor BB and DD and angiopoietin1 are altered in follicular fluid from polycystic ovary syndrome patients.

    PubMed

    Scotti, Leopoldina; Parborell, Fernanda; Irusta, Griselda; De Zuñiga, Ignacio; Bisioli, Claudio; Pettorossi, Hernan; Tesone, Marta; Abramovich, Dalhia

    2014-08-01

    Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age, and is characterized by abnormalities in ovarian angiogenesis, among other features. Consistent with this association, follicular fluid (FF) concentration and ovarian expression of vascular endothelial growth factor (VEGF) are increased in PCOS patients. In this study, we examined the protein levels of platelet-derived growth factor (PDGF) BB and DD (PDGFBB and PDGFDD), angiopoietin 1 and 2 (ANGPT1 and ANGPT2), and their soluble receptor sTIE2 in FF from PCOS and control patients undergoing assisted reproductive techniques. We also analyzed the effect of FF from PCOS and control patients on tight and adherens junction protein expression in an endothelial cell line. PDGFBB and PDGFDD were significantly lower whereas ANGPT1 concentration was significantly higher in FF from PCOS patients than from control patients. No changes were found in the concentration of ANGPT2 or sTIE2. Expression of claudin-5 was significantly increased in endothelial cells incubated for 24 hr in the presence of FF from PCOS versus from control patients, while vascular-endothelial cadherin, β-catenin, and zonula occludens 1 expression were unchanged. The changes observed in the levels of PDGF isoforms and ANGPT1 may prevent VEGF-induced vascular permeability in the PCOS ovary by regulating endothelial-cell-junction protein levels. Restoring the levels of angiogenic factors may provide new insights into PCOS treatment and the prevention of ovarian hyperstimulation syndrome in affected women. © 2014 Wiley Periodicals, Inc.

  6. Probiotics [LGG-BB12 or RC14-GR1] versus placebo as prophylaxis for urinary tract infection in persons with spinal cord injury [ProSCIUTTU]: a study protocol for a randomised controlled trial.

    PubMed

    Lee, Bonsan Bonne; Toh, Swee-Ling; Ryan, Suzanne; Simpson, Judy M; Clezy, Kate; Bossa, Laetitia; Rice, Scott A; Marial, Obaydullah; Weber, Gerard; Kaur, Jasbeer; Boswell-Ruys, Claire; Goodall, Stephen; Middleton, James; Tudehope, Mark; Kotsiou, George

    2016-04-16

    Urinary tract infections [UTIs] are very common in people with Spinal Cord Injury [SCI]. UTIs are increasingly difficult and expensive to treat as the organisms that cause them become more antibiotic resistant. Among the SCI population, there is a high rate of multi-resistant organism [MRO] colonisation. Non-antibiotic prevention strategies are needed to prevent UTI without increasing resistance. Probiotics have been reported to be beneficial in preventing UTIs in post-menopausal women in several in vivo and in vitro studies. The main aim of this study is to determine whether probiotic therapy with combinations of Lactobacillus reuteri RC-14 + Lactobacillus rhamnosus GR-1 [RC14-GR1] and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 [LGG-BB12] are effective in preventing UTI in people with SCI compared to placebo. This is a multi-site randomised double-blind double-dummy placebo-controlled factorial design study conducted in New South Wales, Australia. All participants have a neurogenic bladder as a result of spinal injury. Recruitment started in April 2011. Participants are randomised to one of four arms, designed for factorial analysis of LGG-BB12 and/or RC14-GR1 v Placebo. This involves 24 weeks of daily oral treatment with RC14-GR1 + LGG-BB12, RC14-GR1 + placebo, LGG-BB12 + placebo or two placebo capsules. Randomisation is stratified by bladder management type and inpatient status. Participants are assessed at baseline, three months and six months for Short Form Health Survey [SF-36], microbiological swabs of rectum, nose and groin; urine culture and urinary catheters for subjects with indwelling catheters. A bowel questionnaire is administered at baseline and three months to assess effect of probiotics on bowel function. The primary outcome is time from randomisation to occurrence of symptomatic UTI. The secondary outcomes are change of MRO status and bowel function, quality of life and cost-effectiveness of probiotics in persons

  7. Influence of calcium salts and bovine thrombin on growth factor release from equine platelet-rich gel supernatants.

    PubMed

    Giraldo, Carlos E; Álvarez, María E; Carmona, Jorge U

    2017-01-16

    To compare five activation methods in equine platelet-rich plasma (PRP) by determination of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) concentrations in platelet-rich gel (PRG) supernatants. Platelet-rich plasma from 20 horses was activated by calcium chloride (CC), calcium gluconate (CG), bovine thrombin (BT), and their combinations, BTCC and BTCG. Both growth factor concentrations in PRG supernatants were measured by ELISA and compared with plasma and platelet lysates (PL) over time. Growth factor concentrations were significantly lower in plasma and higher for all PRG supernatants. Platelet lysates contained a significantly lower concentration of PDGF-BB than PRG supernatants and a significantly higher concentration of TGF-β1 than PRG supernatants. Clots from PRP activated with sodium salts were more stable over time and had significant growth factor release, whereas CC produced gross salt deposition. Significant correlations were noticed for platelet with leukocyte concentrations in PRP (r s : 0.76), platelet counts in PRP with TGF-β1 concentrations in PRG supernatants (r s : 0.86), platelet counts in PRP with PDGF-BB concentrations in PRG supernatants (r s : 0.78), leukocyte counts in PRP with TGF-β1 concentrations in PRG supernatants (r s : 0.76), and PDGF-BB concentrations with activating substances (r s : 0.72). Calcium gluconate was the better substance to induce PRP activation. It induced growth factor release free from calcium precipitates in the clots. Use of BT alone or combined with calcium salts was not advantageous for growth factor release.

  8. On the optimality of individual entangling-probe attacks against BB84 quantum key distribution

    NASA Astrophysics Data System (ADS)

    Herbauts, I. M.; Bettelli, S.; Hã¼bel, H.; Peev, M.

    2008-02-01

    Some MIT researchers [Phys. Rev. A 75, 042327 (2007)] have recently claimed that their implementation of the Slutsky-Brandt attack [Phys. Rev. A 57, 2383 (1998); Phys. Rev. A 71, 042312 (2005)] to the BB84 quantum-key-distribution (QKD) protocol puts the security of this protocol “to the test” by simulating “the most powerful individual-photon attack” [Phys. Rev. A 73, 012315 (2006)]. A related unfortunate news feature by a scientific journal [G. Brumfiel, Quantum cryptography is hacked, News @ Nature (april 2007); Nature 447, 372 (2007)] has spurred some concern in the QKD community and among the general public by misinterpreting the implications of this work. The present article proves the existence of a stronger individual attack on QKD protocols with encrypted error correction, for which tight bounds are shown, and clarifies why the claims of the news feature incorrectly suggest a contradiction with the established “old-style” theory of BB84 individual attacks. The full implementation of a quantum cryptographic protocol includes a reconciliation and a privacy-amplification stage, whose choice alters in general both the maximum extractable secret and the optimal eavesdropping attack. The authors of [Phys. Rev. A 75, 042327 (2007)] are concerned only with the error-free part of the so-called sifted string, and do not consider faulty bits, which, in the version of their protocol, are discarded. When using the provably superior reconciliation approach of encrypted error correction (instead of error discard), the Slutsky-Brandt attack is no more optimal and does not “threaten” the security bound derived by Lütkenhaus [Phys. Rev. A 59, 3301 (1999)]. It is shown that the method of Slutsky and collaborators [Phys. Rev. A 57, 2383 (1998)] can be adapted to reconciliation with error correction, and that the optimal entangling probe can be explicitly found. Moreover, this attack fills Lütkenhaus bound, proving that it is tight (a fact which was not

  9. Dietary effects on insulin and nutrient metabolism in mesenteric lymph node cells, splenocytes, and pancreatic islets of BB rats.

    PubMed

    Scott, F W; Olivares, E; Sener, A; Malaisse, W J

    2000-09-01

    The present studies were performed to determine if a protective diet has different effects on the metabolic activity or function of islet cells, as well as the metabolic activity of mesenteric lymph node (MLN) cells and spleen cells, from BioBreeding (BB) rats. Diabetes-prone BB (BBdp) rats and control non-diabetes-prone BB (BBc) rats were fed for about 20 days either a mainly plant-based diabetogenic diet, NIH-07 (NIH), or a protective semipurified diet with hydrolyzed casein (HC) as the amino acid source. At 6 to 8 weeks of age, BBdp rats had high plasma D-glucose and low insulin concentrations, low insulin content, and low metabolic and secretory responses to D-glucose in isolated pancreatic islets. Islet metabolism, as measured by accumulation of 14C-acidic metabolites, amino acids, and the ratio of D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization was increased in control rats fed HC (P < .05); a similar trend in BBdp rats was not significant. Feeding the HC diet increased islet insulin content (P < .01) by 13% in BBdp and 23% in BBc rats; other metabolic and hormonal variables were unaffected. Compared with BBc rats, BBdp rats displayed higher rates of L-[U-14C]glutamine oxidation, D-[5-3H]glucose utilization, and D-[U-14C]glucose oxidation in MLN cells, but not in splenocytes. There was a dramatic decrease of L-[U-14C]glutamine oxidation in MLN cells from BBc and BBdp rats fed HC. Glycolysis was decreased in control rats. We conclude that the protection afforded by feeding BBdp rats a HC diet is associated with increased insulin in target beta cells and downregulation of metabolic activity in gut-associated MLN cells. Metabolic activity in splenocytes, cells representative of the systemic immune system, was less affected. These data suggest that diet-induced metabolic changes occur in the islets and nearby cells of the gut immune system in the period before classic insulitis. Changes in the islets were smaller in comparison to the dramatic

  10. Risk assessment of Soulatrolide and Mammea (A/BA+A/BB) coumarins from Calophyllum brasiliense by a toxicogenomic and toxicological approach.

    PubMed

    Gomez-Verjan, J C; Estrella-Parra, E; Vazquez-Martinez, E R; Gonzalez-Sanchez, I; Guerrero-Magos, G; Mendoza-Villanueva, D; Isus, L; Alfaro, A; Cerbón-Cervantes, M; Aloy, P; Reyes-Chilpa, R

    2016-05-01

    Calophyllum brasiliense (Calophyllaceae) is a tropical rain forest tree distributed in Central and South America. It is an important source of tetracyclic dipyrano coumarins (Soulatrolide) and Mammea type coumarins. Soulatrolide is a potent inhibitor of HIV-1 reverse transcriptase and displays activity against Mycobacterium tuberculosis. Meanwhile, Mammea A/BA and A/BB, pure or as a mixture, are highly active against several human leukemia cell lines, Trypanosoma cruzi and Leishmania amazonensis. Nevertheless, there are few studies evaluating their safety profile. In the present work we performed toxicogenomic and toxicological analysis for both type of compounds. Soulatrolide, and the Mammea A/BA + A/BB mixture (2.1) were slightly toxic accordingly to Lorke assay classification (DL50 > 3000 mg/kg). After a short-term administration (100 mg/kg/daily, orally, 1 week) liver toxicogenomic analysis revealed 46 up and 72 downregulated genes for Mammea coumarins, and 665 up and 1077 downregulated genes for Soulatrolide. Gene enrichment analysis identified transcripts involved in drug metabolism for both compounds. In addition, network analysis through protein-protein interactions, tissue evaluation by TUNEL assay, and histological examination revealed no tissue damage on liver, kidney and spleen after treatments. Our results indicate that both type of coumarins displayed a safety profile, supporting their use in further preclinical studies to determine its therapeutic potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. In vitro gastrointestinal resistance of Lactobacillus acidophilus La-5 and Bifidobacterium animalis Bb-12 in soy and/or milk-based synbiotic apple ice creams.

    PubMed

    Matias, Natalia Silva; Padilha, Marina; Bedani, Raquel; Saad, Susana Marta Isay

    2016-10-03

    The viability and resistance to simulated gastrointestinal (GI) conditions of Lactobacillus acidophilus La-5 and Bifidobacterium animalis Bb-12 in synbiotic ice creams, in which milk was replaced by soy extract and/or whey protein isolate (WPI) with inulin, were investigated. The ice creams were showed to be satisfactory vehicles for La-5 and Bb-12 (populations around 7.5logCFU/g), even after the whole storage period (84days/-18°C). In all formulations, the propidium monoazide qPCR (PMA-qPCR) analysis demonstrated that probiotics could resist the in vitro GI assay, with significant survival levels, achieving survival rates exceeding 50%. Additionally, scanning electron microscopy images evidenced cells with morphological differences, suggesting physiological changes in response to the induced stress during the in vitro assay. Although all formulations provided resistance to the probiotic strains under GI stress, the variation found in probiotic survival suggests that GI tolerance is indeed affected by the choice of the food matrix. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Baccalaureate and Beyond: A First Look at the Employment Experiences and Lives of College Graduates, 4 Years On (B&B:08/12). NCES 2014-141

    ERIC Educational Resources Information Center

    Cataldi, Emily Forrest; Siegel, Peter; Shepherd, Bryan; Cooney, Jennifer

    2014-01-01

    This report presents initial findings about the employment outcomes of bachelor's degree recipients approximately 4 years after they completed their 2007-08 degrees. These findings are based on data from the second follow-up of the Baccalaureate and Beyond Longitudinal Study (B&B:08/12), a nationally representative longitudinal sample survey…

  13. Fitness Costs Related To Selection for Resistance to the Cry3Bb1 Protein in a Genetically Diverse Population of Non-diapausing Western Corn Rootworm

    USDA-ARS?s Scientific Manuscript database

    The western corn rootworm (Diabrotica virgifera virgifera LeConte) is an important pest of maize in North America. Since approved for commercial use in 2003, the acreage planted to maize (Zea mays L.) expressing the Bt derived Cry3Bb1 protein has significantly increased each year in the United State...

  14. Non Target Effect of Cry1 Ab and Cry Ab x Cry3 Bb1 Bt Transgenic Maize on Orius Insidiosus (Hemiptera: Anthocoridae) Abundance

    USDA-ARS?s Scientific Manuscript database

    Non-target effects of Cry1Ab x CP4 EPSPS and Cry1Ab + Cry3Bb1 x CP4 EPSPS Bt transgenic new maize hybrids on insidious flower bugs [Orius insidiosus (Say)] was studied in Nebraska (Mead, C lay Center, and Concord) during 2007 and 2008. The Bt effect was compared to CP4 EPSPS maize (isoline), convent...

  15. Existence and stability, and discrete BB and rank conditions, for general mixed-hybrid finite elements in elasticity

    NASA Technical Reports Server (NTRS)

    Xue, W.-M.; Atluri, S. N.

    1985-01-01

    In this paper, all possible forms of mixed-hybrid finite element methods that are based on multi-field variational principles are examined as to the conditions for existence, stability, and uniqueness of their solutions. The reasons as to why certain 'simplified hybrid-mixed methods' in general, and the so-called 'simplified hybrid-displacement method' in particular (based on the so-called simplified variational principles), become unstable, are discussed. A comprehensive discussion of the 'discrete' BB-conditions, and the rank conditions, of the matrices arising in mixed-hybrid methods, is given. Some recent studies aimed at the assurance of such rank conditions, and the related problem of the avoidance of spurious kinematic modes, are presented.

  16. Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12® and Lactobacillus paracasei ssp. paracasei, L. casei 431® in an influenza vaccination model: a randomised, double-blind, placebo-controlled study.

    PubMed

    Rizzardini, Giuliano; Eskesen, Dorte; Calder, Philip C; Capetti, Amedeo; Jespersen, Lillian; Clerici, Mario

    2012-03-01

    The present study investigated the ability of Bifidobacterium animalis ssp. lactis (BB-12®) and Lactobacillus paracasei ssp. paracasei (L. casei 431®) to modulate the immune system using a vaccination model in healthy subjects. A randomised, double-blind, placebo-controlled, parallel-group study was conducted in 211 subjects (56 % females, mean age 33·2 (sd 13·1) years). Subjects consumed a minimum of 10⁹ colony-forming units of BB-12® (capsule) or L. casei 431® (dairy drink) or a matching placebo once daily for 6 weeks. After 2 weeks, a seasonal influenza vaccination was given. Plasma and saliva samples were collected at baseline and after 6 weeks for the analysis of antibodies, cytokines and innate immune parameters. Changes from baseline in vaccine-specific plasma IgG, IgG1 and IgG3 were significantly greater in both probiotic groups v. the corresponding placebo group (L. casei 431®, P = 0·01 for IgG; P < 0·001 for remaining comparisons). The number of subjects obtaining a substantial increase in specific IgG (defined as ≥ 2-fold above baseline) was significantly greater in both probiotic groups v. placebo (BB-12®, P < 0·001 for IgG, IgG1 and IgG3; L. casei 431®, P < 0·001 for IgG1 and IgG3). Significantly greater mean fold increases for vaccine-specific secretory IgA in saliva were observed in both probiotic groups v. placebo (BB-12®, P = 0·017; L. casei 431®, P = 0·035). Similar results were observed for total antibody concentrations. No differences were found for plasma cytokines or innate immune parameters. Data herein show that supplementation with BB-12® or L. casei 431® may be an effective means to improve immune function by augmenting systemic and mucosal immune responses to challenge.

  17. The Use of Recombinant Human Platelet-Derived Growth Factor for Maxillary Sinus Augmentation.

    PubMed

    Kubota, Atsushi; Sarmiento, Hector; Alqahtani, Mohammed Saad; Llobell, Arturo; Fiorellini, Joseph P

    The maxillary sinus augmentation procedure has become a predictable treatment to regenerate bone for implant placement. The purpose of this study was to evaluate the effect of recombinant human platelet-derived growth factor BB (rhPDGF-BB) combined with a deproteinized cancellous bovine bone graft for sinus augmentation. The lateral window approach was used for maxillary sinuses with minimal residual bone. After a healing period of 4 months, dental implants were placed and then restored following a 2-month osseointegration period. The result demonstrated increased bone height and ISQ values and a 100% survival rate. This study indicates that the addition of rhPDGF-BB to deproteinized cancellous bovine bone accelerated the healing period in maxillary sinuses with minimal native bone.

  18. The TT, TB, EB and BB correlations in anisotropic inflation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Xingang; Emami, Razieh; Firouzjahi, Hassan

    2014-08-01

    The ongoing and future experiments will measure the B-mode from different sky coverage and frequency bands, with the potential to reveal non-trivial features in polarization map. In this work we study the TT, TB, EB and BB correlations associated with the B-mode polarization of CMB map in models of charged anisotropic inflation. The model contains a chaotic-type large field complex inflaton which is charged under the U(1) gauge field. We calculate the statistical anisotropies generated in the power spectra of the curvature perturbation, the tensor perturbation and their cross-correlation. It is shown that the asymmetry in tensor power spectrum ismore » a very sensitive probe of the gauge coupling. While the level of statistical anisotropy in temperature power spectrum can be small and satisfy the observational bounds, the interactions from the gauge coupling can induce large directional dependence in tensor modes. This will leave interesting anisotropic fingerprints in various correlations involving the B-mode polarization such as the TB cross-correlation which may be detected in upcoming Planck polarization data. In addition, the TT correlation receives an anisotropic contribution from the tensor sector which naturally decays after l ∼> 100. We expect that the mechanism of using tensor sector to induce asymmetry at low l to be generic which can also be applied to address other low l CMB anomalies.« less

  19. Deprotonation of a Seemingly Hydridic Diborane(6) To Build a B-B Bond.

    PubMed

    Kaese, Thomas; Budy, Hendrik; Bolte, Michael; Lerner, Hans-Wolfram; Wagner, Matthias

    2017-06-19

    Deprotonation of the doubly arylene-bridged diborane(6) derivative 1H 2 with (Me 3 Si) 3 CLi or (Me 3 Si) 2 NK gives the B-B σ-bonded species M[1H] in essentially quantitative yields (THF, room temperature; M=Li, K, arylene=4,4'-di-tert-butyl-2,2'-biphenylylene). With nBuLi as the base, the yield of Li[1H] drops to 20 % and the 1,1-bis(9-borafluorenyl)butane Li[2H] is formed as a side product (30 %). In addition to the 1,1-butanediyl fragment, the two boron atoms of Li[2H] are linked by a μ-H bridge. In the closely related molecule Li[3H], the corresponding μ-H atom can be abstracted with (Me 3 Si) 3 CLi to afford the B-B-bonded conjugated base Li 2 [3] (THF, 150 °C; 15 %). Li[1H] and Li[2H] were characterized by NMR spectroscopy and X-ray crystallography. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Effect of Lactobacillus rhamnosus LGG® and Bifidobacterium animalis ssp. lactis BB-12® on health-related quality of life in college students affected by upper respiratory infections.

    PubMed

    Smith, Tracey J; Rigassio-Radler, Diane; Denmark, Robert; Haley, Timothy; Touger-Decker, Riva

    2013-06-01

    College students are susceptible to upper respiratory infections (URI) due to inadequate sleep, stress and close living quarters. Certain probiotic strains modulate immune function and may improve health-related quality of life (HRQL) during URI. The present study recruited apparently healthy college students and assessed the effect of probiotics on HRQL outcomes (i.e. self-reported duration, symptom severity and functional impairment of URI) in those who developed URI. Missed school and work days due to URI were also considered. Subjects (n 231) were apparently healthy college students living on campus in residence halls at the Framingham State University (Framingham, MA, USA), and were randomised to receive placebo (n 117) or probiotic-containing powder (daily dose of minimum 1 billion colony-forming units of each Lactobacillus rhamnosus LGG® (LGG®) and Bifidobacterium animalis ssp. lactis BB-12® (BB-12®); n 114) for 12 weeks. Subjects completed The Wisconsin Upper Respiratory Symptom Survey-21 to assess HRQL during URI. The final analyses included 198 subjects (placebo, n 97 and probiotics, n 101). The median duration of URI was significantly shorter by 2 d and median severity score was significantly lower by 34% with probiotics v. placebo (P,0·001), indicating a higher HRQL during URI. Number of missed work days was not different between groups (P=0·429); however, the probiotics group missed significantly fewer school days (mean difference = 0·2 d) compared to the placebo group (P=0·002). LGG® and BB-12® may be beneficial among college students with URI for mitigating decrements in HRQL. More research is warranted regarding mechanisms of action associated with these findings and the cost-benefit of prophylactic supplementation.

  1. Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135.

    PubMed

    De Luca, Maria Antonietta; Castelli, M Paola; Loi, Barbara; Porcu, Alessandra; Martorelli, Mariella; Miliano, Cristina; Kellett, Kathryn; Davidson, Colin; Stair, Jacqueline L; Schifano, Fabrizio; Di Chiara, Gaetano

    2016-06-01

    In order to investigate the in vivo dopamine (DA) stimulant properties of selected 3rd generation Spice/K2 cannabinoids, BB-22, 5F-PB-22, 5F-AKB-48 and STS-135, their in vitro affinity and agonist potency at native rat and mice CB1 receptors was studied. The compounds bind with high affinity to CB1 receptors in rat cerebral cortex homogenates and stimulate CB1-induced [(35)S]GTPγS binding with high potency and efficacy. BB-22 and 5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM), and a potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018 (EC50, 20.2 nM; Emax, 163%). 5F-AKB-48 and STS-135 had higher Ki for CB1 binding, higher EC50 and lower Emax as CB1 agonists than BB-22 and 5F-PB-22 but still comparatively more favourable than JWH-018. The agonist properties of all the compounds were abolished or drastically reduced by the CB1 antagonist/inverse agonist AM251 (0.1 μM). No activation of G-protein was observed in CB1-KO mice. BB-22 (0.003-0.01 mg/kg i.v.) increased dialysate DA in the accumbens shell but not in the core or in the medial prefrontal cortex, with a bell shaped dose-response curve and an effect at 0.01 mg/kg and a biphasic time-course. Systemic AM251 (1.0 mg/kg i.p.) completely prevented the stimulant effect of BB-22 on dialysate DA in the NAc shell. All the other compounds increased dialysate DA in the NAc shell at doses consistent with their in vitro affinity for CB1 receptors (5F-PB-22, 0.01 mg/kg; 5F-AKB-48, 0.1 mg/kg; STS-135, 0.15 mg/kg i.v.). 3rd generation cannabinoids can be even more potent and super-high CB1 receptor agonists compared to JWH-018. Future research will try to establish if these properties can explain the high toxicity and lethality associated with these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Minimally invasive treatment of maxillary anterior gingival recession defects by vestibular incision subperiosteal tunnel access and platelet-derived growth factor BB.

    PubMed

    Zadeh, Homayoun H

    2011-01-01

    An array of therapeutic options are available for treatment of gingival recession defects, though many of these are better suited for treatment of isolated defects. Some of the limitations of current techniques include the need for harvesting of autogenous donor tissues and their associated morbidity, as well as scar formation at the recipient site resulting from surface incisions. Moreover, muscle pull during healing often leads to incomplete root coverage or relapse of the recession. The current case reports introduce a novel, minimally invasive approach applicable for both isolated recession defects as well as multiple contiguous defects in the maxillary anterior region. Access to the surgical site is obtained by means of an approach referred to as vestibular incision subperiosteal tunnel access (VISTA). This entails making an access incision in the maxillary anterior frenum, followed by elevation of a subperiosteal tunnel. VISTA allows for both access as well as an opportunity to coronally reposition the gingival margins of all involved teeth. In this approach, recombinant human platelet-derived growth factor BB saturated onto a matrix of beta-tricalcium phosphate is introduced using VISTA over root dehiscences to enhance periodontal healing. A novel method of stabilization of the gingival margins is also introduced, referred to as coronally anchored suturing, designed to maintain the coronal positioning during healing. The current report describes the technique and two clinical case documentations for treatment of Miller Class I and II defects, demonstrating stable, long-term outcomes. Although VISTA has been applied in other regions, its application is most advantageous in the esthetic zone.

  3. Whole Blood Profiling of Bacillus Calmette–Guérin-Induced Trained Innate Immunity in Infants Identifies Epidermal Growth Factor, IL-6, Platelet-Derived Growth Factor-AB/BB, and Natural Killer Cell Activation

    PubMed Central

    Smith, Steven G.; Kleinnijenhuis, Johanneke; Netea, Mihai G.; Dockrell, Hazel M.

    2017-01-01

    Vaccination of infants with bacillus Calmette–Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli. Our aim was to examine an extensive panel of secreted immune biomarkers to characterize the profile of trained innate immunity in infants. Stimulation of whole blood for 48 h was performed 4 months after BCG vaccination, or in control unvaccinated infants. Stimulants were lipopolysaccharide; Pam3Cys (P3C); heat-killed Candida albicans, Staphylococcus aureus, Escherichia coli, and a lysate of Mycobacterium tuberculosis. Culture supernatants were tested for secreted cytokines and chemokines by 42-plex bead array and monocytes and natural killer (NK) cells assessed for expression of activation markers by flow cytometry. BCG-vaccinated infants displayed increases in 11 cytokines and chemokines in response to different non-specific innate immunity stimuli: epidermal growth factor (EGF); eotaxin; IL-6; IL-7; IL-8; IL-10; IL-12p40; monocyte chemotactic protein-3; macrophage inflammatory protein-1α; soluble CD40 ligand and platelet-derived growth factor (PDGF)-AB/BB. Although each stimulant induced a distinct response profile, three analytes, EGF, IL-6, and PDGF-AB/BB, were commonly higher after stimulation with Pam3Cys, C. albicans, and S. aureus. Conversely, certain cytokines such as interferon gamma-inducible protein-10, IL-2, IL-13, IL-17, GM-CSF, and GRO were suppressed in BCG-vaccinated infants, while no increases in TNFα or IL-1β production

  4. Double-parton scattering effects in D0B+ and B+B+ meson-meson pair production in proton-proton collisions at the LHC

    NASA Astrophysics Data System (ADS)

    Maciuła, Rafał; Szczurek, Antoni

    2018-05-01

    We extend our previous studies of double-parton scattering (DPS) to simultaneous production of c c ¯ and b b ¯ and production of two pairs of b b ¯. The calculation is performed within a factorized ansatz. Each parton scattering is calculated within the kT-factorization approach. The hadronization is done with the help of fragmentation functions. Production of D mesons in our framework was tested in our previous works. Here, we present our predictions for B mesons. A good agreement is achieved with the LHCb data. We present our results for c c ¯b b ¯ and b b ¯b b ¯ final states. For completeness, we compare results for double- and single-parton scattering (SPS). As for the c c ¯c c ¯ final state, the DPS dominates over the SPS, especially for small transverse momenta. We present several distributions and integrated cross sections with realistic cuts for simultaneous production of D0B+ and B+B+, suggesting future experimental studies at the LHC.

  5. Anomalous D-Log E curve with high contrast developer Kodak D8 on ultra fine grain emulsion BB640.

    PubMed

    Ulibarrena, M; Mendez, M; Blaya, S; Fimia, A

    2001-12-03

    D-Log E curves, also known as H-D curves, are used since the XIX century as a tool for describing the characteristics of silver halide emulsions. This curve has a very standard shape, with a linear region, a toe, a shoulder and a solarization region. In this work we present a distortion of the usual curve due to the action of a high contrast developer, Kodak D8, on an ultra fine grain emulsion, BB640\\cite{ov04}. The solarization effect is replaced by a linear zone where developed densities increase with increasing exposures, until all silver halide present in the emulsion is reduced by developer D8 to metallic silver. Densities higher than 11 have been obtained.

  6. Efficacy of topical recombinant human platelet-derived growth factor for treatment of diabetic lower-extremity ulcers: Systematic review and meta-analysis.

    PubMed

    Zhao, Xiao-hong; Gu, Hai-feng; Xu, Zhe-rong; Zhang, Qin; Lv, Xue-ying; Zheng, Xiao-jun; Yang, Yun-mei

    2014-10-01

    Recombinant human platelet-derived growth factor (rhPDGF) is used topically in the treatment of diabetic lower-extremity ulcers. There have been few meta-analyses of the efficacy of rhPDGF in this treatment context. The aim of this study was to perform an updated systematic review and meta-analysis to assess the clinical efficacy of rhPDGF in the treatment of diabetic lower-extremity ulcers. We searched the MEDLINE, Cochrane Library, EMBASE and Web of Knowledge databases up to April 30, 2014. Studies were identified and selected, and data were extracted by two independent reviewers. The primary efficacy outcome was complete healing rate. Adverse events were also assessed. The studies were evaluated for quality and publication bias. A total of 6 randomized controlled trials including 992 patients were selected from 173 identified studies. The studies compared rhPDGF treatment in the context of standard of care (SOC) to placebo or SOC alone. In the absence of study heterogeneity, a fixed-effects model was performed, and the combined odds ratio (OR) indicated a significantly greater complete healing rate in patients treated with rhPDGF compared to placebo or SOC alone. The ORs ranged from 0.58 to 2.77, with a combined OR of 1.53 (95% CI = 1.14 to 2.04, p = 0.004). A sensitivity analysis (leave-one-out method) indicated good study reliability, and a funnel plot with Egger test showed no publication bias. These results indicate that rhPDGF is efficacious in the treatment of diabetic lower-extremity ulcers. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Characterisation of the Poly-(Vinylpyrrolidone)-Poly-(Vinylacetate-Co-Crotonic Acid) (PVP:PVAc-CA) Interpolymer Complex Matrix Microparticles Encapsulating a Bifidobacterium lactis Bb12 Probiotic Strain.

    PubMed

    Mamvura, C I; Moolman, F S; Kalombo, L; Hall, A N; Thantsha, M S

    2011-06-01

    The method of producing poly-(vinylpyrrolidone)-poly-(vinylacetate-co-crotonic acid) (PVP:PVAc-CA) interpolymer complex matrix microparticles in supercritical carbon dioxide (scCO2), encapsulating bacteria, has recently been developed. This study was aimed at probing the external and internal structure of these microparticles, which can be used in food. The encapsulation efficiency and distribution of encapsulated Bifidobacterium lactis Bb12 within these microparticles were also investigated. Scanning electron microscopy (SEM) revealed irregular, mostly small, smooth microparticles with no visible bacterial cells on the surface. However, some of the microparticles appeared to have porous surfaces. The results of a Microtrac S3500 particle size analyzer showed that the PVP:PVAc-CA interpolymer complex matrix microparticles encapsulating B. lactis Bb12 had an average particle size of 166.1 μm (<350 μm designated standard size for microparticles). The D 10, D 50 and D 90 values for these microparticles were 48.16, 166.06 and 382.55 μm, respectively. Both SEM and confocal laser scanning microscopy showed a high density of bacterial cells within the microparticles. An average encapsulation efficiency of 96% was achieved. Consequently, the microparticles have the potential to be evenly distributed in foods, deliver adequate amounts of probiotics and produce minimal adverse effects on the texture and mouth feel of the foods into which they are incorporated.

  8. RCRA, superfund and EPCRA hotline training module. Introduction to: Air emission standards (40 cfr parts 264/265, subparts aa, bb, and cc) updated July 1996

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1996-07-01

    The module provides a regulatory overview of the RCRA air emission standards as they apply to hazardous waste facilities. It outlines the history of RCRA air emission standards as well as the air emission controls required by the standards. It explains the difference in the parts 264/265 and subparts AA, BB and CC, air emission standards. It summarizes the requirements of each of these subparts and identifies the types of units subject to these requirements as well as specific exemptions.

  9. Decreased catecholamine secretion from the adrenal medullae of chronically diabetic BB-Wistar rats

    NASA Technical Reports Server (NTRS)

    Wilke, R. A.; Riley, D. A.; Lelkes, P. I.; Hillard, C. J.

    1993-01-01

    Many humans with IDDM eventually lose the capacity to secrete epinephrine from their adrenal medullae. The mechanism for this pathological change is unknown. We hypothesized that this abnormality is attributable to neuropathic changes in the greater splanchnic nerves or in the chromaffin cells that they innervate. To study this hypothesis, we isolated rat adrenal glands, perfused them ex vivo, and measured the epinephrine content of the perfusate under various conditions of stimulation. We used transmural electrical stimulation (20-80 V, at 10 Hz) to induce epinephrine secretion indirectly by selectively activating residual splanchnic nerve terminals within the isolated glands. Under these conditions, epinephrine secretion was severely attenuated in glands from female BB-Wistar rats with diabetes of 4 mo duration compared with their age-matched, nondiabetic controls. These perfused diabetic adrenal medullae also demonstrated decreased catecholamine release in response to direct chromaffin cell depolarization with 20 mM K+, evidence that a functional alteration exists within the chromaffin cells themselves. Nonetheless, total catecholamine content of adrenal medullae from these diabetic rats was not significantly different from controls, indicating that the secretory defect was not simply attributable to a difference in the amount of catecholamines stored and available for release. Herein, we also provide histological evidence of degenerative changes within the cholinergic nerve terminals that innervate these glands.

  10. 1H, 13C, and 15N resonance assignments for the protein coded by gene locus BB0938 of Bordetella bronchiseptica

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rossi, Paolo; Ramelot, Theresa A.; Xiao, Rong

    2005-11-01

    The product of gene locus BB0938 from Bordetella bronchiseptica (Swiss-Prot ID: Q7WNU7-BORBR; NESG target ID: BoR11; Wunderlich et al., 2004; Pfam ID: PF03476) is a 128-residue protein of unknown function. This broadly conserved protein family is found in eubacteria and eukaryotes. Using triple resonance NMR techniques, we have determined 98% of backbone and 94% of side chain 1H, 13C, and 15N resonance assignments. The chemical shift and 3J(HN?Ha) scalar coupling data reveal a b topology with a seven-residue helical insert, ??????????. BMRB deposit with accession number 6693. Reference: Wunderlich et al. (2004) Proteins, 56, 181?187.

  11. Microtubule-actin crosslinking factor 1 (Macf1) domain function in Balbiani body dissociation and nuclear positioning.

    PubMed

    Escobar-Aguirre, Matias; Zhang, Hong; Jamieson-Lucy, Allison; Mullins, Mary C

    2017-09-01

    Animal-vegetal (AV) polarity of most vertebrate eggs is established during early oogenesis through the formation and disassembly of the Balbiani Body (Bb). The Bb is a structure conserved from insects to humans that appears as a large granule, similar to a mRNP granule composed of mRNA and proteins, that in addition contains mitochondria, ER and Golgi. The components of the Bb, which have amyloid-like properties, include germ cell and axis determinants of the embryo that are anchored to the vegetal cortex upon Bb disassembly. Our lab discovered in zebrafish the only gene known to function in Bb disassembly, microtubule-actin crosslinking factor 1a (macf1a). Macf1 is a conserved, giant multi-domain cytoskeletal linker protein that can interact with microtubules (MTs), actin filaments (AF), and intermediate filaments (IF). In macf1a mutant oocytes the Bb fails to dissociate, the nucleus is acentric, and AV polarity of the oocyte and egg fails to form. The cytoskeleton-dependent mechanism by which Macf1a regulates Bb mRNP granule dissociation was unknown. We found that disruption of AFs phenocopies the macf1a mutant phenotype, while MT disruption does not. We determined that cytokeratins (CK), a type of IF, are enriched in the Bb. We found that Macf1a localizes to the Bb, indicating a direct function in regulating its dissociation. We thus tested if Macf1a functions via its actin binding domain (ABD) and plectin repeat domain (PRD) to integrate cortical actin and Bb CK, respectively, to mediate Bb dissociation at the oocyte cortex. We developed a CRISPR/Cas9 approach to delete the exons encoding these domains from the macf1a endogenous locus, while maintaining the open reading frame. Our analysis shows that Macf1a functions via its ABD to mediate Bb granule dissociation and nuclear positioning, while the PRD is dispensable. We propose that Macf1a does not function via its canonical mechanism of linking two cytoskeletal systems together in dissociating the Bb. Instead

  12. Microtubule-actin crosslinking factor 1 (Macf1) domain function in Balbiani body dissociation and nuclear positioning

    PubMed Central

    Zhang, Hong; Jamieson-Lucy, Allison

    2017-01-01

    Animal-vegetal (AV) polarity of most vertebrate eggs is established during early oogenesis through the formation and disassembly of the Balbiani Body (Bb). The Bb is a structure conserved from insects to humans that appears as a large granule, similar to a mRNP granule composed of mRNA and proteins, that in addition contains mitochondria, ER and Golgi. The components of the Bb, which have amyloid-like properties, include germ cell and axis determinants of the embryo that are anchored to the vegetal cortex upon Bb disassembly. Our lab discovered in zebrafish the only gene known to function in Bb disassembly, microtubule-actin crosslinking factor 1a (macf1a). Macf1 is a conserved, giant multi-domain cytoskeletal linker protein that can interact with microtubules (MTs), actin filaments (AF), and intermediate filaments (IF). In macf1a mutant oocytes the Bb fails to dissociate, the nucleus is acentric, and AV polarity of the oocyte and egg fails to form. The cytoskeleton-dependent mechanism by which Macf1a regulates Bb mRNP granule dissociation was unknown. We found that disruption of AFs phenocopies the macf1a mutant phenotype, while MT disruption does not. We determined that cytokeratins (CK), a type of IF, are enriched in the Bb. We found that Macf1a localizes to the Bb, indicating a direct function in regulating its dissociation. We thus tested if Macf1a functions via its actin binding domain (ABD) and plectin repeat domain (PRD) to integrate cortical actin and Bb CK, respectively, to mediate Bb dissociation at the oocyte cortex. We developed a CRISPR/Cas9 approach to delete the exons encoding these domains from the macf1a endogenous locus, while maintaining the open reading frame. Our analysis shows that Macf1a functions via its ABD to mediate Bb granule dissociation and nuclear positioning, while the PRD is dispensable. We propose that Macf1a does not function via its canonical mechanism of linking two cytoskeletal systems together in dissociating the Bb. Instead

  13. Recent advances on aptamer-based biosensors to detection of platelet-derived growth factor.

    PubMed

    Razmi, Nasrin; Baradaran, Behzad; Hejazi, Maryam; Hasanzadeh, Mohammad; Mosafer, Jafar; Mokhtarzadeh, Ahad; de la Guardia, Miguel

    2018-08-15

    Platelet-derived growth factor (PDGF-BB), a significant serum cytokine, is an important protein biomarker in diagnosis and recognition of cancer, which straightly rolled in proceeding of various cell transformations, including tumor growth and its development. Fibrosis, atherosclerosis are certain appalling diseases, which PDGF-BB is near to them. Generally, the expression amount of PDGF-BB increases in human life-threatening tumors serving as an indicator for tumor angiogenesis. Thus, identification and quantification of PDGF-BB in biomedical fields are particularly important. Affinity chromatography, immunohistochemical methods and enzyme-linked immunosorbent assay (ELISA), conventional methods for PDGF-BB detection, requiring high-cost and complicated instrumentation, take too much time and offer deficient sensitivity and selectivity, which restrict their usage in real applications. Hence, it is essential to design and build enhanced systems and platforms for the recognition and quantification of protein biomarkers. In the past few years, biosensors especially aptasensors have been received noticeable attention for the detection of PDGF-BB owing to their high sensitivity, selectivity, accuracy, fast response, and low cost. Since the role and importance of developing aptasensors in cancer diagnosis is undeniable. In this review, optical and electrochemical aptasensors, which have been applied by many researchers for PDGF-BB cancer biomarker detection, have been mentioned and merits and demerits of them have been explained and compared. Efforts related to design and development of aptamer-based biosensors using nanoparticles for sensitive and selective detection of PDGF-BB have been reviewed considering: Aptamer importance as recognition elements, principal, application and the recent improvements and developments of aptamer based optical and electrochemical methods. In addition, commercial biosensors and future perspectives for rapid and on-site detection of PDGF-BB

  14. 4-1BB Costimulation Ameliorates T Cell Exhaustion Induced by Tonic Signaling of Chimeric Antigen Receptors

    PubMed Central

    Long, Adrienne H.; Haso, Waleed M.; Shern, Jack F.; Wanhainen, Kelsey M.; Murgai, Meera; Ingaramo, Maria; Smith, Jillian P.; Walker, Alec J.; Kohler, M. Eric; Venkateshwara, Vikas R.; Kaplan, Rosandra N.; Patterson, George H.; Fry, Terry J.; Orentas, Rimas J.; Mackall, Crystal L.

    2015-01-01

    Chimeric antigen receptors (CARs) targeting CD19 have mediated dramatic anti-tumor responses in hematologic malignancies, but tumor regression has rarely occurred using CARs targeting other antigens. It remains unknown whether the impressive effects of CD19 CARs relate to greater susceptibility of hematologic malignancies to CAR therapies, or superior functionality of the CD19 CAR itself. We discovered that tonic CAR CD3ζ phosphorylation, triggered by antigen-independent clustering of CAR scFvs, can induce early exhaustion of CAR T cells that limits anti-tumor efficacy. Such activation is present to varying degrees in all CARs studied, with the exception of the highly effective CD19 CAR. We further identify that CD28 costimulation augments, while 4-1BB costimulation ameliorates, exhaustion induced by persistent CAR signaling. Our results provide biological explanations for the dramatic anti-tumor effects of CD19 CARs and for the observations that CD19.BBz CAR T cells are more persistent than CD19.28z CAR T cells in clinical trials. PMID:25939063

  15. Relative binding and biochemical effects of heterodimeric and homodimeric isoforms of platelet-derived growth factor in osteoblast-enriched cultures from fetal rat bone

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Centrella, M.; McCarthy, T.L.; Kusmik, W.F.

    1991-06-01

    Platelet-derived growth factor (PDGF) exists as a homodimer or a heterodimer comprising either PDGF-A or PDGF-B subunits, and each isoform occurs in various tissues, including bone. Although the stimulatory effects of PDGF-BB have been studied in cultures of bone cells and intact bone fragments, the influence of other isoforms that may arise locally or systematically in vivo, has not been reported. Therefore recombinant human PDGF-BB, PDGF-AB, and PDGF-AA were evaluated in osteoblast-enriched cultures from fetal rat bone. Within 24 hours these factors produced a graded response in bone cell DNA and protein synthesis, with half-maximal effects at approximately 0.6, 2.1,more » and 4.8 nM PDGF-BB, PDGF-AB, and PDGF-AA, respectively. Increases in collagen and noncollagen protein synthesis were abrogated when DNA synthesis was blocked with hydroxyurea. Furthermore, each factor reduced alkaline phosphatase activity, PDGF-BB being the most inhibitory. Binding studies with 125I-PDGF-BB or 125I-PDGF-AA and each unlabeled PDGF isoform produced discrete ligand binding and displacement patterns: 125I-PDGF-BB binding was preferentially displaced by PDGF-BB (Ki approximately 0.7 nM), less by PDGF-AB (Ki approximately 2.3 nM) and poorly by PDGF-AA. In contrast, 125I-PDGF-AA binding was measurably reduced by PDGF-AA (Ki approximately 4.0 nM), but was more effectively displaced by PDGF-BB or PDGF-AB (each with Ki approximately 0.7 nM). These studies indicate that each PDGF isoform produces biochemical effects proportional to binding site occupancy and suggest that receptors that favor PDGF-B subunit binding preferentially mediate these results in osteoblast-enriched bone cell cultures.« less

  16. Phage-mediated horizontal gene transfer of both prophage and heterologous DNA by ϕBB-1, a bacteriophage of Borrelia burgdorferi.

    PubMed

    Eggers, Christian H; Gray, Carlie M; Preisig, Alexander M; Glenn, Danielle M; Pereira, Jessica; Ayers, Ryan W; Alshahrani, Mohammad; Acabbo, Christopher; Becker, Maria R; Bruenn, Kimberly N; Cheung, Timothy; Jendras, Taylor M; Shepley, Aron B; Moeller, John T

    2016-12-01

    Horizontal gene transfer (HGT) in Borrelia burgdorferi, the Lyme disease agent, is likely mediated by bacteriophage. Studies of the B. burgdorferi phage, ϕBB-1 and its role in HGT have been hindered by the lack of an assay for readily characterizing phage-mediated DNA movement (transduction). Here we describe an in vitro assay in which a clone of B. burgdorferi strain CA-11.2A encoding kanamycin resistance on a ϕBB-1 prophage is co-cultured with different clones encoding gentamicin resistance on a shuttle vector; transduction is monitored by enumerating colonies selected in the presence of both kanamycin and gentamicin. When both clones used in the assay were derived from CA-11.2A, the frequency of transduction was 1.23 × 10 -6 transductants per cell, and could be increased 5-fold by exposing the phage-producing strain to 5% ethanol. Transduction was also demonstrated between the CA-11.2A clone and clones of both high-passage B. burgdorferi strain B31 and low-passage, virulent B. burgdorferi strain 297, although with lower transduction frequencies. The transductant in the 297 background produced phage capable of transducing another B. burgdorferi clone: this is the first experimental demonstration of transduction from a clone of a virulent strain. In addition to prophage DNA, small Escherichia coli-derived shuttle vectors were also transduced between co-cultured B. burgdorferi strains, suggesting both a broad role for the phage in the HGT of heterologous DNA and a potential use of the phage as a molecular tool. These results enhance our understanding of phage-mediated transduction as a mechanism of HGT in the Lyme disease spirochetes. Furthermore, the reagents and techniques developed herein will facilitate future studies of phage-mediated HGT, especially within the tick vector and vertebrate host. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Evidence that platelet-derived growth factor may be a novel endogenous pyrogen in the central nervous system.

    PubMed

    Pelá, I R; Ferreira, M E; Melo, M C; Silva, C A; Coelho, M M; Valenzuela, C F

    2000-05-01

    Platelet-derived growth factor (PDGF) exerts neurotrophic and neuromodulatory actions in the mammalian central nervous system (CNS). Like the cytokines, PDGF primarily signals through tyrosine phosphorylation-dependent pathways that activate multiple intracellular molecules including Janus family kinases. We previously showed that microinjection of PDGF-BB into the lateral ventricle induced a febrile response in rats that was reduced by pretreatment with Win 41662, a potent inhibitor of PDGF receptors (Pelá IR, Ferreira MES, Melo MCC, Silva CAA, and Valenzuela CF. Ann NY Acad Sci 856: 289-293, 1998). In this study, we further characterized the role of PDGF-BB in the febrile response in rats. Microinjection of PDGF-BB into the third ventricle produced a dose-dependent increase in colonic temperature that peaked 3-4 h postinjection. Win 41662 attenuated fever induced by intraperitoneal injection of bacterial lipopolysaccharide, suggesting that endogenous PDGF participates in the febrile response to this exogenous pyrogen. Importantly, febrile responses induced by tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 were unchanged by Win 41662. Both indomethacin and dexamethasone blocked the PDGF-BB-induced increase in colonic temperature, and, therefore, we postulate that PDGF-BB may act via prostaglandin- and/or inducible enzyme-dependent pathways. Thus our findings suggest that PDGF-BB is an endogenous CNS mediator of the febrile response in rats.

  18. Effects of synbiotic fermented milk containing Lactobacillus acidophilus La-5 and Bifidobacterium animalis ssp. lactis BB-12 on the fecal microbiota of adults with irritable bowel syndrome: A randomized double-blind, placebo-controlled trial.

    PubMed

    Bogovič Matijašić, Bojana; Obermajer, Tanja; Lipoglavšek, Luka; Sernel, Tjaša; Locatelli, Igor; Kos, Mitja; Šmid, Alenka; Rogelj, Irena

    2016-07-01

    We conducted a randomized double-blind, placebo-controlled multicentric study to investigate the influence of a synbiotic fermented milk on the fecal microbiota composition of 30 adults with irritable bowel syndrome (IBS). The synbiotic product contained Lactobacillus acidophilus La-5, Bifidobacterium animalis ssp. lactis BB-12, Streptococcus thermophilus, and dietary fiber (90% inulin, 10% oligofructose), and a heat-treated fermented milk without probiotic bacteria or dietary fiber served as placebo. Stool samples were collected after a run-in period, a 4-wk consumption period, and a 1-wk follow-up period, and were subjected to real-time PCR and 16S rDNA profiling by next-generation sequencing. After 4wk of synbiotic (11 subjects) or placebo (19 subjects) consumption, a greater increase in DNA specific for L. acidophilus La-5 and Bifidobacterium animalis ssp. lactis was detected in the feces of the synbiotic group compared with the placebo group by quantitative real-time PCR. After 1wk of follow-up, the content of L. acidophilus La-5 and B. animalis ssp. lactis decreased to levels close to initial levels. No significant changes with time or differences between the groups were observed for Lactobacillus, Enterobacteriaceae, Bifidobacterium, or all bacteria. The presence of viable BB-12- and La-5-like bacteria in the feces resulting from the intake of synbiotic product was confirmed by random amplification of polymorphic DNA (RAPD)-PCR. At the end of consumption period, the feces of all subjects assigned to the synbiotic group contained viable bacteria with a BB-12-like RAPD profile, and after 1wk of follow-up, BB-12-like bacteria remained in the feces of 87.5% of these subjects. The presence of La-5-like colonies was observed less frequently (37.5 and 25% of subjects, respectively). Next-generation sequencing of 16S rDNA amplicons revealed that only the percentage of sequences assigned to Strep. thermophilus was temporarily increased in both groups, whereas the

  19. Antiproliferation effect of imatinib mesylate on MCF7, T-47D tumorigenic and MCF 10A nontumorigenic breast cell lines via PDGFR-β, PDGF-BB, c-Kit and SCF genes

    PubMed Central

    Kadivar, Ali; Kamalidehghan, Behnam; Akbari Javar, Hamid; Karimi, Benyamin; Sedghi, Reihaneh; Noordin, Mohamed Ibrahim

    2017-01-01

    Recent cancer molecular therapies are targeting main functional molecules to control applicable process of cancer cells. Attractive targets are established by receptor tyrosine kinases, such as platelet-derived growth factor receptors (PDGFRs) and c-Kit as mostly irregular signaling, which is due to either over expression or mutation that is associated with tumorigenesis and cell proliferation. Imatinib mesylate is a selective inhibitor of receptor tyrosine kinase, including PDGFR-β and c-Kit. In this research, we studied how imatinib mesylate would exert effect on MCF7 and T-47D breast cancer and MCF 10A epithelial cell lines, the gene and protein expression of PDGFR-β, c-Kit and their relevant ligands platelet-derived growth factor (PDGF)-BB and stem cell factor (SCF). The MTS assay was conducted in therapeutic relevant concentration of 2–10 µM for 96, 120 and 144 h treatment. In addition, apoptosis induction and cytostatic activity of imatinib mesylate were investigated with the terminal deoxynucleotidyl transferase dUTP nick end labeling TUNEL and cell cycle assays, respectively, in a time-dependent manner. Comparative real-time PCR and Western blot analysis were conducted to evaluate the expression and regulation of imatinib target genes and proteins. Our finding revealed that imatinib mesylate antiproliferation effect, apoptosis induction and cytostatic activity were significantly higher in breast cancer cell lines compared to MCF 10A. This effect might be due to the expression of PDGFR-β, PDGF-BB, c-Kit and SCF, which was expressed by all examined cell lines, except the T-47D cell line which was not expressed c-Kit. However, examined gene and proteins expressed more in cancer cell lines. Therefore, imatinib mesylate was more effective on them. It is concluded that imatinib has at least two potential targets in both examined breast cancer cell lines and can be a promising drug for targeted therapy to treat breast cancer. PMID:28260860

  20. New Method To Estimate Total Polyphenol Excretion: Comparison of Fast Blue BB versus Folin-Ciocalteu Performance in Urine.

    PubMed

    Hinojosa-Nogueira, Daniel; Muros, Joaquín; Rufián-Henares, José A; Pastoriza, Silvia

    2017-05-24

    Polyphenols are bioactive substances of vegetal origin with a significant impact on human health. The assessment of polyphenol intake and excretion is therefore important. The Folin-Ciocalteu (F-C) method is the reference assay to measure polyphenols in foods as well as their excretion in urine. However, many substances can influence the method, making it necessary to conduct a prior cleanup using solid-phase extraction (SPE) cartridges. In this paper, we demonstrate the use of the Fast Blue BB reagent (FBBB) as a new tool to measure the excretion of polyphenols in urine. Contrary to F-C, FBBB showed no interference in urine, negating the time-consuming and costly SPE cleanup. In addition, it showed excellent linearity (r 2 = 0.9997), with a recovery of 96.4% and a precision of 1.86-2.11%. The FBBB method was validated to measure the excretion of polyphenols in spot urine samples from Spanish children, showing a good correlation between polyphenol intake and excretion.

  1. PI3K is involved in PDGF-beta receptor upregulation post-PDGF-BB treatment in mouse HSC.

    PubMed

    Lechuga, Carmen G; Hernández-Nazara, Zamira H; Hernández, Elizabeth; Bustamante, Marcia; Desierto, Gregory; Cotty, Adam; Dharker, Nachiket; Choe, Moran; Rojkind, Marcos

    2006-12-01

    Increased expression of PDGF-beta receptors is a landmark of hepatic stellate cell activation and transdifferentiation into myofibroblasts. However, the molecular mechanisms that regulate the fate of the receptor are lacking. Recent studies suggested that N-acetylcysteine enhances the extracellular degradation of PDGF-beta receptor by cathepsin B, thus suggesting that the absence of PDGF-beta receptors in quiescent cells is due to an active process of elimination and not to a lack of expression. In this communication we investigated further molecular mechanisms involved in PDGF-beta receptor elimination and reappearance after incubation with PDGF-BB. We showed that in culture-activated hepatic stellate cells there is no internal protein pool of receptor, that the protein is maximally phosphorylated by 5 min and completely degraded after 1 h by a lysosomal-dependent mechanism. Inhibition of receptor autophosphorylation by tyrphostin 1296 prevented its degradation, but several proteasomal inhibitors had no effect. We also showed that receptor reappearance is time and dose dependent, being more delayed in cells treated with 50 ng/ml (48 h) compared with 10 ng/ml (24 h).

  2. The type Ia supernova SNLS-03D3bb from a super-Chandrasekhar-masswhite dwarf star

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Howell, D.Andrew; Sullivan, Mark; Nugent, Peter E.

    2006-02-01

    The acceleration of the expansion of the universe, and theneed for Dark Energy, were inferred from the observations of Type Iasupernovae (SNe Ia) 1;2. There is consensus that SNeIa are thermonuclearexplosions that destroy carbon-oxygen white dwarf stars that accretematter from a companion star3, although the nature of this companionremains uncertain. SNe Ia are thought to be reliable distance indicatorsbecause they have a standard amount of fuel and a uniform trigger theyare predicted to explode when the mass of the white dwarf nears theChandrasekhar mass 4 - 1.4 solar masses. Here we show that the highredshift supernova SNLS-03D3bb has an exceptionallymore » high luminosity andlow kinetic energy that both imply a super-Chandrasekhar mass progenitor.Super-Chandrasekhar mass SNeIa shouldpreferentially occur in a youngstellar population, so this may provide an explanation for the observedtrend that overluminous SNe Ia only occur in young environments5;6. Sincethis supernova does not obey the relations that allow them to becalibrated as standard candles, and since no counterparts have been foundat low redshift, future cosmology studies will have to considercontamination from such events.« less

  3. Platelet lysate from whole blood-derived pooled platelet concentrates and apheresis-derived platelet concentrates for the isolation and expansion of human bone marrow mesenchymal stromal cells: production process, content and identification of active components

    PubMed Central

    Fekete, Natalie; Gadelorge, Mélanie; Fürst, Daniel; Maurer, Caroline; Dausend, Julia; Fleury-Cappellesso, Sandrine; Mailänder, Volker; Lotfi, Ramin; Ignatius, Anita; Sensebé, Luc; Bourin, Philippe; Schrezenmeier, Hubert; Rojewski, Markus Thomas

    2012-01-01

    Background aims The clinical use of human mesenchymal stromal cells (MSC) requires ex vivo expansion in media containing supplements such as fetal bovine serum or, alternatively, human platelet lysate (PL). Methods Platelet concentrates were frozen, quarantine stored, thawed and sterile filtered to obtain PL. PL content and its effect on fibroblast-colony-forming unit (CFU-F) formation, MSC proliferation and large-scale expansion were studied. Results PL contained high levels of basic fibroblast growth factor (bFGF), soluble CD40L (sCD40L), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), platelet-derived growth factor AA (PDGF-AA), platelet-derived growth factor AB/BB (PDGF-AB/BB), chemokine (C-C) ligand 5 (CCL5; RANTES) transforming growth factor-β1 (TGF-β1) and chemokine (C-X-C) ligand 1/2/3 (GRO), with low batch-to-batch variability, and most were stable for up to 14 days. Inhibition of PDGF-BB and bFGF decreased MSC proliferation by about 20% and 50%, respectively. The strongest inhibition (about 75%) was observed with a combination of anti-bFGF + anti-PDGF-BB and anti-bFGF + anti-TGF-β1 + anti-PDGF-BB. Interestingly, various combinations of recombinant PDGF-BB, bFGF and TGF-β1 were not sufficient to promote cell proliferation. PL from whole blood-derived pooled platelet concentrates and apheresis platelet concentrates did not differ significantly in their growth-promoting activity on MSC. Conclusions PL enhances MSC proliferation and can be regarded as a safe tool for MSC expansion for clinical purposes. \\in particular, PDGF-BB and bFGF are essential components for the growth-promoting effect of PL, but are not sufficient for MSC proliferation. PMID:22296115

  4. Emission factors for open and domestic biomass burning for use in atmospheric models

    Treesearch

    S. K. Akagi; R. J. Yokelson; C. Wiedinmyer; M. J. Alvarado; J. S. Reid; T. Karl; J. D. Crounse; P. O. Wennberg

    2010-01-01

    Biomass burning (BB) is the second largest source of trace gases and the largest source of primary fine carbonaceous particles in the global troposphere. Many recent BB studies have provided new emission factor (EF) measurements. This is especially 5 true for non methane organic compounds (NMOC), which influence secondary organic aerosol (SOA) and ozone formation. New...

  5. Comparing the impact of personal and parental risk factors, and parental lifespan on all-cause mortality and cardiovascular disease: findings from the Midspan Family cohort study.

    PubMed

    Hart, Carole; McCartney, Gerry; Gruer, Laurence; Watt, Graham

    2015-10-01

    We aimed to identify which personal and parental factors best explained all-cause mortality and cardiovascular disease (CVD). In 1996, data were collected on 2338 adult offspring of the participants in the 1972-1976 Renfrew and Paisley prospective cohort study. Recorded risk factors were assigned to 5 groups: mid-life biological and behavioural (BB), mid-life socioeconomic, parental BB, early-life socioeconomic and parental lifespan. Participants were followed up for mortality and hospital admissions to the end of 2011. Cox proportional hazards models were used to analyse how well each group explained all-cause mortality or CVD. Akaike's Information Criterion (AIC), a measure of goodness-of-fit, identified the most important groups. For all-cause mortality (1997 participants with complete data, 111 deaths), decreases in AIC from the null model (adjusting for age and sex) to models including mid-life BB, mid-life socioeconomic, parental BB, early-life socioeconomic and parental lifespan were 55.8, 21.6, 10.3, 7.3 and 5.9, respectively. For the CVD models (1736 participants, 276 with CVD), decreases were 37.8, 3.7, 6.7, 17.3 and 0.4. Mid-life BB factors were the most important for both all-cause mortality and CVD; mid-life socioeconomic factors were important for all-cause mortality, and early-life socioeconomic factors were important for CVD. Parental lifespan was the weakest factor. As mid-life BB risk factors best explained all-cause mortality and CVD, continued action to reduce these is warranted. Targeting adverse socioeconomic factors in mid-life and early life may contribute to reducing all-cause mortality and CVD risk, respectively. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation.

    PubMed

    Akar, Banu; Jiang, Bin; Somo, Sami I; Appel, Alyssa A; Larson, Jeffery C; Tichauer, Kenneth M; Brey, Eric M

    2015-12-01

    Gradients of soluble factors play an important role in many biological processes, including blood vessel assembly. Gradients can be studied in detail in vitro, but methods that enable the study of spatially distributed soluble factors and multi-cellular processes in vivo are limited. Here, we report on a method for the generation of persistent in vivo gradients of growth factors in a three-dimensional (3D) biomaterial system. Fibrin loaded porous poly (ethylene glycol) (PEG) scaffolds were generated using a particulate leaching method. Platelet derived growth factor BB (PDGF-BB) was encapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres which were placed distal to the tissue-material interface. PLGA provides sustained release of PDGF-BB and its diffusion through the porous structure results in gradient formation. Gradients within the scaffold were confirmed in vivo using near-infrared fluorescence imaging and gradients were present for more than 3 weeks. The diffusion of PDGF-BB was modeled and verified with in vivo imaging findings. The depth of tissue invasion and density of blood vessels formed in response to the biomaterial increased with magnitude of the gradient. This biomaterial system allows for generation of sustained growth factor gradients for the study of tissue response to gradients in vivo. Published by Elsevier Ltd.

  7. A comprehensive proteomics and genomics analysis reveals novel transmembrane proteins in human platelets and mouse megakaryocytes including G6b-B, a novel ITIM protein

    PubMed Central

    Senis, Yotis A.; Tomlinson, Michael G.; García, Ángel; Dumon, Stephanie; Heath, Victoria L.; Herbert, John; Cobbold, Stephen P.; Spalton, Jennifer C.; Ayman, Sinem; Antrobus, Robin; Zitzmann, Nicole; Bicknell, Roy; Frampton, Jon; Authi, Kalwant; Martin, Ashley; Wakelam, Michael J.O.; Watson, Stephen P.

    2007-01-01

    Summary The platelet surface is poorly characterized due to the low abundance of many membrane proteins and the lack of specialist tools for their investigation. In this study we have identified novel human platelet and mouse megakaryocyte membrane proteins using specialist proteomic and genomic approaches. Three separate methods were used to enrich platelet surface proteins prior to identification by liquid chromatography and tandem mass spectrometry: lectin affinity chromatography; biotin/NeutrAvidin affinity chromatography; and free flow electrophoresis. Many known, abundant platelet surface transmembrane proteins and several novel proteins were identified using each receptor enrichment strategy. In total, two or more unique peptides were identified for 46, 68 and 22 surface membrane, intracellular membrane and membrane proteins of unknown sub-cellular localization, respectively. The majority of these were single transmembrane proteins. To complement the proteomic studies, we analysed the transcriptome of a highly purified preparation of mature primary mouse megakaryocytes using serial analysis of gene expression in view of the increasing importance of mutant mouse models in establishing protein function in platelets. This approach identified all of the major classes of platelet transmembrane receptors, including multi-transmembrane proteins. Strikingly, 17 of the 25 most megakaryocyte-specific genes (relative to 30 other SAGE libraries) were transmembrane proteins, illustrating the unique nature of the megakaryocyte/platelet surface. The list of novel plasma membrane proteins identified using proteomics includes the immunoglobulin superfamily member G6b, which undergoes extensive alternate splicing. Specific antibodies were used to demonstrate expression of the G6b-B isoform, which contains an immunoreceptor tyrosine-based inhibition motif. G6b-B undergoes tyrosine phosphorylation and association with the SH2-containing phosphatase, SHP-1, in stimulated

  8. Search for the standard model Higgs boson decaying to a bb pair in events with two oppositely charged leptons using the full CDF data set.

    PubMed

    Aaltonen, T; Álvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Appel, J A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Auerbach, B; Aurisano, A; Azfar, F; Badgett, W; Bae, T; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauce, M; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Binkley, M E; Bisello, D; Bizjak, I; Bland, K R; Blumenfeld, B; Bocci, A; Bodek, A; Bortoletto, D; Boudreau, J; Boveia, A; Brigliadori, L; Bromberg, C; Brucken, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Calamba, A; Calancha, C; Camarda, S; Campanelli, M; Campbell, M; Canelli, F; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chung, W H; Chung, Y S; Ciocci, M A; Clark, A; Clarke, C; Compostella, G; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Crescioli, F; Cuevas, J; Culbertson, R; Dagenhart, D; d'Ascenzo, N; Datta, M; de Barbaro, P; Dell'Orso, M; Demortier, L; Deninno, M; Devoto, F; d'Errico, M; Di Canto, A; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Dorigo, M; Dorigo, T; Ebina, K; Elagin, A; Eppig, A; Erbacher, R; Errede, S; Ershaidat, N; Eusebi, R; Farrington, S; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Funakoshi, Y; Furic, I; Gallinaro, M; Garcia, J E; Garfinkel, A F; Garosi, P; Gerberich, H; Gerchtein, E; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Ginsburg, C M; Giokaris, N; Giromini, P; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldin, D; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Grinstein, S; Grosso-Pilcher, C; Group, R C; Guimaraes da Costa, J; Hahn, S R; Halkiadakis, E; Hamaguchi, A; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harr, R F; Hatakeyama, K; Hays, C; Heck, M; Heinrich, J; Herndon, M; Hewamanage, S; Hocker, A; Hopkins, W; Horn, D; Hou, S; Hughes, R E; Hurwitz, M; Husemann, U; Hussain, N; Hussein, M; Huston, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeans, D T; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Junk, T R; Kamon, T; Karchin, P E; Kasmi, A; Kato, Y; Ketchum, W; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kim, Y J; Kimura, N; Kirby, M; Klimenko, S; Knoepfel, K; Kondo, K; Kong, D J; Konigsberg, J; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Kruse, M; Krutelyov, V; Kuhr, T; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; LeCompte, T; Lee, E; Lee, H S; Lee, J S; Lee, S W; Leo, S; Leone, S; Lewis, J D; Limosani, A; Lin, C-J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, H; Liu, Q; Liu, T; Lockwitz, S; Loginov, A; Lucchesi, D; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; Madrak, R; Maeshima, K; Maestro, P; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Martínez, M; Mastrandrea, P; Matera, K; Mattson, M E; Mazzacane, A; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Mesropian, C; Miao, T; Mietlicki, D; Mitra, A; Miyake, H; Moed, S; Moggi, N; Mondragon, M N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mukherjee, A; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakano, I; Napier, A; Nett, J; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Noh, S Y; Norniella, O; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Ortolan, L; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pilot, J; Pitts, K; Plager, C; Pondrom, L; Poprocki, S; Potamianos, K; Prokoshin, F; Pranko, A; Ptohos, F; Punzi, G; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Rescigno, M; Riddick, T; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Ruffini, F; Ruiz, A; Russ, J; Rusu, V; Safonov, A; Sakumoto, W K; Sakurai, Y; Santi, L; Sato, K; Saveliev, V; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Seidel, S; Seiya, Y; Semenov, A; Sforza, F; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shochet, M; Shreyber-Tecker, I; Simonenko, A; Sinervo, P; Sliwa, K; Smith, J R; Snider, F D; Soha, A; Sorin, V; Song, H; Squillacioti, P; Stancari, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Sudo, Y; Sukhanov, A; Suslov, I; Takemasa, K; Takeuchi, Y; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thome, J; Thompson, G A; Thomson, E; Tipton, P; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Ukegawa, F; Uozumi, S; Varganov, A; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vila, I; Vilar, R; Vizán, J; Vogel, M; Volpi, G; Wagner, P; Wagner, R L; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Wester, W C; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Wick, F; Williams, H H; Wilson, J S; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, H; Wright, T; Wu, X; Wu, Z; Yamamoto, K; Yamato, D; Yang, T; Yang, U K; Yang, Y C; Yao, W-M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanetti, A; Zeng, Y; Zhou, C; Zucchelli, S

    2012-09-14

    We present a search for the standard model Higgs boson produced in association with a Z boson in data collected with the CDF II detector at the Tevatron, corresponding to an integrated luminosity of 9.45  fb(-1). In events consistent with the decay of the Higgs boson to a bottom-quark pair and the Z boson to electron or muon pairs, we set 95% credibility level upper limits on the ZH production cross section times the H→bb branching ratio as a function of Higgs boson mass. At a Higgs boson mass of 125  GeV/c(2), we observe (expect) a limit of 7.1 (3.9) times the standard model value.

  9. Secure polarization-independent subcarrier quantum key distribution in optical fiber channel using BB84 protocol with a strong reference.

    PubMed

    Gleim, A V; Egorov, V I; Nazarov, Yu V; Smirnov, S V; Chistyakov, V V; Bannik, O I; Anisimov, A A; Kynev, S M; Ivanova, A E; Collins, R J; Kozlov, S A; Buller, G S

    2016-02-08

    A quantum key distribution system based on the subcarrier wave modulation method has been demonstrated which employs the BB84 protocol with a strong reference to generate secure bits at a rate of 16.5 kbit/s with an error of 0.5% over an optical channel of 10 dB loss, and 18 bits/s with an error of 0.75% over 25 dB of channel loss. To the best of our knowledge, these results represent the highest channel loss reported for secure quantum key distribution using the subcarrier wave approach. A passive unidirectional scheme has been used to compensate for the polarization dependence of the phase modulators in the receiver module, which resulted in a high visibility of 98.8%. The system is thus fully insensitive to polarization fluctuations and robust to environmental changes, making the approach promising for use in optical telecommunication networks. Further improvements in secure key rate and transmission distance can be achieved by implementing the decoy states protocol or by optimizing the mean photon number used in line with experimental parameters.

  10. Synergistic interaction of platelet derived growth factor (PDGF) with the surface of PLLA/Col/HA and PLLA/HA scaffolds produces rapid osteogenic differentiation.

    PubMed

    Raghavendran, Hanumantha Rao Balaji; Mohan, Saktiswaren; Genasan, Krishnamurithy; Murali, Malliga Raman; Naveen, Sangeetha Vasudevaraj; Talebian, Sepehr; McKean, Robert; Kamarul, Tunku

    2016-03-01

    Scaffolds with structural features similar to the extracellular matrix stimulate rapid osteogenic differentiation in favorable microenvironment and with growth factor supplementation. In this study, the osteogenic potential of electrospun poly-l-lactide/hydroxyapatite/collagen (PLLA/Col/HA, PLLA/HA and PLLA/Col) scaffolds were tested in vitro with the supplementation of platelet derived growth factor-BB (PDGF-BB). Cell attachment and topography, mineralization, extracellular matrix protein localization, and gene expression of the human mesenchymal stromal cells were compared between the fibrous scaffolds PLLA/Col/HA, PLLA/Col, and PLLA/HA. The levels of osteocalcin, calcium, and mineralization were significantly greater in the PLLA/Col/HA and PLLA/HA compared with PLLA/Col. High expression of fibronectin, intracellular adhesion molecule, cadherin, and collagen 1 (Col1) suggests that PLLA/Col/HA and PLLA/HA scaffolds had superior osteoinductivity than PLLA/Col. Additionally, osteopontin, osteocalcin, osterix, Runt-related transcription factor 2 (Runx2), and bone morphogenic protein (BMP2) expression were higher in PLLA/Col/HA and PLLA/HA compared with PLLA/Col. In comparison with PLLA/Col, the PLLA/Col/HA and PLLA/HA scaffolds presented a significant upregulation of the genes Runx2, Col 1, Integrin, osteonectin (ON), bone gamma-carboxyglutamic acid-containing protein (BGALP), osteopontin (OPN), and BMP2. The upregulation of these genes was further increased with PDGF-BB supplementation. These results show that PDGF-BB acts synergistically with PLLA/Col/HA and PLLA/HA to enhance the osteogenic differentiation potential. Therefore, this combination can be used for the rapid expansion of bone marrow stromal cells into bone-forming cells for tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. GLYCOGEN PHOSPHORYLASE ISOENZYME BB PLASMA CONCENTRATION IS ELEVATED IN PREGNANCY AND PRETERM PREECLAMPSIA

    PubMed Central

    Lee, JoonHo; Romero, Roberto; Dong, Zhong; Lee, Deug-Chan; Dong, Yi; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kim, Chong Jai

    2012-01-01

    Glycogen phosphorylase is a key enzyme in glycogenolysis. Released with myocardial ischemia, blood concentration of glycogen phosphorylase isoenzyme BB (GPBB) is a marker of acute coronary syndromes. Pregnancy imposes metabolic stress, and preeclampsia is associated with cardiac complications. However, plasma GPBB concentration during pregnancy is unknown. This study was conducted to determine maternal plasma GPBB concentration in normal pregnancy and in preeclampsia. Plasma samples from six groups (n=396) were studied: non-pregnant women and pregnant women with normal term delivery, term preeclampsia, term small-for-gestational-age neonates, preterm preeclampsia, and preterm small-for-gestational-age neonates. GPBB concentration was measured with a specific immunoassay. Placental tissues (n=45) obtained from pregnant women with preterm and term preeclampsia, spontaneous preterm delivery, and normal term cases were analyzed for potential GPBB expression by immunoblotting. Median plasma GPBB concentration was higher in pregnant women than in non-pregnant women (38.7 ng/ml versus 9.2 ng/mL, P<0.001), which remained significant after adjusting for age, race, and parity. Maternal plasma GPBB concentrations did not change throughout gestation. Preterm but not term preeclampsia cases had higher median plasma GPBB concentration than gestational-age-matched normal pregnancy cases (72.6 ng/ml versus 26.0 ng/ml, P=0.001). Small-for-gestational-age neonates did not affect plasma GPBB concentration. GPBB was detected in the placenta and was less abundant in preterm preeclampsia than in preterm delivery cases (P<0.01). There is physiologic elevation of plasma GPBB concentration during pregnancy; an increase in maternal plasma GPBB is a novel phenotype of preterm preeclampsia. It is strongly suggested that these changes are attributed to GPBB of placental origin. PMID:22215716

  12. According to Hepatitis C Virus (HCV) Infection Stage, Interleukin-7 Plus 4-1BB Triggering Alone or Combined with PD-1 Blockade Increases TRAF1low HCV-Specific CD8+ Cell Reactivity.

    PubMed

    Moreno-Cubero, Elia; Subirá, Dolores; Sanz-de-Villalobos, Eduardo; Parra-Cid, Trinidad; Madejón, Antonio; Miquel, Joaquín; Olveira, Antonio; González-Praetorius, Alejandro; García-Samaniego, Javier; Larrubia, Juan-Ramón

    2018-01-15

    Hepatitis C virus (HCV)-specific CD8 + T cells suffer a progressive exhaustion during persistent infection (PI) with HCV. This process could involve the positive immune checkpoint 4-1BB/4-1BBL through the loss of its signal transducer, TRAF1. To address this issue, peripheral HCV-specific CD8 + T cells (pentamer-positive [pentamer + ]/CD8 + T cells) from patients with PI and resolved infection (RI) after treatment were studied. The duration of HCV infection and the liver fibrosis progression rate inversely correlated with the likelihood of detection of peripheral pentamer + /CD8 + cells. In PI, pentamer + /CD8 + cells had impaired antigen-specific reactivity that worsened when these cells were not detectable ex vivo Short/midduration PI was characterized by detectable peripheral PD-1 + CD127 low TRAF1 low cells. After triggering of T cell receptors (TCR), the TRAF1 level positively correlated with the levels of CD127, Mcl-1, and CD107a expression and proliferation intensity but negatively with PD-1 expression, linking TRAF1 low to exhaustion. In vitro treatment with interleukin-7 (IL-7) upregulated TRAF1 expression, while treatment with transforming growth factor-β1 (TGF-β1) did the opposite, suggesting that the IL-7/TGF-β1 balance, besides TCR stimulation, could be involved in TRAF1 regulation. In fact, the serum TGF-β1 concentration was higher in patients with PI than in patients with RI, and it negatively correlated with TRAF1 expression. In line with IL-7 increasing the level of TRAF1 expression, IL-7 plus 4-1BBL treatment in vitro enhanced T cell reactivity in patients with short/midduration infection. However, in patients with long-lasting PI, anti-PD-L1, in addition to the combination of IL-7 and 4-1BBL, was necessary to reestablish T cell proliferation in individuals with slowly progressing liver fibrosis (slow fibrosers) but had no effect in rapid fibrosers. In conclusion, a peripheral hyporeactive TRAF1 low HCV-specific CD8 + T cell response

  13. Clinical assessment of bone quality of human extraction sockets after conversion with growth factors.

    PubMed

    Ntounis, Athanasios; Geurs, Nico; Vassilopoulos, Philip; Reddy, Michael

    2015-01-01

    The study was conducted to evaluate the effect of mineralized freeze-dried bone allograft (FDBA), alone or in combination with growth factors in extraction sockets, on subjective assessment of bone quality during implant placement. Forty-one patients whose treatment plan involved extraction of anterior or premolar teeth were randomized into four groups: Group 1, collagen plug (control); Group 2, FDBA/β-tricalcium phosphate (β-TCP)/collagen plug; Group 3, FDBA/β-TCP/platelet-rich plasma (PRP)/collagen plug; Group 4, FDBA/β-TCP/recombinant human platelet-derived growth factor BB (rhPDGF-BB)/collagen plug. After 8 weeks of healing, implants were placed. The clinicians assessed bone quality according to the Misch classification. A benchtop calibration exercise test was conducted to evaluate agreement and accuracy of operators in recognizing different bone qualities. Differences were analyzed using one-way analysis of variance (ANOVA) or chi-square tests for continuous and categorical data. Pairwise comparisons were tested using least squares means (LS means). Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders. P < .05 was considered statistically significant. A simple (not weighted) kappa statistic was used to assess the agreement between raters. To assess accuracy in identifying bone quality, a chi-square test was used to compare the percent correct for each rater. The benchtop calibration exercise test demonstrated agreement among clinicians (0.75 and 0.92 between raters 1 and 2 and raters 1 and 3, respectively). Raters were more likely to identify the correct bone quality (P > .05). Inclusion of bone grafting is associated with a shift from D4 quality to D3 quality bone. Inclusion of PRP in bone grafting eliminates the incidence of D4 bone, establishing D3 and D2 quality bone as prevalent (56% vs. 42%, respectively). Inclusion of rhPDGF-BB and β-TCP in combination with the bone grafting has the

  14. The type Ia supernova SNLS-03D3bb from a super-Chandrasekhar-mass white dwarf star.

    PubMed

    Howell, D Andrew; Sullivan, Mark; Nugent, Peter E; Ellis, Richard S; Conley, Alexander J; Le Borgne, Damien; Carlberg, Raymond G; Guy, Julien; Balam, David; Basa, Stephane; Fouchez, Dominique; Hook, Isobel M; Hsiao, Eric Y; Neill, James D; Pain, Reynald; Perrett, Kathryn M; Pritchet, Christopher J

    2006-09-21

    The accelerating expansion of the Universe, and the need for dark energy, were inferred from observations of type Ia supernovae. There is a consensus that type Ia supernovae are thermonuclear explosions that destroy carbon-oxygen white dwarf stars that have accreted matter from a companion star, although the nature of this companion remains uncertain. These supernovae are thought to be reliable distance indicators because they have a standard amount of fuel and a uniform trigger: they are predicted to explode when the mass of the white dwarf nears the Chandrasekhar mass of 1.4 solar masses (M(o)). Here we show that the high-redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy that both imply a super-Chandrasekhar-mass progenitor. Super-Chandrasekhar-mass supernovae should occur preferentially in a young stellar population, so this may provide an explanation for the observed trend that overluminous type Ia supernovae occur only in 'young' environments. As this supernova does not obey the relations that allow type Ia supernovae to be calibrated as standard candles, and as no counterparts have been found at low redshift, future cosmology studies will have to consider possible contamination from such events.

  15. Role of neutrophil elastase in lung injury induced by burn-blast combined injury in rats.

    PubMed

    Chai, Jia-ke; Cai, Jian-hua; Deng, Hu-ping; Zou, Xiao-fang; Liu, Wei; Hu, Qing-gang; Shen, Chuan-an; Yin, Hui-nan; Zhang, Xi-bo; Chi, Yun-fei; Ma, Li; Feng, Rui

    2013-06-01

    Neutrophil elastase (NE) takes part in the pathogenesis of acute lung injury. However, its role in lung injury of burn-blast combined injury is unclear. Our objective was to assess the role of NE, and effect of sivelestat, a specific NE inhibitor, in lung injury induced by burn-blast combined injury in rats. One hundred and sixty male Sprague-Dawley rats were randomly subjected to burn-blast combined injury (BB) group, burn-blast combined injury plus sivelestat treatment (S) group or control (C) group. Blood gas, protein concentration and NE activity in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity, serum concentrations of TNF-α and IL-8, etc. were investigated from 0 h to 7 d post-injury. In BB group, PaO2 decreased, while NE activity in BALF, total protein concentration in BALF, pulmonary MPO activity and W/D ratio, serum concentrations of TNF-α and IL-8 increased with neutrophil infiltration, progressive bleeding and pulmonary oedema. Compared with BB group, sivelestat treatment decreased the NE activity and ameliorated the above indexes. Sivelestat, exerts a protective effect in lung injury after burn-blast combined injury through inhibiting NE activity to decrease pulmonary vascular permeability, neutrophil sequestration, and production of TNF-α and IL-8. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  16. Umbilical cord blood regulatory T-cell expansion and functional effects of tumor necrosis factor receptor family members OX40 and 4-1BB expressed on artificial antigen-presenting cells

    PubMed Central

    Harker-Murray, Paul; Porter, Stephen B.; Merkel, Sarah C.; Londer, Aryel; Taylor, Dawn K.; Bina, Megan; Panoskaltsis-Mortari, Angela; Rubinstein, Pablo; Van Rooijen, Nico; Golovina, Tatiana N.; Suhoski, Megan M.; Miller, Jeffrey S.; Wagner, John E.; June, Carl H.; Riley, James L.

    2008-01-01

    Previously, we showed that human umbilical cord blood (UCB) regulatory T cells (Tregs) could be expanded approximately 100-fold using anti-CD3/28 monoclonal antibody (mAb)–coated beads to provide T-cell receptor and costimulatory signals. Because Treg numbers from a single UCB unit are limited, we explored the use of cell-based artificial antigen-presenting cells (aAPCs) preloaded with anti-CD3/28 mAbs to achieve higher levels of Treg expansion. Compared with beads, aAPCs had similar expansion properties while significantly increasing transforming growth factor β (TGF-β) secretion and the potency of Treg suppressor function. aAPCs modified to coexpress OX40L or 4-1BBL expanded UCB Tregs to a significantly greater extent than bead- or nonmodified aAPC cultures, reaching mean expansion levels exceeding 1250-fold. Despite the high expansion and in contrast to studies using other Treg sources, neither OX40 nor 4-1BB signaling of UCB Tregs reduced in vitro suppression. UCB Tregs expanded with 4-1BBL expressing aAPCs had decreased levels of proapoptotic bim. UCB Tregs expanded with nonmodified or modified aAPCs versus beads resulted in higher survival associated with increased Treg persistence in a xeno-geneic graft-versus-host disease lethality model. These data offer a novel approach for UCB Treg expansion using aAPCs, including those coexpressing OX40L or 4-1BBL. PMID:18645038

  17. [Investigation of mechanisms of action of growth factors of autologous platelet-rich plasma used to treat erectile dysfunction].

    PubMed

    Epifanova, M V; Chalyi, M E; Krasnov, A O

    2017-09-01

    To determine the quantitative and qualitative composition of growth factors (PDGF-AA, PDGF-BB, VEGF, VEGF-D, FGF-acid, FGF-basic) and platelets in various modifications of APRP. Blood of 12 male volunteers (control group) and 12 patients with ED was used to prepare APRP and the subsequently determine the concentration of growth factors. The growth factor concentrations (FGF acid, FGF basic, PDGF-AA, PDGF-BB, VEGF, VEGF-D) was determined using a flow cytometry-based xMAP Luminex (Gen-Probe) system. Concentration of platelets in APRP obtained by two stage centrifugation, reached 1480 (1120-1644) in the control group and 1232 (956-1502) in patients with ED. The concentration of growth factors in the samples prepared without preliminary freezing was: PDGF-AA 842 (22-3700), PDGF-BB 2837 (1460-4100), FGF-basic 7.9 (0.28-127), FGF-acid 3, 4 (0.14-11), VEGF 19 (4.6-46), VEGF-D 21 (14-38). After thawing, the concentration of all growth factors in the samples increased. The study findings suggest that the mechanism of erectile function recovery following the use of APRP is through the active substances detected in APRP, i.e. FGF-basic, PDGF-AA, PDGF-BB, VEGF, VEGF-D and FGF-acid. Also, the study showed that the content of growth factors in APRP after of freezing/thawing is higher than in APRP that has not been frozen. This is due to the cell membrane destruction at extremely low temperatures during freezing.

  18. Doses from beta radiation in sensitive layers of human lung and dose conversion factors due to 222Rn/220Rn progeny.

    PubMed

    Markovic, V M; Stevanovic, N; Nikezic, D

    2011-08-01

    Great deal of work has been devoted to determine doses from alpha particles emitted by (222)Rn and (220)Rn progeny. In contrast, contribution of beta particles to total dose has been neglected by most of the authors. The present work describes a study of the detriment of (222)Rn and (220)Rn progeny to the human lung due to beta particles. The dose conversion factor (DCF) was introduced to relate effective dose and exposure to radon progeny; it is defined as effective dose per unit exposure to inhaled radon or thoron progeny. Doses and DCFs were determined for beta radiation in sensitive layers of bronchi (BB) and bronchioles (bb), taking into account inhaled (222)Rn and (220)Rn progeny deposited in mucus and cilia layer. The nuclei columnar secretory and short basal cells were considered to be sensitive target layers. For dose calculation, electron-absorbed fractions (AFs) in the sensitive layers of the BB and bb regions were used. Activities in the fast and slow mucus of the BB and bb regions were obtained using the LUNGDOSE software developed earlier. Calculated DCFs due to beta radiation were 0.21 mSv/WLM for (222)Rn and 0.06 mSv/WLM for (220)Rn progeny. In addition, the influence of Jacobi room parameters on DCFs was investigated, and it was shown that DCFs vary with these parameters by up to 50%.

  19. Glutaredoxin modulates platelet-derived growth factor-dependent cell signaling by regulating the redox status of low molecular weight protein-tyrosine phosphatase.

    PubMed

    Kanda, Munetake; Ihara, Yoshito; Murata, Hiroaki; Urata, Yoshishige; Kono, Takaaki; Yodoi, Junji; Seto, Shinji; Yano, Katsusuke; Kondo, Takahito

    2006-09-29

    Glutaredoxin (GRX) is a glutathione-disulfide oxidoreductase involved in various cellular functions, including the redox-dependent regulation of certain integral proteins. Here we demonstrated that overexpression of GRX suppressed the proliferation of myocardiac H9c2 cells treated with platelet-derived growth factor (PDGF)-BB. After stimulation with PDGF-BB, the phosphorylation of PDGF receptor (PDGFR) beta was suppressed in GRX gene-transfected cells, compared with controls. Conversely, the phosphorylation was enhanced by depletion of GRX by RNA interference. In this study we focused on the role of low molecular weight protein-tyrosine phosphatase (LMW-PTP) in the dephosphorylation of PDGFRbeta via a redox-dependent mechanism. We found that depletion of LMW-PTP using RNA interference enhanced the PDGF-BB-induced phosphorylation of PDGFRbeta, indicating that LMW-PTP works for PDGFRbeta. The enhancement of the phosphorylation of PDGFRbeta was well correlated with inactivation of LMW-PTP by cellular peroxide generated in the cells stimulated with PDGF-BB. In vitro, with hydrogen peroxide treatment, LMW-PTP showed decreased activity with the concomitant formation of dithiothreitol-reducible oligomers. GRX protected LMW-PTP from hydrogen peroxide-induced oxidation and inactivation in concert with glutathione, NADPH, and glutathione disulfide reductase. This strongly suggests that retention of activity of LMW-PTP by enhanced GRX expression suppresses the proliferation of cells treated with PDGF-BB via enhanced dephosphorylation of PDGFRbeta. Thus, GRX plays an important role in PDGF-BB-dependent cell proliferation by regulating the redox state of LMW-PTP.

  20. Selection for Cry3Bb1 resistance in a genetically diverse population of nondiapausing western corn rootworm (Coleoptera: Chrysomelidae).

    PubMed

    Oswald, Kenneth J; French, B Wade; Nielson, Chad; Bagley, Mark

    2011-06-01

    Five short-diapause laboratory lines of western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), were selected for resistance to MON863, a variety of corn genetically modified with the Bacillus thuringiensis Berliner (Bt) transgene that expresses the Cry3Bb1 delta-endotoxin. Three of the selected lines were developed by incremental increase in the duration of exposure to MON863 over 11 generations (moderate selected lines). Two selected lines were developed from a control group by constant exposure to MON863 for at least 14 d posthatch over seven generations (intense selected lines). At the end of the experiment, survivorship, as measured by adult emergence, was approximately 4 times higher in each of the selected lines reared on MON863 compared with control lines. Estimates of realized heritabilities (h2) were 0.16 and 0.15 for the moderate and intense selected lines, respectively, and are consistent with h2 estimates reported previously from a variety of pest insects. These lines provide data necessary for evaluating the potential for Bt resistance within diabroticite beetles and will be useful for developing improved insect resistance management strategies.

  1. Essential oils and Beauveria bassiana against Dermanyssus gallinae (Acari: Dermanyssidae): Towards new natural acaricides.

    PubMed

    Immediato, Davide; Figueredo, Luciana Aguiar; Iatta, Roberta; Camarda, Antonio; de Luna, Rafaela Lira Nogueira; Giangaspero, Annunziata; Brandão-Filho, Sinval Pinto; Otranto, Domenico; Cafarchia, Claudia

    2016-10-15

    Essential oils (EOs) and entomopathogenic fungi such as Beauveria bassiana (Bb) strains have the potential to be used as alternative insecticides and acaricides for controlling ectoparasites as Dermanyssus gallinae. These compounds have some limitations in their use: the acaricidal effect of EOs is rapid, but short-lived, whilst that of Bb is delayed, but long-lived. To evaluate the effect of both compounds combined against D. gallinae, the non-toxic dose of Eucalyptus globulus, Eucalyptus citriodora, Thymus vulgaris and Eugenia caryophyllata essential oils were firstly calculated for "native" strains of Bb. Subsequently, the effects of the combination of selected EOs with Bb against nymph and adult poultry red mites (PRMs) was assessed. EO concentrations ranging from 0.0015 to 8% v/v (i.e., nine double dilutions) were used to evaluate their effect on germination, sporulation and vegetative growth rates of native strains of Bb. A total of 1440 mites (720 nymphs and 720 adults) were divided into three-treated group (TGs) and one control group (CG). In TGs, mites were exposed to Bb in combination with the selected EO (TG1), EO alone (TG2) or Bb (TG3) alone. In the CG, mites were exposed to 0.1% tween 80 plus EO solvent (CG). E. globulus and E. citriodora were toxic for Bb in concentrations higher than 0.2% and 0.003% respectively, whilst E. caryophyllata and T. vulgaris were toxic at all concentrations tested against Bb. Based on the results of the toxicity assays against Bb, E. globulus was chosen to be tested as acaricide resulting non-toxic for Bb at concentration lower than 0.4%. Increased mortality of D. gallinae adults was recorded in TG1 than those in other TGs from 4days post-infection (T+4DPI). A 100% mortality of D. gallinae was recorded in adults at T+9DPI and at T+10DPI in nymphs in TG1 and later than T+11DPI in the other TGs. Used in combination with E. globulus, Bb displayed an earlier acaricidal effect towards both haematophagous D. gallinae stages

  2. Measurement of $${\\mathcal B}(B^0_s\\rightarrow D_s^{(*)}D_s^{(*)})$$ > and the Lifetime Difference in the $$B_s^0$$ System

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Youn, Sungwoo

    2009-06-01

    We search for the semi-inclusive processmore » $$B^0_s\\rightarrow D_s^{(*)}D_s^{(*)}$$ using 2.8 fb$$^{-1}$$ of $$p \\bar{p}$$ collisions at $$\\sqrt{s} = 1.96$$ TeV recorded by the D0 detector operating at the Fermilab Tevatron Collider. Under certain theoretical assumptions, these double-charm final states saturate CP-even eigenstates in the $$B_s^0$$ decays, allowing the lifetime difference of the $$B_s^0$$ system to be related to the branching ratio. We observe $$26.6\\pm 8.4$$ signal events with a significance above background of 3.2 standard deviations. The branching ratio is measured as $${\\cal B}(B^0_s\\rightarrow D_s^{(*)}D_s^{(*)}) = 0.035\\pm0.010\\text{(stat)}\\pm0.011\\text{(syst)}$$ and, in the Standard Model, the width difference is derived as $$\\Delta \\Gamma_s^{\\rm CP}/\\Gamma_s = 0.072\\pm0.021\\text{(stat)}\\pm0.022\\text{(syst)}$$.« less

  3. Neomycin is a platelet-derived growth factor (PDGF) antagonist that allows discrimination of PDGF alpha- and beta-receptor signals in cells expressing both receptor types.

    PubMed

    Vassbotn, F S; Ostman, A; Siegbahn, A; Holmsen, H; Heldin, C H

    1992-08-05

    The aminoglycoside neomycin has recently been found to affect certain platelet-derived growth factor (PDGF) responses in C3H/10T1/2 C18 fibroblasts. Using porcine aortic endothelial cells transfected with PDGF alpha- or beta-receptors, we explored the possibility that neomycin interferes with the interaction between the different PDGF isoforms and their receptors. We found that neomycin (5 mM) inhibited the binding of 125I-PDGF-BB to the alpha-receptor with only partial effect on the binding of 125I-PDGF-AA; in contrast, the binding of 125I-PDGF-BB to the beta-receptor was not affected by the aminoglycoside. Scatchard analyses showed that neomycin (5 mM) decreased the number of binding sites for PDGF-BB on alpha-receptor-expressing cells by 87%. Together with cross-competition studies with 125I-labeled PDGF homodimers, the effect of neomycin indicates that PDGF-AA and PDGF-BB bind to both common and unique structures on the PDGF alpha-receptor. Neomycin specifically inhibited the autophosphorylation of the alpha-receptor by PDGF-BB, with less effect on the phosphorylation induced by PDGF-AA and no effect on the phosphorylation of the beta-receptor by PDGF-BB. Thus, neomycin is a PDGF isoform- and receptor-specific antagonist that provides a possibility to compare the signal transduction pathways of alpha- and beta-receptors in cells expressing both receptor types. This approach was used to show that activation of PDGF beta-receptors by PDGF-BB mediated a chemotactic response in human fibroblasts, whereas activation of alpha-receptors by the same ligand inhibited chemotaxis.

  4. Effect of volatile oil from Blumea Balsamifera (L.) DC. leaves on wound healing in mice.

    PubMed

    Pang, Yuxin; Wang, Dan; Hu, Xuan; Wang, Hui; Fu, Wanjin; Fan, Zuowang; Chen, Xiaolu; Yu, Fulai

    2014-12-01

    To assess the effectiveness of violate oil from Blumea Balsamifera (L.) DC. leaves (BB oil) on wound healing in mice. Undiluted BB oil and its diluted solutions with olive oil to 1/5 and 1/10 to yield BB oil1/5 and BB oil1/10 were applied to the wounded skin before wound healing conditions were assessed by healing rate, histopathology, and contents of collagen, hydroxyproline, and Neuropeptide Substance P (SP). All above results were compared with the efficacies of the control, pure olive oil, basic fibroblast growth factor (BFGF), and cream of Jing Wan Hong (JWH). BB oil1/5 and BB oil1/10 improved wound contraction and closure. Histopathology study further confirmed a desirable histological organization of wound tissues. BB oil1/5 and BB oil1/10 reduced the number of inflammatory cells, increased wound-healing rates, and significantly increased the hydroxyproline content. Both BB oil1/5 and BB oil1/10 improved formation of collagen, and reduced the frequency of fibroblasts. Moreover, BB oil1/5 and BB oil1/10 markedly promoted SP expression. However, undiluted BB oil may induce skin thickening and hardening, inhibite collagen synthesis and delay complete skin wound healing. The BB oil1/5 and BB oil1/10 promoted capillary regeneration, blood circulation, collagen deposition, granular tissue formation, epithelial deposition, and wound contraction. The mechanism underlying the action might be related to induction of SP secretion, and the proliferation and differentiation of mesenchymal cells.

  5. Carbon-based nanocomposites with aptamer-templated silver nanoclusters for the highly sensitive and selective detection of platelet-derived growth factor.

    PubMed

    Zhang, Zhihong; Guo, Chuanpan; Zhang, Shuai; He, Linghao; Wang, Minghua; Peng, Donglai; Tian, Junfeng; Fang, Shaoming

    2017-03-15

    We synthesized two kinds of carbon-based nanocomposites of silver nanoclusters (AgNCs). An aptamer for targeted platelet-derived growth factor-BB (PDGF-BB) detection was used as the organic phase to produce AgNCs@Apt, three dimensional reduced graphene oxide@AgNCs@Aptamer (3D-rGO@AgNCs@Apt), and graphene quantum dots@AgNCs@Aptamer (GQD@AgNCs@Apt) nanocomposites. The formation mechanism of the developed nanocomposites was described by detailed characterizations of their chemical and crystal structures. Subsequently, the as-synthesized nanoclusters containing aptamer strands were applied as the sensitive layers to fabricate a novel electrochemical aptasensor for the detection of PDGF-BB, which may be directly used to determine the target protein. Electrochemical impedance spectra showed that the developed 3D-rGO@AgNCs@Apt-based biosensor exhibited the highest sensitivity for PDGF-BB detection among three kinds of fabricated aptasensors, with an extremely low detection limit of 0.82pgmL -1 . In addition, the 3D-rGO@AgNCs@Apt-based biosensor showed high selectivity, stability, and applicability for the detection of PDGF-BB. This finding indicated that the AgNC-based nanocomposites prepared by a one-step method could be used as an electrochemical biosensor for various detection procedures in the biomedical field. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Short term storage stability at room temperature of two different platelet-rich plasma preparations from equine donors and potential impact on growth factor concentrations.

    PubMed

    Hauschild, Gregor; Geburek, Florian; Gosheger, Georg; Eveslage, Maria; Serrano, Daniela; Streitbürger, Arne; Johannlükens, Sara; Menzel, Dirk; Mischke, Reinhard

    2017-01-05

    The increasing interest in platelet-rich plasma (PRP) based therapies is as yet accompanied by inconsistent information regarding nearly all aspects of handling and application. Among these storage stability of processed platelet-rich products may be the basis for a more flexible application mode. The objective of this study was (1) to estimate the storage stability of growth factors platelet derived growth factor BB (PDGF-BB) and transforming growth factor ß1 (TGF-ß1) in both, a single-step softspin centrifugation-based pure-PRP (P-PRP, ACP®), and a gravity filtration system-based leukocyte-rich-PRP (L-PRP, E-PET), over a six hours time span after preparation at room temperature and (2) to identify possible factors influencing these growth factor concentrations in an equine model. Growth factor concentrations remained stable over the entire investigation period in L-PRP as well as P-PRP preparations revealing a mean of 3569 pg/ml PDGF-BB for E-PET and means of 1276 pg/ml PDGF-BB and 5086 pg/ml TGF-ß1 for ACP®. Pearson correlations yielded no significant impact of whole blood platelet (PLT), white blood cell (WBC) and red blood cell (RBC) counts on resulting cytokine values. In case of ACP® no significant dependencies between PLT, WBC and RBC counts of the processed platelet-rich product and resulting cytokine content occurred with exception of TGF-ß1 concentrations showing a strong correlation with the WBC content. PDGF-BB content of E-PET preparations showed a strong positive correlation with PLT and a strong negative with WBC of these preparations but not with RBC. L-PRP ad modum E-PET and P-PRP ad modum ACP® are applicable over at least a six hours time span at room temperature without loss of growth factor content. Based on the results of this study factors influencing the resulting growth factor concentrations still remain questionable. Additional studies implicating a further standardization of preparation protocols are necessary to identify

  7. Third-generation CD28/4-1BB chimeric antigen receptor T cells for chemotherapy relapsed or refractory acute lymphoblastic leukaemia: a non-randomised, open-label phase I trial protocol.

    PubMed

    Tang, Xiao-Yi; Sun, Yao; Zhang, Ang; Hu, Guo-Liang; Cao, Wei; Wang, Dan-Hong; Zhang, Bin; Chen, Hu

    2016-12-30

    There is no curative treatment available for patients with chemotherapy relapsed or refractory CD19+ B cells-derived acute lymphoblastic leukaemia (r/r B-ALL). Although CD19-targeting second-generation (2nd-G) chimeric antigen receptor (CAR)-modified T cells carrying CD28 or 4-1BB domains have demonstrated potency in patients with advanced B-ALL, these 2 signalling domains endow CAR-T cells with different and complementary functional properties. Preclinical results have shown that third-generation (3rd-G) CAR-T cells combining 4-1BB and CD28 signalling domains have superior activation and proliferation capacity compared with 2nd-G CAR-T cells carrying CD28 domain. The aim of the current study is therefore to investigate the safety and efficacy of 3rd-G CAR-T cells in adults with r/r B-ALL. This study is a phase I clinical trial for patients with r/r B-ALL to test the safety and preliminary efficacy of 3rd-G CAR-T cells. Before receiving lymphodepleting conditioning regimen, the peripheral blood mononuclear cells from eligible patients will be leukapheresed, and the T cells will be purified, activated, transduced and expanded ex vivo. On day 6 in the protocol, a single dose of 1 million CAR-T cells per kg will be administrated intravenously. The phenotypes of infused CAR-T cells, copy number of CAR transgene and plasma cytokines will be assayed for 2 years after CAR-T infusion using flow cytometry, real-time quantitative PCR and cytometric bead array, respectively. Moreover, several predictive plasma cytokines including interferon-γ, interleukin (IL)-6, IL-8, Soluble Interleukin (sIL)-2R-α, solubleglycoprotein (sgp)130, sIL-6R, Monocyte chemoattractant protein (MCP1), Macrophage inflammatory protein (MIP1)-α, MIP1-β and Granulocyte-macrophage colony-stimulating factor (GM-CSF), which are highly associated with severe cytokine release syndrome (CRS), will be used to forecast CRS to allow doing earlier intervention, and CRS will be managed based on a revised CRS

  8. Minimally invasive esthetic ridge preservation with growth-factor enhanced bone matrix.

    PubMed

    Nevins, Marc L; Said, Sherif

    2017-12-28

    Extraction socket preservation procedures are critical to successful esthetic implant therapy. Conventional surgical approaches are technique sensitive and often result in alteration of the soft tissue architecture, which then requires additional corrective surgical procedures. This case series report presents the ability of flapless surgical techniques combined with a growth factor-enhanced bone matrix to provide esthetic ridge preservation at the time of extraction for compromised sockets. When considering esthetic dental implant therapy, preservation, or further enhancement of the available tissue support at the time of tooth extraction may provide an improved esthetic outcome with reduced postoperative sequelae and decreased treatment duration. Advances in minimally invasive surgical techniques combined with recombinant growth factor technology offer an alternative for bone reconstruction while maintaining the gingival architecture for enhanced esthetic outcome. The combination of freeze-dried bone allograft (FDBA) and rhPDGF-BB (platelet-derived growth factor-BB) provides a growth-factor enhanced matrix to induce bone and soft tissue healing. The use of a growth-factor enhanced matrix is an option for minimally invasive ridge preservation procedures for sites with advanced bone loss. Further studies including randomized clinical trials are needed to better understand the extent and limits of these procedures. The use of minimally invasive techniques with growth factors for esthetic ridge preservation reduces patient morbidity associated with more invasive approaches and increases the predictability for enhanced patient outcomes. By reducing the need for autogenous bone grafts the use of this technology is favorable for patient acceptance and ease of treatment process for esthetic dental implant therapy. © 2017 Wiley Periodicals, Inc.

  9. Field Trial Performance of Herculex XTRA (Cry34Ab1/Cry35Ab1) and SmartStax (Cry34Ab1/Cry35Ab1 + Cry3Bb1) Hybrids and Soil Insecticides Against Western and Northern Corn Rootworms (Coleoptera: Chrysomelidae).

    PubMed

    Johnson, K D; Campbell, L A; Lepping, M D; Rule, D M

    2017-06-01

    Western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), and northern corn rootworm, Diabrotica barberi Smith and Lawrence (Coleoptera: Chrysomelidae), are important insect pests in corn, Zea mays L. For more than a decade, growers have been using transgenic plants expressing proteins from the bacterium Bacillus thuringiensis (Bt) to protect corn roots from feeding. In 2011, western corn rootworm populations were reported to have developed resistance to Bt hybrids expressing Cry3Bb1 and later found to be cross-resistant to hybrids expressing mCry3A and eCry3.1Ab. The identification of resistance to Cry3 (Cry3Bb1, mCry3A, and eCry3.1Ab) hybrids led to concerns about durability and efficacy of products with single traits and of products containing a pyramid of a Cry3 protein and the binary Bt proteins Cry34Ab1 and Cry35Ab1. From 2012 to 2014, 43 field trials were conducted across the central United States to estimate root protection provided by plants expressing Cry34Ab1/Cry35Ab1 alone (Herculex RW) or pyramided with Cry3Bb1 (SmartStax). These technologies were evaluated with and without soil-applied insecticides to determine if additional management measures provided benefit where Cry3 performance was reduced. Trials were categorized for analysis based on rootworm damage levels on Cry3-expressing hybrids and rootworm feeding pressure within each trial. Across scenarios, Cry34Ab1/Cry35Ab1 hybrids provided excellent root protection. Pyramided traits provided greater root and yield protection than non-Bt plus a soil-applied insecticide, and only in trials where larval feeding pressure exceeded two nodes of damage did Cry34Ab1/Cry35Ab1 single-trait hybrids and pyramided hybrids show greater root protection from the addition of soil-applied insecticides. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Risk Factor Intervention for Health Maintenance

    ERIC Educational Resources Information Center

    Breslow, Lester

    1978-01-01

    Risk factors for disease consist of personal habits such as cigarette smoking and excessive alcohol consumption, and bodily characteristics such as hypertension and high serum cholesterol. Progress in identifying, quantifying, and controlling risk factors is opening the way to the prevention of disease. (BB)

  11. Stratifying risk in the prevention of recurrent variceal hemorrhage: Results of an individual patient meta-analysis.

    PubMed

    Albillos, Agustín; Zamora, Javier; Martínez, Javier; Arroyo, David; Ahmad, Irfan; De-la-Peña, Joaquin; Garcia-Pagán, Juan-Carlos; Lo, Gin-Ho; Sarin, Shiv; Sharma, Barjesh; Abraldes, Juan G; Bosch, Jaime; Garcia-Tsao, Guadalupe

    2017-10-01

    Endoscopic variceal ligation plus beta-blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant, and in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all-source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A versus B/C) by means of individual time-to-event patient data meta-analysis from randomized controlled trials. The study used individual data on 389 patients from three trials comparing EVL plus BB versus BB and 416 patients from four trials comparing EVL plus BB versus EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95% confidence interval, 0.18-0.89; P = 0.025) but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (P for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95% confidence interval, 0.25-0.85; P = 0.013). Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity: in patients with preserved liver function (Child A), combination therapy is recommended because it is more effective in preventing rebleeding, without modifying survival, while in patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death compared with combination therapy, underlining that BB is the key element of combination therapy. (Hepatology 2017;66:1219-1231). © 2017 by the American Association for the Study of

  12. Differential growth factor control of bone formation through osteoprogenitor differentiation.

    PubMed

    Chaudhary, L R; Hofmeister, A M; Hruska, K A

    2004-03-01

    The osteogenic factors bone morphogenetic protein (BMP-7), platelet-derived growth factor (PDGF)-BB, and fibroblast growth factor (FGF-2) regulate the recruitment of osteoprogenitor cells and their proliferation and differentiation into mature osteoblasts. However, their mechanisms of action on osteoprogenitor cell growth, differentiation, and bone mineralization remain unclear. Here, we tested the hypothesis that these osteogenic agents were capable of regulating osteoblast differentiation and bone formation in vitro. Normal human bone marrow stromal (HBMS) cells were treated with BMP-7 (40 ng ml(-1)), PDGF-BB (20 ng ml(-1)), FGF-2 (20 ng ml(-1)), or FGF-2 plus BMP-7 for 28 days in a serum-containing medium with 10 mM beta-glycerophosphate and 50 microg ml(-1) ascorbic acid. BMP-7 stimulated a morphological change to cuboidal-shaped cells, increased alkaline phosphatase (ALKP) activity, bone sialoprotein (BSP) gene expression, and alizarin red S positive nodule formation. Hydroxyapatite (HA) crystal deposition in the nodules was demonstrated by Fourier transform infrared (FTIR) spectroscopy only in BMP-7- and dexamethasone (DEX)-treated cells. DEX-treated cells appeared elongated and fibroblast-like compared to BMP-7-treated cells. FGF-2 did not stimulate ALKP, and cell morphology was dystrophic. PDGF-BB had little or no effect on ALKP activity and biomineralization. Alizarin Red S staining of cells and calcium assay indicated that BMP-7, DEX, and FGF-2 enhanced calcium mineral deposition, but FTIR spectroscopic analysis demonstrated no formation of HA similar to human bone in control, PDGF-BB-, and FGF-2-treated samples. Thus, FGF-2 stimulated amorphous octacalcium phosphate mineral deposition that failed to mature into HA. Interestingly, FGF-2 abrogated BMP-7-induced ALKP activity and HA formation. Results demonstrate that BMP-7 was competent as a sole factor in the differentiation of human bone marrow stromal cells to bone-forming osteoblasts confirmed by FTIR

  13. Incorporation of Bacterial Blight Resistance Genes Into Lowland Rice Cultivar Through Marker-Assisted Backcross Breeding.

    PubMed

    Pradhan, Sharat Kumar; Nayak, Deepak Kumar; Pandit, Elssa; Behera, Lambodar; Anandan, Annamalai; Mukherjee, Arup Kumar; Lenka, Srikanta; Barik, Durga Prasad

    2016-07-01

    Bacterial blight (BB) of rice caused by Xanthomonas oryzae pv. oryzae is a major disease of rice in many rice growing countries. Pyramided lines carrying two BB resistance gene combinations (Xa21+xa13 and Xa21+xa5) were developed in a lowland cultivar Jalmagna background through backcross breeding by integrating molecular markers. In each backcross generation, markers closely linked to the disease resistance genes were used to select plants possessing the target genes. Background selection was continued in those plants carrying resistant genes until BC(3) generation. Plants having the maximum contribution from the recurrent parent genome were selected in each generation and hybridized with the recipient parent. The BB-pyramided line having the maximum recipient parent genome recovery of 95% was selected among BC3F1 plants and selfed to isolate homozygous BC(3)F(2) plants with different combinations of BB resistance genes. Twenty pyramided lines with two resistance gene combinations exhibited high levels of tolerance against the BB pathogen. In order to confirm the resistance, the pyramided lines were inoculated with different X. oryzae pv. oryzae strains of Odisha for bioassay. The genotypes with combination of two BB resistance genes conferred high levels of resistance to the predominant X. oryzae pv. oryzae isolates prevalent in the region. The pyramided lines showed similarity with the recipient parent with respect to major agro-morphologic traits.

  14. Measurement of |V(cb)| and the form-factor slope in B --> Dl- nu(l) decays in events tagged by a fully reconstructed B meson.

    PubMed

    Aubert, B; Karyotakis, Y; Lees, J P; Poireau, V; Prencipe, E; Prudent, X; Tisserand, V; Garra Tico, J; Grauges, E; Martinelli, M; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Battaglia, M; Brown, D N; Kerth, L T; Kolomensky, Yu G; Lynch, G; Osipenkov, I L; Tackmann, K; Tanabe, T; Hawkes, C M; Soni, N; Watson, A T; Koch, H; Schroeder, T; Asgeirsson, D J; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Randle-Conde, A; Blinov, V E; Bukin, A D; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Atmacan, H; Gary, J W; Liu, F; Long, O; Vitug, G M; Yasin, Z; Zhang, L; Sharma, V; Campagnari, C; Hong, T M; Kovalskyi, D; Mazur, M A; Richman, J D; Beck, T W; Eisner, A M; Heusch, C A; Kroseberg, J; Lockman, W S; Martinez, A J; Schalk, T; Schumm, B A; Seiden, A; Wang, L; Winstrom, L O; Cheng, C H; Doll, D A; Echenard, B; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Bloom, P C; Ford, W T; Gaz, A; Hirschauer, J F; Nagel, M; Nauenberg, U; Smith, J G; Wagner, S R; Ayad, R; Toki, W H; Wilson, R J; Feltresi, E; Hauke, A; Jasper, H; Karbach, T M; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Kobel, M J; Nogowski, R; Schubert, K R; Schwierz, R; Volk, A; Bernard, D; Latour, E; Verderi, M; Clark, P J; Playfer, S; Watson, J E; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Fioravanti, E; Franchini, P; Luppi, E; Munerato, M; Negrini, M; Petrella, A; Piemontese, L; Santoro, V; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Contri, R; Guido, E; Lo Vetere, M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Tosi, S; Chaisanguanthum, K S; Morii, M; Adametz, A; Marks, J; Schenk, S; Uwer, U; Bernlochner, F U; Klose, V; Lacker, H M; Bard, D J; Dauncey, P D; Tibbetts, M; Behera, P K; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Derkach, D; da Costa, J Firmino; Grosdidier, G; Le Diberder, F; Lepeltier, V; Lutz, A M; Malaescu, B; Pruvot, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; Clarke, C K; Di Lodovico, F; Sacco, R; Sigamani, M; Cowan, G; Paramesvaran, S; Wren, A C; Brown, D N; Davis, C L; Denig, A G; Fritsch, M; Gradl, W; Hafner, A; Alwyn, K E; Bailey, D; Barlow, R J; Jackson, G; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Dallapiccola, C; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Henderson, S W; Sciolla, G; Spitznagel, M; Yamamoto, R K; Zhao, M; Patel, P M; Robertson, S H; Schram, M; Lazzaro, A; Lombardo, V; Palombo, F; Stracka, S; Bauer, J M; Cremaldi, L; Godang, R; Kroeger, R; Sonnek, P; Summers, D J; Zhao, H W; Simard, M; Taras, P; Nicholson, H; De Nardo, G; Lista, L; Monorchio, D; Onorato, G; Sciacca, C; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; LoSecco, J M; Wang, W F; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Sekula, S J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Castelli, G; Gagliardi, N; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Sanchez, P del Amo; Ben-Haim, E; Bonneaud, G R; Briand, H; Chauveau, J; Hamon, O; Leruste, Ph; Marchiori, G; Ocariz, J; Perez, A; Prendki, J; Sitt, S; Gladney, L; Biasini, M; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Calderini, G; Carpinelli, M; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Pegna, D Lopes; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Anulli, F; Baracchini, E; Cavoto, G; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Gioi, L Li; Mazzoni, M A; Morganti, S; Piredda, G; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Wilson, F F; Emery, S; Esteve, L; de Monchenault, G Hamel; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Allen, M T; Aston, D; Bartoldus, R; Benitez, J F; Cenci, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Sevilla, M Franco; Gabareen, A M; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Lindquist, B; Luitz, S; Luth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Messner, R; Muller, D R; Neal, H; Nelson, S; O'Grady, C P; Ofte, I; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; West, C A; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Young, C C; Ziegler, V; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Burchat, P R; Edwards, A J; Miyashita, T S; Ahmed, S; Alam, M S; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Soffer, A; Spanier, S M; Wogsland, B J; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Wray, B C; Drummond, B W; Izen, J M; Lou, X C; Bianchi, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Choi, H H F; Hamano, K; King, G J; Kowalewski, R; Lewczuk, M J; Nugent, I M; Roney, J M; Sobie, R J; Gershon, T J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Puccio, E M T; Band, H R; Chen, X; Dasu, S; Flood, K T; Pan, Y; Prepost, R; Vuosalo, C O; Wu, S L

    2010-01-08

    We present a measurement of the Cabibbo-Kobayashi-Maskawa matrix element |V(cb)| and the form-factor slope rho2 in B --> Dl- nu(l) decays based on 460x10(6) BB events recorded at the Upsilon(4S) resonance with the BABAR detector. B --> Dl- nu(l) decays are selected in events in which a hadronic decay of the second B meson is fully reconstructed. We measure B(B- --> D0 l- nu(l))/B(B- --> Xl- nu(l)) = (0.255+/-0.009+/-0.009) and B(B0 --> D+ l- nu(l))/B(B0 --> Xl- nu(l)) = (0.230+/-0.011+/-0.011), along with the differential decay distribution in B --> Dl- nu(l) decays. We then determine G(1)|V(cb)| = (42.3+/-1.9+/-1.4)x10(-3) and rho2 = 1.20+/-0.09+/-0.04, where G(1) is the hadronic form factor at the point of zero recoil.

  15. Examining the Influence of Beta Blockers and ACE Inhibitors on the Risk for Breast Cancer Recurrence: Results from the LACE Cohort

    PubMed Central

    Ganz, Patricia A.; Habel, Laurel A.; Weltzien, Erin K.; Caan, Bette J.; Cole, Steven W.

    2011-01-01

    There is increasing interest in the relationship between host lifestyle factors and the outcomes of cancer treatment. Behavioral factors, comorbid conditions, and non-cancer related pharmaceutical exposures may affect breast cancer (BC) outcomes. We used observational data from the LACE Study cohort (women with early stage BC from the Kaiser Permanente Northern California Cancer Registry) to examine the association between beta-blockers (BB) and/or angiotensin converting enzyme inhibitors (ACEi) and BC recurrence, BC-specific mortality, and overall mortality. Among 1,779 women, there were 292 BC recurrences, 174 BC deaths, and 323 total deaths. 23% were exposed to either a BB and/or an ACEi. These drugs were associated with older age, postmenopausal status, tamoxifen therapy, greater pre-diagnosis BMI, hypertension, and diabetes. In Cox proportional hazards models, ACEi exposure was associated with BC recurrence (HR 1.56, 95% CI 1.02, 2.39, p=0.04), but not cause-specific mortality or overall mortality. Combined ACEi and BB was associated with overall mortality (HR 1.94, 95% CI 1.22, 3.10, p=0.01). BB exposure was associated with lower hazard of recurrence and cause-specific mortality. However, there was no evidence of a dose response with either medication. For recurrence and cause-specific mortality, BB combined with ACEi was associated with a lower HR for the outcome than when ACEi alone was used. These hypothesis generating findings suggest that BC recurrence and survival were associated with exposure to two commonly used classes of anti-hypertensive medications. These observations need to be confirmed and suggest that greater attention should focus on the potential role of these commonly used medications in BC outcomes. PMID:21479924

  16. A wildland fire emission inventory for the western United States - uncertainty across spatial and temporal scales

    Treesearch

    Shawn Urbanski; WeiMin Hao

    2010-01-01

    Emissions of trace gases and aerosols by biomass burning (BB) have a significant influence on the chemical composition of the atmosphere, air quality, and climate. BB emissions depend on a range of variables including burned area, fuels, meteorology, combustion completeness, and emission factors (EF). Emission algorithms provide BB emission inventories (EI) which serve...

  17. Hyperspectral absorption and backscattering coefficients of bulk water retrieved from a combination of remote-sensing reflectance and attenuation coefficient.

    PubMed

    Lin, Junfang; Lee, Zhongping; Ondrusek, Michael; Liu, Xiaohan

    2018-01-22

    Absorption (a) and backscattering (bb) coefficients play a key role in determining the light field; they also serve as the link between remote sensing and concentrations of optically active water constituents. Here we present an updated scheme to derive hyperspectral a and bb with hyperspectral remote-sensing reflectance (Rrs) and diffuse attenuation coefficient (Kd) as the inputs. Results show that the system works very well from clear open oceans to highly turbid inland waters, with an overall difference less than 25% between these retrievals and those from instrument measurements. This updated scheme advocates the measurement and generation of hyperspectral a and bb from hyperspectral Rrs and Kd, as an independent data source for cross-evaluation of in situ measurements of a and bb and for the development and/or evaluation of remote sensing algorithms for such optical properties.

  18. Regulation of neuroblastoma differentiation by forkhead transcription factors FOXO1/3/4 through the receptor tyrosine kinase PDGFRA

    PubMed Central

    Mei, Yang; Wang, Zhanxiang; Zhang, Lei; Zhang, Yiru; Li, Xiaoyu; Liu, Huihui; Ye, Jing; You, Han

    2012-01-01

    Neuroblastoma is a common childhood malignant tumor originated from the neural crest-derived sympathetic nervous system. A crucial early event in neuroblastoma pathogenesis is arrested differentiation of neuroblasts at various stages. Treatment of neuroblastoma with TPA and PDGF-BB leads to terminal differentiation of neuroblastoma cells. However, the signaling pathways that are involved in this process remain largely unknown. Here, we report that inhibition of endogenous FOXO proteins attenuated TPA/PDGF-BB mediated differentiation of neuroblastoma cells. Activated FOXO transcription factors acted on PDGFRA promoter to direct its basal mRNA expression as well as its induction upon serum deprivation. Depletion of endogenous PDGFRA in neuroblastoma cells significantly diminished neurite formation and extension under TPA/PDGF-BB treatment. Furthermore, ectopic expression of PDGFRA abolished the blockage of neuroblastoma differentiation by FOXOs inhibition. These findings define the FOXO–PDGFRA axis as crucial mechanistic components that govern TPA-induced neuroblastoma differentiation. PMID:22411791

  19. Search for Stellar Streams Based on Data from the RAVE5 and Gaia TGAS Catalogues

    NASA Astrophysics Data System (ADS)

    Bajkova, A. T.; Bobylev, V. V.

    2018-03-01

    We have analyzed the space velocities of stars with the proper motions and trigonometric parallaxes from the Gaia TGAS catalogue in combination with the line-of-sight velocities from the RAVE5 catalogue. In the V, √ {{U^2} + 2{V^2}} velocity plane we have identified three clumps, BB17-1, BB17-2, and BB17-3, in the region of large velocities ( V<-150 km s-1). The stars of the BB17-1 and BB17-2 clumps are associated with the kinematic groups VelHel-6 and VelHel-7 detected previously by Helmi et al. We give the greatest attention to the BB17-3 clump. The latter is shown to be most closely linked with the debris of the globular cluster ω Cen. In the BB17-3 clump we have identified 28 stars with a low velocity dispersion with respect to the center of their distribution. All these stars have very close individual age estimates: log t ≈ 10. The distribution of metallicity indices in this sample is typical for the stars of the globular cluster ω Cen. In our opinion, the BB17-3 clump can be described as a homogeneous stream in the debris of the cluster ω Cen.

  20. Spatial and temporal variability of carbonaceous aerosols: Assessing the impact of biomass burning in the urban environment.

    PubMed

    Titos, G; Del Águila, A; Cazorla, A; Lyamani, H; Casquero-Vera, J A; Colombi, C; Cuccia, E; Gianelle, V; Močnik, G; Alastuey, A; Olmo, F J; Alados-Arboledas, L

    2017-02-01

    Biomass burning (BB) is a significant source of atmospheric particles in many parts of the world. Whereas many studies have demonstrated the importance of BB emissions in central and northern Europe, especially in rural areas, its impact in urban air quality of southern European countries has been sparsely investigated. In this study, highly time resolved multi-wavelength absorption coefficients together with levoglucosan (BB tracer) mass concentrations were combined to apportion carbonaceous aerosol sources. The Aethalometer model takes advantage of the different spectral behavior of BB and fossil fuel (FF) combustion aerosols. The model was found to be more sensitive to the assumed value of the aerosol Ångström exponent (AAE) for FF (AAE ff ) than to the AAE for BB (AAE bb ). As result of various sensitivity tests the model was optimized with AAE ff =1.1 and AAE bb =2. The Aethalometer model and levoglucosan tracer estimates were in good agreement. The Aethalometer model was further applied to data from three sites in Granada urban area to evaluate the spatial variation of CM ff and CM bb (carbonaceous matter from FF or BB origin, respectively) concentrations within the city. The results showed that CM bb was lower in the city centre while it has an unexpected profound impact on the CM levels measured in the suburbs (about 40%). Analysis of BB tracers with respect to wind speed suggested that BB was dominated by sources outside the city, to the west in a rural area. Distinguishing whether it corresponds to agricultural waste burning or with biomass burning for domestic heating was not possible. This study also shows that although traffic restrictions measures contribute to reduce carbonaceous concentrations, the extent of the reduction is very local. Other sources such as BB, which can contribute to CM as much as traffic emissions, should be targeted to reduce air pollution. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Search for Dark Matter Produced in Association with a Higgs Boson Decaying to bb[over ¯] Using 36  fb^{-1} of pp Collisions at sqrt[s]=13  TeV with the ATLAS Detector.

    PubMed

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Smiesko, J; Smirnov, N; Smirnov, S Yu; Smirnov, Y; Smirnova, L N; Smirnova, O; Smith, J W; Smith, M N K; Smith, R W; Smizanska, M; Smolek, K; Snesarev, A A; Snyder, I M; Snyder, S; Sobie, R; Socher, F; Soffer, A; Søgaard, A; Soh, D A; Sokhrannyi, G; Solans Sanchez, C A; Solar, M; Soldatov, E Yu; Soldevila, U; Solodkov, A A; Soloshenko, A; Solovyanov, O V; Solovyev, V; Sommer, P; Son, H; Sopczak, A; Sosa, D; Sotiropoulou, C L; Soualah, R; Soukharev, A M; South, D; Sowden, B C; Spagnolo, S; Spalla, M; Spangenberg, M; Spanò, F; Sperlich, D; Spettel, F; Spieker, T M; Spighi, R; Spigo, G; Spiller, L A; Spousta, M; St Denis, R D; Stabile, A; Stamen, R; Stamm, S; Stanecka, E; Stanek, R W; Stanescu, C; Stanitzki, M M; Stapf, B S; Stapnes, S; Starchenko, E A; Stark, G H; Stark, J; Stark, S H; Staroba, P; Starovoitov, P; Stärz, S; Staszewski, R; Steinberg, P; Stelzer, B; Stelzer, H J; Stelzer-Chilton, O; Stenzel, H; Stewart, G A; Stockton, M C; Stoebe, M; Stoicea, G; Stolte, P; Stonjek, S; Stradling, A R; Straessner, A; Stramaglia, M E; Strandberg, J; Strandberg, S; Strauss, M; Strizenec, P; Ströhmer, R; Strom, D M; Stroynowski, R; Strubig, A; Stucci, S A; Stugu, B; Styles, N A; Su, D; Su, J; Suchek, S; Sugaya, Y; Suk, M; Sulin, V V; Sultan, Dms; Sultansoy, S; Sumida, T; Sun, S; Sun, X; Suruliz, K; Suster, C J E; Sutton, M R; Suzuki, S; Svatos, M; Swiatlowski, M; Swift, S P; Sykora, I; Sykora, T; Ta, D; Tackmann, K; Taenzer, J; Taffard, A; Tafirout, R; Tahirovic, E; Taiblum, N; Takai, H; Takashima, R; Takasugi, E H; Takeshita, T; Takubo, Y; Talby, M; Talyshev, A A; Tanaka, J; Tanaka, M; Tanaka, R; Tanaka, S; Tanioka, R; Tannenwald, B B; Tapia Araya, S; Tapprogge, S; Tarem, S; Tartarelli, G F; Tas, P; Tasevsky, M; Tashiro, T; Tassi, E; Tavares Delgado, A; Tayalati, Y; Taylor, A C; Taylor, G N; Taylor, P T E; Taylor, W; Teixeira-Dias, P; Temple, D; Ten Kate, H; Teng, P K; Teoh, J J; Tepel, F; Terada, S; Terashi, K; Terron, J; Terzo, S; Testa, M; Teuscher, R J; Theveneaux-Pelzer, T; Thiele, F; Thomas, J P; Thomas-Wilsker, J; Thompson, P D; Thompson, A S; Thomsen, L A; Thomson, E; Tibbetts, M J; Ticse Torres, R E; Tikhomirov, V O; Tikhonov, Yu A; Timoshenko, S; Tipton, P; Tisserant, S; Todome, K; Todorova-Nova, S; Todt, S; Tojo, J; Tokár, S; Tokushuku, K; Tolley, E; Tomlinson, L; Tomoto, M; Tompkins, L; Toms, K; Tong, B; Tornambe, P; Torrence, E; Torres, H; Torró Pastor, E; Toth, J; Touchard, F; Tovey, D R; Treado, C J; Trefzger, T; Tresoldi, F; Tricoli, A; Trigger, I M; Trincaz-Duvoid, S; Tripiana, M F; Trischuk, W; Trocmé, B; Trofymov, A; Troncon, C; Trottier-McDonald, M; Trovatelli, M; Truong, L; Trzebinski, M; Trzupek, A; Tsang, K W; Tseng, J C-L; Tsiareshka, P V; Tsipolitis, G; Tsirintanis, N; Tsiskaridze, S; Tsiskaridze, V; Tskhadadze, E G; Tsui, K M; Tsukerman, I I; Tsulaia, V; Tsuno, S; Tsybychev, D; Tu, Y; Tudorache, A; Tudorache, V; Tulbure, T T; Tuna, A N; Tupputi, S A; Turchikhin, S; Turgeman, D; Turk Cakir, I; Turra, R; Tuts, P M; Ucchielli, G; Ueda, I; Ughetto, M; Ukegawa, F; Unal, G; Undrus, A; Unel, G; Ungaro, F C; Unno, Y; Unverdorben, C; Urban, J; Urquijo, P; Urrejola, P; Usai, G; Usui, J; Vacavant, L; Vacek, V; Vachon, B; Vadla, K O H; Vaidya, A; Valderanis, C; Valdes Santurio, E; Valente, M; Valentinetti, S; Valero, A; Valéry, L; Valkar, S; Vallier, A; Valls Ferrer, J A; Van Den Wollenberg, W; van der Graaf, H; van Gemmeren, P; Van Nieuwkoop, J; van Vulpen, I; van Woerden, M C; Vanadia, M; Vandelli, W; Vaniachine, A; Vankov, P; Vardanyan, G; Vari, R; Varnes, E W; Varni, C; Varol, T; Varouchas, D; Vartapetian, A; Varvell, K E; Vasquez, J G; Vasquez, G A; Vazeille, F; Vazquez Schroeder, T; Veatch, J; Veeraraghavan, V; Veloce, L M; Veloso, F; Veneziano, S; Ventura, A; Venturi, M; Venturi, N; Venturini, A; Vercesi, V; Verducci, M; Verkerke, W; Vermeulen, A T; Vermeulen, J C; Vetterli, M C; Viaux Maira, N; Viazlo, O; Vichou, I; Vickey, T; Vickey Boeriu, O E; Viehhauser, G H A; Viel, S; Vigani, L; Villa, M; Villaplana Perez, M; Vilucchi, E; Vincter, M G; Vinogradov, V B; Vishwakarma, A; Vittori, C; Vivarelli, I; Vlachos, S; Vogel, M; Vokac, P; Volpi, G; von der Schmitt, H; von Toerne, E; Vorobel, V; Vorobev, K; Vos, M; Voss, R; Vossebeld, J H; Vranjes, N; Vranjes Milosavljevic, M; Vrba, V; Vreeswijk, M; Vuillermet, R; Vukotic, I; Wagner, P; Wagner, W; Wagner-Kuhr, J; Wahlberg, H; Wahrmund, S; Wakabayashi, J; Walder, J; Walker, R; Walkowiak, W; Wallangen, V; Wang, C; Wang, C; Wang, F; Wang, H; Wang, H; Wang, J; Wang, J; Wang, Q; Wang, R; Wang, S M; Wang, T; Wang, W; Wang, W; Wang, Z; Wanotayaroj, C; Warburton, A; Ward, C P; Wardrope, D R; Washbrook, A; Watkins, P M; Watson, A T; Watson, M F; Watts, G; Watts, S; Waugh, B M; Webb, A F; Webb, S; Weber, M S; Weber, S W; Weber, S A; Webster, J S; Weidberg, A R; Weinert, B; Weingarten, J; Weirich, M; Weiser, C; Weits, H; Wells, P S; Wenaus, T; Wengler, T; Wenig, S; Wermes, N; Werner, M D; Werner, P; Wessels, M; Weston, T D; Whalen, K; Whallon, N L; Wharton, A M; White, A S; White, A; White, M J; White, R; Whiteson, D; Whitmore, B W; Wickens, F J; Wiedenmann, W; Wielers, M; Wiglesworth, C; Wiik-Fuchs, L A M; Wildauer, A; Wilk, F; Wilkens, H G; Williams, H H; Williams, S; Willis, C; Willocq, S; Wilson, J A; Wingerter-Seez, I; Winkels, E; Winklmeier, F; Winston, O J; Winter, B T; Wittgen, M; Wobisch, M; Wolf, T M H; Wolff, R; Wolter, M W; Wolters, H; Wong, V W S; Worm, S D; Wosiek, B K; Wotschack, J; Wozniak, K W; Wu, M; Wu, S L; Wu, X; Wu, Y; Wyatt, T R; Wynne, B M; Xella, S; Xi, Z; Xia, L; Xu, D; Xu, L; Xu, T; Yabsley, B; Yacoob, S; Yamaguchi, D; Yamaguchi, Y; Yamamoto, A; Yamamoto, S; Yamanaka, T; Yamatani, M; Yamauchi, K; Yamazaki, Y; Yan, Z; Yang, H; Yang, H; Yang, Y; Yang, Z; Yao, W-M; Yap, Y C; Yasu, Y; Yatsenko, E; Yau Wong, K H; Ye, J; Ye, S; Yeletskikh, I; Yigitbasi, E; Yildirim, E; Yorita, K; Yoshihara, K; Young, C; Young, C J S; Yu, J; Yu, J; Yuen, S P Y; Yusuff, I; Zabinski, B; Zacharis, G; Zaidan, R; Zaitsev, A M; Zakharchuk, N; Zalieckas, J; Zaman, A; Zambito, S; Zanzi, D; Zeitnitz, C; Zemaityte, G; Zemla, A; Zeng, J C; Zeng, Q; Zenin, O; Ženiš, T; Zerwas, D; Zhang, D; Zhang, F; Zhang, G; Zhang, H; Zhang, J; Zhang, L; Zhang, L; Zhang, M; Zhang, P; Zhang, R; Zhang, R; Zhang, X; Zhang, Y; Zhang, Z; Zhao, X; Zhao, Y; Zhao, Z; Zhemchugov, A; Zhou, B; Zhou, C; Zhou, L; Zhou, M; Zhou, M; Zhou, N; Zhu, C G; Zhu, H; Zhu, J; Zhu, Y; Zhuang, X; Zhukov, K; Zibell, A; Zieminska, D; Zimine, N I; Zimmermann, C; Zimmermann, S; Zinonos, Z; Zinser, M; Ziolkowski, M; Živković, L; Zobernig, G; Zoccoli, A; Zou, R; Zur Nedden, M; Zwalinski, L

    2017-11-03

    Several extensions of the standard model predict associated production of dark-matter particles with a Higgs boson. Such processes are searched for in final states with missing transverse momentum and a Higgs boson decaying to a bb[over ¯] pair with the ATLAS detector using 36.1  fb^{-1} of pp collisions at a center-of-mass energy of 13 TeV at the LHC. The observed data are in agreement with the standard model predictions and limits are placed on the associated production of dark-matter particles and a Higgs boson.

  2. 4-1BB-Enhanced Expansion of CD8+ TIL from Triple-Negative Breast Cancer Unveils Mutation-Specific CD8+ T Cells.

    PubMed

    Harao, Michiko; Forget, Marie-Andrée; Roszik, Jason; Gao, Hui; Babiera, Gildy V; Krishnamurthy, Savitri; Chacon, Jessica A; Li, Shumin; Mittendorf, Elizabeth A; DeSnyder, Sarah M; Rockwood, Korrene F; Bernatchez, Chantale; Ueno, Naoto T; Radvanyi, Laszlo G; Vence, Luis; Haymaker, Cara; Reuben, James M

    2017-06-01

    Triple-negative breast cancer (TNBC) highly infiltrated with CD8 + tumor-infiltrating lymphocytes (TIL) has been associated with improved prognosis. This observation led us to hypothesize that CD8 + TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8 + TILs in solid cancers other than in melanoma. To overcome this obstacle, we used an agonistic antibody (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8 + T cells. This approach was first utilized in melanoma and, in this study, led to advantageous growth of TILs for the majority of TNBC tumors tested. The agonistic antibody was only added in the initial setting of the culture and yet favored the propagation of CD8 + TILs from TNBC tumors. These expanded CD8 + TILs were capable of cytotoxic functions and were successfully utilized to demonstrate the presence of immunogenic mutations in autologous TNBC tumor tissue without recognition of the wild-type counterpart. Our findings open the way for a successful adoptive immunotherapy for TNBC. Cancer Immunol Res; 5(6); 439-45. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. Search for the standard model Higgs boson decaying to a bb pair in events with one charged lepton and large missing transverse energy using the full CDF data set.

    PubMed

    Aaltonen, T; Álvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Appel, J A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Auerbach, B; Aurisano, A; Azfar, F; Badgett, W; Bae, T; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauce, M; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Binkley, M E; Bisello, D; Bizjak, I; Bland, K R; Blumenfeld, B; Bocci, A; Bodek, A; Bortoletto, D; Boudreau, J; Boveia, A; Brigliadori, L; Bromberg, C; Brucken, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Calamba, A; Calancha, C; Camarda, S; Campanelli, M; Campbell, M; Canelli, F; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chung, W H; Chung, Y S; Ciocci, M A; Clark, A; Clarke, C; Compostella, G; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Crescioli, F; Cuevas, J; Culbertson, R; Dagenhart, D; d'Ascenzo, N; Datta, M; de Barbaro, P; Dell'Orso, M; Demortier, L; Deninno, M; Devoto, F; d'Errico, M; Di Canto, A; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Dorigo, M; Dorigo, T; Ebina, K; Elagin, A; Eppig, A; Erbacher, R; Errede, S; Ershaidat, N; Eusebi, R; Farrington, S; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Funakoshi, Y; Furic, I; Gallinaro, M; Garcia, J E; Garfinkel, A F; Garosi, P; Gerberich, H; Gerchtein, E; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Ginsburg, C M; Giokaris, N; Giromini, P; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldin, D; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Grinstein, S; Grosso-Pilcher, C; Group, R C; Guimaraes da Costa, J; Hahn, S R; Halkiadakis, E; Hamaguchi, A; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harr, R F; Hatakeyama, K; Hays, C; Heck, M; Heinrich, J; Herndon, M; Hewamanage, S; Hocker, A; Hopkins, W; Horn, D; Hou, S; Hughes, R E; Hurwitz, M; Husemann, U; Hussain, N; Hussein, M; Huston, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeans, D T; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Junk, T R; Kamon, T; Karchin, P E; Kasmi, A; Kato, Y; Ketchum, W; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kim, Y J; Kimura, N; Kirby, M; Klimenko, S; Knoepfel, K; Kondo, K; Kong, D J; Konigsberg, J; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Kruse, M; Krutelyov, V; Kuhr, T; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; LeCompte, T; Lee, E; Lee, H S; Lee, J S; Lee, S W; Leo, S; Leone, S; Lewis, J D; Limosani, A; Lin, C-J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, H; Liu, Q; Liu, T; Lockwitz, S; Loginov, A; Lucchesi, D; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; Madrak, R; Maeshima, K; Maestro, P; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Martínez, M; Mastrandrea, P; Matera, K; Mattson, M E; Mazzacane, A; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Mesropian, C; Miao, T; Mietlicki, D; Mitra, A; Miyake, H; Moed, S; Moggi, N; Mondragon, M N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mukherjee, A; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakano, I; Napier, A; Nett, J; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Noh, S Y; Norniella, O; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Ortolan, L; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pilot, J; Pitts, K; Plager, C; Pondrom, L; Poprocki, S; Potamianos, K; Prokoshin, F; Pranko, A; Ptohos, F; Punzi, G; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Rescigno, M; Riddick, T; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Ruffini, F; Ruiz, A; Russ, J; Rusu, V; Safonov, A; Sakumoto, W K; Sakurai, Y; Santi, L; Sato, K; Saveliev, V; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Seidel, S; Seiya, Y; Semenov, A; Sforza, F; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shochet, M; Shreyber-Tecker, I; Simonenko, A; Sinervo, P; Sliwa, K; Smith, J R; Snider, F D; Soha, A; Sorin, V; Song, H; Squillacioti, P; Stancari, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Sudo, Y; Sukhanov, A; Suslov, I; Takemasa, K; Takeuchi, Y; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thome, J; Thompson, G A; Thomson, E; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Ukegawa, F; Uozumi, S; Varganov, A; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vila, I; Vilar, R; Vizán, J; Vogel, M; Volpi, G; Wagner, P; Wagner, R L; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Wester, W C; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Wick, F; Williams, H H; Wilson, J S; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, H; Wright, T; Wu, X; Wu, Z; Yamamoto, K; Yamato, D; Yang, T; Yang, U K; Yang, Y C; Yao, W-M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanetti, A; Zeng, Y; Zhou, C; Zucchelli, S

    2012-09-14

    We present a search for the standard model Higgs boson produced in association with a W boson in sqrt[s]=1.96  TeV pp collision data collected with the CDF II detector at the Tevatron corresponding to an integrated luminosity of 9.45  fb(-1). In events consistent with the decay of the Higgs boson to a bottom-quark pair and the W boson to an electron or muon and a neutrino, we set 95% credibility level upper limits on the WH production cross section times the H→bb branching ratio as a function of Higgs boson mass. At a Higgs boson mass of 125  GeV/c(2), we observe (expect) a limit of 4.9 (2.8) times the standard model value.

  4. A histomorphometric comparison of Bio-Oss alone versus Bio-Oss and platelet-derived growth factor for sinus augmentation: a postsurgical assessment.

    PubMed

    Froum, Stuart J; Wallace, Stephen; Cho, Sang-Choon; Rosenburg, Edwin; Froum, Scott; Schoor, Robert; Mascarenhas, Patrick; Tarnow, Dennis P; Corby, Patricia; Elian, Nicolas; Fickl, Stefan; Ricci, John; Hu, Bin; Bromage, Timothy; Khouly, Ismael

    2013-01-01

    The purpose of this study was to assess vital bone formation at 4 to 5 months and 7 to 9 months following sinus augmentation with anorganic bovine bone matrix (ABBM) with and without recombinant human platelet-derived growth factor (rhPDGF). Twenty-four subjects received bilateral sinus elevation surgery with ABBM on one side and ABBM and rhPDGF on the contralateral side. Twelve patients had core sampling at 4 to 5 months and 12 patients at 7 to 9 months postoperatively. In subjects with cores taken at 4 to 5 months, mean vital bone, connective tissue, and residual graft were 11.8%, 54.1%, and 33.6%, respectively, with ABBM alone. Cores of sinuses filled with ABBM and rhPDGF showed mean 21.1% vital bone, 51.4% connective tissue, and 24.8% residual graft. Paired t test showed a statistically significant difference in vital bone. In cores taken at 7 to 9 months, the values for ABBM alone and ABBM + rhPDGF were 21.4% vs 19.5% vital bone, 28.4% vs 44.2% connective tissue, and 40.3% residual graft vs 35.5%. There was no statistically significant difference in vital bone at 7 to 9 months after surgery. Test and control groups showed clinically acceptable levels of vital bone both at 4 to 5 months and 7 to 9 months postsurgery. However, vital bone formation was significantly greater in the 4- to 5-month sections of ABBM + rhPDGF vs the Bio-Oss alone. In the 7- to 9-month specimens, this difference disappeared. More rapid formation of vital bone with the addition of rhPDGF may allow for earlier implant placement.

  5. Dual growth factor-immobilized asymmetrically porous membrane for bone-to-tendon interface regeneration on rat patellar tendon avulsion model.

    PubMed

    Kim, Joong-Hyun; Oh, Se Heang; Min, Hyun Ki; Lee, Jin Ho

    2018-01-01

    Insufficient repair of the bone-to-tendon interface (BTI) with structural/compositional gradients has been a significant challenge in orthopedics. In this study, dual growth factor (platelet-derived growth factor-BB [PDGF-BB] and bone morphogenetic protein-2 [BMP-2])-immobilized polycaprolactone (PCL)/Pluronic F127 asymmetrically porous membrane was fabricated to estimate its feasibility as a potential strategy for effective regeneration of BTI injury. The growth factors immobilized (via heparin-intermediated interactions) on the membrane were continuously released for up to ∼80% of the initial loading amount after 5 weeks without a significant initial burst. From the in vivo animal study using a rat patellar tendon avulsion model, it was observed that the PDGF-BB/BMP-2-immobilized membrane accelerates the regeneration of the BTI injury, probably because of the continuous release of both growth factors (biological stimuli) and their complementary effect to create a multiphasic structure (bone, fibrocartilage, and tendon) like a native structure, as well as the role of the asymmetrically porous membrane as a physical barrier (nanopore side; prevention of fibrous tissue invasion into the defect site) and scaffold (micropore side; guidance for tissue regeneration). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 115-125, 2018. © 2017 Wiley Periodicals, Inc.

  6. Search for a new resonance decaying to a W or Z boson and a Higgs boson in the ℓℓ/ℓν/νν + bb¯ final states with the ATLAS detector

    DOE PAGES

    Aad, G.

    2015-06-16

    A search for a new resonance decaying to a W or Z boson and a Higgs boson in the ℓℓ/ℓν/νν+bb¯ final states is performed using 20.3 fb -1 of pp collision data recorded at √s = 8 TeV with the ATLAS detector at the Large Hadron Collider. The search is conducted by examining the WH / ZH invariant mass distribution for a localized excess. Thus, no significant deviation from the Standard Model background prediction is observed. The results are interpreted in terms of constraints on the Minimal Walking Technicolor model and on a simplified approach based on a phenomenological Lagrangianmore » of Heavy Vector Triplets.« less

  7. Complete mitochondrial genome sequence of black mustard (Brassica nigra; BB) and comparison with Brassica oleracea (CC) and Brassica carinata (BBCC).

    PubMed

    Yamagishi, Hiroshi; Tanaka, Yoshiyuki; Terachi, Toru

    2014-11-01

    Crop species of Brassica (Brassicaceae) consist of three monogenomic species and three amphidiploid species resulting from interspecific hybridizations among them. Until now, mitochondrial genome sequences were available for only five of these species. We sequenced the mitochondrial genome of the sixth species, Brassica nigra (nuclear genome constitution BB), and compared it with those of Brassica oleracea (CC) and Brassica carinata (BBCC). The genome was assembled into a 232 145 bp circular sequence that is slightly larger than that of B. oleracea (219 952 bp). The genome of B. nigra contained 33 protein-coding genes, 3 rRNA genes, and 17 tRNA genes. The cox2-2 gene present in B. oleracea was absent in B. nigra. Although the nucleotide sequences of 52 genes were identical between B. nigra and B. carinata, the second exon of rps3 showed differences including an insertion/deletion (indel) and nucleotide substitutions. A PCR test to detect the indel revealed intraspecific variation in rps3, and in one line of B. nigra it amplified a DNA fragment of the size expected for B. carinata. In addition, the B. carinata lines tested here produced DNA fragments of the size expected for B. nigra. The results indicate that at least two mitotypes of B. nigra were present in the maternal parents of B. carinata.

  8. Effect of chitosan and coagulation factors on the wound repair phenotype of bioengineered blood clots.

    PubMed

    Hoemann, Caroline D; Marchand, Catherine; Rivard, Georges-Etienne; El-Gabalawy, Hani; Poubelle, Patrice E

    2017-11-01

    Controlling the blood clot phenotype in a surgically prepared wound is an evolving concept in scaffold-guided tissue engineering. Here, we investigated the effect of added chitosan (80% or 95% Degree of Deacetylation, DDA) or coagulation factors (recombinant human Factor VIIa, Tissue Factor, thrombin) on inflammatory factors released by blood clots. We tested the hypothesis that 80% DDA chitosan specifically enhances leukotriene B 4 (LTB 4 ) production. Human or rabbit whole blood was combined with isotonic chitosan solutions, coagulation factors, or lipopolysaccharide, cultured in vitro at 37°C, and after 4hours the serum was assayed for LTB 4 or inflammatory factors. Only 80% DDA chitosan clots produced around 15-fold more LTB 4 over other clots including 95% DDA chitosan clots. All serum contained high levels of PDGF-BB and CXCL8. Normal clots produced very low type I cytokines compared to lipopolysaccharide clots, with even lower IL-6 and IL-12 and more CCL3/CCL4 produced by chitosan clots. Coagulation factors had no detectable effect on clot phenotype. Conclusion In blood clots from healthy individuals, 80% DDA chitosan has a unique influence of inducing more LTB 4 , a potent neutrophil chemoattractant, with similar production of PDGF-BB and CXCL8, and lower type I cytokines, compared to whole blood clots. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. The interrelationship of complement-activation fragments and angiogenesis-related factors in early pregnancy and their association with pre-eclampsia

    PubMed Central

    Lynch, AM; Murphy, JR; Gibbs, RS; Levine, RJ; Giclas, PC; Salmon, JE; Holers, VM

    2016-01-01

    Objective To determine the interrelationships during early pregnancy of complement-activation fragments Bb, C3a and sC5b-9, and angiogenesis-related factors placental growth factor (PiGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), and their associations with pre-eclampsia. Design Prospective cohort study. Setting Denver complement study (June 2005–June 2008). Population A total of 668 pregnant women with singleton gestations, recruited between 10 and 15 weeks of gestation. Methods Using univariable and multivariable logistic regression analysis, concentrations of complement-activation fragments and angiogenesis-related factors were compared between 10 and 15 weeks of gestation in women who subsequently did or did not develop pre-eclampsia. Interrelationships between these variables were tested using the non-parametric Spearman rank correlation coefficient. Main outcome measure Pre-eclampsia. The association of complement-activation fragments and angiogenesis-related factors with obesity was also examined. Results The mean (±SD) levels of complement Bb in early pregnancy among women who did and did not develop pre-eclampsia were 0.84 (±0.26) µg/ml and 0.69 (±0.2) µg/ml, respectively (P = 0.001). Concentrations of PiGF were significantly (P = 0.01) lower (31 ± 12 pg/ml) in early pregnancy in the pre-eclamptic group of women, as compared with the normotensive group (39 ± 32 pg/ml). The adjusted odds ratio (AOR) of Bb and PiGF were 2.1 (CI = 1.4–3.1, P < 0.0003) and 0.2 (CI = 0.07–0.7, P = 0.01), respectively. There was no significant difference in the levels of C3a, sC5b-9, sFlt-1 and sEng in early pregnancy among women who developed pre-eclampsia, compared with women who remained normotensive during pregnancy. Higher levels of Bb (P = 0.0001) and C3a (P = 0.03), and lower levels of sFlt-1 (P = 0.0002) and sEng (P = 0.0001) were found among women with obesity, compared with non-obese controls. No meaningful relationships

  10. Comparison of fluence-to-dose conversion coefficients for deuterons, tritons and helions.

    PubMed

    Copeland, Kyle; Friedberg, Wallace; Sato, Tatsuhiko; Niita, Koji

    2012-02-01

    Secondary radiation in aircraft and spacecraft includes deuterons, tritons and helions. Two sets of fluence-to-effective dose conversion coefficients for isotropic exposure to these particles were compared: one used the particle and heavy ion transport code system (PHITS) radiation transport code coupled with the International Commission on Radiological Protection (ICRP) reference phantoms (PHITS-ICRP) and the other the Monte Carlo N-Particle eXtended (MCNPX) radiation transport code coupled with modified BodyBuilder™ phantoms (MCNPX-BB). Also, two sets of fluence-to-effective dose equivalent conversion coefficients calculated using the PHITS-ICRP combination were compared: one used quality factors based on linear energy transfer; the other used quality factors based on lineal energy (y). Finally, PHITS-ICRP effective dose coefficients were compared with PHITS-ICRP effective dose equivalent coefficients. The PHITS-ICRP and MCNPX-BB effective dose coefficients were similar, except at high energies, where MCNPX-BB coefficients were higher. For helions, at most energies effective dose coefficients were much greater than effective dose equivalent coefficients. For deuterons and tritons, coefficients were similar when their radiation weighting factor was set to 2.

  11. Burning of olive tree branches: a major organic aerosol source in the Mediterranean

    NASA Astrophysics Data System (ADS)

    Kostenidou, E.; Kaltsonoudis, C.; Tsiflikiotou, M.; Louvaris, E.; Russell, L. M.; Pandis, S. N.

    2013-09-01

    Aerosol produced during the burning of olive tree branches was characterized with both direct source sampling (using a mobile smog chamber) and with ambient measurements during the burning season. The fresh particles were composed of 80% organic matter, 8-10% black carbon (BC), 5% potassium, 3-4% sulfate, 2-3% nitrate and 0.8% chloride. Almost half of the fresh olive tree branches burning organic aerosol (otBB-OA) consisted of alkane groups. Their mode diameter was close to 70 nm. The oxygen to carbon (O : C) ratio of the fresh otBB-OA was 0.29 ± 0.04. The mass fraction of levoglucosan in PM1 was 0.034-0.043, relatively low in comparison with most fuel types. This may lead to an underestimation of the otBB-OA contribution if levoglucosan is being used as a wood burning tracer. Chemical aging was observed during smog chamber experiments, as f44 and O : C ratio increased, due to reactions with OH radicals and O3. The otBB-OA AMS mass spectrum differs from the other published biomass burning spectra, with a main difference at m/z 60, used as levoglucosan tracer. In addition to particles, volatile organic compounds (VOCs) such as methanol, acetonitrile, acrolein, benzene, toluene and xylenes are also emitted. Positive matrix factorization (PMF) was applied to the ambient organic aerosol data and 3 factors could be identified: OOA (oxygenated organic aerosol, 55%), HOA (hydrocarbon-like organic aerosol, 11.3%) and otBB-OA 33.7%. The fresh chamber otBB-OA AMS spectrum is close to the PMF otBB-OA spectrum and resembles the ambient mass spectrum during olive tree branches burning periods. We estimated an otBB-OA emission factor of 3.5 ± 0.9 g kg-1. Assuming that half of the olive tree branches pruned is burned in Greece, 2300 ± 600 tons of otBB-OA are emitted every year. This activity is one of the most important fine aerosol sources during the winter months in Mediterranean countries.

  12. Burning of olive tree branches: a major organic aerosol source in the Mediterranean

    NASA Astrophysics Data System (ADS)

    Kostenidou, E.; Kaltsonoudis, C.; Tsiflikiotou, M.; Louvaris, E.; Russell, L. M.; Pandis, S. N.

    2013-03-01

    Aerosol produced during the burning of olive tree branches was characterized with both direct source-sampling (using a mobile smog chamber) and with ambient measurements during the burning season. The fresh particles were composed of 80% organic matter, 8-10% black carbon (BC), 5% potassium, 3-4% sulfate, 2-3% nitrate and 0.8% chloride. Almost half of the fresh olive tree branches burning organic aerosol (otBB-OA) consisted of alkane groups. Their mode diameter was close to 70 nm. The oxygen to carbon (O:C) ratio of the fresh otBB-OA was 0.29 ± 0.04. The mass fraction of levoglucosan in PM1 was 0.034-0.043, relatively low in comparison with most fuel types. This may lead to an underestimation of the otBB-OA contribution if levoglucosan is being used as a wood burning tracer. Chemical aging was observed during smog chamber experiments, as f44 and O:C ratio increased, due to reactions with OH radicals and O3. The otBB-OA AMS mass spectrum differs from the other published biomass burning spectra, with a main difference at m/z 60, used as levoglucosan tracer. In addition to particles, volatile organic compounds (VOCs) such as methanol, acetonitrile, acrolein, benzene, toluene and xylenes are also emitted. Positive matrix factorization (PMF) was applied to the ambient organic aerosol data and 3 factors could be identified: OOA (oxygenated organic aerosol, 55%), HOA (hydrocarbon-like organic aerosol, 11.3%) and otBB-OA 33.7%. The fresh chamber otBB-OA AMS spectrum is close to the PMF otBB-OA spectrum and resembles the ambient mass spectrum during olive tree branches burning periods. We estimated an otBB-OA emission factor of 3.5 ± 0.2 g kg-1. Assuming that half of the olive tree branches pruned is burned in Greece 2280 ± 140 tons of otBB-OA are emitted every year. This activity is one of the most important fine aerosol sources during the winter months in the Mediterranean countries.

  13. Protective Effect of a Synbiotic against Multidrug-Resistant Acinetobacter baumannii in a Murine Infection Model

    PubMed Central

    Takahashi, Akira; Yuki, Norikatsu; Kaji, Rumi; Takahashi, Takuya; Nomoto, Koji

    2016-01-01

    This study investigated the ability of the probiotic Bifidobacterium breve strain Yakult (BbY) to protect against infection, as well as the potentiation of BbY activity by the synbiotic combination of BbY and prebiotic galactooligosaccharides (GOS). The study employed a mouse model of lethal intestinal multidrug-resistant Acinetobacter baumannii (MDRAb) infection. The endogenous intestinal microbiota was disrupted by the administration of multiple antibiotics, causing the loss of endogenous Bifidobacterium. Oral infection of these mice with MDRAb resulted in marked growth of this organism. Additional treatment of the infected mice with a sublethal dose of 5-fluorouracil (5-FU) induced systemic invasion by MDRAb and subsequent animal death. The continuous oral administration of BbY increased the survival rate and inhibited the intestinal growth and invasion by MDRAb in the infection model. Disruptions of the intestinal environment and barrier function in the infected mice were attenuated by BbY. Protection against the MDRAb infection was markedly potentiated by a synbiotic combination of BbY and GOS, although GOS by itself did not provide protection. Negative correlations were observed between intestinal MDRAb and BbY counts or acetic acid levels; positive correlations were observed between acetic acid levels and intestinal epithelium expression of tight-junction-related genes. These results demonstrated that the probiotic and synbiotic markedly potentiated protection against fatal intestinal infection caused by a multidrug-resistant bacterium. Probiotics and synbiotics are presumed to provide protection by compensation for the disrupted indigenous populations, thereby maintaining the intestinal environments and barrier functions otherwise targeted during opportunistic infection by MDRAb. PMID:26953197

  14. Percolation analysis for cosmic web with discrete points

    NASA Astrophysics Data System (ADS)

    Zhang, Jiajun; Cheng, Dalong; Chu, Ming-Chung

    2016-03-01

    Percolation analysis has long been used to quantify the connectivity of the cosmic web. Unlike most of the previous works using density field on grids, we have studied percolation analysis based on discrete points. Using a Friends-of-Friends (FoF) algorithm, we generate the S-bb relation, between the fractional mass of the largest connected group (S) and the FoF linking length (bb). We propose a new model, the Probability Cloud Cluster Expansion Theory (PCCET) to relate the S-bb relation with correlation functions. We show that the S-bb relation reflects a combination of all orders of correlation functions. We have studied the S-bb relation with simulation and find that the S-bb relation is robust against redshift distortion and incompleteness in observation. From the Bolshoi simulation, with Halo Abundance Matching (HAM), we have generated a mock galaxy catalogue. Good matching of the projected two-point correlation function with observation is confirmed. However, comparing the mock catalogue with the latest galaxy catalogue from SDSS DR12, we have found significant differences in their S-bb relations. This indicates that the mock catalogue cannot accurately recover higher order correlation functions than the two-point correlation function, which reveals the limit of HAM method.

  15. Salivary mutans streptococci and lactobacilli modulations in young children on consumption of probiotic ice-cream containing Bifidobacterium lactis Bb12 and Lactobacillus acidophilus La5.

    PubMed

    Singh, Richa Polka; Damle, Satyawan Gangaram; Chawla, Amrita

    2011-11-01

    To compare the levels of mutans streptococci and lactobacilli in saliva of school children, before and after consumption of probiotic and control ice-cream. A double-blind, cross-over, placebo-controlled trial was carried out in forty, 12-14 year-old children, with no clinically detectable caries. The selected children were randomized equally into two groups I and II. Following an initial run-in period of 1 week, children in group I and II were given ice-creams 'A' and 'B', respectively, for 10 days. Being a cross-over study, the ice-creams were interchanged in the two groups after a 2-week wash-out period. Saliva samples at baseline and follow-up were assessed using Dentocult SM and Dentocult LB kits. On statistical evaluation, it was seen that probiotic ice-cream brought about a statistically significant reduction (p-value = 0.003) in salivary mutans streptococci levels with no significant effect on lactobacilli levels. In conclusion, probiotic ice-cream containing Bifidobacterium lactis Bb-12 ATCC27536 and Lactobacillus acidophilus La-5 can reduce the levels of certain caries-associated micro-organisms in saliva.

  16. Docking modes of BB-3497 into the PDF active site--a comparison of the pure MM and QM/MM based docking strategies.

    PubMed

    Kumari, Tripti; Issar, Upasana; Kakkar, Rita

    2014-01-01

    Peptide deformylase (PDF) has emerged as an important antibacterial drug target. Considerable effort is being directed toward developing peptidic and non-peptidic inhibitors for this metalloprotein. In this work, the known peptidic inhibitor BB-3497 and its various ionization and tautomeric states are evaluated for their inhibition efficiency against PDF using a molecular mechanics (MM) approach as well as a mixed quantum mechanics/molecular mechanics (QM/MM) approach, with an aim to understand the interactions in the binding site. The evaluated Gibbs energies of binding with the mixed QM/MM approach are shown to have the best predictive power. The experimental pose is found to have the most negative Gibbs energy of binding, and also the smallest strain energy. A quantum mechanical evaluation of the active site reveals the requirement of strong chelation by the ligand with the metal ion. The investigated ligand chelates the metal ion through the two oxygens of its reverse hydroxamate moiety, particularly the N-O(-) oxygen, forming strong covalent bonds with the metal ion, which is penta-coordinated. In the uninhibited state, the metal ion is tetrahedrally coordinated, and hence chelation with the inhibitor is associated with an increase of the metal ion coordination. Thus, the strong binding of the ligand at the binding site is accounted for.

  17. Murrayafoline A Induces a G0/G1-Phase Arrest in Platelet-Derived Growth Factor-Stimulated Vascular Smooth Muscle Cells

    PubMed Central

    Han, Joo-Hui; Kim, Yohan; Jung, Sang-Hyuk; Lee, Jung-Jin; Park, Hyun-Soo; Song, Gyu-Yong; Cuong, Nguyen Manh; Kim, Young Ho

    2015-01-01

    The increased potential for vascular smooth muscle cell (VSMC) growth is a key abnormality in the development of atherosclerosis and post-angioplasty restenosis. Abnormally high activity of platelet-derived growth factor (PDGF) is believed to play a central role in the etiology of these pathophysiological situations. Here, we investigated the anti-proliferative effects and possible mechanism(s) of murrayafoline A, a carbazole alkaloid isolated from Glycosmis stenocarpa Guillamin (Rutaceae), on PDGF-BB-stimulated VSMCs. Murrayafoline A inhibited the PDGF-BB-stimulated proliferation of VSMCs in a concentration-dependent manner, as measured using a non-radioactive colorimetric WST-1 assay and direct cell counting. Furthermore, murrayafoline A suppressed the PDGF-BB-stimulated progression through G0/G1 to S phase of the cell cycle, as measured by [3H]-thymidine incorporation assay and cell cycle progression analysis. This anti-proliferative action of murrayafoline A, arresting cell cycle progression at G0/G1 phase in PDGF-BB-stimulated VSMCs, was mediated via down-regulation of the expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, and proliferating cell nuclear antigen (PCNA), and the phosphorylation of retinoblastoma protein (pRb). These results indicate that murrayafoline A may be useful in preventing the progression of vascular complications such as restenosis after percutaneous transluminal coronary angioplasty and atherosclerosis. PMID:26330754

  18. Glycogen phosphorylase isoenzyme BB plasma kinetics is not related to myocardial ischemia induced by exercise stress echo test.

    PubMed

    Dobric, Milan; Giga, Vojislav; Beleslin, Branko; Ignjatovic, Svetlana; Paunovic, Ivana; Stepanovic, Jelena; Djordjevic-Dikic, Ana; Kostic, Jelena; Nedeljkovic, Ivana; Nedeljkovic, Milan; Tesic, Milorad; Dajak, Marijana; Ostojic, Miodrag

    2013-10-01

    Glycogen phosphorylase BB (GPBB) is released from cardiac cells during myocyte damage. Previous studies have shown contradictory results regarding the relation of enzyme release and reversible myocardial ischemia. The aim of this study was to determine the plasma kinetics of GPBB as a response to the exercise stress echocardiographic test (ESET), and to define the relationship between myocardial ischemia and enzyme plasma concentrations. We studied 46 consecutive patients undergoing ESET, with recent coronary angiography. In all patients, a submaximal stress echo test according to Bruce protocol was performed. Concentration of GPBB was measured in peripheral blood that was sampled 5 min before and 10, 30 and 60 min after ESET. There was significant increase of GPBB concentration after the test (p=0.021). Significant increase was detected 30 min (34.9% increase, p=0.021) and 60 min (34.5% increase, p=0.016) after ESET. There was no significant effect of myocardial ischemia on GPBB concentrations (p=0.126), and no significant interaction between sampling intervals and myocardial ischemia, suggesting a similar release profile of GPBB in ischemic and non-ischemic conditions (p=0.558). Patients in whom ESET was terminated later (stages 4 or 5 of standard Bruce protocol; n=13) had higher GPBB concentrations than patients who terminated ESET earlier (stages 1, 2 or 3; n=33) (p=0.049). Baseline GPBB concentration was not correlated to any of the patients' demographic, clinical and hemodynamic characteristics. GPBB plasma concentration increases after ESET, and it is not related to inducible myocardial ischemia. However, it seems that GPBB release during ESET might be related to exercise load/duration.

  19. Concentration of platelets and growth factors in platelet-rich plasma from Goettingen minipigs.

    PubMed

    Jungbluth, Pascal; Grassmann, Jan-Peter; Thelen, Simon; Wild, Michael; Sager, Martin; Windolf, Joachim; Hakimi, Mohssen

    2014-01-01

    In minipigs little is known about the concentration of growth factors in plasma, despite their major role in several patho-physiological processes such as healing of fractures. This prompted us to study the concentration of platelets and selected growth factors in plasma and platelet-rich plasma (PRP) preparation of sixteen Goettingen minipigs. Platelet concentrations increased significantly in PRP in comparison to native blood plasma. Generally, significant increase in the concentration of all growth factors tested was observed in the PRP in comparison to the corresponding plasma or serum. Five of the plasma samples examined contained detectable levels of bone morphogenic protein 2 (BMP-2) whereas eleven of the plasma or serum samples contained minimal amounts of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF-bb) respectively. On the other hand variable concentrations of bone morphogenic protein 7 (BMP-7) and transforming growth factor β1 (TGF-β1) were measured in all plasma samples. In contrast, all PRP samples contained significantly increased amounts of growth factors. The level of BMP-2, BMP-7, TGF-β1, VEGF and PDGF-bb increased by 17.6, 1.5, 7.1, 7.2 and 103.3 fold, in comparison to the corresponding non-enriched preparations. Moreover significant positive correlations were found between platelet count and the concentrations of BMP-2 (r=0.62, p<0.001), TGF-β1 (r=0.85, p<0.001), VEGF (r=0.46, p<0.01) and PDGF-bb (r=0.9, p<0.001). Our results demonstrate that selected growth factors are present in the platelet-rich plasma of minipigs which might thus serve as a source of autologous growth factors.

  20. Feeding Blueberry Diets to Young Rats Dose-Dependently Inhibits Bone Resorption through Suppression of RANKL in Stromal Cells

    PubMed Central

    Zhang, Jian; Lazarenko, Oxana P.; Kang, Jie; Blackburn, Michael L.; Ronis, Martin J. J.; Badger, Thomas M.; Chen, Jin-Ran

    2013-01-01

    Previous studies have demonstrated that weanling rats fed AIN-93G semi-purified diets supplemented with 10% whole blueberry (BB) powder for two weeks beginning on postnatal day 21 (PND21) significantly increased bone formation at PND35. However, the minimal level of dietary BB needed to produce these effects is, as yet, unknown. The current study examined the effects of three different levels of BB diet supplementation (1, 3, and 5%) for 35 days beginning on PND25 on bone quality, and osteoclastic bone resorption in female rats. Peripheral quantitative CT scan (pQCT) of tibia, demonstrated that bone mineral density (BMD) and content (BMC) were dose-dependently increased in BB-fed rats compared to controls (P<0.05). Significantly increased bone mass after feeding 5% BB extracts was also observed in a TEN (total enteral nutrition) rat model in which daily caloric and food intake was precisely controlled. Expression of RANKL (receptor activator of nuclear factor-κB ligand) a protein essential for osteoclast formation was dose-dependently decreased in the femur of BB animals. In addition, expression of PPARγ (peroxisome proliferator-activated receptor γ) which regulates bone marrow adipogenesis was suppressed in BB diet rats compared to non-BB diet controls. Finally, a set of in vitro cell cultures revealed that the inhibitory effect of BB diet rat serum on RANKL expression was more profound in mesenchymal stromal cells compared to its effect on mature osteoblasts, pre-adipocytes and osteocytes. These results suggest that inhibition of bone resorption may contribute to increased bone mass during early development after BB consumption. PMID:23936431

  1. Search for Higgs boson pair production in the γγbb[over ¯] final state using pp collision data at sqrt[s]=8  TeV from the ATLAS detector.

    PubMed

    Aad, G; Abbott, B; Abdallah, J; Abdel Khalek, S; Abdinov, O; Aben, R; Abi, B; Abolins, M; AbouZeid, O S; Abramowicz, H; Abreu, H; Abreu, R; Abulaiti, Y; Acharya, B S; Adamczyk, L; Adams, D L; Adelman, J; Adomeit, S; Adye, T; Agatonovic-Jovin, T; Aguilar-Saavedra, J A; Agustoni, M; Ahlen, S P; Ahmadov, F; Aielli, G; Akerstedt, H; Åkesson, T P A; Akimoto, G; Akimov, A V; Alberghi, G L; Albert, J; Albrand, S; Alconada Verzini, M J; Aleksa, M; Aleksandrov, I N; Alexa, C; Alexander, G; Alexandre, G; Alexopoulos, T; Alhroob, M; Alimonti, G; Alio, L; Alison, J; Allbrooke, B M M; Allison, L J; Allport, P P; Almond, J; Aloisio, A; Alonso, A; Alonso, F; Alpigiani, C; Altheimer, A; Alvarez Gonzalez, B; Alviggi, M G; Amako, K; Amaral Coutinho, Y; Amelung, C; Amidei, D; Amor Dos Santos, S P; Amorim, A; Amoroso, S; Amram, N; Amundsen, G; Anastopoulos, C; Ancu, L S; Andari, N; Andeen, T; Anders, C F; Anders, G; Anderson, K J; Andreazza, A; Andrei, V; Anduaga, X S; Angelidakis, S; Angelozzi, I; Anger, P; Angerami, A; Anghinolfi, F; Anisenkov, A V; Anjos, N; Annovi, A; Antonaki, A; Antonelli, M; Antonov, A; Antos, J; Anulli, F; Aoki, M; Aperio Bella, L; Apolle, R; Arabidze, G; Aracena, I; Arai, Y; Araque, J P; Arce, A T H; Arguin, J-F; Argyropoulos, S; Arik, M; Armbruster, A J; Arnaez, O; Arnal, V; Arnold, H; Arratia, M; Arslan, O; Artamonov, A; Artoni, G; Asai, S; Asbah, N; Ashkenazi, A; Åsman, B; Asquith, L; Assamagan, K; Astalos, R; Atkinson, M; Atlay, N B; Auerbach, B; Augsten, K; Aurousseau, M; Avolio, G; Azuelos, G; Azuma, Y; Baak, M A; Baas, A; Bacci, C; Bachacou, H; Bachas, K; Backes, M; Backhaus, M; Backus Mayes, J; Badescu, E; Bagiacchi, P; Bagnaia, P; Bai, Y; Bain, T; Baines, J T; Baker, O K; Balek, P; Balli, F; Banas, E; Banerjee, Sw; Bannoura, A A E; Bansal, V; Bansil, H S; Barak, L; Baranov, S P; Barberio, E L; Barberis, D; Barbero, M; Barillari, T; Barisonzi, M; Barklow, T; Barlow, N; Barnett, B M; Barnett, R M; Barnovska, Z; Baroncelli, A; Barone, G; Barr, A J; Barreiro, F; Barreiro Guimarães da Costa, J; Bartoldus, R; Barton, A E; Bartos, P; Bartsch, V; Bassalat, A; Basye, A; Bates, R L; Batkova, L; Batley, J R; Battaglia, M; Battistin, M; Bauer, F; Bawa, H S; Beau, T; Beauchemin, P H; Beccherle, R; Bechtle, P; Beck, H P; Becker, K; Becker, S; Beckingham, M; Becot, C; Beddall, A J; Beddall, A; Bedikian, S; Bednyakov, V A; Bee, C P; Beemster, L J; Beermann, T A; Begel, M; Behr, K; Belanger-Champagne, C; Bell, P J; Bell, W H; Bella, G; Bellagamba, L; Bellerive, A; Bellomo, M; Belotskiy, K; Beltramello, O; Benary, O; Benchekroun, D; Bendtz, K; Benekos, N; Benhammou, Y; Benhar Noccioli, E; Benitez Garcia, J A; Benjamin, D P; Bensinger, J R; Benslama, K; Bentvelsen, S; Berge, D; Bergeaas Kuutmann, E; Berger, N; Berghaus, F; Beringer, J; Bernard, C; Bernat, P; Bernius, C; Bernlochner, F U; Berry, T; Berta, P; Bertella, C; Bertoli, G; Bertolucci, F; Bertsche, D; Besana, M I; Besjes, G J; Bessidskaia Bylund, O; Bessner, M F; Besson, N; Betancourt, C; Bethke, S; 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Ungaro, F C; Unno, Y; Urbaniec, D; Urquijo, P; Usai, G; Usanova, A; Vacavant, L; Vacek, V; Vachon, B; Valencic, N; Valentinetti, S; Valero, A; Valery, L; Valkar, S; Valladolid Gallego, E; Vallecorsa, S; Valls Ferrer, J A; Van Den Wollenberg, W; Van Der Deijl, P C; van der Geer, R; van der Graaf, H; Van Der Leeuw, R; van der Ster, D; van Eldik, N; van Gemmeren, P; Van Nieuwkoop, J; van Vulpen, I; van Woerden, M C; Vanadia, M; Vandelli, W; Vanguri, R; Vaniachine, A; Vankov, P; Vannucci, F; Vardanyan, G; Vari, R; Varnes, E W; Varol, T; Varouchas, D; Vartapetian, A; Varvell, K E; Vazeille, F; Vazquez Schroeder, T; Veatch, J; Veloso, F; Veneziano, S; Ventura, A; Ventura, D; Venturi, M; Venturi, N; Venturini, A; Vercesi, V; Verducci, M; Verkerke, W; Vermeulen, J C; Vest, A; Vetterli, M C; Viazlo, O; Vichou, I; Vickey, T; Vickey Boeriu, O E; Viehhauser, G H A; Viel, S; Vigne, R; Villa, M; Villaplana Perez, M; Vilucchi, E; Vincter, M G; Vinogradov, V B; Virzi, J; Vivarelli, I; Vives Vaque, F; Vlachos, S; Vladoiu, D; Vlasak, M; Vogel, A; Vogel, M; Vokac, P; Volpi, G; Volpi, M; von der Schmitt, H; von Radziewski, H; von Toerne, E; Vorobel, V; Vorobev, K; Vos, M; Voss, R; Vossebeld, J H; Vranjes, N; Vranjes Milosavljevic, M; Vrba, V; Vreeswijk, M; Vu Anh, T; Vuillermet, R; Vukotic, I; Vykydal, Z; Wagner, P; Wagner, W; Wahlberg, H; Wahrmund, S; Wakabayashi, J; Walder, J; Walker, R; Walkowiak, W; Wall, R; Waller, P; Walsh, B; Wang, C; Wang, C; Wang, F; Wang, H; Wang, H; Wang, J; Wang, J; Wang, K; Wang, R; Wang, S M; Wang, T; Wang, X; Wanotayaroj, C; Warburton, A; Ward, C P; Wardrope, D R; Warsinsky, M; Washbrook, A; Wasicki, C; Watkins, P M; Watson, A T; Watson, I J; Watson, M F; Watts, G; Watts, S; Waugh, B M; Webb, S; Weber, M S; Weber, S W; Webster, J S; Weidberg, A R; Weigell, P; Weinert, B; Weingarten, J; Weiser, C; Weits, H; Wells, P S; Wenaus, T; Wendland, D; Weng, Z; Wengler, T; Wenig, S; Wermes, N; Werner, M; Werner, P; Wessels, M; Wetter, J; Whalen, K; White, A; White, M J; White, R; White, S; Whiteson, D; Wicke, D; Wickens, F J; Wiedenmann, W; Wielers, M; Wienemann, P; Wiglesworth, C; Wiik-Fuchs, L A M; Wijeratne, P A; Wildauer, A; Wildt, M A; Wilkens, H G; Will, J Z; Williams, H H; Williams, S; Willis, C; Willocq, S; Wilson, A; Wilson, J A; Wingerter-Seez, I; Winklmeier, F; Winter, B T; Wittgen, M; Wittig, T; Wittkowski, J; Wollstadt, S J; Wolter, M W; Wolters, H; Wosiek, B K; Wotschack, J; Woudstra, M J; Wozniak, K W; Wright, M; Wu, M; Wu, S L; Wu, X; Wu, Y; Wulf, E; Wyatt, T R; Wynne, B M; Xella, S; Xiao, M; Xu, D; Xu, L; Yabsley, B; Yacoob, S; Yamada, M; Yamaguchi, H; Yamaguchi, Y; Yamamoto, A; Yamamoto, K; Yamamoto, S; Yamamura, T; Yamanaka, T; Yamauchi, K; Yamazaki, Y; Yan, Z; Yang, H; Yang, H; Yang, U K; Yang, Y; Yanush, S; Yao, L; Yao, W-M; Yasu, Y; Yatsenko, E; Yau Wong, K H; Ye, J; Ye, S; Yen, A L; Yildirim, E; Yilmaz, M; Yoosoofmiya, R; Yorita, K; Yoshida, R; Yoshihara, K; Young, C; Young, C J S; Youssef, S; Yu, D R; Yu, J; Yu, J M; Yu, J; Yuan, L; Yurkewicz, A; Yusuff, I; Zabinski, B; Zaidan, R; Zaitsev, A M; Zaman, A; Zambito, S; Zanello, L; Zanzi, D; Zeitnitz, C; Zeman, M; Zemla, A; Zengel, K; Zenin, O; Ženiš, T; Zerwas, D; Zevi Della Porta, G; Zhang, D; Zhang, F; Zhang, H; Zhang, J; Zhang, L; Zhang, X; Zhang, Z; Zhao, Z; Zhemchugov, A; Zhong, J; Zhou, B; Zhou, L; Zhou, N; Zhu, C G; Zhu, H; Zhu, J; Zhu, Y; Zhuang, X; Zhukov, K; Zibell, A; Zieminska, D; Zimine, N I; Zimmermann, C; Zimmermann, R; Zimmermann, S; Zimmermann, S; Zinonos, Z; Ziolkowski, M; Zobernig, G; Zoccoli, A; Zur Nedden, M; Zurzolo, G; Zutshi, V; Zwalinski, L

    2015-02-27

    Searches are performed for resonant and nonresonant Higgs boson pair production in the γγbb[over ¯] final state using 20  fb^{-1} of proton-proton collisions at a center-of-mass energy of 8 TeV recorded with the ATLAS detector at the CERN Large Hadron Collider. A 95% confidence level upper limit on the cross section times branching ratio of nonresonant production is set at 2.2 pb, while the expected limit is 1.0 pb. The difference derives from a modest excess of events, corresponding to 2.4 standard deviations from the background-only hypothesis. The limit observed in the search for a narrow X→hh resonance ranges between 0.7 and 3.5 pb as a function of the resonance mass.

  2. Comparative Analysis of Cellular and Growth Factor Composition in Bone Marrow Aspirate Concentrate and Platelet-Rich Plasma.

    PubMed

    Sugaya, Hisashi; Yoshioka, Tomokazu; Kato, Toshiki; Taniguchi, Yu; Kumagai, Hiroshi; Hyodo, Kojiro; Ohneda, Osamu; Yamazaki, Masashi; Mishima, Hajime

    2018-01-01

    The purpose of this study was to quantify the stem cell and growth factor (GF) contents in the bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) prepared from whole blood using a protocol established in our laboratory. We examined 10 patients with osteonecrosis of the femoral head who were treated by autologous BMAC transplantation at our hospital between January 2015 and June 2015. We quantified CD34+ and CD31-CD45-CD90+CD105+ cells in BMAC and PRP by flow cytometry. Additionally, we measured various GFs, that is, basic fibroblast growth factor (b-FGF), platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor (VEGF), transforming growth factor- β 1 (TGF- β 1), and bone morphogenetic protein-2 (BMP-2) in BMAC and PRP using enzyme-linked immunosorbent assays and statistical analyses. CD34+ and CD31-45-90+105+ cells accounted for approximately 1.9% and 0.03% of cells in BMAC and no cells in PRP. The concentration of b-FGF was higher in BMAC than in PRP ( P < 0.001), whereas no significant differences in the levels of PDGF-BB, VEGF, TGF- β 1, and BMP-2 were observed between the two types of sample. BMAC had an average of 1.9% CD34+ and 0.03% CD31-45-90+105+ cells and higher levels of b-FGF than those of PRP.

  3. Synthesis and electrical properties of BaBiO 3 and high resistivity BaTiO 3 –BaBiO 3 ceramics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kumar, Nitish; Golledge, Stephen L.; Cann, David P.

    2016-12-01

    Ceramics of the composition BaBiO3 (BB) were sintered in oxygen to obtain a single phase with monoclinic II2/mm symmetry as suggested by high-resolution X-ray diffraction. X-ray photoelectron spectroscopy confirmed the presence of bismuth in two valence states - 3+ and 5+. Optical spectroscopy showed presence of a direct bandgap at ~ 2.2eV and a possible indirect bandgap at ~ 0.9eV. This combined with determination of the activation energy for conduction of 0.25eV, as obtained from ac impedance spectroscopy, suggested that a polaron-mediated conduction mechanism was prevalent in BB. The BB ceramics were crushed, mixed with BaTiO3 (BT), and sintered tomore » obtain BT–BB solid solutions. All the ceramics had tetragonal symmetry and exhibited a normal ferroelectric-like dielectric response. Using ac impedance and optical spectroscopy, it was shown that resistivity values of BT–BB were orders of magnitude higher than BT or BB alone, indicating a change in the fundamental defect equilibrium conditions. A shift in the site occupancy of Bi to the A-site is proposed to be the mechanism for the increased electrical resistivity.« less

  4. Complement factor B expression profile in a spontaneous uveitis model.

    PubMed

    Zipplies, Johanna K; Kirschfink, Michael; Amann, Barbara; Hauck, Stefanie M; Stangassinger, Manfred; Deeg, Cornelia A

    2010-12-01

    Equine recurrent uveitis serves as a spontaneous model for human autoimmune uveitis. Unpredictable relapses and ongoing inflammation in the eyes of diseased horses as well as in humans lead to destruction of the retina and finally result in blindness. However, the molecular mechanisms leading to inflammation and retinal degeneration are not well understood. An initial screening for differentially regulated proteins in sera of uveitic cases compared to healthy controls revealed an increase of the alternative pathway complement component factor B in ERU cases. To determine the activation status of the complement system, sera were subsequently examined for complement split products. We could demonstrate a significant higher concentration of the activation products B/Ba, B/Bb, Bb neoantigen, iC3b and C3d in uveitic condition compared to healthy controls, whereas for C5b-9 no differences were detected. Additionally, we investigated complement activation directly in the retina by immunohistochemistry, since it is the main target organ of this autoimmune disease. Interestingly, infiltrating cells co-expressed activated factor Bb neoantigen, complement split product C3d as well as CD68, a macrophage marker. In this study, we could demonstrate activation of the complement system both systemically as well as in the eye, the target organ of spontaneous recurrent uveitis. Based on these novel findings, we postulate a novel role for macrophages in connection with complement synthesis at the site of inflammation. Copyright © 2010 Elsevier GmbH. All rights reserved.

  5. Effects of sodium citrate and acid citrate dextrose solutions on cell counts and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel.

    PubMed

    Giraldo, Carlos E; Álvarez, María E; Carmona, Jorge U

    2015-03-14

    There is a lack information on the effects of the most commonly used anticoagulants for equine platelet rich plasmas (PRPs) elaboration on cell counts and growth factor release from platelet rich gels (PRGs). The aims of this study were 1) to compare the effects of the anticoagulants sodium citrate (SC), acid citrate dextrose solution A (ACD-A) and ACD-B on platelet (PLT), leukocyte (WBC) and on some parameters associated to platelet activation including mean platelet volume (MPV) and platelet distribution width (PDW) between whole blood, pure PRP (P-PRP) and platelet-poor plasma (PPP); 2) to compare transforming growth factor beta 1 (TGF-β(1)) and platelet-derived growth factor isoform BB (PDGF-BB) concentrations in supernatants from pure PRG (P-PRG), platelet-poor gel (PPG), P-PRP lysate (positive control) and plasma (negative control); 3) to establish the possible correlations between all the studied cellular and molecular parameters. In all cases the three anticoagulants produced P-PRPs with significantly higher PLT counts compared with whole blood and PPP. The concentrations of WBCs were similar between P-PRP and whole blood, but significantly lower in PPP. The type of anticoagulant did not significantly affect the cell counts for each blood component. The anticoagulants also did not affect the MPV and PDW parameters. Independently of the anticoagulant used, all blood components presented significantly different concentrations of PDGF-BB and TGF-β(1). The highest growth factor (GF) concentrations were observed from P-PRP lysates, followed by PRG supernatants, PPP lysates, PPG supernatants and plasma. Significant correlations were observed between PLT and WBC counts (ρ = 0.80), PLT count and TGF-β(1) concentration (ρ = 0.85), PLT count and PDGF-BB concentration (ρ = 0.80) and PDGF-BB and TGF-β(1) concentrations (ρ = 0.75). The type of anticoagulant was not correlated with any of the variables evaluated. The anticoagulants did not

  6. Temporal and diurnal variations of carbonaceous aerosols and major ions in biomass burning influenced aerosols over Mt. Tai in the North China Plain during MTX2006

    NASA Astrophysics Data System (ADS)

    Boreddy, Suresh K. R.; Kawamura, Kimitaka; Okuzawa, Kazuhiro; Kanaya, Yugo; Wang, Zifa

    2017-04-01

    To better understand the impact of agricultural waste burning on the air quality of free troposphere over the North China Plain (NCP), we collected total suspended particles (TSP) at the summit of Mt. Tai, located in the NCP using a high volume air sampler during 29 May to 28 June 2006, when the field burning of agricultural residue was intense. Temporal variations of all measured species showed that their concentration increases from late May to mid June (major BB period), peaking during 12-14 June, and then significantly decreased towards late June (minor BB period). We noticed that a significant reduction in the concentrations of carbonaceous aerosols during the period of 8-11 June, when the wind direction shifted from southerly to northerly. We found that concentrations of carbonaceous aerosols and some major ions showed several times higher during major BB period than those of minor BB period. We also found that nighttime concentrations are higher than daytime during major BB period, suggesting that a long-range atmospheric transport of biomass burning plumes in the free troposphere, which arrived at the summit of Mt. Tai. In contrast, daytime concentrations are higher than nighttime during minor BB period. We found higher concentrations of secondary organic carbon (SOC) during major BB period, suggesting that formation of secondary organic aerosols through aqueous phase chemistry under high NOx conditions during a long-range atmospheric transport. nss-K+ showed about four times higher concentrations during major BB than those of minor BB. Concentrations of nss-Ca2+ are higher in nighttime during major BB period, implying that a significant long-range atmospheric transport of mineral dust over the sampling site. These results are further supported by the positive matrix factorization (PMF) analysis, which showed that biomass burning was a major source for the carbonaceous aerosols followed by mineral dust sources over the summit of Mt. Tai.

  7. β-Blocker Therapy Prior to Admission for Acute Coronary Syndrome in Patients Without Heart Failure or Left Ventricular Dysfunction Improves In-Hospital and 12-Month Outcome: Results From the GULF-RACE 2 (Gulf Registry of Acute Coronary Events-2).

    PubMed

    Abi Khalil, Charbel; AlHabib, Khalid F; Singh, Rajvir; Asaad, Nidal; Alfaleh, Hussam; Alsheikh-Ali, Alawi A; Sulaiman, Kadhim; Alshamiri, Mostafa; Alshaer, Fayez; AlMahmeed, Wael; Al Suwaidi, Jassim

    2017-12-20

    The prognostic impact of β-blockers (BB) in acute coronary syndrome (ACS) patients without heart failure (HF) or left ventricular dysfunction is controversial, especially in the postreperfusion era. We sought to determine whether a BB therapy before admission for ACS has a favorable in-hospital outcome in patients without HF, and whether they also reduce 12-month mortality if still prescribed on discharge. The GULF-RACE 2 (Gulf Registry of Acute Coronary Events-2) is a prospective multicenter study of ACS in 6 Middle Eastern countries. We studied in-hospital cardiovascular events in patients hospitalized for ACS without HF in relation to BB on admission, and 1-year mortality in relation to BB on discharge. Among the 7903 participants, 7407 did not have HF, of whom 5937 (80.15%) patients were on BB. Patients on BB tended to be older and have more comorbidities. However, they had a lower risk of in-hospital mortality, mitral regurgitation, HF, cardiogenic shock, and ventricular tachycardia/ventricular fibrillation. Furthermore, 4208 patients were discharged alive and had an ejection fraction ≥40%. Among those, 84.1% had a BB prescription. At 12 months, they also had a reduced risk of mortality as compared with the non-BB group. Even after correcting for confounding factors in 2 different models, in-hospital and 12-month mortality risk was still lower in the BB group. In this cohort of ACS, BB therapy before admission for ACS is associated with decreased in-hospital mortality and major cardiovascular events, and 1-year mortality in patients without HF or left ventricular dysfunction if still prescribed on discharge. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  8. Dinosaur bone beds and mass mortality: Implications for the K-T extinction

    NASA Technical Reports Server (NTRS)

    Carpenter, Kenneth

    1988-01-01

    Mass accumulations of fossilized large terrestrial vertebrate skeletons (bone beds: BB) provide a test for K-T catastrophic extinction hypotheses. The two major factors contributing to BB formation are mode of death and sedimentation rate. Catastrophic mass mortality (CMM) is the sudden death of numerous individuals where species, age, health, gender, or social ranking offer no survivorship advantage. Noncatastrophic mass mortality (NCMM) occurs over time and is strongly influenced by species, age, or gender. In addition to cause of death, sedimentation rate is also important in BB formation. Models of BBs can be made. The CMM drops all individuals in their tracks, therefore, the BB should reflect the living population with respect to species, age, or gender. The NCMM results in monospecific BBs skewed in the direction of the less fit, usually the very young or very old, or towards a specific gender. The NCMM and AM BBs may become more similar the more spread out over time NCMM deaths occur because carcasses are widely scattered requiring hydraulic accumulation, and the greater time allows for more disarticulation and weathering. The CMM and NCMM BB appear to be dominated by social animals. Applying this and the characteristics of mortality patterns to the uppermost Cretaceous Hell Creek Formation indicates that only NCMM and AM BB occur. Furthermore, NCMM BB are rare in the upper third of the Hell Creek. Near the K-T boundary, only AM BB are known. The absence of CMM and NCMM BB appears to be real reflecting a decrease in population levels of some dinosaurs prior to the K-T event. The absence of CMM suggests that the K-T event did not lead to an instantaneous extinction of dinosaurs. Nor was there a protracted die-off due to an asteroid impact winter, because no NCMM BB are known at or near the K-T boundary.

  9. The future of recombinant growth factors in wound healing.

    PubMed

    Robson, M C; Mustoe, T A; Hunt, T K

    1998-08-01

    For more than a decade, clinical trials have been conducted of the application of topical exogenous recombinant growth factors in attempts to accelerate the healing of chronic wounds. Although the results of some of these trials have been encouraging, overall the results have been somewhat discouraging. Much of the difficulty lies in the paucity of carefully controlled clinical trials of wound healing. Since wound healing is a complex process that can be influenced, both positively and negatively, by many factors, designing these trials has proved difficult. To date, only a single recombinant growth factor-recombinant human platelet-derived growth factor-BB (rhPDGF-BB)- has been approved by the US Food and Drug Administration; and that only for use in diabetic foot ulcers. It is unlikely, however, that a single growth factor will be able to resolve all issues of repair or strengthen all vulnerabilities of chronic wounds. Our expectation, therefore, is that growth factors, cytokines, and other biologic agents will be used more specifically in the future, for example, by targeting growth factor therapy at those specific components or processes that a given wound uses to heal.

  10. Pore Interconnectivity Influences Growth Factor-Mediated Vascularization in Sphere-Templated Hydrogels

    PubMed Central

    Somo, Sami I.; Akar, Banu; Bayrak, Elif S.; Larson, Jeffery C.; Appel, Alyssa A.; Mehdizadeh, Hamidreza; Cinar, Ali

    2015-01-01

    Rapid and controlled vascularization within biomaterials is essential for many applications in regenerative medicine. The extent of vascularization is influenced by a number of factors, including scaffold architecture. While properties such as pore size and total porosity have been studied extensively, the importance of controlling the interconnectivity of pores has received less attention. A sintering method was used to generate hydrogel scaffolds with controlled pore interconnectivity. Poly(methyl methacrylate) microspheres were used as a sacrificial agent to generate porous poly(ethylene glycol) diacrylate hydrogels with interconnectivity varying based on microsphere sintering conditions. Interconnectivity levels increased with sintering time and temperature with resultant hydrogel structure showing agreement with template structure. Porous hydrogels with a narrow pore size distribution (130–150 μm) and varying interconnectivity were investigated for their ability to influence vascularization in response to gradients of platelet-derived growth factor-BB (PDGF-BB). A rodent subcutaneous model was used to evaluate vascularized tissue formation in the hydrogels in vivo. Vascularized tissue invasion varied with interconnectivity. At week 3, higher interconnectivity hydrogels had completely vascularized with twice as much invasion. Interconnectivity also influenced PDGF-BB transport within the scaffolds. An agent-based model was used to explore the relative roles of steric and transport effects on the observed results. In conclusion, a technique for the preparation of hydrogels with controlled pore interconnectivity has been developed and evaluated. This method has been used to show that pore interconnectivity can independently influence vascularization of biomaterials. PMID:25603533

  11. Air-to-Air Target Acquisition: Factors and Means of Improvement.

    DTIC Science & Technology

    1980-03-01

    and an atmospheric modelo B t - Bb VISTARAQ C - b derived from input quantities and an B atmospheric model Bt Bb RAE/BAC C B derived from input...seair ’ h task in a !static, fielId. I" Osi c r r, I’lut ion is, dependi- ent upon the angle of’ t hr vi:i x is, -ft wh iih -wilil1y is measured and th

  12. Combination Growth Factor Therapy via Electrostatically Assembled Wound Dressings Improves Diabetic Ulcer Healing In Vivo.

    PubMed

    Almquist, Benjamin D; Castleberry, Steven A; Sun, Julia B; Lu, Alice Y; Hammond, Paula T

    2015-10-01

    Chronic skin ulcerations are a common complication of diabetes mellitus, affecting up to one in four diabetic individuals. Despite the prevalence of these wounds, current pharmacologic options for treating them remain limited. Growth factor-based therapies have displayed a mixed ability to drive successful healing, which may be due to nonoptimal delivery strategies. Here, a method for coating commercially available nylon dressings using the layer-by-layer process is described to enable both sustained release and independent control over the release kinetics of vascular endothelial growth factor 165 and platelet-derived growth factor BB. It is shown that the use of strategically spaced diffusion barriers formed spontaneously by disulfide bonds enables independent control over the release rates of incorporated growth factors, and that in vivo these dressings improve several aspects of wound healing in db/db mice. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Performance of Nursing Awassi Ewes Fed Different Levels of Bread By-product

    PubMed Central

    Obeidat, B. S.; Haddad, S. G.; Titi, H. H.; Abu Ishmais, M. A.; Telfah, B. T.

    2012-01-01

    Objective of this experiment was to evaluate the effect of partial substitution of barley grain with bread by-product (BB) on performance of Awassi ewes and their lambs. Forty Awassi ewes rearing single lambs were randomly allotted into four experimental diets containing various levels of BB. The experimental diets contained 0 (BB0), 10 (BB10), 15 (BB15), and 20% (BB20) of BB on dietary dry matter (DM). The study lasted for eight weeks, in which the first week was used as an adaptation period and seven weeks of data collection. Ewes and their lambs were penned individually where they were fed their lactating diets ad libitum. Ewes and lambs body weights were measured at the beginning and at the end of the experiment. However, milk production and composition were evaluated biweekly. Feeding BB had no effect (p>0.05) on dry matter (DM), organic matter (OM), and crude protein (CP) intakes. However, neutral detergent fiber (NDF) intake was the lowest (p<0.05) for the BB20 and BB15 diets followed to BB10 diet (i.e., 640, 677, 772 g/d, respectively) while the highest NDF intake was for the BB0 diet (i.e., 825 g/d). Similarly, NDF intake decreased linearly (p<0.001) as the BB content increased. Acid detergent fiber (ADF) intake was highest (p<0.05) for the BB0 and BB10 diets (425 and 416 g/d, respectively) followed by the BB15 and BB20 diets (359 and 342 g/d, respectively). Moreover, a linear (p<0.001), quadratic (p = 0.04), and cubic (p = 0.04) effects were observed in ADF intake among diets. Nutrient digestibility was similar among different diets. Bread by-product had no effect (p>0.05) on ewes body weight change and on lamb performance (i.e., weaning body weight and average daily gain). Similarly, no differences (p>0.05) were observed either in milk production or composition by the BB substitution. Inclusion of BB reduced feed cost by 9, 14, and 18% for the BB10, BB15, and BB20 diets, respectively. No differences were observed in milk efficiency (DM intake: milk

  14. Prospects of discovering stable double-heavy tetraquarks at a Tera-Z factory

    NASA Astrophysics Data System (ADS)

    Ali, Ahmed; Parkhomenko, Alexander Ya.; Qin, Qin; Wang, Wei

    2018-07-01

    Motivated by a number of theoretical considerations, predicting the deeply bound double-heavy tetraquarks T[ u bar d bar ]{ bb }, T[ u bar s bar ]{ bb } and T[ d bar s bar ]{ bb }, we explore the potential of their discovery at Tera-Z factories. Using the process Z → b b bar b b bar , we calculate, employing the Monte Carlo generators MadGraph5_aMC@NLO and Pythia6, the phase space configuration in which the bb pair is likely to fragment as a diquark. In a jet-cone, defined by an invariant mass interval mbb < M T[ q bar qbar‧ ]{ bb } + ΔM, the sought-after tetraquarks T[ q bar qbar‧ ]{ bb } as well as the double-bottom baryons, Ξbb0,-, and Ωbb- , can be produced. Using the heavy quark-diquark symmetry, we estimate B (Z → T[ u bar d bar ]{ bb } + b bar b bar) = (1.2-0.3+1.0) ×10-6, and about a half of this for the T[ u bar s bar ]{ bb } and T[ d bar s bar ]{ bb } . We also present an estimate of their lifetimes using the heavy quark expansion, yielding τ (T[ q bar qbar‧ ]{ bb }) ≃ 800 fs. Measuring the tetraquark masses would require decays, such as T[ u bar d bar ]{ bb } - →B-D-π+, T [ u bar d bar ]{ bb } - → J / ψK‾0B-, T[ u bar d bar ]{ bb } - → J / ψK-B‾0, T[ u bar s bar ]{ bb } - → Ξbc0 Σ-, and T[ d bar s bar ]{ bb } 0 → Ξbc0 Σbar0, with subsequent decay chains in exclusive non-leptonic final states. We estimate a couple of the decay widths and find that the product branching ratios do not exceed 10-5. Hence, a good fraction of these modes will be required for a discovery of T[ q bar qbar‧ ]{ bb } at a Tera-Z factory.

  15. PDGF-B Gene Therapy Accelerates Bone Engineering and Oral Implant Osseointegration

    PubMed Central

    Chang, Po-Chun; Seol, Yang-Jo; Cirelli, Joni A; Pellegrini, Gaia R.; Jin, Qiming; Franco, Lea M.; Goldstein, Steven A.; Chandler, Lois A.; Sosnowski, Barbara; Giannobile, William V.

    2009-01-01

    Platelet-derived growth factor-BB (PDGF-BB) stimulates repair of healing-impaired chronic wounds such as diabetic ulcers and periodontal lesions. However, limitations in predictability of tissue regeneration occur due in part to transient growth factor bioavailability in vivo. Here, we report that gene delivery of PDGF-B stimulates repair of oral implant extraction socket defects. Alveolar ridge defects were created in rats and were treated at the time of titanium implant installation with a collagen matrix containing an adenoviral (Ad) vector encoding PDGF-B (5.5×108 or 5.5×109 pfu/ml), Ad encoding luciferase (Ad-Luc; 5.5×109 pfu/ml; control) or recombinant human PDGF-BB protein (rhPDGF-BB, 0.3 mg/ml). Bone repair and osseointegration were measured via backscattered SEM, histomorphometry, microcomputed tomography, and biomechanical assessments. Further, a panel of local and systemic safety assessments was performed. Results demonstrated bone repair was accelerated by Ad-PDGF-B and rhPDGF-BB delivery compared to Ad-Luc, with the high dose of Ad-PDGF-B more effective than the low dose. No significant dissemination of the vector construct or alteration of systemic parameters was noted. In summary, gene delivery of Ad-PDGF-B demonstrates regenerative and safety capabilities for bone tissue engineering and osseointegration in alveolar bone defects comparable to rhPDGF-BB protein delivery in vivo. PMID:19741730

  16. Regenerative Endodontic Treatment of an Immature Necrotic Molar with Arrested Root Development by Using Recombinant Human Platelet-derived Growth Factor: A Case Report.

    PubMed

    Zhujiang, Annie; Kim, Sahng G

    2016-01-01

    Regenerative endodontic treatment has provided a treatment option that aims to allow root maturation. The present report describes the regenerative endodontic treatment of a necrotic, immature molar by using recombinant human platelet-derived growth factor (rhPDGF-BB) and shows the continued root maturation in the tooth with arrested root development. A regenerative endodontic procedure that used a growth factor was performed for a necrotic molar with arrested root formation in a 20-year-old patient. Thorough disinfection by using mechanical instrumentation and copious irrigation of antimicrobial agents as well as intracanal medication with calcium hydroxide was performed throughout the first 2 appointments. At the third appointment, the root canals were irrigated with an antimicrobial solution and 17% EDTA, and bleeding was evoked by passing sterile paper points beyond the apex in each canal. Small pieces of a collagen membrane saturated with rhPDGF-BB solution from GEM 21S were packed into each canal. Mineral trioxide aggregate was placed, and Cavit and composite resin were used to restore the tooth. Complete root maturation and resolution of a periapical radiolucency were observed at the 15-month follow-up. The present report presents a regenerative endodontic procedure that uses rhPDGF-BB for a necrotic molar with arrested root development. The finding of continued root development in the present case suggests that regenerative endodontic treatment may be able to resume the root maturation process in teeth with arrested root formation. Further clinical studies are required to investigate the efficacy of rhPDGF-BB in regenerative endodontic treatment. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  17. Preparation of a specific bamboo based activated carbon and its application for ciprofloxacin removal.

    PubMed

    Wang, Y X; Ngo, H H; Guo, W S

    2015-11-15

    The studied bamboo based activated carbon (BbAC) with high specific surface area (SSA) and high micro pore volume was prepared from bamboo scraps by the combined activation of H3PO4 and K2CO3. The BbAC was characterized based on the N2 adsorption isotherm at 77K. The results showed that the SSA and pore volume of BbAC increased with increasing impregnation ratio and reached maxima at the impregnation ratio of 3:1 at 750°C. Under these optimal conditions, the BbAC obtained could have a maximum SSA of 2237 m(2)/g and a maximum total pore volume of 1.23 cm(3)/g with the micro pore ratio of more than 90%. The adsorption performance of ciprofloxacin (CIP) on the BbAC was determined at 298 K. The Langmuir and Freundlich models were employed to describe the adsorption equilibrium and the kinetic data were fitted by pseudo first-order and pseudo second-order kinetic models. The results showed that the Langmuir model and the pseudo second-order kinetic model presented better fittings for the adsorption equilibrium and kinetics data, respectively. The maximum adsorption amount of CIP (613 mg/g) on the BbAC was much higher than the report in the literature. Conclusively, the BbAC could be a promising adsorption material for CIP removal from water. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Developmental GPR mine detection technology known as Balanced Bridge

    NASA Astrophysics Data System (ADS)

    Sherbondy, Kelly D.; Lang, David A.

    1995-06-01

    The Balanced Bridge (BB) detection concept was developed just after the end of WWII. It has been researched for many years since then but it has never truly overcome the following inherent problems: sensitivity to antenna height and tilt variations, detectability of flush mines, sensitivity to soil moisture content, high false alarms, and most importantly, the inability to detect small anti-personnel (AP) mines. Even with all of these shortcomings, the BB sensor technology is still one of the most promising electrmagnetic mine detection systems. This paper will address a new BB detector and its preliminary field performance compared to earlier BB research. The new BB detector has superior capabilities compared to earlier BB efforts involving single frequency or single octave excitation because the new BB operates over a multi-octave bandwidth. The new BB detector also incorporates audio and visual presentations of digitally processed signals where earlier versions only had an audible announcement derived from a simple thresholding algorithm. New BB designs addressing previous BB deficiencies will also be discussed. Design changes include using a broadband printed circuit board antenna, RF transmit and receive components, and a digital signal processor. This new BB detector will be tested at an Advanced Technology Demonstration (ATD) evaluation in FY95. The ATD exit criteria will be discussed and compared to recent field testing of the new BB detector. Preliminary results with the new BB system have demonstrated encouraging results which will be incorporated in this paper.

  19. Study of a Two-Step Centrifugation Protocol for Concentrating Cells and Growth Factors in Bovine Platelet-Rich Plasma

    PubMed Central

    Gutiérrez, Claudia M.; López, Catalina

    2017-01-01

    There is a lack of information about the methods used for bovine platelet-rich plasma (PRP)/platelet-rich gel (PRG) procurement, including information on platelet (PLT), white blood cell (WBC) in PRP, and growth factor release from PRG supernatants. The aims of this study were to compare and to correlate the PLT, WBC, transforming growth factor beta-1 (TGF-β1), and platelet-derived growth factor BB (PDGF-BB) concentrations in bovine whole blood, plasma, and four PRP layers and their respective PRG supernatants: A and B (obtained by a single centrifugation tube method at 720g/5 min) and C and D (obtained by a double centrifugation tube method, by using two centrifugation episodes at 720g/5 min). PLT and WBC counts were significantly higher in PRP-C, followed by whole blood, PRP-A, PRP-B, and PRP-D. TGF-β1 concentrations were significantly higher in PRG-B supernatants and its correspondent PRP-B lysate when compared to the other PRG supernatants and plasma. Supernatants from PRG-A, PRG-B, and PRG-D had equivalent TGF-β1 concentrations. PDGF-BB concentrations were not statistically different between the hemoderivatives. Significant Pearson correlations were noted between PLT counts and WBC counts (0.8) and between PLT counts and PLT distribution width (0.6). Further studies should be performed to assess the potential clinical applications of these PRPs. PMID:29214094

  20. Probing into the aging dynamics of biomass burning aerosol by using satellite measurements of aerosol optical depth and carbon monoxide

    NASA Astrophysics Data System (ADS)

    Konovalov, Igor B.; Beekmann, Matthias; Berezin, Evgeny V.; Formenti, Paola; Andreae, Meinrat O.

    2017-04-01

    Carbonaceous aerosol released into the atmosphere from open biomass burning (BB) is known to undergo considerable chemical and physical transformations (aging). However, there is substantial controversy about the nature and observable effects of these transformations. A shortage of consistent observational evidence on BB aerosol aging processes under different environmental conditions and at various temporal scales hinders development of their adequate representations in chemistry transport models (CTMs). In this study, we obtain insights into the BB aerosol dynamics by using available satellite measurements of aerosol optical depth (AOD) and carbon monoxide (CO). The basic concept of our method is to consider AOD as a function of the BB aerosol photochemical age (that is, the time period characterizing the exposure of BB aerosol emissions to atmospheric oxidation reactions) predicted by means of model tracers. We evaluate the AOD enhancement ratio (ER) defined as the ratio of optical depth of actual BB aerosol with respect to that of a modeled aerosol tracer that is assumed to originate from the same fires as the real BB aerosol but that is not affected by any aging processes. To limit possible effects of model transport errors, the AOD measurements are normalized to CO column amounts that are also retrieved from satellite measurements. The method is applied to the analysis of the meso- and synoptic-scale evolution of aerosol in smoke plumes from major wildfires that occurred in Siberia in summer 2012. AOD and CO retrievals from MODIS and IASI measurements, respectively, are used in combination with simulations performed with the CHIMERE CTM. The analysis indicates that aging processes strongly affected the evolution of BB aerosol in the situation considered, especially in dense plumes (with spatial average PM2. 5 concentration exceeding 100 µg m-3). For such plumes, the ER is found to increase almost 2-fold on the scale of ˜ 10 h of daytime aerosol

  1. Radiative response of biomass-burning aerosols over an urban atmosphere in northern peninsular Southeast Asia.

    PubMed

    Pani, Shantanu Kumar; Lin, Neng-Huei; Chantara, Somporn; Wang, Sheng-Hsiang; Khamkaew, Chanakarn; Prapamontol, Tippawan; Janjai, Serm

    2018-08-15

    A large concentration of finer particulate matter (PM 2.5 ), the primary air-quality concern in northern peninsular Southeast Asia (PSEA), is believed to be closely related to large amounts of biomass burning (BB) particularly in the dry season. In order to quantitatively estimate the contributions of BB to aerosol radiative effects, we thoroughly investigated the physical, chemical, and optical properties of BB aerosols through the integration of ground-based measurements, satellite retrievals, and modelling tools during the Seven South East Asian Studies/Biomass-burning Aerosols & Stratocumulus Environment: Lifecycles & Interactions Experiment (7-SEAS/BASELInE) campaign in 2014. Clusters were made on the basis of measured BB tracers (Levoglucosan, nss-K + , and NO 3 - ) to classify the degree of influence from BB over an urban atmosphere, viz., Chiang Mai (18.795°N, 98.957°E, 354m.s.l.), Thailand in northern PSEA. Cluster-wise contributions of BB to PM 2.5 , organic carbon, and elemental carbon were found to be 54-79%, 42-79%, and 39-77%, respectively. Moreover, the cluster-wise aerosol optical index (aerosol optical depth at 500nm≈0.98-2.45), absorption (single scattering albedo ≈0.87-0.85; absorption aerosol optical depth ≈0.15-0.38 at 440nm; absorption Ångström exponent ≈1.43-1.57), and radiative impacts (atmospheric heating rate ≈1.4-3.6Kd -1 ) displayed consistency with the degree of BB. PM 2.5 during Extreme BB (EBB) was ≈4 times higher than during Low BB (LBB), whereas this factor was ≈2.5 for the magnitude of radiative effects. Severe haze (visibility≈4km) due to substantial BB loadings (BB to PM 2.5 ≈79%) with favorable meteorology can significantly impact the local-to-regional air quality and the, daily life of local inhabitants as well as become a respiratory health threat. Additionally, such enhancements in atmospheric heating could potentially influence the regional hydrological cycle and crop productivity over Chiang Mai in

  2. Air pressure changes in the creation and bursting of the type-1 big bubble in deep anterior lamellar keratoplasty: an ex vivo study.

    PubMed

    AlTaan, S L; Mohammed, I; Said, D G; Dua, H S

    2018-01-01

    PurposeTo measure the pressure and volume of air required to create a big bubble (BB) in simulated deep anterior lamellar keratoplasty (DALK) in donor eyes and ascertain the bursting pressure of the BB.Patients and methodsTwenty-two human sclera-corneal discs were used. Air was injected into the corneal stroma to create a BB and the pressure measured by means of a pressure converter attached to the system via a side port. A special clamp was designed to prevent air leak from the periphery of the discs. The pressure at which air emerged in the corneal tissue; the bursting pressure measured after advancing the needle into the bubble cavity and injecting more air; the volume of air required to create a BB and the volume of the BB were ascertained.ResultsType-1 BB were achieved in 19 and type-2 BB in 3 eyes. The maximum pressure reached to create a BB was 96.25+/- 21.61 kpa; the mean type-1 intrabubble pressure was 10.16 +/- 3.65 kpa. The mean bursting pressure of a type-1 BB was 66.65 +/- 18.65 kpa, while that of a type-2 BB was 14.77 +/- 2.44 kpa. The volume of air required to create a type-1 BB was 0.54 ml and the volume of a type-1 BB was consistently 0.1 ml.ConclusionsDua's layer baring DALK can withstand high intraoperative pressures compared to Descemet's membrane baring DALK. The study suggests that it could be safe to undertake procedures such as DALK-triple with a type-1 BB but not with a type-2 BB.

  3. The Z {yields} cc-bar {yields} {gamma}{gamma}*, Z {yields} bb-bar {yields} {gamma}{gamma}* triangle diagrams and the Z {yields} {gamma}{psi}, Z {yields} {gamma}Y decays

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Achasov, N. N., E-mail: achasov@math.nsc.ru

    2011-03-15

    The approach to the Z {yields} {gamma}{psi} and Z {yields} {gamma}Y decay study is presented in detail, based on the sum rules for the Z {yields} cc-bar {yields} {gamma}{gamma}* and Z {yields} bb-bar {yields} {gamma}{gamma}* amplitudes and their derivatives. The branching ratios of the Z {yields} {gamma}{psi} and Z {yields} {gamma}Y decays are calculated for different hypotheses on saturation of the sum rules. The lower bounds of {Sigma}{sub {psi}} BR(Z {yields} {gamma}{psi}) = 1.95 Multiplication-Sign 10{sup -7} and {Sigma}{sub {upsilon}} BR(Z {yields} {gamma}Y) = 7.23 Multiplication-Sign 10{sup -7} are found. Deviations from the lower bounds are discussed, including the possibilitymore » of BR(Z {yields} {gamma}J/{psi}(1S)) {approx} BR(Z {yields} {gamma}Y(1S)) {approx} 10{sup -6}, that could be probably measured in LHC. The angular distributions in the Z {yields} {gamma}{psi} and Z {yields} {gamma}Y decays are also calculated.« less

  4. Growth of infants fed formula supplemented with Bifidobacterium lactis Bb12 or Lactobacillus GG: a systematic review of randomized controlled trials.

    PubMed

    Szajewska, Hania; Chmielewska, Anna

    2013-11-12

    Growth is an essential outcome measure for evaluating the safety of any new ingredients, including probiotics, added to infant formulae. The aim of this systematic review was to determine the effects of supplementation of infant formulae with Bifidobacterium lactis Bb12 (B lactis) and/or Lactobacillus rhamnosus GG (LGG) compared with unsupplemented formula on the growth of healthy infants. The MEDLINE, EMBASE, and Cochrane Library databases were searched in June 2013 for relevant randomized controlled trials (RCTs) conducted in healthy term infants. Unpublished data were obtained from the manufacturer of B lactis-supplemented formula. The primary outcome measures were weight, length, and head circumference. Nine eligible trials were identified. Compared with unsupplemented controls, supplementation of infant formula with B lactis had no effect on weight gain [4 RCTs, n = 266, mean difference (MD) 0.96 g/day, 95% confidence interval (CI) -0.70 to 2.63)], length gain (4 RCTs, n = 261, MD -0.39 mm/month, 95% CI -1.32 to 0.53), or head circumference gain (3 RCTs, n = 207, MD 0.56 mm/month, 95% CI -0.17 to 1.30). Data limited to one small (n = 105) trial suggest that infants who received standard infant formula supplemented with LGG grew significantly better. No such effect was observed in infants fed hydrolyzed formula supplemented with LGG. Supplementation of infant formula with B lactis results in growth similar to what is found in infants fed unsupplemented formula. Limited data do not allow one to reach a conclusion regarding the effect of LGG supplementation on infant growth.

  5. Flocculation of high purity wheat straw soda lignin.

    PubMed

    Piazza, G J; Lora, J H; Garcia, R A

    2014-01-01

    In industrial process, acidification causes non-sulfonated lignin insolubility. The flocculants poly(diallyldimethylammonium chloride) (pDADMAC) and bovine blood (BB) also caused lignin insolubility while cationic polyacrylamide, chitosan, and soy protein PF 974 were ineffective. Turbidity determined optimal flocculant, but turbidity magnitude with BB was greater than expected. pDADMAC caused negative lignin Zeta potential to became positive, but BB-lignin Zeta potential was always negative. Insoluble lignin did not gravity sediment, and flocculant-lignin mixtures were centrifuged. Pellet and supernatant dry mass and corrected spectroscopic results were in good agreement for optimal pDADMAC and BB. Spectroscopy showed 87-92% loss of supernatant lignin. Nitrogen analysis showed BB concentrated in the pellet until the pellet became saturated with BB. Subtracting ash and BB mass from pellet and supernatant mass confirmed optimal BB. Low levels of alum caused increased lignin flocculation at lower levels of pDADMAC and BB, but alum did not affect optimal flocculant. Published by Elsevier Ltd.

  6. Particulate-phase mercury emissions from biomass burning and impact on resulting deposition: a modelling assessment

    EPA Science Inventory

    Mercury (Hg) emissions from biomass burning (BB) are an important source of atmospheric Hg and a major factor driving the interannual variation of Hg concentrations in the troposphere. The greatest fraction of Hg from BB is released in the form of elemental Hg (Hg0(g)). However, ...

  7. AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists.

    PubMed

    Moody, Terry W; Tashakkori, Nicole; Mantey, Samuel A; Moreno, Paola; Ramos-Alvarez, Irene; Leopoldo, Marcello; Jensen, Robert T

    2017-01-01

    While peptide antagonists for the gastrin-releasing peptide receptor (BB 2 R), neuromedin B receptor (BB 1 R), and bombesin (BB) receptor subtype-3 (BRS-3) exist, there is a need to develop non-peptide small molecule inhibitors for all three BBR. The BB agonist (BA)1 binds with high affinity to the BB 1 R, BB 2 R, and BRS-3. In this communication, small molecule BBR antagonists were evaluated using human lung cancer cells. AM-37 and ST-36 inhibited binding to human BB 1 R, BB 2 R, and BRS-3 with similar affinity ( K i = 1.4-10.8 µM). AM-13 and AM-14 were approximately an order of magnitude less potent than AM-37 and ST-36. The ability of BA1 to elevate cytosolic Ca 2+ in human lung cancer cells transfected with BB 1 R, BB 2 R, and BRS-3 was antagonized by AM-37 and ST-36. BA1 increased tyrosine phosphorylation of the EGFR and ERK in lung cancer cells, which was blocked by AM-37 and ST-36. AM-37 and ST-36 reduced the growth of lung cancer cells that have BBR. The results indicate that AM-37 and ST-36 function as small molecule BB receptor antagonists.

  8. Association between vitamin D receptor BsmI polymorphism and bone mineral density in pediatric patients: A meta-analysis and systematic review of observational studies.

    PubMed

    Bao, Li; Chen, Mingzhi; Lei, Yong; Zhou, Zemin; Shen, Huiping; Le, Feng

    2017-04-01

    Vitamin D and the vitamin D receptor (VDR) are important in the metabolic processes that affect bone mineral density (BMD). However, the effect of VDR BsmI polymorphism on BMD in pediatric patients is still unclear. Eligible studies were identified from the following electronic databases: PubMed, Embase, the Cochrane Library, and the Chinese CNKI and Wanfang databases before October 1, 2016. Data were extracted from the eligible studies, and associations between VDR BsmI polymorphism and BMD in pediatric patients were estimated with weighted mean differences (WMDs) and 95% confidence intervals (CIs). Subgroup analysis of ethnicity and sensitivity analyses were used to identify sources of heterogeneity. A significant difference was observed between VDR BsmI polymorphism and pediatric BMD levels of the lumbar spine (LS) in the corecessive model (bb vs BB + Bb: WMD = -0.23, 95% CI [-0.35, -0.11], P < 0.01). No significant relationship was found in the dominant, recessive, or codominant models for LS BMD (BB vs Bb: WMD = -0.56, 95% CI [-1.58, 0.46], P = 0.29; BB vs bb: WMD = -0.54, 95% CI [-1.49, 0.41], P = 0.27; and BB vs Bb + bb: WMD = -0.45, 95% CI [-1.71, 0.26], P = 0.22). In addition, we found no remarkable association between the BsmI polymorphism and BMD levels of the femoral neck (FN) in children (BB vs Bb: WMD = -1.08, 95% CI [-3.13, 0.96], P = 0.30; BB vs bb: WMD = 0.98, 95% CI [-0.89, 2.85], P = 0.31; BB vs Bb + bb: WMD = -0.061, 95% CI [-0.30, 0.17], P = 0.61; and bb vs BB + Bb: WMD = 0.82, 95% CI [-0.59, 2.32], P = 0.25). Our meta-analysis found that the VDR BsmI genetic polymorphism was correlated with LS BMD level in pediatric patients: compared with those with the B allele, children with the bb genotype were less likely to have lower BMD levels. No significant difference was identified in the pediatric FN BMD levels.

  9. CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results.

    PubMed

    Till, Brian G; Jensen, Michael C; Wang, Jinjuan; Qian, Xiaojun; Gopal, Ajay K; Maloney, David G; Lindgren, Catherine G; Lin, Yukang; Pagel, John M; Budde, Lihua E; Raubitschek, Andrew; Forman, Stephen J; Greenberg, Philip D; Riddell, Stanley R; Press, Oliver W

    2012-04-26

    Cellular immune responses have the potential to elicit dramatic and sustained clinical remissions in lymphoma patients. Recent clinical trial data demonstrate that modification of T cells with chimeric antigen receptors (CARs) is a promising strategy. T cells containing CARs with costimulatory domains exhibit improved activity against tumors. We conducted a pilot clinical trial testing a "third-generation" CD20-specific CAR with CD28 and 4-1BB costimulatory domains in patients with relapsed indolent B-cell and mantle cell lymphomas. Four patients were enrolled, and 3 received T-cell infusions after cyclophosphamide lymphodepletion. Treatment was well tolerated, although one patient developed transient infusional symptoms. Two patients without evaluable disease remained progression-free for 12 and 24 months. The third patient had an objective partial remission and relapsed at 12 months after infusions. Modified T cells were detected by quantitative PCR at tumor sites and up to 1 year in peripheral blood, albeit at low levels. No evidence of host immune responses against infused cells was detected. In conclusion, adoptive immunotherapy with CD20-specific T cells was well tolerated and was associated with antitumor activity. We will pursue alternative gene transfer technologies and culture conditions in future studies to improve CAR expression and cell production efficiency.

  10. Metastasis Risk Reduction Related with Beta-Blocker Treatment in Mexican Women with Breast Cancer.

    PubMed

    Parada-Huerta, E; Alvarez-Dominguez, Tp; Uribe-Escamilla, R; Rodriguez-Joya, Jf; Ponce-Medrano, Ja Diaz; Padron-Lucio, S; Alfaro-Rodriguez, A; Bandala, C

    2016-01-01

    Breast Cancer (BCa) is the most common malignant tumour in Mexican women. In BCa, several studies have linked β2-adrenergic receptor activation with increased tumour growth and progression as related with Epinephrine-NorEpinephrine (E-NE) stimulation. The aim of this study was to describe Beta-Blocker (BB) treatment related with reduction of the risk of metastasis in Mexican patients with BCa. We collected data of 120 patients seen at the High-Specialty Naval General Hospital in Mexico City (HOSGENAES), all of these with a histopathological diagnosis of BCa. Four groups of patients were divided as follows: without Systemic Arterial Hypertension (SAH); with SAH treatment with non-selective BB; with SAH treatment with selective BB, and with SAH treatment with other antihypertensive drugs. Chi-square, Mantel- Haenszel, Student t, and ANOVA tests were performed for data analysis. On average, patients were 54.8±11.8 years of age. Risk factors such as smoking and consuming alcohol exhibited a frequency of 33 and 36.5% respectively. Clinical stages III- IV were found in 50% of patients, while, 30% of patients had arterial hypertension (n=29 and N=96, respectively) and 17.5% used BB. One hundred percent of patients with arterial hypertension treated with BB for β1 - and β2 -adrenergic-receptors did not present metastasis globally, but patients treated with β1 BB presented 30% of metastasis while patients treated with no BB or without SAH had around 70% of metastasis. In Mexican patients with BCa and SAH treated with non-selective (β1- and β2-adrenergic receptors) BB, a decrease in the risk for metastasis was observed at the time of diagnosis.

  11. The effects of energetic and informational masking on The Words-in-Noise Test (WIN).

    PubMed

    Wilson, Richard H; Trivette, Cristine P; Williams, Daniel A; Watts, Kelly L

    2012-01-01

    In certain masking paradigms, the masker can have two components, energetic and informational. Energetic masking is the traditional peripheral masking, whereas informational masking involves confusions (uncertainty) between the signal and masker that originate more centrally in the auditory system. Sperry et al (1997) used Northwestern University Auditory Test No. 6 (NU-6) words in multitalker babble to study the differential effects of energetic and informational masking using babble played temporally forward (FB) and backward (BB). The FB and BB are the same except BB is void of the contextual and semantic content cues that are available in FB. It is these informational cues that are thought to fuel informational masking. Sperry et al found 15% better recognition performance (∼3 dB) on BB than on FB, which can be interpreted as the presence of informational masking in the FB condition and not in the BB condition (Dirks and Bower, 1969). The Words-in-Noise Test (WIN) (Wilson, 2003; Wilson and McArdle, 2007) uses NU-6 words as the signal and multitalker babble as the masker, which is a combination of stimuli that potentially could produce informational masking. The WIN presents 5 or 10 words at each of seven signal-to-noise ratios (S/N, SNR) from 24 to 0 dB in 4 dB decrements with the 50% correct point being the metric of interest. The same recordings of the NU-6 words and multitalker babble used by Sperry et al are used in the WIN. To determine whether informational masking was involved with the WIN. Descriptive, quasi-experimental designs were conducted in three experiments using FB and BB in various paradigms in which FB and BB varied from 4.3 sec concatenated segments to essentially continuous. Eighty young adults with normal hearing and 64 older adults with sensorineural hearing losses participated in a series of three experiments. Experiment 1 compared performance on the normal WIN (FB) with performance on the WIN in which the babble segment with each word

  12. Precision blackbody sources for radiometric standards.

    PubMed

    Sapritsky, V I; Khlevnoy, B B; Khromchenko, V B; Lisiansky, B E; Mekhontsev, S N; Melenevsky, U A; Morozova, S P; Prokhorov, A V; Samoilov, L N; Shapoval, V I; Sudarev, K A; Zelener, M F

    1997-08-01

    The precision blackbody sources developed at the All-Russian Institute for Optical and Physical Measurements (Moscow, Russia) and their characteristics are analyzed. The precision high-temperature graphite blackbody BB22p, large-area high-temperature pyrolytic graphite blackbody BB3200pg, middle-temperature graphite blackbody BB2000, low-temperature blackbody BB300, and gallium fixed-point blackbody BB29gl and their characteristics are described.

  13. Particulate-phase mercury emissions from biomass burning ...

    EPA Pesticide Factsheets

    Mercury (Hg) emissions from biomass burning (BB) are an important source of atmospheric Hg and a major factor driving the interannual variation of Hg concentrations in the troposphere. The greatest fraction of Hg from BB is released in the form of elemental Hg (Hg0(g)). However, little is known about the fraction of Hg bound to particulate matter (HgP) released from BB, and the factors controlling this fraction are also uncertain. In light of the aims of the Minamata Convention to reduce intentional Hg use and emissions from anthropogenic activities, the relative importance of Hg emissions from BB will have an increasing impact on Hg deposition fluxes. Hg speciation is one of the most important factors determining the redistribution of Hg in the atmosphere and the geographical distribution of Hg deposition. Using the latest version of the Global Fire Emissions Database (GFEDv4.1s) and the global Hg chemistry transport model, ECHMERIT, the impact of Hg speciation in BB emissions, and the factors which influence speciation, on Hg deposition have been investigated for the year 2013. The role of other uncertainties related to physical and chemical atmospheric processes involving Hg and the influence of model parametrisations were also investigated, since their interactions with Hg speciation are complex. The comparison with atmospheric HgP concentrations observed at two remote sites, Amsterdam Island (AMD) and Manaus (MAN), in the Amazon showed a significant improve

  14. AM-37 and ST-36 Are Small Molecule Bombesin Receptor Antagonists

    PubMed Central

    Moody, Terry W.; Tashakkori, Nicole; Mantey, Samuel A.; Moreno, Paola; Ramos-Alvarez, Irene; Leopoldo, Marcello; Jensen, Robert T.

    2017-01-01

    While peptide antagonists for the gastrin-releasing peptide receptor (BB2R), neuromedin B receptor (BB1R), and bombesin (BB) receptor subtype-3 (BRS-3) exist, there is a need to develop non-peptide small molecule inhibitors for all three BBR. The BB agonist (BA)1 binds with high affinity to the BB1R, BB2R, and BRS-3. In this communication, small molecule BBR antagonists were evaluated using human lung cancer cells. AM-37 and ST-36 inhibited binding to human BB1R, BB2R, and BRS-3 with similar affinity (Ki = 1.4–10.8 µM). AM-13 and AM-14 were approximately an order of magnitude less potent than AM-37 and ST-36. The ability of BA1 to elevate cytosolic Ca2+ in human lung cancer cells transfected with BB1R, BB2R, and BRS-3 was antagonized by AM-37 and ST-36. BA1 increased tyrosine phosphorylation of the EGFR and ERK in lung cancer cells, which was blocked by AM-37 and ST-36. AM-37 and ST-36 reduced the growth of lung cancer cells that have BBR. The results indicate that AM-37 and ST-36 function as small molecule BB receptor antagonists. PMID:28785244

  15. Demonstration of 1-year duration of immunity for attenuated Bordetella bronchiseptica vaccines in dogs.

    PubMed

    Lehar, Craig; Jayappa, Huchappa; Erskine, Jason; Brown, Alicia; Sweeney, Diane; Wassmoen, Terri

    2008-01-01

    Three groups of healthy dogs with low antibody titers to Bordetella bronchiseptica (Bb), canine parainfluenza virus (CPI), and canine adenovirus type 2 (CAV-2) were used in this study. One group was vaccinated with a single dose of monovalent attenuated Bb vaccine and one group with a trivalent vaccine containing attenuated Bb, CPI, and CAV-2; dogs were vaccinated intranasally with a single dose of the respective vaccines. The third group served as unvaccinated controls. All vaccinated dogs subsequently developed serum antibody titers to Bb that persisted for at least 1 year. Following Bb challenge 1 year after vaccination, all vaccinated dogs, regardless of group, showed significantly fewer clinical signs and shed significantly fewer challenge organisms than unvaccinated controls. These results demonstrate that intranasal administration of a single dose of monovalent attenuated Bb vaccine or trivalent vaccine containing attenuated Bb, CPI, and CAV-2 provides 1 year of protection against Bb.

  16. Bone repair of critical size defects treated with mussel powder associated or not with bovine bone graft: histologic and histomorphometric study in rat calvaria.

    PubMed

    Trotta, Daniel Rizzo; Gorny, Clayton; Zielak, João César; Gonzaga, Carla Castiglia; Giovanini, Allan Fernando; Deliberador, Tatiana Miranda

    2014-09-01

    The objective of this study was to evaluate the bone repair of critical size defects treated with mussel powder with or without additional bovine bone. Critical size defects of 5 mm were realized in the calvaria of 70 rats, which were randomly divided in 5 groups - Control (C), Autogenous Bone (AB), Mussel Powder (MP), Mussel Powder and Bovine Bone (MP-BB) and Bovine Bone (BB). Histological and histomorphometric analysis were performed 30 and 90 days after the surgical procedures (ANOVA e Tukey p < 0.05). After 30 days, the measures of remaining particles were: 28.36% (MP-BB), 26.63% (BB) and 8.64% (MP) with a statistically significant difference between BB and MP. The percentage of osseous matrix after 30 days was, AB (55.17%), 23.31% (BB), 11.66% (MP) and 10.71% (MP-BB) with statistically significant differences among all groups. After 90 days the figures were 25.05% (BB), 21.53% (MP-BB) and 1.97% (MP) with statistically significant differences between MP-BB and MP. Percentages of new bone formation after 90 days were 89.47% (AB), 35.70% (BB), 26.48% (MP-BB) and 7.37% (MP) with statistically significant differences between AB and the other groups. Within the limits of this study, we conclude that mussel powder, with or without additional bovine bone, did not induce new bone formation and did not repair critical size defects in rat calvaria. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  17. Effect of PDGF-BB combined with EDTA gel on adhesion and proliferation to the root surface.

    PubMed

    Belal, Mahmoud Helmy; Watanabe, Hisashi; Ichinose, Shizuko; Ishikawa, Isao

    2012-07-01

    Periodontal regeneration using EDTA or PDGF showed promising results, but the effect of combined application was still unclear. This study aimed to verify the effect of EDTA and/or PDGF application on root adhesion and proliferation of PDL fibroblast cells. Eighty specimens were prepared from forty periodontitis teeth and made five groups: (1) diseased (untreated), (2) SRP (scaling root planing), (3) EDTA (24%), (4) PDGF (25 ng/ml) and (5) Combined application of EDTA and PDGF. Periodontal ligament cells were cultured on the above conditioned dentin plate, and SEM examination was preformed and cells were counted within a representative standard area for both cell morphology and density. All groups including untreated showed significantly increase of adhered cells from baseline to 7 days. Among them, rate of increase was much higher in EDTA, PDGF, and combined groups. ANOVA test indicated that the number of cells in PDGF and combined groups was significantly higher than diseased group at 1 day. On day 7, PDGF and combined groups showed significantly higher number of adhesion cells than that found in the diseased, SRP and EDTA groups. Thus, root conditioning with EDTA enhanced cell adhesion more than SRP alone. There was no significant difference of cell number between PDGF and combined group. Combined application of EDTA and PDGF increased significantly PDL cell adhesion than EDTA alone. PDGF alone, however, also showed comparable effect to combined application at all periods. Thus, synergistic effect between PDGF and EDTA was not observed.

  18. Effects of Bobath-based therapy on depression, shoulder pain and health-related quality of life in patients after stroke.

    PubMed

    Hafsteinsdóttir, Thóra B; Kappelle, Jaap; Grypdonck, Maria H F; Algra, Ale

    2007-10-01

    To measure the effects of Bobath-based (BB) therapy on depression, shoulder pain and health-related quality of life (HRQoL) of patients during one year after stroke. In a prospective, non-randomized design, the use of BB therapy was compared with a more task-oriented therapy and no BB therapy. A total of 324 patients in 12 hospitals. Patients in the intervention group received BB therapy, whereas patients in the control group received no BB therapy and a more task-oriented therapy. HRQoL was measured using the SF-36; depression was measured with the Center of Epidemiological Studies Depression Scale and shoulder pain was measured with the Visual Analogue Scale at discharge, 6 and 12 months. Linear and logistic regression analyses were performed. No effects of BB therapy on HRQoL or shoulder pain were found. After one year fewer patients were depressed in the BB group (30%) than in the non-BB group (43%); the adjusted odds ratio was 0.6 (95% confidence interval 0.3-1.0). BB therapy did not have any effect on HRQoL or shoulder pain in stroke patients. Healthcare professionals should reconsider the use of BB therapy in the care of stroke patients.

  19. [Association between VDR gene polymorphisms and HOMA index for prediabetes in Ningxia].

    PubMed

    Liao, Sha; He, Jun; Li, Xiaoxia; Xu, Honexia; Liu, Xiuying; Zhao, Yi; Zhang, Yuhong

    2016-03-01

    To explore the association between the vitamin D receptor (VDR) gene polymorphisms and HOMA index in prediabetes. On the basis of a cross-sectional study which was conducted in Ningxia during 2008-2012, 339 controls and 468 subjects with prediabetes were selected according to ADA diabetes diagnosis standards. Anthropometric data and blood samples were collected in the field investigation. Blood biochemistry analyses and insulin determination were carried out in the laboratory. The whole blood DNA was extracted for genotyping. The BMI, WC, FPG and HOMA-IR of individuals with prediabetes were higher than those of the controls, while the HOMA-B and HOMA-S in cases were lower than those of the controls (P < 0.05). In BsmI, individuals with prediabetes carrying genotype BB/Bb showed lower HOMA-B than bb carrier, and they showed significantly higher HOMA-S than bb carriers (P < 0.05). After adjusting age, sex, BMI, TC, TG and SBP, low level HOMA-B index was the risk factor of prediabetes in individuals who carried genotype BB/Bb for BsmI and genotype FF/Ff/ff for FokI (OR > 1 , P < 0.05 ), and the genotype ff got the highest risk level (OR = 10.59). In FokI, the Ff carriers with low level HOMA-S and HOM-IR were also the risk factors of prediabetes (OR > 1, P < 0.05). The VDR gene polymorphisms appeared to be associated with HOMA index in prediabetes. The BsmI polymorphism seemed to influence HOMA-B, while the FokI polymorphism influence HOMA-B and HOMA-IR at different levels.

  20. Lithospheric structure of an incipient rift basin: Results from receiver function analysis of Bransfield Strait, NW Antarctic Peninsula

    NASA Astrophysics Data System (ADS)

    Biryol, C. Berk; Lee, Stephen J.; Lees, Jonathan M.; Shore, Michael J.

    2018-06-01

    Bransfield Basin (BB), located northwest of the Antarctic Peninsula (AP) and southeast of the South Shetland Islands (SSI), is the most active section of the Antarctic continental margin. The region has long been (50 Ma) a convergent plate boundary where the Phoenix plate was subducting beneath the Antarctic Plate and is characterized by long-lived arc magmatism and accretion. However, the collision of the Antarctic-Phoenix spreading center with the subduction front near SSI (ca. 4 Ma) gave way to the opening of slab windows and dramatic decrease in the subduction rate of the Phoenix plate beneath AP and SSI. Consequently, the Phoenix slab began to rollback slowly along the South Shetland Trench (SST), giving way to slow extension in the back-arc region and rifting along the BB. Although there is consensus on the factors that control the current deformation and extension of the BB, the origin of the BB and the tectonic configuration of the basin are still unclear. Most of the controversy stems from uncertainties regarding the crustal thickness of the BB. Hence, we computed teleseismic receiver functions for 10 broadband stations in the region that belong to existing permanent and temporary deployments in order obtain robust constraints on the lithospheric structure and crustal thickness of the BB, as well as the AP and SSI. Our results indicate that the crust is thinning from 30 km to 26 km from the AP towards the South Shetland trench and Central BB showing the asymmetrical character of the rift basin. The crustal thickness and Vp/Vs variations are less pronounced along the AP but very significant across the SSB indicating the lithospheric scale segmentation of the South Shetland Block (SSB) and the incipient rift basin under the control of the opening of slab window and the roll-back of stalled Phoenix slab. High Vp/Vs ratios (∼1.9) beneath BB and SSI, agree well with the nascent rift character of BB, the presence of a steep Phoenix slab and consequently a

  1. SGR J1550-5418 Bursts Detected with the Fermi Gamma-Ray Burst Monitor during Its Most Prolific Activity

    NASA Technical Reports Server (NTRS)

    vanderHorst, A. J.; Kouveliotou, C.; Gorgone, N. M.; Kaneko, Y.; Baring, M. G.; Guiriec, S.; Gogus, E,; Granot, J.; Watts, A. L.; Lin, L.; hide

    2012-01-01

    We have performed detailed temporal and time-integrated spectral analysis of 286 bursts from SGR J1550-5418 detected with the Fermi Gamma-ray Burst Monitor (GBM) in 2009 January, resulting in the largest uniform sample of temporal and spectral properties of SGR J1550-5418 bursts. We have used the combination of broadband and high time-resolution data provided with GBM to perform statistical studies for the source properties.We determine the durations, emission times, duty cycles, and rise times for all bursts, and find that they are typical of SGR bursts. We explore various models in our spectral analysis, and conclude that the spectra of SGR J15505418 bursts in the 8-200 keV band are equally well described by optically thin thermal bremsstrahlung (OTTB), a power law (PL) with an exponential cutoff (Comptonized model), and two blackbody (BB) functions (BB+BB). In the spectral fits with the Comptonized model, we find a mean PL index of -0.92, close to the OTTB index of -1. We show that there is an anti-correlation between the Comptonized E(sub peak) and the burst fluence and average flux. For the BB+BBfits, we find that the fluences and emission areas of the two BB functions are correlated. The low-temperature BB has an emission area comparable to the neutron star surface area, independent of the temperature, while the high temperature BB has a much smaller area and shows an anti-correlation between emission area and temperature.We compare the properties of these bursts with bursts observed from other SGR sources during extreme activations, and discuss the implications of our results in the context of magnetar burst models.

  2. Forever Young: The Role of Ubiquitin Receptor DA1 and E3 Ligase BIG BROTHER in Controlling Leaf Growth and Development1[OPEN

    PubMed Central

    Vanhaeren, Hannes; De Milde, Liesbeth

    2017-01-01

    The final size of plant organs is determined by a combination of cell proliferation and cell expansion. Leaves account for a large part of above-ground biomass and provide energy to complete the plant’s life cycle. Although the final size of leaves is remarkably constant under fixed environmental conditions, several genes have been described to enhance leaf growth when their expression is modulated. In Arabidopsis (Arabidopsis thaliana), mutations in DA1 and BB increase leaf size, an effect that is synergistically enhanced in the double mutant. Here, we show that overexpression of a dominant-negative version of DA1 enhances leaf size in a broad range of natural accessions of this species, indicating a highly conserved role of this protein in controlling organ size. We also found that during early stages of development, leaves of da1-1 and bb/eod1-2 mutants were already larger than the isogenic Col-0 wild type, but this phenotype was triggered by different cellular mechanisms. Later during development, da1-1 and bb/eod1-2 leaves showed a prolonged longevity, which was enhanced in the double mutant. Conversely, ectopic expression of DA1 or BB restricted growth and promoted leaf senescence. In concert, shortly upon induction of DA1 and BB expression, several marker genes for the transition from proliferation to expansion were highly up-regulated. Additionally, multiple genes involved in maintaining the mitotic cell cycle were rapidly down-regulated and senescence genes were strongly up-regulated, particularly upon BB induction. With these results, we demonstrate that DA1 and BB restrict leaf size and promote senescence through converging and different mechanisms. PMID:28003326

  3. Comparative efficacy of intranasal and injectable vaccines in stimulating Bordetella bronchiseptica-reactive anamnestic antibody responses in household dogs

    PubMed Central

    Ellis, John A.; Gow, Sheryl P.; Lee, Lindsey B.; Lacoste, Stacey; Ball, Eileen C.

    2017-01-01

    In order to determine the comparative efficacy of injectable and intranasal vaccines to stimulate Bordetella bronchiseptica (Bb)-reactive anamnestic antibodies, a trial was conducted using 144 adult household dogs of various breeds and ages, which had been previously administered intranasal Bb vaccine approximately 12 months before enrollment. Dogs were randomized into 2 groups and blood, nasal swabs, and pharyngeal swabs were collected prior to the administration of single component Bb vaccines intranasally or parenterally. Ten to 14 days later all dogs were resampled to measure changes in systemic and local antibody to Bb. There were no differences in the changes in Bb-reactive serum IgG and nasal IgA between the groups, whereas intranasally vaccinated dogs had significantly higher Bb-reactive serum IgA. These data indicate that both of the current generation of intranasal (modified-live) and injectable (acellular) Bb vaccines can stimulate anamnestic local and systemic antibody responses in previously vaccinated, Bb-seropositive adult household dogs. PMID:28761185

  4. Long-term cytokine and growth factor release from equine platelet-rich fibrin clots obtained with two different centrifugation protocols.

    PubMed

    Jiménez-Aristizabal, Román F; López, Catalina; Álvarez, María E; Giraldo, Carlos; Prades, Marta; Carmona, Jorge U

    2017-09-01

    To compare the temporal release (over three weeks) of tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-1 receptor antagonist (IL-1ra), platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta-1 (TGF-β 1 ) from two platelet-rich fibrin (PRF) preparations from equine blood obtained at either 240g/8min or 416g/10min. Whole blood from 10 horses was used to obtain PRF clots by two different centrifugation protocols. After 1h of rest, PRF clots were deposited in wells with culture medium, which was changed at 6h, 24h and then every 48h to 21days. Cytokines and GFs were measured by ELISA at 1h (serum supernatants from PRF clots) and all time points of culture medium change. A negative control (plasma) and a positive control (blood lysate) were also included. There were no relevant differences between the two protocols for the temporal release of proteins. However, a significant (p=0.01) effect of time was noted. All cytokines were detected after 6h of PRF clot culture until day 21. GF were detected at 1h until day 21. The concentrations for these proteins diminished gradually over time. A highly significant (p=0.01) correlation was noticed between all the proteins evaluated. Leukocytes enmeshed in PRF clots were able to produce cytokines, TGF-β 1 and PDGF-BB. These findings demonstrate a paramount role of leukocytes in wound healing induced or modified by PRF clots in mammals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Improved survival of baby boomer women with early-stage uterine cancer: A Surveillance, Epidemiology and End Results (SEER) Study.

    PubMed

    Elshaikh, Mohamed A; Ruterbusch, Julie; Cote, Michele L; Cattaneo, Richard; Munkarah, Adnan R

    2013-11-01

    To study the prognostic impact of baby boomer (BB) generation on survival end-points of patients with early-stage endometrial carcinoma (EC). Data were obtained from the SEER registry between 1988-2009. Inclusion criteria included women who underwent hysterectomy for stage I-II EC. Patients were divided into two birth cohorts: BB (women born between 1946 and 1964) and pre-boomers (PB) (born between 1926 and 1945). A total of 30,956 patients were analyzed. Considering that women in the PB group were older than those of the BB generation, the statistical analysis was limited to women 50-59 years of age at the time of diagnosis (n=11,473). Baby boomers had a significantly higher percentage of endometrioid histology (p<0.0001), higher percentage of African American women (p<0.0001), lower tumor grade (p<0.0001), higher number of dissected lymph nodes (LN) (p<0.0001), and less utilization of adjuvant radiation therapy (p=0.0003). Overall survival was improved in women in the BB generation compared to the PB generation (p=0.0003) with a trend for improved uterine cancer-specific survival (p=0.0752). On multivariate analysis, birth cohort (BB vs. PB) was not a significant predictor of survival end-points. Factors predictive of survival included: tumor grade, FIGO stage, African-American race, and increased number of dissected LN. Our study suggests that the survival of BB women between 50-60 years of age is better compared to women in the PB generation. As more BB patients are diagnosed with EC, further research is warranted.

  6. Optical coherence tomography characteristics of different types of big bubbles seen in deep anterior lamellar keratoplasty by the big bubble technique

    PubMed Central

    AlTaan, S L; Termote, K; Elalfy, M S; Hogan, E; Werkmeister, R; Schmetterer, L; Holland, S; Dua, H S

    2016-01-01

    Purpose To define optical coherence tomography (OCT) characteristics of type-1, type-2, and mixed big bubbles (BB) seen in deep anterior lamellar keratoplasty. Methods Human sclero-corneal discs were obtained from UK (30) and Canada (16) eye banks. Air was injected into corneal stroma until a BB formed. UK samples were fixed in formalin before scanning with Fourier-domain (FD-OCT). One pair of each type of BB was scanned fresh. All BB obtained from Canada were scanned fresh with time-domain (TD-OCT). For each OCT machine used, type-1 BB from which Descemets membrane (DM) was partially peeled, were also scanned. The morphological characteristics of the scans were studied. Results FD-OCT of the posterior wall of type-1 (Dua's layer (DL) with DM) and type-2 BB (DM alone) both revealed a double-contour hyper-reflective curvilinear image with a hypo-reflective zone in between. The anterior line of type-2 BB was thinner than that seen with type-1 BB. In mixed BB, FD-OCT showed two separate curvilinear images. The anterior image was a single hyper-reflective line (DL), whereas the posterior image, representing the posterior wall of type-2 BB (DM) was made of two hyper-reflective lines with a dark space in between. TD-OCT images were similar with less defined component lines, but the entire extent of the BB could be visualised. Conclusion On OCT examination the DM and DL present distinct features, which can help identify type-1, type-2, and mixed BB. These characteristics will help corneal surgeons interpret intraoperative OCT during lamellar corneal surgery. PMID:27472215

  7. Validation of Improved Broadband Shortwave and Longwave Fluxes Derived From GOES

    NASA Technical Reports Server (NTRS)

    Khaiyer, Mandana M.; Nordeen, Michele L.; Palikonda, Rabindra; Yi, Yuhong; Minnis, Patrick; Doelling, David R.

    2009-01-01

    Broadband (BB) shortwave (SW) and longwave (LW) fluxes at TOA (Top of Atmosphere) are crucial parameters in the study of climate and can be monitored over large portions of the Earth's surface using satellites. The VISST (Visible Infrared Solar Split-Window Technique) satellite retrieval algorithm facilitates derivation of these parameters from the Geostationery Operational Environmental Satellites (GOES). However, only narrowband (NB) fluxes are available from GOES, so this derivation requires use of narrowband-to-broadband (NB-BB) conversion coefficients. The accuracy of these coefficients affects the validity of the derived broadband (BB) fluxes. Most recently, NB-BB fits were re-derived using the NB fluxes from VISST/GOES data with BB fluxes observed by the CERES (Clouds and the Earth's Radiant Energy Budget) instrument aboard Terra, a sun-synchronous polar-orbiting satellite that crosses the equator at 10:30 LT. Subsequent comparison with ARM's (Atmospheric Radiation Measurement) BBHRP (Broadband Heating Rate Profile) BB fluxes revealed that while the derived broadband fluxes agreed well with CERES near the Terra overpass times, the accuracy of both LW and SW fluxes decreased farther away from the overpass times. Terra's orbit hampers the ability of the NB-BB fits to capture diurnal variability. To account for this in the LW, seasonal NB-BB fits are derived separately for day and night. Information from hourly SW BB fluxes from the Meteosat-8 Geostationary Earth Radiation Budget (GERB) is employed to include samples over the complete solar zenith angle (SZA) range sampled by Terra. The BB fluxes derived from these improved NB-BB fits are compared to BB fluxes computed with a radiative transfer model.

  8. Mississippi River: Study of Alternatives for Rehabilitation of Lock and Dam Number 1. Minneapolis, Minnesota. Volume 4. Appendices G-M.

    DTIC Science & Technology

    1976-04-01

    juniper (Juniperus chinensis, var. pfitzeriana), globe juniper (Juni]erus virginiana , var. globosa), dwarf Japanese yew (Taxus cuspidata, var. nana) and...excessively, compacted after planting. Heavy pruning of the tree’s upper branches is recommended at this point, to reduce the load put on root functioning...8217 5@9 BB 500.00 Shrubs-2 Juniperus chinensis 4𔃻 BB 42.00 Juniperus virginiana 31- BB 48.70 Taxus cuspidata 31 BB 38.40 *Cotoneaster apiculata 5’ BB

  9. Gut microbiota mediated benefits of barley kernel products on metabolism, gut hormones, and inflammatory markers as affected by co-ingestion of commercially available probiotics: a randomized controlled study in healthy subjects.

    PubMed

    Nilsson, Anne; Johansson-Boll, Elin; Sandberg, Jonna; Björck, Inger

    2016-10-01

    Barley kernel based products have been shown to induce benefits on blood glucose regulation, cardio-metabolic risk markers and appetite regulating hormones in a time perspective of 11-16 h after intake. The mechanisms have been assigned to gut fermentation of indigestible carbohydrates. The purpose of the present study was to evaluate if the modulatory effects of barley on markers of metabolic- and appetite regulation are affected by a dietary background including a mixture of commercially available probiotics. Barley kernel bread was included in the normal diet of 21 healthy subjects in two 4-day intervention periods; with (BB-pro) or without (BB) dietary supplement with a combination of probiotics (Bifidobacterium animalis DN-173 010, Lactobacillus reuteri DSM 17938, and Lactobacillus plantarum 299v). A white wheat flour based bread was included as a reference product (WWB-ref) in a separate 4-day bread intervention period. A cross-over design was applied concerning BB- and WWB-ref; the BB-pro intervention was last in the test sequence. The BB-pro intervention was preceded by 10 days priming with probiotics. The 4 day BB- and WWB-ref intervention periods included dietary supplementation with placebo, and the interventions were preceded with 10 days priming with the placebo. The day after each intervention period, blood samples were collected at fasting and postprandially after a standardized breakfast (0-210 min) for determination of markers of glucose metabolism (blood glucose, serum (s-) insulin), inflammation (s-IL-6, s-IL-18, s-CRP, PAI-1), and concentrations of gut derived hormones involved in satiety and glucose homeostasis (plasma (p-) PYY, p-GLP-1) and intestinal barrier integrity (p-GLP-2). Breath hydrogen was determined as a marker of colonic fermentation. Four days intervention with BB, in comparison to WWB-ref, lowered blood glucose response after a subsequent standardized breakfast (0-210 min, P < 0.05). BB and BB-pro interventions increased p

  10. HIV-1 Tat-mediated induction of Platelet-derived Growth Factor in Astrocytes: Role of Early Growth Response Gene 1

    PubMed Central

    Bethel-Brown, Crystal; Yao, Honghong; Callen, Shannon; Lee, Young Han; Dash, Prasanta K; Kumar, Anil; Buch, Shilpa

    2011-01-01

    HIV-associated neurological disorders (HAND) are estimated to affect almost 60% of HIV infected individuals. HIV-encephalitis (HIVE), the pathological correlate of the most severe form of HAND is often characterized by glial activation, cytokine/chemokine dysregulation, and neuronal damage and loss. However, the severity of HIVE correlates better with glial activation rather than viral load. Using the macaque model, it has been demonstrated that simian immunodeficiency virus encephalitis (SIVE) correlates with increased expression of the mitogen platelet-derived growth factor-B (PDGF-B) chain in the brain. The present study was aimed at exploring the role of PDGF-B chain in HIV-associated activation and proliferation of astrocytes. Specifically, the data herein demonstrate that exposure of rat and human astrocytes to the HIV-1 protein, Tat resulted in the induction of PDGF at both the mRNA and protein levels. Furthermore, PDGF-BB induction was regulated by activation of ERK1/2 and JNK signaling pathways and the downstream transcription factor, early growth response 1(Egr-1). Chromatin immunoprecipitation (ChIP) assays demonstrated binding of Egr-1 to the PDGF-B promoter. Exposure of astrocytes to PDGF-BB, in turn, led to both increased proliferation and release of pro-inflammatory cytokines MCP-1 and IL-1β. Since astrogliosis is linked to disease severity, understanding its regulation by PDGF-BB could aid in the development of therapeutic intervention strategies for HAND. PMID:21368226

  11. Expression of platelet-derived growth factor B is upregulated in patients with thoracic aortic dissection.

    PubMed

    Meng, Weixin; Liu, Shangdian; Li, Dandan; Liu, Zonghong; Yang, Hui; Sun, Bo; Liu, Hongyu

    2018-04-20

    Thoracic aortic dissection (TAD) is a serious condition requiring urgent treatment to avoid catastrophic consequences. The inflammatory response is involved in the occurrence and development of TAD, possibly potentiated by platelet-derived growth factors (PDGFs). This study aimed to determine whether expression of PDGF-B (a subunit of PDGF-BB) was increased in TAD patients and to explore the factors responsible for its upregulation and subsequent effects on TAD. Full-thickness ascending aorta wall specimens from TAD patients (n = 15) and control patients (n = 10) were examined for expression of PDGF-B and its receptor (PDGFRB) and in terms of morphology, inflammation, and fibrosis. Blood samples from TAD and control patients were collected to detect plasma levels of PDGF-BB and soluble elastins. Expression levels of PDGF-B, PDGFRB, and collagen I were significantly enhanced in ascending aorta wall specimens from TAD patients compared with controls. Furthermore, soluble elastic fragments and PDGF-BB were significantly increased in plasma from TAD patients compared with controls, and numerous irregular elastic fibers and macrophages were seen in the ascending aorta wall in TAD patients. An increase in elastic fragments in the aorta wall might be responsible for inducing the activation and migration of macrophages to injured sites, leading to elevated expression of PDGF-B, which in turn induces deposition of collagen, disrupts extracellular matrix homeostasis, and increases the stiffness of the aorta wall, resulting in compromised aorta compliance. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  12. Thirty Years of Evidence on the Efficacy of Drug Treatments for Chronic Heart Failure With Reduced Ejection Fraction

    PubMed Central

    Earley, Amy; Voors, Adriaan A.; Senni, Michele; McMurray, John J.V.; Deschaseaux, Celine; Cope, Shannon

    2017-01-01

    Background— Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor–neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction. Methods and Results— A systematic literature review identified 57 randomized controlled trials published between 1987 and 2015, which were compared in terms of study and patient characteristics, baseline risk, outcome definitions, and the observed treatment effects. Despite differences identified in terms of study duration, New York Heart Association class, ejection fraction, and use of background digoxin, a network meta-analysis was considered feasible and all trials were analyzed simultaneously. The random-effects network meta-analysis suggested that the combination of ACEI+BB+MRA was associated with a 56% reduction in mortality versus placebo (hazard ratio 0.44, 95% credible interval 0.26–0.66); ARNI+BB+MRA was associated with the greatest reduction in all-cause mortality versus placebo (hazard ratio 0.37, 95% credible interval 0.19–0.65). A sensitivity analysis that did not account for background therapy suggested that ARNI monotherapy is more efficacious than ACEI or ARB monotherapy. Conclusions— The network meta-analysis showed that treatment with ACEI, ARB, BB, MRA, and ARNI and their combinations were better than the treatment with placebo in reducing all-cause mortality, with the exception of ARB monotherapy and ARB plus ACEI. The combination of ARNI+BB+MRA resulted in the greatest mortality reduction. PMID:28087688

  13. Comparison of MODIS and VIIRS On-board Blackbody Performance

    NASA Technical Reports Server (NTRS)

    Xiong, Jack; Butler, Jim; Wu, Aisheng; Chiang, Vincent; McIntire, Jeff; Oudari, Hassan

    2012-01-01

    MODIS has 16 thermal emissive bands (TEBs), covering wavelengths from 3.7 to 14.4 microns. MODIS TEBs are calibrated on-orbit by a v-grooved blackbody (BB) on a scan-by-scan basis. The BB temperatures are measured by a set of 12 thennistors. As expected, the BB temperature uncertainty and stability have direct impact on the quality of TEB calibration and, therefore, the quality of the science products derived from TEB observations. Since launch, Terra and Aqua MODIS have successfully operated for more than 12 and 10 years, respectively. Their on-board BB performance has been satisfactory in meeting the TEB calibration requirements. The first VIIRS, launched on-board the Suomi NPP spacecraft on October 28, 2011, has successfully completed its initial Intensive Calibration and Validation (ICV) phase. VIIRS has 7 thermal emissive bands (TEBs), covering wavelengths from 3.7 to 12.4 microns. Designed with strong MODIS heritage, VIIRS uses a similar BB for its TEB calibration. Like MODIS, VIIRS BB is nominally controlled at a pre-determined temperature (set point). Periodically, a BB Warm-Up and Cool-Down (WUCD) operation is performed, during which the BB temperatures vary from instrument ambient (temperature) to 315K. This paper examines NPP VIIRS BB on-orbit performance. It focuses on its BB temperature scan-to-scan variations at nominally controlled temperature as well as during its WUCD operation and their impact on TEB calibration uncertainty. Comparisons of VIIRS (NPP) and MODIS (Terra and Aqua) BB on-orbit performance and lessons learned for future improvements are also presented in this paper.

  14. Velocity specificity of training in bodybuilders.

    PubMed

    Bell, D G; Jacobs, I

    1992-03-01

    This study investigated the effects of many years of bodybuilding on muscular strength and endurance. Eight bodybuilders (BB), 4 males and 4 females, and 8 controls (C), 4 males and 4 females, performed a muscle fatigue test (MFT) consisting of 25 maximal leg extensions at angular velocities of 180 and 300 degrees/s. The results for strength showed that at both the slow and fast contraction speeds, BB were significantly stronger than C and males were significantly stronger than females. For muscular endurance the results showed that at the slow contraction speed the torques and torque decline were greater in the BB than in the C, and greater in the males than the females. At the faster contraction speed, torque decline was similar in all groups while torques for the BB and male-C were similar and significantly greater than the torques for the female-C. The ratio of torques (fast/slow) for both strength and muscular endurance showed a main effect due to training status which supported the velocity specificity hypothesis. However, when the relative torques over the 25 contractions at both speeds were looked at, no velocity specificity occurred for muscular endurance. The data suggest a definite velocity specificity for the strength factor in BB whereas the same conclusion is not as clear for the muscular endurance factor.

  15. Multi-instrument comparison and compilation of non-methane organic gas emissions from biomass burning and implications for smoke-derived secondary organic aerosol precursors

    NASA Astrophysics Data System (ADS)

    Hatch, Lindsay E.; Yokelson, Robert J.; Stockwell, Chelsea E.; Veres, Patrick R.; Simpson, Isobel J.; Blake, Donald R.; Orlando, John J.; Barsanti, Kelley C.

    2017-01-01

    Multiple trace-gas instruments were deployed during the fourth Fire Lab at Missoula Experiment (FLAME-4), including the first application of proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOFMS) and comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS) for laboratory biomass burning (BB) measurements. Open-path Fourier transform infrared spectroscopy (OP-FTIR) was also deployed, as well as whole-air sampling (WAS) with one-dimensional gas chromatography-mass spectrometry (GC-MS) analysis. This combination of instruments provided an unprecedented level of detection and chemical speciation. The chemical composition and emission factors (EFs) determined by these four analytical techniques were compared for four representative fuels. The results demonstrate that the instruments are highly complementary, with each covering some unique and important ranges of compositional space, thus demonstrating the need for multi-instrument approaches to adequately characterize BB smoke emissions. Emission factors for overlapping compounds generally compared within experimental uncertainty, despite some outliers, including monoterpenes. Data from all measurements were synthesized into a single EF database that includes over 500 non-methane organic gases (NMOGs) to provide a comprehensive picture of speciated, gaseous BB emissions. The identified compounds were assessed as a function of volatility; 6-11 % of the total NMOG EF was associated with intermediate-volatility organic compounds (IVOCs). These atmospherically relevant compounds historically have been unresolved in BB smoke measurements and thus are largely missing from emission inventories. Additionally, the identified compounds were screened for published secondary organic aerosol (SOA) yields. Of the total reactive carbon (defined as EF scaled by the OH rate constant and carbon number of each compound) in the BB emissions, 55-77 % was associated with compounds for

  16. Scale Closure in Upper Ocean Optical Properties: From Single Particles to Ocean Color

    NASA Technical Reports Server (NTRS)

    Green, Rebecca E.

    2002-01-01

    Predictions of chlorophyll concentration from satellite ocean color are an indicator of primary productivity, with implications for foodwebs, fisheries, and the global carbon cycle. Models describing the relationship between optical properties and chlorophyll do not account for much of the optical variability observed in natural waters, because of the presence of seawater constituents that do not covary with phytoplankton pigments. in order to understand variability in these models, the optical contributions of seawater constituents were investigated. A combination of Mie theory and flow cytometry was used to determine the diameter, complex refractive index, and optical cross-sections of individual particles. In New England continental shelf waters, eukaryotic phytoplankton were the main particle contributors to absorption and scaftering. Minerals were the main contributor to backscattering (bb) in the spring, whereas in the summer both minerals and detritus contributed to bb. Synechococcus and heterotrophic bacteria were relatively unimportant optically. Seasonal differences in the spectral shape of remote sensing reflectance, Rrs, were contributed to approximately equally by eukaryotic phytoplankton absorption, dissolved absorption, and non-phytoplankton bb. Differences between measurements of bb and Prs and modeled values based on chlorophyll concentration were caused by higher dissolved absorption and non-phytoplankton bb than were assumed by the model.

  17. Dietary Blueberry Attenuates Whole-Body Insulin Resistance in High Fat-Fed Mice by Reducing Adipocyte Death and Its Inflammatory Sequelae1–3

    PubMed Central

    DeFuria, Jason; Bennett, Grace; Strissel, Katherine J.; Perfield, James W.; Milbury, Paul E.; Greenberg, Andrew S.; Obin, Martin S.

    2009-01-01

    Adipose tissue (AT) inflammation promotes insulin resistance (IR) and other obesity complications. AT inflammation and IR are associated with oxidative stress, adipocyte death, and the scavenging of dead adipocytes by proinflammatory CD11c+ AT macrophages (ATMΦ). We tested the hypothesis that supplementation of an obesitogenic (high-fat) diet with whole blueberry (BB) powder protects against AT inflammation and IR. Male C57Bl/6j mice were maintained for 8 wk on 1 of 3 diets: low-fat (10% of energy) diet (LFD), high-fat (60% of energy) diet (HFD) or the HFD containing 4% (wt:wt) whole BB powder (1:1 Vaccinium ashei and V. corymbosum) (HFD+B). BB supplementation (2.7% of total energy) did not affect HFD-associated alterations in energy intake, metabolic rate, body weight, or adiposity. We observed an emerging pattern of gene expression in AT of HFD mice indicating a shift toward global upregulation of inflammatory genes (tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein 1, inducible nitric oxide synthase), increased M1-polarized ATMΦ (CD11c+), and increased oxidative stress (reduced glutathione peroxidase 3). This shift was attenuated or nonexistent in HFD+B-fed mice. Furthermore, mice fed the HFD+B were protected from IR and hyperglycemia coincident with reductions in adipocyte death. Salutary effects of BB on adipocyte physiology and ATMΦ gene expression may reflect the ability of BB anthocyanins to alter mitogen-activated protein kinase and nuclear factor-κB stress signaling pathways, which regulate cell fate and inflammatory genes. These results suggest that cytoprotective and antiinflammatory actions of dietary BB can provide metabolic benefits to combat obesity-associated pathology. PMID:19515743

  18. Search for the standard model Higgs boson in ZH→ℓ(+)ℓ(-)bb production with the D0 detector in 9.7 fb(-1) of pp collisions at √s = 1.96 TeV.

    PubMed

    Abazov, V M; Abbott, B; Acharya, B S; Adams, M; Adams, T; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Askew, A; Atkins, S; Augsten, K; Avila, C; Badaud, F; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Barberis, E; Baringer, P; Bartlett, J F; Bassler, U; Bazterra, V; Bean, A; Begalli, M; Bellantoni, L; Beri, S B; Bernardi, G; Bernhard, R; Bertram, I; Besançon, M; Beuselinck, R; Bhat, P C; Bhatia, S; Bhatnagar, V; Blazey, G; Blessing, S; Bloom, K; Boehnlein, A; Boline, D; Boos, E E; Borissov, G; Bose, T; Brandt, A; Brandt, O; Brock, R; Bross, A; Brown, D; Brown, J; Bu, X B; Buehler, M; Buescher, V; Bunichev, V; Burdin, S; Buszello, C P; Camacho-Pérez, E; Casey, B C K; Castilla-Valdez, H; Caughron, S; Chakrabarti, S; Chakraborty, D; Chan, K M; Chandra, A; Chapon, E; Chen, G; Chevalier-Théry, S; Cho, D K; Cho, S W; Choi, S; Choudhary, B; Cihangir, S; Claes, D; Clutter, J; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Croc, A; Cutts, D; Das, A; Davies, G; de Jong, S J; De La Cruz-Burelo, E; Déliot, F; Demina, R; Denisov, D; Denisov, S P; Desai, S; Deterre, C; Devaughan, K; Diehl, H T; Diesburg, M; Ding, P F; Dominguez, A; Dubey, A; Dudko, L V; Duggan, D; Duperrin, A; Dutt, S; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Evans, H; Evdokimov, A; Evdokimov, V N; Facini, G; Feng, L; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Fortner, M; Fox, H; Fuess, S; Garcia-Bellido, A; García-González, J A; García-Guerra, G A; Gavrilov, V; Gay, P; Geng, W; Gerbaudo, D; Gerber, C E; Gershtein, Y; Ginther, G; Golovanov, G; Goussiou, A; Grannis, P D; Greder, S; Greenlee, H; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guillemin, T; Gutierrez, G; Gutierrez, P; Hagopian, S; Haley, J; Han, L; Harder, K; Harel, A; Hauptman, J M; Hays, J; Head, T; Hebbeker, T; Hedin, D; Hegab, H; Heinson, A P; Heintz, U; Hensel, C; Heredia-De La Cruz, I; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hoang, T; Hobbs, J D; Hoeneisen, B; Hogan, J; Hohlfeld, M; Howley, I; Hubacek, Z; Hynek, V; Iashvili, I; Ilchenko, Y; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jayasinghe, A; Jeong, M S; Jesik, R; Jiang, P; Johns, K; Johnson, E; Johnson, M; Jonckheere, A; Jonsson, P; Joshi, J; Jung, A W; Juste, A; Kaadze, K; Kajfasz, E; Karmanov, D; Kasper, P A; Katsanos, I; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y N; Kiselevich, I; Kohli, J M; Kozelov, A V; Kraus, J; Kulikov, S; Kumar, A; Kupco, A; Kurča, T; Kuzmin, V A; Lammers, S; Landsberg, G; Lebrun, P; Lee, H S; Lee, S W; Lee, W M; Lei, X; Lellouch, J; Li, D; Li, H; Li, L; Li, Q Z; Lim, J K; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, H; Liu, Y; Lobodenko, A; Lokajicek, M; Lopes de Sa, R; Lubatti, H J; Luna-Garcia, R; Lyon, A L; Maciel, A K A; Madar, R; Magaña-Villalba, R; Malik, S; Malyshev, V L; Maravin, Y; Martínez-Ortega, J; McCarthy, R; McGivern, C L; Meijer, M M; Melnitchouk, A; Menezes, D; Mercadante, P G; Merkin, M; Meyer, A; Meyer, J; Miconi, F; Mondal, N K; Mulhearn, M; Nagy, E; Naimuddin, M; Narain, M; Nayyar, R; Neal, H A; Negret, J P; Neustroev, P; Nguyen, H T; Nunnemann, T; Orduna, J; Osman, N; Osta, J; Padilla, M; Pal, A; Parashar, N; Parihar, V; Park, S K; Partridge, R; Parua, N; Patwa, A; Penning, B; Perfilov, M; Peters, Y; Petridis, K; Petrillo, G; Pétroff, P; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Popov, A V; Prewitt, M; Price, D; Prokopenko, N; Qian, J; Quadt, A; Quinn, B; Rangel, M S; Ranjan, K; Ratoff, P N; Razumov, I; Renkel, P; Ripp-Baudot, I; Rizatdinova, F; Rominsky, M; Ross, A; Royon, C; Rubinov, P; Ruchti, R; Sajot, G; Salcido, P; Sánchez-Hernández, A; Sanders, M P; Santos, A S; Savage, G; Sawyer, L; Scanlon, T; Schamberger, R D; Scheglov, Y; Schellman, H; Schlobohm, S; Schwanenberger, C; Schwienhorst, R; Sekaric, J; Severini, H; Shabalina, E; Shary, V; Shaw, S; Shchukin, A A; Shivpuri, R K; Simak, V; Skubic, P; Slattery, P; Smirnov, D; Smith, K J; Snow, G R; Snow, J; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Soustruznik, K; Stark, J; Stoyanova, D A; Strauss, M; Suter, L; Svoisky, P; Takahashi, M; Titov, M; Tokmenin, V V; Tsai, Y-T; Tschann-Grimm, K; Tsybychev, D; Tuchming, B; Tully, C; Uvarov, L; Uvarov, S; Uzunyan, S; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vasilyev, I A; Verdier, P; Verkheev, A Y; Vertogradov, L S; Verzocchi, M; Vesterinen, M; Vilanova, D; Vokac, P; Wahl, H D; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weichert, J; Welty-Rieger, L; White, A; Wicke, D; Williams, M R J; Wilson, G W; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Yamada, R; Yang, S; Yang, W-C; Yasuda, T; Yatsunenko, Y A; Ye, W; Ye, Z; Yin, H; Yip, K; Youn, S W; Yu, J M; Zennamo, J; Zhao, T; Zhao, T G; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zivkovic, L

    2012-09-21

    We present a search for the standard model (SM) Higgs boson produced in association with a Z boson in 9.7 fb(-1) of pp collisions collected with the D0 detector at the Fermilab Tevatron Collider at √s = 1.96 TeV. Selected events contain one reconstructed Z→e(+)e(-) or Z→μ(+)μ(-) candidate and at least two jets, including at least one jet identified as likely to contain a b quark. To validate the search procedure, we also measure the cross section for ZZ production in the same final state. It is found to be consistent with its SM prediction. We set upper limits on the ZH production cross section times branching ratio for H→bb at the 95% C.L. for Higgs boson masses 90 ≤ M(H) ≤ 150 GeV. The observed (expected) limit for M(H) = 125 GeV is 7.1 (5.1) times the SM cross section.

  19. Intrinsic and Extrinsic Modifiers of the Regulative Capacity of the Developing Liver

    PubMed Central

    Shin, Donghun; Weidinger, Gilbert; Moon, Randall T.; Stainier, Didier Y.R.

    2012-01-01

    Zebrafish wnt2bb mutants initially fail to form a liver, but surprisingly the liver eventually forms in a majority of these embryos which then develop into fertile adults. This unexpected result raised the possibility that identifying the mechanisms of liver formation in wnt2bb mutants could provide insights into the poorly understood yet general principle of regulative development, a process by which some cells can change fate in order to compensate for a deficiency. Here, we identify two factors that underlie the regulative capacity of endodermal tissues: an intrinsic factor, Sox32, a transcription factor of the SoxF subfamily, and an extrinsic factor, Fgf10a. sox32 is expressed in the extrahepatic duct primordium which is not affected in wnt2bb mutants. Blocking Sox32 function prevented liver formation in most wnt2bb mutants. fgf10a, which is expressed in the mesenchyme surrounding non-hepatic endodermal cells, negatively impacts the regulative capacity of endodermal tissues. In Wnt/β-catenin signaling deficient embryos, in which the liver completely fails to form, the repression of Fgf10a function allowed liver formation. Altogether, these studies reveal that there is more than one way to form a liver, and provide molecular insights into the phenomenon of tissue plasticity. PMID:22313811

  20. A Bilobalide-Producing Endophytic Fungus, Pestalotiopsis uvicola from Medicinal Plant Ginkgo biloba.

    PubMed

    Qian, Yi-Xin; Kang, Ji-Chuan; Luo, Yi-Kai; Zhao, Jun-Jie; He, Jun; Geng, Kun

    2016-08-01

    For screening bilobalide (BB)-producing endophytic fungi from medicinal plant Ginkgo biloba, a total of 57 fungal isolates were isolated from the internal stem, root, leaf, and bark of the plant G. biloba. Fermentation processes using BB-producing fungi other than G. biloba may become a novel way to produce BB, which is a terpene trilactones exhibiting neuroprotective effects. In this study, a BB-producing endophytic fungal strain GZUYX13 was isolated from the leaves of G. biloba grown in the campus of Guizhou University, Guiyang city, Guizhou province, China. The strain produced BB when grown in potato dextrose liquid medium. The amount of BB produced by this endophytic fungus was quantified to be 106 μg/L via high-performance liquid chromatography (HPLC), substantially lower than that produced by the host tissue. The fungal BB which was analyzed by thin layer chromatography (TLC) and HPLC was proven to be identical to authentic BB. The strain GZUYX13 was identified as Pestalotiopsis uvicola via morphology and ITS rDNA phylogeny. To the best of our knowledge, this is the first report concerning the isolation and identification of endophytic BB-producing Pestalotiopsis spp. from the host plant, which further proved that endophytic fungi have the potential to produce bioactive compounds.

  1. First measurement of the charge asymmetry in beauty-quark pair production.

    PubMed

    Aaij, R; Adeva, B; Adinolfi, M; Affolder, A; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Anderson, J; Andreassen, R; Andreotti, M; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Badalov, A; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M-O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Borsato, M; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brodzicka, J; Brook, N H; Brown, H; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Calabrese, R; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carranza-Mejia, H; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cenci, R; Charles, M; Charpentier, Ph; Chen, S; Cheung, S-F; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coco, V; Cogan, J; Cogneras, E; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Corvo, M; Counts, I; Couturier, B; Cowan, G A; Craik, D C; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; Dalseno, J; David, P; David, P N Y; Davis, A; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Donleavy, S; Dordei, F; Dorigo, M; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dreimanis, K; Dujany, G; Dupertuis, F; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Ely, S; Esen, S; Evans, H-M; Evans, T; Falabella, A; Färber, C; Farinelli, C; Farley, N; Farry, S; Fay, Rf; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Fu, J; Furfaro, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; García Pardiñas, J; Garofoli, J; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gavardi, L; Gavrilov, G; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianelle, A; Giani', S; Gibson, V; Giubega, L; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gordon, H; Gotti, C; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Griffith, P; Grillo, L; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hamilton, B; Hampson, T; Han, X; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; He, J; Head, T; Heijne, V; Hennessy, K; Henrard, P; Henry, L; Hernando Morata, J A; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hoballah, M; Hombach, C; Hulsbergen, W; Hunt, P; Hussain, N; Hutchcroft, D; Hynds, D; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jalocha, J; Jans, E; Jaton, P; Jawahery, A; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kaballo, M; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Karodia, S; Kelsey, M; Kenyon, I R; Ketel, T; Khanji, B; Khurewathanakul, C; Klaver, S; Klimaszewski, K; Kochebina, O; Kolpin, M; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kurek, K; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanciotti, E; Lanfranchi, G; Langenbruch, C; Langhans, B; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Liles, M; Lindner, R; Linn, C; Lionetto, F; Liu, B; Liu, G; Lohn, S; Longstaff, I; Lopes, J H; Lopez-March, N; Lowdon, P; Lu, H; Lucchesi, D; Luo, H; Lupato, A; Luppi, E; Lupton, O; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Manca, G; Mancinelli, G; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marino, P; Märki, R; Marks, J; Martellotti, G; Martens, A; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Mazurov, A; McCann, M; McCarthy, J; McNab, A; McNulty, R; McSkelly, B; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M-N; Moggi, N; Molina Rodriguez, J; Monteil, S; Morandin, M; Morawski, P; Mordà, A; Morello, M J; Moron, J; Morris, A-B; Mountain, R; Muheim, F; Müller, K; Muresan, R; Mussini, M; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Novoselov, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Onderwater, G; Orlandea, M; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palombo, F; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrignani, C; Pazos Alvarez, A; Pearce, A; Pellegrino, A; Pepe Altarelli, M; Perazzini, S; Perez Trigo, E; Perret, P; Perrin-Terrin, M; Pescatore, L; Pesen, E; Petridis, K; Petrolini, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Pistone, A; Playfer, S; Plo Casasus, M; Polci, F; Poluektov, A; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Price, E; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rachwal, B; Rademacker, J H; Rakotomiaramanana, B; Rama, M; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Reichert, S; Reid, M M; Dos Reis, A C; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Rodrigues, A B; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rotondo, M; Rouvinet, J; Ruf, T; Ruffini, F; Ruiz, H; Ruiz Valls, P; Sabatino, G; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salustino Guimaraes, V; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sapunov, M; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrie, M; Savrina, D; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Sepp, I; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Shires, A; Silva Coutinho, R; Simi, G; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, N A; Smith, E; Smith, E; Smith, J; Smith, M; Snoek, H; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Stagni, F; Stahl, M; Stahl, S; Steinkamp, O; Stenyakin, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Stracka, S; Straticiuc, M; Straumann, U; Stroili, R; Subbiah, V K; Sun, L; Sutcliffe, W; Swientek, K; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szilard, D; Szumlak, T; T'Jampens, S; Teklishyn, M; Tellarini, G; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vagnoni, V; Valenti, G; Vallier, A; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vieites Diaz, M; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; de Vries, J A; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Websdale, D; Whitehead, M; Wicht, J; Wiedner, D; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wimberley, J; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, Z; Xu, Z; Yang, Z; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

    2014-08-22

    The difference in the angular distributions between beauty quarks and antiquarks, referred to as the charge asymmetry, is measured for the first time in bb pair production at a hadron collider. The data used correspond to an integrated luminosity of 1.0 fb(-1) collected at 7 TeV center-of-mass energy in proton-proton collisions with the LHCb detector. The measurement is performed in three regions of the invariant mass of the bb system. The results obtained are A(C)(bb))(40bb))<75 GeV/c(2)) = 0.4 ± 0.4 ± 0.3%, A(C)(bb))(75bb)) < 105 GeV/c(2)) = 2.0 ± 0.9 ± 0.6%, A(C)(bb)(M(bb)) > 105 GeV/c(2)) = 1.6 ± 1.7 ± 0.6%, where A(C)(bb)) is defined as the asymmetry in the difference in rapidity between jets formed from the beauty quark and antiquark, where in each case the first uncertainty is statistical and the second systematic. The beauty jets are required to satisfy 2 < η < 4, E(T) >20 GeV, and have an opening angle in the transverse plane Δ ϕ > 2.6 rad. These measurements are consistent with the predictions of the standard model.

  2. Analysis of EEG activity in response to binaural beats with different frequencies.

    PubMed

    Gao, Xiang; Cao, Hongbao; Ming, Dong; Qi, Hongzhi; Wang, Xuemin; Wang, Xiaolu; Chen, Runge; Zhou, Peng

    2014-12-01

    When two coherent sounds with nearly similar frequencies are presented to each ear respectively with stereo headphones, the brain integrates the two signals and produces a sensation of a third sound called binaural beat (BB). Although earlier studies showed that BB could influence behavior and cognition, common agreement on the mechanism of BB has not been reached yet. In this work, we employed Relative Power (RP), Phase Locking Value (PLV) and Cross-Mutual Information (CMI) to track EEG changes during BB stimulations. EEG signals were acquired from 13 healthy subjects. Five-minute BBs with four different frequencies were tested: delta band (1 Hz), theta band (5 Hz), alpha band (10 Hz) and beta band (20 Hz). We observed RP increase in theta and alpha bands and decrease in beta band during delta and alpha BB stimulations. RP decreased in beta band during theta BB, while RP decreased in theta band during beta BB. However, no clear brainwave entrainment effect was identified. Connectivity changes were detected following the variation of RP during BB stimulations. Our observation supports the hypothesis that BBs could affect functional brain connectivity, suggesting that the mechanism of BB-brain interaction is worth further study. Copyright © 2014. Published by Elsevier B.V.

  3. Orbit and Stellar Properties of the Young Triple V807 Tau

    DTIC Science & Technology

    2012-09-10

    Kharchenko & Roeser 2009 (V band); (2) Cutri et al. 2003 ( 2MASS J, H, Ks); (3) White & Ghez 2001 (V, K); (4) flux ratio (A:Ba:Bb) combined with Johnson V...All-sky compiled Catalog (Kharchenko & Roeser 2009) and 2MASS J, H, K; (5) calibrated FGS; (6) flux ratio (Ba:Bb) combined with White & Ghez (2001...K−L color in excess of 0.4 (e.g., Prato et al. 2003). Convert- ing the Two Micron All Sky Survey ( 2MASS ) Ks magnitudes to the Bessell–Brett

  4. Not all Beta-Blockers are Equal in the Management of Long QT Syndrome Types 1 and 2: Higher Recurrence of Events under Metoprolol

    PubMed Central

    Chockalingam, Priya; Crotti, Lia; Girardengo, Giulia; Johnson, Jonathan N.; Harris, Katy M.; van der Heijden, Jeroen F.; Hauer, Richard N.W.; Beckmann, Britt M.; Spazzolini, Carla; Rordorf, Roberto; Rydberg, Annika; Clur, Sally-Ann B.; Fischer, Markus; van den Heuvel, Freek; Kääb, Stefan; Blom, Nico A.; Ackerman, Michael J.; Schwartz, Peter J.; Wilde, Arthur A.M.

    2012-01-01

    Objectives To compare the efficacy of beta-blockers (BB) in congenital long QT syndrome (LQTS). Background BB are the mainstay in managing LQTS. Studies comparing the efficacy of commonly-used BB are lacking and clinicians generally assume they are equally effective. Methods ECG and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n=134), metoprolol (n=147), and nadolol (n=101) were analyzed, excluding patients aged <1 year at BB initiation. Symptoms prior to therapy and the first breakthrough cardiac events (BCEs) were documented. Results Patients (56% females, 27% symptomatic, HR 76±16 bpm, QTc 472±46 ms) were started on BB therapy at a median age of 14 years (IQR 8–32 years). QTc-shortening with propranolol was significantly greater than with other BB in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n=101), 15 had BCEs (all syncopes). QTc-shortening was significantly less-pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of other two BB combined, after adjustment for genotype (OR 3.95, 95% CI 1.2–13.1, p=0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients on metoprolol compared to propranolol/nadolol. Conclusions Propranolol has a significantly better QTc-shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used in symptomatic LQT1 and LQT2 patients. PMID:23083782

  5. Forever Young: The Role of Ubiquitin Receptor DA1 and E3 Ligase BIG BROTHER in Controlling Leaf Growth and Development.

    PubMed

    Vanhaeren, Hannes; Nam, Youn-Jeong; De Milde, Liesbeth; Chae, Eunyoung; Storme, Veronique; Weigel, Detlef; Gonzalez, Nathalie; Inzé, Dirk

    2017-02-01

    The final size of plant organs is determined by a combination of cell proliferation and cell expansion. Leaves account for a large part of above-ground biomass and provide energy to complete the plant's life cycle. Although the final size of leaves is remarkably constant under fixed environmental conditions, several genes have been described to enhance leaf growth when their expression is modulated. In Arabidopsis (Arabidopsis thaliana), mutations in DA1 and BB increase leaf size, an effect that is synergistically enhanced in the double mutant. Here, we show that overexpression of a dominant-negative version of DA1 enhances leaf size in a broad range of natural accessions of this species, indicating a highly conserved role of this protein in controlling organ size. We also found that during early stages of development, leaves of da1-1 and bb/eod1-2 mutants were already larger than the isogenic Col-0 wild type, but this phenotype was triggered by different cellular mechanisms. Later during development, da1-1 and bb/eod1-2 leaves showed a prolonged longevity, which was enhanced in the double mutant. Conversely, ectopic expression of DA1 or BB restricted growth and promoted leaf senescence. In concert, shortly upon induction of DA1 and BB expression, several marker genes for the transition from proliferation to expansion were highly up-regulated. Additionally, multiple genes involved in maintaining the mitotic cell cycle were rapidly down-regulated and senescence genes were strongly up-regulated, particularly upon BB induction. With these results, we demonstrate that DA1 and BB restrict leaf size and promote senescence through converging and different mechanisms. © 2017 American Society of Plant Biologists. All Rights Reserved.

  6. Effects of the breed, sex and age on cellular content and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel.

    PubMed

    Giraldo, Carlos E; López, Catalina; Álvarez, María E; Samudio, Ismael J; Prades, Marta; Carmona, Jorge U

    2013-02-12

    There is no information on the effects of the breed, gender and age on the cellular content and growth factor (GF) release from equine pure-platelet rich plasma (P-PRP) and pure-platelet rich gel (P-PRG). The objectives of this study were: 1) to compare the cellular composition of P-PRP with whole blood and platelet poor plasma (PPP); 2) to compare the concentration of transforming GF beta 1 (TGF-β1) and platelet derived GF isoform BB (PDGF-BB) between P-PRP treated with non-ionic detergent (P-PRP+NID), P-PRG (activated with calcium gluconate -CG-), PPP+NID, PPP gel (PPG), and plasma and; 3) to evaluate and to correlate the effect of the breed, gender and age on the cellular and GF concentration for each blood component. Forty adult horses, 20 Argentinean Creole Horses (ACH) and, 20 Colombian Creole Horses (CCH) were included. Data were analyzed by parametric (i.e.: t-test, one way ANOVA) and non parametric (Kruskal-Wallis test, Wilcoxon test) tests. Correlation analysis was also performed by using the Spearman and Pearson tests. A p ≤ 0.05 was set as significant for all tests. All the blood components were compared for platelet (PLT), leukocyte (WBC), TGF-β1 and PDGF-BB concentrations. The effect of the breed, gender and age on these variables was analyzed. A P ≤ 0.05 was accepted as significant for all the tests. PLT counts were 1.8 and 0.6 times higher in P-PRP than in whole blood and PPP, respectively; WBC counts were 0.5 and 0.1 times lower in P-PRP, in comparison with whole blood and PPP, respectively. TGF-β1 and PDGF-BB concentrations were 2.3 and 262 times higher, respectively, in P-PRG than in plasma, and 0.59 and 0.48 times higher, respectively, in P-PRG than in PPG. P-PRG derived from CCH females or young horses presented significantly (P < 0.001) higher PDGF-BB concentrations than P-PRG derived from ACH males or older horses. Our results indicated that P-PRP obtained by a manual method was affected by intrinsic factors such as the breed

  7. BICEP2 III: Instrumental systematics

    DOE PAGES

    Ade, P. A. R.

    2015-11-23

    In a companion paper, we have reported a >5σ detection of degree scale B-mode polarization at 150 GHz by the Bicep2 experiment. Here we provide a detailed study of potential instrumental systematic contamination to that measurement. We focus extensively on spurious polarization that can potentially arise from beam imperfections. We present a heuristic classification of beam imperfections according to their symmetries and uniformities, and discuss how resulting contamination adds or cancels in maps that combine observations made at multiple orientations of the telescope about its boresight axis. We introduce a technique, which we call "deprojection," for filtering the leading ordermore » beam-induced contamination from time-ordered data, and show that it reduces power in Bicep2's actual and null-test BB spectra consistent with predictions using high signal-to-noise beam shape measurements. We detail the simulation pipeline that we use to directly simulate instrumental systematics and the calibration data used as input to that pipeline. Finally, we present the constraints on BB contamination from individual sources of potential systematics. We find that systematics contribute BB power that is a factor of ~10× below Bicep2's three-year statistical uncertainty, and negligible compared to the observed BB signal. Lastly, the contribution to the best-fit tensor/scalar ratio is at a level equivalent to r = (3–6) × 10 –3.« less

  8. BICEP2 III: Instrumental systematics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ade, P. A. R.

    In a companion paper, we have reported a >5σ detection of degree scale B-mode polarization at 150 GHz by the Bicep2 experiment. Here we provide a detailed study of potential instrumental systematic contamination to that measurement. We focus extensively on spurious polarization that can potentially arise from beam imperfections. We present a heuristic classification of beam imperfections according to their symmetries and uniformities, and discuss how resulting contamination adds or cancels in maps that combine observations made at multiple orientations of the telescope about its boresight axis. We introduce a technique, which we call "deprojection," for filtering the leading ordermore » beam-induced contamination from time-ordered data, and show that it reduces power in Bicep2's actual and null-test BB spectra consistent with predictions using high signal-to-noise beam shape measurements. We detail the simulation pipeline that we use to directly simulate instrumental systematics and the calibration data used as input to that pipeline. Finally, we present the constraints on BB contamination from individual sources of potential systematics. We find that systematics contribute BB power that is a factor of ~10× below Bicep2's three-year statistical uncertainty, and negligible compared to the observed BB signal. Lastly, the contribution to the best-fit tensor/scalar ratio is at a level equivalent to r = (3–6) × 10 –3.« less

  9. Synthesis, electrochemistry, and electrogenerated chemiluminescence of two BODIPY-appended bipyridine homologues.

    PubMed

    Qi, Honglan; Teesdale, Justin J; Pupillo, Rachel C; Rosenthal, Joel; Bard, Allen J

    2013-09-11

    Two new 2,2'-bipyridine (bpy) derivatives containing ancillary BODIPY chromophores attached at the 5- and 5'-positions (BB3) or 6- and 6'-positions (BB4) were prepared and characterized. In this work, the basic photophysics, electrochemistry, and electrogenerated chemiluminescence (ECL) of BB3 and BB4 are compared with those previously reported for a related bpy-BODIPY derivative (BB2) (J. Phys. Chem. C 2011, 115, 17993-18001). Cyclic voltammetry revealed that BB3 and BB4 display reversible 2e(-) oxidation and reduction waves, which consist of two closely spaced (50-70 mV) 1e(-) events. This redox behavior is consistent with the frontier molecular orbitals calculated for BB3 and BB4 and indicates that the 2,2'-bipyridine spacer of each bpy-BODIPY homologue does not facilitate efficient electronic communication between the tethered indacene units. In the presence of a coreactant such as tri-n-propylamine (TPA) or benzoyl peroxide (BPO), BB3 and BB4 exhibit strong ECL and produce spectra that are very similar to their corresponding photoluminescence profiles. The ECL signal obtained under annihilation conditions, however, is significantly different and is characterized by two distinct bands. One of these bands is centered at ∼570 nm and is attributed to emission via an S- or T-route. The second band occurs at longer wavelengths and is centered around ∼740 nm. The shape and concentration dependence of this long-wavelength ECL signal is not indicative of emission from an excimer or aggregate, but rather it suggests that a new emissive species is formed from the bpy-BODIPY luminophores during the annihilation process.

  10. Losartan added to β-blockade therapy for aortic root dilation in Marfan syndrome: a randomized, open-label pilot study.

    PubMed

    Chiu, Hsin-Hui; Wu, Mei-Hwan; Wang, Jou-Kou; Lu, Chun-Wei; Chiu, Shuenn-Nan; Chen, Chun-An; Lin, Ming-Tai; Hu, Fu-Chang

    2013-03-01

    To assess the tolerability and efficacy of the investigational use of the angiotensin II receptor blocker losartan added to β-blockade (BB) to prevent progressive aortic root dilation in patients with Marfan syndrome (MFS). Between May 1, 2007, and September 31, 2011, 28 patients with MFS (11 males [39%]; mean ± SD age, 13.1±6.3 years) with recognized aortic root dilation (z score >2.0) and receiving BB (atenolol or propranolol) treatment were enrolled. They were randomized to receive BB (BB: 13 patients) or β-blockade and losartan (BB-L: 15 patients) for 35 months. In the BB-L group, aortic root dilation was reduced with treatment, and the annual dilation rate of the aortic root was significantly lower than that of the BB group (0.10 mm/yr vs 0.89 mm/yr; P=.02). The absolute aortic diameters at the sinus of Valsalva, annulus, and sinotubular junction showed similar trends, with a reduced rate of dilation in the BB-L group (P=.02, P=.03, and P=.03, respectively). Five patients (33%) treated with BB-L were noted to have a reduced aortic root diameter. However, the differences between the groups regarding changes in aortic stiffness and cross-sectional compliance were not statistically significant. This randomized, open-label, active controlled trial mostly based on a pediatric population demonstrated for the first time that losartan add-on BB therapy is safe and provides more effective protection to slow the progression of aortic root dilation than does BB treatment alone in patients with MFS. clinicaltrials.gov Identifier: NCT00651235. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  11. Synthesis, Electrochemistry and Electrogenerated Chemiluminesce of two BODIPY-Appended Bipyridine Homologues

    PubMed Central

    Qi, Honglan; Teesdale, Justin J.; Pupillo, Rachel C.

    2014-01-01

    Two new 2,2’-bipyridine (bpy) derivatives containing ancillary BODIPY chromophores attached at the 5- and 5’-positions (BB3) or 6- and 6’-positions (BB4) were prepared and characterized. In this work, the basic photophysics, electrochemistry and electrogenerated chemiluminescence (ECL) of BB3 and BB4 are compared with those previously reported for a related bpy-BODIPY derivative (BB2) (J. Phys. Chem. C 2011, 115, 17993–18001). Cyclic voltammetry revealed that BB3 and BB4 display reversible 2e− oxidation and reduction waves, which consist of two closely spaced (50 – 70 mV) 1e− events. This redox behavior is consistent with the frontier molecular orbitals calculated for BB3 and BB4 and indicates that the 2,2’-bipyridine spacer of each bpy- BODIPY homologue does not facilitate efficient electronic communication between the tethered indacene units. In the presence of a coreactant such as tri-n-propylamine (TPA) or benzoyl peroxide (BPO), BB3 and BB4 exhibit strong ECL and produce spectra that are very similar to their corresponding photoluminescence profiles. The ECL signal obtained under annihilation conditions, however, is significantly different and is characterized by two distinct bands. One of these bands is centered at ~570 nm and is attributed to emission via an S- or T-route. The second band, occurs at longer wavelengths and is centered around ~740 nm. The shape and concentration dependence of this long-wavelength ECL signal is not indicative of emission from an excimer or aggregate, but rather is suggests that a new emissive species is formed from the bpy-BODIPY luminophores during the annihilation process. PMID:23980850

  12. Stress Intensity Factors for Cracked Metallic Structures Under Rapid Thermal Loading

    DTIC Science & Technology

    1987-10-01

    if applicable ) Flight Dynamics Laboratory (AFWAL/FIBFC) APTECH Engineering Services Air Force Wright Aeronautical Laboratories 6c. ADDRESS (City...SPONSORING Bb OFFICE SYMBOL 9 PROCUREMENT INSTRUMENT IDENTIFICATION NUMBER ORGANIZATION (If applicable ) DOD SBIR Program Office F33615-86-C-3217 8c...flawed components requires the application of fracture mechanics wherein crack tip -tress intensity factors are used to provide a quantitative means

  13. Characterizing Atmospheric Processing of Aerosols from Forest Fires at the Mt. Bachelor Observatory during BBOP

    NASA Astrophysics Data System (ADS)

    Zhou, S.; Collier, S.; Hee, J.; Wigder, N. L.; Jaffe, D. A.; Zhang, Q.

    2014-12-01

    This study investigates the physical and chemical characteristics and atmospheric processing of aerosols from uncontrolled forest fires across the Pacific Northwest. The measurements were made at the Mt. Bachelor Observatory (MBO) located at the summit of Mt. Bachelor in central Oregon (43.9794° N, 121.6885° W, 2,763 m asl) in summer 2013 during the DOE sponsored Biomass Burning Observation Project (BBOP) field campaign. We utilized an Aerodyne High Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) coupled with a thermodenuder. Observations during periods affected by biomass burning (BB) pollution showed elevated non-refractory submicron aerosol (NR-PM1) concentration up to 140 μg/m3. NR-PM1 correlated well with PM light scattering (up to ~ 600 Mm-1 at 550 nm) and gas phase CO (up to ~0.4 ppmv). The AMS BB tracer, f60, i.e., fraction of organic signals at m/z = 60, was also enhanced with a maximum of ~ 2%. Organic aerosol (OA) dominated the PM composition in BB plumes (94.1% of the NR-PM1 mass) with an average concentration of 13.9 μg/m3. Three distinctive BBOA factors were identified by Positive Matrix Factorization (PMF): a fresh BBOA-I factor (O/C=0.27, H/C=1.52, f60 = 2.26%) that correlates well with ammonium nitrate; an intermediately oxidized BBOA-II (O/C=0.52, H/C=1.47, f60 = 1.05%), and a highly oxidized BBOA-III (O/C=0.95, H/C=1.02) with a low f60 (< 0.01%) and enhanced tracer ions for carboxylic acids (e.g., CHO2+). During persistent BB plume events from fixed fire sources, fresh BBOA-I initially dominated the OA composition, but decreased as the more oxidized BBOA-II increased while BBOA-III remained unchanged. These events shed light on the chemical transformation of BB aerosol during atmospheric aging. We will examine the enhancement of different BBOA factors relative to CO to investigate secondary organic aerosol (SOA) formation processes in BB plumes.

  14. Vitamin D receptor gene polymorphisms and the risk of rickets among Asians: a meta-analysis.

    PubMed

    Mao, Song; Huang, Songming

    2014-03-01

    To evaluate the association between vitamin D receptor (VDR) gene polymorphisms and the risk of rickets among Asians. Eligible studies were included in our meta-analysis by searching PubMed, Embase, Cochrane and China National Knowledge Infrastructure databases according to a predefined criteria. A random effects model was used to calculate the combined ORs and its corresponding 95% CI. 16 studies were recruited for the analysis of the association between VDR BsmI (rs1544410), TaqI (rs731236), FokI (rs2228570) and ApaI (rs7975232) gene polymorphisms and the risk of rickets among Asians, most of whom were from China. B allele/BB genotype was associated with the susceptibility of rickets (p=0.017 and 0.044, respectively), and bb genotype was associated with lower risk of rickets (p=0.033). F allele/FF genotype was associated with the susceptibility of rickets (p<10(-4)), and ff genotype was associated with lower risk of rickets (p<10(-4)). AA genotype was associated with the onset of rickets (p=0.044). No significant association was observed between TaqI polymorphism the risk of rickets. A allele/aa genotype was not associated with the risk of rickets. No evidence of publication bias was observed. B allele/BB genotype at the BsmI site, F allele/FF genotype at the FokI site and AA genotype at the ApaI site may be risk factors for the onset of rickets among Asians; bb genotype at the BsmI site and ff genotype at the FokI site may be protective factors against the risk of rickets among Asians.

  15. Use of a Cyclooxygenase-2 Inhibitor Does Not Inhibit Platelet Activation or Growth Factor Release From Platelet-Rich Plasma.

    PubMed

    Ludwig, Hilary C; Birdwhistell, Kate E; Brainard, Benjamin M; Franklin, Samuel P

    2017-12-01

    It remains unestablished whether use of cyclooxygenase (COX)-2 inhibitors impairs platelet activation and anabolic growth factor release from platelets in platelet-rich plasma (PRP). The purpose of this study was to assess the effects of a COX-2 inhibitor on platelet activation and anabolic growth factor release from canine PRP when using a clinically applicable PRP activator and to determine whether a 3-day washout would be sufficient to abrogate any COX-2 inhibitor-related impairment on platelet function. Controlled laboratory study. Ten healthy dogs underwent blood collection and PRP preparation. Dogs were then administered a COX-2 inhibitor for 7 days, after which PRP preparation was repeated. The COX-2 inhibitor was continued for 4 more days and PRP preparation performed a third time, 3 days after discontinuation of the COX-2 inhibitor. Immediately after PRP preparation, the PRP was divided into 4 aliquots: 2 unactivated and 2 activated using human γ-thrombin (HGT). One activated and 1 unactivated sample were assessed using flow cytometry for platelet expression of CD62P and platelet-bound fibrinogen using the canine activated platelet-1 (CAP1) antibody. The 2 remaining samples were centrifuged and the supernatant assayed for transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-BB (PDGF-BB), and thromboxane B2 (TXB2) concentrations. Differences in platelet activation and TGF-β1, PDGF-BB, and TXB2 concentrations over the 3 study weeks were evaluated using a 1-way repeated-measures ANOVA, and comparisons between activated and unactivated samples within a study week were assessed with paired t tests. There were no statistically significant ( P > .05) effects of the COX-2 inhibitor on percentage of platelets positive for CD62P or CAP1 or on concentrations of TGF-β1, PDGF-BB, or TXB2. All unactivated samples had low levels of activation or growth factor concentrations and significantly ( P < .05) greater activation and growth factor

  16. HIV prevalence and high-risk behaviour of young brothel and non-brothel based female sex workers in Nigeria.

    PubMed

    Okafor, Uchenna Onyekachi; Crutzen, Rik; Ifeanyi, Okekearu; Adebajo, Sylvia; Van den Borne, Hubertus

    2017-08-10

    Female sex workers (FSWs) have been identified as a core group in the transmission of HIV and other sexually transmitted infections (STIs). Young FSWs are particularly more vulnerable to HIV due to the combination of vulnerabilities associated with their youth and the sex work they engage in. This study aims to give more insight into HIV prevalence and sexual risk behaviour of young FSWs in Nigeria, by focusing on the differences between BB and NBB young FSWs. Data was obtained from the Nigeria Integrated Biological and Behavioural Surveillance Survey (IBBSS) for high-risk groups conducted in 2010. IBBSS is a quantitative survey conducted amongst identified high-risk sub populations within Nigeria. HIV prevalence and risk behaviour data for young BB and NBB FSWs aged 15-24 years for nine states was extracted and analysed. A total of 1796 FSWs aged 15-24 years were interviewed during the survey, 746 (41.5%) were BB while 1050 (58.5%) were NBB. The HIV prevalence was higher among BB FSWs compared to the NBB FSWs (21.0% vs. 15.5%). BB FSWs reported less condom use with boyfriends and casual partners than NBB FSWs (26.3% vs. 45.5%) and (55.1% vs. 61.1%) respectively while risk of HIV infection due to injecting drug use was higher in NBB compared to BB FSWs (6.6% vs. 1.2%). Existing and future interventions on HIV prevention should focus on empowering young FSWs with innovative and sustainable approaches aimed at improving their health and wellbeing.

  17. Risk Mitigation Testing with the BepiColombo MPO SADA

    NASA Astrophysics Data System (ADS)

    Zemann, J.; Heinrich, B.; Skulicz, A.; Madsen, M.; Weisenstein, W.; Modugno, F.; Althaus, F.; Panhofer, T.; Osterseher, G.

    2013-09-01

    A Solar Array (SA) Drive Assembly (SADA) for the BepiColombo mission is being developed and qualified at RUAG Space Zürich (RSSZ). The system is consisting of the Solar Array Drive Mechanism (SADM) and the Solar Array Drive Electronics (SADE) which is subcontracted to RUAG Space Austria (RSA).This paper deals with the risk mitigation activities and the lesson learnt from this development. In specific following topics substantiated by bread board (BB) test results will be addressed in detail:Slipring Bread Board Test: Verification of lifetime and electrical performance of carbon brush technology Potentiometer BB Tests: Focus on lifetime verification (> 650000 revolution) and accuracy requirement SADM EM BB Test: Subcomponent (front-bearing and gearbox) characterization; complete test campaign equivalent to QM test.EM SADM/ SADE Combined Test: Verification of combined performance (accuracy, torque margin) and micro-vibration testing of SADA systemSADE Bread Board Test: Parameter optimization; Test campaign equivalent to QM testThe main improvements identified in frame of BB testing and already implemented in the SADM EM/QM and SADE EQM are:• Improved preload device for gearbox• Improved motor ball-bearing assembly• Position sensor improvements• Calibration process for potentiometer• SADE motor controller optimization toachieve required running smoothness• Overall improvement of test equipment.

  18. Measurement of the branching fractions of exclusive _B-->D(*)(pi)l-_nu l decays in events with a fully reconstructed B meson.

    PubMed

    Aubert, B; Bona, M; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Garra Tico, J; Grauges, E; Lopez, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lynch, G; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabe, T; Wenzel, W A; del Amo Sanchez, P; Hawkes, C M; Soni, N; Watson, A T; Koch, H; Schroeder, T; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Gary, J W; Liu, F; Long, O; Shen, B C; Vitug, G M; Yasin, Z; Zhang, L; Paar, H P; Rahatlou, S; Sharma, V; Campagnari, C; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Doll, D A; Echenard, B; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Ayad, R; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Karbach, M; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Playfer, S; Robertson, A I; Watson, J E; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Nash, J A; Panduro Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Firmino da Costa, J; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Sacco, R; Sigamani, M; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Alwyn, K E; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Dallapiccola, C; Hertzbach, S S; Li, X; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Lombardo, V; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, G; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; LoSecco, J M; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Sekula, S J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Castelli, G; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; Hamon, O; Leruste, Ph; Malclès, J; Ocariz, J; Perez, A; Prendki, J; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Morganti, M; Mazur, M A; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Biesiada, J; Lau, Y P; Lopes Pegna, D; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Baracchini, E; Cavoto, G; del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Roethel, W; Wilson, F F; Emery, S; Escalier, M; Gaidot, A; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Benitez, J F; Cenci, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Lindquist, B; Luitz, S; Luth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Messner, R; Muller, D R; Neal, H; Nelson, S; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Yi, K; Young, C C; Ziegler, V; Burchat, P R; Edwards, A J; Majewski, S A; Miyashita, T S; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Spanier, S M; Wogsland, B J; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Gershon, T J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Hollar, J J; Kutter, P E; Pan, Y; Pierini, M; Prepost, R; Vuosalo, C O; Wu, S L

    2008-04-18

    We report a measurement of the branching fractions for _B-->D(*)(pi)l- _nu(l) decays based on 341.1 fb(-1) of data collected at the Upsilon(4S) resonance with the BABAR detector at the SLAC PEP-II e+ e- storage rings. Events are tagged by fully reconstructing one of the B mesons in a hadronic decay mode. We obtain B(B- -->D(0)l-_nu(l)=(2.33+/-0.09(stat)+/-0.09(syst)%, B(B- -->D(*0)l-_nu(l)=(5.83+/-0.15(stat) +/-0.30(syst) %, B(_B(0)-->D+l-_nu(l)=(2.21+/-0.11(stat) +/-0.12(syst)%, B(_B(0)-->D(*)l-_nu(l)=(5.49+/-0.16(stat)+/-0.25(syst)%, B(B- -->D+pi-l-_nu(l)=(0.42+/-0.06(stat)+/-0.03(syst)%, B(B- -->D(*)+pi-l-_nu(l)=(0.59+/-0.05(stat)+/-0.04(syst)%, B(_B(0)-->D(0)pi+l-_nu(l)=(0.43+/-0.08(stat)+/-0.03(syst)%, and B(_B(0)-->D(*0)pi+l-_nu(l)=(0.48+/-0.08(stat)+/-0.04(syst)%.

  19. Synergistic Combinations of a Pyrethroid Insecticide and an Emulsifiable Oil Formulation of Beauveria bassiana to Overcome Insecticide Resistance in Listronotus maculicollis (Coleoptera: Curculionidae).

    PubMed

    Wu, Shaohui; Kostromytska, Olga S; Koppenhöfer, Albrecht M

    2017-08-01

    The annual bluegrass weevil, Listronotus maculicollis (Kirby), is a major pest of golf course turf in eastern North America and has become particularly problematic owing to widespread development of insecticide resistance. As an alternative option to manage resistant adult L. maculicollis, we explored combinations of the pyrethroid insecticide bifenthrin with an emulsifiable oil formulation of the entomopathogenic fungus Beauveria bassiana strain GHA (Bb ES). Combinations synergistically enhanced mortality in both insecticide-susceptible and insecticide-resistant L. maculicollis adults in the laboratory when bifenthrin was used at LC50s for each population. To determine the component behind the synergism, technical spores of B. bassiana GHA and the emulsifiable oil carrier in the fungal formulation were tested separately or in combination with bifenthrin. In both separate and combined applications, the emulsifiable oil carrier was responsible for high mortality within 3 d after treatment and interacted synergistically with bifenthrin, whereas fungus-induced mortality started later. Strong synergism was also observed in three field experiments with a relatively resistant L. maculicollis population. Combinations of Bb ES and bifenthrin hold promise as an effective L. maculicollis management tool, particularly of pyrethroid-resistant populations. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Biomass burning in Indo-China peninsula and its impacts on regional air quality and global climate change-a review.

    PubMed

    Yadav, Ishwar Chandra; Linthoingambi Devi, Ningombam; Li, Jun; Syed, Jabir Hussain; Zhang, Gan; Watanabe, Hirozumi

    2017-08-01

    Although, many biomass burning (BB) emissions products (particulate matter and trace gases) are believed to be trans-boundary pollutants that originates from India and China (the two most populous countries in Asia), the information about BB emission and related contents is limited for Indo-China Peninsula (ICP) region. This motivated us to review this region pertaining to BB emission. The main objective of the review is to document the current status of BB emission in ICP region. In order to highlight the impact of BB on regional air quality and global climate change, the role of BB emission in ICP region is also discussed. Based on the available literature and modeling simulations studies, it is evidenced that ICP is one of the hotspot regional source for aerosols in terms of BB emissions. In addition, regional emissions through BB have significant implications for regional air quality especially in the neighboring countries such as China, Taiwan and India. Our assessment highlight that there is still a general lack of reliable data and research studies addressing BB related issues in context of environmental and human health. There is therefore a critical need to improve the current knowledge base, which should build upon the research experience and further research into these issues is considered vital to help inform future policies/control strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Lack of association between vitamin D receptor genotypes and osteoporosis in Koreans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lim, Sung Kil; Park, Young Suk; Park, Jae Min

    To evaluate whether common allelic variants in the gene encoding the vitamin D receptor (VDR) were useful in predicting differences in bone mineral density (BMD) and bone turnover rate in Koreans, we analyzed the restriction pattern of the polymerase chain reaction product of the VDR gene with the Bsm1 enzyme and serum osteocalcin in patients with osteoporosis. The prevalence of the BB genotype in the controls was extremely low when compared with that in other reports: the BB, Bb, and bb genotypes accounted for 1.4%, 12.9%, and 85.7%, respectively. Only 2.8% of those patients with osteoporosis had the BB genotype.more » In contrast, 12.5% had the Bb genotype, and 84.7% had the bb genotype. The prevalence of the BB genotype in patients with severe osteoporosis was also extremely low: the BB, Bb and bb genotypes accounted for 0%, 12.4%, and 87.6%, respectively. Compared with the mean serum osteocalcin level of the pre- and post-menopausal controls, the levels in patients with severe osteoporosis was higher, and this was statistically significant. As expected, a negative correlation was observed between the serum osteocalcin levels and the age-matched Z scores for spinal BMD. However, no correlation was found in the femoral neck BMD. These results suggest that restriction fragment length polymorphism analysis of the VDR gene with a Bsm1 restriction enzyme in Koreans is not helpful for early detection of patients at risk of developing osteoporosis. This is true even in patients with a high rate of bone turnover. Our data suggest extreme ethnic differences in the pattern of prevalence of the VDR allele. 19 refs., 5 figs., 2 tabs.« less

  2. RP-1776, a novel cyclic peptide produced by Streptomyces sp., inhibits the binding of PDGF to the extracellular domain of its receptor.

    PubMed

    Toki, S; Agatsuma, T; Ochiai, K; Saitoh, Y; Ando, K; Nakanishi, S; Lokker, N A; Giese, N A; Matsuda, Y

    2001-05-01

    RP-1776, a novel cyclic peptide, was isolated from the culture broth of Streptomyces sp. KY11784. RP-1776 selectively inhibited the binding of PDGF BB to the extracellular domain of the PDGF beta-receptor with an IC50 value of 11 +/- 6 microM. Detailed binding experiments suggested that RP-1776 directly interacts with PDGF BB. RP-1776 inhibited the phosphorylation of the PDGF beta-receptor induced by PDGF BB. These results suggested that RP-1776 antagonizes the signaling of PDGF BB probably through the inhibition of PDGF BB binding to the PDGF beta-receptor.

  3. Influence of biomass burning on mixing state of sub-micron aerosol particles in the North China Plain

    NASA Astrophysics Data System (ADS)

    Kecorius, Simonas; Ma, Nan; Teich, Monique; van Pinxteren, Dominik; Zhang, Shenglan; Gröβ, Johannes; Spindler, Gerald; Müller, Konrad; Iinuma, Yoshiteru; Hu, Min; Herrmann, Hartmut; Wiedensohler, Alfred

    2017-09-01

    Particulate emissions from crop residue burning decrease the air quality as well as influence aerosol radiative properties on a regional scale. The North China Plain (NCP) is known for the large scale biomass burning (BB) of field residues, which often results in heavy haze pollution episodes across the region. We have been able to capture a unique BB episode during the international CAREBeijing-NCP intensive field campaign in Wangdu in the NCP (38.6°N, 115.2°E) from June to July 2014. It was found that aerosol particles originating from this BB event showed a significantly different mixing state compared with clean and non-BB pollution episodes. BB originated particles showed a narrower probability density function (PDF) of shrink factor (SF). And the maximum was found at shrink factor of 0.6, which is higher than in other episodes. The non-volatile particle number fraction during the BB episode decreased to 3% and was the lowest measured value compared to all other predefined episodes. To evaluate the influence of particle mixing state on aerosol single scattering albedo (SSA), SSA at different RHs was simulated using the measured aerosol physical-chemical properties. The differences between the calculated SSA for biomass burning, clean and pollution episodes are significant, meaning that the variation of SSA in different pollution conditions needs to be considered in the evaluation of aerosol direct radiative effects in the NCP. And the calculated SSA was found to be quite sensitive on the mixing state of BC, especially at low-RH condition. The simulated SSA was also compared with the measured values. For all the three predefined episodes, the measured SSA are very close to the calculated ones with assumed mixing states of homogeneously internal and core-shell internal mixing, indicating that both of the conception models are appropriate for the calculation of ambient SSA in the NCP.

  4. AhR-dependent secretion of PDGF-BB by human classically activated macrophages exposed to DEP extracts stimulates lung fibroblast proliferation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jaguin, Marie; Fardel, Olivier; Pôle Biologie, Centre Hospitalier Universitaire

    2015-06-15

    Lung diseases are aggravated by exposure to diesel exhaust particles (DEPs) found in air pollution. Macrophages are thought to play a crucial role in lung immune response to these pollutants, even if the mechanisms involved remain incompletely characterized. In the present study, we demonstrated that classically and alternative human macrophages (MΦ) exhibited increased secretion of PDGF-B in response to DEP extract (DEPe). This occurred via aryl hydrocarbon receptor (AhR)-activation because DEPe-induced PDGF-B overexpression was abrogated after AhR expression knock-down by RNA interference, in both M1 and M2 polarizing MΦ. In addition, TCDD and benzo(a)pyrene, two potent AhR ligands, also significantlymore » increased mRNA expression of PDGF-B in M1 MΦ, whereas some weak ligands of AhR did not. We next evaluated the impact of conditioned media (CM) from MΦ culture exposed to DEPe or of recombinant PDGF-B onto lung fibroblast proliferation. The tyrosine kinase inhibitor, AG-1295, prevents phosphorylations of PDGF-Rβ, AKT and ERK1/2 and the proliferation of MRC-5 fibroblasts induced by recombinant PDGF-B and by CM from M1 polarizing MΦ, strongly suggesting that the PDGF-BB secreted by DEPe-exposed MΦ is sufficient to activate the PDGF-Rβ pathway of human lung fibroblasts. In conclusion, we demonstrated that human MΦ, whatever their polarization status, secrete PDGF-B in response to DEPe and that PDGF-B is a target gene of AhR. Therefore, induction of PDGF-B by DEP may participate in the deleterious effects towards human health triggered by such environmental urban contaminants. - Highlights: • PDGF-B expression and secretion are increased by DEPe exposure in human M1 and M2 MΦ. • DEPe-induced PDGF-B expression is aryl-hydrocarbon-dependent. • DEPe-exposed M1 MΦ secrete sufficient PDGF-B to increase lung fibroblast proliferation.« less

  5. Clinical and Genetic Modifiers of Long-term Survival in Heart Failure

    PubMed Central

    Cresci, Sharon; Kelly, Reagan J; Cappola, Thomas P; ScM; Diwan, Abhinav; Dries, Daniel; Kardia, Sharon LR; Dorn, Gerald W

    2009-01-01

    Objective To identify genetic modifiers of β-blocker (BB) response and long-term survival in heart failure (HF). Background Differences in BB treatment effect between Caucasians and African Americans with HF have been reported. Methods Prospective cohort study of 2,460 patients (711 African American; 1,749 Caucasian) enrolled between 1999 and 2007. 2039 (81.7%) were treated with BB. Each was genotyped for β1-adrenergic receptor (ADRB1) Arg389>Gly and G-protein receptor kinase 5 (GRK5) Gln41>Leu polymorphisms, which are more prevalent among African Americans than Caucasians. Primary endpoint was survival time from HF onset. Results There were 765 deaths during follow up (median 46 months). BB treatment increased survival in Caucasians (Log Rank P=0.00038) but not African Americans (Log Rank P=0.327). Among patients not taking BB, ADRB1 Gly389 was associated with decreased survival in Caucasians (HR = 1.98, 95% CI = 1.1 − 3.7, P = 0.03) while GRK5 Leu41 was associated with improved survival in African Americans (HR = 0.325, CI = 0.133 − 0.796, P = 0.01). ADRB1 Gly389 GRK5 Gln41Gln African Americans derived similar survival benefit from BB therapy (HR = 0.385 95% CI = 0.182 − 0.813, P = 0.012) as ADRB1 Gly389 GRK5 Gln41Gln Caucasians (HR = 0.529, 95% CI = 0.326 − 0.858, P=0.0098). Conclusions These data demonstrate that differences caused by β-adrenergic receptor signaling pathway gene polymorphisms, rather than race, are the major factors contributing to apparent differences in BB treatment effect between Caucasians and African Americans; proper evaluation of treatment response should account for genetic variance. PMID:19628119

  6. Aviation System Safety Risk Management Tool Analysis. Volume 2: Appendices

    DTIC Science & Technology

    1993-10-01

    Part Number FY AMC Case Number BATERY BB433AA 81 E 810421201 E’ BATTERY BB433AA 81 E 810421181 [’ BATTERY BB433AA 81 E 810514141 [’ BATIERY BB433AA 81...830520061 [- BAT=ERY NOT REC 83 E 830514071 -l BATTERY NOT REC 82 E 811102131 El BATERY NOT REC 82 E 820715191 " BATTERY NOT REC 82 E 820902051 "- BATERY NOT

  7. Understanding the Decision to Enroll in Graduate Business Programs: Influence of Sociological and Economic Factors and Gender

    ERIC Educational Resources Information Center

    Douglas, Stephanie

    2017-01-01

    This ex post facto study describes the associations of economic factors as well as social and cultural capital variables on enrollment in business master's degree programs and differences of associations by gender and race/ethnicity. Data from the 2008/2012 Baccalaureate and Beyond Longitudinal Study (B&B: 08/12) of those who completed a…

  8. Use of biopartitioning micellar chromatography and RP-HPLC for the determination of blood-brain barrier penetration of α-adrenergic/imidazoline receptor ligands, and QSPR analysis.

    PubMed

    Vucicevic, J; Popovic, M; Nikolic, K; Filipic, S; Obradovic, D; Agbaba, D

    2017-03-01

    For this study, 31 compounds, including 16 imidazoline/α-adrenergic receptor (IRs/α-ARs) ligands and 15 central nervous system (CNS) drugs, were characterized in terms of the retention factors (k) obtained using biopartitioning micellar and classical reversed phase chromatography (log k BMC and log k wRP , respectively). Based on the retention factor (log k wRP ) and slope of the linear curve (S) the isocratic parameter (φ 0 ) was calculated. Obtained retention factors were correlated with experimental log BB values for the group of examined compounds. High correlations were obtained between logarithm of biopartitioning micellar chromatography (BMC) retention factor and effective permeability (r(log k BMC /log BB): 0.77), while for RP-HPLC system the correlations were lower (r(log k wRP /log BB): 0.58; r(S/log BB): -0.50; r(φ 0 /P e ): 0.61). Based on the log k BMC retention data and calculated molecular parameters of the examined compounds, quantitative structure-permeability relationship (QSPR) models were developed using partial least squares, stepwise multiple linear regression, support vector machine and artificial neural network methodologies. A high degree of structural diversity of the analysed IRs/α-ARs ligands and CNS drugs provides wide applicability domain of the QSPR models for estimation of blood-brain barrier penetration of the related compounds.

  9. Effect of beta-blocker therapy on heart rate response in patients with hypertension and newly diagnosed untreated obstructive sleep apnea syndrome.

    PubMed

    Wolf, Jacek; Drozdowski, Jacek; Czechowicz, Krzysztof; Winklewski, Paweł J; Jassem, Ewa; Kara, Tomas; Somers, Virend K; Narkiewicz, Krzysztof

    2016-01-01

    Beta1-receptor antagonists (BBs) are commonly administered in the treatment of cardiovascular disease (CVD). The reported benefits of BB use in CVD patients with concomitant obstructive sleep apnea (OSA) may be limited by their impact on apnea-induced bradycardias. Therefore the aim of the study was to test the influence of BBs on periapneic heart rate (HR) fluctuations in hypertensive patients with newly-detected and untreated OSA. We studied 88 hypertensive patients (56 on BBs and 32 BB naive) with newly-diagnosed moderate-to-severe OSA who were free of major pulmonary comorbidities and did not require antiarrhythmic therapy. ECGs recorded during sleep were investigated for heart rate (HR) responses to apneas allowing to compare extreme HR accelerations and decelerations between the groups. Average sleep-time HR was comparable in BB-naive (BB-) and BB-treated (BB+) patients. Direct comparisons showed that HR decelerations were also similar in the two subgroups (53.8±9.6 vs. 54.4±7.8 bpm; P=0.78, for BB- and BB+, respectively) however, BBs blunted the OSA-induced HR accelerations (82.3±12.2 vs. 74.3±10.0; P=0.003). After adjusting for baseline HR and magnitude of desaturations, HR decelerations were more evident in BB-naive group whereas tachycardic responses remained blunted in the BB+ group. The incidence of ectopies and conduction abnormalities were comparable across two groups. Beta-blockers do not potentiate apnea-induced HR decelerations, attenuate apnea-induced increases in heart rate and do not influence incidence of ectopies and conduction abnormalities in patients with hypertension and moderate-to-severe, untreated OSA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Biomass burning emissions of trace gases and particles in marine air at Cape Grim, Tasmania

    NASA Astrophysics Data System (ADS)

    Lawson, S. J.; Keywood, M. D.; Galbally, I. E.; Gras, J. L.; Cainey, J. M.; Cope, M. E.; Krummel, P. B.; Fraser, P. J.; Steele, L. P.; Bentley, S. T.; Meyer, C. P.; Ristovski, Z.; Goldstein, A. H.

    2015-12-01

    Biomass burning (BB) plumes were measured at the Cape Grim Baseline Air Pollution Station during the 2006 Precursors to Particles campaign, when emissions from a fire on nearby Robbins Island impacted the station. Measurements made included non-methane organic compounds (NMOCs) (PTR-MS), particle number size distribution, condensation nuclei (CN) > 3 nm, black carbon (BC) concentration, cloud condensation nuclei (CCN) number, ozone (O3), methane (CH4), carbon monoxide (CO), hydrogen (H2), carbon dioxide (CO2), nitrous oxide (N2O), halocarbons and meteorology. During the first plume strike event (BB1), a 4 h enhancement of CO (max ~ 2100 ppb), BC (~ 1400 ng m-3) and particles > 3 nm (~ 13 000 cm-3) with dominant particle mode of 120 nm were observed overnight. A wind direction change lead to a dramatic reduction in BB tracers and a drop in the dominant particle mode to 50 nm. The dominant mode increased in size to 80 nm over 5 h in calm sunny conditions, accompanied by an increase in ozone. Due to an enhancement in BC but not CO during particle growth, the presence of BB emissions during this period could not be confirmed. The ability of particles > 80 nm (CN80) to act as CCN at 0.5 % supersaturation was investigated. The ΔCCN / ΔCN80 ratio was lowest during the fresh BB plume (56 ± 8 %), higher during the particle growth period (77 ± 4 %) and higher still (104 ± 3 %) in background marine air. Particle size distributions indicate that changes to particle chemical composition, rather than particle size, are driving these changes. Hourly average CCN during both BB events were between 2000 and 5000 CCN cm-3, which were enhanced above typical background levels by a factor of 6-34, highlighting the dramatic impact BB plumes can have on CCN number in clean marine regions. During the 29 h of the second plume strike event (BB2) CO, BC and a range of NMOCs including acetonitrile and hydrogen cyanide (HCN) were clearly enhanced and some enhancements in O3 were observed

  11. Light-absorbing organic carbon from prescribed and laboratory biomass burning and gasoline vehicle emissions.

    PubMed

    Xie, Mingjie; Hays, Michael D; Holder, Amara L

    2017-08-04

    Light-absorbing organic carbon (OC), also termed brown carbon (BrC), from laboratory-based biomass burning (BB) has been studied intensively to understand the contribution of BB to radiative forcing. However, relatively few measurements have been conducted on field-based BB and even fewer measurements have examined BrC from anthropogenic combustion sources like motor vehicle emissions. In this work, the light absorption of methanol-extractable OC from prescribed and laboratory BB and gasoline vehicle emissions was examined using spectrophotometry. The light absorption of methanol extracts showed a strong wavelength dependence for both BB and gasoline vehicle emissions. The mass absorption coefficients at 365 nm (MAC 365 , m 2 g -1 C) - used as a measurement proxy for BrC - were significantly correlated (p < 0.05) to the elemental carbon (EC)/OC ratios when examined by each BB fuel type. No significant correlation was observed when pooling fuels, indicating that both burn conditions and fuel types may impact BB BrC characteristics. The average MAC 365 of gasoline vehicle emission samples is 0.62 ± 0.76 m 2  g -1 C, which is similar in magnitude to the BB samples (1.27 ± 0.76 m 2  g -1 C). These results suggest that in addition to BB, gasoline vehicle emissions may also be an important BrC source in urban areas.

  12. Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect.

    PubMed

    Yin, Juntao; Hou, Yantao; Yin, Yuyun; Song, Xiaoyong

    2017-01-01

    Diabetes mellitus is an incurable metabolic disorder that seriously threatens human health. At present, there is no effective medication available to defeat it. This work intended to develop selenium-coated nanostructured lipid carriers (SeNLCs) for enhancing the oral bioavailability and the curative effect of berberine, an antidiabetic phytomedicine. Berberine-loaded SeNLCs (BB-SeNLCs) were prepared by hot-melt dispersion/homogenization procedure followed by in situ reduction. BB-SeNLCs were characterized by particle size, morphology, entrapment efficiency (EE) and in vitro release. Pharmacokinetics of berberine solution, berberine-loaded NLCs (BB-NLCs) and BB-SeNLCs were studied in Sprague Dawley rats administered by oral gavage. The prepared BB-SeNLCs were around 160 nm in particle size with an EE of 90%. In addition, BB-SeNLCs exhibited a better sustained release of berberine compared to the plain NLCs. After oral administration, BB-SeNLCs greatly enhanced the oral bioavailability of berberine, which was approximately 6.63 times as much as that of berberine solution. The hypoglycemic effect of BB-SeNLCs was also significantly superior to that of BB-NLCs and berberine solution. It turned out that sustained drug release and good intestinal absorption, plus the synergy of selenium, were basically responsible for enhanced oral bioavailability and hypoglycemic effect. Our findings show that SeNLCs are promising nanocarriers for oral delivery of berberine to strengthen the antidiabetic action.

  13. Selenium-coated nanostructured lipid carriers used for oral delivery of berberine to accomplish a synergic hypoglycemic effect

    PubMed Central

    Yin, Juntao; Hou, Yantao; Yin, Yuyun; Song, Xiaoyong

    2017-01-01

    Diabetes mellitus is an incurable metabolic disorder that seriously threatens human health. At present, there is no effective medication available to defeat it. This work intended to develop selenium-coated nanostructured lipid carriers (SeNLCs) for enhancing the oral bioavailability and the curative effect of berberine, an antidiabetic phytomedicine. Berberine-loaded SeNLCs (BB-SeNLCs) were prepared by hot-melt dispersion/homogenization procedure followed by in situ reduction. BB-SeNLCs were characterized by particle size, morphology, entrapment efficiency (EE) and in vitro release. Pharmacokinetics of berberine solution, berberine-loaded NLCs (BB-NLCs) and BB-SeNLCs were studied in Sprague Dawley rats administered by oral gavage. The prepared BB-SeNLCs were around 160 nm in particle size with an EE of 90%. In addition, BB-SeNLCs exhibited a better sustained release of berberine compared to the plain NLCs. After oral administration, BB-SeNLCs greatly enhanced the oral bioavailability of berberine, which was approximately 6.63 times as much as that of berberine solution. The hypoglycemic effect of BB-SeNLCs was also significantly superior to that of BB-NLCs and berberine solution. It turned out that sustained drug release and good intestinal absorption, plus the synergy of selenium, were basically responsible for enhanced oral bioavailability and hypoglycemic effect. Our findings show that SeNLCs are promising nanocarriers for oral delivery of berberine to strengthen the antidiabetic action. PMID:29263662

  14. A plant Kunitz-type inhibitor mimics bradykinin-induced cytosolic calcium increase and intestinal smooth muscle contraction.

    PubMed

    Andrade, Sheila Siqueira; Smaili, Soraya Soubhi; Monteforte, Priscila Totarelli; Miranda, Antônio; Kouyoumdjian, Maria; Sampaio, Misako Uemura; Lopes, Guiomar Silva; Oliva, Maria Luiza V

    2012-09-01

    BbKI is a kallikrein inhibitor with a reactive site sequence similar to that of kinins, the vasoactive peptides inserted in kininogen moieties. This structural similarity probably contributes to the strong interaction with plasma kallikrein, the enzyme that releases, from high-molecular weight kininogen (HMWK), the proinflammatory peptide bradykinin, which acts on B(2) receptors (B(2)R). BbKI was examined on smooth muscle contraction and Ca(2+) mobilization, in which the kallikrein-kinin system is involved. Contrary to expectations, BbKI (1.8 μm) increased [Ca(2+)](c) and contraction, as observed with BK (2.0 μm). Not blocked by B(1) receptors (B(1)R), the BbKI agonistic effect was blocked by the B(2)R antagonist, HOE-140 (6 μm), and the involvement of B(2)R was confirmed in B(2)R-knockout mice intestine. The same tissue response was obtained using a synthetic peptide derived from the BbKI reactive site structure, more resistant than BK to angiotensin I-converting enzyme (ACE) hydrolysis. Depending on the concentration, BbKI has a dual effect. At a low concentration, BbKI acts as a potent kallikrein inhibitor; however, due to the similarity to BK, in high concentrations, BbKI greatly increases Ca(2+) release from internal storages, as a consequence of its interaction with B(2)R. Therefore, the antagonistic and agonistic effects of BbKI may be considered in conditions of B(2)R involvement.

  15. On the Vertical Nature of Biomass Burning Plumes by the California Coast and Their Relationship with Marine Boundary Layer Clouds

    NASA Astrophysics Data System (ADS)

    Hu, L.; Montzka, S. A.; Godwin, D.; Andrews, A. E.; Thoning, K. W.; Miller, B. R.; Sweeney, C.; Miller, J. B.; Lehman, S.; Siso, C.; Mondeel, D. J.; Hall, B. D.; Nance, J. D.; Tans, P. P.; Elkins, J. W.

    2016-12-01

    Biomass burning (BB) plumes can significantly impact stratocumulus clouds (Sc), the dominant cloud type by global area, by altering their microphysical properties. The California (CA) coast is home to one of the three major semi-permanent stratocumulus (Sc) cloud decks in the world and BB emissions are of growing concern in the western United States, owing to both a warmer climate and fire-control strategies over recent decades. The thickness and vertical position of BB plumes, especially relative to clouds, is critical to understand how the aerosol will affect the thermodynamic structure of the atmosphere, cloud properties, and radiative forcing. This study reports on the characterization of the vertical, spatial, and temporal nature of BB aerosol over coastal CA, based on airborne data collected in the months of July and August for 2013 and 2016. Results from over 100 soundings indicate that multiple BB plume layers exist above clouds, with the thickness of BB plumes and their vertical position relative to cloud top varying significantly as a function of distance from coastline. Comparison of soundings at a given location at two different times of day reveals significant variation in BB characteristics. Intercomparisons for BB plume characteristics are explored between the field data, NAAPS, and CALIPSO.

  16. On the Vertical Nature of Biomass Burning Plumes by the California Coast and Their Relationship with Marine Boundary Layer Clouds

    NASA Astrophysics Data System (ADS)

    Hossein Mardi, A.; MacDonald, A. B.; Dadashazar, H.; Crosbie, E.; WANG, Z.; Lynch, P.; Campbell, J. R.; Jonsson, H.; Sorooshian, A.

    2017-12-01

    Biomass burning (BB) plumes can significantly impact stratocumulus clouds (Sc), the dominant cloud type by global area, by altering their microphysical properties. The California (CA) coast is home to one of the three major semi-permanent stratocumulus (Sc) cloud decks in the world and BB emissions are of growing concern in the western United States, owing to both a warmer climate and fire-control strategies over recent decades. The thickness and vertical position of BB plumes, especially relative to clouds, is critical to understand how the aerosol will affect the thermodynamic structure of the atmosphere, cloud properties, and radiative forcing. This study reports on the characterization of the vertical, spatial, and temporal nature of BB aerosol over coastal CA, based on airborne data collected in the months of July and August for 2013 and 2016. Results from over 100 soundings indicate that multiple BB plume layers exist above clouds, with the thickness of BB plumes and their vertical position relative to cloud top varying significantly as a function of distance from coastline. Comparison of soundings at a given location at two different times of day reveals significant variation in BB characteristics. Intercomparisons for BB plume characteristics are explored between the field data, NAAPS, and CALIPSO.

  17. Global biomass burning - Atmospheric, climatic, and biospheric implications

    NASA Technical Reports Server (NTRS)

    Levine, Joel S.

    1990-01-01

    Topics discussed at the March 1990 American Geophysical Union's Conference on biomass burning which was attended by more than 175 participants representing 19 countries are presented. Conference highlights include discussion of remote sensing data concerning biomass burning (BB), gaseous and particle emissions resulting from BB in the tropics, BB in temperate and boreal ecosystems, the historic and prehistoric perspectives on BB, BB and global budgets for carbon, nitrogen, and oxygen, and the BB and the greenhouse effect. Global estimates of annual amounts of biomass burning and of the resulting release of carbon to the atmosphere and the mean gaseous emission ratios for fires in wetlands, chaparral, and boreal ecosystems are given. An overview is presented of some conference discussions including global burning from 1850-1980, the global impact of biomass burning, the great Chinese/Soviet fire of 1987, and burning and biogenic emissions.

  18. Probiotic Dahi containing Lactobacillus acidophilus and Bifidobacterium bifidum modulates the formation of aberrant crypt foci, mucin-depleted foci, and cell proliferation on 1,2-dimethylhydrazine-induced colorectal carcinogenesis in Wistar rats.

    PubMed

    Mohania, Dheeraj; Kansal, Vinod K; Kruzliak, Peter; Kumari, Archana

    2014-08-01

    Aberrant crypt foci (ACF) and mucin-depleted foci (MDF) are pre-neoplastic lesions identified in the colon of carcinogen-treated rodents and in humans at high risk for colon cancer. The present study was carried out to divulge the protective potential of the probiotic Dahi containing Lactobacillus acidophilus LaVK2 and Bifidobacterium bifidum BbVK3 alone or in combination with piroxicam (PXC) on the development of early biomarkers of colorectal carcinogenesis in male Wistar rats administered 1,2-dimethylhydrazine (DMH). DMH was injected subcutaneously at the rate of 40 mg/kg body weight per animal twice a week for 2 weeks. A total of 120 male Wistar rats were randomly allocated to five groups, each group having 24 animals. The rats were fed with buffalo milk or probiotic supplement (20 grams) alone or as an adjunct with PXC in addition to a basal diet ad libitum for 32 weeks. Group I was offered buffalo milk (BM) and served as the control group. Group II was administered DMH along with BM and served as the DMH-control group; group III was administered BM-DMH-PXC, in which besides administering BM-DMH, PXC was also offered. Group IV was offered probiotic LaBb Dahi and DMH, and group V was offered both probiotic LaBb Dahi and PXC along with DMH. The rats were euthanized at the 8(th), 16(th), and 32(nd) week of the experiment and examined for development of ACF, aberrant crypts per ACF (AC/ACF), mucin-depleted foci (MDF), large MDF, and proliferating cell nuclear antigen (PCNA) labeling index. Administration of DMH in rats induced pre-neoplastic lesions (ACF and MDF) and increased the PCNA index in colorectal tissue. A significant (p<0.05) reduction in the number of ACF, AC/ACF, MDF, large MDF, and PCNA labeling index were observed in the probiotic LaBb Dahi group compared with the DMH control group. Feeding rats with LaBb Dahi or treatment with PXC diminished the initiation and progression of DMH-induced pre-neoplastic lesions and the PCNA index, and treatment with

  19. Does more favourable handling of the cerebrospinal fluid increase the diagnostic sensitivity of Borrelia burgdorferi sensu lato-specific PCR in Lyme neuroborreliosis?

    PubMed

    Forselv, Kristine J N; Lorentzen, Åslaug R; Ljøstad, Unn; Mygland, Åse; Eikeland, Randi; Kjelland, Vivian; Noraas, Sølvi; Quarsten, Hanne

    2018-04-01

    Tests for direct detection of Borrelia burgdorferi sensu lato (Bb) in Lyme neuroborreliosis (LNB) are needed. Detection of Bb DNA using PCR is promising, but clinical utility is hampered by low diagnostic sensitivity. We aimed to examine whether diagnostic sensitivity can be improved by the use of larger cerebrospinal fluid (CSF) volumes and faster handling of samples. Patients who underwent CSF examination for LNB were included. We collected two millilitres of CSF for PCR analysis, extracted DNA from the pellets within 24 h and analysed the eluate by two real-time PCR protocols (16S rRNA and OspA). Patients who fulfilled diagnostic criteria for LNB were classified as LNB cases and the rest as controls. Bb DNA in CSF was detected by PCR in seven of 28 adults with LNB. Two were Bb antibody negative. No Bb DNA was detected in CSF from 137 controls. Diagnostic sensitivity was 25% and specificity 100%. There was a non-significant trend towards larger CSF sample volume, faster handling of the sample, shorter duration of symptoms, and higher CSF cell count in the PCR-positive cases. We did not find that optimized handling of CSF increased diagnostic sensitivity of PCR in adults with LNB. However, our case series is small and we hypothesize that the importance of these factors will be clarified in further studies with larger case series and altered study design. PCR for diagnosis of LNB may be useful in cases without Bb antibodies due to short duration of symptoms.

  20. Foreign Body Ingestion in Children: Should Button Batteries in the Stomach Be Urgently Removed?

    PubMed

    Lee, Jun Hee; Lee, Jee Hoo; Shim, Jung Ok; Lee, Jung Hwa; Eun, Baik-Lin; Yoo, Kee Hwan

    2016-03-01

    Foreign body (FB) ingestion is common in children, and button battery (BB) ingestion has been increasing in recent years. This study was to identify factors related to outcomes of FB ingestion, particularly BBs in the stomach. We evaluated whether the current recommendations are appropriate and aimed to suggest indications for endoscopic removal of BB in the stomach in young children. We investigated patient age, shape, size, location of FBs, spontaneous passage time and resulting complications among 76 children. We observed types, size, location of BB and outcomes, and analyzed their associations with complications. Coins and BB were the two most common FBs. Their shapes and sizes were not associated with the spontaneous passage time. Size, spontaneous passage time, and age were also not associated with any specific complications. For BB ingestion, all 5 cases with lithium batteries (≥1.5 cm, 3 V) presented moderate to major complications in the esophagus and stomach without any symptoms, even when the batteries were in the stomach and beyond the duodenum, while no complications were noted in 7 cases with alkaline batteries (<1.5 cm, 1.5 V) (p=0.001). All endoscopies were conducted within 24 hours after ingestion. The type and voltage of the battery should be considered when determining whether endoscopy is required to remove a BB in the stomach. For lithium battery ingestion in young children, urgent endoscopic removal might be important in order to prevent complications, even if the child is asymptomatic and the battery is smaller than 2 cm.

  1. The development of allergic inflammation in a murine house dust mite asthma model is suppressed by synbiotic mixtures of non-digestible oligosaccharides and Bifidobacterium breve M-16V.

    PubMed

    Verheijden, K A T; Willemsen, L E M; Braber, S; Leusink-Muis, T; Jeurink, P V; Garssen, J; Kraneveld, A D; Folkerts, G

    2016-04-01

    The incidence and severity of allergic asthma is rising, and novel strategies to prevent or treat this disease are needed. This study investigated the effects of different mixtures of non-digestible oligosaccharides combined with Bifidobacterium breve M-16V (BB) on the development of allergic airway inflammation in an animal model for house dust mite (HDM)-induced allergic asthma. BALB/c mice were sensitized intranasally (i.n.) with HDM and subsequently challenged (i.n.) with PBS or HDM while being fed diets containing different oligosaccharide mixtures in combination with BB or an isocaloric identical control diet. Bronchoalveolar lavage fluid (BALF) inflammatory cell influx, chemokine and cytokine concentrations in lung homogenates and supernatants of ex vivo HDM-restimulated lung cells were analyzed. The HDM-induced influx of eosinophils and lymphocytes was reduced by the diet containing the short-chain and long-chain fructo-oligosaccharides and BB (FFBB). In addition to the HDM-induced cell influx, concentrations of IL-33, CCL17, CCL22, IL-6, IL-13 and IL-5 were increased in supernatants of lung homogenates or BALF and IL-4, IFN-γ and IL-10 were increased in restimulated lung cell suspensions of HDM-allergic mice. The diet containing FFBB reduced IL-6, IFN-γ, IL-4 and IL-10 concentrations, whereas the combination of galacto-oligosaccharides and long-chain fructo-oligosaccharides with BB was less potent in this model. These findings show that synbiotic dietary supplementation can affect respiratory allergic inflammation induced by HDM. The combination of FFBB was most effective in the prevention of HDM-induced airway inflammation in mice.

  2. Better Efficacy of Synchrotron Spatially Microfractionated Radiation Therapy Than Uniform Radiation Therapy on Glioma.

    PubMed

    Bouchet, Audrey; Bräuer-Krisch, Elke; Prezado, Yolanda; El Atifi, Michèle; Rogalev, Léonid; Le Clec'h, Céline; Laissue, Jean Albert; Pelletier, Laurent; Le Duc, Géraldine

    2016-08-01

    Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred grays. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial locations. However, mechanisms responsible for such a property are not fully understood. Thanks to recent progress in dosimetry, we compared the effect of MRT and synchrotron broad beam (BB) radiation therapy delivered at comparable doses (equivalent to MRT valley dose) on tumor growth control and on classical radiobiological functions by histologic evaluation and/or transcriptomic analysis. MRT significantly improved survival of rats bearing 9L intracranial glioma compared with BB radiation therapy delivered at a comparable dose (P<.001); the efficacy of MRT and BB radiation therapy was similar when the MRT dose was half that of BB. The greater efficacy of MRT was not correlated with a difference in cell proliferation (Mki67 and proliferating cell nuclear antigen) or in transcriptomic stimulation of angiogenesis (vascular endothelial growth factor A or tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) but was correlated with a higher cell death rate (factor for apoptosis signals) and higher recruitment of macrophages (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and CD68 transcripts) a few days after MRT. These results show the superiority of MRT over BB radiation therapy when applied at comparable doses, suggesting that spatial fractionation is responsible for a specific and particularly efficient tissue response. The higher induction of cell death and immune cell activation in brain tumors treated by MRT may be involved in such responses. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Better Efficacy of Synchrotron Spatially Microfractionated Radiation Therapy Than Uniform Radiation Therapy on Glioma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bouchet, Audrey, E-mail: audrey.m.bouchet@gmail.com; Biomedical Beamline, European Synchrotron Radiation Facility, Grenoble; Bräuer-Krisch, Elke

    Purpose: Synchrotron microbeam radiation therapy (MRT) is based on the spatial fractionation of the incident, highly focused synchrotron beam into arrays of parallel microbeams, typically a few tens of microns wide and depositing several hundred grays. This irradiation modality was shown to have a high therapeutic impact on tumors, especially in intracranial locations. However, mechanisms responsible for such a property are not fully understood. Methods and Materials: Thanks to recent progress in dosimetry, we compared the effect of MRT and synchrotron broad beam (BB) radiation therapy delivered at comparable doses (equivalent to MRT valley dose) on tumor growth control andmore » on classical radiobiological functions by histologic evaluation and/or transcriptomic analysis. Results: MRT significantly improved survival of rats bearing 9L intracranial glioma compared with BB radiation therapy delivered at a comparable dose (P<.001); the efficacy of MRT and BB radiation therapy was similar when the MRT dose was half that of BB. The greater efficacy of MRT was not correlated with a difference in cell proliferation (Mki67 and proliferating cell nuclear antigen) or in transcriptomic stimulation of angiogenesis (vascular endothelial growth factor A or tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2) but was correlated with a higher cell death rate (factor for apoptosis signals) and higher recruitment of macrophages (tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 and CD68 transcripts) a few days after MRT. Conclusions: These results show the superiority of MRT over BB radiation therapy when applied at comparable doses, suggesting that spatial fractionation is responsible for a specific and particularly efficient tissue response. The higher induction of cell death and immune cell activation in brain tumors treated by MRT may be involved in such responses.« less

  4. Skeletal muscle hypertrophy and structure and function of skeletal muscle fibres in male body builders

    PubMed Central

    D'Antona, Giuseppe; Lanfranconi, Francesca; Pellegrino, Maria Antonietta; Brocca, Lorenza; Adami, Raffaella; Rossi, Rosetta; Moro, Giorgio; Miotti, Danilo; Canepari, Monica; Bottinelli, Roberto

    2006-01-01

    Needle biopsy samples were taken from vastus lateralis muscle (VL) of five male body builders (BB, age 27.4 ± 0.93 years; mean ±s.e.m.), who had being performing hypertrophic heavy resistance exercise (HHRE) for at least 2 years, and from five male active, but untrained control subjects (CTRL, age 29.9 ± 2.01 years). The following determinations were performed: anatomical cross-sectional area and volume of the quadriceps and VL muscles in vivo by magnetic resonance imaging (MRI); myosin heavy chain isoform (MHC) distribution of the whole biopsy samples by SDS-PAGE; cross-sectional area (CSA), force (Po), specific force (Po/CSA) and maximum shortening velocity (Vo) of a large population (n= 524) of single skinned muscle fibres classified on the basis of MHC isoform composition by SDS-PAGE; actin sliding velocity (Vf) on pure myosin isoforms by in vitro motility assays. In BB a preferential hypertrophy of fast and especially type 2X fibres was observed. The very large hypertrophy of VL in vivo could not be fully accounted for by single muscle fibre hypertrophy. CSA of VL in vivo was, in fact, 54% larger in BB than in CTRL, whereas mean fibre area was only 14% larger in BB than in CTRL. MHC isoform distribution was shifted towards 2X fibres in BB. Po/CSA was significantly lower in type 1 fibres from BB than in type 1 fibres from CTRL whereas both type 2A and type 2X fibres were significantly stronger in BB than in CTRL. Vo of type 1 fibres and Vf of myosin 1 were significantly lower in BB than in CTRL, whereas no difference was observed among fast fibres and myosin 2A. The findings indicate that skeletal muscle of BB was markedly adapted to HHRE through extreme hypertrophy, a shift towards the stronger and more powerful fibre types and an increase in specific force of muscle fibres. Such adaptations could not be fully accounted for by well known mechanisms of muscle plasticity, i.e. by the hypertrophy of single muscle fibre (quantitative mechanism) and by a

  5. 32 CFR 552.102 - Requirements for possession and use.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-defined and privately-owned firearms, ammunition, BB and pellet guns, knives, bows and arrows, and crossbows under the following conditions: (a) Privately-owned firearms, crossbows, BB and pellet guns..., registered crossbows, registered BB and pellet guns and registered firearms within their quarters. (c...

  6. Pre-injury neuro-psychiatric medication use, alone or in combination with cardiac medications, may affect outcomes in trauma patients.

    PubMed

    Wisler, J R; Springer, A N; Hateley, K; Mo, X M; Evans, D C; Cook, C H; Gerlach, A T; Murphy, C V; Eiferman, D S; Steinberg, S M; Bergese, S D; Papadimos, T J; Stawicki, S P

    2014-01-01

    Recent review of older (≥45-years-old) patients admitted to our trauma center showed that more than one-third were using neuro-psychiatric medications (NPMs) prior to their injury-related admission. Previously published data suggests that use of NPMs may increase patients' risk and severity of injury. We sought to examine the impact of pre-injury NPM use on older trauma patients' morbidity and mortality. Retrospective record review included medication regimen characteristics and NPM use (antidepressants-AD, antipsychotics-AP, anxiolytics-AA). Hospital morbidity, mortality, and 90-day survival were examined. Comparisons included regimens involving NPMs, further focusing on their interactions with various cardiac medications (beta blocker - BB; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker - ACE/ARB; calcium channel blocker - CCB). 712 patient records were reviewed (399 males, mean age 63.5 years, median ISS 8). 245 patients were taking at least 1 NPM: AD (158), AP (35), or AA (108) before injury. There was no effect of NPM monotherapy on hospital mortality. Patients taking ≥3 NPMs had significantly lower 90-day survival compared to patients taking ≤2 NPMs (81% for 3 or more NPMs, 95% for no NPMs, and 89% 1-2 NPMs, P < 0.01). Several AD-cardiac medication (CM) combinations were associated with increased mortality compared to monotherapy with either agent (BB-AD 14.7% mortality versus 7.0% for AD monotherapy or 4.8% BB monotherapy, P < 0.05). Combinations of ACE/ARB-AA were associated with increased mortality compared to ACE/ARB monotherapy (11.5% vs 4.9, P = 0.04). Finally, ACE/ARB-AD co-administration had higher mortality than ACE/ARB monotherapy (13.5% vs 4.9%, P = 0.01). Large proportion of older trauma patients was using pre-injury NPMs. Several regimens involving NPMs and CMs were associated with increased in-hospital mortality. Additionally, use of ≥3 NPMs was associated with lower 90-day survival.

  7. Direct binding to antigen-coated beads refines the specificity and cross-reactivity of four monoclonal antibodies that recognize polymorphic epitopes of HLA class I molecules.

    PubMed

    Hilton, H G; Parham, P

    2013-04-01

    Monoclonal antibodies with specificity for human leukocyte antigen (HLA) class I determinants of HLA were originally characterized using serological assays in which the targets were cells expressing three to six HLA class I variants. Because of this complexity, the specificities of the antibodies were defined indirectly by correlation. Here we use a direct binding assay, in which the targets are synthetic beads coated with 1 of 111 HLA class I variants, representing the full range of HLA-A, -B and -C variation. We studied one monoclonal antibody with monomorphic specificity (W6/32) and four with polymorphic specificity (MA2.1, PA2.1, BB7.2 and BB7.1) and compared the results with those obtained previously. W6/32 reacted with all HLA class I variants. MA2.1 not only exhibits high specificity for HLA-A*02, -B*57 and -B*58, but also exhibited cross-reactivity with HLA-A*11 and -B*15:16. At low concentration (1 µg/ml), PA2.1 and BB7.2 were both specific for HLA-A*02 and -A*69, and at high concentration (50 µg/ml) exhibited significant cross-reactions with HLA-A*68, -A*23 and -A*24. BB7.1 exhibits specificity for HLA-B*07 and -B*42, as previously described, but reacts equally well with HLA-B*81, a rare allotype defined some 16 years after the description of BB7.1. The results obtained with cell-based and bead-based assays are consistent and, in combination with amino acid sequence comparison, increase understanding of the polymorphic epitopes recognized by the MA2.1, PA2.1, BB7.2 and BB7.1 antibodies. Comparison of two overlapping but distinctive bead sets from two sources gave similar results, but the overall levels of binding were significantly different. Several weaker reactions were observed with only one of the bead sets. © 2013 John Wiley & Sons A/S.

  8. Direct binding to antigen-coated beads refines the specificity and cross-reactivity of four monoclonal antibodies that recognize polymorphic epitopes of HLA class I molecules

    PubMed Central

    Hilton, Hugo G; Parham, Peter

    2013-01-01

    Monoclonal antibodies with specificity for HLA class I determinants of HLA were originally characterized using serological assays in which the targets were cells expressing 3-6 HLA class I variants. Because of this complexity, the specificities of the antibodies were defined indirectly by correlation. Here we use a direct binding assay, in which the targets are synthetic beads coated with one of 111 HLA class I variants, representing the full range of HLA-A, -B and -C variation. We studied one monoclonal antibody with monomorphic specificity (W6/32) and four with polymorphic specificity (MA2.1, PA2.1, BB7.2 and BB7.1) and compared the results with those obtained previously. W6/32 reacted with all HLA class I variants. MA2.1 exhibits high specificity for HLA-A*02, -B*57 and -B*58, but also exhibited cross-reactivity with HLA-A*11 and -B*15:16. At low concentration (1μg/ml) PA2.1 and BB7.2 were both specific for HLA-A*02 and -A*69, and at high concentration (50μg/ml) exhibited significant cross-reactions with HLA-A*68, -A*23, and -A*24. BB7.1 exhibits specificity for HLA-B*07 and -B*42, as previously described, but reacts equally well with HLA-B*81, a rare allotype defined some 16 years after the description of BB7.1. The results obtained with cell-based and bead-based assays are consistent and, in combination with amino acid sequence comparison, increase understanding of the polymorphic epitopes recognized by the MA2.1, PA2.1, BB7.2 and BB7.1 antibodies. Comparison of two overlapping but distinctive bead sets from two sources gave similar results, but the overall levels of binding were significantly different. Several weaker reactions were observed with only one of the bead sets. PMID:23510417

  9. Short-term blueberry-enriched diet prevents and reverses object recognition memory loss in aging rats.

    PubMed

    Malin, David H; Lee, David R; Goyarzu, Pilar; Chang, Yu-Hsuan; Ennis, Lalanya J; Beckett, Elizabeth; Shukitt-Hale, Barbara; Joseph, James A

    2011-03-01

    Previously, 4 mo of a blueberry-enriched (BB) antioxidant diet prevented impaired object recognition memory in aging rats. Experiment 1 determined whether 1- and 2-mo BB diets would have a similar effect and whether the benefits would disappear promptly after terminating the diets. Experiment 2 determined whether a 1-mo BB diet could subsequently reverse existing object memory impairment in aging rats. In experiment 1, Fischer-344 rats were maintained on an appropriate control diet or on 1 or 2 mo of the BB diet before testing object memory at 19 mo postnatally. In experiment 2, rats were tested for object recognition memory at 19 mo and again at 20 mo after 1 mo of maintenance on a 2% BB or control diet. In experiment 1, the control group performed no better than chance, whereas the 1- and 2-mo BB diet groups performed similarly and significantly better than controls. The 2-mo BB-diet group, but not the 1-mo group, maintained its performance over a subsequent month on a standard laboratory diet. In experiment 2, the 19-mo-old rats performed near chance. At 20 mo of age, the rats subsequently maintained on the BB diet significantly increased their object memory scores, whereas the control diet group exhibited a non-significant decline. The change in object memory scores differed significantly between the two diet groups. These results suggest that a considerable degree of age-related object memory decline can be prevented and reversed by brief maintenance on BB diets. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Measurement of the decays B--> phiK and B--> phiK*.

    PubMed

    Aubert, B; Boutigny, D; Gaillard, J M; Hicheur, A; Karyotakis, Y; Lees, J P; Robbe, P; Tisserand, V; Palano, A; Chen, G P; Chen, J C; Qi, N D; Rong, G; Wang, P; Zhu, Y S; Eigen, G; Reinertsen, P L; Stugu, B; Abbott, B; Abrams, G S; Borgland, A W; Breon, A B; Brown, D N; Button-Shafer, J; Cahn, R N; Clark, A R; Fan, Q; Gill, M S; Gowdy, S J; Gritsan, A; Groysman, Y; Jacobsen, R G; Kadel, R W; Kadyk, J; Kerth, L T; Kluth, S; Kolomensky, Y G; Kral, J F; LeClerc, C; Levi, M E; Liu, T; Lynch, G; Meyer, A B; Momayezi, M; Oddone, P J; Perazzo, A; Pripstein, M; Roe, N A; Romosan, A; Ronan, M T; Shelkov, V G; Telnov, A V; Wenzel, W A; Bright-Thomas, P G; Harrison, T J; Hawkes, C M; Kirk, A; Knowles, D J; O'Neale, S W; Penny, R C; Watson, A T; Watson, N K; Deppermann, T; Koch, H; Krug, J; Kunze, M; Lewandowski, B; Peters, K; Schmuecker, H; Steinke, M; Andress, J C; Barlow, N R; Bhimji, W; Chevalier, N; Clark, P J; Cottingham, W N; De Groot, N; Dyce, N; Foster, B; Mass, A; McFall, J D; Wallom, D; Wilson, F F; Abe, K; Hearty, C; Mattison, T S; McKenna, J A; Thiessen, D; Camanzi, B; Jolly, S; McKemey, A K; Tinslay, J; Blinov, V E; Bukin, A D; Bukin, D A; Buzykaev, A R; Dubrovin, M S; Golubev, V B; Ivanchenko, V N; Korol, A A; Kravchenko, E A; Onuchin, A P; Salnikov, A A; Serednyakov, S I; Skovpen, Y I; Telnov, V I; Yushkov, A N; Lankford, A J; Mandelkern, M; McMahon, S; Stoker, D P; Ahsan, A; Arisaka, K; Buchanan, C; Chun, S; Branson, J G; MacFarlane, D B; Prell, S; Rahatlou, S; Raven, G; Sharma, V; Campagnari, C; Dahmes, B; Hart, P A; Kuznetsova, N; Levy, S L; Long, O; Lu, A; Richman, J D; Verkerke, W; Witherell, M; Yellin, S; Beringer, J; Dorfan, D E; Eisner, A M; Frey, A; Grillo, A A; Grothe, M; Heusch, C A; Johnson, R P; Kroeger, W; Lockman, W S; Pulliam, T; Sadrozinski, H; Schalk, T; Schmitz, R E; Schumm, B A; Seiden, A; Turri, M; Walkowiak, W; Williams, D C; Wilson, M G; Chen, E; Dubois-Felsmann, G P; Dvoretskii, A; Hitlin, D G; Metzler, S; Oyang, J; Porter, F C; Ryd, A; Samuel, A; Weaver, M; Yang, S; Zhu, R Y; Devmal, S; Geld, T L; Jayatilleke, S; Mancinelli, G; Meadows, B T; Sokoloff, M D; Bloom, P; Fahey, S; Ford, W T; Gaede, F; Johnson, D R; Michael, A K; Nauenberg, U; Olivas, A; Park, H; Rankin, P; Roy, J; Sen, S; Smith, J G; van Hoek, W C; Wagner, D L; Blouw, J; Harton, J L; Krishnamurthy, M; Soffer, A; Toki, W H; Wilson, R J; Zhang, J; Brandt, T; Brose, J; Colberg, T; Dahlinger, G; Dickopp, M; Dubitzky, R S; Maly, E; Müller-Pfefferkorn, R; Otto, S; Schubert, K R; Schwierz, R; Spaan, B; Wilden, L; Behr, L; Bernard, D; Bonneaud, G R; Brochard, F; Cohen-Tanugi, J; Ferrag, S; Roussot, E; T'Jampens, S; Thiebaux, C; Vasileiadis, G; Verderi, M; Anjomshoaa, A; Bernet, R; Di Lodovico, F; Khan, A; Muheim, F; Playfer, S; Swain, J E; Falbo, M; Bozzi, C; Dittongo, S; Folegani, M; Piemontese, L; Treadwell, E; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Falciai, D; Finocchiaro, G; Patteri, P; Peruzzi, I M; Piccolo, M; Xie, Y; Zallo, A; Bagnasco, S; Buzzo, A; Contri, R; Crosetti, G; Fabbricatore, P; Farinon, S; Lo Vetere, M; Macri, M; Monge, M R; Musenich, R; Pallavicini, M; Parodi, R; Passaggio, S; Pastore, F C; Patrignani, C; Pia, M G; Priano, C; Robutti, E; Santroni, A; Morii, M; Bartoldus, R; Dignan, T; Hamilton, R; Mallik, U; Cochran, J; Crawley, H B; Fischer, P A; Lamsa, J; Meyer, W T; Rosenberg, E I; Benkebil, M; Grosdidier, G; Hast, C; Höcker, A; Lacker, H M; LePeltier, V; Lutz, A M; Plaszczynski, S; Schune, M H; Trincaz-Duvoid, S; Valassi, A; Wormser, G; Bionta, R M; Brigljevic, V; Fackler, O; Fujino, D; Lange, D J; Mugge, M; Shi, X; van Bibber, K; Wenaus, T J; Wright, D M; Wuest, C R; Carroll, M; Fry, J R; Gabathuler, E; Gamet, R; George, M; Kay, M; Payne, D J; Sloane, R J; Touramanis, C; Aspinwall, M L; Bowerman, D A; Dauncey, P D; Egede, U; Eschrich, I; Gunawardane, N J; Martin, R; Nash, J A; Sanders, P; Smith, D; Azzopardi, D E; Back, J J; Dixon, P; Harrison, P F; Potter, R J; Shorthouse, H W; Strother, P; Vidal, P B; Williams, M I; Cowan, G; George, S; Green, M G; Kurup, A; Marker, C E; McGrath, P; McMahon, T R; Ricciardi, S; Salvatore, F; Scott, I; Vaitsas, G; Brown, D; Davis, C L; Allison, J; Barlow, R J; Boyd, J T; Forti, A; Fullwood, J; Jackson, F; Lafferty, G D; Savvas, N; Simopoulos, E T; Weatherall, J H; Farbin, A; Jawahery, A; Lillard, V; Olsen, J; Roberts, D A; Schieck, J R; Blaylock, G; Dallapiccola, C; Flood, K T; Hertzbach, S S; Kofler, R; Lin, C S; Moore, T B; Staengle, H; Willocq, S; Wittlin, J; Brau, B; Cowan, R; Sciolla, G; Taylor, F; Yamamoto, R K; Britton, D I; Milek, M; Patel, P M; Trischuk, J; Lanni, F; Palombo, F; Bauer, J M; Booke, M; Cremaldi, L; Eschenburg, V; Kroeger, R; Reidy, J; Sanders, D A; Summers, D J; Martin, J P; Nief, J Y; Seitz, R; Taras, P; Zacek, V; Nicholson, H; Sutton, C S; Cartaro, C; Cavallo, N; De Nardo, G; Fabozzi, F; Gatto, C; Lista, L; Paolucci, P; Piccolo, D; Sciacca, C; LoSecco, J M; Alsmiller, J R; Gabriel, T A; Handler, T; Brau, J; Frey, R; Iwasaki, M; Sinev, N B; Strom, D; Colecchia, F; Dal Corso, F; Dorigo, A; Galeazzi, F; Margoni, M; Michelon, G; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Torassa, E; Voci, C; Benayoun, M; Briand, H; Chauveau, J; David, P; De La Vaissière, C; Del Buono, L; Hamon, O; Le Diberder, F; Leruste, P; Lory, J; Roos, L; Stark, J; Versillé, S; Manfredi, P F; Re, V; Speziali, V; Frank, E D; Gladney, L; Guo, Q H; Panetta, J H; Angelini, C; Batignani, G; Bettarini, S; Bondioli, M; Carpinelli, M; Forti, F; Giorgi, M A; Lusiani, A; Martinez-Vidal, F; Morganti, M; Neri, N; Paoloni, E; Rama, M; Rizzo, G; Sandrelli, F; Simi, G; Triggiani, G; Walsh, J; Haire, M; Judd, D; Paick, K; Turnbull, L; Wagoner, D E; Albert, J; Bula, C; Lu, C; McDonald, K T; Miftakov, V; Schaffner, S F; Smith, A J; Tumanov, A; Varnes, E W; Cavoto, G; del Re, D; Faccini, R; Ferrarotto, F; Ferroni, F; Fratini, K; Lamanna, E; Leonardi, E; Mazzoni, M A; Morganti, S; Piredda, G; Safai Tehrani, F; Serra, M; Voena, C; Christ, S; Waldi, R; Adye, T; Franek, B; Geddes, N I; Gopal, G P; Xella, S M; Aleksan, R; De Domenico, G; Emery, S; Gaidot, A; Ganzhur, S F; Giraud, P F; Hamel De Monchenault, G; Kozanecki, W; Langer, M; London, G W; Mayer, B; Serfass, B; Vasseur, G; Yeche, C; Zito, M; Copty, N; Purohit, M V; Singh, H; Yumiceva, F X; Adam, I; Anthony, P L; Aston, D; Baird, K; Bartelt, J; Bloom, E; Boyarski, A M; Bulos, F; Calderini, G; Claus, R; Convery, M R; Coupal, D P; Coward, D H; Dorfan, J; Doser, M; Dunwoodie, W; Field, R C; Glanzman, T; Godfrey, G L; Grosso, P; Himel, T; Huffer, M E; Innes, W R; Jessop, C P; Kelsey, M H; Kim, P; Kocian, M L; Langenegger, U; Leith, D W; Luitz, S; Luth, V; Lynch, H L; Manzin, G; Marsiske, H; Menke, S; Messner, R; Moffeit, K C; Mount, R; Muller, D R; O'Grady, C P; Petrak, S; Quinn, H; Ratcliff, B N; Robertson, S H; Rochester, L S; Roodman, A; Schietinger, T; Schindler, R H; Schwiening, J; Serbo, V V; Snyder, A; Soha, A; Spanier, S M; Stahl, A; Stelzer, J; Su, D; Sullivan, M K; Talby, M; Tanaka, H A; Trunov, A; Va'vra, J; Wagner, S R; Weinstein, A J; Wisniewski, W J; Young, C C; Burchat, P R; Cheng, C H; Kirkby, D; Meyer, T I; Roat, C; De Silva, A; Henderson, R; Bugg, W; Cohn, H; Hart, E; Weidemann, A W; Benninger, T; Izen, J M; Kitayama, I; Lou, X C; Turcotte, M; Bianchi, F; Bona, M; Di Girolamo, B; Gamba, D; Smol, A; Zanin, D; Bosisio, L; Della Ricca, G; Lanceri, L; Pompili, A; Poropat, P; Prest, M; Vallazza, E; Vuagnin, G; Panvini, R S; Brown, C M; Kowalewski, R; Roney, J M; Band, H R; Charles, E; Dasu, S; Elmer, P; Hu, H; Johnson, J R; Liu, R; Nielsen, J; Orejudos, W; Pan, Y; Prepost, R; Scott, I J; Sekula, S J; von Wimmersperg-Toeller, J H; Wu, S L; Yu, Z; Zobering, H; Kordich, T M; Neal, H

    2001-10-08

    We have observed the decays B--> phiK and phiK(*) in a sample of over 45 million B mesons collected with the BABAR detector at the PEP-II collider. The measured branching fractions are B(B+--> phiK+) = (7.7(+1.6)(-1.4)+/-0.8)x10(-6), B(B0--> phiK0) = (8.1(+3.1)(-2.5)+/-0.8)x10(-6), B(B+--> phiK(*+)) = (9.7(+4.2)(-3.4)+/-1.7)x10(-6), and B(B0--> phiK(*0)) = (8.7(+2.5)(-2.1)+/-1.1)x10(-6). We also report the upper limit B(B+--> phipi(+))<1.4x10(-6) ( 90% C.L.).

  11. Comparison of phenolic acid profiles and anti-inflammatory effects of two major species of blueberries in the US

    USDA-ARS?s Scientific Manuscript database

    Blueberries (BB) contain high levels of polyphenols. Among them, phenolic acids (PAs) have been recently suggested as a group of important bioactive compounds. Highbush BB (Vaccinium corymbosum) and lowbush “wild" BB (Vaccinium angustifolium) are two predominant species in North America. The first o...

  12. Health behaviors associated with use of body building, weight loss, and performance enhancing supplements.

    PubMed

    Kao, Tzu-Cheg; Deuster, Patricia A; Burnett, Daniel; Stephens, Mark

    2012-05-01

    To identify health-related behaviors associated with potentially harmful dietary supplements (DS) - body building (BB), weight loss (WL) and performance enhancing (PE), explore common reasons and sources of information for DS use. Based on the 2005 Survey of 16,146 U.S. military personnel, BB users were dichotomized as yes (regular use - taking any supplement of BB at least once a week in past 12 months) or no; similarly defined for WL and PE. Weighted logistic regression models are used. BB, WL and PE were used by 19.4%, 17.0%, and 8.0% of participants, respectively. Significantly more users were overweight or obese: BMI ≥25 (vs. BMI<25); heavy drinkers (vs. abstainers); and users of taking steroids in their lifetime (vs. not). Most common reasons of BB, WL, and PE users wanted to increase muscle mass, lose weight, and improve physical performance (BB: 45.8%, WL: 54.8%, PE: 38.5%). Fewer than 30% discussed dietary supplements use with their healthcare providers. The leading source of dietary supplements information (BB: 27.8%, WL: 23.6%, PE: 30.0%) was magazines. The dietary supplements: BB, WL and PE were used by significant proportions of service members, and associated with risk-taking behaviors that may affect overall military readiness and public health. Published by Elsevier Inc.

  13. Statistical molecular design of building blocks for combinatorial chemistry.

    PubMed

    Linusson, A; Gottfries, J; Lindgren, F; Wold, S

    2000-04-06

    The reduction of the size of a combinatorial library can be made in two ways, either base the selection on the building blocks (BB's) or base it on the full set of virtually constructed products. In this paper we have investigated the effects of applying statistical designs to BB sets compared to selections based on the final products. The two sets of BB's and the virtually constructed library were described by structural parameters, and the correlation between the two characterizations was investigated. Three different selection approaches were used both for the BB sets and for the products. In the first two the selection algorithms were applied directly to the data sets (D-optimal design and space-filling design), while for the third a cluster analysis preceded the selection (cluster-based design). The selections were compared using visual inspection, the Tanimoto coefficient, the Euclidean distance, the condition number, and the determinant of the resulting data matrix. No difference in efficiency was found between selections made in the BB space and in the product space. However, it is of critical importance to investigate the BB space carefully and to select an appropriate number of BB's to result in an adequate diversity. An example from the pharmaceutical industry is then presented, where selection via BB's was made using a cluster-based design.

  14. Evaluation of carotid stenosis with axial high-resolution black-blood MR imaging.

    PubMed

    U-King-Im, Jean M; Trivedi, Rikin A; Sala, Evis; Graves, Martin J; Gaskarth, Mathew; Higgins, Nicholas J; Cross, Justin C; Hollingworth, William; Coulden, Richard A; Kirkpatrick, Peter J; Antoun, Nagui M; Gillard, Jonathan H

    2004-07-01

    High-resolution axial black-blood MR imaging (BB MRI) has been shown to be able to characterise carotid plaque morphology. The aim of this study was to explore the accuracy of this technique in quantifying the severity of carotid stenosis. A prospective study of 54 patients with symptomatic carotid disease was conducted, comparing BB MRI to the gold standard, conventional digital subtraction X-ray angiography (DSA). The BB MRI sequence was a fast-spin echo acquisition (TE = 42 ms, ETL = 24, field of view = 100 x 100 mm, slice thickness = 3.0 mm) at 1.5 T using a custom-built phased-array coil. Linear measurements of luminal and outer carotid wall diameter were made directly from the axial BB MRI slices by three independent blinded readers and stenosis was calculated according to European Carotid Surgery Trial (ECST) criteria. There was good agreement between BB MRI and DSA (intraclass correlation = 0.83). Inter-observer agreement was good (average kappa = 0.77). BB MRI was accurate for detection of severe stenosis (> or = 80%) with sensitivity and specificity of 87 and 81%, respectively. Eight cases of "DSA-defined" moderate stenosis were overestimated as severe by BB MRI and this may be related to non-circular lumens. Axial imaging with BB MRI could potentially be used to provide useful information about severity of carotid stenosis. Copyright 2004 Springer-Verlag

  15. [Effect of vitamin D receptor gene polymorphism and lifestyle on bone mineral density and bone mineral density decrement rate].

    PubMed

    Yamagata, Z; Miyamura, T; Iijima, S; Asaka, A

    1995-12-01

    The effects of genetic and environmental factors on bone mineral density (BMD) were investigated in 108 healthy Japanese women. Of the 108 subjects, BMD (from the second to forth lumbar vertebrae) was measured in 1992 in 103, in 1993 in 100, and in both years in 95 by dual energy X-ray absorptiometry. Vitamin D receptor (VDR) gene polymorphism in intron 8 was used as a genetic marker. Information on menstruation, health status, lifestyle, quantities of nutrient intake and frequencies of food intake was obtained by questionnaire. The frequency of allele B (825bp), whose polymerase chain reaction (PCR) products cannot be cut with BsmI, was 0.259 and the frequency of allele b (650bp), whose PCR products can be cut with BsmI, was 0.741. The subjects in our study obeyed the Hardy-Weinberg law. While the frequency of allele B was 0.448 in European whites as reported by Morrison et al, it was 0.259 in our Japanese subjects, suggesting a racial difference. Z score values (average value 0, standard deviation 1) increased in the order BB, Bb and bb. This result indicates that allele B is associated with the lower BMD in Japanese, as in European whites. The BMD decrement rate increased in the order bb, Bb and BB, indicating that VDR gene polymorphism may be a regulatory factor for losing BMD. Most of lifestyle variables, calcium intake and vitamin D intake were not correlated with BMD, but the food frequency score (which was defined as values weighted in each of three food categories obtained by factor analysis) was significantly correlated with BMD. Multiple regression analysis showed significant influences of years after menopause, the food frequency score and VDR genotype on BMD. VDR genotype and years after menopause influenced the BMD decrement rate significantly in multiple regression analysis. Neither a relationship between BMD and calcium intake nor between BMD and vitamin D intake by VDR genotype was found. These results suggest that the VDR gene is a genetic factor

  16. Nonradioactive Screening Method for Isolation of Disease-Specific Probes To Diagnose Plant Diseases Caused by Mycoplasmalike Organisms

    PubMed Central

    Lee, Ing-Ming; Davis, Robert E.; DeWitt, Natalie D.

    1990-01-01

    DNA fragments of tomato big bud (BB) mycoplasmalike organism (MLO) in diseased periwinkle plants (Catharanthus roseus L.) were cloned to pSP6 plasmid vectors and amplified in Escherichia coli JM83. A nonradioactive method was developed and used to screen for MLO-specific recombinants. Cloned DNA probes were prepared by nick translation of the MLO recombinant plasmids by using biotinylated nucleotides. The probes all hybridized with nucleic acid from BB MLO-infected, but not healthy, plants. Results from dot hybridization analyses indicated that several MLOs, e.g., those of Italian tomato big bud, periwinkle little leaf, and clover phyllody, are closely related to BB MLO. The Maryland strain of aster yellows and maize bushy stunt MLOs are also related to BB MLO. Among the remaining MLOs used in this study, Vinca virescence and elm yellows MLOs may be very distantly related, if at all, to BB MLO. Potato witches' broom, clover proliferation, ash yellows, western X, and Canada X MLOs are distantly related to BB MLO. Southern hybridization analyses revealed that BB MLO contains extrachromosomal DNA that shares sequence homologies with extrachromosomal DNAs from aster yellows and periwinkle little leaf MLOs. Images PMID:16348195

  17. Respiratory muscle adaptations: a comparison between bodybuilders and endurance athletes.

    PubMed

    Hackett, D A; Johnson, N; Chow, C

    2013-04-01

    The purpose of this study was to compare the respiratory muscle and lung function measures of bodybuilders (BB) and endurance athletes (EA). Forty-two male subjects (22 BB and 20 EA) aged 20-35 years underwent respiratory muscle strength measurements (MIP and MEP), lung function testing (FEV1, FVC, FEV1/FVC%, IC, ERV, FRC, RV, and TLC), hydrostatic weighing and VO2max testing. One-repetition maximum (1RM) for bench press, squat and deadlift was performed by BB. BB had significantly greater MIP and MEP compared to EA by 43% and 53% respectively (P<0.01). Moderate correlation was found for MEP and 1RM bench press (P<0.01), and weak correlations found for the squat and deadlift (P<0.01). Fat-free mass was significantly greater for BB compared with EA (P<0.01), while VO2max was significantly greater for EA compared with BB (P<0.01). No differences in lung function indices were observed between groups. When compared to EA, BB exhibited significantly greater respiratory muscle strength. The maximal load lifted for bench press predicted expiratory muscle strength gain. Lung function measures did not differ between the groups.

  18. BostonBreathes: Improving pediatric asthma care with a home-based interactive website for patient education, monitoring, and clinical teamwork

    PubMed Central

    Wiecha, John M.; Adams, William G.

    2006-01-01

    The BostonBreathes (BB) system is an interactive website enabling physician-physician and physician-patient communication, monitoring (peak-flow, medication use, symptoms) of asthma patients in the home, and patient and family asthma education. The system helps primary care physicians to function in team relationships with asthma specialists and nurses. Patients and families can interact with their health professionals online as members of the care team. BB uniquely combines patient education, monitoring, and clinical teamwork functions into one integrated web environment. PMID:17238763

  19. An in vitro study on bacterial growth interactions and intestinal epithelial cell adhesion characteristics of probiotic combinations.

    PubMed

    Moussavi, Mahta; Adams, Michelle Catherine

    2010-05-01

    The aims of this study were to examine long-term growth interactions of five probiotic strains (Lactobacillus casei 01, Lactobacillus plantarum HA8, Lactobacillus rhamnosus GG, Lactobacillus reuteri ATCC 55730 and Bifidobacterium lactis Bb12) either alone or in combination with Propionibacterium jensenii 702 in a co-culture system and to determine their adhesion ability to human colon adenocarcinoma cell line Caco-2. Growth patterns of probiotic Lactobacillus strains were not considerably affected by the presence of P. jensenii 702, whereas lactobacilli exerted a strong antagonistic action against P. jensenii 702. In the co-culture of Bif. lactis Bb12 and P. jensenii 702, a significant synergistic influence on growth of both bacteria was observed (P < 0.05). The results of adhesion assay showed that when probiotic strains were tested in combination, there was evidence of an associated effect on percentage adherence. However, in most cases these differences were not statistically significant (P < 0.05). Adhesion percentage of Lb. casei 01 and Lb. rhamnosus GG both decreased significantly in the presence of P. jensenii 702 compared to their adhesion levels when alone (P < 0.05). These results show that the survival and percentage adhesion of some probiotic strains may be influenced by the presence of other strains and this should be considered when formulating in the probiotic products.

  20. 32 CFR 552.128 - Requirements for possession and use.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., ammunition, pellet and BB guns, knives, bows and arrows, and crossbows under the following conditions: (a) Privately-owned firearms, crossbows, pellet and BB guns possessed or stored on the installation must be... pellet and BB guns, and registered firearms within their quarters. (c) Personnel residing in troop...

  1. Localization and function of KLF4 in cytoplasm of vascular smooth muscle cell

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Yan; The Third Hospital of Hebei Medical University, Shijazhuang; Zheng, Bin

    2013-06-28

    Highlights: •PDGF-BB prompts the translocation of KLF4 to the cytoplasm. •PDGF-BB promotes interaction between KLF4 and actin in the cytoplasm. •Phosphorylation and SUMOylation of KLF4 participates in regulation of cytoskeletal organization. •KLF4 regulates cytoskeleton by promoting the expression of contraction-associated genes. -- Abstract: The Krüppel-like factor 4 is a DNA-binding transcriptional regulator that regulates a diverse array of cellular processes, including development, differentiation, proliferation, and apoptosis. The previous studies about KLF4 functions mainly focused on its role as a transcription factor, its functions in the cytoplasm are still unknown. In this study, we found that PDGF-BB could prompt the translocationmore » of KLF4 to the cytoplasm through CRM1-mediated nuclear export pathway in vascular smooth muscle cells (VSMCs) and increased the interaction of KLF4 with actin in the cytoplasm. Further study showed that both KLF4 phosphorylation and SUMOylation induced by PDGF-BB participates in regulation of cytoskeletal organization by stabilizing the actin cytoskeleton in VSMCs. In conclusion, these results identify that KLF4 participates in the cytoskeletal organization by stabilizing cytoskeleton in the cytoplasm of VSMCs.« less

  2. Firing rate modulation of human motor units in different muscles during isometric contraction with various forces.

    PubMed

    Seki, K; Narusawa, M

    1996-05-06

    To examine the factors affecting the control of human motor units, rate coding strategies of the motor units were investigated in upper limb and intrinsic hand muscles during voluntary isometric contraction of steady force levels up to 80% of maximal voluntary contraction. Numerous spike trains from single motor units were recorded from the m. first dorsal interosseous (FDI) and the m. biceps brachii (BB) of eight human subjects by means of tungsten micro-electrodes, and the mean firing rate (MFR) was calculated for each subject and inter-individual comparisons made. The MFRs of the FDI were larger than that of the BB at the higher force level, and substantial differences were not found between these muscles at the lower force level. The slope of the linear regression line of MFRs vs. exerted forces for the FDI was more than twice that for the BB. Therefore, isometric force control of the FDI depends more on the rate coding strategy. The difference in rate coding between the FDI and BB motor units may be determined by factors other than muscle fiber composition, because both muscles are known to possess a similar composition of fiber types. Possible mechanisms underlying these characteristics of rate coding strategy are considered in this report.

  3. Crocin prevents platelet‑derived growth factor BB‑induced vascular smooth muscle cells proliferation and phenotypic switch.

    PubMed

    Tong, Lijian; Qi, Guoxian

    2018-06-01

    The phenotypic switch of vascular smooth muscle cells (VSMCs) is a major initiating factor for atherosclerotic cardiovascular diseases. Platelet‑derived growth factor‑BB (PDGF‑BB) initiates a number of biological processes that contribute to VSMC proliferation and phenotypic switch. Crocin, a component of saffron, has been reported to inhibit atheromatous plaque formation. However, the effects of crocin on PDGF‑BB‑induced VSMC proliferation and phenotypic switch remain unclear. The aim of the present study was to investigate the role of crocin on PDGF‑BB‑induced VSMCs proliferation and phenotypic switch and its underlying mechanisms. Cell proliferation and markers of VSMCs phenotypic switch were measured using a Cell Counting Kit‑8 assay and western blot analysis, respectively. The signaling pathways involved in the effects of crocin on VSMCs were validated by western blot analysis with or without the use of specific pathway inhibitors. Crocin significantly inhibited PDGF‑BB‑induced VSMCs proliferation compared with the PDGF‑BB only group (P<0.05). In addition, crocin significantly abrogated the PDGF‑BB‑induced increase in contractile protein α‑smooth muscle actin, calponin and decrease in synthetic proteins osteopontin (OPN) in a concentration dependent manner (P<0.05). In addition, crocin slowed PDGF‑BB‑induced Janus kinase (JAK)‑signal transducer and activator of transcription 3 (STAT3) and extracellular signal‑regulated kinase (ERK)/Kruppel‑like factor 4 (KLF4) signaling activation in VSMCs. By applying the JAK inhibitor (AG490) and ERK1/2 inhibitor (U0126), the results suggested that the crocin inhibited PDGF‑BB‑induced VSMCs phenotypic switch through the JAK/STAT3 and ERK/KLF4 signaling pathways. These results suggested that crocin may effectively prevent PDGF‑BB‑induced VSMCs proliferation and phenotypic switch and may be a promising candidate for the therapy of atherosclerotic cardiovascular diseases.

  4. A prebiotic mixture improved Lactobacillus acidophilus and Bifidobacterium animalis gastrointestinal in vitro resistance in petit-suisse.

    PubMed

    Padilha, Marina; Villarreal Morales, Martha Lissete; Vieira, Antonio Diogo Silva; Costa, Mayra Garcia Maia; Saad, Susana Marta Isay

    2016-05-18

    The survival of two probiotic strains -Lactobacillus acidophilus La-5 and Bifidobacterium animalis Bb-12 - incorporated into probiotic (PC) and into synbiotic (SC, with inulin + fructooligosaccharides, respectively, at 7.5 and at 2.5 g per 100 g) petit-suisse cheese was investigated in the beginning (day 1) and at the end (28 days) of storage at 4 °C when the food products were subjected to in vitro gastrointestinal simulated assays. Species-specific quantitative real time PCR (qPCR) combined with propidium monoazide (PMA-qPCR) was employed to quantify the strains. Initial La-5 and Bb-12 populations were always above 7 log CFU g(-1). The presence of the prebiotic ingredients in SC improved the Bb-12 and La-5 resistance after the 6 h assay, with higher populations in all the in vitro stages and throughout the storage period (p < 0.05), leading to equal or superior survival rates (SR) in SC of both probiotic strains, in the beginning as well as at the end of storage. The mean La-5 SR were 58% (PC) and 67% (SC), whereas the mean Bb-12 SR were 60% (PC) and 79% (SC). Our findings suggest that the addition of a prebiotic mixture in petit-suisse cheese was advantageous, since it improved both the Bb-12 and La-5 viability and tolerance under in vitro gastrointestinal simulated conditions, both in the fresh product and in the product refrigerated for 28 days.

  5. Difference in production routes of water-soluble organic carbon in PM2.5 observed during non-biomass and biomass burning periods in Gwangju, Korea.

    PubMed

    Yu, Geun-Hye; Cho, Sung-Yong; Bae, Min-Suk; Park, Seung-Shik

    2014-07-01

    4 h integrated PM2.5 samples were collected from an urban site of Gwangju, Korea, for five days and analyzed for organic carbon and elemental carbon (OC and EC), total water-soluble OC (WSOC), hydrophilic and hydrophobic WSOC fractions (WSOCHPI and WSOCHPO), oxalate, and inorganic ionic species (sodium (Na(+)), ammonium (NH4(+)), potassium (K(+)), calcium (Ca(2+)), magnesium (Mg(2+)), chloride (Cl(-)), nitrate (NO3(-)), and sulfate (SO4(2-))) to investigate the possible sources of water-soluble organic aerosols. Two types of sampling periods were classified according to the regression relationship between black carbon (BC) concentrations measured at wavelengths of 370 nm (BC370nm) and 880 nm (BC880nm) using an aethalometer; the first period was traffic emission influence ("non-biomass burning (BB) period") and the second was biomass burning influence ("BB period"). The slope of the regression equation (BC370nm/BC880nm) was 0.95 for the non-BB period and 1.29 for the BB period. However, no noticeable difference in the WSOC/OC ratio, which can be used to infer the extent of secondary organic aerosol (SOA) formation, was found between the non-BB (0.61, range = 0.43-0.75) and BB (0.61, range = 0.52-0.68) periods, due to significant contribution of primary BB emissions to the WSOC. The concentrations of OC, WSOC and K(+), which were used as the BB emission markers, were 15.7 μg C m(-3) (11.5-24.3), 9.4 μg C m(-3) (7.0-12.7), and 1.2 μg m(-3) (0.6-2.7), respectively, during the BB period, and these results were approximately 1.7, 1.7, and 3.9 times higher than those during the non-BB period. During the non-BB period, good correlations among WSOC, SO4(2-) and oxalate, and poor correlations among WSOC, EC, and K(+) suggest that SOA is probably an important source of WSOC (and WSOCHPI) concentration. For the WSOC fractions, better correlations among WSOCHPI, oxalate (R(2) = 0.52), and SO4(2-) (R(2) = 0.57) were found than among WSOCHPO, oxalate (R(2) = 0.23), and SO4

  6. Association of vitamin D receptor BsmI rs1544410 and ApaI rs7975232 polymorphisms with susceptibility to adolescent idiopathic scoliosis

    PubMed Central

    Yin, Xin; Wang, Huadong; Guo, Jidong; Zhang, Liang; Zhang, Yupeng; Li, Li; Hou, Shuxun

    2018-01-01

    Abstract Background: AIS is the most common spinal deformity disease, yet its etiology remains uncertain. Significant associations have been found between AIS risk and vitamin D receptor (VDR) gene polymorphisms; however, some of these results are controversial. The aim of this study was to determine whether VDR BsmI rs1544410 and ApaI rs7975232 polymorphisms are correlated with AIS. Methods: Databases, including PubMed, EMBASE, Web of Science, the Cochrane Library, the Chinese Biomedical Literature Database, and the Wanfang Database, were systematically searched, and eligible case–control studies that explored the association of VDR (BsmI and ApaI) and the susceptibility to AIS were selected. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study population. Results: A total of 5 studies with 717 cases and 554 controls fulfilled the inclusion criteria after assessment by 2 reviewers. Generally, significant correlations were found between the BsmI polymorphism and AIS risk in overall populations and in Asian populations (overall population: B vs b: OR = 2.12, 95% CI = 1.21–3.75, P = .009; BB vs bb: OR = 3.38, 95% CI = 1.08–10.57, P = .036; Bb vs bb: OR = 2.50, 95% CI = 1.29–4.82, P = .006; BB/Bb vs bb: OR = 2.71, 95% CI = 1.31–5.63, P = .007; Asian population: B vs b: OR = 2.42, 95% CI = 1.27–4.61, P = .007; BB vs bb: OR = 4.09, 95% CI = 1.03–16.22, P = .045; Bb vs bb: OR =  2.94, 95% CI = 1.42–6.10, P = .004; BB/Bb vs bb: OR = 3.23, 95% CI = 1.42–7.35, P = .005). There was no significant association observed in Caucasian populations (all P > .05). With regard to the ApaI polymorphism, we found that it significantly decreased the risk of AIS (Aa vs AA: OR = 0.43, 95% CI = 0.24–0.77, P = .004; Aa/aa vs

  7. Olive Tree Branches Burning: A major pollution source in the Mediterranean

    NASA Astrophysics Data System (ADS)

    Kostenidou, Evangelia; Kaltsonoudis, Christos; Tsiflikiotou, Maria; Louvaris, Evangelos; Russell, Lynn; Pandis, Spyros

    2013-04-01

    Olive tree branches burning is a common agricultural waste management practice after the annual pruning of olive trees from November to February. Almost 1 billion (90%) of the olive trees in our planet are located around the Mediterranean, so the corresponding emissions of olive tree branches burning can be a significant source of fine aerosols during the cold months. Organic aerosol produced during the burning of olive tree branches (otBB-OA) was characterized with both direct source-sampling (using a mobile smog chamber) and ambient measurements during the burning season in the area of Patras, Greece. The aerosol emitted consists of organics, black carbon (BC), potassium, chloride, nitrate and sulfate. In addition to NOx, O3, CO and CO2, Volatile Organic Compounds (VOCs) such as methanol, acetonitrile, benzene and toluene were also produced. The Aerosol Mass Spectrometry (AMS) mass spectrum of otBB-OA is characterized by the m-z's27, 29, 39, 41, 43, 44, 55, 57, 67, 69 and 91 and changes as the emissions react with OH and O3. Fourier Transform Infrared Spectroscopy (FTIR) analysis showed that otBB-OA was composed of 48% alkane groups, 27% organic hydroxyl groups, 11% carboxylic acid groups, 11% primary amine groups and 4% carbonyl groups. The oxygen to carbon (O:C) ratio is 0.29±0.04. The otBB-OA AMS mass spectrum differs from the other published biomass burning spectra. The m-z60, used as levoglucosan tracer, is lower than in most biomass burning sources. This is confirmed by Gas Chromatography Mass Spectroscopy (GC-MS) analysis on filters where the levoglucosan to OC mass ratio was between 0.034 and 0.043, close to the lower limit of the reported values for most fuel types. This may lead to an underestimation of the otBB-OA contribution in Southern Europe if levoglucosan is being used as a wood burning tracer. During the olive tree branches burning season, 20 days of ambient measurements were performed. Applying positive matrix factorization (PMF) to the

  8. In-planta detection and monitorization of endophytic colonization by a Beauveria bassiana strain using a new-developed nested and quantitative PCR-based assay and confocal laser scanning microscopy.

    PubMed

    Landa, B B; López-Díaz, C; Jiménez-Fernández, D; Montes-Borrego, M; Muñoz-Ledesma, F J; Ortiz-Urquiza, A; Quesada-Moraga, E

    2013-10-01

    Beauveria bassiana strain 04/01-Tip obtained from larvae of the opium poppy stem gall Iraella luteipes endophytically colonizes opium poppy plants and protect it against this pest. Development of a specific, rapid and sensitive technique that allows accurately determining the process and factors leading to the establishment of this strain in opium poppy plants would be essential to achieve its efficient control in a large field scale. For that purpose in the present study, species-specific primers that can be used in conventional or quantitative PCR protocols were developed for specifically identification and detection of B. bassiana in plant tissues. The combination of the designed BB.fw/BB.rv primer set with the universal ITS1-F/ITS4 primer set in a two-step nested-PCR approach, has allowed the amplification of up to 10fg of B. bassiana. This represented an increase in sensitivity of 10000- and 1000-fold of detection than when using the BB.fw/BB.rv primers in a single or single-tube semi-nested PCR approaches, respectively. The BB.fw and BB.rv primer set were subsequently optimized to be used in real time quantitative PCR assays and allowed to accurately quantify B. bassiana DNA in different plant DNA backgrounds (leaves and seeds) without losing accuracy and efficiency. The qPCR protocol was used to monitor the endophytic colonization of opium poppy leaves byB. bassiana after inoculation with the strain EABb 04/01-Tip, detecting as low as 26fg of target DNA in leaves and a decrease in fungal biomass over time. PCR quantification data were supported in parallel with CLMS by the monitoring of spatial and temporal patterns of leaf and stem colonization using a GFP-tagged transformant of the B. bassiana EABb 04/01-Tip strain, which enabled to demonstrate that B. bassiana effectively colonizes aerial tissues of opium poppy plants mainly through intercellular spaces and even leaf trichomes. A decline in endophytic colonization was also observed by the last sampling

  9. MODIS On-Board Blackbody Function and Performance

    NASA Technical Reports Server (NTRS)

    Xiaoxiong, Xiong; Wenny, Brian N.; Wu, Aisheng; Barnes, William

    2009-01-01

    Two MODIS instruments are currently in orbit, making continuous global observations in visible to long-wave infrared wavelengths. Compared to heritage sensors, MODIS was built with an advanced set of on-board calibrators, providing sensor radiometric, spectral, and spatial calibration and characterization during on-orbit operation. For the thermal emissive bands (TEB) with wavelengths from 3.7 m to 14.4 m, a v-grooved blackbody (BB) is used as the primary calibration source. The BB temperature is accurately measured each scan (1.47s) using a set of 12 temperature sensors traceable to NIST temperature standards. The onboard BB is nominally operated at a fixed temperature, 290K for Terra MODIS and 285K for Aqua MODIS, to compute the TEB linear calibration coefficients. Periodically, its temperature is varied from 270K (instrument ambient) to 315K in order to evaluate and update the nonlinear calibration coefficients. This paper describes MODIS on-board BB functions with emphasis on on-orbit operation and performance. It examines the BB temperature uncertainties under different operational conditions and their impact on TEB calibration and data product quality. The temperature uniformity of the BB is also evaluated using TEB detector responses at different operating temperatures. On-orbit results demonstrate excellent short-term and long-term stability for both the Terra and Aqua MODIS on-board BB. The on-orbit BB temperature uncertainty is estimated to be 10mK for Terra MODIS at 290K and 5mK for Aqua MODIS at 285K, thus meeting the TEB design specifications. In addition, there has been no measurable BB temperature drift over the entire mission of both Terra and Aqua MODIS.

  10. Susceptibility to fatty acid-induced β-cell dysfunction is enhanced in prediabetic diabetes-prone biobreeding rats: a potential link between β-cell lipotoxicity and islet inflammation.

    PubMed

    Tang, Christine; Naassan, Anthony E; Chamson-Reig, Astrid; Koulajian, Khajag; Goh, Tracy T; Yoon, Frederick; Oprescu, Andrei I; Ghanim, Husam; Lewis, Gary F; Dandona, Paresh; Donath, Marc Y; Ehses, Jan A; Arany, Edith; Giacca, Adria

    2013-01-01

    β-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes. However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes. Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity may be synergistic. Thus, β-cell lipotoxicity could be enhanced in models of autoimmune diabetes. To determine this, we examined the effects of prolonged free fatty acids elevation on β-cell secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth (WF) rats. Rats received a 48-h iv infusion of saline or Intralipid plus heparin (IH) (to elevate free fatty acid levels ~2-fold) followed by hyperglycemic clamp or islet secretion studies ex vivo. IH significantly decreased β-cell function, assessed both by the disposition index (insulin secretion corrected for IH-induced insulin resistance) and in isolated islets, in dp-BB, but not in dr-BB or WF, rats, and the effect of IH was inhibited by the antioxidant N-acetylcysteine. Furthermore, IH significantly increased islet cytokine mRNA and plasma cytokine levels (monocyte chemoattractant protein-1 and IL-10) in dp-BB, but not in dr-BB or WF, rats. All dp-BB rats had mononuclear infiltration of islets, which was absent in dr-BB and WF rats. In conclusion, the presence of insulitis was permissive for IH-induced β-cell dysfunction in the BB rat, which suggests a link between β-cell lipotoxicity and islet inflammation.

  11. The effect of music with and without binaural beat audio on operative anxiety in patients undergoing cataract surgery: a randomized controlled trial

    PubMed Central

    Wiwatwongwana, D; Vichitvejpaisal, P; Thaikruea, L; Klaphajone, J; Tantong, A; Wiwatwongwana, A

    2016-01-01

    Purpose To investigate the anxiolytic effects of binaural beat embedded audio in patients undergoing cataract surgery under local anesthesia. Methods This prospective RCT included 141 patients undergoing cataract surgery under local anesthesia. The patients were randomized into three groups; the Binaural beat music group (BB), the plain music intervention group (MI), and a control group (ear phones with no music). Blood pressure (BP) and heart rate were measured on admission, at the beginning of and 20 min after the start of the operation. Peri-operative anxiety level was assessed using the State-Trait Anxiety Inventory questionnaire (STAI). Results The BB and MI groups comprised 44 patients each and the control group 47. Patients in the MI group and BB group showed significant reduction of STAI state scores after music intervention compared with the control group (P<0.001) but the difference was not significant between the MI and BB group (STAI-S score MI group −7.0, BB group −9.0, P=0.085). Systolic BP was significantly lower in both MI (P=0.043) and BB (0.040) groups although there was no difference between the two groups (P=1.000). A significant reduction in heart rate was seen only in the BB group (BB vs control P=0.004, BB vs MI P=0.050, MI vs control P=0.303). Conclusion Music, both with and without binaural beat, was proven to decrease anxiety level and lower systolic BP. Patients who received binaural beat audio showed additional decrease in heart rate. Binaural beat embedded musical intervention may have benefit over musical intervention alone in decreasing operative anxiety. PMID:27740618

  12. Motor unit potentials of the erector spinae muscle by concentric needle electromyography.

    PubMed

    Posa, Andreas; Niśkiewicz, Izabela; Emmer, Alexander; Kluge, Yorck; Kornhuber, Malte E

    2017-03-01

    The needle electromyography (EMG) serves to supply additional information in patients with suspected neuromuscular disorders. We aimed to provide motor unit potential (MUP) data by concentric needle EMG in the erector spinae (ES) in comparison with biceps brachii (BB) and lateral vastus (LV). Electromyography MUP data ( n ) were obtained in ES (517), BB (539), and LV (627) in 32 healthy volunteers (16f). Motor unit potential data: amplitude (μV) 393 ± 174 (ES), 375 ± 162 (BB), and 577 ± 304 (LV); duration (ms) 10.4 ± 2.4 (ES), 10.1 ± 2.1 (BB), and 11.1 ± 2.3 (LV), area (μV × ms) 585 ± 327 (ES), 538 ± 267 (BB), and 881 ± 492 (LV); phase number 3.23 ± 0.94 (ES), 2.98 ± 0.76 (BB), and 3.19 ± 0.81 (LV); size index 0.60 ± 0.56 (ES), 0.51 ± 0.53 (BB), and 0.96 ± 0.55 (LV). LV displayed higher values ( p at least <.001) for MUP amplitude, duration, area, and size index as compared to both, BB and ES. Concentric needle EMG investigations in healthy adult human subjects revealed similar MUP parameters in the ES and BB muscles, while in the LV muscle MUP amplitude, duration, area, and size index were significantly larger. Different neuromuscular disorders display a predominant involvement of proximally located muscles such as truncal muscles. The present results given here may facilitate the diagnosis of neuromuscular disorders.

  13. The effect of music with and without binaural beat audio on operative anxiety in patients undergoing cataract surgery: a randomized controlled trial.

    PubMed

    Wiwatwongwana, D; Vichitvejpaisal, P; Thaikruea, L; Klaphajone, J; Tantong, A; Wiwatwongwana, A

    2016-11-01

    PurposeTo investigate the anxiolytic effects of binaural beat embedded audio in patients undergoing cataract surgery under local anesthesia.MethodsThis prospective RCT included 141 patients undergoing cataract surgery under local anesthesia. The patients were randomized into three groups; the Binaural beat music group (BB), the plain music intervention group (MI), and a control group (ear phones with no music). Blood pressure (BP) and heart rate were measured on admission, at the beginning of and 20 min after the start of the operation. Peri-operative anxiety level was assessed using the State-Trait Anxiety Inventory questionnaire (STAI).ResultsThe BB and MI groups comprised 44 patients each and the control group 47. Patients in the MI group and BB group showed significant reduction of STAI state scores after music intervention compared with the control group (P<0.001) but the difference was not significant between the MI and BB group (STAI-S score MI group -7.0, BB group -9.0, P=0.085). Systolic BP was significantly lower in both MI (P=0.043) and BB (0.040) groups although there was no difference between the two groups (P=1.000). A significant reduction in heart rate was seen only in the BB group (BB vs control P=0.004, BB vs MI P=0.050, MI vs control P=0.303).ConclusionMusic, both with and without binaural beat, was proven to decrease anxiety level and lower systolic BP. Patients who received binaural beat audio showed additional decrease in heart rate. Binaural beat embedded musical intervention may have benefit over musical intervention alone in decreasing operative anxiety.

  14. Infectious agents is a risk factor for myxomatous mitral valve degeneration: A case control study.

    PubMed

    Tiveron, Marcos Gradim; Pomerantzeff, Pablo Maria Alberto; de Lourdes Higuchi, Maria; Reis, Marcia Martins; de Jesus Pereira, Jaqueline; Kawakami, Joyce Tieko; Ikegami, Renata Nishiyama; de Almeida Brandao, Carlos Manuel; Jatene, Fabio Biscegli

    2017-04-21

    The etiology of myxomatous mitral valve degeneration (MVD) is not fully understood and may depend on time or environmental factors for which the interaction of infectious agents has not been documented. The purpose of the study is to analyze the effect of Mycoplasma pneumoniae (Mp), Chlamydophila pneumoniae (Cp) and Borrelia burgdorferi (Bb) on myxomatous mitral valve degeneration pathogenesis and establish whether increased in inflammation and collagen degradation in myxomatous mitral valve degeneration etiopathogenesis. An immunohistochemical test was performed to detect the inflammatory cells (CD20, CD45, CD68) and Mp, Bb and MMP9 antigens in two groups. The in situ hybridization was performed to detect Chlamydophila pneumoniae and the bacteria study was performed using transmission electron microscopy. Group 1 (n = 20), surgical specimen composed by myxomatous mitral valve degeneration, and group 2 (n = 20), autopsy specimen composed by normal mitral valve. The data were analyzed using SigmaStat version 20 (SPSS Inc., Chicago, IL, USA). The groups were compared using Student's t test, Mann-Whitney test. A correlation analysis was performed using Spearman's correlation test. P values lower than 0.05 were considered statistically significant. By immunohistochemistry, there was a higher inflammatory cells/mm2 for CD20 and CD45 in group 1, and CD68 in group 2. Higher number of Mp and Cp antigens was observed in group 1 and more Bb antigens was detected in group 2. The group 1 exhibited a positive correlation between the Bb and MVD percentage, between CD45 and Mp, and between MMP9 with Mp. These correlations were not observed in the group 2. Electron microscopy revealed the presence of structures compatible with microorganisms that feature Borrelia and Mycoplasma characteristics. The presence of infectious agents, inflammatory cells and collagenases in mitral valves appear to contribute to the pathogenesis of MVD. Mycoplasma pneumoniae was strongly related with

  15. Delivering Beauveria bassiana with electrostatic powder for the control of stored-product beetles.

    PubMed

    Athanassiou, Christos G; Rumbos, Christos I; Sakka, Maria; Potin, Olivier; Storm, Clare; Dillon, Aoife B

    2017-08-01

    The efficacy of a Beauveria bassiana-based formulation (Bb38) with Entostat, an electrostatically charged powder, was investigated as a surface treatment against Cryptolestes ferrugineus, Oryzaephilus surinamensis and Sitophilus granarius adults. In lab bioassays, the efficacy of Bb38 against the aforementioned species was examined on concrete, plywood, steel and ceramic, whereas its residual efficacy against the same species was assessed on concrete and steel in the presence or absence of illumination. Finally, the efficacy of Bb38 against O. surinamensis and S. granarius adults was assessed in a commercial grain storage facility under realistic field conditions. In the lab trials, O. surinamensis and C. ferrugineus were much more susceptible to Bb38 than S. granarius on all types of surfaces. Moreover, Bb38 was, at least for O. surinamensis and C. ferrugineus, as effective as the chemical standard (deltamethrin) for at least 2 months after the application, regardless of the presence or absence of illumination. Finally, in the field trial Bb38 provided a satisfactory level of control against O. surinamensis. Bb38 is an effective surface treatment, but its efficacy varies according to the target species, the type of surface and the time post-application. This is the first published report that examines the efficacy of Bb38 as a surface treatment for wider uses in empty warehouses and related storage facilities. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  16. Investigation of the CCN Activity, BC and UVBC Mass Concentrations of Biomass Burning Aerosols during the 2013 BASELInE Campaign

    NASA Technical Reports Server (NTRS)

    Hsiao, Ta-Chih; Ye, Wei-Cheng; Wang, Sheng-Hsiang; Tsay, Si-Chee; Chen, Wei-Nai; Lin, Neng-Huei; Lee, Chung-Te; Hung, Hui-Ming; Chuang, Ming-Tung; Chantara, Somporn

    2015-01-01

    Biomass-burning (BB) aerosols, acting as cloud condensation nuclei (CCN), can influence cloud microphysical and radiative properties. In this study, we present CCN measured near the BB source regions over northern Southeast Asia (Doi Ang Khang, Thailand) and at downwind receptor areas (Lulin Atmospheric Background Station, Taiwan), focusing exclusively on 13-20 March 2013 as part of 2013 spring campaign of the Seven SouthEast Asian Studies (7-SEAS) intensive observation. One of the campaigns objectives is to characterize BB aerosols serving as CCN in SouthEast Asia (SEA). CCN concentrations were measured by a CCN counter at 5 supersaturation (SS) levels: 0.15%, 0.30%, 0.45%, 0.60%, and 0.75%. In addition, PM2.5 and black carbon mass concentrations were analyzed by using a tapered element oscillating microbalance and an aethalometer. It was found the number-size distributions and the characteristics of hygroscopicity (e.g., activation ratio and k) of BB aerosols in SEA have a strong diurnal pattern, and different behaviors of patterns were characterized under two distinct weather systems. The overall average value was low (0.05-0.1) but comparable with previous CCN studies in other BB source regions. Furthermore, a large fraction of UV-absorbing organic material (UVBC) and high Delta-C among BB aerosols were also observed, which suggest the existence of substantial particulate organic matter in fresh BB aerosols. These data provide the most extensive characterization of BB aerosols in SEA until now.

  17. Survey of selected tick-borne diseases in dogs in Finland.

    PubMed

    Pérez Vera, Cristina; Kapiainen, Suvi; Junnikkala, Sami; Aaltonen, Kirsi; Spillmann, Thomas; Vapalahti, Olli

    2014-06-23

    Due to climate changes during the last decades, ticks have progressively spread into higher latitudes in northern Europe. Although some tick borne diseases are known to be endemic in Finland, to date there is limited information with regard to the prevalence of these infections in companion animals. We determined the antibody and DNA prevalence of the following organisms in randomly selected client-owned and clinically healthy hunting dogs living in Finland: Ehrlichia canis (Ec), Anaplasma phagocytophilum (Ap), Borrelia burgdorferi (Bb) and Bartonella. Anti-Ap, -Bb and -Ec antibodies were determined in 340 Finnish pet dogs and 50 healthy hunting dogs using the 4DX Snap®Test (IDEXX Laboratories). In addition, PCRs for the detection of Ap and Bartonella DNA were performed. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with seropositivity to a vector borne agent. The overall seroprevalence was highest for Ap (5.3%), followed by Bb (2.9%), and Ec (0.3%). Seropositivities to Ap and Bb were significantly higher in the Åland Islands (p <0.001), with prevalence of Ap and Bb antibodies of 45 and 20%, respectively. In healthy hunting dogs, seropositivity rates of 4% (2/50) and 2% (1/50) were recorded for Ap and Bb, respectively. One client-owned dog and one hunting dog, both healthy, were infected with Ap as determined by PCR, while being seronegative. For Bartonella spp., none of the dogs tested was positive by PCR. This study represents the first data of seroprevalence to tick borne diseases in the Finnish dog population. Our results indicate that dogs in Finland are exposed to vector borne diseases, with Ap being the most seroprevalent of the diseases tested, followed by Bb. Almost 50% of dogs living in Åland Islands were Ap seropositive. This finding suggests the possibility of a high incidence of Ap infection in humans in this region. Knowing the distribution of seroprevalence in dogs may help predict the

  18. Importance of compensatory heart rate increase during myocardial ischemia to preserve appropriate oxygen kinetics.

    PubMed

    Yoshida, Sadamitsu; Adachi, Hitoshi; Murata, Makoto; Tomono, Junichi; Oshima, Shigeru; Kurabayashi, Masahiko

    2017-09-01

    Myocardial ischemia induces cardiac dysfunction, resulting in insufficient oxygen supply to peripheral tissues and mismatched energy production during exercise. To relieve the insufficient oxygen supply, heart rate (HR) response is augmented; however, beta-adrenergic receptor blockers (BB) restrict HR response. Although BB are essential drugs for angina pectoris, the effect of BB on exercise tolerance in patients with angina has not been studied. The aim of this study was to clarify the importance of HR augmentation to preserve exercise tolerance in patients with angina pectoris. Forty-two subjects who underwent cardiopulmonary exercise testing (CPX) to detect myocardial ischemia were enrolled. CPX was performed until exhaustion or onset of significant myocardial ischemia using a ramp protocol. Subjects were assigned to three groups (Group A: with ST depression during CPX with significant coronary stenosis and taking BB; Group B: with ST depression and not taking BB; Group C: without ST depression and not taking BB). HR response to exercise was evaluated during the following two periods: below and above ischemic threshold (IT). In Group C, it was evaluated during the first 2min and the last 2min of a ramp exercise. No significant differences were observed among the three groups with regard to patients' basic characteristics. Below IT, there were no differences in oxygen pulse/watt (O 2 pulse increasing rate), HR/watt (ΔHR/ΔWR), and ΔV˙O 2 /ΔWR. Above IT, O 2 pulse increasing rate was greater in Group A than in Group B. ΔHR/ΔWR was smaller in Group A than in Group B. ΔV˙O 2 /ΔWR became smaller in Group A than in Group B. There was no difference in anaerobic threshold, and peak V˙O 2 was smaller in Group A than in Group B. Restriction of HR response by a BB is shown to be one of the important factors in diminished exercise tolerance. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  19. Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system.

    PubMed

    Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S; Philipp, Mario T

    2017-02-02

    Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi (Bb), affects both the central and peripheral nervous systems. Previously, we reported that in a model of acute LNB in rhesus monkeys, treatment with the anti-inflammatory drug dexamethasone significantly reduced both pleocytosis and levels of cerebrospinal fluid (CSF) immune mediators that were induced by Bb. Dexamethasone also inhibited the formation of inflammatory, neurodegenerative, and demyelinating lesions in the brain and spinal cord of these animals. In contrast, these signs were evident in the infected animals that were left untreated or in those that were treated with meloxicam, a non-steroidal anti-inflammatory drug. To address the differential anti-inflammatory effects of dexamethasone and meloxicam in the central nervous system (CNS), we evaluated the potential of these drugs to alter the levels of Bb-induced inflammatory mediators in culture supernatants of rhesus frontal cortex (FC) explants, primary rhesus astrocytes and microglia, and human oligodendrocytes. We also ascertained the potential of dexamethasone to modulate Bb-induced apoptosis in rhesus FC explants. As meloxicam is a known COX-2 inhibitor, we evaluated whether meloxicam altered the levels of COX-2 as induced by live Bb in cell lysates of primary rhesus astrocytes and microglia. Dexamethasone but not meloxicam significantly reduced the levels of several Bb-induced immune mediators in culture supernatants of FC explants, astrocytes, microglia, and oligodendrocytes. Dexamethasone also had a protective effect on Bb-induced neuronal and oligodendrocyte apoptosis in rhesus FC explants. Further, meloxicam significantly reduced the levels of Bb-induced COX-2 in microglia, while both Bb and meloxicam were unable to alter the constitutive levels of COX-2 in astrocytes. These data indicate that dexamethasone and meloxicam have differential anti-inflammatory effects on Bb-induced inflammation in glial and neuronal cells

  20. A potential oncogenic activity of platelet-derived growth factor d in prostate cancer progression.

    PubMed

    Ustach, Carolyn V; Taube, Marcus E; Hurst, Newton J; Bhagat, Sunita; Bonfil, R Daniel; Cher, Michael L; Schuger, Lucia; Kim, Hyeong-Reh Choi

    2004-03-01

    The platelet-derived growth factor (PDGF) proteins are potent stimulators of cell proliferation/transformation and play a major role in cell-cell communication. For over two decades, PDGFs were thought to exist as three dimeric polypeptides (the homodimers AA and BB and the heterodimer AB). Recently, however, the PDGF C and D chains were discovered in a BLAST search of the expressed sequence tag databases. The PDGF CC and DD dimers have a unique two-domain structure with an NH(2)-terminal CUB (compliment subcomponents C1r/C1s, Uegf, and Bmp1) domain and a COOH-terminal PDGF/vascular endothelial growth factor domain. Whereas secreted PDGF AA, BB, and AB readily activate their cell surface receptors, it was suggested that extracellular proteolytic removal of the CUB domain is required for the PDGF/vascular endothelial growth factor domain of PDGF CC and DD to activate PDGF receptors. In the present study, we examined the processing of latent PDGF D into its active form and the effects of PDGF D expression on prostate cancer progression. We show that LNCaP cells auto-activate latent PDGF DD into the active PDGF domain, which can induce phosphorylation of the beta-PDGF receptor and stimulates LNCaP cell proliferation in an autocrine manner. Additionally, LNCaP-PDGF D-conditioned medium induces migration of the prostate fibroblast cell line 1532-FTX, indicating LNCaP-processed PDGF DD is active in a paracrine manner as well. In a severe combined immunodeficient mouse model, PDGF DD expression accelerates early onset of prostate tumor growth and drastically enhances prostate carcinoma cell interaction with surrounding stromal cells. These demonstrate a potential oncogenic activity of PDGF DD in the development and/or progression of prostate cancer.

  1. A Potential Oncogenic Activity of Platelet-Derived Growth Factor D in Prostate Cancer Progression

    PubMed Central

    Ustach, Carolyn V.; Taube, Marcus E.; Hurst, Newton J.; Bhagat, Sunita; Bonfil, R. Daniel; Cher, Michael L.; Schuger, Lucia; Kim, Hyeong-Reh Choi

    2014-01-01

    The platelet-derived growth factor (PDGF) proteins are potent stimulators of cell proliferation/transformation and play a major role in cell-cell communication. For over two decades, PDGFs were thought to exist as three dimeric polypeptides (the homodimers AA and BB and the heterodimer AB). Recently, however, the PDGF C and D chains were discovered in a BLAST search of the expressed sequence tag databases. The PDGF CC and DD dimers have a unique two-domain structure with an NH2-terminal CUB (compliment subcomponents C1r/C1s, Uegf, and Bmp1) domain and a COOH-terminal PDGF/vascular endothelial growth factor domain. Whereas secreted PDGF AA, BB, and AB readily activate their cell surface receptors, it was suggested that extracellular proteolytic removal of the CUB domain is required for the PDGF/vascular endothelial growth factor domain of PDGF CC and DD to activate PDGF receptors. In the present study, we examined the processing of latent PDGF D into its active form and the effects of PDGF D expression on prostate cancer progression. We show that LNCaP cells auto-activate latent PDGF DD into the active PDGF domain, which can induce phosphorylation of the β-PDGF receptor and stimulates LNCaP cell proliferation in an autocrine manner. Additionally, LNCaP-PDGF D-conditioned medium induces migration of the prostate fibroblast cell line 1532-FTX, indicating LNCaP-processed PDGF DD is active in a paracrine manner as well. In a severe combined immunodeficient mouse model, PDGF DD expression accelerates early onset of prostate tumor growth and drastically enhances prostate carcinoma cell interaction with surrounding stromal cells. These demonstrate a potential oncogenic activity of PDGF DD in the development and/or progression of prostate cancer. PMID:14996732

  2. Suppression of a methionine synthase by calmodulin under environmental stress in the entomopathogenic fungus Beauveria bassiana.

    PubMed

    Kim, Jiyoung; Oh, Junsang; Yoon, Deok-Hyo; Sung, Gi-Ho

    2017-10-01

    Methionine synthase (MetE, EC 2.1.1.14) catalyses the final step in the methionine biosynthetic pathway. Methionine biosynthesis plays a major role in protein biogenesis and is the source of S-adenosyl methionine (SAM), the universal donor of methyl groups. In this study, we demonstrated that BbMetE acts as a typical MetE enzyme in the entomopathogenic fungus Beauveria bassiana. In addition, we found that BbMetE binds to calmodulin (CaM) in vitro and in vivo. The functional role of CaM binding to BbMetE was to negatively regulate BbMetE activity in B. bassiana. Our proton-nuclear magnetic resonance data revealed that CaM inhibitor W-7 increases methionine content in B. bassiana, suggesting that CaM negatively regulates the BbMetE activity. Environmental stress stimuli such as salt, H 2 O 2 and heat suppressed BbMetE activity in B. bassiana. W-7 reversed this effect, suggesting that the inhibitory mechanism is mediated through stimulation of CaM activity. Therefore, this work suggests that BbMetE plays an important role in methionine biosynthesis, which is mediated by environmental stress stimuli via the CaM signalling pathway. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. Role of Glutathione Conjugation in 1-Bromobutane-induced Immunotoxicity in Mice.

    PubMed

    Lee, Sang Kyu; Lee, Dong Ju; Jeon, Tae Won; Ko, Gyu Sub; Yoo, Se Hyun; Ha, Hyun Woo; Kang, Mi Jeong; Kang, Wonku; Kim, Sang Kyum; Jeong, Tae Cheon

    2010-06-01

    Halogenated organic compounds, such as 1-bromobutane (1-BB) , have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.

  4. Blueberries improve glucose tolerance and lipid handling without altering body composition in obese postmenopausal mice

    PubMed Central

    Elks, Carrie M.; Terrebonne, Jennifer D.; Ingram, Donald K.; Stephens, Jacqueline M.

    2014-01-01

    Objective Metabolic syndrome (MetS) risk increases significantly during menopause and remains elevated post-menopause. Several botanicals, including blueberries (BB), have been shown to delay MetS progression, but few studies have been conducted in postmenopausal animal models. Here, we examined the effects of BB supplementation on obese postmenopausal mice using a chemically-induced menopause model. Design and Methods After induction of menopause, mice were fed a high-fat diet or the same diet supplemented with 4% BB powder for 12 weeks. Body weight and body composition were measured, and mice were subjected to glucose and insulin tolerance tests. Serum triglycerides and adiponectin were measured, and liver histology and hepatic gene expression were assessed. Results: Menopausal and BB-supplemented mice had significantly higher body weights and fat mass than control mice, while menopausal mice had impaired glucose tolerance and higher serum triglycerides when compared with control and BB-supplemented mice. Menopausal mice also had hepatic steatosis that was prevented by BB supplementation and correlated with expression of genes involved in hepatic fatty acid oxidation. Conclusions We conclude that BB supplementation prevents the glucose intolerance and hepatic steatosis that occur in obese postmenopausal mice, and that these effects are independent of body weight. PMID:25611327

  5. Perceptions, opinions and knowledge of pharmacists towards the use of complementary medicines by people living with cancer.

    PubMed

    Harnett, Joanna; Le, Trong Quy; Smith, Lorraine; Krass, Ines

    2018-05-09

    Background Biologically-based complementary medicine (BB-CM) use is prevalent amongst people living with cancer. Pharmacists play an important role in the provision of standard treatments for cancer. Less is known about pharmacist's provision of BB-CM information. Objective This study investigated the opinions, perceptions and knowledge of pharmacists regarding the use of BB-CMs by people living with cancer and the facilitators and barriers to providing information and advice. Setting Australia. Method A cross-sectional 53-item survey was developed and the survey link distributed in two professional associations newsletters. The associations represent ~29,000 pharmacists. Questions were categories into pharmacist's perceptions, opinions, and knowledge towards the use of BB-CM in cancer. Main Outcome Measure Scores obtained from responses to perception, opinion and knowledge statements and responses to demographic questions Results Respondents (n=70) were predominantly female (73%), Caucasian (66%) and under 40 years of age (78%). Respondents estimated that 19% of daily inquiries related to BB-CMs. Seventy-two per cent of respondents believed they had a responsibility to advise about the concomitant use of BB-CM with standard cancer treatments despite 60% reporting a lack of confidence in their knowledge. There was a moderate positive association (Spearman's rho 0.41 p= 0.001) between a pharmacists confidence in their level of knowledge and their total knowledge scores. The main barriers to providing information about BB-CMs reported were inadequate training in BB-CMs (94%) and reservations about the evidence base for efficacy and safety (50%). Conclusion Pharmacists have a role to play in counselling people living with cancer about their use of BB-CMs and this role could be maximized with further training and education in this area.

  6. Text-Based Conferencing: Features vs. Functionality

    ERIC Educational Resources Information Center

    Anderson, Lynn; McCarthy, Cathy

    2005-01-01

    This report examines three text-based conferencing products: "WowBB", "Invision Power Board", and "vBulletin". Their selection was prompted by a feature-by-feature comparison of the same products on the "WowBB" website. The comparison chart painted a misleading impression of "WowBB's" features in relation to the other two products; so the…

  7. Backward Blocking and Interference between Cues Are Empirically Equivalent in Non-Causally Framed Learning Tasks

    ERIC Educational Resources Information Center

    Luque, David; Moris, Joaquin; Orgaz, Cristina; Cobos, Pedro L.; Matute, Helena

    2011-01-01

    Backward blocking (BB) and interference between cues (IbC) are cue competition effects produced by very similar manipulations. In a standard BB design, both effects might occur simultaneously, which implies a potential problem for studying BB. In the present study with humans, the magnitude of both effects was compared using a non-causal scenario…

  8. Typical values of the electric drift E × B/B2 in the inner radiation belt and slot region as determined from Van Allen Probe measurements

    NASA Astrophysics Data System (ADS)

    Lejosne, Solène; Mozer, F. S.

    2016-12-01

    The electric drift E × B/B2 plays a fundamental role for the description of plasma flow and particle acceleration. Yet it is not well-known in the inner belt and slot region because of a lack of reliable in situ measurements. In this article, we present an analysis of the electric drifts measured below L 3 by both Van Allen Probes A and B from September 2012 to December 2014. The objective is to determine the typical components of the equatorial electric drift in both radial and azimuthal directions. The dependences of the components on radial distance, magnetic local time, and geographic longitude are examined. The results from Van Allen Probe A agree with Van Allen Probe B. They show, among other things, a typical corotation lag of the order of 5 to 10% below L 2.6, as well as a slight radial transport of the order of 20 m s-1. The magnetic local time dependence of the electric drift is consistent with that of the ionosphere wind dynamo below L 2 and with that of a solar wind-driven convection electric field above L 2. A secondary longitudinal dependence of the electric field is also found. Therefore, this work also demonstrates that the instruments on board Van Allen Probes are able to perform accurate measurements of the electric drift below L 3.

  9. Integrating marker-assisted background analysis with foreground selection for pyramiding bacterial blight resistance genes into Basmati rice.

    PubMed

    Baliyan, Nikita; Malik, Rekha; Rani, Reema; Mehta, Kirti; Vashisth, Urvashi; Dhillon, Santosh; Boora, Khazan Singh

    2018-01-01

    Bacterial leaf blight (BB), caused by the bacterium Xanthomonas oryzae pv. Oryzae (Xoo), is the major constraint amongst rice diseases in India. CSR-30 is a very popular high-yielding, salt-tolerant Basmati variety widely grown in Haryana, India, but highly susceptible to BB. In the present study, we have successfully introgressed three BB resistance genes (Xa21, xa13 and xa5) from BB-resistant donor variety IRBB-60 into the BB-susceptible Basmati variety CSR-30 through marker-assisted selection (MAS) exercised with stringent phenotypic selection without compromising the Basmati traits. Background analysis using 131 polymorphic SSR markers revealed that recurrent parent genome (RPG) recovery ranged up to 97.1% among 15 BC 3 F 1 three-gene-pyramided genotypes. Based on agronomic evaluation, BB reaction, aroma, percentage recovery of RPG, and grain quality evaluation, four genotypes, viz., IC-R28, IC-R68, IC-R32, and IC-R42, were found promising and advanced to BC 3 F 2 generation. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

  10. Flattop regulates basal body docking and positioning in mono- and multiciliated cells

    PubMed Central

    Gegg, Moritz; Böttcher, Anika; Burtscher, Ingo; Hasenoeder, Stefan; Van Campenhout, Claude; Aichler, Michaela; Walch, Axel; Grant, Seth G N; Lickert, Heiko

    2014-01-01

    Planar cell polarity (PCP) regulates basal body (BB) docking and positioning during cilia formation, but the underlying mechanisms remain elusive. In this study, we investigate the uncharacterized gene Flattop (Fltp) that is transcriptionally activated during PCP acquisition in ciliated tissues. Fltp knock-out mice show BB docking and ciliogenesis defects in multiciliated lung cells. Furthermore, Fltp is necessary for kinocilium positioning in monociliated inner ear hair cells. In these cells, the core PCP molecule Dishevelled 2, the BB/spindle positioning protein Dlg3, and Fltp localize directly adjacent to the apical plasma membrane, physically interact and surround the BB at the interface of the microtubule and actin cytoskeleton. Dlg3 and Fltp knock-outs suggest that both cooperatively translate PCP cues for BB positioning in the inner ear. Taken together, the identification of novel BB/spindle positioning components as potential mediators of PCP signaling might have broader implications for other cell types, ciliary disease, and asymmetric cell division. DOI: http://dx.doi.org/10.7554/eLife.03842.001 PMID:25296022

  11. On-Orbit Operation and Performance of MODIS Blackbody

    NASA Technical Reports Server (NTRS)

    Xiong, X.; Chang, T.; Barnes, W.

    2009-01-01

    MODIS collects data in 36 spectral bands, including 20 reflective solar bands (RSB) and 16 thermal emissive bands (TES). The TEB on-orbit calibration is performed on a scan-by-scan basis using a quadratic algorithm that relates the detector response with the calibration radiance from the sensor on-board blackbody (BB). The calibration radiance is accurately determined each scan from the BB temperature measured using a set of 12 thermistors. The BB thermistors were calibrated pre-launch with traceability to the NIST temperature standard. Unlike many heritage sensors, the MODIS BB can be operated at a constant temperature or with the temperature continuously varying between instrument ambient (about 270K) and 315K. In this paper, we provide an overview of both Terra and Aqua MODIS on-board BB operations, functions, and on-orbit performance. We also examine the impact of key calibration parameters, such as BB emissivity and temperature (stability and gradient) determined from its thermistors, on the TEB calibration and Level I (LIB) data product uncertainty.

  12. The regime of biomass burning aerosols over the Mediterranean basin based on satellite observations

    NASA Astrophysics Data System (ADS)

    Kalaitzi, Nikoleta; Gkikas, Antonis; Papadimas, Christos. D.; Hatzianastassiou, Nikolaos; Torres, Omar; Mihalopoulos, Nikolaos

    2016-04-01

    Biomass burning (BB) aerosol particles have significant effects on global and regional climate, as well as on regional air quality, visibility, cloud processes and human health.Biomass burning contributes by about 40% to the global emission of black carbonBC, and BB aerosols can exert a significant positive radiative forcing. The BB aerosols can originate from natural fires and human induced burning, such as wood or agricultural waste. However, the magnitude, but also the sign of the radiative forcing of BB aerosols is still uncertain, according to the third assessment report of IPCC (2013). Moreover, there are significant differences between different models as to their representation (inventories) of BB aerosols, more than for others, e.g. of fossil fuel origin. Therefore, it is important to better understand the spatial and temporal regime of BB aerosols. This is attempted here for the broader Mediterranean basin, which is a very interesting study area for aerosols, also being one of the most climaticallysensitive world regions. The determination of spatial and temporal regime of Mediterranean BB aerosols premises the identification of these particles at a complete spatial and long temporal coverage. Such a complete coverage is only ensured by contemporary satellite observations, which offer a challenging ability to characterize the existence of BB aerosols. This is possible thanks to the current availability of derived satellite products offering information on the size and absorption/scattering ability of aerosol particles. A synergistic use of such satellite aerosol data is made here, in conjunction with a developed algorithm, in order to identify the existence of BB aerosols over the Mediterranean basin over the 11-year period from 2005 to 2015. The algorithm operates, on a daily basis and at 1°×1°latitude-longitude resolution, setting threshold values (criteria) for specific physical and optical properties, which are representative of BB aerosols. More

  13. Leptonic Decays of the Charged B Meson

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Corwin, Luke A.

    2008-01-01

    We present a search for the decay B + → ℓ +ν ( = τ, μ, or e) in (458.9±5.1)×10 6 Υ(4S) decays recorded with the BABAR detector at the SLAC PEP-II B-Factory. A sample of events with one reconstructed exclusive semi-leptonic B decay (B - → D 0ℓ -more » $$\\bar{v}$$X) is selected, and in the recoil a search for B + →ℓ +ν ℓ signal is performed. The τ is identified in the following channels: τ + → e +ν e$$\\bar{v}$$ τ , τ + → μ +ν μ$$\\bar{v}$$ τ , τ + → π +$$\\bar{v}$$ τ , and τ + → π +π 0$$\\bar{v}$$ τ . The analysis strategy and the statistical procedure is set up for branching fraction extraction or upper limit determination. We determine from the dataset a preliminary measurement of B(B + → τ +ν τ) = (1.8 ± 0.8 ± 0.1) × 10 -4, which excludes zero at 2.4σ, and f B = 255 ± 58 MeV. Combination with the hadronically tagged measurement yields B(B + → τ +ν τ) = (1.8 ± 0.6) × 10 -4. We also set preliminary limits on the branching fractions at B(B + → e +ν e) < 7.7 × 10 -6 (90% C.L.), B(B + → μ +ν μ) < 11 × 10 -6 (90% C.L.), and B(B + → τ +ν τ ) < 3.2 × 10 -4(90% C.L.).« less

  14. Biomass burning contributions estimated by synergistic coupling of daily and hourly aerosol composition records.

    PubMed

    Nava, S; Lucarelli, F; Amato, F; Becagli, S; Calzolai, G; Chiari, M; Giannoni, M; Traversi, R; Udisti, R

    2015-04-01

    Biomass burning (BB) is a significant source of particulate matter (PM) in many parts of the world. Whereas numerous studies demonstrate the relevance of BB emissions in central and northern Europe, the quantification of this source has been assessed only in few cities in southern European countries. In this work, the application of Positive Matrix Factorisation (PMF) allowed a clear identification and quantification of an unexpected very high biomass burning contribution in Tuscany (central Italy), in the most polluted site of the PATOS project. In this urban background site, BB accounted for 37% of the mass of PM10 (particulate matter with aerodynamic diameter<10 μm) as annual average, and more than 50% during winter, being the main cause of all the PM10 limit exceedances. Due to the chemical complexity of BB emissions, an accurate assessment of this source contribution is not always easily achievable using just a single tracer. The present work takes advantage of the combination of a long-term daily data-set, characterized by an extended chemical speciation, with a short-term high time resolution (1-hour) and size-segregated data-set, obtained by PIXE analyses of streaker samples. The hourly time pattern of the BB source, characterised by a periodic behaviour with peaks starting at about 6 p.m. and lasting all the evening-night, and its strong seasonality, with higher values in the winter period, clearly confirmed the hypothesis of a domestic heating source (also excluding important contributions from wildfires and agricultural wastes burning). Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Ball-in-ball ZrO2 nanostructure for simultaneous CT imaging and highly efficient synergic microwave ablation and tri-stimuli-responsive chemotherapy of tumors.

    PubMed

    Long, Dan; Niu, Meng; Tan, Longfei; Fu, Changhui; Ren, Xiangling; Xu, Ke; Zhong, Hongshan; Wang, Jingzhuo; Li, Laifeng; Meng, Xianwei

    2017-06-29

    Combined thermo-chemotherapy displays outstanding synergically therapeutic efficiency when compared with standalone thermotherapy and chemotherapy. Herein, we developed a smart tri-stimuli-responsive drug delivery system involving X@BB-ZrO 2 NPs (X represents loaded IL, DOX, keratin and tetradecanol) based on novel ball-in-ball-structured ZrO 2 nanoparticles (BB-ZrO 2 NPs). The microwave energy conversion efficiency of BB-ZrO 2 NPs was 41.2% higher than that of traditional single-layer NPs due to the cooperative action of self-reflection and spatial confinement effect of the special two-layer hollow nanostructure. The tri-stimuli-responsive controlled release strategy indicate that integrated pH, redox and microwaves in single NPs based on keratin and tetradecanol could effectively enhance the specific controlled release of DOX. The release of DOX was only 8.1% in PBS with pH = 7.2 and GSH = 20 μM. However, the release could reach about 50% at the tumor site (pH = 5.5, GSH = 13 mM) under microwave ablation. The as-made X@BB-ZrO 2 NPs exhibited perfect synergic therapy effect of chemotherapy and microwave ablation both in subcutaneous tumors (H22 tumor-bearing mice) and deep tumors (liver transplantation VX2 tumor-bearing rabbit model). There was no recurrence and death in the X@BB-ZrO 2 + MW group during the therapy of subcutaneous tumors even on the 42 nd day. The growth rates in the deep tumor of the control, MW and X@BB-ZrO 2 + MW groups were 290.1%, 14.1% and -42% 6 days after ablation, respectively. Dual-source CT was used to monitor the metabolism behavior of the as-made BB-ZrO 2 NPs and traditional CT was utilized to monitor the tumor growth in rabbits. Frozen section examination and ICP results indicated the precise control of drug delivery and enhanced cytotoxicity by the tri-stimuli-responsive controlled release strategy. The ball-in-ball ZrO 2 NPs with high microwave energy conversion efficiency were first developed for synergic microwave ablation and

  16. Ultrastructure and growth factor content of equine platelet-rich fibrin gels.

    PubMed

    Textor, Jamie A; Murphy, Kaitlin C; Leach, J Kent; Tablin, Fern

    2014-04-01

    To compare fiber diameter, pore area, compressive stiffness, gelation properties, and selected growth factor content of platelet-rich fibrin gels (PRFGs) and conventional fibrin gels (FGs). PRFGs and conventional FGs prepared from the blood of 10 healthy horses. Autologous fibrinogen was used to form conventional FGs. The PRFGs were formed from autologous platelet-rich plasma of various platelet concentrations (100 × 10³ platelets/μL, 250 × 10³ platelets/μL, 500 × 10³ platelets/μL, and 1,000 × 10³ platelets/μL). All gels contained an identical fibrinogen concentration (20 mg/mL). Fiber diameter and pore area were evaluated with scanning electron microscopy. Maximum gelation rate was assessed with spectrophotometry, and gel stiffness was determined by measuring the compressive modulus. Gel weights were measured serially over 14 days as an index of contraction (volume loss). Platelet-derived growth factor-BB and transforming growth factor-β1 concentrations were quantified with ELISAs. Fiber diameters were significantly larger and mean pore areas were significantly smaller in PRFGs than in conventional FGs. Gel weight decreased significantly over time, differed significantly between PRFGs and conventional FGs, and was significantly correlated with platelet concentration. Platelet-derived growth factor-BB and transforming growth factor-β1 concentrations were highest in gels and releasates derived from 1,000 × 10³ platelets/μL. The inclusion of platelets in FGs altered the architecture and increased the growth factor content of the resulting scaffold. Platelets may represent a useful means of modifying these gels for applications in veterinary and human regenerative medicine.

  17. Role of magnolol in the proliferation of vascular smooth muscle cells.

    PubMed

    Wu, L; Zou, H; Xia, W; Dong, Q; Wang, L

    2015-05-01

    Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of vascular remodeling. Recently, magnolol has been reported to have a potential role in regulating tumor necrosis factor α-induced proliferation of VSMCs. However, the role of magnolol in platelet-derived growth factor (PDGF)-induced proliferation of VSMCs remains unknown. Our purpose was to elucidate the effect of magnolol on the proliferation of VSMCs induced by PDGF-BB and to investigate the underlying molecular mechanisms. Our data demonstrated that magnolol inhibited rat VSMC proliferation and DNA synthesis stimulated by 20 ng/ml PDGF-BB without causing cell cytotoxicity. Flow cytometric analysis showed that magnolol inhibited S-phase entry of VSMCs. We also demonstrated that magnolol caused this effect by inhibiting the mRNA and protein expression of cyclin D1, cyclin E, and cyclin-dependent kinases 2 and 4 in PDGF-BB-stimulated VSMCs. Further analysis showed that the inhibitory effect of magnolol on the proliferation of VSMCs was associated with the inhibition of the PDGF-BB-stimulated production of intracellular reactive oxygen species (ROS) and Ras, MEK, and ERK1/2 activation. These results demonstrate that magnolol can block the proliferation of VSMCs through inhibition of intracellular ROS production and Ras-MEK-ERK1/2 pathways. Magnolol, therefore, has a potential application in preventing atherosclerosis and restenosis.

  18. Genome-wide analysis of basic/helix-loop-helix gene family in peanut and assessment of its roles in pod development.

    PubMed

    Gao, Chao; Sun, Jianlei; Wang, Chongqi; Dong, Yumei; Xiao, Shouhua; Wang, Xingjun; Jiao, Zigao

    2017-01-01

    The basic/helix-loop-helix (bHLH) proteins constitute a superfamily of transcription factors that are known to play a range of regulatory roles in eukaryotes. Over the past few decades, many bHLH family genes have been well-characterized in model plants, such as Arabidopsis, rice and tomato. However, the bHLH protein family in peanuts has not yet been systematically identified and characterized. Here, 132 and 129 bHLH proteins were identified from two wild ancestral diploid subgenomes of cultivated tetraploid peanuts, Arachis duranensis (AA) and Arachis ipaensis (BB), respectively. Phylogenetic analysis indicated that these bHLHs could be classified into 19 subfamilies. Distribution mapping results showed that peanut bHLH genes were randomly and unevenly distributed within the 10 AA chromosomes and 10 BB chromosomes. In addition, 120 bHLH gene pairs between the AA-subgenome and BB-subgenome were found to be orthologous and 101 of these pairs were highly syntenic in AA and BB chromosomes. Furthermore, we confirmed that 184 bHLH genes expressed in different tissues, 22 of which exhibited tissue-specific expression. Meanwhile, we identified 61 bHLH genes that may be potentially involved in peanut-specific subterranean. Our comprehensive genomic analysis provides a foundation for future functional dissection and understanding of the regulatory mechanisms of bHLH transcription factors in peanuts.

  19. (-)-Epicatechin-3-O-β-D-allopyranoside from Davallia formosana prevents diabetes and dyslipidemia in streptozotocin-induced diabetic mice.

    PubMed

    Lin, Cheng-Hsiu; Wu, Jin-Bin; Jian, Jia-Ying; Shih, Chun-Ching

    2017-01-01

    The objective of this study was to evaluate the effects and molecular mechanism of (-)-epicatechin-3-O-β-D-allopyranoside from Davallia formosana (BB) (also known as Gu-Sui-Bu) on type 1 diabetes mellitus and dyslipidemia in streptozotocin (STZ)-induced diabetic mice. This plant was demonstrated to display antioxidant activities and possess polyphenol contents. Diabetic mice were randomly divided into six groups and were given daily oral gavage doses of either BB (at three dosage levels), metformin (Metf) (at 0.3 g/kg body weight), fenofibrate (Feno) (at 0.25 g/kg body weight) or vehicle (distilled water) and a group of control (CON) mice were gavaged with vehicle over a period of 4 weeks. Treatment with BB led to reduced levels of blood glucose, HbA1C, triglycerides and leptin and to increased levels of insulin and adiponectin compared with the vehicle-treated STZ group. The diabetic islets showed retraction from their classic round-shaped as compared with the control islets. The BB-treated groups (at middle and high dosages) showed improvement in islets size and number of Langerhans islet cells. The membrane levels of skeletal muscular glucose transporter 4 (GLUT4) were significantly higher in BB-treated mice. This resulted in a net glucose lowering effect among BB-treated mice. Moreover, BB enhanced the expression of skeletal muscle phospho-AMPK in treated mice. BB-treated mice increased expression of fatty acid oxidation enzymes, including peroxisome proliferator-activated receptor α (PPARα) and mRNA levels of carnitine palmitoyl transferase Ia (CPT1a). These mice also expressed lower levels of lipogenic genes such as fatty acid synthase (FAS), as well as lower mRNA levels of sterol regulatory element binding protein 1c (SREBP1c) and liver adipocyte fatty acid binding protein 2 (aP2). This resulted in a reduction in plasma triglyceride levels. BB-treated mice also expressed lower levels of PPARγ and FAS protein. This led to reduced adipogenesis, fatty acid

  20. Enhancing PC Cluster-Based Parallel Branch-and-Bound Algorithms for the Graph Coloring Problem

    NASA Astrophysics Data System (ADS)

    Taoka, Satoshi; Takafuji, Daisuke; Watanabe, Toshimasa

    A branch-and-bound algorithm (BB for short) is the most general technique to deal with various combinatorial optimization problems. Even if it is used, computation time is likely to increase exponentially. So we consider its parallelization to reduce it. It has been reported that the computation time of a parallel BB heavily depends upon node-variable selection strategies. And, in case of a parallel BB, it is also necessary to prevent increase in communication time. So, it is important to pay attention to how many and what kind of nodes are to be transferred (called sending-node selection strategy). In this paper, for the graph coloring problem, we propose some sending-node selection strategies for a parallel BB algorithm by adopting MPI for parallelization and experimentally evaluate how these strategies affect computation time of a parallel BB on a PC cluster network.

  1. Human basal body basics.

    PubMed

    Vertii, Anastassiia; Hung, Hui-Fang; Hehnly, Heidi; Doxsey, Stephen

    2016-01-01

    In human cells, the basal body (BB) core comprises a ninefold microtubule-triplet cylindrical structure. Distal and subdistal appendages are located at the distal end of BB, where they play indispensable roles in cilium formation and function. Most cells that arrest in the G0 stage of the cell cycle initiate BB docking at the plasma membrane followed by BB-mediated growth of a solitary primary cilium, a structure required for sensing the extracellular environment and cell signaling. In addition to the primary cilium, motile cilia are present in specialized cells, such as sperm and airway epithelium. Mutations that affect BB function result in cilia dysfunction. This can generate syndromic disorders, collectively called ciliopathies, for which there are no effective treatments. In this review, we focus on the features and functions of BBs and centrosomes in Homo sapiens.

  2. Maternal and fetal alternative complement pathway activation in early severe preeclampsia.

    PubMed

    Hoffman, M Camille; Rumer, Kristen K; Kramer, Anita; Lynch, Anne M; Winn, Virginia D

    2014-01-01

    We sought to determine whether alternative complement activation fragment Bb (Bb) levels are elevated in the maternal, fetal, and placental blood in cases of severe preeclampsia (PE) compared with normotensive controls. This was a cross-sectional study of women admitted at ≥24 weeks gestation with or without severe PE. Maternal plasma was collected at the time of enrollment. Umbilical venous cord and intervillous space blood were collected at delivery. Plasma Bb levels were assessed using ELISA. Bb levels were compared between cases and controls. Median Bb levels were higher in the maternal plasma of severe PE subjects (n = 24) than in controls (n = 20), 1.45 ± 1.03 versus 0.65 ± 0.23 μg/mL, P < 0.001. In umbilical venous plasma, Bb levels were higher in severe PE subjects (n = 15) compared with controls (n = 15), 2.48 ± 1.40 versus 1.01 ± 0.57 μg/mL, P = 0.01. Activation fragment Bb is increased in the maternal and umbilical venous blood of cases of severe PE when compared with normotensive controls. These data provide support for alternative complement pathway involvement in the pathogenesis of severe PE and demonstrate that alternative complement activation occurs not only in the maternal but also in the fetal compartment. © 2013 John Wiley & Sons Ltd.

  3. Functional characterization of a serine-threonine protein kinase from Bambusa balcooa that implicates in cellulose overproduction and superior quality fiber formation

    PubMed Central

    2013-01-01

    Background Molecular markers allow rapid identification of biologically important germplasm/s having desired character. Previously we have reported a genotype specific molecular marker, Balco1128 [GenBank ID EU258678] of Bambusa balcooa containing an ORF (375 bp) having high similarity with receptor like cytoplasmic kinase of Arabidopsis and Oryza. Balco1128 was found to be associated only with bamboo genotypes endowed with high cellulose and low lignin contents of fibers. Under the above backdrop, it was necessitated to characterize this genetic marker for better understanding of its biological significance in context of superior quality fiber development. Results The full length cDNA (3342 bp) of BbKst, a serine-threonine protein kinase was isolated from B. balcooa comprising of six LRR domains at the N-terminal end and a kinase domain at the C-terminal end. Bacteria-expressed BbKst-kinase domain (3339 bp long) showed Mg2+ dependent kinase activity at pH 7.0, 28°C. Bioinformatics study followed by phospho-amino analysis further confirmed that BbKst-kinase belongs to the serine/threonine protein kinase family. Transcript analysis of the BbKst gene following RNA slot blot hybridization and qPCR revealed higher expression of BbKst during initiation and elongation stages of fiber development. Tissue specific expression studies showed much higher expression of BbKst transcript in stems and internodes of B. balcooa than in leaves and rhizomes. Southern analysis revealed single copy insertion of BbKst in most of the Agrobacterium mediated transgenic tobacco plants. Real-time PCR detected 150-200 fold enhanced expression of BbKst in different T1 tobacco lines than that of the vector transformed plants. Heterologous expression of BbKst under control of 35S promoter in transgenic tobacco showed high cellulose deposition in the xylem fibers. Number of xylary fibers was higher in transgenic T0 and T1 plants than that of empty-vector transformed tobacco plants offering

  4. Early snow melts and biomass burning over Eastern Eurasia and their impacts on the air quality in Northern Japan

    NASA Astrophysics Data System (ADS)

    Yasunari, T. J.; daSilva, A.; Akiyama, M.; Hayasaki, M.; Murao, N.; Kim, K. M.

    2016-12-01

    We investigated monthly characteristics including a couple of large biomass burnings (BB) in Eastern Eurasia during 2003 and 2014, and the smoke impacts on Northern Japan. The new re-analyses data including the aerosol data assimilation, called MERRA-2, which was produced by the NASA's Global Modeling and Assimilation Office (GMAO), the monthly mean MODIS snow cover fraction (SCF) data (MOD10CM; further re-gridded), and the observations on PM2.5, elemental carbon (EC), and organic carbon (OC) in Sapporo city (Hokkaido, Japan), were used in our analyses. For the MERRA-2 and MODIS SCF data, we calculated 12-year climatology for each month and these anomalies from the climatology on the focused variables. Three-month means of the anomalies for the last three months until the BB months were calculated except for the SCF. For the SCF, the three-month mean anomalies until the one month before the BB months were also calculated. Here we start especially focusing on the identified fire months with the MERRA-2 data (May 2003, April 2008, and July 2014) in terms of these smoke impacts on the air qualities in Northern Japan (i.e., Hokkaido). We identified two types of biomass burning patterns within these three months. For the BBs in May 2003 and April 2008, the main BB areas were seen in the eastern part of the Lake Baikal. In July 2014, the main BB area was in the Sakha Republic and close to the Arctic region. Then, the MERRA-2 data overestimated the observations (EC, OC, and PM2.5) in Sapporo (Hokkaido, Japan) during the smoke transports, but the elevated timings were well reproduced. For all the three BB cases, abnormally reduced SCF were seen by the one month before the Eurasian BB generations (i.e., earlier than the BB generations). The positive and negative anomalies of 2-m temperature and surface soil wetness, covering the three-month until the BB months, were identified. These suggest that early snow-melting anomalies for these three years could make the following BB

  5. 77 FR 61797 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-11

    ..., MM, RP, 3, or 4 and removal flags are defined as Flags BB, MT, N, W, PI, PR, or 6. Where a Member..., BB and PI where they satisfy the volume tier requirements for the Mega Tier in Footnote 1. Currently... removing liquidity and the rate for Flags N, W, 6, BB, and PI subject to the volume thresholds in Footnotes...

  6. Physical Parameters of Components in Close Binary Systems. V

    NASA Astrophysics Data System (ADS)

    Zola, S.; Kreiner, J. M.; Zakrzewski, B.; Kjurkchieva, D. P.; Marchev, D. V.; Baran, A.; Rucinski, S. M.; Ogloza, W.; Siwak, M.; Koziel, D.; Drozdz, M.; Pokrzywka, B.

    2005-12-01

    The paper presents combined spectroscopic and photometric orbital solutions for ten close binary systems: CN And, V776 Cas, FU Dra, UV Lyn, BB Peg, V592 Per, OU Ser, EQ Tau, HN UMa and HT Vir. The photometric data consist of new multicolor light curves, while the spectroscopy has been recently obtained within the radial velocity program at the David Dunlap Observatory (DDO). Absolute parameters of the components for these binary systems are derived. Our results confirm that CN And is not a contact system. Its configuration is semi-detached with the secondary component filling its Roche lobe. The configuration of nine other systems is contact. Three systems (V776 Cas, V592 Per and OU Ser) have high (44-77%) and six (FU Dra, UV Lyn, BB Peg, EQ Tau, HN UMa and HT Vir) low or intermediate (8-32%) fill-out factors. The absolute physical parameters are derived.

  7. The enhancement of PM2.5 mass and water-soluble ions of biosmoke transported from Southeast Asia over the Mountain Lulin site in Taiwan

    NASA Astrophysics Data System (ADS)

    Lee, Chung-Te; Chuang, Ming-Tung; Lin, Neng-Huei; Wang, Jia-Lin; Sheu, Guey-Rong; Chang, Shuenn-Chin; Wang, Sheng-Hsiang; Huang, Hill; Chen, Horng-Wen; Liu, Yuan-Liang; Weng, Guo-Hau; Lai, Hsin-Yo; Hsu, Shao-Peng

    2011-10-01

    Biomass burning (BB) in Southeast Asia (Indochina and southern China) occurs frequently in March and April every year. The burning plume is ordinarily transported eastward by the prevailing westerly, further affecting downstream air quality in East Asia. In this study, atmospheric aerosols were collected at the downstream Lulin Atmospheric Background Station (LABS, 2862 m a.s.l., central Taiwan) from April 2003 to April 2009. Results show that monthly means of PM2.5 were highest during the BB period, especially in March. The PM2.5 mean for BB activity was 17.5 μg m-3, while the daily PM2.5 mean can sometimes be above 40 μg m-3. The background PM2.5 level in free troposphere of the West Pacific was at 3.7 ± 1.8 μg m-3. This mean is roughly the same regardless of the air masses moving from China, Pacific Ocean, and South China Sea toward LABS. In addition, the highest PM2.5 level occurred in 2004, making it the most active year of BB for the whole observation period. Greater amounts of nitrate and potassium ions were observed in the PM2.5 collected during the BB period compared to the non-BB (NBB) period. Linear regression analysis on PM2.5 water-soluble ions shows a moderate correlation (R2 = 0.59) between non-sea-salt potassium and nitrate ions during the BB period. Furthermore, for all trajectory source origins, ammonium ion had the best correlation (R2 = 0.84) with non-sea-salt sulfate when the air masses were influenced by anthropogenic sources during the NBB period. The enhancement ratios of nitrate ion during the BB period could reach 6.7 and 9.7 relative to air masses from the BB source region and from the pristine area during the NBB period, respectively. During the study period, ammonia gas was found to be insufficient to neutralize sulfuric and nitric gases. Therefore, most aerosols were more acidic than basic. Our long-term observation of atmospheric aerosols with inter-annual variability is valuable in providing data for verifying BB source inventory

  8. Biomass burning emissions of trace gases and particles in marine air at Cape Grim, Tasmania, 41° S

    NASA Astrophysics Data System (ADS)

    Lawson, S. J.; Keywood, M. D.; Galbally, I. E.; Gras, J. L.; Cainey, J. M.; Cope, M. E.; Krummel, P. B.; Fraser, P. J.; Steele, L. P.; Bentley, S. T.; Meyer, C. P.; Ristovski, Z.; Goldstein, A. H.

    2015-07-01

    Biomass burning (BB) plumes were measured at the Cape Grim Baseline Air Pollution Station during the 2006 Precursors to Particles campaign, when emissions from a fire on nearby Robbins Island impacted the station. Measurements made included non methane organic compounds (NMOCs) (PTR-MS), particle number size distribution, condensation nuclei (CN) > 3 nm, black carbon (BC) concentration, cloud condensation nuclei (CCN) number, ozone (O3), methane (CH4), carbon monixide (CO), hydrogen (H2), carbon dioxide (CO2), nitrous oxide (N2O), halocarbons and meteorology. During the first plume strike event (BB1), a four hour enhancement of CO (max ~ 2100 ppb), BC (~ 1400 ng m-3) and particles > 3 nm (~ 13 000 cm-3) with dominant particle mode of 120 nm were observed overnight. Dilution of the plume resulted in a drop in the dominant particle mode to 50 nm, and then growth to 80 nm over 5 h. This was accompanied by an increase in O3, suggesting that photochemical processing of air and condensation of low volatility oxidation products may be driving particle growth. The ability of particles > 80 nm (CN80) to act as CCN at 0.5 % supersaturation was investigated. The ΔCCN / ΔCN80 ratio was lowest during the fresh BB plume (56 %), higher during the particle growth event (77 %) and higher still (104 %) in background marine air. Particle size distributions indicate that changes to particle chemical composition, rather than particle size, are driving these changes. Hourly average CCN during both BB events were between 2000-5000 CCN cm-3, which were enhanced above typical background levels by a factor of 6-34, highlighting the dramatic impact BB plumes can have on CCN number in clean marine regions. During the 29 h of the second plume strike event (BB2) CO, BC and a range of NMOCs including acetonitrile and hydrogen cyanide (HCN) were clearly enhanced and some enhancements in O3 were observed (ΔO3 / ΔCO 0.001-0.074). A shortlived increase in NMOCs by a factor of 10 corresponded

  9. Impact of the biomass burning on methane variability during dry years in the Amazon measured from an aircraft and the AIRS sensor.

    PubMed

    Ribeiro, Igor Oliveira; Andreoli, Rita Valéria; Kayano, Mary Toshie; de Sousa, Thaiane Rodrigues; Medeiros, Adan Sady; Guimarães, Patrícia Costa; Barbosa, Cybelli G G; Godoi, Ricardo H M; Martin, Scot T; de Souza, Rodrigo Augusto Ferreira

    2018-05-15

    The present study examines the spatiotemporal variability and interrelations of the atmospheric methane (CH 4 ), carbon monoxide (CO) and biomass burning (BB) outbreaks retrieved from satellite data over the Amazon region during the 2003-2012 period. In the climatological context, we found consistent seasonal cycles of BB outbreaks and CO in the Amazon, both variables showing a peak during the dry season. The dominant CO variability mode features the largest positive loadings in the southern Amazon, and describes the interannual CO variations related to BB outbreaks along the deforestation arc during the dry season. In line with CO variability and BB outbreaks, the results show strong correspondence with the spatiotemporal variability of CH 4 in the southern Amazon during years of intense drought. Indeed, the areas with the largest positive CH 4 anomalies in southern Amazon overlap the areas with high BB outbreaks and positive CO anomalies. The analyses also showed that high (low) BB outbreaks in the southern Amazon occur during dry (wet) years. In consequence, the interannual climate variability modulates the BB outbreaks in the southern Amazon, which in turn have considerable impacts on CO and CH 4 interannual variability in the region. Therefore, the BB outbreaks might play a major role in modulating the CH 4 and CO variations, at least in the southern Amazon. This study also provides a comparison between the estimate of satellite and aircraft measurements for the CH 4 over the southern Amazon, which indicates relatively small differences from the aircraft measurements in the lower troposphere, with errors ranging from 0.18% to 1.76%. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Identification of chemical fingerprints in long-range transport of burning induced upper tropospheric ozone from Colorado to the North Atlantic Ocean.

    PubMed

    Jeon, Wonbae; Choi, Yunsoo; Souri, Amir Hossein; Roy, Anirban; Diao, Lijun; Pan, Shuai; Lee, Hwa Woon; Lee, Soon-Hwan

    2018-02-01

    This study investigates a significant biomass burning (BB) event occurred in Colorado of the United States in 2012 using the Community Multi-scale Air Quality (CMAQ) model. The simulation reasonably reproduced the significantly high upper tropospheric O 3 concentrations (up to 145ppb) caused by BB emissions. We find the BB-induced O 3 was primarily affected by chemical reactions and dispersion during its transport. In the early period of transport, high NO x and VOCs emissions caused O 3 production due to reactions with the peroxide and hydroxyl radicals, HO 2 and OH. Here, NO x played a key role in O 3 formation in the BB plume. The results indicated that HO 2 in the BB plume primarily came from formaldehyde (HCHO+hv=2HO 2 +CO), a secondary alkoxy radical (ROR=HO 2 ). CO played an important role in the production of recycled HO 2 (OH+CO=HO 2 ) because of its abundance in the BB plume. The chemically produced HO 2 was largely converted to OH by the reactions with NO (HO 2 +NO=OH+NO 2 ) from BB emissions. This is in contrast to the surface, where HO 2 and OH are strongly affected by VOC and HONO, respectively. In the late stages of transport, the O 3 concentration was primarily controlled by dispersion. It stayed longer in the upper troposphere compared to the surface due to sustained depletion of NO x . Sensitivity analysis results support that O 3 in the BB plume is significantly more sensitive to NO x than VOCs. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Mycelial fungi completely remediate di(2-ethylhexyl)phthalate, the hazardous plasticizer in PVC blood storage bag.

    PubMed

    Pradeep, S; Benjamin, Sailas

    2012-10-15

    This pioneering work describes how simply, inexpensively and efficiently novel fungi utilize the alarming plasticizer, di(2-ethylhexyl)phthalate (DEHP) blended in PVC blood storage bags (BB). In order to quantify total DEHP (33.5%, w/w) present in BB, it was extracted using n-hexane and confirmed by GC-MS. Three mycelial fungi, viz., Aspergillus parasiticus, Fusarium subglutinans and Penicillium funiculosum isolated in our laboratory form heavily plastics-contaminated soil - either singly or in consortium - completely consumed intact DEHP physically bound to BB by static submerged growth (28 °C) in simple basal salt medium (BSM). A two-stage cultivation strategy was adopted for the complete removal of DEHP from BB in situ. During the first growth stage, almost 70% DEHP contained in the BB was consumed in 2 weeks, accompanied by increased fungal biomass (~0.15-0.35 g/g BB; OD ~7 at 600 nm) and a sharp declining (3.3) of initial pH (7.2). Spent BSM was replaced at this stagnant growth state (low pH), thus in the second stage, remaining DEHP bound to BB utilized completely (over 99%). Furthermore, A. parasiticus and F. subglutinans also grew well on scrapes of PVC water pipes in BSM. F. subglutinans was as efficient independently as consortium in completely utilizing the DEHP bound to BB, and these fungi offer great potentials for the inexpensive and eco-friendly bioremediation of phthalates in medical and allied PVC wastes on a large scale through a batch process in alleviating the plactics waste management issue. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Influence of CO2 on growth and hydrocarbon production in Botryococcus braunii.

    PubMed

    Ranga Rao, A; Sarada, R; Ravishankar, G A

    2007-03-01

    Botryococcus braunii is a green colonial fresh water microalga and it is recognized as one of the renewable resources for production of liquid hydrocarbons. CFTRI-Bb-1 and CFTRI-Bb-2 have been reported for the first time and their performance with regard to growth and biochemical profile is presented here. The present study focused on effect of carbon dioxide (CO2) on biomass, hydrocarbon, carbohydrate production, fatty acid profile, and carotenoid content in various species of B. braunii (LB-572, SAG 30.81, MCRC-Bb, N-836, CFTRI-Bb-1, and CFTRI-Bb-2) at 0.5, 1.0, and 2.0% (v/v) levels using a two-tier flask. CO2 at 2.0% (v/v) level enhanced growth of the organism, and a two-fold increase in biomass and carotenoid contents was observed in all the B. braunii strains studied compared with control culture (without CO2 supplementation). At 1% and 2% (v/v) CO2 concentrations, palmitic acid and oleic acid levels increased by 2.5 to 3 folds in one of the strains of B. braunii (LB-572). Hydrocarbon content was found to be above 20% at 2% CO2 level in the B. braunii LB-572, CFTRI-Bb-2, CFTRI-Bb-1, and N-836 strains, whereas it was less than 20% in the SAG 30.81 and MCRC-Bb strains compared with control culture. This culture methodology will provide information on CO2 requirement for growth of algae and metabolite production. B. braunii spp. can be grown at the tested levels of CO2 concentration without much influence on culture pH.

  13. Exploration of a variation of the bottle buoyancy technique for the assessment of body composition.

    PubMed

    Gulick, Dawn T; Geigle, Paula Richley

    2003-05-01

    Hydrostatic weighing has long been recognized as a reliable and valid method for the assessment of body composition. An alternative method known as bottle buoyancy (BB) was introduced by Katch, Hortobagyi, and Denahan in 1989. The purpose of this clinical investigation was to determine the accuracy of the BB technique using an 11-L container. Sixteen individuals (8 men, 8 women) were weighed hydrostatically using a chair/scale and the BB technique. The overall intraclass correlation coefficient for the two techniques was 0.9537. A 2-variable ANOVA was significant for gender but not for technique, and there was no interaction between variables. Thus, the BB technique appears to be an accurate substitute for the chair/scale technique for hydrostatic weighing. The BB method does not involve elaborate equipment and is portable. It could be improved with the use of multiple bottles of various volumes or a calibrated bottle to minimize the number of trials needed for accurate measurements. BB is a valuable, simple clinical tool for assessing body composition based on the principles of hydrostatic weighing and can be performed in any high school, college, or community swimming pool.

  14. A study on the levels of a polybrominated biphenyl in Chinese human milk samples collected in 2007 and 2011.

    PubMed

    Liu, Xiao; Wen, Sheng; Li, Jingguang; Zhang, Lei; Zhao, Yunfeng; Wu, Yongning

    2016-09-01

    The levels of a 2,2',4,4',5,5'-hexabromobiphenyl (BB-153) were measured in human milk samples collected in 2007 and 2011 from residents in China by high-resolution gas chromatography-high-resolution mass chromatography (HRGC-HRMS) with isotope dilution. The median concentrations of BB-153 from the samples collected in 2007 and 2011 were 8.3 and 7.2 pg/g lipid weight, respectively. The levels of BB-153 in the human milk collected from rural areas were not significantly different to those collected from the urban areas in China. Meanwhile, significant positive correlations were found between the levels of BB-153 in human milk and the consumption of animal-origin foods. In the present study, the mean levels of BB-153 in human milk from Chinese mothers were found to be lower than those from European and American mothers.

  15. Observation of Z_{b}(10610) and Z_{b}(10650) Decaying to B Mesons.

    PubMed

    Garmash, A; Abdesselam, A; Adachi, I; Aihara, H; Asner, D M; Aushev, T; Ayad, R; Aziz, T; Babu, V; Badhrees, I; Bakich, A M; Behera, P; Bhardwaj, V; Bhuyan, B; Bobrov, A; Bondar, A; Bonvicini, G; Bozek, A; Bračko, M; Browder, T E; Červenkov, D; Chekelian, V; Chen, A; Cheon, B G; Chilikin, K; Cho, K; Chobanova, V; Choi, Y; Cinabro, D; Dalseno, J; Danilov, M; Dash, N; Doležal, Z; Drutskoy, A; Dutta, D; Eidelman, S; Epifanov, D; Farhat, H; Fast, J E; Ferber, T; Fulsom, B G; Gaur, V; Gabyshev, N; Gillard, R; Goh, Y M; Goldenzweig, P; Golob, B; Hara, T; Hayasaka, K; Hayashii, H; Iijima, T; Ishikawa, A; Itoh, R; Iwasaki, Y; Jaegle, I; Joffe, D; Joo, K K; Julius, T; Kang, K H; Kato, E; Kawasaki, T; Kim, D Y; Kim, J B; Kim, K T; Kim, M J; Kim, S H; Kim, Y J; Kinoshita, K; Korpar, S; Križan, P; Krokovny, P; Kuhr, T; Kuzmin, A; Kwon, Y-J; Lange, J S; Lee, I S; Li, C; Li, H; Li, L; Li Gioi, L; Libby, J; Liventsev, D; Lukin, P; Masuda, M; Matvienko, D; Miyabayashi, K; Miyata, H; Mizuk, R; Mohanty, G B; Moll, A; Mori, T; Mussa, R; Nakano, E; Nakao, M; Nanut, T; Natkaniec, Z; Nishida, S; Olsen, S L; Pakhlov, P; Pakhlova, G; Pal, B; Park, H; Pedlar, T K; Pestotnik, R; Petrič, M; Piilonen, L E; Pulvermacher, C; Ribežl, E; Ritter, M; Rostomyan, A; Sahoo, H; Sakai, Y; Sandilya, S; Sanuki, T; Savinov, V; Schneider, O; Schnell, G; Schwanda, C; Seino, Y; Semmler, D; Senyo, K; Seong, I S; Sevior, M E; Shebalin, V; Shen, C P; Shibata, T-A; Shiu, J-G; Shwartz, B; Simon, F; Sohn, Y-S; Solovieva, E; Starič, M; Sumiyoshi, T; Tamponi, U; Tanida, K; Teramoto, Y; Trabelsi, K; Uchida, M; Uehara, S; Uglov, T; Uno, S; Van Hulse, C; Vanhoefer, P; Varner, G; Vorobyev, V; Wagner, M N; Wang, C H; Wang, M-Z; Wang, P; Watanabe, Y; Williams, K M; Won, E; Yamamoto, H; Yamaoka, J; Yashchenko, S; Yelton, J; Yook, Y; Yuan, C Z; Zhang, Z P; Zhilich, V; Zhulanov, V; Zupanc, A

    2016-05-27

    We report the analysis of the three-body e^{+}e^{-}→BB[over ¯]π^{±}, BB[over ¯]^{*}π^{±}, and B^{*}B[over ¯]^{*}π^{±} processes, including the first observations of the Z_{b}^{±}(10610)→[BB[over ¯]^{*}+c.c.]^{±} and Z_{b}^{±}(10650)→[B^{*}B[over ¯]^{*}]^{±} transitions that are found to dominate the corresponding final states. We measure Born cross sections for the three-body production of σ(e^{+}e^{-}→[BB[over ¯]^{*}+c.c.]^{±}π^{∓})=[17.4±1.6(stat)±1.9(syst)]  pb and σ(e^{+}e^{-}→[B^{*}B[over ¯]^{*}]^{±}π^{∓})=[8.75±1.15(stat)±1.04(syst)]  pb and set a 90% C.L. upper limit of σ(e^{+}e^{-}→[BB[over ¯

  16. Association of Lyme Disease and Schizoaffective Disorder, Bipolar Type: Is it Inflammation Mediated?

    PubMed

    Mattingley, David William; Koola, Maju Mathew

    2015-01-01

    Lyme disease has been reported to be associated with various psychiatric presentations. Borreliaburgdorferi (Bb) can present with symptoms similar to schizophrenia and bipolar disorder. It has been suggested that inflammation incurred during the Bb infection leads to neurodegenerative changes that result in schizophrenia-like presentations. We report a case of a 41-year-old male with a past history of Bb infection who presents with psychosis. Later in the course of his hospitalization, he developed mood symptoms and was diagnosed with schizoaffective disorder, bipolar type. This case highlights the diagnosis and treatment of a patient with the unique presentation of schizoaffective disorder, bipolar type in the setting of previous Bb infection.

  17. Doctor says you are cured, but you still feel the pain. Borrelia DNA persistence in Lyme disease.

    PubMed

    Cervantes, Jorge

    Lyme disease is a zoonosis caused by infection with Borrelia burgdorferi (Bb). A great amount of research has attempted to elucidate the mechanisms by which Bb causes inflammation and chronic symptomatology in some patients. Patients often seek unconventional treatments that lack scientific evidence, as medical care is unable to effectively explain and treat their illness. Bb-DNA can persist for long periods of time in some individuals, even after antibiotic therapy. Herein, scientific rationale is presented for a new therapeutic approach against remaining bacterial DNA, and/or increasing the ability of human macrophages to remove extracellular Bb DNA. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  18. Cosmological space-times with resolved Big Bang in Yang-Mills matrix models

    NASA Astrophysics Data System (ADS)

    Steinacker, Harold C.

    2018-02-01

    We present simple solutions of IKKT-type matrix models that can be viewed as quantized homogeneous and isotropic cosmological space-times, with finite density of microstates and a regular Big Bang (BB). The BB arises from a signature change of the effective metric on a fuzzy brane embedded in Lorentzian target space, in the presence of a quantized 4-volume form. The Hubble parameter is singular at the BB, and becomes small at late times. There is no singularity from the target space point of view, and the brane is Euclidean "before" the BB. Both recollapsing and expanding universe solutions are obtained, depending on the mass parameters.

  19. 77 FR 77040 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-31

    ... Laser Guided Bombs, 162 FMU-152 bomb fuzes, 150 BLU-111B/B 500-lb Conical Fin General Purpose Bombs (Freefall Tail), 60 BLU-111B/B 500-lb Retarded Fin General Purpose Bombs (Ballute Tail), and 32 CBU-105 Wind... (AMRAAM), 162 GBU-12 PAVEWAY II 500-lb Laser Guided Bombs, 162 FMU-152 bomb fuzes, 150 BLU- 111B/B 500-lb...

  20. The effect of dietary prebiotics and probiotics on body weight, large intestine indices, and fecal bile acid profile in wild type and IL10-/- mice.

    PubMed

    Kuo, Shiu-Ming; Merhige, Patricia M; Hagey, Lee R

    2013-01-01

    Previous studies have suggested roles of probiotics and prebiotics on body weight management and intestinal function. Here, the effects of a dietary prebiotic, inulin (50 mg/g diet), and probiotic, Bfidobacterium animalis subsp. lactis (Bb12) (final dose verified at 10(5) colony forming unit (cfu)/g diet, comparable to human consumption), were determined separately and in combination in mice using cellulose-based AIN-93G diets under conditions allowed for the growth of commensal bacteria. Continuous consumption of Bb12 and/or inulin did not affect food intake or body, liver, and spleen weights of young and adult mice. Fecal bile acid profiles were determined by nanoESI-MS/MS tandem mass spectrometry. In the presence of inulin, more bacterial deconjugation of taurine from primary bile acids was observed along with an increased cecal weight. Consumption of inulin in the absence or presence of Bb12 also increased the villus cell height in the proximal colon along with a trend of higher bile acid sulfation by intestinal cells. Feeding Bb12 alone at the physiological dose did not affect bile acid deconjugation and had little effect on other intestinal indices. Although interleukin (IL)10-null mice are susceptible to enterocolitis, they maintained the same body weight as the wild type mice under our specific pathogen-free housing condition and showed no signs of inflammation. Nevertheless, they had smaller cecum suggesting a mildly compromised intestinal development even before the disease manifestation. Our results are consistent with the notion that dietary factors such as prebiotics play important roles in the growth of intestinal microbiota and may impact on the intestinal health. In addition, fecal bile acid profiling could potentially be a non-invasive tool in monitoring the intestinal environment.