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  1. Prognostic Value of Basic Fibroblast Growth Factor (bFGF) in Lung Cancer: A Systematic Review with Meta-Analysis

    PubMed Central

    Hu, Mingming; Hu, Ying; He, Jiabei; Li, Baolan

    2016-01-01

    Background Basic fibroblast growth factor (bFGF) is known to stimulate angiogenesis and thus to influence the proliferation, migration and survival of tumor cells. Many studies examined the relationship between human bFGF overexpression and survival in lung cancer patients, but the results have been mixed. To systematically summarize the clinical prognostic function of bFGF in lung cancer, we performed this systematic review with meta-analysis. Method Studies were identified by an electronic search of PubMed, EMBASE, China National Knowledge Infrastructure and Wanfang databases, including publications prior toAugust 2014. Pooled hazard ratios (HR) for overall survival (OS) were aggregated and quantitatively analyzed by meta-analysis. Results Twenty-two studies (n = 2154) were evaluated in the meta-analysis. Combined HR suggested that bFGF overexpression had an adverse impact on survival of patients with lung cancer(HR = 1.202,95%CI, 1.022–1.382). Our subgroup analysis revealed that the combined HR evaluating bFGF expression on OS in operable non-small cell lung cancer (NSCLC) was 1.553 (95%CI, 1.120–1.986); the combined HR in small cell lung cancer (SCLC) was 1.667 (95%CI, 1.035–2.299). There was no significant impact of bFGF expression on survival in advanced NSCLC. Conclusion This meta-analysis showed that bFGF overexpression is a potential indicator of worse prognosis for patients with operable NSCLC and SCLC, but is not associated with outcome in advanced NSCLC. The data suggests that high bFGF expression is highly related to poor prognosis. Nevertheless,more high-quality studies should be performed in order to provide additional evidence for the prognostic value of bFGF in lung cancer. PMID:26824699

  2. Blocking Infralimbic Basic Fibroblast Growth Factor (bFGF or FGF2) Facilitates Extinction of Drug Seeking After Cocaine Self-Administration.

    PubMed

    Hafenbreidel, Madalyn; Twining, Robert C; Rafa Todd, Carolynn; Mueller, Devin

    2015-12-01

    Drug exposure results in structural and functional changes in brain regions that regulate reward and these changes may underlie the persistence of compulsive drug seeking and relapse. Neurotrophic factors, such as basic fibroblast growth factor (bFGF or FGF2), are necessary for neuronal survival, growth, and differentiation, and may contribute to these drug-induced changes. Following cocaine exposure, bFGF is increased in addiction-related brain regions, including the infralimbic medial prefrontal cortex (IL-mPFC). The IL-mPFC is necessary for extinction, but whether drug-induced overexpression of bFGF in this region affects extinction of drug seeking is unknown. Thus, we determined whether blocking bFGF in IL-mPFC would facilitate extinction following cocaine self-administration. Rats were trained to lever press for intravenous infusions of cocaine before extinction. Blocking bFGF in IL-mPFC before four extinction sessions resulted in facilitated extinction. In contrast, blocking bFGF alone was not sufficient to facilitate extinction, as blocking bFGF and returning rats to their home cage had no effect on subsequent extinction. Furthermore, bFGF protein expression increased in IL-mPFC following cocaine self-administration, an effect reversed by extinction. These results suggest that cocaine-induced overexpression of bFGF inhibits extinction, as blocking bFGF during extinction permits rapid extinction. Therefore, targeted reductions in bFGF during therapeutic interventions could enhance treatment outcomes for addiction. PMID:25994078

  3. Entrapment of basic fibroblast growth factor (bFGF) in a succinylated chitosan nanoparticle delivery system and release profile.

    PubMed

    Butko, Alison; Bonat Celli, Giovana; Paulson, Allan; Ghanem, Amyl

    2016-07-01

    Basic fibroblast growth factor (bFGF) helps to regulate the proliferation and migration of fibroblasts, the proliferation of endothelial cells, and aids the development of angiogenesis. Its in vivo half-life is on the order of minutes due to extensive degradation and inactivation, which could be potentially reduced by controlled release vehicles. In this study, bFGF was entrapped into chitosan (CS) and N-succinyl-chitosan (SC) nanoparticles, with and without heparin, at two levels of initial loading, followed by further characterization of the particles. Release studies were conducted using radiolabeled bFGF-loaded nanoparticles. Both types of nanoparticles loaded similar amounts of bFGF (60.2 and 68.6% for CS and SC, respectively). The release profile varied greatly among the samples, and a burst release was observed in most cases, with the release amount approaching its final value in the first 6 h. The final amount released varied from 1.5 to 18% of the amount of bFGF-entrapped. The concomitant encapsulation of heparin and the use of SC as a nanoparticle matrix contributed to the largest amount of bFGF release (18%) over the time investigated. PMID:27146359

  4. Comparison of human dermal fibroblasts (HDFs) growth rate in culture media supplemented with or without basic fibroblast growth factor (bFGF).

    PubMed

    Abdian, Narges; Ghasemi-Dehkordi, Payam; Hashemzadeh-Chaleshtori, Morteza; Ganji-Arjenaki, Mahbobe; Doosti, Abbas; Amiri, Beheshteh

    2015-12-01

    Basic fibroblast growth factor (bFGF or FGF-2) is a member of the FGF family secreted by different kinds of cells like HDFs and it is an important nutritional factor for cell growth and differentiation. The HDFs release bFGF in culture media at very low. The present study aims to investigate the HDFs growth rate in culture media supplemented either with or without bFGF. In brief, HDFs were isolated from human foreskin sample and were cultured in vitro in media containing bFGF and lack of this factor. The cells growth rate was calculated by trypan blue. The karyotyping was performed using G-banding to investigate the chromosomal abnormality of HDFs in both groups. Total RNA of each groups were extracted and cDNA samples were synthesized then, real-time Q-PCR was used to measure the expression level of p27kip1 and cyclin D1 genes normalized to internal control gene (GAPDH). The karyotype analysis showed that HDFs cultured in media or without bFGF had normal karyotype (46 chromosomes, XY) and chromosomal abnormalities were not observed. The cell growth rates in both groups were normal with proliferated exponentially but the slope of growth curve in HDFs cultured in media containing bFGF was increased. Karyotyp test showed that bFGF does not affect on cytogenetic stability of cells. The survey of p27kip1 and cyclin D1 genes by real-time Q-PCR showed that the expression level of these genes were up-regulated when adding bFGF in culture media (p < 0.05). The findings of the present study demonstrate that appropriate supplementation of culture media with growth factor like bFGF could enhance the proliferation and differentiation capacity of cells and improve cells growth rate. Similarly, fibroblast growth factors did not induce any chromosomal abnormality in cells. Furthermore, in HDFs cultured in bFGF supplemented media, the p27kip1 and cyclin D1 genes were up-regulated and suggesting an important role for bFGF in cell-cycle regulation and progression and fibroblast

  5. Functional restoration using basic fibroblast growth factor (bFGF) infusion in Kainic acid induced cognitive dysfunction in rat: neurobehavioural and neurochemical studies.

    PubMed

    Srivastava, Nishi; Seth, Kavita; Srivastava, Nalini; Khanna, Vinay K; Agrawal, Ashok Kumar

    2008-07-01

    Neurogenesis occurs in dentate gyrus of adult hippocampus under the influence of various mitogenic factors. Growth factors besides instigating the proliferation of neuronal progenitor cells (NPCs) in dentate gyrus, also supports their differentiation to cholinergic neurons. In the present study, an attempt has been made to investigate the neurotrophic effect of bFGF in Kainic acid (KA) induced cognitive dysfunction in rats. Stereotaxic lesioning using (KA) was performed in hippocampal CA3 region of rat's brain. Four-weeks post lesioning rats were assessed for impairment in learning and memory using Y maze followed by bFGF infusion in dentate gyrus region. The recovery was evaluated after bFGF infusion using neurochemical, neurobehavioural and immunohistochemical approaches and compared with lesioned group. Significant impairment in learning and memory (P < 0.01) observed in lesioned animals, four weeks post lesioning exhibited significant restoration (P < 0.001) following bFGF infusion twice at one and four week post lesion. The bFGF infused animals exhibited recovery in hippocampus cholinergic (76%)/ dopaminergic (46%) receptor binding and enhanced Choline acetyltransferase (ChAT) immunoreactivity in CA3 region. The results suggest restorative potential of bFGF in cognitive dysfunctions, possibly due to mitogenic effect on dentate gyrus neurogenic area leading to generation and migration of newer cholinergic neurons. PMID:17955369

  6. Expression Pattern of Neuronal Markers in PB-MSCs Treated by Growth Factors Noggin, bFGF and EGF

    PubMed Central

    Fazeli, Zahra; Ghaderian, Sayyed Mohammad Hossein; Rajabibazl, Masoumeh; Salami, Siamak; Vazifeh Shiran, Nader; Omrani, Mir Davood

    2015-01-01

    Mesenchymal stem cells (MSCs) have the ability to differentiate into neuronal like cells under appropriate culture condition. In this study, we investigated whether MSCs derived from human peripheral blood (PB-MSCs) can differentiate into neuronal like cells by synergic effect of the growth factors EGF, bFGF and Noggin. For this purpose, the expression of five neuronal markers (Nestin, β III tubulin, NFM, MAP2 and NSE) were evaluated in treated PB-MSCs by SYBR Green Real time PCR. The expression analysis showed a higher expression of β-tubulin and NFM in treated BP-MSCs compared with untreated PB-MSCs as a control group. The expression of Nestin was also diminished in PB-MSCs treated with Noggin. This study suggested that the treatment of PB- MSCs with Noggin alongside with bFGF and EGF might differentiate these cells into neuronal lineage cells. The obtained results could be further developed for useful applications in regenerative medicine. PMID:27014645

  7. Regulation of cyclic adenosine 3',5'-monophosphate-dependent protein kinase activity and regulatory subunit RII beta content by basic fibroblast growth factor (bFGF) during granulosa cell differentiation: possible implication of protein kinase C in bFGF action.

    PubMed

    Oury, F; Faucher, C; Rives, I; Bensaïd, M; Bouche, G; Darbon, J M

    1992-08-01

    We have previously shown that basic fibroblast growth factor (bFGF) inhibits the FSH-induced differentiation of cultured rat granulosa cells, as manifested by prominent reduction of the LH receptor expression. We now investigate the possible sites and mechanism of action of bFGF. Whereas bFGF decreased the cAMP formation induced by FSH, it enhanced the cAMP production caused by cholera toxin and forskolin, suggesting that bFGF exerted its inhibitory action on cell differentiation at a step to cAMP production. Photoaffinity labeling with 8-azido-[32P]cAMP revealed that bFGF markedly reduced the FSH-induced increase in the level of regulatory subunit RII beta of the cAMP-dependent protein kinase (PKA) type II. In contrast to its striking effect on RII beta expression (70-80% inhibition), bFGF decreased PKA enzymatic activity by only 30%. On the other hand, transforming growth factor-beta (TGF beta) slightly amplified the stimulatory action of FSH and antagonized the bFGF inhibitory effect on both LH receptor expression and RII beta synthesis. We report that the protein kinase C (PKC) activator 12-O-tetradecanoylphorbol-13-acetate (TPA), which impaired granulosa cell differentiation, also abolished the RII beta synthesis induced by FSH. The activation of PKC by bFGF in granulosa cells was supported by the following findings: (i) bFGF markedly enhanced the production of diacylglycerol (2.3-fold stimulation at 5 min), the intracellular activator of PKC; (ii) bFGF promoted tight association of PKC to cellular membranes, a process that is believed to correlate with the enzyme activation; (iii) bFGF induced the phosphorylation of an endogenous M(r) 78,000/pI 4.7 protein that appears as a specific PKC substrate; (iv) bFGF mimicked the TPA-induced transmodulation of the epidermal growth factor (EGF) receptor, reducing by 36% the 125I-EGF binding on granulosa cells. We conclude that bFGF may exert its repressive action on RII beta synthesis, PKA activity, and granulosa cell

  8. Insulin-like growth factor-binding protein-3 inhibits IGF-1-induced proliferation of human hepatocellular carcinoma cells by controlling bFGF and PDGF autocrine/paracrine loops.

    PubMed

    Ma, Yang; Han, Chen-Chen; Li, Yifan; Wang, Yang; Wei, Wei

    2016-09-16

    Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) produced by hepatocellular carcinoma (HCC) cells are responsible for the growth of HCC cells. Accumulating evidence shows that insulin-like growth factor-binding protein-3 (IGFBP-3) suppresses HCC cell proliferation in both IGF-dependent and independent manners. It's unknown, however, whether treatment with exogenous IGFBP-3 inhibits bFGF and PDGF production in HCC cells. The present study demonstrates that IGFBP-3 suppressed IGF-1-induced bFGF and PDGF expression while it does not affect their expression in the absence of IGF-1. To delineate the underlying mechanism, western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1 (EGR1) is involved in IGFBP-3 regulation of bFGF and PDGF. IGFBP-3 inhibition of type 1 insulin-like growth factor receptor (IGF1R), ERK and AKT activation is IGF-1-dependent. Furthermore, transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1, bFGF and PDGF expression. In conclusion, these findings suggest that IGFBP-3 suppresses transcription of EGR1 and its target genes bFGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation. It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation, suggesting that IGFBP-3 could be a target for the treatment of HCC. PMID:27521890

  9. Growth factor expression during rat development: a comparison of TGF-beta 3, TGF-alpha, bFGF, PDGF and PDGF-R.

    PubMed Central

    Burton, P. B.; Quirke, P.; Sorensen, C. M.; Nehlsen-Cannarella, S. L.; Bailey, L. L.; Knight, D. E.

    1993-01-01

    At least part of the mechanism underlying fetal development appears to be the production of a number of growth factors considered important in the process of tumour formation. Using immunocytochemistry, we have investigated the temporal and spatial pattern of expression of some of the important growth factors, by the fetus. We describe here the cellular localization of transforming growth factor beta 3 (TGF-beta 3), platelet derived growth factor (PDGF) and its receptor (PDGF-R), TGF-alpha and basic fibroblast growth factor (bFGF) in the fetal rat from day 13 to 21 of gestation. Using antisera raised against an N-terminal portion of TGF-beta 3, immunoreactivity peaked around day 16 and was seen predominantly within epithelial cells. However, using antisera raised against the C-terminal of this molecule immunoreactivity was seen exclusively within the extracellular matrix underlying adjacent epithelia, and was maintained up until day 21 of gestation. Strong expression of TGF-alpha was seen in cells of most organs throughout the gestation period studied. Immunoreactivity for bFGF, PDGF and PDGF-R peaked around day 18 in both epithelial and mesenchymal cells of all major organ systems and then declined by day 21. These data suggest distinct roles for each factor during embryogenesis and tumorigenesis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8471538

  10. [The sensitivity of mesenchymal stromal cell subpopulations with different times of adhesion property manifestation and derived from hemopoietic organs to growth factors EGF, bFGF, and PDGF].

    PubMed

    Molchanova, E A; Bueverova, E I; Starostin, V I; Domaratskaia, E I

    2011-01-01

    The action of three growth factors (EGF, bFGF, and PDGF) on mesenchymal stromal cell (MSC) subpopulations from mature bone marrow (BM) and rat embryo liver (EL) was investigated. These cells are plastic-adhesive and have different rates of adhesion (AC1-AC4 subpopulations). The efficiency of colony-formation, the size of colonies, and the number of early osteogenic progenitors with alkaline phosphatase activity in colonies and induced osteogenesis were analyzed. It was shown that EGF increased the number of bone marrow (BM) MSC colonies, but it had no influence on osteogenic differentiation. bFGF suppressed colony formation, but it stimulated both early and late stages of steogenesis. PDGF increased the size and the number of colonies in AC2 and AC3 subpopulations, but it stimulated only the ostegenesis terminal stage. The distinction between MSC subpopulations from two organs were found: MSC from EL had small osteogenic capacities and low sensitivity to grow factors; MSC from BM had no such characteristics. MSC subpopulations with different adhesion properties and from different tissues had compatible sensitivity to growth factors. Thus, these cells have no parent-progeny relationship. PMID:21506387

  11. 5. Accelerated Fracture Healing Targeting Periosteal Cells: Possibility of Combined Therapy of Low-Intensity Pulsed Ultrasound (LIPUS), Bone Graft, and Growth Factor (bFGF).

    PubMed

    Uchida, Kentaro; Urabe, Ken; Naruse, Koji; Mikuni-Takagaki, Yuko; Inoue, Gen; Takaso, Masashi

    2016-08-01

    We have studied the mechanism of fracture healing, and the effect of LIPUS, bone graft and growth factor on accelerating fracture healing. We present here the results of our research. To examine callus formation cells in fracture healing, we made marrow GFP chimera mice and a fracture model of marrow mesenchymal stem cell GFP chimera mice. It was demonstrated that periosteal cells were essential for callus formation. We focused on periosteal cells and examined the effect of LIPUS. In an in vitro experiment using a cultured part of the femur, LIPUS promoted ossification of the periosteal tissue. Further, LIPUS accelerated VEGF expression in the experiment using the femoral fracture model of mice. From these results, it was suggested that activation of periosteal cells might play a role in the fracture healing mechanism of LIPUS. Next, we discussed the possibility of combined therapy of LIPUS, bone graft and growth factor. Therapy involving the topical administration of bFGF using a controlled release system and bone graft could promote callus formation. In addition, LIPUS was able to promote membranaceous ossification after the bone graft. It was suggested that combined therapy of LIPUS, bone graft and bFGF could be a new option for treating fractures. PMID:27441766

  12. Staphylococcus aureus induces TGF-β1 and bFGF expression through the activation of AP-1 and NF-κB transcription factors in bovine mammary gland fibroblasts.

    PubMed

    Wu, Jianmei; Ding, Yulin; Bi, Yannan; Wang, Yi; Zhi, Yu; Wang, Jinling; Wang, Fenglong

    2016-06-01

    Staphylococcus aureus is a common Gram-positive pathogen that causes bovine mastitis, a persistent infection of the bovine mammary gland. To better understand the importance of bovine mammary fibroblasts (BMFBs) and the roles of the TLR-NF-κB and TLR-AP-1 signaling pathways in the regulation of S. aureus-associated mastitis and mammary fibosis, BMFBs cultured in vitro were stimulated with different concentrations of heat-inactivated S. aureus to analyze the gene and protein expression of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), transforming growth factor beta 1 (TGF-β1), basic fibroblast growth factor (bFGF) as well as the protein expression of nuclear factor-kappa B (NF-κB) and activation protein-1 (AP-1) by means of quantitative polymerase chain reaction (qPCR) and western blotting, respectively. Specific NF-κB and AP-1 inhibitors were also used to investigate their effects on the regulation of TGF-β1 and bFGF expression. The results indicated that, in addition to increasing mRNA and protein expression of TLR2 and TLR4, S. aureus could also upregulate TGF-β1 and bFGF mRNA expression and secretion through the activation of NF-κB and AP-1. The increase in TGF-β1 and bFGF expression was shown to be inhibited by AP-1- and NF-κB-specific inhibitors. Taken together, S. aureus induces TGF-β1 and bFGF expression through the activation of AP-1 and NF-κB in BMFBs. This information offers new potential targets for the treatment of bovine mammary fibrosis. PMID:26948281

  13. Stem cells with FGF4-bFGF fused gene enhances the expression of bFGF and improves myocardial repair in rats

    SciTech Connect

    Chen, Xiang-Qi; Chen, Liang-Long Fan, Lin; Fang, Jun; Chen, Zhao-Yang; Li, Wei-Wei

    2014-04-25

    Highlights: • BFGF exists only in the cytoplasm of live cells. • BFGF cannot be secreted into the extracellular space to promote cell growth. • We combine the secretion-promoting signal peptide of FGF4. • We successfully modified BMSCs with the fused genes of FGF4-bFGF. • We promoted the therapeutic effects of transplanted BMSCs in myocardial infarction. - Abstract: The aim of this study was to investigate whether the modification of bone marrow-derived mesenchymal stem cells (BMSCs) with the fused FGF4 (fibroblast growth factor 4)-bFGF (basic fibroblast growth factor) gene could improve the expression and secretion of BFGF, and increase the efficacies in repairing infarcted myocardium. We used In-Fusion technique to construct recombinant lentiviral vectors containing the individual gene of bFGF, enhanced green fluorescent protein (EGFP), or genes of FGF4-bFGF and EGFP, and then transfected these lentiviruses into rat BMSCs. We conducted an in vitro experiment to compare the secretion of bFGF in BMSCs infected by these lentiviruses and also examined their therapeutic effects in the treatment of myocardial infraction in a rodent study. Sixty rats were tested in the following five conditions: Group-SHAM received only sham operation as controls; Group-AMI received only injection of placebo PBS buffer; Group-BMSC, Group-bFGF and Group-FGF4-bFGF received implantation of BMSCs with empty lentivirus, bFGF lentivirus, and FGF4-bFGF lentivirus, respectively. Our results found out that the transplanted FGF4-bFGF BMSCs had the highest survival rate, and also the highest myocardial expression of bFGF and microvascular density as evidenced by Western blotting and immunohistochemistry, respectively. As compared to other groups, the Group-FGF4-BFGF rats had the lowest myocardial fibrotic fraction, and the highest left ventricular ejection fraction. These results suggest that the modification of BMSCs with the FGF4-bFGF fused gene can not only increase the expression of

  14. The stability of bFGF against thermal denaturation.

    PubMed

    Vemuri, S; Beylin, I; Sluzky, V; Stratton, P; Eberlein, G; Wang, Y J

    1994-06-01

    The influence of sulphated ligand and pH on thermal denaturation of basic fibroblast growth factor (bFGF) was investigated by differential scanning calorimetry (DSC), and verified by fluorescence spectrophotometry. Purity of bFGF before and after heat denaturation was assessed by SDS-PAGE analysis. In DSC studies the samples were heated to 95 degrees C. The midpoint of the temperature change in the thermogram was designated as Tm. Sulphated ligand experiments were undertaken in potassium phosphate (pH 6.5) and sodium acetate buffers. Control thermograms (with no ligand) showed a Tm at 59 degrees C in potassium phosphate buffer. Higher Tm values were noted as sulphated ligand concentration was increased. Similarly when heparin was added, the Tm moved to a higher temperature. A ratio as low as 0.3:1 of heparin to bFGF, increased the Tm to 90 degrees C, which is a 31 degrees C shift in Tm. The effect of pH on thermal denaturation of bFGF was studied in a citrate-phosphate-borate buffer system. A shift in Tm from 46 to 65 degrees C was observed as the pH is changed from 4 to 8. Changes in protein conformation as a function of pH were monitored by fluorescence spectroscopy. It was found that a pH range from 5 to 9 is optimal for the stability of bFGF formulations. In a stability study it was noted that heparin protected bFGF from thermal denaturation only at high temperature. PMID:7932043

  15. Delivery of bFGF for Tissue Engineering by Tethering to the ECM

    PubMed Central

    Suttinont, Chawapun; Mashimo, Yasumasa; Mie, Masayasu; Kobatake, Eiry

    2015-01-01

    Delivery of growth factors to target cells is an important subject in tissue engineering. Towards that end, we have developed a growth factor-tethered extracellular matrix (ECM). Here, basic fibroblast growth factor (bFGF) was tethered to extracellular matrix noncovalently. The designed ECM was comprised of 12 repeats of the APGVGV peptide motif derived from elastin as a stable structural unit and included the well-known cell adhesive RGD peptide as an active functional unit. To bind bFGF to the ECM, an acidic amino acid-rich sequence was introduced at the C-terminus of the ECM protein. It consisted of 5 repeats of 4 aspartic acids and a serine, DDDDS. bFGF has a highly basic amino acid domain. Therefore, bFGF was tethered to the ECM protein by electrostatic interaction. Cells cultured on bFGF-tethered ECM were well attached to the ECM and induced proliferation without addition of soluble bFGF. PMID:26539469

  16. The incorporation of bFGF mediated by heparin into PCL/gelatin composite fiber meshes for guided bone regeneration.

    PubMed

    Lee, Ji-hye; Lee, Young Jun; Cho, Hyeong-jin; Kim, Dong Wan; Shin, Heungsoo

    2015-04-01

    The concept of guided bone regeneration facilitated by barrier membranes has been widely considered to achieve enhanced bone healing in maxillofacial surgery. However, the currently available membranes are limited in their active regulation of cellular activities. In this study, we fabricated polycaprolactone/gelatin composite electrospun nanofibers incorporated with basic fibroblast growth factor (bFGF) to direct bone regeneration. The fibrous morphology was maintained after the crosslinking and subsequent conjugation of heparin. Release of bFGF from electrospun nanofibers without heparin resulted in a spontaneous burst, while the heparin-mediated release of bFGF decreased the burst release in 24 h. The bFGF released from the nanofibers enhanced the proliferation and migration of human mesenchymal stem cells as well as the tubule formation of human umbilical cord blood cells. The subcutaneous implantation of fibers incorporated with bFGF mobilized a large number of cells positive for CD31 and smooth muscle alpha actin within 2 weeks. The effect of the nanofibers incorporated with bFGF on bone regeneration was evaluated on a calvarial critical size defect model. As compared to the mice that received fibers without bFGF, which presented minimal new bone formation (5.36 ± 3.4 % of the defect), those that received implants of heparinized nanofibers incorporated with 50 or 100 ng/mL bFGF significantly enhanced new bone formation (10.82 ± 2.2 and 17.55 ± 6.08 %). Taken together, our results suggest that the electrospun nanofibers incorporating bFGF have the potential to be used as an advanced membrane that actively enhances bone regeneration. PMID:25787740

  17. Therapeutic effects of complex rearing or bFGF after perinatal frontal lesions.

    PubMed

    Comeau, Wendy; Gibb, Robbin; Hastings, Erica; Cioe, Jan; Kolb, Bryan

    2008-03-01

    We investigated the effects of an enriched environment and/or basic fibroblast growth factor (bFGF) on recovery from neonatal frontal injury in rats. Rats received medial frontal lesions, or sham surgery, on postnatal day (P) 2/3. In the first set of experiments (Experiments 1 and 2), rats were housed in enriched environments that consisted of a large enclosure with multiple objects (or standard housing) for 90 days beginning at weaning (P22) or in adulthood (P110). In Experiment 3, the rats either received 7 days of subcutaneous bFGF beginning on the day after surgery or bFGF plus enriched housing beginning at weaning. After the 90-day housing period, the animals were tested on a spatial navigation task and a skilled reaching task. Early lesions of the medial frontal cortex caused severe impairments in spatial learning but this deficit was markedly reduced with enriched housing, bFGF, or a combination of both, with the latter being most effective. The housing effects varied with age, however: the earlier the experience began, the better the outcome. Enriched housing increased dendritic length in cortical pyramidal neurons, an effect that was greater in the lesion than the control animals, and enriched housing reversed the lesion-induced decrease in spine density. Enriched environment increased the thickness of the cortical mantle in both lesion and controls whereas bFGF had no effect. Experience thus can affect functional and anatomical outcome after early brain injury but the effects vary with age at experience and may be facilitated by treatment with bFGF. PMID:18286581

  18. Probing the conformation of protein (bFGF) precipitates by fluorescence spectroscopy.

    PubMed

    Shahrokh, Z; Eberlein, G; Wang, Y J

    1994-08-01

    Aggregation and precipitation are major events in the handling and aging of most protein pharmaceuticals. We demonstrate the utility of fluorescence spectroscopy in determining protein conformation in precipitates using basic fibroblast growth factor (bFGF) as an example. Conversion of the native to the soluble denatured from by chaotropes was accompanied by an increase in tryptophan emission. The emission spectra of resuspended precipitates were as reproducible as the spectra of the soluble form. The sum of emission spectra of native soluble bFGF and denatured precipitated bFGF was superimposable on the spectrum of the unfractionated suspension, suggesting that quantitative analysis of denatured aggregates in turbid protein formulations is possible. The ratio of tryptophan to tyrosine emissions increased with increasing extent of denaturation both in solution and in suspension. For example, salting out by ammonium sulphate increased the fluorescence index (indicative of denaturation) which was reversible upon dissolution. In addition, aging (35 degrees C) of bFGF in the presence of sulphated ligands produced precipitates with native-like fluorescence index, in contrast to denatured precipitates formed without ligands. PMID:7819377

  19. Changes in vitreous VEGF, bFGF and fibrosis in proliferative diabetic retinopathy after intravitreal bevacizumab

    PubMed Central

    Li, Jiu-Ke; Wei, Fang; Jin, Xiao-Hong; Dai, Yuan-Min; Cui, Hu-Shan; Li, Yu-Min

    2015-01-01

    AIM To evaluate the relationship between intravitreal bevacizumab (IVB) treatment and the levels of vitreous vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and vitreous-retina surface fibrosis in patients with proliferative diabetic retinopathy (PDR). METHODS This study was a prospective, open-label, controlled, randomized clinical trial. Sixty-eight eyes of PDR patients (n=53) and macular hole patients (n=15) were enrolled in this study. Thirty-four eyes of the PDR patients received IVB before vitrectomy. Twenty-three of the 34 PDR patients received IVB treatment 5d before vitrectomy (subgroup a), and 11 of the 34 PDR patients received IVB treatment greater than 2wk prior to vitrectomy (subgroup b). Nineteen of the PDR patients did not receive IVB treatment at any time prior to vitrectomy. The levels of bFGF and VEGF in vitreous samples were measured using enzyme-linked immunosorbent assay (ELISA) and the degree of vitreoretinal fibrosis was characterized using clinical data and data obtained intra-operatively. RESULTS In PDR patients, VEGF and bFGF levels were significantly increased compared to non-PDR (control) subject's eyes (P<0.01). In PDR patients, vitreous VEGF levels were significantly decreased following IVB treatment compared to PDR patients that did not receive IVB treatment (P<0.01). The degree of vitreoretinal fibrosis was significantly increased in subgroup b compared to subgroup a(P<0.05) and to patients that did not receive IVB (P<0.05). Vitreous bFGF levels were significantly greater in subgroup b than subgroup a (P<0.01) or in patients who did not receive IVB treatment (P<0.05). A Spearman's rank correlation test indicated that higher levels of vitreous bFGF, but not VEGF, correlated with the degree of vitreoretinal fibrosis. CONCLUSION We found that bFGF levels increase in PDR patient's vitreous after IVB treatment longer than two weeks prior to vitrectomy and correlated with the degree of fibrosis after IVB

  20. FSH and bFGF regulate the expression of genes involved in Sertoli cell energetic metabolism.

    PubMed

    Regueira, Mariana; Riera, María Fernanda; Galardo, María Noel; Camberos, María Del Carmen; Pellizzari, Eliana Herminia; Cigorraga, Selva Beatriz; Meroni, Silvina Beatriz

    2015-10-01

    The purpose of this study was to investigate if FSH and bFGF regulate fatty acid (FA) metabolism and mitochondrial biogenesis in Sertoli cells (SC). SC cultures obtained from 20-day-old rats were incubated with 100ng/ml FSH or 30ng/ml bFGF for 6, 12, 24 and 48h. The expression of genes involved in transport and metabolism of FA such as: fatty acid transporter CD36 (FAT/CD36), carnitine-palmitoyltransferase 1 (CPT1), long- and medium-chain 3-hydroxyacyl-CoA dehydrogenases (LCAD, MCAD), and of genes involved in mitochondrial biogenesis such as: nuclear respiratory factors 1 and 2 (NRF1, NRF2) and transcription factor A (Tfam), was analyzed. FSH stimulated FAT/CD36, CPT1, MCAD, NRF1, NRF2 and Tfam mRNA levels while bFGF only stimulated CPT1 expression. A possible participation of PPARβ/δ activation in the regulation of gene expression and lactate production was then evaluated. SC cultures were incubated with FSH or bFGF in the presence of the PPARβ/δ antagonist GSK3787 (GSK; 20μM). bFGF stimulation of CPT1 expression and lactate production were inhibited by GSK. On the other hand, FSH effects were not inhibited by GSK indicating that FSH regulates the expression of genes involved in FA transport and metabolism and in mitochondrial biogenesis, independently of PPARβ/δ activation. FA oxidation and mitochondrial biogenesis as well as lactate production are essential for the energetic metabolism of the seminiferous tubule. The fact that these processes are regulated by hormones in a different way reflects the multifarious regulation of molecular mechanisms involved in Sertoli cell function. PMID:26315388

  1. Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson’s Disease Model

    PubMed Central

    Cai, Pingtao; Ye, Jingjing; Zhu, Jingjing; Liu, Dan; Chen, Daqing; Wei, Xiaojie; Johnson, Noah R.; Wang, Zhouguang; Zhang, Hongyu; Cao, Guodong; Xiao, Jian; Ye, Junming; Lin, Li

    2016-01-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder with complicated pathophysiologic mechanisms. Endoplasmic reticulum (ER) stress appears to play a critical role in the progression of PD. We demonstrated that basic fibroblast growth factor (bFGF), as a neurotropic factor, inhibited ER stress-induced neuronal cell apoptosis and that 6-hydroxydopamine (6-OHDA)-induced ER stress was involved in the progression of PD in rats. bFGF administration improved motor function recovery, increased tyrosine hydroxylase (TH)-positive neuron survival, and upregulated the levels of neurotransmitters in PD rats. The 6-OHDA-induced ER stress response proteins were inhibited by bFGF treatment. Meanwhile, bFGF also increased expression of TH. The administration of bFGF activated the downstream signals PI3K/Akt and Erk1/2 in vivo and in vitro. Inhibition of the PI3K/Akt and Erk1/2 pathways by specific inhibitors partially reduced the protective effect of bFGF. This study provides new insight towards bFGF translational drug development for PD involving the regulation of ER stress. PMID:27493838

  2. Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson's Disease Model.

    PubMed

    Cai, Pingtao; Ye, Jingjing; Zhu, Jingjing; Liu, Dan; Chen, Daqing; Wei, Xiaojie; Johnson, Noah R; Wang, Zhouguang; Zhang, Hongyu; Cao, Guodong; Xiao, Jian; Ye, Junming; Lin, Li

    2016-08-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder with complicated pathophysiologic mechanisms. Endoplasmic reticulum (ER) stress appears to play a critical role in the progression of PD. We demonstrated that basic fibroblast growth factor (bFGF), as a neurotropic factor, inhibited ER stress-induced neuronal cell apoptosis and that 6-hydroxydopamine (6-OHDA)-induced ER stress was involved in the progression of PD in rats. bFGF administration improved motor function recovery, increased tyrosine hydroxylase (TH)-positive neuron survival, and upregulated the levels of neurotransmitters in PD rats. The 6-OHDA-induced ER stress response proteins were inhibited by bFGF treatment. Meanwhile, bFGF also increased expression of TH. The administration of bFGF activated the downstream signals PI3K/Akt and Erk1/2 in vivo and in vitro. Inhibition of the PI3K/Akt and Erk1/2 pathways by specific inhibitors partially reduced the protective effect of bFGF. This study provides new insight towards bFGF translational drug development for PD involving the regulation of ER stress. PMID:27493838

  3. Controlling the release of bFGF from silk fibroin membrane.

    PubMed

    Ji, Ya Wei; Kong, Yan; Zhao, Ya Hong; Wang, Ya Ling; Zhao, Jing; Zhang, Lu Zhong; Yang, Yu Min

    2014-12-01

    Since neurotrophic factor is easy to degrade and aggregate, it usually has a short half-life in vitro. To overcome this shortage, neurotrophic factor has been combined with the silk fibroin (SF) membrane to realize less degradation, optimal loading efficiency, sustained release, and good adsorption. By optimizing its binding conditions, main parameters were investigated and its optimal loading efficiency was obtained. bFGF was combined to SF membrane by layer by layer (LbL) static adsorption technique. The natural and nontoxic chondroitin sulfate (CS) was used as a crosslinking agent. Optimization was carried out in three aspects: the concentration of bFGF, the concentration of CS, and the reaction time. This experiment provides a better environment for the growth of cells and offers a new kind material of absorbing neurotrophic factor to meet increasing demand for biological materials. PMID:25484015

  4. Heparin oligosaccharides: inhibitors of the biological activity of bFGF on Caco-2 cells.

    PubMed Central

    Jayson, G. C.; Gallagher, J. T.

    1997-01-01

    A number of growth factors, including members of the fibroblast growth factor (FGF) family - hepatocyte growth factor, vascular endothelial growth factor and heparin-binding epidermal growth factor - are dependent on heparan sulphate (HS) for biological activity mediated through their high-affinity signal-transducing receptors. This obligate requirement for HS prompted the search for antagonists of HS function that could be used as anti-growth factor drugs for the treatment of cancer. Basic FGF (bFGF) was the focus of this study. Caco-2, a human colon carcinoma cell line, was adapted to growth in serum-free medium so that investigation of its growth factor requirements for growth and migration could be performed in defined conditions (Jayson GC, Evans GS, Pemberton PW, Lobley RW, Allen T 1994, Cancer Res, 54, 5718-5723). This cell line multiplied and moved in a dose-dependent manner in response to bFGF. Here, we show that the mitogenic response to bFGF is dependent on the presence of heparan sulphate. A library of heparin oligosaccharides with uniform composition but variable length was generated [general formula [IdoA(2S)-GlcNS(6S)n], and oligosaccharides of defined lengths were tested for their ability to inhibit the biological activity of bFGF. While intact heparin and heparin-derived fragments of 12 monosaccharide units did not affect bFGF-induced cell division or bFGF-induced cell migration, octasaccharides and decasaccharides potently inhibited the bFGF-induced growth and migration responses. In particular, octasaccharides completely inhibited these biological activities at 10 microg ml-, a clinically achievable and tolerable concentration. This study shows that the length of an oligosaccharide determines its ability to block the biological activity of bFGF. The observation that the biological activity of cell-surface heparan sulphate can be antagonized in this way in a human carcinoma cell line suggests that oligosaccharides should be investigated further as

  5. b-FGF Induces Corneal Blood and Lymphatic Growth in a Spatially Distinct Pattern

    PubMed Central

    Hajrasouliha, Amir R.; Sadrai, Zahra; Chauhan, Sunil K.; Dana, Reza

    2013-01-01

    Purpose To study the spatial variances in ligand expression and angiogenic effect in response to the inflammatory response induced by b-FGF. Methods b-FGF micropellets (80ng) were implanted in the temporal side of the cornea of Balbc/c mice. On days 1, 3, and 7 blood (heme) and lymph-angiogenesis were observed by immunofluorescence staining of corneal flat mounts with LYVE-1 and CD31 to identify lymphatic and blood vessels, respectively. A second group of corneas were harvested for quantitative RT-PCR. Each cornea was divided in two different area defines as (i) pre-pellet area and (ii) opposite-pellet area. Expression of VEGF ligands were evaluated using Real-time PCR in each respective zone. Results Blood vessels grew into the cornea from the pre-pellet area while corneal lymphatic vessels grew from the opposite-pellet area toward the center of the cornea. VEGF-A was upregulated in the pre-pellet while VEGF-D expression was mostly observed in the opposite-pellet area. VEGF-C level increased simultaneously in both areas. Conclusion A single inducing factor, i.e., b-FGF, may simultaneously provoke heme-and lymph-angiogenesis in different locations of the cornea through differential expression of VEGF ligands. This distinctive spatial pattern should be considered while evaluating the corneal predilection for inflammation beyond that which is directly visible by slit lamp examination. PMID:22467003

  6. Rod outer segment maintenance is enhanced in the presence of bFGF, CNTF and GDNF.

    PubMed

    Carwile, M E; Culbert, R B; Sturdivant, R L; Kraft, T W

    1998-06-01

    We employed a morphological assay of outer segment collapse to determine if growth factors or other supplements directly affect dissociated rod photoreceptors in vitro. The morphological changes in outer segments were correlated with the light responsiveness of rods. Time-lapse video microscopy was used to observe the collapse of rod outer segments from isolated single cells and small clumps of cells. A consistent pattern of outer segment collapse into the inner segment was observed, yielding a convenient assay of the effects of neurotrophic factors on photoreceptor functional maintenance. The functional state of rods, defined as light-responsiveness, was measured with suction electrode recordings and matched with the various stages of outer segment collapse. Ciliary neurotrophic factor (CNTF) and glial cell-line-derived neurotrophic factor (GDNF) at a high concentration, yielded statistically significant improvements in rat outer segment survival times. Basic fibroblast growth factor (bFGF), which rescues photoreceptors in several rodent models of retinal degeneration, produced a significant increase in survival time in the presence of the cofactor heparin. In 4 out of 10 cases using human tisue, bFGF also yielded a significant increase in survival times. When brain-derived neurotrophic factor (BDNF) was applied to rat rods, outer segment survival times did not change. Outer segments collapsed more quickly when either pigment epithelial cell derived factor (PEDF) or sugar N-acetyl D-galactosamine (NAD-gal) were present. Our results show that rod photoreceptors can respond to bFGF, GDNF and CNTF in vitro and provide evidence for a direct effect of these neurotrophic factors on rods. The rapid collapse of isolated photoreceptors in this model provides a convenient means for testing various neurotrophic agents and the induced cellular responses. PMID:9657912

  7. Regulation of VEGF and bFGF mRNA expression and other proliferative compounds in skeletal muscle cells.

    PubMed

    Jensen, L; Schjerling, P; Hellsten, Y

    2004-01-01

    The role of muscle contraction, prostanoids, nitric oxide and adenosine in the regulation of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endothelial cell proliferative compounds in skeletal muscle cell cultures was examined. VEGF and bFGF mRNA, protein release as well as the proliferative effect of extracellular medium was determined in non-stimulated and electro-stimulated rat and human skeletal muscle cells. In rat skeletal muscle cells these aspects were also determined after treatment with inhibitors and/or donors of nitric oxide (NO), prostanoids and adenosine. Electro-stimulation caused an elevation in the VEGF and bFGF mRNA levels of rat muscle cells by 33% and 43% (P < 0.05), respectively, and in human muscle cells VEGF mRNA was elevated by 24%. Medium from electro-stimulated human, but not rat muscle cells induced a 126% higher (P < 0.05) endothelial cell proliferation than medium from non-stimulated cells. Cyclooxygenase inhibition of rat muscle cells induced a 172% increase (P < 0.05) in VEGF mRNA and a 104% increase in the basal VEGF release. Treatment with the NO donor SNAP (0.5 microM) decreased (P < 0.05) VEGF and bFGF mRNA by 42 and 38%, respectively. Medium from SNAP treated muscle cells induced a 45% lower (P < 0.05) proliferation of endothelial cells than control medium. Adenosine enhanced the basal VEGF release from muscle cells by 75% compared to control. The present data demonstrate that contractile activity, NO, adenosine and products of cyclooxygenase regulate the expression of VEGF and bFGF mRNA in skeletal muscle cells and that contractile activity and NO regulate endothelial cell proliferative compounds in muscle extracellular fluid. PMID:15609080

  8. bFGF signaling-mediated reprogramming of porcine primordial germ cells.

    PubMed

    Zhang, Yu; Ma, Jing; Li, Hai; Lv, Jiawei; Wei, Renyue; Cong, Yimei; Liu, Zhonghua

    2016-05-01

    Primordial germ cells (PGCs) have the ability to be reprogrammed into embryonic germ cells (EGCs) in vitro and are an alternative source of embryonic stem cells. Other than for the mouse, the systematic characterization of mammalian PGCs is still lacking, especially the process by which PGCs convert to pluripotency. This hampers the understanding of germ cell development and the derivation of authenticated EGCs from other species. We observed the morphological development of the genital ridge from Bama miniature pigs and found primary sexual differentiation in the E28 porcine embryo, coinciding with Blimp1 nuclear exclusion in PGCs. To explore molecular events involved in porcine PGC reprogramming, transcriptome data of porcine EGCs and fetal fibroblasts (FFs) were assembled and 1169 differentially expressed genes were used for Gene Ontology analysis. These genes were significantly enriched in cell-surface receptor-linked signal transduction, in agreement with the activation of LIF/Stat3 signaling and FGF signaling during the derivation of porcine EG-like cells. Using a growth-factor-defined culture system, we explored the effects of bFGF on the process and found that bFGF not only functioned at the very beginning of PGC dedifferentiation by impeding Blimp1 nuclear expression via a PI3K/AKT-dependent pathway but also maintained the viability of cultured PGCs thereafter. These results provide further insights into the development of germ cells from livestock and the mechanism of porcine PGC reprogramming. PMID:26613602

  9. The Role of bFGF in the Excessive Activation of Astrocytes Is Related to the Inhibition of TLR4/NFκB Signals

    PubMed Central

    Ye, Libing; Yang, Ying; Zhang, Xie; Cai, Pingtao; Li, Rui; Chen, Daqing; Wei, Xiaojie; Zhang, Xuesong; Xu, Huazi; Xiao, Jian; Li, Xiaokun; Lin, Li; Zhang, Hongyu

    2015-01-01

    Astrocytes have critical roles in immune defense, homeostasis, metabolism, and synaptic remodeling and function in the central nervous system (CNS); however, excessive activation of astrocytes with increased intermediate filaments following neuronal trauma, infection, ischemia, stroke, and neurodegenerative diseases results in a pro-inflammatory environment and promotes neuronal death. As an important neurotrophic factor, the secretion of endogenous basic fibroblast growth factor (bFGF) contributes to the protective effect of neuronal cells, but the mechanism of bFGF in reactive astrogliosis is still unclear. In this study, we demonstrated that exogenous bFGF attenuated astrocyte activation by reducing the expression of glial fibrillary acidic protein (GFAP) and other markers, including neurocan and vimentin, but not nestin and decreased the levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), via the regulation of the upstream toll-like receptor 4/nuclear factor κB (TLR4/NFκB) signaling pathway. Our study suggests that the function of bFGF is not only related to the neuroprotective and neurotrophic effect but also involved in the inhibition of excessive astrogliosis and glial scarring after neuronal injury. PMID:26729092

  10. Effects of estradiol on VEGF and bFGF by Akt in endometrial cancer cells are mediated through the NF-κB pathway.

    PubMed

    Zhang, Jieqing; Song, Honglin; Lu, Yanqiong; Chen, Haiyan; Jiang, Si; Li, Li

    2016-08-01

    Endometrial carcinogenesis may be related to the long-term effects of estradiol with no antagonism. However, how estradiol regulates cell proliferation is unknown. In the present study, through investigating the molecular events involved in estradiol induced angiogenics factors VEGF and bFGF, we found that estradiol induced endometrial cancer cell division, proliferation, migratory and invasive capacity in vitro and upregulated mRNA expression and protein synthesis of VEGF and bFGF. The estradiol-dependent induction of the expression of VEGF and bFGF was blocked by ER inhibitor, AKT inhibitor and NF-κB inhibitor (PDTC) in estrogen receptor positive Ishikawa cells and blocked by AKT inhibitor, NF-κB inhibitor (PDTC) in estrogen receptor negative HEC-1A cells. Moreover, estradiol activation of AKT was also blocked by AKT antagonist. NF-κB activation was restricted by estradiol concentration and time. Estradiol leading to VEGF and bFGF induction was also confirmed by the development of xenograft tumors in vivo. Taken together, our data suggest that estradiol induces the production of angiogenic factors via a mechanism involving AKT-mediated NF-κB activation partly in non-genomic manner without the estrogen receptor. PMID:27349969

  11. VEGF and BFGF Expression and Histological Characteristics of the Bone-Tendon Junction during Acute Injury Healing

    PubMed Central

    Wang, Lin; Gao, Weiwei; Xiong, Kaiyu; Hu, Kuan; Liu, Xincun; He, Hui

    2014-01-01

    Bone-tendon junction (BTJ) injuries are common and may be caused by acute trauma and delayed healing during exercise or work. To understand the nature of the healing process of BTJ injuries would help to prevent injuries and improve treatment. Thirty-three mature female rabbit hindlimbs were assigned to normal control (CON, n = 7) and injury groups (n = 26). The acute injury was established by administering one 7 plum-blossom needle puncture. Specimens were harvested post injury at 1, 2, 4, and 8 weeks (ND1W, n = 6; ND2W, n = 6; ND4W, n = 7; and ND8W, n = 7). The injury existed in all of the injury groups. Compared with the CON group, all of the animals in the injury group showed poor cell profiles, an unclear or undetectable tide mark, a proteoglycan area and profile changes; the BTJ cell density diminished significantly in the ND1W (p < 0.01), ND2W (p < 0.05), ND4W (p < 0.01), and ND8W groups (p < 0.01); the fibrocartilage zone thickness in all injury groups was significantly thicker than in the CON group (p < 0.05), but no significant difference was found among the injury groups (p>0.05). The basic fibroblast growth factor (bFGF) expression in the CON group was significantly less than in the ND1W group (p<0.01), but no significant difference was found when compared with the ND2W, ND4W, and ND8W groups. The bFGF expression in the ND1W group was higher than that of the ND4W (p < 0.05) and ND8W groups (p < 0.01). The vascular endothelial growth factor (VEGF) levels were not significantly different among the groups (p > 0.05). The bFGF and VEGF expression levels indicated that the healing process stopped at 8 weeks post injury or was not activated, although the injury had not healed by histological examination. A repeatable animal model of BTJ acute injury was established in this study, and the results described the BTJ acute injury healing difficult concerned with the repairing stop. Key Points This study described the bone-tendon junction acute injury nature

  12. Acceleration of segmental bone regeneration in a rabbit model by strontium-doped calcium polyphosphate scaffold through stimulating VEGF and bFGF secretion from osteoblasts.

    PubMed

    Gu, Zhipeng; Zhang, Xu; Li, Li; Wang, Qiguang; Yu, Xixun; Feng, Ting

    2013-01-01

    The development of suitable bioactive three-dimensional scaffold for the promotion of bone regeneration is critical in bone tissue engineering. The purpose of this study was to investigate in vivo osteogenesis of the porous strontium-doped calcium polyphosphate (SCPP) scaffolds for bone repair, as well as the relationship between osteogenic properties of SCPP scaffolds and the secretion of bFGF and VEGF from osteoblasts stimulated by SCPP. Besides, the advantages of scaffolds seeded with mesenchymal stem cells (MSCs) for bone repair were also studied. Firstly, the bone repair evaluation of scaffolds was performed on a rabbit segmental bony defects model over a period of 16 weeks by histology combined with X-ray microradiography. And then, in order to avoid the influence from the other factors such as hypoxia which emerge in vivo study and affect the secretion of VEGF and bFGF from host cells, human osteoblast-like cells (MG63) were seeded to SCPP, CPP and HA scaffolds in vitro to determine the ability of these scaffolds to stimulate the secretion of angiogenic growth factors (VEGF and bFGF) from MG63 and further explore the reason for the better osteogenic properties of SCPP scaffolds. The histological and X-ray microradiographic results showed that the SCPP scaffolds presented better osteogenic potential than CPP and HA scaffolds, when combined with MSCs, the SCPP scaffolds could further accelerate the bone repair. And the amounts of VEGF measured by ELISA assay in SCPP, CPP and HA groups after cultured for 7 days were about 364.989 pg/mL, 244.035 pg/mL and 232.785 pg/mL, respectively. Accordingly, the amounts of bFGF were about 27.085 pg/mL, 15.727 pg/mL and 8.326 pg/mL. The results revealed that the SCPP scaffolds significantly enhanced the bFGF and VEGF secretion compared with other scaffolds. The results presented in vivo and in vitro study demonstrated that the SCPP could accelerate bone formation through stimulating the secretion of VEGF and bFGF from

  13. Combined use of bFGF and GDF-5 enhances the healing of medial collateral ligament injury

    SciTech Connect

    Saiga, Kenta; Furumatsu, Takayuki; Yoshida, Aki; Masuda, Shin; Takihira, Shota; Abe, Nobuhiro; Ozaki, Toshifumi

    2010-11-12

    Research highlights: {yields} bFGF/GDF-5 treatment increases cellular proliferation and migration of MCL fibroblasts. {yields} bFGF/GDF-5 hydrogels stimulate the healing of MCL injury in vivo. {yields} bFGF/GDF-5 hydrogels stimulate Col1a1 expression and type I collagen synthesis. {yields} Combined use of bFGF/GDF-5 enhances MCL healing. -- Abstract: Basic fibroblast growth factor (bFGF) and growth and differentiation factor (GDF)-5 stimulate the healing of medial collateral ligament (MCL) injury. However, the effect of isolated and combined use of bFGF/GDF-5 remains still unclear. We investigated cellular proliferation and migration responding to bFGF/GDF-5 using rabbit MCL fibroblasts. Rabbit MCL injury was treated by bFGF and/or GDF-5 with peptide hydrogels. Gene expression and deposition of collagens in healing tissues were evaluated. bFGF/GDF-5 treatment additively enhanced cell proliferation and migration. bFGF/GDF-5 hydrogels stimulated Col1a1 expression without increasing Col3a1 expression. Combined use of bFGF/GDF-5 stimulated type I collagen deposition and the reorganization of fiber alignment, and induced better morphology of fibroblasts in healing MCLs. Our study indicates that combined use of bFGF/GDF-5 might enhance MCL healing by increasing proliferation and migration of MCL fibroblasts, and by regulating collagen synthesis and connective fiber alignment.

  14. Dual delivery of BMP-2 and bFGF from a new nano-composite scaffold, loaded with vascular stents for large-size mandibular defect regeneration.

    PubMed

    Su, Jiansheng; Xu, Hongzhen; Sun, Jun; Gong, Xue; Zhao, Hang

    2013-01-01

    The aim of this study was to investigate the feasibility and advantages of the dual delivery of bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) from nano-composite scaffolds (PLGA/PCL/nHA) loaded with vascular stents (PLCL/Col/nHA) for large bone defect regeneration in rabbit mandibles. Thirty-six large bone defects were repaired in rabbits using engineering bone composed of allogeneic bone marrow mesenchymal stem cells (BMSCs), bFGF, BMP-2 and scaffolds composed of PLGA/PCL/nHA loaded with PLCL/Col/nHA. The experiments were divided into six groups: BMSCs/bFGF/BMP-2/scaffold, BMSCs/BMP-2/scaffold, BMSCs/bFGF/scaffold, BMSCs/scaffold, scaffold alone and no treatment. Sodium alginate hydrogel was used as the carrier for BMP-2 and bFGF and its features, including gelling, degradation and controlled release properties, was detected by the determination of gelation and degradation time coupled with a controlled release study of bovine serum albumin (BSA). AlamarBlue assay and alkaline phosphatase (ALP) activity were used to evaluate the proliferation and osteogenic differentiation of BMSCs in different groups. X-ray and histological examinations of the samples were performed after 4 and 12 weeks post-implantation to clarify new bone formation in the mandible defects. The results verified that the use of sodium alginate hydrogel as a controlled release carrier has good sustained release ability, and the combined application of bFGF and BMP-2 could significantly promote the proliferation and osteogenic differentiation of BMSCs (p < 0.05 or p < 0.01). In addition, X-ray and histological examinations of the samples exhibited that the dual release group had significantly higher bone formation than the other groups. The above results indicate that the delivery of both growth factors could enhance new bone formation and vascularization compared with delivery of BMP-2 or bFGF alone, and may supply a promising way of repairing large bone defects in

  15. Neurogenesis of Neural Crest Derived Periodontal Ligament Stem Cells by EGF and bFGF

    PubMed Central

    Fortino, Veronica R.; Chen, Ren-Shiang; Pelaez, Daniel; Cheung, Herman S.

    2013-01-01

    Neuroregenerative medicine is an ever-growing field in which regeneration of lost cells/tissues due to a neurodegenerative disease is the ultimate goal. With the scarcity of available replacement alternatives, stem cells provide an attractive source for regenerating neural tissue. While many stem cell sources exist, including: mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs), the limited cellular potency, technical difficulties, and ethical considerations associated with these make finding alternate sources a desirable goal. Periodontal ligament stem cells (PDLSCs) derived from the neural crest were induced into neural-like cells using a combination of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Morphological changes were evident in our treated group, seen under both light microscopy and scanning electron microscopy (SEM). A statistically significant increase in the expression of neuron-specific β-tubulin III and the neural stem/progenitor cell marker nestin, along with positive immunohistochemical staining for glial fibrillary acidic protein (GFAP), demonstrated the success of our treatment in inducing both neuronal and glial phenotypes. Positive staining for synaptophysin demonstrated neural connections and electrophysiological recordings indicated that when subjected to whole cell patch clamping, our treated cells displayed inward currents conducted through voltage-gated sodium (Na+) channels. Taken together, our results indicate the success of our treatment in inducing PDLSCs to neural-like cells. The ease of sourcing and expansion, their embryologic neural crest origin, and the lack of ethical implications in their use make PDLSCs an attractive source for use in neuroregenerative medicine. PMID:24105823

  16. A Novel In Vivo Model of Focal Light Emitting Diode-Induced Cone-Photoreceptor Phototoxicity: Neuroprotection Afforded by Brimonidine, BDNF, PEDF or bFGF

    PubMed Central

    García-Ayuso, Diego; Alarcón-Martínez, Luis; Jiménez-López, Manuel; Bernal-Garro, José Manuel; Nieto-López, Leticia; Nadal-Nicolás, Francisco Manuel; Villegas-Pérez, María Paz; Wheeler, Larry A.; Vidal-Sanz, Manuel

    2014-01-01

    We have investigated the effects of light-emitting diode (LED)-induced phototoxicity (LIP) on cone-photoreceptors and their protection with brimonidine (BMD), brain-derived neurotrophic factor (BDNF), pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF) or basic fibroblast growth factor (bFGF). In anesthetized, dark adapted, adult albino rats a blue (400 nm) LED was placed perpendicular to the cornea (10 sec, 200 lux) and the effects were investigated using Spectral Domain Optical Coherence Tomography (SD-OCT) and/or analysing the retina in oriented cross-sections or wholemounts immune-labelled for L- and S-opsin and counterstained with the nuclear stain DAPI. The effects of topical BMD (1%) or, intravitreally injected BDNF (5 µg), PEDF (2 µg), CNTF (0.4 µg) or bFGF (1 µg) after LIP were examined on wholemounts at 7 days. SD-OCT showed damage in a circular region of the superotemporal retina, whose diameter varied from 1,842.4±84.5 µm (at 24 hours) to 1,407.7±52.8 µm (at 7 days). This region had a progressive thickness diminution from 183.4±5 µm (at 12 h) to 114.6±6 µm (at 7 d). Oriented cross-sections showed within the light-damaged region of the retina massive loss of rods and cone-photoreceptors. Wholemounts documented a circular region containing lower numbers of L- and S-cones. Within a circular area (1 mm or 1.3 mm radius, respectively) in the left and in its corresponding region of the contralateral-fellow-retina, total L- or S-cones were 7,118±842 or 661±125 for the LED exposed retinas (n = 7) and 14,040±1,860 or 2,255±193 for the fellow retinas (n = 7), respectively. BMD, BDNF, PEDF and bFGF but not CNTF showed significant neuroprotective effects on L- or S-cones. We conclude that LIP results in rod and cone-photoreceptor loss, and is a reliable, quantifiable model to study cone-photoreceptor degeneration. Intravitreal BDNF, PEDF or bFGF, or topical BMD afford significant cone neuroprotection in this model

  17. Topical treatment with basic fibroblast growth factor promotes wound healing and barrier recovery induced by skin abrasion.

    PubMed

    Nakamizo, S; Egawa, G; Doi, H; Natsuaki, Y; Miyachi, Y; Kabashima, K

    2013-01-01

    It has been reported that basic fibroblast growth factor (bFGF) promotes the healing of skin ulceration by inducing fibroblast proliferation, yet the role of bFGF on epidermal barrier function, especially from the perspective of scratch-induced skin abrasion, remains unknown. To this end, we initially developed an epidermal abrasion mouse model induced by scratching with a stainless-steel wire brush, and examined the effects of bFGF on the wound healing induced by skin abrasion. This procedure induced a significant elevation of transepidermal water loss (TEWL) in a scratch-count-dependent manner. This elevated TEWL was significantly decreased following topical application of bFGF to the skin. In addition, bFGF increased the expression of Ki67 in keratinocytes following mechanical scratching. These results suggest that bFGF enhances keratinocyte proliferation, which, in turn, repairs the skin barrier disruption and wounds caused by scratching in mice. Consistently, bFGF stimulated proliferation of normal human epidermal keratinocytes (NHEK). Intriguingly, the effect of bFGF and other growth factors on NHEK proliferation was additive. However, high cell density diminished the effect of bFGF on NHEK proliferation. This particular result can be explained by our observation that FGF receptor mRNA expression in NHEK was low under conditions of high cell density. Our findings suggest that bFGF stimulates keratinocyte proliferation, especially in a lower cell density environment, to repair skin wound in accord with skin barrier recovery. PMID:23108135

  18. DIABETES MELLITUS COMO FACTOR DE RIESGO DE DEMENCIA EN LA POBLACIÓN ADULTA MAYOR MEXICANA

    PubMed Central

    Silvia, Mejía-Arango; Clemente, y Zúñiga-Gil

    2012-01-01

    Introduccion La diabetes mellitus y las demencias constituyen dos problemas crecientes de salud entre la población adulta mayor del mundo y en particular de los paises en desarrollo. Hacen falta estudios longitudinales sobre el papel de la diabetes como factor de riesgo para demencia. Objetivo Determinar el riesgo de demencia en sujetos Mexicanos con diabetes mellitus tipo 2. Materiales y Metodos Los sujetos diabéticos libres de demencia pertenecientes al Estudio Nacional de Salud y Envejecimiento en México fueron evaluados a los dos años de la línea de base. Se estudió el papel de los factores sociodemográficos, de otras comorbilidades y del tipo de tratamiento en la conversión a demencia. Resultados Durante la línea de base 749 sujetos (13.8%) tuvieron diabetes. El riesgo de desarrollar demencia en estos individuos fue el doble (RR, 2.08 IC 95%, 1.59–2.73). Se encontró un riesgo mayor en individuos de 80 años y más (RR 2.44 IC 95%, 1.46–4.08), en los hombres (RR, 2.25 IC 95%, 1.46–3.49) y en sujetos con nivel educativo menor de 7 años. El estar bajo tratamiento con insulina incrementó el riesgo de demencia (RR, 2.83, IC 95%, 1.58–5.06). Las otras comorbilidades que aumentaron el riesgo de demencia en los pacientes diabéticos fueron la hipertensión (RR, 2.75, IC 95%, 1.86–4.06) y la depresión (RR, 3.78, 95% IC 2.37–6.04). Conclusión Los sujetos con diabetes mellitus tienen un riesgo mayor de desarrollar demencia, La baja escolaridad y otras comorbilidades altamente prevalentes en la población Mexicana contribuyen a la asociación diabetes-demencia. PMID:21948010

  19. Co-delivery of VEGF and bFGF via a PLGA nanoparticle-modified BAM for effective contracture inhibition of regenerated bladder tissue in rabbits

    NASA Astrophysics Data System (ADS)

    Jiang, Xincheng; Lin, Houwei; Jiang, Dapeng; Xu, Guofeng; Fang, Xiaoliang; He, Lei; Xu, Maosheng; Tang, Bingqiang; Wang, Zhiyong; Cui, Daxiang; Chen, Fang; Geng, Hongquan

    2016-02-01

    Graft contracture is a common problem associated with the regeneration processes of tissue-engineered bladders. Currently, most strategies used for incorporating bioactive molecules into biomaterial designs do not work during all phases of tissue regeneration. In this study, we used a growth factor-PLGA nanoparticle thermo-sensitive gel system (i.e., BAM with incorporated VEGF and bFGF-loaded PLGA nanoparticles and mixed with a hydrophilic gel) to promote bladder tissue regeneration in a rabbit model. At 4 and 12 weeks after surgery, contracture rate assessment and histological examination were conducted to evaluate bladder tissue regeneration. The results indicated that the functional composite scaffold continuously and effectively released VEGF and bFGF and promoted bladder reconstruction with a significant decrease in graft contracture. In addition, the number and arrangement of regenerated urothelial cells and smooth muscle cells as well as microvascular density and maturity were improved in the VEGF/bFGF nanoparticle group compared with the single factor VEGF or bFGF nanoparticle group and BAM alone. The nanoparticle thermo-sensitive gel system, which exhibited favourable performance, may effectively inhibit graft contracture and promote bladder tissue regeneration in rabbits.

  20. Co-delivery of VEGF and bFGF via a PLGA nanoparticle-modified BAM for effective contracture inhibition of regenerated bladder tissue in rabbits

    PubMed Central

    Jiang, Xincheng; Lin, Houwei; Jiang, Dapeng; Xu, Guofeng; Fang, Xiaoliang; He, Lei; Xu, Maosheng; Tang, Bingqiang; Wang, Zhiyong; Cui, Daxiang; Chen, Fang; Geng, Hongquan

    2016-01-01

    Graft contracture is a common problem associated with the regeneration processes of tissue-engineered bladders. Currently, most strategies used for incorporating bioactive molecules into biomaterial designs do not work during all phases of tissue regeneration. In this study, we used a growth factor-PLGA nanoparticle thermo-sensitive gel system (i.e., BAM with incorporated VEGF and bFGF-loaded PLGA nanoparticles and mixed with a hydrophilic gel) to promote bladder tissue regeneration in a rabbit model. At 4 and 12 weeks after surgery, contracture rate assessment and histological examination were conducted to evaluate bladder tissue regeneration. The results indicated that the functional composite scaffold continuously and effectively released VEGF and bFGF and promoted bladder reconstruction with a significant decrease in graft contracture. In addition, the number and arrangement of regenerated urothelial cells and smooth muscle cells as well as microvascular density and maturity were improved in the VEGF/bFGF nanoparticle group compared with the single factor VEGF or bFGF nanoparticle group and BAM alone. The nanoparticle thermo-sensitive gel system, which exhibited favourable performance, may effectively inhibit graft contracture and promote bladder tissue regeneration in rabbits. PMID:26854200

  1. Clinical significance of joint detection of serum CEA, SCCA, and bFGF in the diagnosis of lung cancer

    PubMed Central

    Zhao, Wei; Yu, Haixiang; Han, Zhifeng; Gao, Nan; Xue, Jinru; Wang, Yan

    2015-01-01

    Lung cancer is a type of malignant tumor with highest morbidity and mortality. This study tested three tumor marker levels including CEA, SCCA, and bFGF to explore their value in lung cancer diagnosis and pathological type judgment. Venous blood was extracted from lung cancer patients, lung benign lesion patients and healthy control. Electrochemiluminescence immunoassay was applied to detect serum CEA and SCCA content. ELISA was used to test serum bFGF level. Serum CEA, SCCA, and bFGF levels and positive rates were significantly higher in lung cancer group than that of lung benign disease group and health control (P < 0.05). bFGF showed higher detection sensitivity than CEA in lung cancer (P < 0.05). Three joint detection sensitivity was higher than single test (P < 0.05), while its specificity was lower (P < 0.05), and the accuracy presented no significant difference. Serum CEA and SCCA levels and positive rates were obviously higher in non-small cell lung cancer patients when compared with small cell lung cancer patients (P < 0.05), while bFGF level was similar between small cell lung cancer and non-small cell lung cancer. bFGF showed higher detection rate than SCCA in small cell lung cancer (P < 0.05). Three joint detection exhibited higher positive rate in small cell lung cancer and non-small lung cancer than single test. Serum CEA, SCCA and bFGF joint detection improved detection sensitivity in lung cancer and had important reference value for pathological type deduction. PMID:26464712

  2. Effect of basic fibroblast growth factor in mouse embryonic stem cell culture and osteogenic differentiation.

    PubMed

    Rose, Laura C; Fitzsimmons, Ross; Lee, Poh; Krawetz, Roman; Rancourt, Derrick E; Uludağ, Hasan

    2013-05-01

    Embryonic stem cells are actively explored as a cell source in tissue engineering and regenerative medicine involving bone repair. Basic fibroblast growth factor (bFGF) has been a valuable growth factor to support the culture of human stem cells as well as their osteogenic differentiation, but the influence of bFGF on mouse embryonic stem (mES) cells is not known. Towards this goal, D3 cells were treated with bFGF during maintenance conditions and during spontaneous and osteogenic differentiation. In feeder-free monolayers, up to 40 ng/ml of exogenous bFGF did not support self-renewal of mES without LIF during cell expansion. During spontaneous differentiation in high-density cultures, bFGF stimulated cell proliferation under certain conditions but did not influence differentiation, as judged by stage-specific embryonic antigen-1 expression. The addition of bFGF reduced the alkaline phosphatase (ALP) activity associated with osteoblast activity during differentiation induced by osteogenic supplements, although the extent of mineralization was unaffected by bFGF. The bFGF increased the mesenchymal stem cell marker Sca-1 in an mES cell population and led to an enhanced increase in osteocalcin and runx2 expression in combination with BMP-2. These results suggest that bFGF could be utilized to expand the cell population in high-density cultures in addition to enriching the BMP-2 responsiveness of mES cells. PMID:22674886

  3. MicroRNA Expression Profile of Neural Progenitor-Like Cells Derived from Rat Bone Marrow Mesenchymal Stem Cells under the Influence of IGF-1, bFGF and EGF

    PubMed Central

    Huat, Tee Jong; Khan, Amir Ali; Abdullah, Jafri Malin; Idris, Fauziah Mohamad; Jaafar, Hasnan

    2015-01-01

    Insulin-like growth factor 1 (IGF-1) enhances cellular proliferation and reduces apoptosis during the early differentiation of bone marrow derived mesenchymal stem cells (BMSCs) into neural progenitor-like cells (NPCs) in the presence of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). BMSCs were differentiated in three groups of growth factors: (A) EGF + bFGF, (B) EGF + bFGF + IGF-1, and (C) without growth factor. To unravel the molecular mechanisms of the NPCs derivation, microarray analysis using GeneChip® miRNA arrays was performed. The profiles were compared among the groups. Annotated microRNA fingerprints (GSE60060) delineated 46 microRNAs temporally up-regulated or down-regulated compared to group C. The expressions of selected microRNAs were validated by real-time PCR. Among the 46 microRNAs, 30 were consistently expressed for minimum of two consecutive time intervals. In Group B, only miR-496 was up-regulated and 12 microRNAs, including the let-7 family, miR-1224, miR-125a-3p, miR-214, miR-22, miR-320, miR-708, and miR-93, were down-regulated. Bioinformatics analysis reveals that some of these microRNAs (miR-22, miR-214, miR-125a-3p, miR-320 and let-7 family) are associated with reduction of apoptosis. Here, we summarize the roles of key microRNAs associated with IGF-1 in the differentiation of BMSCs into NPCs. These findings may provide clues to further our understanding of the mechanisms and roles of microRNAs as key regulators of BMSC-derived NPC maintenance. PMID:25938966

  4. Heparin modulation of the neurotropic effects of acidic and basic fibroblast growth factors and nerve growth factor on PC12 cells

    SciTech Connect

    Neufeld, G.; Gospodarowicz, D.; Dodge, L.; Fujii, D.K.

    1987-04-01

    Nerve growth factor (NGF) and acidic or basic fibroblast growth factor (aFGF and bFGF, respectively) induce neurite outgrowth from the rat pheochromocytoma cell line, PC12. The neurites induced by these three factors are stable for up to a month in cell culture in the continued presence of any of the above growth factors. bFGF (ED50 = 30 pg/ml) is 800 fold more potent in stimulating neurite outgrowth than aFGF (ED50 = 25 ng/ml) and 260 fold more potent than NGF (ED50 = 8 ng/ml). While the neurotropic activities of aFGF and NGF are potentiated by heparin, that of bFGF is both partially inhibited or stimulated, depending upon the concentration of bFGF. Radioreceptor binding experiments show that aFGF and bFGF bind to a common binding site on the PC12 cell surface. Affinity labeling studies demonstrate a single receptor with an apparent molecular weight of 145,000 daltons, which corresponds to the high molecular weight receptor identified in BHK-21 cells. NGF does not appear to compete with aFGF or bFGF for binding to the receptor. Heparin blocked the binding of bFGF to the receptor but had only a small inhibitory effect on the binding of aFGF to the receptor. Thus, it appears that heparin inhibition of the neurotropic effects of bFGF occurs, at least in part, by impairing the interaction of bFGF with the receptor, while having little effect on that of aFGF. The stimulatory effects of heparin on the neurotropic activity of aFGF, bFGF, and NGF may occur through a site not associated with the respective cellular receptor for the growth factors.

  5. Basic fibroblast growth factor selectively amplifies the functional state of neurons producing neuropeptide Y but not somatostatin in cultures of fetal brain cells: evidence for a cooperative interaction with insulin-like growth factor-I.

    PubMed

    Barnea, A; Cho, G

    1993-10-01

    The role of basic fibroblast growth factor (bFGF) in regulating the functional state of neuropeptide Y (NPY) neurons in the brain was investigated, using aggregate cultures, derived from 17-day-old fetal rat cortex maintained for 16 days in serum-free medium, as a model. The criterion for the functional state was NPY production in response to a 24-h exposure to forskolin + phorbol 12-myristate 13-acetate (For + PMA). bFGF (0.1 nM) induced a approximately 2-fold increase in NPY production under basal conditions as well as after For + PMA (p < 0.001 vs control). To address the possibility that bFGF may interact with other growth factors, we assessed the effect of bFGF in the presence of long R3-insulin-like growth factor-I (l-IGF-I; 1 nM) and found that NPY production in response to For + PMA was even greater than with bFGF alone (2-fold; p < 0.001); even though l-IGF-I by itself was ineffective; suggesting that bFGF is the driving force of this amplification. To assess the selectivity of this process, we evaluated SRIF production in response to For + PMA and found that it was not amplified by bFGF, l-IGF-I, or bFGF + l-IGF-I. These results are consistent with bFGF selectively amplifying the functional state of the cAMP and protein kinase C (PKC) pathways leading to increased NPY-production, with cooperative interaction(s) between bFGF and IGF-I, and with a role for bFGF and IGF-I in the developmental expression/survival of the NPY neurons. PMID:8104779

  6. Stable Expression of Basic Fibroblast Growth Factor in Chloroplasts of Tobacco.

    PubMed

    Wang, Yun-Peng; Wei, Zheng-Yi; Zhong, Xiao-Fang; Lin, Chun-Jing; Cai, Yu-Hong; Ma, Jian; Zhang, Yu-Ying; Liu, Yan-Zhi; Xing, Shao-Chen

    2016-01-01

    Basic fibroblast growth factor (bFGF) is a multifunctional factor in acceleration of cell proliferation, differentiation and transference, and therefore widely used in clinical applications. In this study, expression vector pWX-Nt03 harboring a codon-optimized bFGF gene was constructed and introduced into the tobacco chloroplasts by particle bombardment. After four rounds of selection, bFGF was proved to integrate into the chloroplast genome of regenerated plants and two of four transgenic plants were confirmed to be homoplastomic by PCR and Southern hybridization. ELISA assay indicated that bFGF represented approximately 0.1% of total soluble protein in the leaves of transplastomic tobacco plants. This is the first report of bFGF expression via chloroplast transformation in model plant, providing an additional option for the production of chloroplast-produced therapeutic proteins. PMID:26703590

  7. Stable Expression of Basic Fibroblast Growth Factor in Chloroplasts of Tobacco

    PubMed Central

    Wang, Yun-Peng; Wei, Zheng-Yi; Zhong, Xiao-Fang; Lin, Chun-Jing; Cai, Yu-Hong; Ma, Jian; Zhang, Yu-Ying; Liu, Yan-Zhi; Xing, Shao-Chen

    2015-01-01

    Basic fibroblast growth factor (bFGF) is a multifunctional factor in acceleration of cell proliferation, differentiation and transference, and therefore widely used in clinical applications. In this study, expression vector pWX-Nt03 harboring a codon-optimized bFGF gene was constructed and introduced into the tobacco chloroplasts by particle bombardment. After four rounds of selection, bFGF was proved to integrate into the chloroplast genome of regenerated plants and two of four transgenic plants were confirmed to be homoplastomic by PCR and Southern hybridization. ELISA assay indicated that bFGF represented approximately 0.1% of total soluble protein in the leaves of transplastomic tobacco plants. This is the first report of bFGF expression via chloroplast transformation in model plant, providing an additional option for the production of chloroplast-produced therapeutic proteins. PMID:26703590

  8. Human mast cell basic fibroblast growth factor in pulmonary fibrotic disorders.

    PubMed Central

    Inoue, Y.; King, T. E.; Tinkle, S. S.; Dockstader, K.; Newman, L. S.

    1996-01-01

    Mast cells (MCs) are abundant in fibrotic tissue, although their role in fibrogenesis remains obscure. Recent studies suggest MCs may produce basic fibroblast growth factor (bFGF). To evaluate the hypothesis that MC bFGF contributes to the fibrotic response in human interstitial lung disease, we studied lung tissue, bronchoalveolar lavage fluid and serum in 1) idiopathic pulmonary fibrosis, 2) chronic beryllium disease and sarcoidosis, 3) control subjects with no disease or who were beryllium sensitized with normal lung histology. Diseased subjects underwent clinical assessments to stage disease severity. We determined that most bFGF+ cells in lung interstitium are MCs and are most abundant in idiopathic pulmonary fibrosis. Distribution of bFGF+ MCs matched that of extracellular matrix deposition and correlated with the extent of fibrosis morphometrically. Only one bFGF isoform (17.8 kd) was found in idiopathic pulmonary fibrosis and chronic beryllium disease lung tissues and interacted with heparin-like molecules in the lung. Using a human MC line, we verified that MCs express bFGF mRNA and protein that localizes to cytoplasmic granules. Clinically, bFGF concentrations in bronchoalveolar lavage fluid and serum were highest in disease states and correlated with bronchoalveolar lavage cellularity and severity of gas exchange abnormalities, supporting a role for MC bFGF in the pulmonary fibrotic response and its clinical consequence. Images Figure 1 Figure 2 Figure 7 Figure 10 Figure 11 Figure 12 PMID:8952537

  9. Basic Fibroblast Growth Factor Regulates Persistent ERK Osciliations in Premaligant but not Malignant JB6 Cells

    SciTech Connect

    Weber, Thomas J.; Shankaran, Harish; Wiley, H. S.; Opresko, Lee K.; Chrisler, William B.; Quesenberry, Ryan D.

    2010-05-02

    basic fibroblast growth factor (bFGF or FGF2) plays an important role in epidermal wound healing in vivo and is associated with a persistent increased in the extracellular signal-regulated kinase (ERK) pathway in vitro. Here we have examined whether bFGF induces the closure of an experimental scratch wound in JB6 mouse epidermal cells and have explored the regulation of the ERK pathway by bFGF in the context of kinase oscillations. bFGF stimulation is associated with increases in cellular phospho-ERK and phospho-c-Jun levels. In addition, bFGF increases cell proliferation and a change in cell morphology (stellate appearance) in a dose-dependent fashion (0.1 – 100 ng/ml). bFGF treatment also promoted the closure of an experimental scratch wound in vitro. JB6 cells were stably transfected with an ERK1-GFP chimera to follow temporal ERK subcellular distribution patterns. We observe a persistent upregulation of the ERK pathway, as evidenced by a significant increase in nuclear ERK1-GFP levels at time points up to 24 hr after bFGF treatment. Interestingly, at the single cell level, ERK is observed to oscillate between nuclear and cytosolic compartments in response to bFGF treatment. Because this oscillatory behavior is asynchronous in the cell population, it is only clearly resolved at the single cell level. Collectively, data presented here are consistent with an important role for bFGF in wound healing and suggest a more complex regulation of the ERK pathway by bFGF than has previously been appreciated.

  10. In situ detection of basic fibroblast growth factor by highly specific antibodies.

    PubMed Central

    Schulze-Osthoff, K.; Risau, W.; Vollmer, E.; Sorg, C.

    1990-01-01

    Basic fibroblast growth factor (bFGF) is thought to be of major importance for fibrosis and angiogenesis. Despite intensive studies dealing with the biochemistry and multiple biologic effects of bFGF, the cellular distribution is virtually unknown. Therefore, using the indirect immunoperoxidase technique, we examined the effect of bFGF on a large pattern of normal, inflammatory, and tumorous human tissues. Staining was performed on cryostat sections with a highly specific affinity-purified antiserum. In normal tissues, especially those of the thymus and placenta, mainly dendritic cells contained the growth factor. High levels of bFGF were also detected in basal cells and gland epithelial cells of skin biopsies. A conspicuous expression was observed in chronic inflammatory tissues corresponding to a generally pronounced proliferation of fibroblasts and endothelial cells in these situations. Tumors revealed a very heterogenous staining pattern. In some lesions, bFGF was predominantly present in infiltrating and endothelial cells. In several, neoplasms tumor cells exhibited an intensive staining. In some, especially vascular tumors, bFGF could not be detected. From the staining results it is concluded that angiogenesis is not simply controlled by the presence of bFGF but is mediated by a balance of several angiogenic inducers and inhibitors. Images Figure 1 Figure 2 PMID:1695484

  11. Shear stress-induced release of basic fibroblast growth factor from endothelial cells is mediated by matrix interaction via integrin alpha(v)beta3.

    PubMed

    Gloe, Torsten; Sohn, Hae Young; Meininger, Gerald A; Pohl, Ulrich

    2002-06-28

    Considering that chronic elevation of shear stress results in remodeling of the vasculature, we analyzed whether mechanical load could mediate basic fibroblast growth factor (bFGF) release and whether bFGF would act as mediator of shear stress-induced endothelial proliferation and differentiation. Supernatant media of shear stress-exposed endothelial cells (EC) contained significantly higher amounts of bFGF than medium from static cells. Released bFGF was fully intact with regard to its function as an inductor of proliferation and differentiation. Shear stress-conditioned media induced capillary-like structure formation, whereas static control medium did not. Likewise, only shear stress-conditioned medium induced proliferation of serum starved EC. Both capillary-like structure formation and proliferation could be inhibited by neutralization of bFGF or its receptor. The release of bFGF was subject to specific, integrin-mediated control, since inhibition of alpha(v)beta(3) integrin prevented it, whereas inhibition of alpha(5)beta(1) integrin had no effect. We conclude that shear stress induces the release of bFGF from EC in a tightly controlled manner. The release is dependent on specific cell-matrix interactions via alpha(v)beta(3) integrins. The effects on cell proliferation and differentiation suggest that release of bFGF is functionally significant and may represent a necessary initial step in adaptive remodeling processes induced by shear stress. PMID:11976347

  12. A novel chemical-defined medium with bFGF and N2B27 supplements supports undifferentiated growth in human embryonic stem cells

    SciTech Connect

    Liu Yanxia; Song Zhihua; Zhao Yang; Qin Han; Cai Jun; Zhang Hong; Yu Tianxin; Jiang Siming; Wang Guangwen; Ding Mingxiao; Deng Hongkui . E-mail: hongkui_deng@pku.edu.cn

    2006-07-21

    Traditionally, undifferentiated human embryonic stem cells (hESCs) are maintained on mouse embryonic fibroblast (MEF) cells or on matrigel with an MEF-conditioned medium (CM), which hampers the clinical applications of hESCs due to the contamination by animal pathogens. Here we report a novel chemical-defined medium using DMEM/F12 supplemented with N2, B27, and basic fibroblast growth factor (bFGF) [termed NBF]. This medium can support prolonged self-renewal of hESCs. hESCs cultured in NBF maintain an undifferentiated state and normal karyotype, are able to form embryoid bodies in vitro, and differentiate into three germ layers and extraembryonic cells. Furthermore, we find that hESCs cultured in NBF possess a low apoptosis rate and a high proliferation rate compared with those cultured in MEF-CM. Our findings provide a novel, simplified chemical-defined culture medium suitable for further therapeutic applications and developmental studies of hESCs.

  13. Basic Fibroblast Growth Factor Ameliorates Endothelial Dysfunction in Radiation-Induced Bladder Injury

    PubMed Central

    Zhang, Shiwei; Qiu, Xuefeng; Zhang, Yanting; Fu, Kai; Zhao, Xiaozhi; Wu, Jinhui; Hu, Yiqiao; Zhu, Weiming; Guo, Hongqian

    2015-01-01

    This study was designed to explore the effect of basic fibroblast growth factor (bFGF) on radiation-induced endothelial dysfunction and histological changes in the urinary bladder. bFGF was administrated to human umbilical vein cells (HUVEC) or urinary bladder immediately after radiation. Reduced expression of thrombomodulin (TM) was indicated in the HUVEC and urinary bladder after treatment with radiation. Decreased apoptosis was observed in HUVEC treated with bFGF. Administration of bFGF increased the expression of TM in HUVEC medium, as well as in the urinary bladder at the early and delayed phases of radiation-induced bladder injury (RIBI). At the early phase, injection of bFGF increased the thickness of urothelium and reduced inflammation within the urinary bladder. At the delayed phase, bFGF was effective in reducing fibrosis within the urinary bladder. Our results indicate that endothelial dysfunction is a prominent feature of RIBI. Administration of bFGF can ameliorate radiation-induced endothelial dysfunction in urinary bladder and preserve bladder histology at early and delayed phases of RIBI. PMID:26351640

  14. Fibroblast growth factor is an inhibitor of chondrocyte terminal differentiation

    SciTech Connect

    Kato, Y.; Iwamoto, M. )

    1990-04-05

    The effects of basic fibroblast growth factor (bFGF) on terminal differentiation of chondrocytes and cartilage-matrix calcification were investigated. Rabbit growth-plate chondrocytes maintained as a pelleted mass in a centrifuge tube produced an abundant proteoglycan matrix during the matrix-maturation stage, yielding a cartilage-like tissue. Thereafter, they terminally differentiated to hypertrophic chondrocytes which produced high levels of alkaline phosphatase. These cells induced extensive calcification of the matrix in the absence of additional phosphate. Addition of bFGF to the chondrocyte cultures abolished the increases in alkaline phosphatase activity, {sup 45}Ca deposition, and the calcium content. These effects were dose-dependent, reversible, and observed in the presence of cytosine arabinoside, an inhibitor of DNA synthesis. The inhibitory effects could be observed only when chondrocytes were exposed to bFGF in a transition period between the matrix-maturation and hypertrophic stages. As chondrocytes differentiated to hypertrophic cells, bFGF became less effective in inhibiting the expression of the mineralization-related phenotypes. The present study also shows that although the rate of ({sup 35}S)sulfate incorporation into large, chondroitin sulfate proteoglycan in the cell-matrix fraction is very high during the matrix-maturation stage, it abruptly decreases by 90% after terminal differentiation. Furthermore, the terminal differentiation-associated decrease in proteoglycan synthesis was delayed by bFGF. These results provide evidence that bFGF inhibits terminal differentiation of chondrocytes and calcification.

  15. Combination of basic fibroblast growth factor and epidermal growth factor enhances proliferation and neuronal/glial differential of postnatal human enteric neurosphere cells in vitro.

    PubMed

    Pan, Wei-Kang; Yu, Hui; Wu, A-Li; Gao, Ya; Zheng, Bai-Jun; Li, Peng; Yang, Wei-Li; Huang, Qiang; Wang, Huai-Jie; Ge, Xin

    2016-08-01

    Human enteric neural stem cells (hENSCs) proliferate and differentiate into neurons and glial cells in response to a complex network of neurotrophic factors to form the enteric nervous system. The primary aim of this study was to determine the effect of basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) on in-vitro expansion and differentiation of postnatal hENSCs-containing enteric neurosphere cells. Enteric neurosphere cells were isolated from rectal polyp specimens of 75 children (age, 1-13 years) and conditioned with bFGF, EGF, bFGF+EGF, or plain culture media. Proliferation of enteric neurosphere cells was examined using the methyl thiazolyl tetrazolium colorimetric assay over 7 days of culture. Fetal bovine serum (10%) was added to induce the differentiation of parental enteric neurosphere cells, and differentiated offspring cells were immunophenotyped against p75 neutrophin receptor (neural stem cells), peripherin (neuronal cells), and glial fibrillary acidic protein (glial cells). Combining bFGF and EGF significantly improved the proliferation of enteric neurosphere cells compared with bFGF or EGF alone (both P<0.01) throughout 7 days of culture. The addition of bFGF drove a significantly greater proportion of enteric neurosphere cells to differentiate into neuronal cells than that of EGF (P<0.01), whereas addition of EGF resulted in significantly more glial differentiation compared with addition of bFGF (P<0.01). Combining bFGF and EGF drove enteric neurosphere cells to differentiate into neuronal cells in a proportion similar to glial cells. Our results showed that the combination of bFGF and EGF significantly enhanced the proliferation and differentiation of postnatal hENSCs-containing enteric neurosphere cells in vitro. PMID:27306591

  16. Comparative Study of Heparin-Poloxamer Hydrogel Modified bFGF and aFGF for in Vivo Wound Healing Efficiency.

    PubMed

    Wu, Jiang; Zhu, Jingjing; He, Chaochao; Xiao, Zecong; Ye, Jingjing; Li, Yi; Chen, Anqi; Zhang, Hongyu; Li, Xiaokun; Lin, Li; Zhao, Yingzheng; Zheng, Jie; Xiao, Jian

    2016-07-27

    Wound therapy remains a clinical challenge. Incorporation of growth factors (GFs) into heparin-functionalized polymer hydrogel is considered as a promising strategy to improve wound healing efficiency. However, different GFs incorporation into the same heparin-based hydrogels often lead to different wound healing effects, and the underlying GF-induced wound healing mechanisms still remain elusive. Herein, we developed a thermos-sensitive heparin-poloxamer (HP) hydrogel to load and deliver different GFs (aFGF and bFGF) for wound healing in vivo. The resulting GFs-based hydrogels with and without HP hydrogels were systematically evaluated and compared for their wound healing efficiency by extensive in vivo tests, including wound closure rate, granulation formation, re-epithelization, cell proliferation, collagen, and angiogenesis expressions. While all GFs-based dressings with and without HP hydrogels exhibited better wound healing efficacy than controls, both HP-aFGF and HP-bFGF hydrogels demonstrated their superior healing activity to improve wound closure, granulation formation, re-epithelization, and blood vessel density by up-regulation of PCNA proliferation and collagen synthesis, as compared to GF dressings alone. More importantly, HP-aFGF dressings exhibited the higher healing efficacy than HP-bFGF dressings, indicating that different a/bFGF surface properties lead to different binding and release behaviors in HP hydrogels, both of which will affect different wound healing efficiency. On the basis of experimental observations, the working mechanisms of different healing effects of HP-GFs on full skin removal wound were proposed. This work provides different views of the design and development of an effective hydrogel-based delivery system for GFs toward rapid wound healing. PMID:27384134

  17. A heparin-mimicking polymer conjugate stabilizes basic fibroblast growth factor

    NASA Astrophysics Data System (ADS)

    Nguyen, Thi H.; Kim, Sung-Hye; Decker, Caitlin G.; Wong, Darice Y.; Loo, Joseph A.; Maynard, Heather D.

    2013-03-01

    Basic fibroblast growth factor (bFGF) is a protein that plays a crucial role in diverse cellular functions, from wound healing to bone regeneration. However, a major obstacle to the widespread application of bFGF is its inherent instability during storage and delivery. Here, we describe the stabilization of bFGF by covalent conjugation with a heparin-mimicking polymer, a copolymer consisting of styrene sulfonate units and methyl methacrylate units bearing poly(ethylene glycol) side chains. The bFGF conjugate of this polymer retained bioactivity after synthesis and was stable to a variety of environmentally and therapeutically relevant stressors—such as heat, mild and harsh acidic conditions, storage and proteolytic degradation—unlike native bFGF. Following the application of stress, the conjugate was also significantly more active than the control conjugate system in which the styrene sulfonate units were omitted from the polymer structure. This research has important implications for the clinical use of bFGF and for the stabilization of heparin-binding growth factors in general.

  18. Differentiation of central nervous system neuronal cells by fibroblast-derived growth factor requires at least two signaling pathways: roles for Ras and Src.

    PubMed Central

    Kuo, W L; Chung, K C; Rosner, M R

    1997-01-01

    To evaluate the role of mitogen-activated protein (MAP) kinase and other signaling pathways in neuronal cell differentiation by basic fibroblast-derived growth factor (bFGF), we used a conditionally immortalized cell line from rat hippocampal neurons (H19-7). Previous studies have shown that activation of MAP kinase kinase (MEK) is insufficient to induce neuronal differentiation of H19-7 cells. To test the requirement for MEK and MAP kinase (ERK1 and ERK2), H19-7 cells were treated with the MEK inhibitor PD098059. Although the MEK inhibitor blocked the induction of differentiation by constitutively activated Raf, the H19-7 cells still underwent differentiation by bFGF. These results suggest that an alternative pathway is utilized by bFGF for differentiation of the hippocampal neuronal cells. Expression in the H19-7 cells of a dominant-negative Ras (N17-Ras) or Raf (C4-Raf) blocked differentiation by bFGF, suggesting that Ras and probably Raf are required. Expression of dominant-negative Src (pcSrc295Arg) or microinjection of an anti-Src antibody blocked differentiation by bFGF in H19-7 cells, indicating that bFGF also signals through a Src kinase-mediated pathway. Although neither constitutively activated MEK (MEK-2E) nor v-Src was sufficient individually to differentiate the H19-7 cells, coexpression of constitutively activated MEK and v-Src induced neurite outgrowth. These results suggest that (i) activation of MAP kinase (ERK1 and ERK2) is neither necessary nor sufficient for differentiation by bFGF; (ii) activation of Src kinases is necessary but not sufficient for differentiation by bFGF; and (iii) differentiation of H19-7 neuronal cells by bFGF requires at least two signaling pathways activated by Ras and Src. PMID:9234720

  19. Histological Effect of Basic Fibroblast Growth Factor on Chronic Vocal Fold Scarring in a Rat Model

    PubMed Central

    Tateya, Ichiro; Tateya, Tomoko; Sohn, Jin-Ho; Bless, Diane M.

    2016-01-01

    Objectives Vocal fold scarring is one of the most challenging laryngeal disorders to treat and there are currently no consistently effective treatments available. Our previous studies have shown the therapeutic potential of basic fibroblast growth factor (bFGF) for vocal fold scarring. However, the histological effects of bFGF on scarred vocal fold have not been elucidated. The aim of this study was to examine the histological effects of bFGF on chronic vocal fold scarring. Methods Sprague-Dawley rats were divided into phosphate buffered saline (sham) and bFGF groups. Unilateral vocal fold stripping was performed and the drug was injected into the scarred vocal fold for each group 2 months postoperatively. Injections were performed weekly for 4 weeks. Two months after the last injection, larynges were harvested and histologically analyzed. Results A significant increase of hyaluronic acid was observed in the vocal fold of the bFGF group compared with that of the sham group. However, there was no remarkable change in collagen expression nor in vocal fold contraction. Conclusion Significant increase of hyaluronic acid by local bFGF injection was thought to contribute to the therapeutic effects on chronic vocal fold scarring. PMID:26976028

  20. Short-term administration of basic fibroblast growth factor enhances coronary collateral development without exacerbating atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic rabbits with acute myocardial infarction.

    PubMed

    Zhang, Chunxiang; Yang, Jian; Feng, Jianzhang; Jennings, Lisa K

    2002-08-01

    We evaluated the effect of basic fibroblast growth factor (bFGF) on the extent of atherosclerosis and balloon injury-induced vasoproliferation in atherosclerotic animals with acute myocardial infarction (AMI). Fifty-six rabbits were fed a 1% cholesterol diet. Balloon injury of iliac arteries and experimental acute myocardial infarction were induced in the same animals. Rabbits were then randomized to a bFGF group (20 pg/day, intravenously) or a control group (intravenous saline solution). The beneficial effects of bFGF on cardiac function, infarct size, and collateral vessel development, and the possible effect on vasoproliferation of balloon-injured vessels, were measured after 1 and 2 weeks. The extent of atherosclerosis was measured after 1, 2, and 4 weeks. Our results showed that bFGF significantly reduced infarct size and increased collateral-vessel density (P <.01) in infarct areas. Cardiac function was better in the bFGF group than in corresponding controls (P <.05). Similar beneficial effects of bFGF were noted in animals after 1- and 2-week treatments. However, the extent of atherosclerosis and the vasoproliferation in chronic atherosclerotic vessels induced by balloon injury and cholesterol diet were not significantly different between the two groups. Our results suggest that short-term treatment with bFGF enhances collateral development and produces maximum therapeutic benefits without exacerbating atherosclerosis and cell proliferation in stenotic vessels after AMI in atherosclerotic rabbits. PMID:12228768

  1. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca)

    PubMed Central

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W.; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro. PMID:26375397

  2. Basic Fibroblast Growth Factor Stimulates the Proliferation of Bone Marrow Mesenchymal Stem Cells in Giant Panda (Ailuropoda melanoleuca).

    PubMed

    Wang, Jun-Jie; Liu, Yu-Liang; Sun, Yuan-Chao; Ge, Wei; Wang, Yong-Yong; Dyce, Paul W; Hou, Rong; Shen, Wei

    2015-01-01

    It has been widely known that the giant panda (Ailuropoda melanoleuca) is one of the most endangered species in the world. An optimized platform for maintaining the proliferation of giant panda mesenchymal stem cells (MSCs) is very necessary for current giant panda protection strategies. Basic fibroblast growth factor (bFGF), a member of the FGF family, is widely considered as a growth factor and differentiation inducer within the stem cell research field. However, the role of bFGF on promoting the proliferation of MSCs derived from giant panda bone marrow (BM) has not been reported. In this study, we aimed to investigate the role of bFGF on the proliferation of BM-MSCs derived from giant panda. MSCs were cultured for cell proliferation analysis at 24, 48 and 72 hrs following the addition of bFGF. With increasing concentrations of bFGF, cell numbers gradually increased. This was further demonstrated by performing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) cell proliferation assay, 5-Bromo-2-deoxyUridine (BrdU) labeling and cell cycle testing. Furthermore, the percentage of MSCs that were OCT4 positive increased slightly following treatment with 5 ng/ml bFGF. Moreover, we demonstrated that the extracellular signal-regulated kinase (ERK) signaling pathway may play an important role in the proliferation of panda MSCs stimulated by bFGF. In conclusion, this study suggests that giant panda BM-MSCs have a high proliferative capacity with the addition of 5 ng/ml bFGF in vitro. PMID:26375397

  3. Basic fibroblast growth factor is pro-adipogenic in rat skeletal muscle progenitor clone, 2G11 cells.

    PubMed

    Nakano, Shin-ichi; Nakamura, Katsuyuki; Teramoto, Naomi; Yamanouchi, Keitaro; Nishihara, Masugi

    2016-01-01

    Intramuscular adipose tissue (IMAT) formation is a hallmark of marbling in cattle. IMAT is considered to originate from skeletal muscle progenitor cells with adipogenic potential. However, the mechanism involved in IMAT formation from these progenitor cells in vivo remains unclear. In the present study, among the growth factors tested, which were known to be expressed in skeletal muscle, we found only basic fibroblast growth factor (bFGF) has a pro-adipogenic effect on skeletal muscle derived adipogenic progenitor clone, 2G11 cells. Pre-exposure of 2G11 cells to bFGF did not affect initial gene expressions of CCAAT/enhancer-binding protein (C/EBP)β and C/EBPδ, while resulting in an enhancement of subsequent expressions of C/EBPα and proliferator-activated receptor gamma (PPARγ) during adipogenesis, indicating that bFGF is acting on the transcriptional regulation of C/EBPα and PPARγ. In addition, the effect of bFGF is mediated via two types of FGF receptor (FGFR) isoforms: FGFR1 and FGFR2 IIIc, and both receptors are prerequisite for bFGF to express its pro-adipogenic effect. These results suggest that bFGF plays an important role as a key trigger of IMAT formation in vivo. PMID:26154243

  4. Incorporation of basic fibroblast growth factor by a layer-by-layer assembly technique to produce bioactive substrates.

    PubMed

    Ma, Lie; Zhou, Jie; Gao, Changyou; Shen, Jiacong

    2007-10-01

    Basic fibroblast growth factor (bFGF) was immobilized onto quartz slides and collagen films by assembly with chondroitin sulfate (CS) in a layer-by-layer (LBL) manner. First, the LBL-deposition process on the amino-silanized quartz slides was monitored by UV-vis spectroscopy and water contact angle measurement. By substituting the normal bFGF with rhodamine-labeled one (Rd-bFGF), a linear increase of the absorbance versus bilayer number was recorded. The water contact angle oscillated between the odd CS and the even bFGF layers, demonstrating the alternating change of the surface chemistry. Scanning force microscopy (SFM) revealed that the surface topography was altered slightly after multilayer assembly. In vitro incubation of the CS/bFGF multilayers in PBS showed that approximately 30% of the incorporated bFGF was released within 8 days. In vitro cell culture found that the fibroblasts showed star-like morphology with plenty of pseudopods on the bFGF-incorporated collagen film after cultured for 1 day, and the collagen films assembled with bFGF possess improved bioactivity than that of the virgin one and the bFGF control. Since the immobilized growth factors can maximally retain their bioactivity, the LBL assembly would be a potential approach to construct a bioactive substrate for biomedical applications. PMID:17385225

  5. The effect of basic fibroblast growth factor on regeneration in a surgical wound model of rat submandibular glands.

    PubMed

    Kobayashi, Fumitaka; Matsuzaka, Kenichi; Inoue, Takashi

    2016-03-01

    This study developed an animal model of surgically wounded submandibular glands (SMGs) and investigated the effects of collagen gel with basic fibroblast growth factor (bFGF) on tissue regeneration of surgically wounded SMGs in vivo. The animal model was produced by creating a surgical wound using a 3-mm diameter biopsy punch in SMGs. The wound was filled with collagen gel with bFGF (bFGF group) or without bFGF (control group). In the animal model of surgically wounded SMGs, salivary glands without scar tissue around the wound area were observed with smaller areas of collagen gel. Small round and spindle-shape cells invaded the collagen gel in both groups after operation day (AOD) 5, and this invasion dramatically increased at AOD 7. Host tissue completely replaced the collagen gel at AOD 21. The invading immune cells in the group treated with collagen gel with bFGF were positive for vimentin, α-smooth muscle actin (αSMA), CD49f, c-kit and AQP5 at AOD 7. Similarly, the mRNA expression of vimentin, αSMA, CD49f, keratin19 and AQP5 was also increased. This study suggests that the use of collagen gels with bFGF improves salivary gland regeneration. PMID:27025261

  6. The effect of basic fibroblast growth factor on regeneration in a surgical wound model of rat submandibular glands

    PubMed Central

    Kobayashi, Fumitaka; Matsuzaka, Kenichi; Inoue, Takashi

    2016-01-01

    This study developed an animal model of surgically wounded submandibular glands (SMGs) and investigated the effects of collagen gel with basic fibroblast growth factor (bFGF) on tissue regeneration of surgically wounded SMGs in vivo. The animal model was produced by creating a surgical wound using a 3-mm diameter biopsy punch in SMGs. The wound was filled with collagen gel with bFGF (bFGF group) or without bFGF (control group). In the animal model of surgically wounded SMGs, salivary glands without scar tissue around the wound area were observed with smaller areas of collagen gel. Small round and spindle-shape cells invaded the collagen gel in both groups after operation day (AOD) 5, and this invasion dramatically increased at AOD 7. Host tissue completely replaced the collagen gel at AOD 21. The invading immune cells in the group treated with collagen gel with bFGF were positive for vimentin, α-smooth muscle actin (αSMA), CD49f, c-kit and AQP5 at AOD 7. Similarly, the mRNA expression of vimentin, αSMA, CD49f, keratin19 and AQP5 was also increased. This study suggests that the use of collagen gels with bFGF improves salivary gland regeneration. PMID:27025261

  7. Cross talk among tyrosine kinase receptors in PC12 cells: desensitization of mitogenic epidermal growth factor receptors by the neurotrophic factors, nerve growth factor and basic fibroblast growth factor.

    PubMed Central

    Mothe, I; Ballotti, R; Tartare, S; Kowalski-Chauvel, A; Van Obberghen, E

    1993-01-01

    We have studied the effects of nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) on epidermal growth factor (EGF) binding to PC12 cells. We show that NGF and bFGF rapidly induce a reduction in 125I-EGF binding to PC12 cells in a dose-dependent manner. This decrease amounts to 50% for NGF and 35% for bFGF. Both factors appear to act through a protein kinase C(PKC)-independent pathway, because their effect persists in PKC-downregulated PC12 cells. Scatchard analysis indicates that NGF and bFGF decrease the number of high affinity EGF binding sites. In addition to their effect on EGF binding, NGF and bFGF activate in intact PC12 cells one or several serine/threonine kinases leading to EGF receptor threonine phosphorylation. Using an in vitro phosphorylation system, we show that NGF- or bFGF-activated extracellular regulated kinase 1 (ERK1) is able to phosphorylate a kinase-deficient EGF receptor. Phosphoamino acid analysis indicates that this phosphorylation occurs mainly on threonine residues. Furthermore, two comparable phosphopeptides are observed in the EGF receptor, phosphorylated either in vivo after NGF treatment or in a cell-free system by NGF-activated ERK1. Finally, a good correlation was found between the time courses of ERK1 activation and 125I-EGF binding inhibition after NGF or bFGF treatment. In conclusion, in PC12 cells the NGF- and bFGF-stimulated ERK1 appears to be involved in the induction of the threonine phosphorylation of the EGF receptor and the decrease in the number of high affinity EGF binding sites. Images PMID:8400459

  8. Neurogenesis of neural crest-derived periodontal ligament stem cells by EGF and bFGF.

    PubMed

    Fortino, Veronica R; Chen, Ren-Shiang; Pelaez, Daniel; Cheung, Herman S

    2014-04-01

    Neuroregenerative medicine is an ever-growing field in which regeneration of lost cells/tissues due to a neurodegenerative disease is the ultimate goal. With the scarcity of available replacement alternatives, stem cells provide an attractive source for regenerating neural tissue. While many stem cell sources exist, including: mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells, the limited cellular potency, technical difficulties, and ethical considerations associated with these make finding alternate sources a desirable goal. Periodontal ligament stem cells (PDLSCs) derived from the neural crest were induced into neural-like cells using a combination of epidermal growth factor, and basic fibroblast growth factor. Morphological changes were evident in our treated group, seen under both light microscopy and scanning electron microscopy. A statistically significant increase in the expression of neuron-specific β-tubulin III and the neural stem/progenitor cell marker nestin, along with positive immunohistochemical staining for glial fibrillary acidic protein, demonstrated the success of our treatment in inducing both neuronal and glial phenotypes. Positive staining for synaptophysin demonstrated neural connections and electrophysiological recordings indicated that when subjected to whole-cell patch clamping, our treated cells displayed inward currents conducted through voltage-gated sodium (Na(+) ) channels. Taken together, our results indicate the success of our treatment in inducing PDLSCs to neural-like cells. The ease of sourcing and expansion, their embryologic neural crest origin, and the lack of ethical implications in their use make PDLSCs an attractive source for use in neuroregenerative medicine. PMID:24105823

  9. Basic fibroblast growth factor: its role in the control of smooth muscle cell migration.

    PubMed Central

    Jackson, C. L.; Reidy, M. A.

    1993-01-01

    The formation of an intimal lesion in an injured artery is the consequence of the replication and migration of smooth muscle cells. Recent studies have implicated basic fibroblast growth factor (bFGF) as an important mediator of replication in the arterial media, and platelet-derived growth factor as an important mediator of migration. However, the degree of arterial trauma produced during injury has a significant influence on the time of onset of intimal thickening, suggesting that factors released from damaged smooth muscle cells may affect migration. We have investigated the role of one of these factors, bFGF, in smooth muscle cell migration in vivo. We found that 1) deendothelialization of the rat carotid artery results in significantly more migration when it is accompanied by traumatic injury to the underlying smooth muscle; 2) the rate of migration in arteries that have been gently deendothelialized is significantly stimulated by systemic injection of bFGF; and 3) inhibition of bFGF with a blocking antibody significantly reduces the amount of migration after traumatic deendothelializing injury with a balloon catheter. These findings suggest that bFGF plays an important role in the mediation of smooth muscle cell migration after arterial injury. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:8213998

  10. Using basic fibroblast growth factor nanoliposome combined with ultrasound-introduced technology to early intervene the diabetic cardiomyopathy.

    PubMed

    Zhao, Ying-Zheng; Zhang, Ming; Tian, Xin-Qiao; Zheng, Lei; Lu, Cui-Tao

    2016-01-01

    Basic fibroblast growth factor (bFGF)-loaded liposome (bFGF-lip) combined with ultrasound-targeted microbubble destruction (UTMD) technique was investigated to prevent diabetic cardiomyopathy (DCM). Cardiac function and myocardial ultrastructure were assessed. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining, immunohistochemistry staining, and Western blot assay were used to investigate the signal pathway underlying the expression of bFGF in DCM treatment. From Mason staining and TUNEL staining, bFGF-lip + UTMD group showed significant differences from the diabetes group and other groups treated with bFGF or bFGF-lip. The diabetes group showed similar results (myocardial capillary density, collagen volume fraction, and cardiac myocyte apoptosis index) to other bFGF treatment groups. Indexes from transthoracic echocardiography and hemodynamic evaluation also proved the same conclusion. These results confirmed that the abnormalities including diastolic dysfunctions, myocardial fibrosis, and metabolic disturbances could be suppressed by the different extents of twice-weekly bFGF treatments for 12 consecutive weeks (free bFGF or bFGF-lip +/- UTMD), with the strongest improvements observed in the bFGF-lip + UTMD group. The group combining bFGF-lip with UTMD demonstrated the highest level of bFGF expression among all the groups. The bFGF activated the PI3K/AKT signal pathway, causing the reduction of myocardial cell apoptosis and increase of microvascular density. This strategy using bFGF-lip and UTMD is a potential strategy in early intervention of DCM in diabetes. PMID:26937188

  11. Using basic fibroblast growth factor nanoliposome combined with ultrasound-introduced technology to early intervene the diabetic cardiomyopathy

    PubMed Central

    Zhao, Ying-Zheng; Zhang, Ming; Tian, Xin-Qiao; Zheng, Lei; Lu, Cui-Tao

    2016-01-01

    Basic fibroblast growth factor (bFGF)-loaded liposome (bFGF-lip) combined with ultrasound-targeted microbubble destruction (UTMD) technique was investigated to prevent diabetic cardiomyopathy (DCM). Cardiac function and myocardial ultrastructure were assessed. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining, immunohistochemistry staining, and Western blot assay were used to investigate the signal pathway underlying the expression of bFGF in DCM treatment. From Mason staining and TUNEL staining, bFGF-lip + UTMD group showed significant differences from the diabetes group and other groups treated with bFGF or bFGF-lip. The diabetes group showed similar results (myocardial capillary density, collagen volume fraction, and cardiac myocyte apoptosis index) to other bFGF treatment groups. Indexes from transthoracic echocardiography and hemodynamic evaluation also proved the same conclusion. These results confirmed that the abnormalities including diastolic dysfunctions, myocardial fibrosis, and metabolic disturbances could be suppressed by the different extents of twice-weekly bFGF treatments for 12 consecutive weeks (free bFGF or bFGF-lip +/− UTMD), with the strongest improvements observed in the bFGF-lip + UTMD group. The group combining bFGF-lip with UTMD demonstrated the highest level of bFGF expression among all the groups. The bFGF activated the PI3K/AKT signal pathway, causing the reduction of myocardial cell apoptosis and increase of microvascular density. This strategy using bFGF-lip and UTMD is a potential strategy in early intervention of DCM in diabetes. PMID:26937188

  12. Effects of growth factors on temporomandibular joint disc cells.

    PubMed

    Detamore, Michael S; Athanasiou, Kyriacos A

    2004-07-01

    The effects of growth factors on cartilaginous tissues are well documented. An exception is the temporomandibular joint (TMJ) disc, where data for growth factor effects on proliferation and biosynthesis are very limited. The purpose of this study was to quantify proliferation of and synthesis by TMJ disc cells cultured in monolayer with either platelet derived growth factor-AB (PDGF), basic fibroblast growth factor (bFGF) or insulin-like growth factor-I (IGF), at either a low (10 ng/ml) or high (100 ng/ml) concentration. Proliferation was assessed with a DNA quantitation technique, collagen synthesis was measured via a hydroxyproline assay, and GAG synthesis was determined with a dimethylmethylene blue dye binding assay at 14 days. Overall, the most beneficial growth factor was bFGF, which was most potent in increasing proliferation and GAG synthesis, and also effective in promoting collagen synthesis. At the high concentration, bFGF resulted in 96% more cells than the control and 30 to 45% more cells than PDGF and IGF. PDGF and bFGF were the most potent upregulators of GAG synthesis, producing 2-3 times more GAG than the control. IGF had no significant effect on GAG production, although at its higher concentration it increased collagen production by 4.5 times over the control. Collagen synthesis was promoted by bFGF at its lower concentration, with levels 4.2 times higher than the control, whereas PDGF had no significant effect on collagen production. In general, higher concentrations increased proliferation, whereas lower concentrations favoured biosynthesis. PMID:15126139

  13. Basic fibroblast growth factor promotes proliferation of rat glomerular visceral epithelial cells in vitro.

    PubMed Central

    Takeuchi, A.; Yoshizawa, N.; Yamamoto, M.; Sawasaki, Y.; Oda, T.; Senoo, A.; Niwa, H.; Fuse, Y.

    1992-01-01

    Glomerular visceral epithelial cells (vGEC) play an important role in the synthesis of the glomerular basement membrane (GBM), and together with glomerular endothelial cells and the GBM, in glomerular ultrafiltration. Therefore clarification of the properties of vGEC is essential to investigations of glomerular morphology and function in both physiologic and pathologic conditions. This article demonstrates that basic fibroblast growth factor (bFGF) is mitogenic to vGEC in vitro. Its effect was found at concentrations as low as 1.25 ng/ml, and was synergistic with epidermal growth factor (EGF). In contrast, EGF by itself had no demonstrable mitogenic effect at concentrations of 1.25-100 ng/ml. In addition, mRNA for bFGF was identified in cultured vGEC by the method of reverse transcriptase polymerase chain reaction and the immunoreactivity of bFGF was found in GEC of the Sprague-Dawley rat kidney. These results suggest that bFGF stimulates the proliferation of vGEC in an autocrine manner in vivo. A unique relationship similar to that observed in endothelial cells may also exist among bFGF, vGEC, and the extracellular matrix (ECM). In a word, bFGF may be produced by vGEC and stored in the ECM, that is the GBM, and may be one factor that stimulates vGEC to proliferate when vGEC are injured and lost in vivo. Images Figure 1 Figure 2 Figure 3 Figure 6 Figure 8 PMID:1632456

  14. Maintenance of high proliferation and multipotent potential of human hair follicle-derived mesenchymal stem cells by growth factors.

    PubMed

    Zhang, Xueyan; Wang, Yimei; Gao, Yunhe; Liu, Xuejuan; Bai, Tingting; Li, Meiying; Li, Lisha; Chi, Guanfan; Xu, Hui; Liu, Feilin; Liu, Jin Yu; Li, Yulin

    2013-04-01

    Cell therapy and cell-based tissue engineering is becoming increasingly important in regenerative medicine. Stem cells that are characterized by self-renewal, high proliferation and multiple differentiation potentials have attracted attention in cell-based regenerative medicine. Maintaining the aforementioned characteristics of stem cells is the first key step in cell-based regenerative medicine. Basic fibroblast growth factor (bFGF) is a well-known growth factor that efficiently maintains the self-renewal, high proliferation and multilineage differentiation potential of stem cells. Whether or not other growth factors, such as acidic fibroblast growth factor (aFGF) and epidermal growth factor (EGF) have similar effects has yet to be fully elucidated. Human hair follicle-derived mesenchymal stem cells (HF-MSCs) were obtained by organ culture. They exhibited surface markers of bone marrow mesenchymal stem cells as shown by positive staining for CD44, CD73, CD90 and CD105, and they also displayed trilineage differentiation potentials into adipocytes, chondrocytes and osteoblasts by cytochemistry and qRT-PCR. Flow cytometry analysis showed that up to 70% of HF-MSCs cultured in the presence of aFGF, bFGF or EGF stayed at the G0/G1 phase. Proliferation analysis showed that both bFGF and EGF at as low as 1 ng/ml and aFGF at above 5 ng/ml levels significantly increased the proliferation of HF-MSCs by cell counting. Consistent with proliferation analysis, immunofluorescence staining showed that more than 95% of HF-MSCs cultured in the presence of aFGF, bFGF and EGF were positively stained for proliferating cell nuclear antigen. HF-MSCs cultured in the presence of aFGF, bFGF or EGF retained marked trilineage differentiation potentials. By contrast, HF-MSCs cultured in the absence of bFGF, aFGF and EGF lost multipotency. PMID:23403715

  15. Immunohistochemical localization of basic fibroblast growth factor in bovine ovarian follicles.

    PubMed

    van Wezel, I L; Umapathysivam, K; Tilley, W D; Rodgers, R J

    1995-12-29

    Basic fibroblast growth factor (bFGF, FGF2) controls cell proliferation and differentiation in many organs and tissues. In the ovary, cells proliferate and differentiate during folliculogenesis and during formation of the corpus luteum. While previous studies have inferred a role for bFGF in these processes, the precise contribution of bFGF to follicular activation or recruitment has not been established. For this reason, bFGF was immunolocalized in bovine follicles, using anti-bFGF immunoglobulin specific for the 1-24-amino acid terminus of the 18-kDa peptide. Basic FGF was immunolocalized to the cytoplasm of oocytes from bovine primordial and primary follicles. Strong immunostaining was also observed in corpora lutea, the ovarian surface epithelium, and smooth muscle cells surrounding blood vessels, while substantial levels of immunostaining were also present in cells of the theca interna. In most of the healthy antral follicles examined, the three or so layers of granulosa cells which were closest to the basement membrane were also stained, with greatest levels of staining at the most basal region of each cell. Atretic antral follicles had significant and uniform levels of immunostaining throughout the theca interna and the membrana granulosa. Immunostaining as described above was reduced to background levels when the primary specific immunoglobulin was preabsorbed with a 350 molar excess of peptide comprising the NH2-terminal 24 amino acids of bFGF. Based upon our previous observations and those reported here, we propose that basic fibroblast growth factor is synthesized by immature oocytes, especially those from primordial and primary follicles, and that bFGF has a potential role in activating follicle growth via stimulation of granulosa cell proliferation and follicular basement membrane synthesis. PMID:8824888

  16. Induction of endothelial cell proliferation by angiogenic factors released by activated monocytes

    SciTech Connect

    Pakala, Rajbabu; Watanabe, Takuya; Benedict, Claude R

    2002-06-01

    Introduction: Cell-cell interaction is an essential component of atherosclerotic plaque development. Activated monocytes appear to play a central role in the development of atherosclerosis, not only through foam cell formation but also via the production of various growth factors that induce proliferation of different cell types that are involved in the plaque development. Using serum free co-culture method, we determined the effect of monocytes on endothelial cell proliferation. Methods: Endothelial cell proliferation is determined by the amount of [{sup 3}H]thymidine incorporated in to the DNA. Basic fibroblast growth factor (b-FGF), vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) levels in the conditioned medium were determined by ELISA. Results: Conditioned medium from unactivated monocytes partially inhibited endothelial cell proliferation, whereas conditioned medium from activated monocytes promoted endothelial cell proliferation. The mitogenic effect of conditioned medium derived from activated monocytes is due to the presence of b-FGF, VEGF and IL-8. Neutralizing antibodies against b-FGF, VEGF and IL-8 partially reversed the mitogenic effect of conditioned medium derived from activated monocytes. When b-FGF, VEGF and IL-8 were immunoprecipitated from conditioned medium derived from activated monocytes, it is less mitogenic to endothelial cells. Conclusion: Activated monocytes may play an important role in the development of atherosclerotic plaque by producing endothelial cell growth factors.

  17. Basic fibroblast growth factor enhances the coupling of intimal hyperplasia and proliferation of vasa vasorum in injured rat arteries.

    PubMed Central

    Edelman, E R; Nugent, M A; Smith, L T; Karnovsky, M J

    1992-01-01

    Basic fibroblast growth factor (bFGF) is mitogenic for smooth muscle cells (SMC) and angiogenic. We examined the in vivo effects of bFGF in balloon denuded carotid arteries of laboratory rats. bFGF was administered continuously from polymer-based devices at 34 ng/d into the periadventitial space of rat carotid arteries for 2 wk. Intimal hyperplasia was not observed in the absence of injury or with lipopolysaccharide induced endothelial dysfunction. Different degrees of vascular injury produced proportionally more intimal hyperplasia. bFGF increased the intimal hyperplastic response 1.3-fold with severe vascular injury, and 2.4-fold with more mild injury. Increased cell proliferation, not extracellular matrix production, accounted for these effects. Cell density was unchanged for the control and bFGF-treated groups, and the number of proliferating intimal cells at 2 wk rose to an amount equivalent to the increase in mass; 1.9- and 4.0-fold for severe and lesser injury, respectively. The relative ability of heparin to reduce SMC proliferation was not altered by the presence of bFGF.bFGF also induced profound angiogenesis within and surrounding the polymeric releasing device, and in the vasa vasorum immediately around the injured arteries. bFGF's effect on vasa was linearly related to the amount of SMC proliferation within the blood vessel. Thus, the in vivo mitogenic and angiogenic potential of bFGF are coupled, and may be similarly modulated by the products of local injury and/or factors in the vessel wall. Images PMID:1371124

  18. TUBERCULOSIS COMO ENFERMEDAD OCUPACIONAL

    PubMed Central

    Mendoza-Ticona, Alberto

    2014-01-01

    Existe evidencia suficiente para declarar a la tuberculosis como enfermedad ocupacional en diversos profesionales especialmente entre los trabajadores de salud. En el Perú están normados y reglamentados los derechos laborales inherentes a la tuberculosis como enfermedad ocupacional, como la cobertura por discapacidad temporal o permanente. Sin embargo, estos derechos aún no han sido suficientemente socializados. En este trabajo se presenta información sobre el riesgo de adquirir tuberculosis en el lugar de trabajo, se revisan las evidencias para declarar a la tuberculosis como enfermedad ocupacional en trabajadores de salud y se presenta la legislación peruana vigente al respecto. PMID:22858771

  19. Binding, internalization, and degradation of basic fibroblast growth factor in human microvascular endothelial cells

    SciTech Connect

    Bikfalvi, A.; Dupuy, E.; Inyang, A.L.; Tobelem, G. ); Fayein, N.; Courtois, Y. ); Leseche, G. )

    1989-03-01

    The binding, internalization, and degradation of basic fibroblast growth factor (bFGF) in human omental microvascular endothelial cells (HOME cells) were investigated. Binding studies of bFGF in human endothelial cells have not yet been reported. Basic FGF bound to HOME cells. The number of low-affinity binding sites was found to be variable. Washing the cells with 2 M phosphate-buffered saline removed completely {sup 125}I-bFGF bound to low-affinity binding sites but decreased also the high-affinity binding. The majority of the surface-bound {sup 125}I-bFGF was removed by washing the cells with acetic acid buffer at pH 3. At this temperature, degradation of the internalized ligand was followed after 1 hour by the appearance of three major bands of 15,000 10,000, and 8,000 Da and was inhibited by chloroquine. These results demonstrated two classes of binding sites for bFGF in HOME cells; the number of high-affinity binding sites being larger than the number reported for bovine capillary endothelial cells. The intracellular processing of bFGF in HOME cells seems to be different from that of heparin binding growth factor-1 in murine lung capillary endothelial cells and of eye-derived growth factor-1 in Chinese hamster fibroblasts.

  20. Recombinant basic fibroblast growth factor accelerates wound healing.

    PubMed

    McGee, G S; Davidson, J M; Buckley, A; Sommer, A; Woodward, S C; Aquino, A M; Barbour, R; Demetriou, A A

    1988-07-01

    Basic fibroblast growth factor (bFGF) stimulates extracellular matrix metabolism, growth, and movement of mesodermally derived cells. We have previously shown that collagen content in polyvinyl alcohol sponges increased after bFGF treatment. We hypothesized that bFGF-treated incisional wounds would heal more rapidly. After intraperitoneal pentobarbital anesthesia, male, 200- to 250-g, Sprague-Dawley rats (n = 27) each underwent two sets of paired, transverse, dorsal incisions closed with steel sutures. On Day 3 postwounding, 0.4 ml of bFGF (recombinant, 400 ng. Synergen) or normal saline was injected into one of each paired incisions. Animals were killed with ether on postwounding Days 5, 6, and 7 and their dorsal pelts were excised. Fresh or formalin-fixed wound strips were subjected to tensile strength measurements using a tensiometer. Breaking energy was calculated. Wound collagen content (hydroxyproline) was measured in wound-edge samples following hydrolysis using high-performance liquid chromatography. There was an overall significant increase in fresh wound tensile strength (13.7 +/- 1.06 vs 19.1 +/- 1.99 g/mm, P less than 0.01) and wound breaking energy (476 +/- 47 vs 747 +/- 76 mm2, P less than 0.001) in bFGF-treated incisions. There was an increase in wound collagen content which was not statistically significant and there was no difference in fixed incisional tensile strength. Histologic examination showed better organization and maturation in bFGF wounds. Recombinant bFGF accelerates normal rat wound healing. This may be due to earlier accumulation of collagen and fibroblasts and/or to greater collagen crosslinking in bFGF-treated wounds. PMID:3392988

  1. Osmotic Induction of Angiogenic Growth Factor Expression in Human Retinal Pigment Epithelial Cells

    PubMed Central

    Reichenbach, Andreas; Wiedemann, Peter; Kohen, Leon; Bringmann, Andreas

    2016-01-01

    Background Although systemic hypertension is a risk factor of age-related macular degeneration, antihypertensive medications do not affect the risk of the disease. One condition that induces hypertension is high intake of dietary salt resulting in increased blood osmolarity. In order to prove the assumption that, in addition to hypertension, high osmolarity may aggravate neovascular retinal diseases, we determined the effect of extracellular hyperosmolarity on the expression of angiogenic cytokines in cultured human retinal pigment epithelial (RPE) cells. Methodology/Principal Findings Hyperosmolarity was induced by the addition of 100 mM NaCl or sucrose to the culture medium. Hypoxia and oxidative stress were induced by the addition of the hypoxia mimetic CoCl2 and H2O2, respectively. Alterations in gene expression were determined with real-time RT-PCR. Secretion of bFGF was evaluated by ELISA. Cell viability was determined by trypan blue exclusion. Nuclear factor of activated T cell 5 (NFAT5) expression was knocked down with siRNA. Hyperosmolarity induced transcriptional activation of bFGF, HB-EGF, and VEGF genes, while the expression of other cytokines such as EGF, PDGF-A, TGF-β1, HGF, and PEDF was not or moderately altered. Hypoxia induced increased expression of the HB-EGF, EGF, PDGF-A, TGF-β1, and VEGF genes, but not of the bFGF gene. Oxidative stress induced gene expression of HB-EGF, but not of bFGF. The hyperosmotic expression of the bFGF gene was dependent on the activation of p38α/β MAPK, JNK, PI3K, and the transcriptional activity of NFAT5. The hyperosmotic expression of the HB-EGF gene was dependent on the activation of p38α/β MAPK, ERK1/2, and JNK. The hyperosmotic expression of bFGF, HB-EGF, and VEGF genes was reduced by inhibitors of TGF-β1 superfamily activin receptor-like kinase receptors and the FGF receptor kinase, respectively. Hyperosmolarity induced secretion of bFGF that was reduced by inhibition of autocrine/paracrine TGF-β1

  2. In vitro stress effect on degradation and drug release behaviors of basic fibroblast growth factor – poly(lactic-co-glycolic-acid) microsphere

    PubMed Central

    Xiong, Yan; Yu, Zeping; Lang, Yun; Hu, Juanyu; Li, Hong; Yan, Yonggang; Tu, Chongqi; Yang, Tianfu; Song, Yueming; Duan, Hong; Pei, Fuxing

    2016-01-01

    Objective To study the degradation and basic fibroblast growth factor (bFGF) release activity of bFGF – poly(lactic-co-glycolic-acid) microsphere (bFGF-PLGA MS) under stress in vitro, including the static pressure and shearing force-simulating mechanical environment of the joint cavity. Method First, bFGF-PLGA MSs were created. Meanwhile, two self-made experimental instruments (static pressure and shearing force loading instruments) were initially explored to provide stress-simulating mechanical environment of the joint cavity. Then, bFGF-PLGA MSs were loaded into the two instruments respectively, to study microsphere degradation and drug release experiments. In the static pressure loading experiment, normal atmospheric pressure loading (approximately 0.1 MPa), 0.35 MPa, and 4.0 MPa pressure loading and shaking flask oscillation groups were designed to study bFGF-PLGA MS degradation and bFGF release. In the shearing force loading experiment, a pulsating pump was used to give the experimental group an output of 1,000 mL/min and the control group an output of 10 mL/min to carry out bFGF-PLGA MS degradation and drug release experiments. Changes of bFGF-PLGA MSs, including microsphere morphology, quality, weight-average molecular weight of polymer, and microsphere degradation and bFGF release, were analyzed respectively. Results In the static pressure loading experiment, bFGF-PLGA MSs at different pressure were stable initially. The trend of molecular weight change, quality loss, and bFGF release was consistent. Meanwhile, microsphere degradation and bFGF release rates in the 4.0 MPa pressure loading group were faster than those in the normal and 0.35 MPa pressure loading groups. It was the fastest in the shaking flask group, showing a statistically significant difference (P<0.0001). In the shearing force loading experiment, there were no distinctive differences in the rates of microsphere degradation and bFGF release between experimental and control group. Meanwhile

  3. Regulation of Transforming Growth Factor β1, Platelet-Derived Growth Factor, and Basic Fibroblast Growth Factor by Silicone Gel Sheeting in Early-Stage Scarring

    PubMed Central

    Choi, Jaehoon; Lee, Eun Hee; Park, Sang Woo

    2015-01-01

    Background Hypertrophic scars and keloids are associated with abnormal levels of growth factors. Silicone gel sheets are effective in treating and preventing hypertrophic scars and keloids. There has been no report on the change in growth factors in the scar tissue following the use of silicone gel sheeting for scar prevention. A prospective controlled trial was performed to evaluate whether growth factors are altered by the application of a silicone gel sheet on a fresh surgical scar. Methods Four of seven enrolled patients completed the study. Transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) were investigated immunohistochemically in biopsies taken from five scars at 4 months following surgery. Results In both the epidermis and the dermis, the expression of TGF-β1 (P=0.042 and P=0.042) and PDGF (P=0.043 and P=0.042) was significantly lower in the case of silicone gel sheet-treated scars than in the case of untreated scars. The expression of bFGF in the dermis was significantly higher in the case of silicone gel sheet-treated scars than in the case of untreated scars (P=0.042), but in the epidermis, the expression of bFGF showed no significant difference between the groups (P=0.655). Conclusions The levels of TGF-β1, PDGF, and bFGF are altered by the silicone gel sheet treatment, which might be one of the mechanisms of action in scar prevention. PMID:25606485

  4. Intracellular signaling pathways required for rat vascular smooth muscle cell migration. Interactions between basic fibroblast growth factor and platelet-derived growth factor.

    PubMed Central

    Bilato, C; Pauly, R R; Melillo, G; Monticone, R; Gorelick-Feldman, D; Gluzband, Y A; Sollott, S J; Ziman, B; Lakatta, E G; Crow, M T

    1995-01-01

    Intracellular signaling pathways activated by both PDGF and basic fibroblast growth factor (bFGF) have been implicated in the migration of vascular smooth muscle cells (VSMC), a key step in the pathogenesis of many vascular diseases. We demonstrate here that, while bFGF is a weak chemoattractant for VSMCs, it is required for the PDGF-directed migration of VSMCs and the activation of calcium/calmodulin-dependent protein kinase II (CamKinase II), an intracellular event that we have previously shown to be important in the regulation of VSMC migration. Neutralizing antibodies to bFGF caused a dramatic reduction in the size of the intracellular calcium transient normally seen after PDGF stimulation and inhibited both PDGF-directed VSMC migration and CamKinase II activation. Partially restoring the calcium transient with ionomycin restored migration and CamKinase II activation as did the forced expression of a mutant CamKinase II that had been "locked" in the active state by site-directed mutagenesis. These results suggest that bFGF links PDGF receptor stimulation to changes in intracellular calcium and CamKinase II activation, reinforcing the central role played by CamKinase II in regulating VSMC migration. Images PMID:7560082

  5. Distinct Roles for Fibroblast Growth Factor Signaling in Cerebellar Development and Medulloblastoma

    PubMed Central

    Emmenegger, Brian A.; Hwang, Eugene I.; Moore, Colin; Markant, Shirley L.; Brun, Sonja N.; Dutton, John W.; Read, Tracy-Ann; Fogarty, Marie P.; Singh, Alok R.; Durden, Donald L.; Yang, Chaofeng; McKeehan, Wallace L.; Wechsler-Reya, Robert J.

    2013-01-01

    Cerebellar granule neurons are the most abundant neurons in the brain, and a critical element of the circuitry that controls motor coordination and learning. In addition, granule neuron precursors (GNPs) are thought to represent cells of origin for medulloblastoma, the most common malignant brain tumor in children. Thus, understanding the signals that control the growth and differentiation of these cells has important implications for neurobiology and neuro-oncology. Our previous studies have shown that proliferation of GNPs is regulated by Sonic hedgehog (Shh), and that aberrant activation of the Shh pathway can lead to medulloblastoma. Moreover, we have demonstrated that Shh-dependent proliferation of GNPs and medulloblastoma cells can be blocked by basic fibroblast growth factor (bFGF). But while the mitogenic effects of Shh signaling have been confirmed in vivo, the inhibitory effects of bFGF have primarily been studied in culture. Here we demonstrate that mice lacking FGF signaling in GNPs exhibit no discernable changes in GNP proliferation or differentiation. In contrast, activation of FGF signaling has a potent effect on tumor growth: treatment of medulloblastoma cells with bFGF prevents them from forming tumors following transplantation, and inoculation of tumor-bearing mice with bFGF markedly inhibits tumor growth in vivo. These results suggest that activators of FGF signaling may be useful for targeting medulloblastoma and other Shh-dependent tumors. PMID:23045271

  6. Tenogenic induction of equine mesenchymal stem cells by means of growth factors and low-level laser technology.

    PubMed

    Gomiero, Chiara; Bertolutti, Giulia; Martinello, Tiziana; Van Bruaene, Nathalie; Broeckx, Sarah Y; Patruno, Marco; Spaas, Jan H

    2016-03-01

    Tendons regenerate poorly due to a dense extracellular matrix and low cellularity. Cellular therapies aim to improve tendon repair using mesenchymal stem cells and tenocytes; however, a current limitation is the low proliferative potential of tenocytes in cases of severe trauma. The purpose of this study was to develop a method useful in veterinary medicine to improve the differentiation of Peripheral Blood equine mesenchymal stem cells (PB-MSCs) into tenocytes. PB-MSCs were used to study the effects of the addition of some growth factors (GFs) as TGFβ3 (transforming growth factor), EGF2 (Epidermal growth factor), bFGF2 (Fibroblast growth factor) and IGF-1 (insulin-like growth factor) in presence or without Low Level Laser Technology (LLLT) on the mRNA expression levels of genes important in the tenogenic induction as Early Growth Response Protein-1 (EGR1), Tenascin (TNC) and Decorin (DCN). The singular addition of GFs did not show any influence on the mRNA expression of tenogenic genes whereas the specific combinations that arrested cell proliferation in favour of differentiation were the following: bFGF2 + TGFβ3 and bFGF2 + TGFβ3 + LLLT. Indeed, the supplement of bFGF2 and TGFβ3 significantly upregulated the expression of Early Growth Response Protein-1 and Decorin, while the use of LLLT induced a significant increase of Tenascin C levels. In conclusion, the present study might furnish significant suggestions for developing an efficient approach for tenocyte induction since the external administration of bFGF2 and TGFβ3, along with LLLT, influences the differentiation of PB-MSCs towards the tenogenic fate. PMID:26757735

  7. Fibroblast Growth Factor Receptor-2 Contributes to the Basic Fibroblast Growth Factor-Induced Neuronal Differentiation in Canine Bone Marrow Stromal Cells via Phosphoinositide 3-Kinase/Akt Signaling Pathway

    PubMed Central

    Nakano, Rei; Edamura, Kazuya; Nakayama, Tomohiro; Narita, Takanori; Okabayashi, Ken; Sugiya, Hiroshi

    2015-01-01

    Bone marrow stromal cells (BMSCs) are considered as candidates for regenerative therapy and a useful model for studying neuronal differentiation. The role of basic fibroblast growth factor (bFGF) in neuronal differentiation has been previously studied; however, the signaling pathway involved in this process remains poorly understood. In this study, we investigated the signaling pathway in the bFGF-induced neuronal differentiation of canine BMSCs. bFGF induced the mRNA expression of the neuron marker, microtubule associated protein-2 (MAP2) and the neuron-like morphological change in canine BMSCs. In the presence of inhibitors of fibroblast growth factor receptors (FGFR), phosphatidylinositol 3-kinase (PI3K) and Akt, i.e., SU5402, LY294002, and MK2206, respectively, bFGF failed to induce the MAP2 mRNA expression and the neuron-like morphological change. bFGF induced Akt phosphorylation, but it was attenuated by the FGFR inhibitor SU5402 and the PI3K inhibitor LY294002. In canine BMSCs, expression of FGFR-1 and FGFR-2 was confirmed, but only FGFR-2 activation was detected by cross-linking and immunoprecipitation analysis. Small interfering RNA-mediated knockdown of FGFR-2 in canine BMSCs resulted in the attenuation of bFGF-induced Akt phosphorylation. These results suggest that the FGFR-2/PI3K/Akt signaling pathway is involved in the bFGF-induced neuronal differentiation of canine BMSCs. PMID:26523832

  8. Growth factor modulation of fibroblast proliferation, differentiation, and invasion: implications for tissue valve engineering.

    PubMed

    Narine, Kishan; De Wever, Olivier; Van Valckenborgh, Dillis; Francois, Katrien; Bracke, Marc; DeSmet, Stefaan; Mareel, Marc; Van Nooten, Guido

    2006-10-01

    We have previously shown that transforming growth factor-beta1 (TGF-beta1) stimulates transdifferentiation of fibroblasts into smooth muscle alpha-actin (alpha-SMA) positive myofibroblasts. However, TGF-beta, as such, is unsuitable for effective population of a heart valve matrix, because it dose-dependently inhibits growth of fibroblasts. The aim of this study was to investigate combinations of other growth factors with TGF-beta to stimulate the proliferation of suitably differentiated cells and to enhance their invasion into aortic valve matrices. Human dermal mesenchymal cells (hDMC1.1) were treated with combinations of growth factors to stimulate these cells to trans-differentiate into myofibroblasts, to proliferate, and to invade. Growth factors were chosen after expression of their respective receptors was confirmed in hDMC1.1 using reverse transcriptase polymerase chain reaction. We combined TGF-beta with several growth factors such as insulin-like growth factor (IGF-1, IGF-2), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor (PDGF-AA, PDGF-BB, and PDGFAB). Nuclear Ki67 staining, MTT assay, and cell counting revealed that only EGF and bFGF were capable of overcoming TGF-beta-induced growth inhibition. However, bFGF but not EGF inhibited TGF-beta-induced alpha-SMA expression, as evidenced by immuno-cytochemistry and Western blotting. A growth factor cocktail (TGF-beta, EGF, bFGF) has been established that maintains TGF-beta-induced trans-differentiation but overcomes TGF-beta-induced growth inhibition while stimulating fibroblast proliferation and invasion. PMID:17518640

  9. Cardiomyogenic differentiation of human sternal bone marrow mesenchymal stem cells using a combination of basic fibroblast growth factor and hydrocortisone.

    PubMed

    Hafez, Pezhman; Jose, Shinsmon; Chowdhury, Shiplu R; Ng, Min Hwei; Ruszymah, B H I; Abdul Rahman Mohd, Ramzisham

    2016-01-01

    The alarming rate of increase in myocardial infarction and marginal success in efforts to regenerate the damaged myocardium through conventional treatments creates an exceptional avenue for cell-based therapy. Adult bone marrow mesenchymal stem cells (MSCs) can be differentiated into cardiomyocytes, by treatment with 5-azacytidine, thus, have been anticipated as a therapeutic tool for myocardial infarction treatment. In this study, we investigated the ability of basic fibroblastic growth factor (bFGF) and hydrocortisone as a combined treatment to stimulate the differentiation of MSCs into cardiomyocytes. MSCs were isolated from sternal marrow of patients undergoing heart surgery (CABG). The isolated cells were initially monitored for the growth pattern, followed by characterization using ISCT recommendations. Cells were then differentiated using a combination of bFGF and hydrocortisone and evaluated for the expression of characteristic cardiac markers such as CTnI, CTnC, and Cnx43 at protein level using immunocytochemistry and flow cytometry, and CTnC and CTnT at mRNA level. The expression levels and pattern of the cardiac markers upon analysis with ICC and qRT-PCR were similar to that of 5-azacytidine induced cells and cultured primary human cardiomyocytes. However, flow cytometric evaluation revealed that induction with bFGF and hydrocortisone drives MSC differentiation to cardiomyocytes with a marginally higher efficiency. These results indicate that combination treatment of bFGF and hydrocortisone can be used as an alternative induction method for cardiomyogenic differentiation of MSCs for future clinical applications. PMID:26289249

  10. Robust, flexible, and bioadhesive free-standing films for the co-delivery of antibiotics and growth factors.

    PubMed

    Chen, Dongdong; Wu, Mingda; Chen, Jie; Zhang, Chunqiu; Pan, Tiezheng; Zhang, Bing; Tian, Huayu; Chen, Xuesi; Sun, Junqi

    2014-11-25

    Free-standing polymer films that adhere strongly to tissue and can codeliver multiple therapeutic agents in a controlled manner are useful as medical plasters. In this study, a bilayer polymer film comprising a drug reservoir layer and a supporting layer is fabricated by spin-coating poly(lactic-co-glycolic acid) (PLGA) on top of a layer-by-layer assembled film of poly(β-amino esters) (PAE), alginate sodium (ALG), and recombinant human basic fibroblast growth factor (bFGF). Apart from bFGF, the bilayer film can also load antibiotic drug ceftriaxone sodium (CTX) by a postdiffusion process. The PLGA supporting layer facilitates the direct peeling of the bilayer film from substrate to produce a robust and flexible free-standing film with excellent adhesion onto the human skin and porcine liver. The excellent adhesion of the bilayer film originates from the ALG component in the drug reservoir layer. CTX is quickly released by easily breaking its electrostatic interaction with the drug reservoir layer, whereas the sustained release of bFGF is due to the slow degradation of PAE component in the drug reservoir layer. Wounds can be synergetically treated by fast release of CTX to effectively eradicate invasive bacteria and by sustained release of bFGF to accelerate wound healing. Our results serve as a basis for designing multifunctional free-standing films with combination therapy for biomedical applications. PMID:25353985

  11. Layer-by-Layer assembled growth factor reservoirs for steering the response of 3T3-cells.

    PubMed

    Naves, Alliny F; Motay, Marvin; Mérindol, Rémi; Davi, Christiane P; Felix, Olivier; Catalani, Luiz H; Decher, Gero

    2016-03-01

    Layer-by-Layer (LbL) assemblies of heparin (Hep) and chitosan (Chi) were prepared for use as reservoirs for acidic and basic fibroblast growth factors (aFGFs and bFGFs, respectively). The effects of the architecture and composition of the reservoirs on the viability and proliferation of NIH-3T3 fibroblast cells were studied under starvation conditions. The reservoir stability was monitored by ellipsometry. The aFGF and bFGF loadings were determined using a dissipation-enhanced quartz crystal microbalance (QCM-D). Stability and release assays were performed in a phosphate buffer at physiological conditions. The results demonstrated that the amount of aFGF and bFGF loaded into and released from LbL reservoirs composed of 3 and 6 layer pairs could be controlled. Cell culture assays in low serum culture medium (LSCM) demonstrated that incorporating very small amounts of aFGF and bFGF into the (Hep/Chi)n multilayers significantly improved the proliferation of the NIH-3T3 fibroblasts. The cells did not proliferate on (Hep/Chi)n assemblies prepared in the absence of FGF under identical conditions. The LbL reservoirs were highly effective for the long-term storage (up to 9 months) of aFGF and bFGF. This work demonstrates the potential of LbL reservoirs for use as biomaterial coatings. PMID:26700236

  12. Moral Responsibility and Confidence as Factors That Influence Teacher Involvement in Educational Change (Responsabilidad moral y confianza como factores que influyen en la participación del profesor en el cambio educativo)

    ERIC Educational Resources Information Center

    López, Cecilio

    2010-01-01

    Various factors that are not easily observed have a strong impact on educational change. In this paper, I examine some of the issues that emerged from the data collected while exploring my informants' perceptions and attitudes towards their changing roles when confronted with curriculum innovation. This research demonstrates that the…

  13. CORNEAL ANGIOGENIC PRIVILEGE: ANGIOGENIC AND ANTIANGIOGENIC FACTORS IN CORNEAL AVASCULARITY, VASCULOGENESIS, AND WOUND HEALING (AN AMERICAN OPHTHALMOLOGICAL SOCIETY THESIS)

    PubMed Central

    Azar, Dimitri T.

    2006-01-01

    Purpose To determine the molecular basis of corneal avascularity during wound healing and determine the role of angiogenic and antiangiogenic factors in corneal vasculogenesis. Methods The expression of proangiogenic factors (vascular endothelial growth factor [VEGF]; basic fibroblast growth factor [bFGF]; matrix metalloproteinase-2 [MMP-2]; and membrane-type 1-MMP [MT1-MMP]) and antiangiogenic factors (pigment epithelium–derived factor [PEDF]; angiostatin; restin; and endostatin) was analyzed in avascular corneas and in models of corneal neovascularization (bFGF pellet implantation, intrastromal injection of MT1-MMP cDNA, and surgically induced partial limbal deficiency). Results Immunohistochemistry demonstrated the presence of antiangiogenic factors (PEDF, angiostatin, restin, and endostatin) and proangiogenic molecules (VEGF, bFGF, MMP-2, and MT1-MMP) in the cornea after wounding. Proangiogenic MMPs were upregulated in stromal fibroblasts in the vicinity of invading vessels following bFGF pellet implantation. Corneal neovascularization (NV) was also induced by intrastromal injection of MT1-MMP naked cDNA in conjunction with de-epithelialization. Partial limbal deficiency (HLD-) resulted in corneal NV in MMP-7 and MMP-3 knockout mice but not in wild type controls. Conclusions Corneal angiogenic privilege is an active process involving the production of antiangiogenic factors to counterbalance the proangiogenic factors (which are upregulated after wound healing even in the absence of new vessels). Our finding that the potent antiangiogenic factors, angiostatin and endostatin, are colocalized with several MMPs during wound healing suggests that MMPs may be involved in the elaboration of these antiangiogenic molecules by proteolytic processing of substrates within the cornea. PMID:17471348

  14. Contrasting effects of basic fibroblast growth factor and neurotrophin 3 on cell cycle kinetics of mouse cortical stem cells

    PubMed Central

    Lukaszewicz, Agnès; Savatier, Pierre; Cortay, Véronique; Kennedy, Henry; Dehay, Colette

    2002-01-01

    Basic fibroblast growth factor (bFGF) exerts a mitogenic effect on cortical neuroblasts, whereas neurotrophin 3 (NT3) promotes differentiation in these cells. Here we provide evidence that both the mitogenic effect of bFGF and the differentiation-promoting effect of NT3 are linked with modifications of cell cycle kinetics in mouse cortical precursor cells. We adapted an in vitro assay, which makes it possible to evaluate (1) the speed of progression of the cortical precursors through the cell cycle, (2) the duration of individual phases of the cell cycle, (3) the proportion of proliferative versus differentiative divisions, and (4) the influence on neuroglial differentiation. Contrary to what has been claimed previously, bFGF promotes proliferation via a change in cell cycle kinetics by simultaneously decreasing G1 duration and increasing the proportion of proliferative divisions. In contrast, NT3 lengthens G1 and promotes differentiative divisions. We investigated the molecular foundations of these effects and show that bFGF downregulates p27kip1 and upregulates cyclin D2 expression. This contrasts with NT3, which upregulates p27kip1 and downregulates cyclin D2 expression. Neither bFGF nor NT3 influences the proportion of glia or neurons in short to medium term cultures. The data point to links between the length of the G1 phase and the type of division of cortical precursors: differentiative divisions are correlated with long G1 durations, whereas proliferative divisions correlate with short G1 durations. The present results suggest that concerted mechanisms control the progressive increase in the cell cycle duration and proportion of differentiative divisions that is observed as corticogenesis proceeds. PMID:12151540

  15. Migrational changes of mesenchymal stem cells in response to cytokines, growth factors, hypoxia, and aging.

    PubMed

    Naaldijk, Yahaira; Johnson, Adiv A; Ishak, Stefan; Meisel, Hans Jörg; Hohaus, Christian; Stolzing, Alexandra

    2015-10-15

    Mesenchymal stem cells (MSCs) are non-immunogenic, multipotent cells with at least trilineage differentiation potential. They promote wound healing, improve regeneration of injured tissue, and mediate numerous other health effects. MSCs migrate to sites of injury and stimulate repair either through direct differentiation or indirectly through the stimulation of endogenous repair mechanisms. Using the in vitro scratch assay, we show that the inflammatory cytokines, chemokines, and growth factors TNF-α, SDF-1, PDGF, and bFGF enhance migration of rat MSCs under normoxic conditions, while TNF-α, IFN-γ, PDGF, and bFGF promote MSC migration under hypoxic conditions. This indicates that the oxygen concentration affects how MSCs will migrate in response to specific factors and, consistent with this, differential expression of cytokines was observed under hypoxic versus normoxic conditions. Using the transwell migration assay, we find that TNF-α, IFN-γ, bFGF, IGF-1, PDGF, and SDF-1 significantly increase transmigration of rat MSCs compared to unstimulated medium. MSCs derived from aged rats exhibited comparable migration to MSCs derived from young rats under hypoxic and normoxic conditions, even after application with specific factors. Similarly, migration in MSCs from aged, human donors did not statistically differ compared to migration in MSCs derived from human umbilical cord tissue or younger donors. PMID:26335540

  16. Assessment of expressions of Bcl-XL, b-FGF, Bmp-2, Caspase-3, PDGFR-α, Smad1 and TGF-β1 genes in a rat model of lung ischemia/reperfusion

    PubMed Central

    Şimşek, Hasan; Demiryürek, Şeniz; Demir, Tuncer; Atabay, Hüsne Didem; Çeribasi, Ali Osman; Bayraktar, Recep; Kaplan, Davut Sinan; Öztuzcu, Serdar; Cengiz, Beyhan

    2016-01-01

    Objective(s): Ischemia is described as organs and tissues are destitute of oxygen due to decreased arterial or venous blood flow. Many mechanisms play role in cell death happened as a consequence of a new blood flow is needed for both cell regeneration and to clean toxic metabolites during ischemia and later. Lung damage induced by ischemia/reperfusion (I/R) is a frequent problem in lung transplantation. Apoptosis (programmed cell death) is known as cell suicide, and plays a key role in embryonic developmental and in maintain adult tissue’s life. Materials and Methods: It is investigated expressions of Smad1, Bmp-2, Bcl-XL, b-FGF, Caspase-3, TGF-β1, PDGFR-α genes for molecular changes in lung tissues, after I/R is formed, in this study. For this, we included 40 Wistar albino rats to this study and divided 4 groups (n=10). The Groups were determined as Control (C), Group 1= 1 hr ischemia (I), Group 2= 1 hr ischemia+2 hr reperfusion (I+2R), Group 3= 1 hr ischemia+4 hr reperfusion (I+4R). Besides, molecular analysis and histopathologic examinations of tissues were performed, and the results were evaluated by normalization and statistics analysis. Results: We have found a significant increase in expression of Bcl-XL (P=0.046) and Caspase-3 (P=0.026) genes of group 1, and it was not monitored any significant difference in Group 2 and Group 3. In all groups, the changes in b-FGF (P=0.087), Bmp-2 (P=0.457), TGF-β1 (P=0.201) and PDGFR-α (P=0.116) were not significant compared to control group. We did not see any mRNA expression of Smad1 gene in all groups include control. Conclusion: These findings suggest that I/R injury may trigger apoptotic mechanism in lung. PMID:27081467

  17. Modulation of extracellular signal-related kinase, cyclin D1, glial fibrillary acidic protein, and vimentin expression in estradiol-pretreated astrocyte cultures treated with competence and progression growth factors.

    PubMed

    Bramanti, Vincenzo; Grasso, Sonia; Tibullo, Daniele; Giallongo, Cesarina; Raciti, Giuseppina; Viola, Maria; Avola, Roberto

    2015-09-01

    The present study seeks to elucidate the interactions between the "competence" growth factor basic fibroblast growth factor (bFGF) and/or estrogen 17β-estradiol and the "progression" growth factors epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and insulin (INS) on DNA labeling and also cyclin D1, extracellular signal-related kinase 1/2 (ERK1/2), glial fibrillary acidic protein (GFAP), and vimentin expression in astroglial cultures under different experimental conditions. Pretreatment for 24 hr with bFGF and subsequent exposure for 36 hr to estradiol (E2 ) and EGF, IGF-I, or INS stimulated DNA labeling in the last 12 hr, especially when the cultures were treated with progression growth factors. bFGF pretreatment and subsequent treatment with E2 for 36 hr stimulated DNA labeling. The 36-hr E2 treatment alone did not significantly decrease DNA labeling, but contemporary addition of E2 with two or three growth factors stimulated DNA labeling remarkably. When E2 was coadded with growth factors, a significantly increased DNA labeling was observed, demonstrating an astroglial synergistic mitogenic effect evoked by contemporary treatment with growth factors in the presence of estrogens. Cyclin D1 expression was markedly increased when astrocyte cultures were pretreated for 36 hr with E2 and subsequently treated with two or three competence and progression growth factors. A highly significant increase of ERK1/2 expression was observed after all the treatments (EGF, bFGF, INS, IGF-I alone or in combination with two or three growth factors). GFAP and vimentin expression was markedly increased when the cultures were treated with two or three growth factors. In conclusion, our data demonstrate estradiol-growth factor cross-talk during astroglial cell proliferation and differentiation in culture. PMID:26053243

  18. Growth factor array fabrication using a color ink jet printer.

    PubMed

    Watanabe, Kohei; Miyazaki, Takeshi; Matsuda, Ryoichi

    2003-04-01

    We have developed a novel method for growth factor analysis using a commercial color ink jet printer to fabricate substrata patterned with growth factors. We prepared substrata with insulin printed in a simple pattern or containing multiple areas of varying quantities of printed insulin. When we cultured the mouse myoblast cell line, C2C12, on the insulin-patterned substrata, the cells were grown in the same pattern with the insulin-printed pattern. Cell culture with the latter substrata demonstrated that quantity control of insulin deposition by a color ink jet printer is possible. For further applications, we developed substrata with insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) spotted in 16 different areas in varying combinations and concentrations (growth factor array). With this growth factor array, C2C12 cells were cultured, and the onset of muscle cell differentiation was monitored for the expression of the myogenic regulator myogenin. The ratio of cells expressing myogenin varied with the doses of IGF-I and bFGF in the sections, demonstrating a feasibility of growth factor array fabrication by a color ink jet printer. Since a printer manipulates several colors, this method can be easily applied to multivariate analyses of growth factors and attachment factors affecting cell growth and differentiation. This method may provide a powerful tool for cell biology and tissue engineering, especially for stem cell research in investigating unknown conditions for differentiation. PMID:12719645

  19. Stability and biological activity evaluations of PEGylated human basic fibroblast growth factor

    PubMed Central

    Hadadian, Shahin; Shamassebi, Dariush Norouzian; Mirzahoseini, Hasan; Shokrgozar, Mohamad Ali; Bouzari, Saeid; Sepahi, Mina

    2015-01-01

    Background: Human basic fibroblast growth factor (hBFGF) is a heparin-binding growth factor and stimulates the proliferation of a wide variety of cells and tissues causing survival properties and its stability and biological activity improvements have received much attention. Materials and Methods: In the present work, hBFGF produced by engineered Escherichia coli and purified by cation exchange and heparin affinity chromatography, was PEGylated under appropriate condition employing 10 kD polyethylene glycol. The PEGylated form was separated by size exclusion chromatography. Structural, biological activity, and stability evaluations were performed using Fourier transform infrared (FITR) spectroscopy, 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay and effect denaturing agent, respectively. Results: FITR spectroscopy revealed that both PEGylated and native forms had the same structures. MTT assay showed that PEGyalated form had a 30% reduced biological activity. Fluorescence spectrophotometry indicated that the PEGylated form denatured at higher concentrations of guanidine HCl (1.2 M) compared with native, which denatured at 0.8 M guanidine HCl. Conclusions: PEGylation of hBFGF makes it more stable against denaturing agent but reduces its bioactivity up to 30%. PMID:26605215

  20. Heparinized magnetic mesoporous silica nanoparticles as multifunctional growth factor delivery carriers

    NASA Astrophysics Data System (ADS)

    Wu, Qiang; Liu, Chaoqun; Fan, Luna; Shi, Jiahua; Liu, Zhiqiang; Li, Ruifang; Sun, Liwei

    2012-12-01

    Well-defined magnetic mesoporous silica nanoparticles (MMSNs) with a core/shell structure were prepared via a one pot synthesis. Sphere-like magnetite aggregates were obtained as cores of the final nanoparticles by assembly in the presence of polyvinyl pyrrolidone and cetyltrimethylammonium bromide. The nanoparticles have the property of superparamagnetism with a saturation magnetization value of 20.3 emu g-1. In addition, the combination of heparin and fluorescence-labeled MMSNs endows the resultant particles (denoted as MFMSNs-HP) with magnetism and fluorescence properties, excellent dispersity in the buffer solutions and cell culture media, anticoagulant activity in the blood stream, and the controlled release of basic fibroblast growth factor (bFGF). Furthermore, the bFGF cell viability assays indicate that MFMSNs-HP has nearly no toxicity to human umbilical vein endothelial cells (HUVEC) up to a concentration of 200 μg ml-1, and the proliferation activity of bFGF incorporated into MFMSNs-HP could be retained for at least 6 days. All of these suggest that MFMSNs-HP may serve as a multifunctional carrier for the delivery of growth factors.

  1. Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells.

    PubMed Central

    Pinzani, M; Gesualdo, L; Sabbah, G M; Abboud, H E

    1989-01-01

    In vitro and in vivo studies suggest that liver fat-storing cells (FSC) may play an important role in the development of liver fibrosis. We explored the effects of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor (TGF)-alpha and TGF-beta, and basic fibroblast growth factor (bFGF) on DNA synthesis and growth of rat liver FSC. PDGF, EGF, TGF-alpha, and bFGF induced a dose-dependent increase in DNA synthesis with a peak effect at 24 h. PDGF produced the most striking effect with a maximum 18-fold increase over control. EGF, TGF-alpha, and bFGF elicited a maximum three- to fourfold increase in DNA synthesis. Analysis of growth curves revealed a similar pattern of potency of the growth factors. TGF-beta did not affect DNA synthesis of FSC; however, TGF-beta markedly potentiated the stimulatory effects of both EGF and PDGF. FSC showed high specific binding of 125I-PDGF and Scatchard analysis revealed high affinity receptors with an apparent Kd of 2.3 x 10(-10) M. Our data suggest that PDGF is a key mitogen for FSC and that the coordinate release of other growth factors together with PDGF by inflammatory cells represents a potent potential stimulus for FSC proliferation in conditions of chronic self-perpetuating liver inflammation. Images PMID:2592560

  2. Novel magnetic fibrin hydrogel scaffolds containing thrombin and growth factors conjugated iron oxide nanoparticles for tissue engineering

    PubMed Central

    Ziv-Polat, Ofra; Skaat, Hadas; Shahar, Abraham; Margel, Shlomo

    2012-01-01

    Novel tissue-engineered magnetic fibrin hydrogel scaffolds were prepared by the interaction of thrombin-conjugated iron oxide magnetic nanoparticles with fibrinogen. In addition, stabilization of basal fibroblast growth factor (bFGF) was achieved by the covalent and physical conjugation of the growth factor to the magnetic nanoparticles. Adult nasal olfactory mucosa (NOM) cells were seeded in the transparent fibrin scaffolds in the absence or presence of the free or conjugated bFGF-iron oxide nanoparticles. The conjugated bFGF enhanced significantly the growth and differentiation of the NOM cells in the fibrin scaffolds, compared to the same or even five times higher concentration of the free bFGF. In the presence of the bFGF-conjugated magnetic nanoparticles, the cultured NOM cells proliferated and formed a three-dimensional interconnected network composed mainly of tapered bipolar cells. The magnetic properties of these matrices are due to the integration of the thrombin- and bFGF-conjugated magnetic nanoparticles within the scaffolds. The magnetic properties of these scaffolds may be used in future work for various applications, such as magnetic resonance visualization of the scaffolds after implantation and reloading the scaffolds via magnetic forces with bioactive agents, eg, growth factors bound to the iron oxide magnetic nanoparticles. PMID:22419873

  3. Gelatin/chitosan/hyaluronan ternary complex scaffold containing basic fibroblast growth factor for cartilage tissue engineering.

    PubMed

    Tan, Huaping; Gong, Yihong; Lao, Lihong; Mao, Zhengwei; Gao, Changyou

    2007-10-01

    Gelatin, chitosan and hyaluronan with a weight ratio of 82.6%, 16.5% and 0.1% were chosen as a scaffold material to mimic the composition of natural cartilage matrix for cartilage tissue engineering. Water soluble carbodiimide was added into the biomacromolecule solution with a concentration of 5% to crosslink the complex. Following a freeze-drying procedure, a porous scaffold (control) was then prepared. To enhance chondrogenesis, heparin was covalently immobilized onto the scaffold by carbodiimide chemistry, through which basic fibroblast growth factor (bFGF) was further incorporated by a bioaffinity force. Incubation in phosphate buffered saline (PBS, pH 7.4) at 37 degrees C caused the weight loss of all kinds of the scaffolds, which could be brought by both the degradation and dissolution of the biomacromolecules. Compared with the control, however, the heparinized scaffold showed stronger ability to resist the weight loss, implying that a higher crosslinking degree was achieved by incorporation of the heparin. Rabbit auricular chondrocytes were seeded onto the ternary complex scaffold containing bFGF to assess cell response. Chondrocytes could adhere and proliferate in all kinds of the scaffold, regardless of the existence of bFGF. No significant difference on glycosaminoglycan (GAG) secretion was recorded between these scaffolds after cultured for 7 and 21 days too, although the absolute value from the Scaffold-heparin-bFGF was somewhat higher. However, chondrocytes seeded in the Scaffold-heparin-bFGF indeed showed significant higher viability than that on the control scaffold. These results reveal that the ternary complex scaffolds, in particular the one containing bFGF, are a potential candidate for cartilage tissue engineering. PMID:17554603

  4. Vascular regeneration by pinpoint delivery of growth factors using a microcatheter reservoir system in a rabbit hind-limb ischemia model

    PubMed Central

    NITTA, NORIHISA; NITTA-SEKO, AYUMI; SONODA, AKINAGA; WATANABE, SHOBU; TSUCHIYA, KEIKO; MURATA, KIYOSHI; TABATA, YASUHIKO

    2012-01-01

    The purpose of this study was to compare the results of delivering low doses of growth factor iteratively (20 μg x5) via a reservoir system with results obtained following a single administration of 100 μg of growth factor. The delivery systems using gelatin microspheres (GMS) facilitate the controlled release of drugs. The controlled release of growth factors at specific sites is essential for vascular regeneration. An ischemic hind-limb model was established in nine rabbits. A reservoir system was implanted in each rabbit. GMS impregnated with basic fibroblast growth factor (bFGF) through an indwelling 2-Fr catheter was infused in the reservoir system. The rabbits were divided into three equal groups: group 1 received 20 μg iteratively (x5) via the reservoir, a single dose of 100 μg growth factor was administered to group 2 and group 3 was the saline control. The therapeutic effects were evaluated by measuring the thigh temperature, blood pressure and blood flow. An immunohistological analysis was also performed for CD31. No significant difference was observed between preand post-treatment (4 weeks following bFGF infusion) in the thigh temperature, blood pressure and blood flow results from each group. Pathological analysis revealed that the number of regenerated vessels was significantly higher in the group treated iteratively with low-dose bFGF. PMID:23139710

  5. Vascular regeneration by pinpoint delivery of growth factors using a microcatheter reservoir system in a rabbit hind-limb ischemia model.

    PubMed

    Nitta, Norihisa; Nitta-Seko, Ayumi; Sonoda, Akinaga; Watanabe, Shobu; Tsuchiya, Keiko; Murata, Kiyoshi; Tabata, Yasuhiko

    2012-08-01

    The purpose of this study was to compare the results of delivering low doses of growth factor iteratively (20 μg x5) via a reservoir system with results obtained following a single administration of 100 μg of growth factor. The delivery systems using gelatin microspheres (GMS) facilitate the controlled release of drugs. The controlled release of growth factors at specific sites is essential for vascular regeneration. An ischemic hind-limb model was established in nine rabbits. A reservoir system was implanted in each rabbit. GMS impregnated with basic fibroblast growth factor (bFGF) through an indwelling 2-Fr catheter was infused in the reservoir system. The rabbits were divided into three equal groups: group 1 received 20 μg iteratively (x5) via the reservoir, a single dose of 100 μg growth factor was administered to group 2 and group 3 was the saline control. The therapeutic effects were evaluated by measuring the thigh temperature, blood pressure and blood flow. An immunohistological analysis was also performed for CD31. No significant difference was observed between preand post-treatment (4 weeks following bFGF infusion) in the thigh temperature, blood pressure and blood flow results from each group. Pathological analysis revealed that the number of regenerated vessels was significantly higher in the group treated iteratively with low-dose bFGF. PMID:23139710

  6. Generation and Characterization of Leukemia Inhibitory Factor-Dependent Equine Induced Pluripotent Stem Cells from Adult Dermal Fibroblasts

    PubMed Central

    Ovchinnikov, Dmitry A.; Sun, Jane; Fortuna, Patrick R.J.; Wolvetang, Ernst J.

    2014-01-01

    In this study we have reprogrammed dermal fibroblasts from an adult female horse into equine induced pluripotent stem cells (equiPSCs). These equiPSCs are dependent only on leukemia inhibitory factor (LIF), placing them in striking contrast to previously derived equiPSCs that have been shown to be co-dependent on both LIF and basic fibroblast growth factor (bFGF). These equiPSCs have a normal karyotype and have been maintained beyond 60 passages. They possess alkaline phosphatase activity and express eqNANOG, eqOCT4, and eqTERT mRNA. Immunocytochemistry confirmed that they produce NANOG, REX1, SSEA4, TRA1-60, and TRA1-81. While our equiPSCs are LIF dependent, bFGF co-stimulates their proliferation via the PI3K/AKT pathway. EquiPSCs lack expression of eqXIST and immunostaining for H3K27me3, suggesting that during reprogramming the inactive X chromosome has likely been reactivated to generate cells that have two active X chromosomes. EquiPSCs form embryoid bodies and in vitro teratomas that contain derivatives of all three germ layers. These LIF-dependent equiPSCs likely reflect a more naive state of pluripotency than equiPSCs that are co-dependent on both LIF and bFGF and so provide a novel resource for understanding pluripotency in the horse. PMID:24555755

  7. Growth Factors Cross-Linked to Collagen Microcarriers Promote Expansion and Chondrogenic Differentiation of Human Mesenchymal Stem Cells.

    PubMed

    Bertolo, Alessandro; Arcolino, Fanny; Capossela, Simona; Taddei, Anna Rita; Baur, Martin; Pötzel, Tobias; Stoyanov, Jivko

    2015-10-01

    Tissue engineering is a field in progressive expansion and requires constant updates in methods and devices. One of the central fields is the development of biocompatible, biodegradable, and injectable scaffolds, such as collagen microcarriers. To enhance cell attachment and produce a cost-effective cell culture solution with local stimulation of cells, basic fibroblast growth factor (bFGF) or transforming growth factor-β1 (TGF-β1) was covalently immobilized on microcarriers either by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) or riboflavin/UV (RB/UV) light-mediated cross-linking. Collagen microcarriers cross-linked with bFGF or TGF-β1 were used for expansion and chondrogenic differentiation of human mesenchymal stem cells (MSCs). Evaluation methods included cell viability test, chondrogenic marker expression (aggrecan and collagen type I and type II), histological detection of proteoglycans, and immunohistochemical analysis. Cross-linking strengthened the collagen structure of the microcarriers and reduced collagenase-mediated degradation. MSCs effectively proliferated on microcarriers cross-linked with bFGF, especially by EDC/NHS cross-linking. Chondrogenic differentiation of MSCs was induced by TGF-β1 cross-linked on microcarriers, promoting gene expression and protein accumulation of aggrecan and collagen type I and type II, as well as proteoglycans. Cross-linking by RB/UV enhanced chondrogenesis more than any other group. In addition, cross-linking reduced scaffold shrinkage exerted by MSCs during chondrogenesis, a desirable feature for microcarriers if used as tissue defect filler. In conclusion, cross-linking of bFGF or TGF-β1 to collagen microcarriers supported in vitro proliferation and chondrogenesis, respectively. If translated in vivo and in clinical practice, such approach might lead a step closer to development of a cost-effective and locally acting device for cell-based therapy. PMID:26222829

  8. Effect of Control-released Basic Fibroblast Growth Factor Incorporated in β-Tricalcium Phosphate for Murine Cranial Model

    PubMed Central

    Shimizu, Azusa; Tajima, Satoshi; Tobita, Morikuni; Tanaka, Rica; Tabata, Yasuhiko

    2014-01-01

    Background: β-Tricalcium phosphate (β-TCP) is used clinically as a bone substitute, but complete osteoinduction is slow. Basic fibroblast growth factor (bFGF) is important in bone regeneration, but the biological effects are very limited because of the short half-life of the free form. Incorporation in gelatin allows slow release of growth factors during degradation. The present study evaluated whether control-released bFGF incorporated in β-TCP can promote bone regeneration in a murine cranial defect model. Methods: Bilateral cranial defects of 4 mm in diameter were made in 10-week-old male Sprague-Dawley rats treated as follows: group 1, 20 μl saline as control; group 2, β-TCP disk in 20 μl saline; group 3, β-TCP disk in 50 μg bFGF solution; and group 4, β-TCP disk in 50 μg bFGF-containing gelatin hydrogel (n = 6 each). Histological and imaging analyses were performed at 1, 2, and 4 weeks after surgery. Results: The computed tomography value was lower in groups 3 and 4, whereas the rate of osteogenesis was higher histologically in group 4 than in the other groups. The appearance of tartrate-resistant acid phosphate–positive cells and osteocalcin-positive cells and disappearance of osteopontin-positive cells occurred earlier in group 4 than in the other groups. Conclusions: These findings suggest that control-released bFGF incorporated in β-TCP can accelerate bone regeneration in the murine cranial defect model and may be promising for the clinical treatment of cranial defects. PMID:25289319

  9. Effects of Cyclic Strain and Growth Factors on Vascular Smooth Muscle Cell Responses

    PubMed Central

    Kona, Soujanya; Chellamuthu, Prithiviraj; Xu, Hao; Hills, Seth R; Nguyen, Kytai Truong

    2009-01-01

    Under physiological and pathological conditions, vascular smooth muscle cells (SMC) are exposed to different biochemical factors and biomechanical forces. Previous studies pertaining to SMC responses have not investigated the effects of both factors on SMCs. Thus, in our research we investigated the combined effects of growth factors like Bfgf (basic fibroblast growth factor), TGF-β (transforming growth factor β) and PDGF (platelet-derived growth factor) along with physiological cyclic strain on SMC responses. Physiological cyclic strain (10% strain) significantly reduced SMC proliferation compared to static controls while addition of growth factors bFGF, TGF-β or PDGF-AB had a positive influence on SMC growth compared to strain alone. Microarray analysis of SMCs exposed to these growth factors and cyclic strain showed that several bioactive genes (vascular endothelial growth factor, epidermal growth factor receptor, etc.) were altered upon exposure. Further work involving biochemical and pathological cyclic strain stimulation will help us better understand the role of cyclic strain and growth factors in vascular functions and development of vascular disorders. PMID:19812708

  10. Biological characterization of human fibroblast-derived mitogenic factors for human melanocytes.

    PubMed Central

    Imokawa, G; Yada, Y; Morisaki, N; Kimura, M

    1998-01-01

    To clarify the paracrine linkage between human fibroblasts and melanocytes in cutaneous pigmentation, we studied the effects of human fibroblast-derived factors on the proliferation of human melanocytes. In medium conditioned for 4 days with human fibroblast culture, factors were produced that markedly stimulated DNA synthesis of human melanocytes. The stimulatory effect was higher in medium conditioned with fibroblasts from aged skin than in medium conditioned with fibroblasts from young skin, and was interrupted by inhibitors of tyrosine kinase, such as tyrphostin, genistein and herbimycin, but not by inhibitors of protein kinases C and A, such as H-7 and phloretin. The conditioned medium was also capable of activating mitogen-activated protein kinase of human melanocytes, with old fibroblasts being more effective than young ones. Analysis of factors released into the conditioned medium revealed that levels of hepatocyte growth factor (HGF) and stem cell factor (SCF) were increased in old-fibroblast-conditioned medium compared with young-fibroblast-conditioned medium. In contrast, levels of basic fibroblast growth factor (bFGF) were similar in both media. When the conditioned medium was treated with HGF antibody with or without SCF antibody, the increase in DNA synthesis by human melanocytes was decreased to 20% of the elevated level, whereas antibodies to bFGF had no effect. Analysis of the medium conditioned for 4 days after cytokine application demonstrated that, of the cytokines tested, interleukin 1alpha and tumour necrosis factor alpha are highly effective in stimulating HGF secretion by old fibroblasts. HGF and SCF, but not bFGF, were markedly increased in culture medium in the presence of IL-1alpha, and this stimulatory effect was confined to young human fibroblasts. These findings suggest that SCF and HGF derived from human fibroblasts may play a part in regulating cutaneous pigmentation during inflammation and aging. PMID:9494091

  11. Suppression of autocrine and paracrine functions of basic fibroblast growth factor by stable expression of perlecan antisense cDNA.

    PubMed Central

    Aviezer, D; Iozzo, R V; Noonan, D M; Yayon, A

    1997-01-01

    Heparan sulfate proteoglycans (HSPG) play a critical role in the formation of distinct fibroblast growth factor (FGF)-HS complexes, augmenting high-affinity binding and receptor activation. Perlecan, a secreted HSPG abundant in proliferating cells, is capable of inducing FGF-receptor interactions in vitro and angiogenesis in vivo. Stable and specific reduction of perlecan levels in mouse NIH 3T3 fibroblasts and human metastatic melanoma cells has been achieved by expression of antisense cDNA corresponding to the N-terminal and HS attachment domains of perlecan. Long-term perlecan downregulation is evidenced by reduced levels of perlecan mRNA and core protein as indicated by Northern blot analysis, immunoblots, and immunohistochemistry, using DNA probes and antibodies specific to mouse or human perlecan. The response of antisense perlecan-expressing cells to increasing concentrations of basic FGF (bFGF) is dramatically reduced in comparison to that in wild-type or vector-transfected cells, as measured by thymidine incorporation and rate of proliferation. Furthermore, receptor binding and affinity labeling of antisense perlecan-transfected cells with 125I-bFGF is markedly inhibited, indicating that eliminating perlecan expression results in reduced high-affinity bFGF binding. Both the binding and mitogenic response of antisense-perlecan-expressing clones to bFGF can be rescued by exogenous heparin or perlecan. These results support the notion that perlecan is a major accessory receptor for bFGF in mouse fibroblasts and human melanomas and point to the possible use of perlecan antisense constructs as specific modulators of bFGF-mediated responses. PMID:9121441

  12. Novel collagen/gelatin scaffold with sustained release of basic fibroblast growth factor: clinical trial for chronic skin ulcers.

    PubMed

    Morimoto, Naoki; Yoshimura, Kenichi; Niimi, Miyuki; Ito, Tatsuya; Aya, Rino; Fujitaka, Junpei; Tada, Harue; Teramukai, Satoshi; Murayama, Toshinori; Toyooka, Chikako; Miura, Kazumi; Takemoto, Satoru; Kanda, Norikazu; Kawai, Katsuya; Yokode, Masayuki; Shimizu, Akira; Suzuki, Shigehiko

    2013-09-01

    Chronic skin ulcers such as diabetic ulcers and venous leg ulcers are increasing and are a costly problem in healthcare. We have developed a novel artificial dermis, collagen/gelatin sponge (CGS), which is capable of sustained release of basic fibroblast growth factor (bFGF) for more than 10 days. The objective of this study was to investigate the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers. Patients with chronic skin ulcers that had not healed in at least 4 weeks were treated with CGS impregnated with bFGF at 7 or 14 μg/cm(2) after debridement, and the wound bed improvement was assessed 14 days after application. Wound bed improvement was defined as a granulated and epithelialized area on day 14 with a proportion to the baseline wound area after debridement of 50% or higher. The wound area, the wound area on day 14, and the granulation area on day 14 were independently measured by blinded reviewers in a central review using digital images of wounds taken with a calibrator. Patients were followed up until 28 days after application to observe the adverse reactions related to the application of CGS. From May 2010 to June 2011, 17 patients were enrolled and, in 16 patients, the wound bed improved. Among the randomized patients in step 2, no significant difference was seen between the low-dose group and the high-dose group. No serious adverse reactions were observed. Adverse reactions with a clear causal relationship to the study treatment were mild and patients quickly recovered from them. This study is the first-in-man clinical trial of CGS and showed the safety and efficacy of CGS impregnated with bFGF in the treatment of chronic skin ulcers. This combination therapy could be a promising therapy for chronic skin ulcers. PMID:23541061

  13. Isolation, growth and differentiation of equine mesenchymal stem cells: effect of donor, source, amount of tissue and supplementation with basic fibroblast growth factor.

    PubMed

    Colleoni, Silvia; Bottani, Emanuela; Tessaro, Irene; Mari, Gaetano; Merlo, Barbara; Romagnoli, Noemi; Spadari, Alessandro; Galli, Cesare; Lazzari, Giovanna

    2009-12-01

    Mesenchymal stem cells (MSC) are increasingly used as therapeutical aid for the orthopaedic injuries in the horse. MSC populate different tissues but the most commonly used for clinical purposes are isolated from bone marrow or adipose tissue. The first objective of this study was to investigate if the donor animal, the tissue of origin and the technique of isolation could influence the number of MSC available for transplantation after a short-term expansion. The second aim was to devise a culture system capable of increasing MSC lifespan and we tested the effect of basic fibroblast growth factor (bFGF). Results indicate that MSC can be efficiently isolated from both sources and supplementation of bFGF enhances proliferation rate maintaining differentiation potential. In addition, this study shows that collection, expansion and storage of frozen MSC can be performed for later therapeutic use. PMID:19472068

  14. The constitutive level of vascular endothelial growth factor (VEGF) is more important than hypoxia-induced VEGF up-regulation in the angiogenesis of human melanoma xenografts

    PubMed Central

    Danielsen, T; Rofstad, E K

    2000-01-01

    Angiogenesis of tumours might develop as a result of environmental conditions, such as hypoxia, and/or as a result of genetic alterations specific for tumour cells. The relative contributions of these mechanisms were investigated by comparing the in vivo expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to the hypoxic fraction, the angiogenic potential and the vascular density of four human melanoma lines (A-07, D-12, R-18, U-25) grown intradermally in Balb/c nu/nu mice. VEGF expression, bFGF expression and expression of pimonidazole, a marker of hypoxic cells, were investigated by immunohistochemistry. An association between high VEGF and bFGF expression and high angiogenic potential was detected, suggesting an important role for VEGF/bFGF in the angiogenesis of melanomas. High VEGF/bFGF expression was also related to low hypoxic fraction and high vascular density. Thus, the constitutive, genetically determined level of VEGF was probably more important than hypoxia-induced upregulation in the angiogenesis of the melanoma xenografts. © 2000 Cancer Research Campaign PMID:10789719

  15. Bridging nigrostriatal pathway with fibroblast growth factor-primed peripheral nerves and fetal ventral mesencephalon transplant recuperates from deficits in parkinsonian rats.

    PubMed

    Chiang, Yung-Hsiao; Lin, Shinn-Zong; Zhou, Feng C

    2006-01-01

    Previous studies have indicated that the nigrostriatal dopaminergic (DA) pathway can be reconstructed in hemiparkinsonian rats with a bridge transplantation technique involving fetal ventral mesencephalic transplants and glial cell line-derived neurotrophic factor. In this study, we examined if the nigrostriatal pathway can be restored by combining peripheral nervous tissue with the fetal ventral mesencephalon transplants. Adult rats were injected with 6-hydroxydopamine into left median forebrain bundle. Those with marked rotational behavior, which has been previously shown to indicate complete DA dennervtion, were used for transplant treatments. One month after the lesion, fetal ventral mesencephalic cells were transplanted into the nigral region followed by nigral-striatal grafting of peripheral nerves as a bridge. The bridging nerves (sciatic or intercostals) were pretreated with basic fibrous growth factor (nerve+bFGF+) or Hank's saline (nerve+bFGF-). We found that (a) animals receiving transplants of VM and bFGF+ nerve had a reduction in rotational behavior; (b) animals receiving bFGF-- nerve bridge only had a partial improvement in rotation. Reinnervation of tyrosine hydroxylase (TH)-immunoreactive (ir) fibers into the striatum was found in both of the above groups with more innervation in the former than in the latter. No TH-ir fibers in lesioned striatum or reduction in rotational behavior were found in animals receiving VM only, or VM plus bFGF. Taken together, our data indicate that peripheral nerve, with the aid of bFGF, greatly facilitates the reconstitution of the TH pathway from nigra to striatum and improves motor function in hemiparkinsonian rats. PMID:17121158

  16. Effect of intestinal ischemia-reperfusion on expressions of endogenous basic fibroblast growth factor and transforming growth factor betain lung and its relation with lung repair.

    PubMed

    Fu, Xiao-Bing; Yang, Yin-Hui; Sun, Tong-Zhu; Gu, Xiao-Man; Jiang, Li-Xian; Sun, Xiao-Qing; Sheng, Zhi-Yong

    2000-06-01

    AIM:To study the changes of endogenous transforming growth factor beta(TGFbeta) and basic fibroblast growth factor (bFGF) in lung following intestinal ischemia and reperfusion injury and their effects on lung injury and repair.METHODS:Sixty Wistar rats were divided into five groups, which underwent sham-operation, ischemia (45 minutes), and reperfusion (6, 24 and 48 hours, respectively) after ischemia (45 minutes). Immunohistochemical method was used to observe the localization and amounts of both growth factors.RESULTS:Positive signals of both growth factors could be found in normal lung, mainly in alveolar cells and endothelial cells of vein. After ischemia and reperfusion insult, expressions of both growth factors were increased and their amounts at 6 hours were larger than those of normal control or of 24 and 48 hours after insult.CONCLUSION:The endogenous bFGF and TGF beta expression appears to be upregulated in the lung following intestinal ischemia and reperfusion, suggesting that both growth factors may be involved in the process of lung injury and repair. PMID:11819596

  17. Synergistic upregulation of metalloproteinase-9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF-kappa B.

    PubMed

    Bond, M; Fabunmi, R P; Baker, A H; Newby, A C

    1998-09-11

    Matrix metalloproteinase (MMPs) enzymes are implicated in matrix remodelling during proliferative inflammatory processes including wound healing. We report here synergistic upregulation of MMP-9 protein and mRNA by platelet-derived growth factor (PDGF) or basic fibroblast growth factor (bFGF) in combination with interleukin-1alpha (IL-1alpha) or tumour necrosis factor-alpha (TNF-alpha) in primary rabbit and human dermal fibroblasts. The synergistic interaction between growth factors and cytokines implies that basement membrane remodelling is maximal physiologically when both are present together. The signalling pathways mediating this synergistic regulation are not understood, although analysis of the MMP-9 promoter has identified an essential proximal AP-1 element and an upstream nuclear factor kappa-B (NF-kappaB) site. Using electromobility shift assays, binding to the AP-1 site was only slightly increased by growth factors and cytokines. NF-kappaB binding was rapidly induced by IL-1alpha or TNF-alpha but was neither induced nor potentiated by bFGF or PDGF. Neither AP-1 nor NF-kappaB was therefore sufficient on its own for synergistic regulation. Using a recently developed adenovirus that overexpresses the inhibitory subunit, IkappaB alpha, we demonstrated an absolute requirement for NF-kappaB in upregulation of MMP-9. Activation of NF-kappaB binding by inflammatory cytokines was therefore necessary but not sufficient for synergistic upregulation of MMP-9. PMID:9755853

  18. Bevacizumab changes vascular structure and modulates the expression of angiogenic factors in recurrent malignant gliomas.

    PubMed

    Okamoto, Saori; Nitta, Masayuki; Maruyama, Takashi; Sawada, Tatsuo; Komori, Takashi; Okada, Yoshikazu; Muragaki, Yoshihiro

    2016-04-01

    Bevacizumab (BV), a monoclonal antibody against vascular endothelial growth factor (VEGF), is currently used in the treatment of malignant glioma. To understand mechanisms of resistance to BV, we investigated morphological changes in tumor vessels and expression of angiogenic factors, such as VEGF, Flt-1, basic fibroblast growth factor (bFGF), and platelet-derived growth factor-BB (PDGF-BB), in four autopsied tumors after BV treatment. Three patients had glioblastomas; the fourth had a secondary glioblastoma that developed from a diffuse astrocytoma. BV was administered because of recurrence following the use of the Stupp regimen in these four patients. We compared the initial surgical specimen with that obtained after death following BV treatment. Immunohistochemical staining of the autopsied tumors showed that Flt-1 expression increased while VEGF expression was significantly reduced. Additionally, other angiogenic factors, particularly bFGF, were enhanced. Interestingly, the proliferation of endothelial cells was reduced, but remarkable proliferation of pericytes was observed. These results suggest that following BV treatment, glioblastomas can grow tumor vessels by expressing various angiogenic factors. These mechanisms might be important for rapid regrowth and blood brain barrier repair after BV treatment. Inhibition of multiple angiogenic factors will be required to control tumor vessels in glioblastoma. PMID:26826105

  19. Evaluation of Polycaprolactone Scaffold with Basic Fibroblast Growth Factor and Fibroblasts in an Athymic Rat Model for Anterior Cruciate Ligament Reconstruction

    PubMed Central

    Kabir, Nima; Arshi, Armin; Nazemi, Azadeh; Wu, Ben; Petrigliano, Frank A.; McAllister, David R.

    2015-01-01

    Anterior cruciate ligament (ACL) rupture is a common ligamentous injury often necessitating surgery. Current surgical treatment options include ligament reconstruction with autograft or allograft, which have their inherent limitations. Thus, there is interest in a tissue-engineered substitute for use in ACL regeneration. However, there have been relatively few in vivo studies to date. In this study, an athymic rat model of ACL reconstruction was used to evaluate electrospun polycaprolactone (PCL) grafts, with and without the addition of basic fibroblast growth factor (bFGF) and human foreskin fibroblasts. We examined the regenerative potential of tissue-engineered ACL grafts using histology, immunohistochemistry, and mechanical testing up to 16 weeks postoperatively. Histology showed infiltration of the grafts with cells, and immunohistochemistry demonstrated aligned collagen deposition with minimal inflammatory reaction. Mechanical testing of the grafts demonstrated significantly higher mechanical properties than immediately postimplantation. Acellular grafts loaded with bFGF achieved 58.8% of the stiffness and 40.7% of the peak load of healthy native ACL. Grafts without bFGF achieved 31.3% of the stiffness and 28.2% of the peak load of healthy native ACL. In this in vivo rodent model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regenerative potential of our electrospun PCL ligament graft. PMID:25744933

  20. Evaluation of polycaprolactone scaffold with basic fibroblast growth factor and fibroblasts in an athymic rat model for anterior cruciate ligament reconstruction.

    PubMed

    Leong, Natalie Luanne; Kabir, Nima; Arshi, Armin; Nazemi, Azadeh; Wu, Ben; Petrigliano, Frank A; McAllister, David R

    2015-06-01

    Anterior cruciate ligament (ACL) rupture is a common ligamentous injury often necessitating surgery. Current surgical treatment options include ligament reconstruction with autograft or allograft, which have their inherent limitations. Thus, there is interest in a tissue-engineered substitute for use in ACL regeneration. However, there have been relatively few in vivo studies to date. In this study, an athymic rat model of ACL reconstruction was used to evaluate electrospun polycaprolactone (PCL) grafts, with and without the addition of basic fibroblast growth factor (bFGF) and human foreskin fibroblasts. We examined the regenerative potential of tissue-engineered ACL grafts using histology, immunohistochemistry, and mechanical testing up to 16 weeks postoperatively. Histology showed infiltration of the grafts with cells, and immunohistochemistry demonstrated aligned collagen deposition with minimal inflammatory reaction. Mechanical testing of the grafts demonstrated significantly higher mechanical properties than immediately postimplantation. Acellular grafts loaded with bFGF achieved 58.8% of the stiffness and 40.7% of the peak load of healthy native ACL. Grafts without bFGF achieved 31.3% of the stiffness and 28.2% of the peak load of healthy native ACL. In this in vivo rodent model study for ACL reconstruction, the histological and mechanical evaluation demonstrated excellent healing and regenerative potential of our electrospun PCL ligament graft. PMID:25744933

  1. Arterial Hypertension Is Characterized by Imbalance of Pro-Angiogenic versus Anti-Angiogenic Factors

    PubMed Central

    Marek-Trzonkowska, Natalia; Kwieczyńska, Anna; Reiwer-Gostomska, Magdalena; Koliński, Tomasz; Molisz, Andrzej; Siebert, Janusz

    2015-01-01

    Objective Hypertension is the most common cardiovascular disease and the main risk factor for stroke, peripheral arterial disease, arterial aneurysms and kidney disease. It has been reported recently that hypertensive patients and animals are characterized by decreased density of arterioles and capillaries in the tissues, called rarefaction. Rarefaction significantly increases peripheral resistance which results in elevated blood pressure, leads to vessel damage and induction of inflammation. Therefore, we hypothesized that hypertension is associated with decreased serum concentration of physiological pro-angiogenic factors and concomitant increased production of angiogenesis inhibitors. Materials and Methods 82 patients diagnosed with hypertension and 34 healthy volunteers were recruited to the study. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) techniques were used to measure serum levels of the following cytokines: endostatin, vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), angiogenin, and basic fibroblast growth factor (bFGF). Results Hypertensive patients were characterized by increased serum concentration of endostatin which is an anti-angiogenic factor. In addition, hypertension was associated with decreased levels of physiological pro-angiogenic mediators such as: angiogenin and bFGF. The hypertensive group was also characterized by elevated levels of CRP, VEGF and IL-8 that are the hallmarks of inflammation. Conclusions Presented results show that hypertension is characterized by imbalance of pro-angiogenic and anti-angiogenic factors in the background of inflammation. PMID:25951297

  2. Sustained calcium influx activated by basic fibroblast growth factor in Balb-c 3T3 fibroblasts.

    PubMed Central

    Munaron, L; Distasi, C; Carabelli, V; Baccino, F M; Bonelli, G; Lovisolo, D

    1995-01-01

    1. We have investigated the ionic events elicited in Balb-c 3T3 fibroblasts by basic fibroblast growth factor (bFGF), a peptide that binds to membrane receptors with tyrosine kinase activity and has a mitogenic action on many cell types. The peptide (0.2-100 ng ml-1) caused the appearance of an inward current, as observed in whole-cell patch-clamp experiments at a holding potential of -50 mV, that could last for tens of minutes and had a peak density of 4.6 +/- 2.6 pA pF-1. The reversal potential was 18.8 +/- 16.7 mV. 2. The current was reversibly abolished by removal of bFGF from the external bath. Inhibition of low-affinity FGF receptors had no effect on the activation of the inward current; it was completely abolished when cells were pre-incubated with tyrphostin or 5'-methylthioadenosine (MTA), two inhibitors of the tyrosine kinase activity of the high-affinity FGF receptors. The inward current was not activated by the emptying of internal calcium stores, as tested with 200 nM thapsigargin. 3. Values of peak current density comparable to control ones were obtained when either all Na+ ions or all Ca2+ ions were removed from the external solution; when both ions were completely removed, no inward current could be observed. The inward current was not affected by 2 microM nifedipine, and was reversibly blocked by the imidazole derivative SK&F 96365-A. 4. Measurements of free intracellular calcium concentration ([Ca2+]i) with the dye fura-2 showed that bFGF elicited sustained increases in [Ca2+]i that were completely dependent on external calcium and on the presence of the agonist and could last more than 1 h. 5. Single channel currents (conductance 7.9 pS) in response to bFGF stimulation could be recorded in the cell-attached configuration with 100 mM CaCl2 in the pipette. When the resting potential was brought near to 0 mV by external perfusion in a high-K+ solution, Vrev was about 0 mV. 6. We conclude that in Balb-c 3T3 cells bFGF induces an inward current that

  3. Sustained calcium influx activated by basic fibroblast growth factor in Balb-c 3T3 fibroblasts.

    PubMed

    Munaron, L; Distasi, C; Carabelli, V; Baccino, F M; Bonelli, G; Lovisolo, D

    1995-05-01

    1. We have investigated the ionic events elicited in Balb-c 3T3 fibroblasts by basic fibroblast growth factor (bFGF), a peptide that binds to membrane receptors with tyrosine kinase activity and has a mitogenic action on many cell types. The peptide (0.2-100 ng ml-1) caused the appearance of an inward current, as observed in whole-cell patch-clamp experiments at a holding potential of -50 mV, that could last for tens of minutes and had a peak density of 4.6 +/- 2.6 pA pF-1. The reversal potential was 18.8 +/- 16.7 mV. 2. The current was reversibly abolished by removal of bFGF from the external bath. Inhibition of low-affinity FGF receptors had no effect on the activation of the inward current; it was completely abolished when cells were pre-incubated with tyrphostin or 5'-methylthioadenosine (MTA), two inhibitors of the tyrosine kinase activity of the high-affinity FGF receptors. The inward current was not activated by the emptying of internal calcium stores, as tested with 200 nM thapsigargin. 3. Values of peak current density comparable to control ones were obtained when either all Na+ ions or all Ca2+ ions were removed from the external solution; when both ions were completely removed, no inward current could be observed. The inward current was not affected by 2 microM nifedipine, and was reversibly blocked by the imidazole derivative SK&F 96365-A. 4. Measurements of free intracellular calcium concentration ([Ca2+]i) with the dye fura-2 showed that bFGF elicited sustained increases in [Ca2+]i that were completely dependent on external calcium and on the presence of the agonist and could last more than 1 h. 5. Single channel currents (conductance 7.9 pS) in response to bFGF stimulation could be recorded in the cell-attached configuration with 100 mM CaCl2 in the pipette. When the resting potential was brought near to 0 mV by external perfusion in a high-K+ solution, Vrev was about 0 mV. 6. We conclude that in Balb-c 3T3 cells bFGF induces an inward current that

  4. Ethanol Alters Production and Secretion of Estrogen-Regulated Growth Factors That Control Prolactin-Secreting Tumors in the Pituitary

    PubMed Central

    Sarkar, Dipak K.; Boyadjieva, Nadka I.

    2010-01-01

    Background Chronic administration of ethanol increases plasma prolactin levels and enhances estradiol’s mitogenic action on the lactotropes of the pituitary gland. The present study was conducted to determine whether ethanol’s lactotropic cell-proliferating action, like estradiol’s, is associated with alteration in the production of 3 peptides that regulate cell growth: transforming growth factor beta 1 (TGF-β1), TGF-β3 and basic fibroblast growth factor (bFGF). Methods Using ovariectomized Fischer-344 female rats, we determined ethanol’s and estradiol’s actions on lactotropic cell proliferation and growth-regulatory peptide production and release in the pituitary gland during tumorigenesis. Results Ethanol increased basal and estradiol-enhanced mitosis of lactotropes in the pituitary glands of ovariectomized rats. The level of growth-inhibitory TGF-β1 was reduced in the pituitary following ethanol and/or estradiol treatment for 2 and 4 weeks. In contrast, ethanol and estradiol alone as well as together increased levels of growth-stimulatory TGF-β3 and bFGF in the pituitary at 2 and 4 weeks. In primary cultures of pituitary cells, both ethanol and estradiol reduced TGF-β1 release and increased TGF-β3 and bFGF release at 24 hours. Ethanol’s effect on growth factor levels in the pituitary or growth factor release from the pituitary cells was less than that of estradiol. When ethanol and estradiol were applied together, their individual effects on these growth factors were amplified. Conclusions These results confirm estradiol’s modulation of pituitary growth factor production and release, and provide evidence that ethanol, like estradiol, alters the production and secretion of growth-regulatory peptides controlling lactotropic cell proliferation. PMID:18034699

  5. Angiogenic factors in chronic lymphocytic leukaemia (CLL): Where do we stand?

    PubMed

    Aguirre Palma, Luis Mario; Gehrke, Iris; Kreuzer, Karl-Anton

    2015-03-01

    The role of angiogenesis in haematological malignancies such as chronic lymphocytic leukaemia (CLL) is difficult to envision, because leukaemia cells are not dependent on a network of blood vessels to support basic physiological requirements. Regardless, CLL cells secrete high levels of major angiogenic factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF). Nonetheless, it remains unclear how most angiogenic factors regulate accumulation and delayed apoptosis of CLL cells. Angiogenic factors such as leptin, granulocyte colony-stimulating factor (G-CSF), follistatin, angiopoietin-1 (Ang1), angiogenin (ANG), midkine (MK), pleiotrophin (PTN), progranulin (PGRN), proliferin (PLF), placental growth factor (PIGF), and endothelial locus-1 (Del-1), represent novel therapeutic targets of future CLL research but have remained widely overlooked. This review aims to outline our current understanding of angiogenic growth factors and their relationship with CLL, a still uncured haematopoietic malignancy. PMID:25459668

  6. Como Lo Hago Yo: Myelomeningocele

    PubMed Central

    Lazareff, Jorge

    2014-01-01

    Fortificación con ádico fólico es efectiva, pero aún falta conciencia en los jóvenes. La legalidad del aborto aumenta la importancia de la consulta prenatal. Realizo la cirugía bajo microcoscopio por razones didácticas. Irrigación continua para reducir la temperatura del tejido. Trato a la plaqueta como tejido viable. No suturo la plaqueta. No cierro músculo. ATB por una semana después de cirugía. Hidrocefalia: Válvula en todos los casos de ventriculomegalia. Médula anclada: Desanclar una sola vez. Chiari II: Revisar la válvula. Incluir en el seguimiento rendimiento escolar, puede indicar obstrucción de la válvula o médula anclada. PMID:24791217

  7. Energetic characterization of the basic fibroblast growth factor-heparin interaction: identification of the heparin binding domain.

    PubMed

    Thompson, L D; Pantoliano, M W; Springer, B A

    1994-04-01

    Fibroblast growth factors (FGF's) interact on cell surfaces with "low-affinity" heparan sulfate proteoglycans (HSPG) and "high-affinity" FGF receptors (FGFR) to initiate cell proliferation. Previous reports have implicated the binding of heparin, or heparan sulfate, to FGF as essential for FGF-mediated signal transduction and mitogenicity. However, the molecular recognition events which dictate the specificity of this interaction have remained elusive. Amino acid residues on the surface of basic FGF (bFGF) were targeted as potential heparin contacts on the basis of the position of sulfate anions in the X-ray crystal structure of bFGF and of a modeled pentasaccharide heparin-bFGF complex. Each identified amino acid was replaced individually with alanine by site-directed mutagenesis, and the resulting mutant proteins were characterized for differences in binding to a low molecular weight heparin (approximately 3000) by isothermal titrating calorimetry and also for differences in [NaCl] elution from a heparin-Sepharose affinity resin. The combination of site-directed mutagenesis and titrating calorimetry permitted an analysis of the energetic contributions of individual bFGF residues in the binding of heparin to bFGF. The key amino acids which comprise the heparin binding domain on bFGF constitute a discontinuous binding epitope and include K26, N27, R81, K119, R120, T121, Q123, K125, K129, Q134, and K135. Addition of the observed delta delta G degrees of binding for each single site mutant accounts for 8.56 kcal/mol (> 95%) of the free energy of binding. The delta delta G degrees values for N27A, R120A, K125A, and Q134A are all greater than 1 kcal/mol each, and these four amino acids together contribute 4.8 kcal/mol (56%) to the total binding free energy. Amino acid residues K119 through K135 reside in the C-terminal domain of bFGF and collectively contribute 6.6 kcal/mol (76%) of the binding free energy. Although 7 out of the 11 identified amino acids in the heparin

  8. Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis.

    PubMed Central

    Yoshida, S; Ono, M; Shono, T; Izumi, H; Ishibashi, T; Suzuki, H; Kuwano, M

    1997-01-01

    Tumor necrosis factor alpha (TNF-alpha) is a macrophage/monocyte-derived polypeptide which modulates the expression of various genes in vascular endothelial cells and induces angiogenesis. However, the underlying mechanism by which TNF-alpha mediates angiogenesis is not completely understood. In this study, we assessed whether TNF-alpha-induced angiogenesis is mediated through TNF-alpha itself or indirectly through other TNF-alpha-induced angiogenesis-promoting factors. Cellular mRNA levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and their receptors were increased after the treatment of human microvascular endothelial cells with TNF-alpha (100 U/ml). TNF-alpha-dependent tubular morphogenesis in vascular endothelial cells was inhibited by the administration of anti-IL-8, anti-VEGF, and anti-bFGF antibodies, and coadministration of all three antibodies almost completely abrogated tubular formation. Moreover, treatment with Sp1, NF-kappaB, and c-Jun antisense oligonucleotides inhibited TNF-alpha-dependent tubular morphogenesis by microvascular endothelial cells. Administration of a NF-kappaB antisense oligonucleotide almost completely inhibited TNF-alpha-dependent IL-8 production and partially abrogated TNF-alpha-dependent VEGF production, and an Sp1 antisense sequence partially inhibited TNF-alpha-dependent production of VEGF. A c-Jun antisense oligonucleotide significantly inhibited TNF-alpha-dependent bFGF production but did not affect the production of IL-8 and VEGF. Administration of an anti-IL-8 or anti-VEGF antibody also blocked TNF-alpha-induced neovascularization in the rabbit cornea in vivo. Thus, angiogenesis by TNF-alpha appears to be modulated through various angiogenic factors, both in vitro and in vivo, and this pathway is controlled through paracrine and/or autocrine mechanisms. PMID:9199336

  9. Fabrication of chondroitin sulfate-chitosan composite artificial extracellular matrix for stabilization of fibroblast growth factor.

    PubMed

    Mi, Fwu-Long; Shyu, Shin-Shing; Peng, Chih-Kang; Wu, Yu-Bey; Sung, Hsing-Wen; Wang, Pei-Shan; Huang, Chi-Chuan

    2006-01-01

    The development of a novel, three-dimensional, macroporous artificial extracellular matrix (AECM) based on chondroitin sulfate (ChS)-chitosan (Chito) combination is reported. The composite AECM composed of ChS-Chito conjugated network was prepared by a homogenizing interpolyelectrolyte complex/covalent conjugation technique through co-crosslinked with N,N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide (EDC) and N-hydroxysuccinimide (NHS). In contrast to EDC/NHS, two different reagents, calcium ion and glutaraldehyde, were used to react with ChS or Chito for the preparation of ChS-Chito composites containing crosslinked ChS or Chito network in the matrix. The stability and in vitro enzymatic degradability of the glutaraldehyde-, EDC/NHS-, and Ca2+ -crosslinked ChS-Chito composite AECMs were all investigated in this study. The results showed that crosslinking improved the stability of prepared ChS-Chito AECMs in physiological buffer solution (PBS) and provided superior protective effect against the enzymatic hydrolysis of ChS, compared with their non-crosslinked counterpart. Because ChS was a heparin-like glycosaminoglycan (GAG), the ChS-Chito composite AECMs appeared to promote binding efficiency for basic fibroblast growth factor (bFGF). The bFGF releasing from the ChS-Chito composite AECMs retained its biological activity as examined by the in vitro proliferation of human fibroblast, depending on the crosslinking mode for the preparation of these composite AECMs. Histological assay showed that the EDC/NHS-crosslinked ChS-Chito composite AECM, after incorporated with bFGF, was biodegradable and could result in a significantly enhanced vascularization effect and tissue penetration. These results suggest that the ChS-Chito composite AECMs fabricated in this study may be a promising approach for tissue-engineering application. PMID:16224775

  10. Nanoscale growth factor patterns by immobilization on a heparin-mimicking polymer.

    PubMed

    Christman, Karen L; Vázquez-Dorbatt, Vimary; Schopf, Eric; Kolodziej, Christopher M; Li, Ronald C; Broyer, Rebecca M; Chen, Yong; Maynard, Heather D

    2008-12-10

    In this study, electrostatic interactions between sulfonate groups of an immobilized polymer and the heparin binding domains of growth factors important in cell signaling were exploited to nanopattern the proteins. Poly(sodium 4-styrenesulfonate-co-poly(ethylene glycol) methacrylate) (pSS-co-pPEGMA) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization using ethyl S-thiobenzoyl-2-thiopropionate as a chain transfer agent and 2,2'-azoisobutyronitrile (AIBN) as the initiator. The resulting polymer (1) was characterized by 1H NMR, GPC, FT-IR, and UV-vis and had a number average molecular weight (Mn) of 24,000 and a polydispersity index (PDI) of 1.17. The dithioester end group of 1 was reduced to the thiol, and the polymer was subsequently immobilized on a gold substrate. Binding of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) to the polymer via the heparin binding domains was then confirmed by surface plasmon resonance (SPR). The interactions were stable at physiological salt concentrations. Polymer 1 was cross-linked onto silicon wafers using an electron beam writer forming micro- and nanopatterns. Resolutions of 100 nm and arbitrary nanoscale features such as concentric circles and contiguous squares and triangles were achieved. Fluorescence microscopy confirmed that bFGF and VEGF were subsequently immobilized to the polymer micro- and nanopatterns. PMID:19554729

  11. Cynaropicrin from Cynara scolymus L. suppresses photoaging of skin by inhibiting the transcription activity of nuclear factor-kappa B.

    PubMed

    Tanaka, Yuka Tsuda; Tanaka, Kiyotaka; Kojima, Hiroyuki; Hamada, Tomoji; Masutani, Teruaki; Tsuboi, Makoto; Akao, Yukihiro

    2013-01-15

    Aging of skin is characterized by skin wrinkling, laxity, and pigmentation induced by several environmental stress factors. Histological changes during the photoaging of skin include hyperproliferation of keratinocytes and melanocytes causing skin wrinkles and pigmentation. Nuclear factor kappa B (NF-κB) is one of the representative transcription factors active in conjunction with inflammation. NF-κB is activated by stimulation such as ultraviolet rays and inflammatory cytokines and induces the expression of various genes such as those of basic fibroblast growth factor (bFGF) and matrix metalloprotease-1 (MMP-1). We screened several plant extracts for their possible inhibitory effect on the transcriptional activity of NF-κB. One of them, an extract from Cynara scolymus L., showed a greatest effect on the suppression of NF-κB transactivation. As a result, we found that cynaropicrin, which is a sesquiterpene lactone, inhibited the NF-κB-mediated transactivation of bFGF and MMP-1. Furthermore, it was confirmed that in an in vivo mouse model cynaropicrin prevented skin photoaging processes leading to the hyperproliferation of keratinocytes and melanocytes. These findings taken together indicate that cynaropicrin is an effective antiphotoaging agent that acts by inhibiting NF-κB-mediated transactivation. PMID:23232059

  12. Acoustic droplet–hydrogel composites for spatial and temporal control of growth factor delivery and scaffold stiffness

    PubMed Central

    Fabiilli, Mario L.; Wilson, Christopher G.; Padilla, Frédéric; Martín-Saavedra, Francisco M.; Fowlkes, J. Brian; Franceschi, Renny T.

    2013-01-01

    Wound healing is regulated by temporally and spatially restricted patterns of growth factor signaling, but there are few delivery vehicles capable of the “on-demand” release necessary for recapitulating these patterns. Recently we described a perfluorocarbon double emulsion that selectively releases a protein payload upon exposure to ultrasound through a process known as acoustic droplet vaporization (ADV). In this study, we describe a delivery system composed of fibrin hydrogels doped with growth factor-loaded double emulsion for applications in tissue regeneration. Release of immunoreactive basic fibroblast growth factor (bFGF) from the composites increased up to 5-fold following ADV and delayed release was achieved by delaying exposure to ultrasound. Releasates of ultrasound-treated materials significantly increased the proliferation of endothelial cells compared to sham controls, indicating that the released bFGF was bioactive. ADV also triggered changes in the ultrastructure and mechanical properties of the fibrin as bubble formation and consolidation of the fibrin in ultrasound-treated composites were accompanied by up to a 22-fold increase in shear stiffness. ADV did not reduce the viability of cells suspended in composite scaffolds. These results demonstrate that an acoustic droplet–hydrogel composite could have broad utility in promoting wound healing through on-demand control of growth factor release and/or scaffold architecture. PMID:23535233

  13. Basic fibroblast growth factor: a potential new therapeutic tool for the treatment of hypertrophic and keloid scars.

    PubMed

    Tiede, Stephan; Ernst, Nancy; Bayat, Ardeshir; Paus, Ralf; Tronnier, Volker; Zechel, Christina

    2009-01-01

    Numerous tissue niches in the human body, such as skin, are now recognized to harbour adult stem cells. In this study, we analyze multipotent human dermis-derived progenitor cell populations, isolated and propagated from mechanically and enzymatically processed adult scalp skin. The populations encompass Nestin-positive and -negative cells, which may serve as a convenient and abundant source for various therapeutic applications in regenerative medicine. Here, we show that these cultures exhibit a strong tendency to differentiate into mesodermal derivatives, particularly myofibroblasts, when maintained in media containing serum. Since undesired and excessive myofibroblast formation is a frequent postsurgical complication, we sought culture conditions that would prevent myofibroblast formation. In particular, we analyzed the effect of growth factors, such as epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and platelet-derived growth factor AB (PDGF AB). Our results demonstrate that bFGF is a potent inhibitor of mesodermal differentiation, whereas PDFG AB favours myofibroblast formation and up-regulates expression of TGFbeta receptors I and II. This interesting discovery may help in the prevention and treatment of tissue fibrosis and in particular in the eradication of hypertrophic and keloid scars. PMID:19071002

  14. Purified human pancreatic duct cell culture conditions defined by serum-free high-content growth factor screening.

    PubMed

    Hoesli, Corinne A; Johnson, James D; Piret, James M

    2012-01-01

    The proliferation of pancreatic duct-like CK19+ cells has implications for multiple disease states including pancreatic cancer and diabetes mellitus. The in vitro study of this important cell type has been hampered by their limited expansion compared to fibroblast-like vimentin+ cells that overgrow primary cultures. We aimed to develop a screening platform for duct cell mitogens after depletion of the vimentin+ population. The CD90 cell surface marker was used to remove the vimentin+ cells from islet-depleted human pancreas cell cultures by magnetic-activated cell sorting. Cell sorting decreased CD90+ cell contamination of the cultures from 34±20% to 1.3±0.6%, yielding purified CK19+ cultures with epithelial morphology. A full-factorial experimental design was then applied to test the mitogenic effects of bFGF, EGF, HGF, KGF and VEGF. After 6 days in test conditions, the cells were labelled with BrdU, stained and analyzed by high-throughput imaging. This screening assay confirmed the expected mitogenic effects of bFGF, EGF, HGF and KGF on CK19+ cells and additionally revealed interactions between these factors and VEGF. A serum-free medium containing bFGF, EGF, HGF and KGF led to CK19+ cell expansion comparable to the addition of 10% serum. The methods developed in this work should advance pancreatic cancer and diabetes research by providing effective cell culture and high-throughput screening platforms to study purified primary pancreatic CK19+ cells. PMID:22442738

  15. Reinforcement of transvaginal repair using polypropylene mesh functionalized with basic fibroblast growth factor.

    PubMed

    Zhang, Dandan; Lin, Zhi Yuan William; Cheng, Ruoyu; Wu, Wei; Yu, Jia; Zhao, Xin; Chen, Xinliang; Cui, Wenguo

    2016-06-01

    Numerous modifications have been developed over the past two decades seeking to improve the transvaginal repair in the pelvic organ prolapse (POP) by using polypropylene (PP) mesh implants. The hydrophobicity of PP, however, presents a great hindrance for translating potential technologies into viable clinical applications. In this study, by manipulating self-polymerization and strong adhesive characteristics of dopamine, we developed a facile method to enhance the transvaginal repair by modifying PP meshes with polydopamine (PDA), which allowed easy grafting of basic fibroblast growth factor (bFGF) onto the surface of PP. Such surface modification of PP meshes with bFGF was found to efficiently promote bioactivity without changing the morphology or mechanical properties of the PP meshes. Additionally, bFGF-modified PP meshes significantly promoted cell viability and adhesion compared to the unmodified PP. Ultimately, after three months of implantation, the bFGF-modified PP meshes exhibited improved tissue repair with greater degree of organization of deposited collagen, increased tensile strength and reduced inflammatory response. Overall, the surface-modified PP meshes will be highly practical as templates for transvaginal repair in the POP treatment. PMID:26925721

  16. Pedagogical Factors That Influence EFL Teaching: Some Considerations for Teachers' Professional Development (Factores pedagógicos que influyen en la enseñanza del inglés como lengua extranjera: algunas consideraciones para el desarrollo profesional de docentes)

    ERIC Educational Resources Information Center

    Abad, José Vicente

    2013-01-01

    In this article we present the results of a qualitative research study on the pedagogical factors that influence English teaching in four public schools of Medellín, Colombia. Twelve teachers were interviewed regarding three linguistic principles: communicative competence, native language effect, and interlanguage. The data analysis led to the…

  17. General pharmacology of recombinant human basic fibroblast growth factor.

    PubMed

    Okumura, M; Yajima, M; Nishimura, T; Ikeda, H; Nishimori, T

    1996-07-01

    General pharmacological effects of recombinant human basic fibroblast growth factor (bFGF) were investigated. 1. Central nervous system: Basic FGF produced almost no effect on the general symptoms and behaviors of mice. Basic FGF did not influence the spontaneous motor activity, hexobarbital-induced anesthesia, electroshock seizure threshold, pentylenetetrazole-induced seizure in mice and normal body temperature and spinal reflex in rats up to a dose of 1 mg/kg (s.c., i.v.). As regards pain sensation, it inhibited the acetic acid-induced writhing at 1 mg/kg (s.c.). No abnormal waves were observed in spontaneous EEG of the rabbit up to 1 mg/kg (i.v.) of bFGF, but at 0.1 mg/kg it had a slight effect on the ratio of EEG levels and at 1 mg/kg induced an increase in rest period, disappearance in the period of fast wave sleep and a decrease in the period of deep sleep. 2. Somatic nervous system: Basic FGF did not influence the corneal reflex, twitch response of the skin and diaphragm-phrenic nerve preparations. 3. Autonomic nervous system and smooth muscle: Basic FGF showed little effects on the spontaneous movement of the isolated ileum, contraction induced by various agonists in isolated ileum, resting tension and noradrenaline(NA)-induced contraction of the aorta, resting tension and histamine-induced contraction of isolated trachea, spontaneous movement and 5-HT-induced contraction of isolated strips of stomach fundus, NA-induced contraction of isolated vas deferens of the rat up to the concentration of 10(-4) g/ml. Basic FGF augmented the tone of the isolated non-pregnant uterus at the concentrations of 10(-5) g/ml and above and inhibited or tended to inhibit the contractile tension of non-pregnant or pregnant uterus at 10(-4) g/ml, but it did not influence the spontaneous movement of the uterus, either the non-pregnant or pregnant, under in situ conditions even at a dose of 1 mg/kg (i.v.). Basic FGF did not influence the pupil size. 4. Respiratory and circulatory

  18. Como Lo Hago Yo: Mielomeningocele En Bolivia

    PubMed Central

    Dabdoub, Carlos F.; Dabdoub, Carlos B.; Villavicencio, Ramiro; Quevedo, Germán

    2014-01-01

    ón: En esta serie, el diagnóstico prenatal del MMC fue ocasional y la derivación al HUJ de los recién nacidos con esta malformación fue generalmente tardía. No hubo predominio de género y la mayoría de los casos presentaron sus lesiones en la región lumbar y lumbosacra. La mortalidad general y postoperatoria fue similar a la reportada en la literatura. Pocos enfermos realizaron controles posteriores al alta hospitalaria. Igual que otros países de Sudamérica, las falencias en el sistema público de salud y el nivel sociocultural, son factores determinantes para un mal pronóstico en estos niños. Por sus múltiples complicaciones, el MMC requiere de una especial atención gubernamental, sobre todo de carácter preventivo mediante el uso de ácido fólico en mujeres fértiles, como también de un equipo profesional multidisciplinario, a fin de realizar un tratamiento adecuado y oportuno. Al mismo tiempo, trabajos multicéntricos en hospitales de América Latina, ayudarán al mejor manejo de estos pacientes. PMID:24791220

  19. Transforming growth factor-beta1-induced activation of the Raf-MEK-MAPK signaling pathway in rat lung fibroblasts via a PKC-dependent mechanism.

    PubMed

    Axmann, A; Seidel, D; Reimann, T; Hempel, U; Wenzel, K W

    1998-08-19

    In fibroblasts transforming growth factor-beta1 (TGF-beta1) regulates cell proliferation and turnover of macromolecular components of the extracellular matrix. Here, intracellular signaling events in growth-inhibited embryonic rat lung fibroblasts (RFL-6) upon stimulation with TGF-beta1 were investigated. TGF-beta1 rapidly induced the activation of c-Raf-1, MEK-1, and MAPK p42 and p44. The activation of this pathway by TGF-beta1 did not depend on autocrine platelet-derived growth factor (PDGF) or basic fibroblast growth factor (bFGF). Inhibition of the binding of growth factors to their tyrosine kinase receptors did not affect MAPK activation by TGF-beta1. Ras activation by TGF-beta1 was significantly lower compared to the activation by PDGF or bFGF. The intracellular transduction of the TGF-beta1 signal was completely suppressed by depletion or inhibition of protein kinase C (PKC). It is shown that calcium-dependent isoforms of PKC are required for MAPK activation by TGF-beta1. PMID:9712718

  20. An In Vivo Characterization of Trophic Factor Production Following Neural Precursor Cell or Bone Marrow Stromal Cell Transplantation for Spinal Cord Injury

    PubMed Central

    Hawryluk, Gregory W.J.; Mothe, Andrea; Wang, Jian; Wang, Shelly; Tator, Charles

    2012-01-01

    Cellular transplantation strategies for repairing the injured spinal cord have shown consistent benefit in preclinical models, and human clinical trials have begun. Interactions between transplanted cells and host tissue remain poorly understood. Trophic factor secretion is postulated a primary or supplementary mechanism of action for many transplanted cells, however, there is little direct evidence to support trophin production by transplanted cells in situ. In the present study, trophic factor expression was characterized in uninjured, injured-untreated, injured-treated with transplanted cells, and corresponding control tissue from the adult rat spinal cord. Candidate trophic factors were identified in a literature search, and primers were designed for these genes. We examined in vivo trophin expression in 3 paradigms involving transplantation of either brain or spinal cord-derived neural precursor cells (NPCs) or bone marrow stromal cells (BMSCs). Injury without further treatment led to a significant elevation of nerve growth factor (NGF), leukemia inhibitory factor (LIF), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β1 (TGF-β1), and lower expression of vascular endothelial growth factor isoform A (VEGF-A) and platelet-derived growth factor-A (PDGF-A). Transplantation of NPCs led to modest changes in trophin expression, and the co-administration of intrathecal trophins resulted in significant elevation of the neurotrophins, glial-derived neurotrophic factor (GDNF), LIF, and basic fibroblast growth factor (bFGF). BMSCs transplantation upregulated NGF, LIF, and IGF-1. NPCs isolated after transplantation into the injured spinal cord expressed the neurotrophins, ciliary neurotrophic factor (CNTF), epidermal growth factor (EGF), and bFGF at higher levels than host cord. These data show that trophin expression in the spinal cord is influenced by injury and cell transplantation, particularly when combined with intrathecal trophin infusion

  1. Silk fibroin sponges with cell growth-promoting activity induced by genetically fused basic fibroblast growth factor.

    PubMed

    Kambe, Yusuke; Kojima, Katsura; Tamada, Yasushi; Tomita, Naohide; Kameda, Tsunenori

    2016-01-01

    Transgenic silkworm technology has enabled the biological properties of silk fibroin protein to be altered by fusion to recombinant bioactive proteins. However, few studies have reported the fabrication of genetically modified fibroin proteins into three-dimensional spongy structures to serve as scaffolds for tissue engineering. We generated a transgenic silkworm strain that produces fibroin fused to basic fibroblast growth factor (bFGF) and processed the fibroin into a spongy structure using a simple freeze/thaw method. NIH3T3 mouse embryonic fibroblasts grown on bFGF-fused fibroin sponges proliferated and spread out well, showing half the population doubling time of cells cultured on wild-type fibroin sponges. Furthermore, the number of primary rabbit articular chondrocytes growing on bFGF-fused fibroin sponges was around five-times higher than that of the wild-type control at 3-days post cell-seeding. As the physical properties of wild-type and bFGF-fused fibroin sponges were almost identical, it is suggested that bFGF fused to fibroin retained its biological activity, even after the bFGF-fused fibroin was fabricated into the spongy structure. The bFGF-fused fibroin sponge has the potential for widespread application in the field of tissue engineering, and the method of fabricating this structure could be applicable to other recombinant bioactive fibroin proteins. PMID:26190702

  2. Modulation of the binding of basic fibroblast growth factor and heparanase activity by purified λ-carrageenan oligosaccharides.

    PubMed

    Niu, Ting-Ting; Zhang, Dong-Sheng; Chen, Hai-Min; Yan, Xiao-Jun

    2015-07-10

    Inhibitors of angiogenesis and tumor metastasis are increasingly emerging as promising agents for cancer therapy. Here, we report λ-carrageenan oligosaccharides (λ-COs), highly-sulfated oligosaccharides acting as a basic fibroblast growth factor (bFGF) antagonist and heparanase inhibitor. λ-COs with degree of polymerization (DP) from 2 to 8 degraded by λ-carrageenase were separated and purified. The structures were identified by mass spectrometry. The activities of λ-COs are closely related with DP. λ-COs showed no cytotoxicity, but inactivated bFGF-induced cell proliferation; among them, λ-carraheptaose showed highest capability. Only λ-carraheptaose can effectively bind to bFGF. Binding kinetics showed that λ-carraheptaose and suramin had different binding modes, i.e., suramin displayed a fast association and fast dissociation, but λ-carraheptaose exhibited a slow association and slow dissociation. In addition, λ-COs showed the highest heparanase inhibitory ability and abolished the endothelial cell invasion. Thus, λ-COs may provide a tool to develop of new carbohydrate-based therapeutics against cancer and angiogenesis. PMID:25857962

  3. Glial cell line-derived neurotrophic factor in combination with insulin-like growth factor 1 and basic fibroblast growth factor promote in vitro culture of goat spermatogonial stem cells.

    PubMed

    Bahadorani, M; Hosseini, S M; Abedi, P; Abbasi, H; Nasr-Esfahani, M H

    2015-01-01

    Growth factors are increasingly considered as important regulators of spermatogonial stem cells (SSCs). This study investigated the effects of various growth factors (GDNF, IGF1, bFGF, EGF and GFRalpha-1) on purification and colonization of undifferentiated goat SSCs under in vitro and in vivo conditions. Irrespective of the culture condition used, the first signs of developing colonies were observed from day 4 of culture onwards. The number of colonies developed in GDNF + IGF1 + bFGF culture condition was significantly higher than the other groups (p < 0.05). In contrast, the size of colonies developed in GDNF + EGF + LIF culture condition was significantly higher than the other groups (p < 0.05). Immunocytochemical stationing for specific biomarkers of somatic cells (vimentin, alpha-inhibin and α-SMA) and spermatogonial cells (PLZF, THY 1, VASA, alpha-1 integrin, bet-1 integrin and DBA) revealed that both cell types existed in developing colonies, irrespective of the culture condition used. Even though, the relative abundance of VASA, FGFR3, OCT4, PLZF, BCL6B and THY1 transcription factors in GDNF + IGF1 + bFGF treatment group was significantly higher than the other groups (p < 0.05). Additionally, goat SSCs developed in the latter culture condition could colonize within the seminiferous tubules of the germ-cell depleted recipient mice following xenotransplantation. Obtained results demonstrated that combination of GDNF with IGF1 and bFGF promote in vitro culture of goat SSCs while precludes uncontrolled proliferation of somatic cells. PMID:26154310

  4. Evaluation of Three Growth Factors for TMJ Disc Tissue Engineering

    PubMed Central

    Detamore, Michael S.; Athanasiou, Kyriacos A.

    2015-01-01

    Arguably one of the most complex joints in the body, the temporomandibular joint (TMJ) presents one of the most difficult problems in modern medicine. Tissue engineering, for the TMJ disc in particular, has been proposed as a potential breakthrough treatment strategy for TMJ disorders. Central to tissue engineering is understanding growth factor effects on TMJ disc cells, and to the best of our knowledge, this is the first 3D growth factor study for these cells. The purpose was to examine the effects of high and low concentrations of basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF), and transforming growth factor-β1 (TGF-β) on porcine TMJ disc cells. Cells were seeded onto non-woven PGA scaffolds (95% porosity) in spinner flasks, then cultured with a growth factor for 6 weeks. Constructs were analyzed for mechanical and structural integrity, cell number, and matrix biosynthesis. All growth factors improved mechanical and structural integrity compared to the control. IGF and TGF-β were most effective at promoting collagen synthesis, although there were no significant differences in glycosaminoglycan synthesis or cell number between any groups. After considering the economic advantage of IGF over TGF-β, the conclusion of this study is to use IGF in future TMJ disc tissue engineering experiments. PMID:15868729

  5. In vitro and in vivo evaluation of a novel collagen/cellulose nanocrystals scaffold for achieving the sustained release of basic fibroblast growth factor.

    PubMed

    Li, Weichang; Lan, Yong; Guo, Rui; Zhang, Yi; Xue, Wei; Zhang, Yuanming

    2015-01-01

    Tissue-engineered dermis is thought to be the best treatment for skin defects; however, slow vascularization of these biomaterial scaffolds limits their clinical application. Exogenous administration of angiogenic growth factors is highly desirable for tissue regeneration. In this study, biodegradable gelatin microspheres (GMs) containing basic fibroblast growth factor (bFGF) were fabricated and incorporated into a porous collagen/cellulose nanocrystals (CNCs) scaffold, as a platform for long-term release and consequent angiogenic boosting. The physicochemical properties of these scaffolds were examined and the in vitro release pattern of bFGF from scaffolds was measured by ELISA. Collagen/CNCs scaffolds with and without bFGF-GMs were incubated with human umbilical vein endothelial cells for 1 week, results showed that the scaffolds with bFGF-GMs significantly augmented cell proliferation. Then, four different groups of scaffolds were implanted subcutaneously into Sprague-Dawley rats to study angiogenesis in vivo via macroscopic observation, and hematoxylin and eosin and immunohistochemical staining. The results suggested that the collagen/CNCs/bFGF-GMs scaffolds had a significantly higher number of newly formed and mature blood vessels, and the fastest degradation rate. This study demonstrated that collagen/CNCs/bFGF-GMs scaffolds have great potential in skin tissue engineering. PMID:25114196

  6. Differentiation of ionic currents in CNS progenitor cells: dependence upon substrate attachment and epidermal growth factor.

    PubMed

    Feldman, D H; Thinschmidt, J S; Peel, A L; Papke, R L; Reier, P J

    1996-08-01

    Multipotential progenitor cells grown from central nervous system (CNS) tissues in defined media supplemented with epidermal growth factor (EGF), when attached to a suitable substratum, differentiate to express neural and glial histochemical markers and morphologies. To assess the functional characteristics of such cells, expression of voltage-gated Na+ and K+ currents (INa, IK) was studied by whole-cell patch clamp methods in progenitors raised from postnatal rat forebrain. Undifferentiated cells were acutely dissociated from proliferative "spheres," and differentiated cells were studied 1-25 days after plating spheres onto polylysine/laminin-treated coverslips. INa and IK were detected together in 58%, INa alone in 11%, and IK alone in 19% of differentiated cells recorded with K(+)-containing pipettes. With internal Cs+ (to isolate INa), INa up to 45 pA/pF was observed in some cells within 1 day after plating. I Na ranged up to 150 pA/pF subsequently. Overall, 84% of cells expressed I Na, with an average of 38 pA/pF. INa had fast kinetics, as in neurons, but steadystate inactivation curves were strongly negative, resembling those of glial INa. Inward tail currents sensitive to [K+]out were observed upon repolarization after the 10-ms test pulse with internal Cs+, indicating the expression of K+ channels in 82% of cells. In contrast to the substantial currents observed in differentiating cells, little or no INa or Ik-tail currents were detected in recordings from cells acutely dissociated from spheres. Thus, in the presence of EGF, ionic currents develop early during differentiation induced by attachment to an appropriate substratum. Cells switched from EGF to basic fibroblast growth factor (bFGF) when plated onto coverslips showed greatly reduced proliferation and developed less neuron-like morphologies than cells plated in the presence of EGF. INa was observed in only 53% of bFGF-treated cells, with an average of 9 pA/pF. Thus, in contrast to reports that bFGF

  7. Nerve growth factor-induced migration of endothelial cells.

    PubMed

    Dollé, Jean-Pierre; Rezvan, Amir; Allen, Fred D; Lazarovici, Philip; Lelkes, Peter I

    2005-12-01

    Nerve growth factor (NGF) is a well known neurotropic and neurotrophic agonist in the nervous system, which recently was shown to also induce angiogenic effects in endothelial cells (ECs). To measure NGF effects on the migration of cultured ECs, an important step in neoangiogenesis, we optimized an omnidirectional migration assay using human aortic endothelial cells (HAECs) and validated the assay with human recombinant basic fibroblast growth factor (rhbFGF) and human recombinant vascular endothelial growth factor (rhVEGF). The potencies of nerve growth factor purified from various species (viper, mouse, and recombinant human) to stimulate HAEC migration was similar to that of VEGF and basic fibroblast growth factor (bFGF) (EC50 of approximately 0.5 ng/ml). Recombinant human bFGF was significantly more efficacious than either viper NGF or rhVEGF, both of which stimulated HAEC migration by approximately 30% over basal spontaneous migration. NGF-mediated stimulation of HAEC migration was completely blocked by the NGF/TrkA receptor antagonist K252a [(8R*,9S*,11S*)-(/)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8,11-epoxy-1H,-8H,11H-2,7b,11a-triazadibenzo(a,g)cycloocta(c,d,e)trindene-1-one] (30 nM) but not by the VEGF/Flk receptor antagonist SU-5416 [3-[(2,4-dimethylpyrrol-5-yl) methylidenyl]-indolin-2-one] (250 nM), indicating a direct effect of NGF via TrkA receptor activation on HAEC migration. Viper NGF stimulation of HAEC migration was additively increased by either rhVEGF or rhbFGF, suggesting a potentiating interaction between their tyrosine kinase receptor signaling pathways. Viper NGF represents a novel pharmacological tool to investigate possible TrkA receptor subtypes in endothelial cells. The ability of NGF to stimulate migration of HAEC cells in vitro implies that this factor may play an important role in the cardiovascular system besides its well known effects in the nervous system. PMID:16123305

  8. Mitogenic signaling pathways of growth factors can be distinguished by the involvement of pertussis toxin-sensitive guanosine triphosphate-binding protein and of protein kinase C.

    PubMed Central

    Nishizawa, N; Okano, Y; Chatani, Y; Amano, F; Tanaka, E; Nomoto, H; Nozawa, Y; Kohno, M

    1990-01-01

    We have examined the possible involvements of pertussis toxin (PT)-sensitive guanosine triphosphate (GTP)-binding protein (Gp) and protein kinase C (PKC) in the mitogenic signaling pathways of various growth factors by the use of PT-pretreated and/or 12-O-tetradecanoyl phorbol-13-acetate (TPA)-pretreated mouse fibroblasts. Effects of PT pretreatment (inactivation of PT-sensitive Gp) and TPA pretreatment (depletion of PKC) on mitogen-induced DNA synthesis varied significantly and systematically in response to growth factors: mitogenic responses of cells to thrombin, bombesin, and bradykinin were almost completely abolished both in PT- and TPA-pretreated cells; responses to epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and vanadate were reduced to approximately 50% both in PT- and TPA-pretreated cells compared with native cells; response to basic fibroblast growth factor (bFGF) was not affected in PT-pretreated cells but was inhibited to some extent in TPA-pretreated cells. Thus, growth factors examined have been classified into three groups with regard to the involvements of PT-sensitive Gp and PKC in their signal transduction pathways. Binding of each growth factor to its receptor was not affected significantly by pretreatment of cells with PT or TPA. Inhibitory effects of PT and TPA pretreatment on each mitogen-induced DNA synthesis were not additive, suggesting that the functions of PT-sensitive Gp and PKC lie on an identical signal transduction pathway. Although all three groups of mitogens activated PKC, signaling of each growth factor depends to a varying extent on the function of PKC. Our results indicate that a single peptide growth factor such as EGF, PDGF, or bFGF acts through multiple signaling pathways to induce cell proliferation. Images PMID:2129194

  9. Molecular Imaging for Comparison of Different Growth Factors on Bone Marrow-Derived Mesenchymal Stromal Cells' Survival and Proliferation In Vivo.

    PubMed

    Qiao, Hongyu; Zhang, Ran; Gao, Lina; Guo, Yanjie; Wang, Jinda; Zhang, Rongqing; Li, Xiujuan; Li, Congye; Chen, Yundai; Cao, Feng

    2016-01-01

    Introduction. Bone marrow-derived mesenchymal stromal cells (BMSCs) have emerged as promising cell candidates but with poor survival after transplantation. This study was designed to investigate the efficacy of VEGF, bFGF, and IGF-1 on BMSCs' viability and proliferation both in vivo and in vitro using bioluminescence imaging (BLI). Methods. BMSCs were isolated from β-actin-Fluc(+) transgenic FVB mice, which constitutively express firefly luciferase. Apoptosis was induced by hypoxia preconditioning for up to 24 h followed by flow cytometry and TUNEL assay. 10(6) BMSCs with/without growth factors were injected subcutaneously into wild type FVB mice's backs. Survival of BMSCs was longitudinally monitored using bioluminescence imaging (BLI) for 5 weeks. Protein expression of Akt, p-Akt, PARP, and caspase-3 was detected by Western blot. Results. Hypoxia-induced apoptosis was significantly attenuated by bFGF and IGF-1 compared with VEGF and control group in vitro (P < 0.05). When combined with matrigel, IGF-1 showed the most beneficial effects in protecting BMSCs from apoptosis in vivo. The phosphorylation of Akt had a higher ratio in the cells from IGF-1 group. Conclusion. IGF-1 could protect BMSCs from hypoxia-induced apoptosis through activation of p-Akt/Akt pathway. PMID:27419126

  10. Molecular Imaging for Comparison of Different Growth Factors on Bone Marrow-Derived Mesenchymal Stromal Cells' Survival and Proliferation In Vivo

    PubMed Central

    Qiao, Hongyu; Zhang, Ran; Gao, Lina; Guo, Yanjie; Wang, Jinda; Zhang, Rongqing; Li, Xiujuan; Li, Congye; Chen, Yundai; Cao, Feng

    2016-01-01

    Introduction. Bone marrow-derived mesenchymal stromal cells (BMSCs) have emerged as promising cell candidates but with poor survival after transplantation. This study was designed to investigate the efficacy of VEGF, bFGF, and IGF-1 on BMSCs' viability and proliferation both in vivo and in vitro using bioluminescence imaging (BLI). Methods. BMSCs were isolated from β-actin-Fluc+ transgenic FVB mice, which constitutively express firefly luciferase. Apoptosis was induced by hypoxia preconditioning for up to 24 h followed by flow cytometry and TUNEL assay. 106 BMSCs with/without growth factors were injected subcutaneously into wild type FVB mice's backs. Survival of BMSCs was longitudinally monitored using bioluminescence imaging (BLI) for 5 weeks. Protein expression of Akt, p-Akt, PARP, and caspase-3 was detected by Western blot. Results. Hypoxia-induced apoptosis was significantly attenuated by bFGF and IGF-1 compared with VEGF and control group in vitro (P < 0.05). When combined with matrigel, IGF-1 showed the most beneficial effects in protecting BMSCs from apoptosis in vivo. The phosphorylation of Akt had a higher ratio in the cells from IGF-1 group. Conclusion. IGF-1 could protect BMSCs from hypoxia-induced apoptosis through activation of p-Akt/Akt pathway. PMID:27419126

  11. Characterization and estrogen regulation of uterine growth factor activity

    SciTech Connect

    Beck, C.A.

    1988-01-01

    Acid extracts of rat, bovine and rabbit uterus stimulated glucose transport, measured by phosphorylation of 2-deoxyglucose and DNA synthesis, measured by {sup 3}H-thymidne incorporation, in uterine tumor cells and in primary cultures of rat uterine cells. The stimulation of glucose transport was of the same magnitude and followed the same time course as estradiol stimulation in vivo. Uteri from estradiol-treated rat uteri contained 4 times more glucose transport-stimulating activity as control uteri. DNA synthetic activity in rat uterine homogenates was elevated 3-fold within 18-24 h after estradiol injection. Gel filtration showed molecular weight heterogeneity with activity eluting between 10-30 kDA. Both activities were acid and heat stable, were reduced by trypsin but not by dextran-coated charcoal. The effect of purified growth factors on DNA synthesis in primary cultures of rat uterine cells was examined. Epidermal growth factor (EGF), basic fibroblasts growth factor (bFGF), and transforming growth factor-{beta} (TGF{beta}) had no effect on {sup 3}H-thymidine incorporation.

  12. Acceleration of bone formation during fracture healing by poly(pro-hyp-gly)10 and basic fibroblast growth factor containing polycystic kidney disease and collagen-binding domains from Clostridium histolyticum collagenase.

    PubMed

    Sekiguchi, Hiroyuki; Uchida, Kentaro; Inoue, Gen; Matsushita, Osamu; Saito, Wataru; Aikawa, Jun; Tanaka, Keisuke; Fujimaki, Hisako; Miyagi, Masayuki; Takaso, Masashi

    2016-06-01

    Growth factor delivered in combination with animal-derived collagen materials has been used to accelerate bone fracture healing in human patients. However, the introduction of bovine proteins into humans carries the risk of zoonotic and immunologic complications. Here, we developed a collagen-like polypeptide-based bone formation system consisting of poly(Pro-Hyp-Gly)10 , which mimics the triple helical conformation of collagen, and basic fibroblast growth factor (bFGF) fused to the polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) of Clostridium histolyticum collagenase. Circular dichroism spectral analysis showed that when pepsin-soluble bovine type I collagen was treated at 50°C, a positive signal corresponding to the collagen triple helix at 220 nm was not detected. In contrast, poly(Pro-Hyp-Gly)10 retained the 220-nm positive peak, even when treated at 80°C. The combination of the collagen binding-bFGF fusion protein (bFGF-PKD-CBD) with poly(Pro-Hyp-Gly)10 induced greater bone formation compared to bFGF alone in mice bone fracture models. Taken together, these properties suggest that the bFGF-PKD-CBD/poly(Pro-Hyp-Gly)10 composite is a promising material for bone repair in the clinical setting. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1372-1378, 2016. PMID:26833780

  13. TLR4 inhibitor attenuates amyloid-β-induced angiogenic and inflammatory factors in ARPE-19 cells: Implications for age-related macular degeneration.

    PubMed

    Chen, Li; Bai, Yujing; Zhao, Min; Jiang, Yanrong

    2016-04-01

    Subretinally-deposited amyloid-β (Aβ) is an important factor in age‑related macular degradation (AMD) often leading to irreversible blindness in the elderly population. The molecular mechanism underlying Aβ deposition during AMD remains unclear. The expression of inflammatory and angiogenic factors was examined by treatment of retinal pigment epithelial (RPE) cells with the oligomeric form of Aβ (OAβ1-42). Changes in the mRNA expression levels of various cytokines was detected by the QuantiGenePlex 6.0 Reagent system, and the protein expression level was determined by western blotting. Culture supernatants were detected using a multiplex cytokine assay and enzyme-linked immunosorbent assays. The in vitro tube formation was evaluated by a Matrigel assay. The present study highlights that OAβ1‑42 activates the toll-like receptor 4 (TLR4), myeloid differentiation factor 88 and phosphorylation nuclear factor-κB signaling pathway in RPE cells. Additionally, it increased the mRNA and protein expression of interleukin (IL)-6, IL-8, IL-33, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiopoietin 2. Furthermore, the TLR4 inhibitor (COBRA) attenuated the expression of inflammatory and angiogenesis factors, particularly IL-6, IL-8, IL-33, bFGF and VEGF. When human umbilical vein endothelial cells (HUVECs) were co-cultured with the COBRA-treated RPE cell culture supernatant the length of the endothelial cell network (measured by calculating tip cell lengths of endothelial cells) was impaired when compared with the HUVECs that were co‑cultured with the cell supernatant exposed to OAβ1‑42. These results suggest that the TLR4-associated pathway may be a potential target for the treatment of AMD. PMID:26936827

  14. Cultured human foreskin fibroblasts produce a factor that stimulates their growth with properties similar to basic fibroblast growth factor

    SciTech Connect

    Story, M.T. )

    1989-05-01

    To determine if fibroblasts could be a source of fibroblast growth factor (FGF) in tissue, cells were initiated in culture from newborn human foreskin. Fibroblast cell lysates promoted radiolabeled thymidine uptake by cultured quiescent fibroblasts. Seventy-nine percent of the growth-promoting activity of lysates was recovered from heparin-Sepharose. The heparin-binding growth factor reacted on immunoblots with antiserum to human placenta-derived basic FGF and competed with iodinated basic FGF for binding to antiserum to (1-24)bFGF synthetic peptide. To confirm that fibroblasts were the source of the growth factor, cell lysates were prepared from cells incubated with radiolabeled methionine. Heparin affinity purified material was immunoprecipitated with basic FGF antiserum and electrophoresed. Radiolabeled material was detected on gel autoradiographs in the same molecular weight region as authentic iodinated basic FGF. The findings are consistant with the notion that cultured fibroblasts express basic FGF. As these cells also respond to the mitogen, it is possible that the regulation of their growth is under autocrine control. Fibroblasts may be an important source of the growth factor in tissue.

  15. Intranasal nanoparticles of basic fibroblast growth factor for brain delivery to treat Alzheimer's disease.

    PubMed

    Zhang, Chi; Chen, Jie; Feng, Chengcheng; Shao, Xiayan; Liu, Qingfeng; Zhang, Qizhi; Pang, Zhiqing; Jiang, Xinguo

    2014-01-30

    Disabilities caused by neurodegeneration have become one of the main causes of mortality in elderly population, with drug distribution to the brain remaining one of the most difficult challenges in the treatment of the central nervous system (CNS) diseases due to the existence of blood-brain barrier. Lectins modified polyethylene glycol-polylactide-polyglycolide (PEG-PLGA) nanoparticles could enhance the drug delivery to the brain following intranasal administration. In this study, basic fibroblast growth factor (bFGF) was entrapped in nanoparticles conjugated with Solanum tuberosum lectin (STL), which selectively binds to N-acetylglucosamine on the nasal epithelial membrane for its brain delivery. The resulting nanoparticles had uniform particle size and negative zeta potential. The brain distribution of the formulations following intranasal administration was assessed using radioisotopic tracing method. The areas under the concentration-time curve of (125)I-bFGF in the olfactory bulb, cerebrum, and cerebellum of rats following nasal application of STL modified nanoparticles (STL-bFGF-NP) were 1.79-5.17 folds of that of rats with intravenous administration, and 0.61-2.21 and 0.19-1.07 folds higher compared with intranasal solution and unmodified nanoparticles, respectively. Neuroprotective effect was evaluated using Mirror water maze task in rats with intracerebroventricular injection of β-amyloid25-35 and ibotenic acid. The spatial learning and memory of Alzheimer's disease (AD) rats in STL-bFGF-NP group were significantly improved compared with AD model group, and were also better than other preparations. The results were consistent with the value of choline acetyltransferase activity of rat hippocampus as well as the histological observations of rat hippocampal region. The histopathology assays also confirmed the in vivo safety of STL-bFGF-NP. These results clearly indicated that STL-NP was a promising drug delivery system for peptide and protein drugs such as

  16. Heterogeneity of cytokine and growth factor gene expression in human melanoma cells with different metastatic potentials.

    PubMed

    Singh, R K; Gutman, M; Radinsky, R

    1995-01-01

    The purpose of this study was to determine the mRNA expression level of multiple cytokine and growth factor genes in human malignant melanoma. Melanoma cells were isolated from several surgical specimens, adapted to growth in culture, characterized for their ability to produce experimental metastases in nude mice, and assessed for cytokine and growth factor steady-state gene expression. Highly metastatic in vivo- and in vitro-derived variants isolated from a single melanoma, A375, were also analyzed. Northern blot analyses revealed that all melanomas analyzed constitutively expressed steady-state mRNA transcripts for the growth and angiogenic factors, basic fibroblast growth factor (bFGF), and transforming growth factor alpha (TGF-alpha), which correlated with metastatic propensity. Only one highly metastatic melanoma, TXM-1, originally isolated from a lymph node metastasis, expressed mRNA transcripts specific for monocyte chemotactic and activating factor (MCAF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Similarly, of the nine melanomas examined, only TXM-1 expressed interleukin (IL)-1 alpha, IL-1 beta, and IL-6, important immunomodulatory cytokines. These data demonstrate the differential and heterogeneous expression of cytokine and growth factor genes in human malignant melanoma. PMID:7648437

  17. Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved.

    PubMed

    Pratsinis, Harris; Kletsas, Dimitris

    2015-01-01

    Intervertebral disc (IVD) degeneration is strongly associated with low back pain, a major cause of disability worldwide. An in-depth understanding of IVD cell physiology is required for the design of novel regenerative therapies. Accordingly, aim of this work was the study of IVD cell responses to mitogenic growth factors in a three-dimensional (3D) organotypic milieu, comprising characteristic molecules of IVD's extracellular matrix. In particular, annulus fibrosus (AF) cells were cultured inside collagen type-I gels, while nucleus pulposus (NP) cells in chondroitin sulfate A (CSA) supplemented collagen gels, and the effects of Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF), and Insulin-Like Growth Factor-I (IGF-I) were assessed. All three growth factors stimulated DNA synthesis in both AF and NP 3D cell cultures, with potencies similar to those observed previously in monolayers. CSA supplementation inhibited basal DNA synthesis rates, without affecting the response to growth factors. ERK and Akt were found to be phosphorylated following growth factor stimulation. Blockade of these two signaling pathways using pharmacologic inhibitors significantly, though not completely, inhibited growth factor-induced DNA synthesis. The proposed culture systems may prove useful for further in vitro studies aiming at future interventions for IVD regeneration. PMID:26583105

  18. Organotypic Cultures of Intervertebral Disc Cells: Responses to Growth Factors and Signaling Pathways Involved

    PubMed Central

    Pratsinis, Harris; Kletsas, Dimitris

    2015-01-01

    Intervertebral disc (IVD) degeneration is strongly associated with low back pain, a major cause of disability worldwide. An in-depth understanding of IVD cell physiology is required for the design of novel regenerative therapies. Accordingly, aim of this work was the study of IVD cell responses to mitogenic growth factors in a three-dimensional (3D) organotypic milieu, comprising characteristic molecules of IVD's extracellular matrix. In particular, annulus fibrosus (AF) cells were cultured inside collagen type-I gels, while nucleus pulposus (NP) cells in chondroitin sulfate A (CSA) supplemented collagen gels, and the effects of Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF), and Insulin-Like Growth Factor-I (IGF-I) were assessed. All three growth factors stimulated DNA synthesis in both AF and NP 3D cell cultures, with potencies similar to those observed previously in monolayers. CSA supplementation inhibited basal DNA synthesis rates, without affecting the response to growth factors. ERK and Akt were found to be phosphorylated following growth factor stimulation. Blockade of these two signaling pathways using pharmacologic inhibitors significantly, though not completely, inhibited growth factor-induced DNA synthesis. The proposed culture systems may prove useful for further in vitro studies aiming at future interventions for IVD regeneration. PMID:26583105

  19. The hormone prolactin is a novel, endogenous trophic factor able to regulate reactive glia and to limit retinal degeneration.

    PubMed

    Arnold, Edith; Thebault, Stéphanie; Baeza-Cruz, German; Arredondo Zamarripa, David; Adán, Norma; Quintanar-Stéphano, Andrés; Condés-Lara, Miguel; Rojas-Piloni, Gerardo; Binart, Nadine; Martínez de la Escalera, Gonzalo; Clapp, Carmen

    2014-01-29

    Retinal degeneration is characterized by the progressive destruction of retinal cells, causing the deterioration and eventual loss of vision. We explored whether the hormone prolactin provides trophic support to retinal cells, thus protecting the retina from degenerative pressure. Inducing hyperprolactinemia limited photoreceptor apoptosis, gliosis, and changes in neurotrophin expression, and it preserved the photoresponse in the phototoxicity model of retinal degeneration, in which continuous exposure of rats to bright light leads to retinal cell death and retinal dysfunction. In this model, the expression levels of prolactin receptors in the retina were upregulated. Moreover, retinas from prolactin receptor-deficient mice exhibited photoresponsive dysfunction and gliosis that correlated with decreased levels of retinal bFGF, GDNF, and BDNF. Collectively, these data unveiled prolactin as a retinal trophic factor that may regulate glial-neuronal cell interactions and is a potential therapeutic molecule against retinal degeneration. PMID:24478366

  20. Safety and efficacy of sustained release of basic fibroblast growth factor using gelatin hydrogel in patients with critical limb ischemia.

    PubMed

    Kumagai, Motoyuki; Marui, Akira; Tabata, Yasuhiko; Takeda, Takahide; Yamamoto, Masaya; Yonezawa, Atsushi; Tanaka, Shiro; Yanagi, Shigeki; Ito-Ihara, Toshiko; Ikeda, Takafumi; Murayama, Toshinori; Teramukai, Satoshi; Katsura, Toshiya; Matsubara, Kazuo; Kawakami, Koji; Yokode, Masayuki; Shimizu, Akira; Sakata, Ryuzo

    2016-05-01

    As a form of therapeutic angiogenesis, we sought to investigate the safety and efficacy of a sustained-release system of basic fibroblast growth factor (bFGF) using biodegradable gelatin hydrogel in patients with critical limb ischemia (CLI). We conducted a phase I-IIa study that analyzed 10 CLI patients following a 200-μg intramuscular injection of bFGF-incorporated gelatin hydrogel microspheres into the ischemic limb. Primary endpoints were safety and transcutaneous oxygen pressure (TcO2) at 4 and 24 weeks after treatment. During the follow-up, there was no death or serious procedure-related adverse event. After 24 weeks, TcO2 (28.4 ± 8.4 vs. 46.2 ± 13.0 mmHg for pretreatment vs after 24 weeks, p < 0.01) showed significant improvement. Regarding secondary endpoints, the distance walked in 6 min (255 ± 105 vs. 318 ± 127 m, p = 0.02), the Rutherford classification (4.4 ± 0.5 vs. 3.1 ± 1.4, p = 0.02), the rest pain scale (1.7 ± 1.0 vs. 1.2 ± 1.3, p = 0.03), and the cyanotic scale (2.0 ± 1.1 vs. 0.9 ± 0.9, p < 0.01) also showed improvement. The blood levels of bFGF were within the normal range in all patients. A subanalysis of patients with arteriosclerosis obliterans (n = 7) or thromboangiitis obliterans (Buerger's disease) (n = 3) revealed that TcO2 had significantly improved in both subgroups. TcO2 did not differ between patients with or without chronic kidney disease. The sustained release of bFGF from biodegradable gelatin hydrogel may offer a safe and effective form of angiogenesis for patients with CLI. PMID:25861983

  1. 15. Como gatehouse (outlet tower) and access bridge, looking west ...

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

    15. Como gatehouse (outlet tower) and access bridge, looking west from dam crest (Trash rack visible in reservoir pool behind and right of tower) - Bitter Root Irrigation Project, Como Dam, West of U.S. Highway 93, Darby, Ravalli County, MT

  2. Delivery of Alginate Scaffold Releasing Two Trophic Factors for Spinal Cord Injury Repair

    PubMed Central

    Grulova, I.; Slovinska, L.; Blaško, J.; Devaux, S.; Wisztorski, M.; Salzet, M.; Fournier, I.; Kryukov, O.; Cohen, S.; Cizkova, D.

    2015-01-01

    Spinal cord injury (SCI) has been implicated in neural cell loss and consequently functional motor and sensory impairment. In this study, we propose an alginate -based neurobridge enriched with/without trophic growth factors (GFs) that can be utilized as a therapeutic approach for spinal cord repair. The bioavailability of key GFs, such as Epidermal Growth factor (EGF) and basic Fibroblast Growth Factor (bFGF) released from injected alginate biomaterial to the central lesion site significantly enhanced the sparing of spinal cord tissue and increased the number of surviving neurons (choline acetyltransferase positive motoneurons) and sensory fibres. In addition, we document enhanced outgrowth of corticospinal tract axons and presence of blood vessels at the central lesion. Tissue proteomics was performed at 3, 7 and 10 days after SCI in rats indicated the presence of anti-inflammatory factors in segments above the central lesion site, whereas in segments below, neurite outgrowth factors, inflammatory cytokines and chondroitin sulfate proteoglycan of the lectican protein family were overexpressed. Collectively, based on our data, we confirm that functional recovery was significantly improved in SCI groups receiving alginate scaffold with affinity-bound growth factors (ALG +GFs), compared to SCI animals without biomaterial treatment. PMID:26348665

  3. Glucose and glucosamine regulate growth factor gene expression in vascular smooth muscle cells.

    PubMed Central

    McClain, D A; Paterson, A J; Roos, M D; Wei, X; Kudlow, J E

    1992-01-01

    We have investigated the regulation of the expression of two growth factors found in vascular smooth muscle, transforming growth factor alpha (TGF alpha) and basic fibroblast growth factor (bFGF). Cells cultured in medium containing 30 mM glucose exhibited a 2-fold increase in TGF alpha mRNA and a 3-fold increase in bFGF mRNA compared with cells grown in normal (5.5 mM) glucose. Glucosamine was more potent than glucose, leading to a 6-fold increase in TGF alpha mRNA. TGF alpha protein levels were also increased by glucosamine treatment, and the predominant species present was the membrane-bound precursor form of TGF alpha. To examine further the regulation of growth factors by sugars, cultured rat aortic smooth muscle cells were transfected with a plasmid construct consisting of a 1.2-kilobase-pair fragment of the TGF alpha promoter linked to a luciferase reporter gene. Increasing the concentration of glucose in the culture medium from 5.5 mM to 30 mM led to a rapid, 1.7-fold increase in the activity of the TGF alpha promoter. Glucosamine was much more potent than glucose in this stimulation, with 2 mM glucosamine causing a 12-fold increase in TGF alpha promoter activity. Insulin had no effect on luciferase activity in either the presence or the absence of added sugars. The glucose response element of the TGF alpha gene maps to a 130-base-pair segment that includes three potential binding sites for the transcription factor Sp1. We conclude that high glucose concentrations such as are reached in diabetes mellitus can stimulate the transcription of the genes for growth factors in vascular smooth muscle cells. This signaling pathway apparently involves the metabolism of glucose to glucosamine. This effect could be representative of nutritional regulation of a family of genes and could contribute to the toxicity of hyperglycemia and the vascular complications of diabetes. Images PMID:1518840

  4. Basic fibroblast growth factor binds to subendothelial extracellular matrix and is released by heparitinase and heparin-like molecules

    SciTech Connect

    Bashkin, P.; Doctrow, S.; Klagsbrun, M.; Svahn, C.M.; Folkman, J.; Vlodavsky, I. )

    1989-02-21

    Basic fibroblast growth factor (bFGF) exhibits specific binding to the extracellular matrix (ECM) produced by cultured endothelial cells. Binding was saturable as a function both of time and of concentration of {sup 125}I-bFGF. Scatchard analysis of FGF binding revealed the presence of about 1.5 x 10{sup 12} binding sites/mm{sup 2} ECM with an apparent k{sub D} of 610 nM. FGF binds to heparan sulfate (HS) in ECM as evidenced by (i) inhibition of binding in the presence of heparin or HS at 0.1-1 {mu}g/mL, but not by chondroitin sulfate, keratan sulfate, or hyaluronic acid at 10 {mu}g/mL, (ii) lack of binding to ECM pretreated with heparitinase, but not with chondroitinase ABC, and (iii) rapid release of up to 90% of ECM-bound FGF by exposure to heparin, HS, or heparitinase, but not to chondroitin sulfate, keratan sulfate, hyaluronic acid, or chondroitinase ABC. Oligosaccharides derived from depolymerized heparin, and as small as the tetrasaccharide, released the ECM-bound FGF, but there was little or no release of FGF by modified nonanticoagulant heparins such as totally desulfated heparin, N-desulfated heparin, and N-acetylated heparin. FGF released from ECM was biologically active, as indicated by its stimulation of cell proliferation and DNA synthesis in vascular endothelial cells and 3T3 fibroblasts. Similar results were obtained in studies on release of endogenous FGF-like mitogenic activity from Descement's membranes of bovine corneas. It is suggested that ECM storage and release of bFGF provide a novel mechanism for regulation of capillary blood vessel growth. Whereas ECM-bound FGF may be prevented from acting on endothelial cells, its displacement by heparin-like molecules and/or HS-degrading enzymes may elicit a neovascular response.

  5. Dual blockade of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) exhibits potent anti-angiogenic effects.

    PubMed

    Li, Dong; Xie, Kun; Zhang, Longzhen; Yao, Xuejing; Li, Hongwen; Xu, Qiaoyu; Wang, Xin; Jiang, Jing; Fang, Jianmin

    2016-07-28

    Both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF or FGF-2) are potent pro-angiogenic factors and play a critical role in cancer development and progression. Clinical anti-VEGF therapy trials had a major challenge due to upregulated expression of other pro-angiogenic factor, like FGF-2. This study developed a novel chimeric decoy receptor VF-Trap fusion protein to simultaneously block activity of both VEGF and FGF pathways in order to achieve an additive or synergistic anti-tumor effect. Our in vitro data showed that VF-Trap potently blocked proliferation and migration of both VEGF- and FGF-2-induced vascular endothelial cells. In animal models, treatment of xenograft tumors with VF-Trap resulted in significant inhibition of tumor growth compared to blockage of the single molecule, like VEGF or FGF blocker. In addition, VF-Trap was also more potent in inhibition of ocular angiogenesis in a mouse oxygen-induced retinopathy (OIR) model. These data demonstrated the potent anti-angiogenic effects of this novel VF-Trap fusion protein on blockage of VEGF and FGF-2 activity in vitro and in animal models. Further study will assess its effects in clinic as a therapeutic agent for angiogenesis-related disorders, such as cancer and ocular vascular diseases. PMID:27130666

  6. Growth factors in the treatment of early osteoarthritis

    PubMed Central

    Civinini, Roberto; Nistri, Lorenzo; Martini, Caterina; Redl, Birgit; Ristori, Gabriele; Innocenti, Massimo

    2013-01-01

    Summary Regenerative medicine is the science that studies the regeneration of biological tissues obtained through use of cells, with the aid of support structures and with biomolecules such as growth factors. As regards the growth factors the PRP, or the platelet-rich plasma, obtained from a withdrawal of autologous blood, concentrating the platelets, represents a safe, economical, easy to prepare and easy to apply source of growth factors. Numerous growth factors are in fact within the platelets and in particular a large number of them have a specific activity on neo-proliferation, on cartilage regeneration and in particular also an antiapoptotic effect on chondroblasts: - The PDGF which regulates the secretion and synthesis of collagen;- The EGF that causes cellular proliferation, endothelial chemotaxis and angiogenesis;- The VEGF that increases angiogenesis and vascular permeability;- The TGF-beta that stimulates the proliferation of undifferentiated MSC, stimulates chemotaxis of endothelial cells and angiogenesis;- The bFGF that promotes the growth and differentiation of chondrocytes and osteoblasts stimulates mitogenesis of mesenchymal cells, chondrocytes and osteoblasts. These properties have led to the development of studies that evaluated the efficacy of treatment of infiltrations in the knee and hip with platelet-derived growth factors. Regarding the knee it was demonstrated that in patients with moderate degree of gonarthrosis, the PRP is able to significantly reduce the pain and improve joint function, both on placebo and towards infiltrations with hyaluronic acid. The success of the treatment was proportional to the age of and inversely proportional to the severity of osteoarthritis according to Kellgren and Lawrence classification. The possibility of infiltrations guided with ultrasound into the hip led us to extend the indications also to hip arthrosis, as already showed by Sanchez. Even in coxarthrosis preliminary results at 6 and 12 months show that

  7. Protective effect of basic fibroblast growth factor on retinal injury induced by argon laser photocoagulation

    NASA Astrophysics Data System (ADS)

    Chen, P.; Zhang, C. P.; San, Q.; Wang, C. Z.; Yang, Z. F.; Kang, H. X.; Qian, H. W.

    2010-12-01

    Laser photocoagulation treatment is often complicated by a side effect of visual impairment, which is caused by the unavoidable laser-induced retinal destruction. At present no specific is found to cure this retinopathy. The aim of this study was to observe the neuroprotective effect of bFGF on laser-induced retinal injury. Chinchilla rabbits were divided into three groups and argon laser lesions were created in the retinas. Then bFGF or dexamethasone, a widely used ophthalmic preparation, or saline was given severally by retrobulbar injection. The retinal lesions were evaluated histologically and morphometrically, and visual function was examined by ERG. The results showed that bFGF administration better preserved morphology of retinal photoreceptors and significantly diminished the area of the lesions. Furthermore, bFGF promoted the restoration of the ERG b-wave amplitude. In rabbits treated with dexamethasone, however, the lesions showed almost no ameliorative changes. This is the first study to investigate the potential role of bFGF as a remedial agent in laser photocoagulation treatment. These findings suggest that bFGF has significant neuroprotective properties in the retina and this type of neuroprotection may be of clinical significance in reducing iatrogenic laser-induced retinal injuries in humans.

  8. The Transcription Factor MEF2C Negatively Controls Angiogenic Sprouting of Endothelial Cells Depending on Oxygen

    PubMed Central

    Sturtzel, Caterina; Testori, Julia; Schweighofer, Bernhard; Bilban, Martin; Hofer, Erhard

    2014-01-01

    The MADS box transcription factor MEF2C has been detected by us to be upregulated by the angiogenic factors VEGF-A and bFGF in endothelial cells. We have here investigated its potential role for angiogenesis. MEF2C was surprisingly found to strongly inhibit angiogenic sprouting, whereas a dominant negative mutant rather induced sprouting. The factor mainly affected migratory processes of endothelial cells, but not proliferation. In gene profiling experiments we delineated the alpha-2-macroglobulin gene to be highly upregulated by MEF2C. Further data confirmed that MEF2C in endothelial cells indeed induces alpha-2-macroglobulin mRNA as well as the secretion of alpha-2-macroglobulin and that conditioned supernatants of cells overexpressing MEF2C inhibit sprouting. Alpha-2-macroglobulin mediates, at least to a large extent, the inhibitory effects of MEF2C as is shown by knockdown of alpha-2-macroglobulin mRNA by lentiviral shRNA expression which reduces the inhibitory effect. However, under hypoxic conditions the VEGF-A/bFGF-mediated upregulation of MEF2C is reduced and the production of alpha-2-macroglobulin largely abolished. Taken together, this suggests that the MEF2C/alpha-2-macroglobulin axis functions in endothelial cells as a negative feed-back mechanism that adapts sprouting activity to the oxygen concentration thus diminishing inappropriate and excess angiogenesis. PMID:24988463

  9. Scatter factor influences the formation of prostate epithelial cell colonies on bone marrow stroma in vitro.

    PubMed

    Lang, S H; Clarke, N W; George, N J; Testa, N G

    1999-06-01

    Prostate cancer metastases form selectively in the bone marrow. Previously we demonstrated motility was important for the formation of primary prostatic epithelial cell colonies in bone marrow stroma (BMS) co-culture. In this study we looked at the influence of motility factors on the colony formation of epithelial cells derived from benign (bPEC) or malignant (mPEC) prostate tissue. After 7 days co-culture we found that anti-scatter factor consistently inhibited prostate epithelial cell colony formation on BMS (7/7 mPEC and 4/7 bPEC samples showed significant inhibition). Antibodies against bFGF and 5T4 did not significantly affect colony formation. Addition of fibroblast conditioned media (derived from benign prostates) to co-cultures stimulated the colony formation of bPEC (170%) and mPEC (252%). This stimulation was eliminated by depletion of SF from the conditioned media. Immunohistochemical staining found c-Met expression in 5/6 bPEC cultures and 7/9 mPEC cultures. When grown in BMS co-culture expression of c-Met was positive in 3/6 bPEC and 2/7 mPEC samples. In conclusion, scatter factor influences the in vitro formation of prostate epithelial cell colonies on BMS co-culture. PMID:10545020

  10. hCG-dependent regulation of angiogenic factors in human granulosa lutein cells.

    PubMed

    Phan, B; Rakenius, A; Pietrowski, D; Bettendorf, H; Keck, C; Herr, D

    2006-07-01

    As prerequisite for development and maintenance of many diseases angiogenesis is of particular interest in medicine. Pathologic angiogenesis takes place in chronic arthritis, collagen diseases, arteriosclerosis, retinopathy associated with diabetes, and particularly in cancers. However, angiogenesis as a physiological process regularly occurs in the ovary. After ovulation the corpus luteum is formed by rapid vascularization of initially avascular granulosa lutein cell tissue. This process is regulated by gonadotropic hormones. In order to gain further insights in the regulatory mechanisms of angiogenesis in the ovary, we investigated these mechanisms in cell culture of human granulosa lutein cells. In particular, we determined the expression and production of several angiogenic factors including tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), Leptin, connective tissue growth factor (CTGF), meningioma-associated complimentary DNA (Mac25), basic fibroblast growth factor (bFGF), and Midkine. In addition, we showed that human chorionic gonadotropin (hCG) has distinct effects on their expression and production. hCG enhances the expression and production of TIMP-1, whereas it downregulates the expression of CTGF and Mac25. Furthermore it decreases the expression of Leptin. Our results provide evidence that hCG determines growth and development of the corpus luteum by mediating angiogenic pathways in human granulosa lutein cells. Hence we describe a further approach to understand the regulation of angiogenesis in the ovary. PMID:16596638

  11. The generation of germline transgenic silkworms for the production of biologically active recombinant fusion proteins of fibroin and human basic fibroblast growth factor.

    PubMed

    Hino, Rika; Tomita, Masahiro; Yoshizato, Katsutoshi

    2006-11-01

    We generated germline transgenic silkworms bearing a fibroin light chain (FL) promoter-driven FL gene whose 3'-end was flanked with human basic fibroblast growth factor (bFGF) gene, FL/bFGF gene. The cocoons from transgenic worms were trypsinized to remove sericin layers, and treated with solution containing CaCl(2), ethanol, and water at a molar ratio of 1:2:8 (CaCl(2)/ethanol/water) to solubilize fibroin layers. Western blot analysis showed that the recombinant protein, r(FL/bFGF), was solubilized with CaCl(2)/ethanol/water, but not with trypsin, indicating that r(FL/bFGF) was in fibroin layers. Thus, it was concluded that the worms spun cocoons whose fibroin layers were composed of the inherent gene-derived natural fibroin (nF) and r(FL/bFGF). The mixture of nF and r(FL/bFGF) was dubbed r(FL/bFGF)nF. The solubilized r(FL/bFGF)nF was refolded using the glutathione redox system. Human umbilical vein endothelial cells (HUVECs) grew in the refolded r(FL/bFGF)nF-containing culture media, showing that bFGF in r(FL/bFGF) was biologically active. r(FL/bFGF)nF immobilized on a culture dish also supported the growth of HUVECs in bFGF-free media, suggesting the usefulness of r(FL/bFGF)nF as a new biomaterial for tissue engineering. The currently developed transgenic silkworms will be suitable for mass production of fibroins bearing a variety of biological activities. PMID:16905183

  12. Effect of Local Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor on Subcutaneously Allotransplanted Ovarian Tissue in Ovariectomized Mice

    PubMed Central

    Gao, Jiangman; Huang, Ying; Li, Min; Zhao, Hongcui; Zhao, Yue; Li, Rong; Yan, Jie; Yu, Yang; Qiao, Jie

    2015-01-01

    Objective One of the major obstacles to ovarian tissue preservation is delayed angiogenesis that leads follicles lost after transplantation. The aim of the present study was to investigate the effects of bFGF and VEGF on heterotopic transplanted ovarian tissue using a mouse model. Methods Female mice underwent bilateral ovariectomy. Ovarian tissues encapsulated by fibrin hydrogels were transplanted subcutaneously into recipient mice, in which ovarian hormonal cyclicity was absent. The fibrinogen solution was mixed with bFGF, VEGF, or a mixture of bFGF and VEGF. The grafts were recovered 21 days after transplantation. Follicle morphology and follicle numbers were observed by H&E staining. Blood vessels were observed in transplanted intra-ovarian tissue by CD31 antibody IHC staining. Daily vaginal cytology was performed to determine estrous cycle and functional restoration of transplanted ovarian tissue. Blood was collected weekly and serum FSH levels were measured with a radioimmunoassay kit. Apoptosis analysis was performed by anti-AC-3 staining and survivin mRNA expression. Results The number of primordial follicles and secondary follicles in the bFGF+VEGF group was significantly higher than in the control group. The vascular density in the bFGF+VEGF groups were significantly higher than in the bFGF and the VEGF groups; there was no significant difference between the bFGF and VEGF groups. Estrous cycle was earlier in the bFGF+VEGF group compared with the control group; all mice in this group restored ovarian function. Serum FSH levels in the bFGF+VEGF group were significantly lower than in the control group by day 14 post-transplantation. The AC-3-positive in control group was significantly higher compared with bFGF group and VEGF group, and in bFGF+VEGF group was significantly lower than bFGF group and VEGF group. Survivin mRNA expression in bFGF+VEGF group was significantly higher than control group. Conclusion The combination of bFGF and VEGF has beneficial

  13. Expression of factors involved in the regulation of angiogenesis in the full-term human placenta: Effects of in vitro fertilization.

    PubMed

    Li, Chanjuan; Zhang, Yuan; Tang, Lisha; Zhao, Haijun; Gao, Chao; Gao, Li; Cui, Yugui; Liu, Jiayin

    2016-06-01

    The effects of assisted reproductive technologies (ARTs) on the safety of pregnancy and the resulting offspring remain controversial. Studies of placental functions, especially vasculogenesis and angiogenesis, in pregnancies established through ART are helpful for furthering our understanding of the safety of ART. This study compares the expression profiles of angiogenic factors in human term placentas obtained from natural (NAT) pregnancies vs. placentas obtained from pregnancies that resulted from ART. Term placentas were obtained from women who underwent an ART procedure (n=4), and these were compared with term placentas that were obtained from women who had experienced a spontaneous pregnancy (controls, n=4). An array analysis was performed using the Human Angiogenesis Antibody Array to detect 43 angiogenic factors and to identify which of these factors were differentially expressed between the two groups. The expression of six of these factors was greater in the ART group than in the NAT group. The levels of four of them, including vascular endothelial growth factor receptor-3 (VEGFR3), basic fibroblast growth factor (bFGF), interferon gamma (IFNG) and matrix metalloproteinase 1 (MMP1), were quantified using western blot analysis. These factors were examined using immunohistochemistry and microscopy in vascular endothelial cells or the cytoplasm and membranes of syncytiotrophoblast cells. Our finding that selected angiogenic factors exhibit altered expression profiles in ART placentas might be significant when evaluating ART safety. PMID:27288334

  14. Harold Varmus investido bajo juramento como 14.º director d

    Cancer.gov

    Ganador del Premio Nobel, doctor Harold E. Varmus, prestó juramento hoy como 14.º director del Instituto Nacional del Cáncer (NCI).  "Es muy estimulante que estés de regreso con nosotros", dijo la secretaria del Departamento de Salud y Servicios Humanos K

  15. Engineering a growth factor embedded nanofiber matrix niche to promote vascularization for functional cardiac regeneration.

    PubMed

    Lakshmanan, Rajesh; Kumaraswamy, Priyadharshini; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2016-08-01

    The major loss of tissue extracellular matrix (ECM) after myocardial ischemia is a serious burden that gradually leads to heart failure. Due to lack of available treatment methods to restore the cardiac function, various research strategies have come up to treat the ischemic myocardium. However these have met with limited success due to the complexity of the cardiac tissue, which exhibits a nanofibrous collagenous matrix with spatio-temporal localization of a combination of growth factors. To mimic the topographical and chemical cues of the natural cardiac tissue, we have fabricated a growth factor embedded nanofibrous scaffold through electrospinning. In our previous work, we have reported a nanofibrous matrix made of PLCL and PEOz with an average diameter of 500 nm. The scaffold properties were specifically characterized in vitro for cardio-compatibility. In the present study, we have loaded dual growth factors VEGF and bFGF in the nanofiber matrix and investigated its suitability for cardiac tissue engineering. The encapsulation and release of dual growth factors from the matrix were studied using XPS and ELISA. Bioactivity of the loaded growth factors towards proliferation and migration of endothelial cells (HUVECs) was evaluated through MTS and Boyden chamber assays respectively. The efficiency of growth factors on the nanofibrous matrix to activate signaling molecules was studied in HUVECs through gene expression analysis. Preclinical evaluation of the growth factor embedded nanofibrous patch in a rabbit acute myocardial infarction (AMI) model was studied and cardiac function assessment was made through ECG and echocardiography. The evidence for angiogenesis in the patch secured regions was analyzed through histopathology and immunohistochemistry. Our results confirm the effectiveness of growth factor embedded nanofiber matrix in restoration of cardiac function after ischemia when compared to conventional patch material thereby exhibiting promise as a

  16. Expression of angiogenic factors and luteinizing hormone receptors in the corpus luteum of mares induced to ovulate with deslorelin acetate.

    PubMed

    Maia, Victor N; Batista, André M; Cunha Neto, Sylvio; Silva, Diogo M F; Adrião, Manoel; Wischral, Aurea

    2016-02-01

    The effects of deslorelin acetate use in inducing ovulation need to be clarified to improve the results of equine embryo transfer. The mRNA abundance for angiogenic factors and LH receptor (LHR) in corpus luteum (CL) was studied in mares with natural (control group [CG]) and induced ovulation with deslorelin acetate (treatment group [TG]; follicles: ≥ 35 mm). Transrectal ultrasonography was used to verify the ovulation day, and on Days 4, 8, and 12 after ovulation (Day 0), CL samples were obtained through ultrasound-guided biopsy. The messenger RNA expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and LHR genes were analyzed by real-time polymerase chain reaction. A positive correlation was observed between VEGF and LHR (P < 0.00001, r = 0.78), and it was possible to detect higher LHR expression in the TG than in the CG on Day 4 (P < 0.05). Moreover, this expression was higher on Days 4 and 8 than on Day 12 in the TG. Basic fibroblast growth factor was also expressed in luteal tissue on all days for both groups; however, these differences were not significant. In conclusion, deslorelin acetate was effective for the induction of ovulation in mares, resulting in higher expression of LHR, especially on the fourth day after ovulation. In addition, VEGF expression was influenced by induced ovulation, with a lower level on Day 12, which is expected in nonpregnant mares. PMID:26476595

  17. Vascular Endothelium Growth Factor, Surgical Delay, and Skin Flap Survival

    PubMed Central

    Lineaweaver, William C.; Lei, Man-Ping; Mustain, William; Oswald, Tanya M.; Cui, Dongmei; Zhang, Feng

    2004-01-01

    Objective: Cytokines may be a mechanism by which surgical delay can increase flap survival. We previously found that preoperative vascular endothelium growth factor (VEGF) administration in the rat transverse rectus abdominis myocutaneous (TRAM) flap could improve skin paddle survival. In this study, we used partial elevation of the rat TRAM flap as a surgical delay to assess endogenous cytokine expression and tissue survival comparable to undelayed TRAM flaps. Methods: In Part I, TRAM flaps underwent surgical delay procedures; 7 days later, the flaps were completely elevated and reinset. At the same time, other flaps were raised and reinset without delay. Skin paddle survival in both groups was evaluated at 7 days. In Part II, skin biopsies from TRAM zones I to IV were taken at the time of delay and at intervals of 12, 24, 48, and 72 hours. Specimens were assessed for selected cytokine gene expression by reverse transcription-polymerase chain reaction analysis (TR-PCR). Results: Surgical delay significantly (P < 0.001) increased skin paddle survival in the delayed TRAM flaps (16.14 ± 1.53 cm, 81.9%) compared with undelayed flaps (7.68 ± 3.16 cm, 40.9%). TGF-β and PDGF expressions were not changed by surgical delay, but basic fibroblast growth factor (bFGF) and VEGF expressions increased significantly (P < 0.05 and P < 0.01) after delay. Conclusions: In the rat TRAM model, surgical delay resulted in increased VEGF expression and increased skin paddle survival. These results correlate with previous studies showing the preoperative injection of VEGF increases skin paddle survival. VEGF may be an important element in the delay phenomenon and may be an agent for pharmacological delay. PMID:15166966

  18. LA BIOÉTICA COMO QUEHACER FILOSÓFICO

    PubMed Central

    Ferrer, Jorge José

    2009-01-01

    El artículo examina el estatuto epistemológico de la bioética como disciplina académica. El autor sostiene que el estatuto epistemológico de un discurso lo determina la pregunta fundamental que se plantea y la respuesta que se busca, focos integradores del discurso. En el caso de la bioética, la pregunta fundamental es de índole moral. La bioética es pues una disciplina ética que tiene su hogar epistemológico en la filosofía. El autor también defiende el concepto de “éticas aplicadas”. Sugiere finalmente que el método de la bioética, sobre todo la que se hace desde nuestras latitudes, debería adoptar el círculo hermenéutico como metodología para su filosofar. PMID:20463860

  19. Recent DDT and PCB contamination in the sediment and biota of the Como Bay (Lake Como, Italy).

    PubMed

    Bettinetti, R; Quadroni, S; Boggio, E; Galassi, S

    2016-01-15

    Due to its peculiar geographical and morphological characteristics, Lake Como (Northern Italy) represents an interesting study-case for investigating the sub-basin scale circulation of persistent organic pollutants (POPs) that, despite being banned since the 1970s, have reached surprisingly high concentrations in some southern alpine lakes as a consequence of their release from melting glaciers in recent years. In particular, the Como Bay, which is located in the city of Como, seems noteworthy because its waters have a longer residence time than the other areas of the lake. The analyses of the historical concentration of PCBs, pp′DDT and its metabolites in a sediment core sampled from the Como Bay covering a time-period from their ban to recent times, showed that the DDTs have never experienced a significant (p < 0.05) decrease over time, with concentrations of the most abundant homologue, pp′DDE, ranging from 27 to 75 ng g(-1) d.w. Conversely PCBs significantly (p < 0.05) decreased towards recent times, reaching concentrations around 80 ng g(-1) d.w. The contribution of high altitude and local sources was recorded also in the food web: both zooplankton and the zooplanktivorous fish agone were mainly contaminated by pp′DDE (81.4 ng g(-1) w.w. and 534.6 ng g(-1) w.w. respectively) and by the PCB metabolite hexa-CB (449.7 ng g(-1) w.w. and 1672.1 ng g(-1) w.w. respectively). The DDT concentrations in the agone (sampled during the years 2006–2009) never exceeded the limits for human consumption in Italy, while concentrations of six selected PCBs exceeded human health advisory recommendations in one of the fish samples analysed, when it was approximately two times higher than the recommended value of 125 ng g(-1) w.w. PMID:26520265

  20. Ca2+ channels in retinal pigment epithelial cells regulate vascular endothelial growth factor secretion rates in health and disease

    PubMed Central

    Rosenthal, Rita; Heimann, Heinrich; Agostini, Hansjürgen; Martin, Gottfried; Hansen, Lutz Lothar

    2007-01-01

    Purpose Choroidal neovascularization (CNV) is the most severe complication in age-related macular degeneration. The major angiogenic factor involved is vascular endothelial growth factor (VEGF) secreted by the retinal pigment epithelium (RPE). Since RPE cells express neuroendocrine L-type Ca2+ channels we investigated their involvement in VEGF secretion in normal RPE cells and RPE cells from patients with CNV. Methods Freshly isolated and cultured RPE cells were studied using the patch-clamp technique and ELISA-based secretion assays. Results Both freshly isolated and cultured cells showed whole-cell Ba2+ currents with properties of L-type Ca2+ currents: high activation threshold, sensitivity to dihydropyridines (10 μM nifedipine) and slow inactivation. VEGF-A secretion was elevated by BayK8644 (10 μM) or basic fibroblast growth factor (bFGF, 10 ng/ml), both of which are able to activate L-type channels. Cells from CNV tissue also showed nifedipine-sensitive Ba2+ currents, which displayed a voltage-dependent activation at more negative potentials, faster inactivation and changed regulation by tyrosine kinase pp60c-src. The CNV RPE cells showed higher VEGF secretion rates which were reduced by nifedipine. Conclusions Thus, L-type Ca2+ channels in normal RPE cells regulate the secretion of VEGF. RPE cells from eyes with CNV maintain a VEGF secretion regulated by nifedipine-sensitve Ca2+ channels which might be of importance for the development of CNV. PMID:17417605

  1. Protection of photoreceptor cells from phototoxicity by transplanted retinal pigment epithelial cells expressing different neurotrophic factors.

    PubMed

    Abe, Toshiaki; Saigo, Yoko; Hojo, Masayoshi; Kano, Tetsuya; Wakusawa, Ryosuke; Tokita, Yumi; Tamai, Makoto

    2005-01-01

    Transplantation of cells or tissues and the intravitreal injection of neurotrophic factors are two methods that have been used to treat retinal diseases. The purpose of this study was to examine the effects of combining both methods: the transplantation of retinal pigment epithelial (RPE) cells expressing different neurotrophic factors. The neutrophic factors were Axokine, brain derived-neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF). The enhanced green fluorescence protein (eGFP) gene was used as a reporter gene. These genes were transduced into RPE cells by lipofection, selected by antibiotics, and transplanted into the subretinal space of 108 rats. The rats were examined at 1 week and 3 months after the transplantation to determine whether the transduced cells were present, were expressing the protein, and were able to protect photoreceptors against phototoxicity. The survival of the transplanted cells was monitored by the presence of eGFP. The degree of protection was determined by the thickness of the outer nuclear layer. Our results showed that the degree of photoreceptor protection was different for the different types of neurotrophic factors at 1 week. After 3 months, the number of surviving transplanted cell was markedly reduced, and protection was observed only with the BDNF-transduced RPE cells. A significant degree of rescue was also observed by BDNF-transduced RPE cells in the nontransplanted area of the retina at both the early and late times. Lymphocytic infiltration was not detected in the vitreous, retina, and choroid at any time. We conclude that the transplantation of BDNF-transduced RPE cells can reduce the photoreceptor damage induced by phototoxicity in the transplanted area and weakly in the nontransplanted area. PMID:16454354

  2. Valorisation of Como Historical Cadastral Maps Through Modern Web Geoservices

    NASA Astrophysics Data System (ADS)

    Brovelli, M. A.; Minghini, M.; Zamboni, G.

    2012-07-01

    Cartographic cultural heritage preserved in worldwide archives is often stored in the original paper version only, thus restricting both the chances of utilization and the range of possible users. The Web C.A.R.T.E. system addressed this issue with regard to the precious cadastral maps preserved at the State Archive of Como. Aim of the project was to improve the visibility and accessibility of this heritage using the latest free and open source tools for processing, cataloguing and web publishing the maps. The resulting architecture should therefore assist the State Archive of Como in managing its cartographic contents. After a pre-processing consisting of digitization and georeferencing steps, maps were provided with metadata, compiled according to the current Italian standards and managed through an ad hoc version of the GeoNetwork Opensource geocatalog software. A dedicated MapFish-based webGIS client, with an optimized version also for mobile platforms, was built for maps publication and 2D navigation. A module for 3D visualization of cadastral maps was finally developed using the NASA World Wind Virtual Globe. Thanks to a temporal slidebar, time was also included in the system producing a 4D Graphical User Interface. The overall architecture was totally built with free and open source software and allows a direct and intuitive consultation of historical maps. Besides the notable advantage of keeping original paper maps intact, the system greatly simplifies the work of the State Archive of Como common users and together widens the same range of users thanks to the modernization of map consultation tools.

  3. 78 FR 36163 - Bitterroot National Forest, Darby Ranger District, Como Forest Health Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-17

    ... FHP covers approximately 5,640 acres of national forest land between Lake Como and Lost Horse Roads... project area lies between Lake Como Road and Lost Horse Road, about three miles northwest of...

  4. Effects of valproic acid on the expression of trophic factors in human bone marrow mesenchymal stromal cells.

    PubMed

    Cho, Goang-Won; Kang, Byung Yong; Kim, Kyung-Suk; Kim, Seung Hyun

    2012-09-27

    The potential of human bone marrow-mesenchymal stromal cells (hBM-MSCs) to differentiate into diverse cell types and secrete a variety of trophic factors makes them an excellent cell therapy tool for intractable diseases. However, their therapeutic efficacy has not yet been satisfied in preclinical and/or clinical trials with autologous or allogenic stem cells. To improve the efficacy of stem cell therapy, optimized conditions for stem cells need to be defined. In this study, we evaluated the effects of valproic acid (VPA), an HDAC inhibitor, in human BM-MSCs and assessed the expression of trophic factors (ANG, BDNF, ECGF1, bFGF-2, GDNF, HGF, IGF-1, PIGF, TGF-β1, and β-Pix) in MSCs treated with 200μg/ml VPA for 12h. Under these conditions the features of MSCs were not changed. The VPA-treated MSCs also showed an increased cell protective effect against oxidative injuries in MTT assays and improved migratory ability when examined by the Boyden chamber assay. This suggests that MSCs may be improved by treatment with an optimal VPA dose and incubation time, which may increase the efficacy of stem cell therapy. PMID:22917608

  5. Ixora coccinea Enhances Cutaneous Wound Healing by Upregulating the Expression of Collagen and Basic Fibroblast Growth Factor.

    PubMed

    Upadhyay, Aadesh; Chattopadhyay, Pronobesh; Goyary, Danswrang; Mitra Mazumder, Papiya; Veer, Vijay

    2014-01-01

    Background. Ixora coccinea L. (Rubiaceae) has been documented for traditional use in hypertension, menstrual irregularities, sprain, chronic ulcer, and skin diseases. In the present study, I. coccinea was subjected to in vitro and in vivo wound healing investigation. Methods. Petroleum ether, chloroform, methanol, and water sequential I. coccinea leaves extracts were evaluated for in vitro antioxidant, antimicrobial, and fibroblast proliferation activities. The promising I. coccinea methanol extract (IxME) was screened for in vivo wound healing activity in Wistar rat using circular excision model. Wound contraction measurement, hydroxyproline quantification, and western blot for collagen type III (COL3A1), basic fibroblast growth factor (bFGF), and Smad-2, -3, -4, and -7 was performed with 7-day postoperative wound granulation tissue. Gentamicin sulfate (0.01% w/w) hydrogel was used as reference standard. Results. IxME showed the potent antimicrobial, antioxidant activities, with significant fibroblast proliferation inducing activity, as compared to all other extracts. In vivo study confirmed the wound healing accelerating potential of IxME, as evidenced by faster wound contraction, higher hydroxyproline content, and improved histopathology of granulation tissue. Western blot analysis revealed that the topical application of I. coccinea methanol extract stimulates the fibroblast growth factor and Smad mediated collagen production in wound tissue. PMID:24624303

  6. Ixora coccinea Enhances Cutaneous Wound Healing by Upregulating the Expression of Collagen and Basic Fibroblast Growth Factor

    PubMed Central

    Upadhyay, Aadesh; Chattopadhyay, Pronobesh; Goyary, Danswrang; Mitra Mazumder, Papiya; Veer, Vijay

    2014-01-01

    Background. Ixora coccinea L. (Rubiaceae) has been documented for traditional use in hypertension, menstrual irregularities, sprain, chronic ulcer, and skin diseases. In the present study, I. coccinea was subjected to in vitro and in vivo wound healing investigation. Methods. Petroleum ether, chloroform, methanol, and water sequential I. coccinea leaves extracts were evaluated for in vitro antioxidant, antimicrobial, and fibroblast proliferation activities. The promising I. coccinea methanol extract (IxME) was screened for in vivo wound healing activity in Wistar rat using circular excision model. Wound contraction measurement, hydroxyproline quantification, and western blot for collagen type III (COL3A1), basic fibroblast growth factor (bFGF), and Smad-2, -3, -4, and -7 was performed with 7-day postoperative wound granulation tissue. Gentamicin sulfate (0.01% w/w) hydrogel was used as reference standard. Results. IxME showed the potent antimicrobial, antioxidant activities, with significant fibroblast proliferation inducing activity, as compared to all other extracts. In vivo study confirmed the wound healing accelerating potential of IxME, as evidenced by faster wound contraction, higher hydroxyproline content, and improved histopathology of granulation tissue. Western blot analysis revealed that the topical application of I. coccinea methanol extract stimulates the fibroblast growth factor and Smad mediated collagen production in wound tissue. PMID:24624303

  7. Morphological investigation of nanostructured CoMo catalysts

    NASA Astrophysics Data System (ADS)

    Pawelec, B.; Castaño, P.; Zepeda, T. A.

    2008-04-01

    This work reports the morphological investigation of nanostructured sulfided CoMo catalysts by means of high-resolution transmission electron microscopy (HRTEM). The catalysts were supported on Ti-modified hexagonal mesoporous silica (HMS-Ti) and P-modified HMS-Ti (P/HMS-Ti) materials. The oxide precursors were characterized by specific surface area (S BET), temperature-programmed reduction (TPR), diffuse reflectance infrared Fourier transform spectroscopy in the OH region (DRIFTS-OH) and X-ray photoelectron spectroscopy (XPS) in order to elucidate the influence of the impregnation sequence (successive vs. simultaneous) and the effect of P-incorporation into HMS-Ti material on the morphology of calcined CoMo catalysts. Both TPR and XPS measurements indicate that the catalysts prepared by successive impregnation possess well-dispersed MoO 3 and CoO phases, whereas their counterparts prepared by simultaneous impregnation additionally possess the CoMoO 4 phase. For all sulfided catalysts, the presence of MoS 2 phase with particle size in the range 3.3-4.4 nm was confirmed by HRTEM. Catalytic activity was evaluated in the reaction of hydrodesulfurization (HDS) of dibenzothiophene (DBT) carried out in a flow reactor at 593 K and hydrogen pressure of 5.5 MPa. P-incorporation into the HMS-Ti material led to an overall increase in HDS activity and the hydrogenation ability of the sulfided catalysts. All catalysts proved to be stable during 10 h time-on-stream (TOS) operation. The activity of sulfide catalysts in the target reaction depends linearly on the surface exposure of Co species in the oxide precursors, as determined by XPS, and on the morphology of the sulfide form of catalysts (surface density of MoS 2 particles and their sizes) as determined by HRTEM.

  8. Growth factor treated tensioned synoviocyte neotissues: towards meniscal bioscaffold tissue engineering.

    PubMed

    Warnock, J J; Bobe, G; Duesterdieck-Zellmer, K F; Spina, J; Ott, J; Baltzer, W I; Bay, B K

    2014-04-01

    Meniscal injury is a common cause of osteoarthritis, pain, and disability in dogs and humans, but tissue-engineered bioscaffolds could be a treatment option for meniscal deficiency. The objective of this study was to compare meniscus-like matrix histology, composition, and biomechanical properties of autologous tensioned synoviocyte neotissues (TSN) treated with fetal bovine serum (TSNfbs) or three chondrogenic growth factors (TSNgf). Fourth passage canine synoviocytes from 10 dogs were grown in hyperconfluent monolayer culture, formed into TSN, and then cultured for 3 weeks with 17.7% FBS or three human recombinant TSNgf (bFGF, TGF-β1, and IGF-1). Cell viability was determined with laser microscopy. Histological architecture and the composition of fibrocartilage matrix were evaluated in TSN by staining tissues for glycosaminoglycan (GAG), α-smooth muscle actin, and collagen 1 and 2; quantifying the content of GAG, DNA, and hydroxyproline; and measuring the gene expression of collagens type 1α and 2α, the GAG aggrecan, and transcription factor Sry-type Homeobox Protein-9 (SOX9). Biomechanical properties were determined by materials testing force-deformation curves. The TSN contained components and histological features of mensical fibrocartilage extracellular matrix. Growth factor-treated TSN had higher DNA content but lower cell viability than TSNfbs. TSNgf had greater fibrocartilage-like matrix content (collagen 2 and GAG content with increased collagen 2α and SOX9 gene expression). Additionally, TSNgf collagen was more organized histologically and so had greater tensile biomechanical properties. The results indicate the potential of TSN when cultured with growth factors as implantable bioscaffolds for the treatment of canine meniscal deficiency. PMID:24559744

  9. Prevalence of previously undiagnosed abdominal aortic aneurysms in the area of Como: the ComoCuore "looking for AAA" ultrasonography screening.

    PubMed

    Corrado, Giovanni; Durante, Alessandro; Genchi, Vincenzo; Trabattoni, Loris; Beretta, Sandro; Rovelli, Enza; Foglia-Manzillo, Giovanni; Ferrari, Giovanni

    2016-08-01

    The prognosis for abdominal aortic aneurysm (AAA) rupture is poor. Long-term follow-up of population-based randomized trials has demonstrated that ultrasound (US) screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related mortality rates and is cost-effective. We though to prospectively perform during a 26-month period a limited US examination of the infrarenal aorta in volunteers of both gender aged 60-85 years without history of AAA living in the area of Como, Italy. From September 2010 to November 2013 ComoCuore, a no-profit nongovernmental association, enrolled 1555 people (aged 68.8 ± 6.8 years; 48.6 % males). Clinical data and a US imaging of the aorta were collected for each participant. AAA was found in 22 volunteers (1.4 %) mainly males (2.5 % in males vs. 0.4 % in females p = 0.005). Overall, the prevalence of cardiovascular risk factors was higher in patients with vs. without AAA (mean 2.9 ± 3.0 vs. 1.4 ± 1.0 respectively, p < 0.0001). Independent predictors of AAA on multivariate analysis were age (OR 1.14, 1.06-1.22; p < 0.0001), male gender (OR 8.23, 1.79-37.91; p = 0.007), and both current (OR 4.98, 1.57-15.79; p = 0.007) and previous smoking (OR 2.76, 1.12-8.94; p = 0.03). Our study confirms the feasibility of one time US screening for AAA in a large cohort of asymptomatic people. Independent predictors of AAA were male sex, older age and a history of smoking. Accordingly to recent data the prevalence of AAA seems to be declining, maybe due to a reduction of smoking in Italy. PMID:27215751

  10. Aerosol delivery of eukaryotic translation initiation factor 4E-binding protein 1 effectively suppresses lung tumorigenesis in K-rasLA1 mice.

    PubMed

    Chang, S-H; Kim, J-E; Lee, J-H; Minai-Tehrani, A; Han, K; Chae, C; Cho, Y-H; Yun, J-H; Park, K; Kim, Y-S; Cho, M-H

    2013-06-01

    Conventional radiotherapy or chemotherapy for the long-term survival of patients with lung cancer is still difficult for treatment in metastatic and advanced tumors. Therefore, the safe and effective approaches to the treatment of lung cancer are needed. In this study, the effect of delivered eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1) on lung cancer progression was evaluated. Recombinant adeno-associated virus (rAAV)-M3/4E-BP1 was delivered into 6-week-old K-rasLA1 lung cancer model mice through a nose-only inhalation system twice a week for 4 weeks. Long-term repeated delivery of 4E-BP1 effectively reduced tumor progression in the lungs of K-rasLA1 mice. Reduction of eIF4E by overexpression of 4E-BP1 resulted in suppression of cap-dependent protein expression of basic fibroblast growth factor (bFGF or FGF-2) and vascular endothelial growth factor (VEGF). In addition, delivered 4E-BP1 inhibited the proliferation of lung cancer cells in K-rasLA1 mice model. Our results suggest that long-term repeated viral delivery of 4E-BP1 may provide a useful tool for designing lung cancer treatment. PMID:23640516

  11. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

    SciTech Connect

    Colleoni, Silvia; Giannelli, Serena G.; Armentero, Marie-Therese; Blandini, Fabio; Broccoli, Vania; Lazzari, Giovanna

    2010-04-15

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  12. Proangiogenic role of ephrinB1/EphB1 in basic fibroblast growth factor-induced corneal angiogenesis.

    PubMed

    Kojima, Takashi; Chang, Jin-Hong; Azar, Dimitri T

    2007-02-01

    Corneal neovascularization is a vision-threatening condition caused by various ocular pathological conditions. The aim of this study was to evaluate the function of the ephrin ligands and Eph receptors in vitro and in vivo in corneal angiogenesis in a mouse model. The Eph tyrosine kinase receptors and their ligands, ephrins, are expressed on the cell surface. The functions of Eph and ephrins have been shown to regulate axonal guidance, segmentation, cell migration, and angiogenesis. Understanding the roles of Eph and ephrin in corneal angiogenesis may provide a therapeutic intervention for the treatment of angiogenesis-related disorders. Immunohistochemical studies demonstrated that ephrinB1 and EphB1 were expressed in basic fibroblast growth factor (bFGF)-induced vascularized corneas. EphB1 was specifically colocalized with vascular endothelial marker CD31 surrounded by type IV collagen. EphrinB1 was expressed in corneal-resident keratocytes and neutrophils. Recombinant ephrinB1-Fc, which induces EphB receptor activation, enhanced bFGF-induced tube formation in an in vitro aortic ring assay and promoted bFGF-induced corneal angiogenesis in vivo in a corneal pocket assay. Synergistically enhanced and sustained activation of extracellular signal-regulated kinase was noted in vascular endothelial cell lines after stimulation with ephrin B1 and bFGF combinations. These results suggest that ephrinB1 plays a synergistic role in corneal neovascularization. PMID:17255342

  13. Factor XII (Hageman factor) deficiency

    MedlinePlus

    ... takes longer than normal to clot in a test tube. Factor XII deficiency is a rare inherited disorder. Symptoms There are usually no symptoms. Exams and Tests Factor XII deficiency is most often found when ...

  14. Enhanced trophic factor secretion by mesenchymal stem/stromal cells with Glycine-Histidine-Lysine (GHK)-modified alginate hydrogels

    PubMed Central

    Jose, Soumia; Hughbanks, Marissa L.; Binder, Bernard Y.K.; Ingavle, Ganesh C.; Leach, J. Kent

    2014-01-01

    Recombinant proteins and cytokines are under broad preclinical and clinical investigation to promote angiogenesis, but their success is limited by ineffective delivery, lack of long-term stability, and excessive cost. Mesenchymal stem/stromal cells (MSC) secrete bioactive trophic factors, and thus, may provide an effective alternative to address these challenges. Glycine-Histidine-Lysine (GHK) is a peptide fragment of osteonectin (SPARC), a matricellular protein with reported proangiogenic potential. We examined the capacity of GHK to upregulate secretion of proangiogenic factors from human MSC in culture and when covalently coupled to alginate hydrogels. GHK had no apparent cytotoxic effects on MSC in culture over a wide range of concentrations. We detected a dose-dependent increase in vascular endothelial growth factor (VEGF) concentration in media conditioned by GHK-treated MSC, which increased endothelial cell proliferation, migration, and tubule formation. We covalently coupled GHK to alginate using carbodiimide chemistry, and human MSC were entrapped in alginate hydrogels to assess VEGF secretion. Similar to monolayer culture, MSC responded to GHK-modified gels by secreting increased concentrations of VEGF and basic fibroblast growth factor (bFGF) compared to unmodified gels. The pre-treatment of MSC with antibodies to α6 and β1 integrins prior to entrapment in GHK-modified gels abrogated VEGF secretion, suggesting that the proangiogenic response of MSC was integrin-mediated. These data demonstrate that the proangiogenic potential of MSC can be significantly increased by the presentation of GHK with a biodegradable carrier, therefore increasing their clinical potential when used for tissue repair. PMID:24468583

  15. Protective effect of basic fibroblast growth factor on laser induced retinopathy

    PubMed Central

    Kartal, Unal; Koptagel, Emel; Bulut, H. Eray; Erdogan, Haydar

    2013-01-01

    AIM To investigate the side effects of the commonly used laser treatment along with testing the neuroprotective effect of bFGF on a potential retinal impairment. METHODS To do this, 30 chinchilla pigmented adult male rabbits were divided into the control and experimental groups. The control and experimental groups underwent both laser application and bFGF treatment. The retinal tissue impairment and its renewal rate were tested under the light and electron microscopical levels. RESULTS The focal laser application on rabbit eyes caused morphological alterations both in the application region and in the neighbouring areas. In the damaged areas, the outer nuclear layer of the neural retina was almost disappeared, retina pigment epithelium was interrupted, the retina pigment epithelium migrated intraretinally, and the damaged region along with neighbouring areas seemed to be not separated. bFGF application just after the laser photocoagulation, revealed better results in application areas. CONCLUSION It could be suggested that the bFGF application following laser photocoagulation might have protective, repairing and wound healing effects on the retina. PMID:24392319

  16. Quality factors

    SciTech Connect

    Kerr, G.D.

    1986-01-01

    The quality factor, Q, is a dimensionless modifier used in converting absorbed dose, expressed in rads (or grays), to dose equivalent, expressed in rems (or seiverts). The dose equivalent is used in radiation protection to account for the biological effectiveness of different kinds of radiation. The quality factor is related to both the linear energy transfer (LET) and relative biological effectiveness (RBE). The RBE's obtained from biological experiments depend in a complex way on the observed biological effect, the specific test organism, and the experimental conditions. Judgement is involved, therefore, in the choice of the quality factor. Questions regarding the adequacy of current Q values for neutrons were raised first in a 1980 statement by the National Council on Radiation Protection (NCRP) and later in a 1985 statement by the International Commission on Radiological Protection (ICRP). In 1980, the NCRP alerted the technical community to possible future increases between a factor of three and ten in the Q for neutrons, and in 1985, the ICRP suggested an increase by a factor of two in Q for neutrons. Both the ICRP and NRCP are now recommending essentially the same guidance with regard to Q for neutrons: an increase by a factor of two. The Q for neutrons is based on a large, albeit unfocused, body of experimental data. In spite of the lack of focus, the data supporting a change in the neutron quality factor are substantial. However, the proposed doubling of Q for neutrons is clouded by other issues regarding its application. 33 refs., 4 figs., 6 tabs.

  17. Cytokine, chemokine, and growth factor profile of platelet-rich plasma.

    PubMed

    Mussano, F; Genova, T; Munaron, L; Petrillo, S; Erovigni, F; Carossa, S

    2016-07-01

    During wound healing, biologically active molecules are released from platelets. The rationale of using platelet-rich plasma (PRP) relies on the concentration of bioactive molecules and subsequent delivery to healing sites. These bioactive molecules have been seldom simultaneously quantified within the same PRP preparation. In the present study, the flexible Bio-Plex system was employed to assess the concentration of a large range of cytokines, chemokines, and growth factors in 16 healthy volunteers so as to determine whether significant baseline differences may be found. Besides IL-1b, IL-1ra, IL-4, IL-6, IL-8, IL-12, IL-13, IL-17, INF-γ, TNF-α, MCP-1, MIP-1a, RANTES, bFGF, PDGF, and VEGF that were already quantified elsewhere, the authors reported also on the presence of IL-2, IL-5, IL-7, IL-9, IL-10, IL-15 G-CSF, GM-CSF, Eotaxin, CXCL10 chemokine (IP-10), and MIP 1b. Among the most interesting results, it is convenient to mention the high concentrations of the HIV-suppressive and inflammatory cytokine RANTES and a statistically significant difference between males and females in the content of PDGF-BB. These data are consistent with previous reports pointing out that gender, diet, and test system affect the results of platelet function in healthy subjects, but seem contradictory when compared to other quantification assays in serum and plasma. The inconsistencies affecting the experimental results found in literature, along with the variability found in the content of bioactive molecules, urge further research, hopefully in form of randomized controlled clinical trials, in order to find definitive evidence of the efficacy of PRP treatment in various pathologic and regenerative conditions. PMID:26950533

  18. Endothelium-mediated survival of leukemic cells and angiogenesis-related factors are affected by lenalidomide treatment in chronic lymphocytic leukemia.

    PubMed

    Maffei, Rossana; Fiorcari, Stefania; Bulgarelli, Jenny; Rizzotto, Lara; Martinelli, Silvia; Rigolin, Gian Matteo; Debbia, Giulia; Castelli, Ilaria; Bonacorsi, Goretta; Santachiara, Rita; Forconi, Francesco; Rossi, Davide; Laurenti, Luca; Palumbo, Giuseppe A; Vallisa, Daniele; Cuneo, Antonio; Gaidano, Gianluca; Luppi, Mario; Marasca, Roberto

    2014-02-01

    Lenalidomide is an IMID immunomodulatory agent clinically active in patients with chronic lymphocytic leukemia (CLL). We evaluated the activity of lenalidomide inside an in vitro coculture system of endothelial and CLL cells. Lenalidomide was able to inhibit CLL survival advantage mediated by endothelial contact. Moreover, the marked increase of in vitro angiogenesis determined by CLL-derived conditioned media was reduced by lenalidomide. We also analyzed peripheral blood collected from 27 patients with relapsed or refractory CLL being treated with lenalidomide within a phase II trial. Plasma levels of VEGF and THBS-1 decreased, whereas Ang2 and Ang increased during treatment. Patients who respond to lenalidomide showed a more pronounced decrease of VEGF and bFGF than did patients with stable or progressive disease (p = 0.007 and p = 0.005). Furthermore, lenalidomide reduced circulating endothelial cells and endothelial progenitors by increasing the percentage of apoptotic cells. Conversely, for six matched bone marrow biopsies available before and after treatment, we did not detect any modification in vessel density, suggesting a possible mechanism of vessel normalization rather than regression. In conclusion, our study provides further evidence that the anti-CLL effect of lenalidomide is mediated through the alteration of microenvironmental elements, implying the modulation of several angiogenesis-related factors and disruption of CLL crosstalk with endothelial cells. PMID:24212063

  19. Psychometric analysis in children with mental retardation due to perinatal hypoxia treated with fibroblast growth factor (FGF) and showing improvement in mental development.

    PubMed

    Aguilar, L C; Islas, A; Rosique, P; Hernandez, B; Portillo, E; Herrera, J M; Cortes, R; Cruz, S; Alfaro, F; Martin, R

    1993-12-01

    Basic fibroblast growth factor (bFGF) has shown a neurotrophic effect in the neurons of several CNS areas. In vivo, it contributes to restore neurochemical and morphological deficits in different rodent models of brain damage, including rats with brain damage induced by hypoxia/ischemia when FGF was intramuscularly (i.m.) administered. Toxicological and immunological studies performed in rats, mice and volunteers showed no evidence of side-effects. Bovine FGF was i.m. administered in children with mental retardation caused by perinatal hypoxia, aged 1-15 years, at dosages of 0.4 or 0.28 microgram kg-1, once or twice a month, over 7-12 months. Group A [n = 12; 6 treated (T), 6 controls (Ct)], group B (n = 16; 8 T, 8 Ct) and group C (n = 67; 45 T, 22 Ct) were evaluated with the P. A. R. scale, the WISC-RM and the Gesell scale, respectively. Development increased significantly in treated children from groups A (P < 0.02) and C (P < 0.001), and IQ rose by more than 10 points (P < 0.001) in group B patients. PMID:8123997

  20. 78 FR 38287 - Bitterroot National Forest, Darby Ranger District, Como Forest Health Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-26

    .... Correction In the Federal Register of June 17, 2013, in FR DOC 2013- 14229 on page 36163 in the second column...,640 acres of national forest between Lake Como and Lost Horse roads, about 6 miles northwest of...

  1. Rethinking Factors

    ERIC Educational Resources Information Center

    Feldman, Ziv

    2014-01-01

    This article describes an exciting exploration-based activity in which students develop an alternative definition of factor that can help them solve problems like the one presented above. Students work in groups to collect data, analyze the data to make conjectures, and then spend a significant amount of time debating and justifying their…

  2. The importance of growth factors for the treatment of chronic wounds in the case of diabetic foot ulcers

    PubMed Central

    Buchberger, Barbara; Follmann, Markus; Freyer, Daniela; Huppertz, Hendrik; Ehm, Alexandra; Wasem, Jürgen

    2010-01-01

    Introduction Ulcers as a result of diabetes mellitus are a serious problem with an enormous impact on the overall global disease burden due to the increasing prevalence of diabetes. Because of long hospital stays, rehabilitation, often required home care and the use of social services diabetic foot complications are costly. Therapy with growth factors could be an effective and innovative add-on to standard wound care. Research questions What is the benefit of therapies with growth factors alone or in combination with other technologies in the treatment of diabetic foot ulcer assessed regarding medical, economical, social, ethical and juridical aspects? Methods We systematically searched relevant databases limited to English and German language and publications since 1990. Cost values were adjusted to the price level of 2008 and converted into Euro. A review and an assessment of the quality of publications were conducted following approved methodical standards conforming to evidence-based medicine and health economics. Results We identified 25 studies (14 randomized controlled trials (RCT), nine cost-effectiveness analyses, two meta-analyses). The RCT compared an add-on therapy to standard wound care with standard wound care/placebo alone or extracellular wound matrix: in six studies becaplermin, in two rhEGF, in one bFGF, and in five studies the metabolically active skin grafts Dermagraft and Apligraf. The study duration ranged from twelve to 20 weeks and the study population included between 17 to 382 patients, average 130 patients. The treatment with becaplermin, rhEGF and skin implants Dermagraft and Apligraf showed in eight out of 13 studies an advantage concerning complete wound closure and the time to complete wound healing. Evidence for a benefit of treatment with bFGF could not be found. In four out of 14 studies the proportion of adverse events was 30% per study group with no difference between the treatment groups. The methodological quality of the

  3. Enhanced cell survival and paracrine effects of mesenchymal stem cells overexpressing hepatocyte growth factor promote cardioprotection in myocardial infarction.

    PubMed

    Zhao, Liyan; Liu, Xiaolin; Zhang, Yuelin; Liang, Xiaoting; Ding, Yue; Xu, Yan; Fang, Zhen; Zhang, Fengxiang

    2016-05-15

    Poor cell survival post transplantation compromises the therapeutic benefits of mesenchymal stem cells (MSCs) in myocardial infarction (MI). Hepatocyte growth factor (HGF) is an important cytokine for angiogenesis, anti-inflammation and anti-apoptosis. This study aimed to evaluate the cardioprotective effects of MSCs overexpressing HGF in a mouse model of MI. The apoptosis of umbilical cord-derived MSCs (UC-MSCs) and HGF-UC-MSCs under normoxic and hypoxic conditions was detected. The conditioned medium (CdM) of UC-MSCs and HGF-UC-MSCs under a hypoxic condition was harvested and its protective effect on neonatal cardiomyocytes (NCMs) exposed to a hypoxic challenge was examined. UC-MSCs and HGF-UC-MSCs were transplanted into the peri-infarct region in mice following MI and heart function assessed 4 weeks post transplantation. The apoptosis of HGF-UC-MSCs under hypoxic conditions was markedly decreased compared with that of UC-MSCs. NCMs treated with HGF-UC-MSC hypoxic CdM (HGF-UC-MSCs-hy-CdM) exhibited less cell apoptosis in response to hypoxic challenge than those treated with UC-MSC hypoxic CdM (UC-MSCs-hy-CdM). HGF-UC-MSCs-hy-CdM released the inhibited p-Akt and lowered the enhanced ratio of Bax/Bcl-2 induced by hypoxia in the NCMs. HGF-UC-MSCs-hy-CdM expressed higher levels of HGF, EGF, bFGF and VEGF than UC-MSCs-hy-CdM. Transplantation of HGF-UC-MSCs or UC-MSCs greatly improved heart function in the mouse model of MI. Compared with UC-MSCs, transplantation of HGF-UC-MSCs was associated with less cardiomyocyte apoptosis, enhanced angiogenesis and increased proliferation of cardiomyocytes. This study may provide a novel therapeutic strategy for MSC-based therapy in cardiovascular disease. PMID:27025401

  4. Chondroitinase and growth factors enhance activation and oligodendrocyte differentiation of endogenous neural precursor cells after spinal cord injury.

    PubMed

    Karimi-Abdolrezaee, Soheila; Schut, Desiree; Wang, Jian; Fehlings, Michael G

    2012-01-01

    The adult spinal cord harbours a population of multipotent neural precursor cells (NPCs) with the ability to replace oligodendrocytes. However, despite this capacity, proliferation and endogenous remyelination is severely limited after spinal cord injury (SCI). In the post-traumatic microenvironment following SCI, endogenous spinal NPCs mainly differentiate into astrocytes which could contribute to astrogliosis that exacerbate the outcomes of SCI. These findings emphasize a key role for the post-SCI niche in modulating the behaviour of spinal NPCs after SCI. We recently reported that chondroitin sulphate proteoglycans (CSPGs) in the glial scar restrict the outcomes of NPC transplantation in SCI by reducing the survival, migration and integration of engrafted NPCs within the injured spinal cord. These inhibitory effects were attenuated by administration of chondroitinase (ChABC) prior to NPC transplantation. Here, in a rat model of compressive SCI, we show that perturbing CSPGs by ChABC in combination with sustained infusion of growth factors (EGF, bFGF and PDGF-AA) optimize the activation and oligodendroglial differentiation of spinal NPCs after injury. Four days following SCI, we intrathecally delivered ChABC and/or GFs for seven days. We performed BrdU incorporation to label proliferating cells during the treatment period after SCI. This strategy increased the proliferation of spinal NPCs, reduced the generation of new astrocytes and promoted their differentiation along an oligodendroglial lineage, a prerequisite for remyelination. Furthermore, ChABC and GF treatments enhanced the response of non-neural cells by increasing the generation of new vascular endothelial cells and decreasing the number of proliferating macrophages/microglia after SCI. In conclusions, our data strongly suggest that optimization of the behaviour of endogenous spinal NPCs after SCI is critical not only to promote endogenous oligodendrocyte replacement, but also to reverse the otherwise

  5. Como preparar un programa de informacion sobre la asistencia economica (Planning a Financial Aid Awareness Program).

    ERIC Educational Resources Information Center

    Department of Education, Washington, DC.

    This booklet, written in Spanish, is intended to be used with a set of slides as part of a presentation to students on "How To Apply for Federal Student Aid" ("Como Solicitar la Asistencia Economica Federal para Estudiantes"). The first part of the book is a script based on the slides. After the script is a guide to hosting a financial aid…

  6. Localisation of vascular endothelial growth factor and its receptors to cells of vascular and avascular epiretinal membranes

    PubMed Central

    Chen, Y.; Hackett, S.; Schoenfeld, C.; Vinores, M.; Vinores, S.; Campochiaro, P.

    1997-01-01

    AIMS/BACKGROUND—Epiretinal membranes (ERMs) arise from a variety of causes or, in some cases, for unknown reasons. Once established, ERMs tend to progress, becoming more extensive and exerting increasing traction along the inner surface of the retina. One possible cause for their progression is the production of growth factors by cells within ERMs that may provide autocrine or paracrine stimulation. Platelet derived growth factor (PDGF) and its receptors have been localised to cells of ERMs and may play such a role. In this study, comparative data were sought for several other growth factors that have been implicated in ERM formation.
METHODS—Immunohistochemical staining of ERMs was done for PDGF-A, PDGF-B, basic fibroblast growth factor (bFGF), three isoforms of transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF) and its receptors, flt-1 and flk-1/KDR. Expression of flt-1 and flk-1/KDR was examined in cultured retinal pigmented epithelial (RPE) cells and retinal glia from postmortem eyes by immunohistochemistry and by reverse transcription coupled to polymerase chain reaction (RT-PCR).
RESULTS—Staining was most intense and most frequently observed for VEGF and PDGF-A, both in vascular and avascular ERMs. The majority of cells stained for VEGF in nine of 11 (81.8%) diabetic ERMs and in 14 of 24 (58.3%) proliferative vitreoretinopathy ERMs. The receptors for VEGF, flt-1, and flk-1/KDR were also identified on cells in ERMs and on cultured RPE cells. By RT-PCR, mRNA for flt-1 was identified in RPE cells and retinal glia, and mRNA for flk-1/KDR was identified in RPE cells.
CONCLUSIONS—These data show that VEGF and its receptors are localised to both vascular and avascular ERMs and suggest that VEGF, like PDGF-A, may be an autocrine and paracrine stimulator that may contribute to progression of vascular and avascular ERMs.

 PMID:9486038

  7. Synergistic effects of transplanted adult neural stem/progenitor cells, chondroitinase, and growth factors promote functional repair and plasticity of the chronically injured spinal cord.

    PubMed

    Karimi-Abdolrezaee, Soheila; Eftekharpour, Eftekhar; Wang, Jian; Schut, Desiree; Fehlings, Michael G

    2010-02-01

    The transplantation of neural stem/progenitor cells (NPCs) is a promising therapeutic strategy for spinal cord injury (SCI). However, to date NPC transplantation has exhibited only limited success in the treatment of chronic SCI. Here, we show that chondroitin sulfate proteoglycans (CSPGs) in the glial scar around the site of chronic SCI negatively influence the long-term survival and integration of transplanted NPCs and their therapeutic potential for promoting functional repair and plasticity. We targeted CSPGs in the chronically injured spinal cord by sustained infusion of chondroitinase ABC (ChABC). One week later, the same rats were treated with transplants of NPCs and transient infusion of growth factors, EGF, bFGF, and PDGF-AA. We demonstrate that perturbing CSPGs dramatically optimizes NPC transplantation in chronic SCI. Engrafted NPCs successfully integrate and extensively migrate within the host spinal cord and principally differentiate into oligodendrocytes. Furthermore, this combined strategy promoted the axonal integrity and plasticity of the corticospinal tract and enhanced the plasticity of descending serotonergic pathways. These neuroanatomical changes were also associated with significantly improved neurobehavioral recovery after chronic SCI. Importantly, this strategy did not enhance the aberrant synaptic connectivity of pain afferents, nor did it exacerbate posttraumatic neuropathic pain. For the first time, we demonstrate key biological and functional benefits for the combined use of ChABC, growth factors, and NPCs to repair the chronically injured spinal cord. These findings could potentially bring us closer to the application of NPCs for patients suffering from chronic SCI or other conditions characterized by the formation of a glial scar. PMID:20130176

  8. Structural insights into the interaction of human S100B and basic fibroblast growth factor (FGF2): Effects on FGFR1 receptor signaling.

    PubMed

    Gupta, Arun A; Chou, Ruey-Hwang; Li, Hongchun; Yang, Lee-Wei; Yu, Chin

    2013-12-01

    S100B is a calcium sensing protein belonging to the S100 protein family with intracellular and extracellular roles. It is one of the EF hand homodimeric proteins, which is known to interact with various protein targets to regulate varied biological functions. Extracellular S100B has been recently reported to interact with FGF2 in a RAGE-independent manner. However, the recognition mechanism of S100B-FGF2 interaction at the molecular level remains unclear. In this study, the critical residues on S100B-FGF2 interface were mapped by combined information derived from NMR spectroscopy and site directed mutagenesis experiments. Utilizing NMR titration data, we generated the structural models of S100B-FGF2 complex from the computational docking program, HADDOCK which were further proved stable during 15ns unrestrained molecular dynamics (MD) simulations. Isothermal titration calorimetry studies indicated S100B interaction with FGF2 is an entropically favored process implying dominant role of hydrophobic contacts at the protein-protein interface. Residue level information of S100B interaction with FGF2 was useful to understand the varied target recognition ability of S100B and further explained its role in effecting extracellular signaling diversity. Mechanistic insights into the S100B-FGF2 complex interface and cell-based assay studies involving mutants led us to conclude the novel role of S100B in FGF2 mediated FGFR1 receptor inactivation. PMID:24063890

  9. Factor X deficiency

    MedlinePlus

    Factor X (ten) deficiency is a disorder caused by a lack of a protein called factor X in the blood. It leads to problems with ... or are not functioning like they should. Factor X is one such coagulation factor. Factor X deficiency ...

  10. The Sefwi-Comoé belt Ghana/Ivory Coast : a major crustal shear zone ?

    NASA Astrophysics Data System (ADS)

    Jessell, Mark

    2010-05-01

    The Palaeoproterozoic Sefwi-Comoé region that straddles Ghana and the Ivory Coast in West Africa has been characterised as resulting from a combination of compression and simple shear during late synkinematic leucogranite intrusion. The analysis of regional geophysical datasets allows us to better define the geometry of the major lithostratigraphic packages and their structural contacts in this region. This analysis reveals a series of well defined leucogranites intrusions enveloped by high strain zones. Recent finite element modelling of two-phase aggregates has shown that we can analyse the geometry of these systems both in terms of their finite defomation and their mechanical contrast. We interpret the geometries we see in the Sefwi-Comoé region as reflecting the activity of a major crustal deformation zone which was dominated by simple shear. The comparison with the modelling suggests a finite shear strain of approximately 5 gamma, which in turn implies a lateral displacement of 400 km across the belt. Our analysis suggests that the leucogranites were already acting as more rigid bodies during the (dextral?) shearing, suggesting that their emplacement was predominantly pre-kinematic, and which has implications for their potential subsequent remobilization by gravitational forces.

  11. Differential activation of nuclear transcription factor kappaB, gene expression, and proteins by amifostine's free thiol in human microvascular endothelial and glioma cells.

    PubMed

    Grdina, David J; Murley, Jeffrey S; Kataoka, Yasushi; Calvin, Douglas P

    2002-01-01

    The effects of WR1065 (SH), the free thiol form of amifostine, on nuclear transcription factor kappaB (NFkappaB) activation, manganese superoxide dismutase (MnSOD) gene expression, and secretion of human vascular endothelial cell growth factor (hVEGF), basic fibroblast growth factor (bFGF), tumor necrosis factor-alpha (TNF-alpha), vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, P-selectin, and interleukins IL-1alpha, IL-6, and IL-8 were investigated and compared in human microvascular endothelial (HMEC) and human glioma cells. WR1065 was evaluated at 2 concentrations, 4 mmol/L, ie, its most effective cytoprotective dose, and 40 micromol/L, a noncytoprotective but highly effective dose capable of preventing radiation and chemotherapeutic drug-induced mutations in exposed cells. A 30-minute exposure of HMEC and glioma cell lines U87 and U251 to WR1065 at either of the concentrations resulted in a marked activation of NFkappaB as determined by a gel shift assay, with the maximum effect observed between 30 minutes and 1 hour after treatment. Using a supershift assay, WR1065 exposure was observed to affect only the p50-p65 heterodimer, and not the homodimers or heterodimers containing p52 or c-Rel subunits of NFkappaB. WR1065 was also found to enhance MnSOD gene expression in both HMEC and glioma cells. Gene expression was enhanced 1.8-fold over control levels in HMEC over a period ranging from 12 to 24 hours after the time of maximum activation of NFkappaB. In contrast, MnSOD gene expression in U87 cells rose 3.5 times above control levels over this same period. WR1065 had no effect on the levels of adhesion molecules, cytokines, and growth factors secreted by cells exposed for up to 24 hours as measured by enzyme-linked immunosorbent assay. PMID:11917294

  12. Basic FGF attenuates amyloid beta-peptide-induced oxidative stress, mitochondrial dysfunction, and impairment of Na+/K+-ATPase activity in hippocampal neurons.

    PubMed

    Mark, R J; Keller, J N; Kruman, I; Mattson, M P

    1997-05-01

    Basic fibroblast growth factor (bFGF) exhibits trophic activity for many populations of neurons in the brain, and can protect those neurons against excitotoxic, metabolic and oxidative insults. In Alzheimer's disease (AD), amyloid beta-peptide (A beta) fibrils accumulate in plaques which are associated with degenerating neurons. A beta can be neurotoxic by a mechanism that appears to involve induction of oxidative stress and disruption of calcium homeostasis. Plaques in AD brain contain high levels of bFGF suggesting a possible modulatory role for bFGF in the neurodegenerative process. We now report that bFGF can protect cultured hippocampal neurons against A beta25-35 toxicity by a mechanism that involves suppression of reactive oxygen species (ROS) accumulation and maintenance of Na+/K+-ATPase activity. A beta25-35 induced lipid peroxidation, accumulation of H2O2, mitochondrial ROS accumulation, and a decrease in mitochondrial transmembrane potential; each of these effects of A beta25-35 was abrogated in cultures pre-treated with bFGF. Na+/K+-ATPase activity was significantly reduced following exposure to A beta25-35 in control cultures, but not in cultures pre-treated with bFGF. bFGF did not protect neurons from death induced by ouabain (a specific inhibitor of the Na+/K+-ATPase) or 4-hydroxynonenal (an aldehydic product of lipid peroxidation) consistent with a site of action of bFGF prior to induction of oxidative stress and impairment of ion-motive ATPases. By suppressing accumulation of oxyradicals, bFGF may slow A beta-induced neurodegenerative cascades. PMID:9187334

  13. ISS Payload Human Factors

    NASA Technical Reports Server (NTRS)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  14. Factor V deficiency

    MedlinePlus

    Blood clotting is a complex process involving as many as 20 different proteins in blood plasma. These proteins ... by a lack of Factor V. When certain blood clotting factors are low or missing, your blood does ...

  15. Factoring Polynomials and Fibonacci.

    ERIC Educational Resources Information Center

    Schwartzman, Steven

    1986-01-01

    Discusses the factoring of polynomials and Fibonacci numbers, offering several challenges teachers can give students. For example, they can give students a polynomial containing large numbers and challenge them to factor it. (JN)

  16. Factor VII deficiency

    MedlinePlus

    ... may be done include: Partial thromboplastin time ( PTT ) Plasma factor VII activity Prothrombin time ( PT ) Mixing study ... controlled by getting intravenous (IV) infusions of normal plasma, concentrates of factor VII, or genetically produced (recombinant) ...

  17. Heart disease - risk factors

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000106.htm Heart disease - risk factors To use the sharing features on this ... may help you live a longer, healthier life. Risk Factors You Cannot Change Some of your heart ...

  18. Factor V deficiency

    MedlinePlus

    ... as many as 20 different proteins in blood plasma. These proteins are called blood coagulation factors. Factor ... You will be given fresh blood plasma or fresh frozen plasma infusions ... These treatments will correct the deficiency temporarily.

  19. A phase I dose-escalation study to a predefined dose of a transforming growth factor-β1 monoclonal antibody (TβM1) in patients with metastatic cancer

    PubMed Central

    COHN, ALLEN; LAHN, MICHAEL M.; WILLIAMS, KRISTEN E.; CLEVERLY, ANN L.; PITOU, CELINE; KADAM, SUNIL K.; FARMEN, MARK W.; DESAIAH, DURISALA; RAJU, ROBERT; CONKLING, PAUL; RICHARDS, DONALD

    2014-01-01

    Transforming growth factor β (TGF-β) plays an important role in cancer. Monoclonal antibodies (mAb) designed to specifically block the TGF-β ligands, are expected to inhibit tumor progression in patients with metastatic cancer. TβM1 is a humanized mAb optimized for neutralizing activity against TGF-β1. The objective of this clinical trial was to assess the safety and tolerability of TβM1 in patients with metastatic cancer. In this phase I, uncontrolled, non-randomized, dose-escalation study, 18 eligible adult patients who had measurable disease per RECIST and a performance status of ≤2 on the ECOG scale were administered TβM1 intravenously over 10 min at doses of 20, 60, 120 and 240 mg on day 1 of each 28-day cycle. Safety was assessed by adverse events (as defined by CTCAE version 3.0) and possible relationship to study drug, dose-limiting toxicities and laboratory changes. Systemic drug exposure and pharmacodynamic (PD) parameters were assessed. TβM1 was safe when administered once monthly. The pharmacokinetic (PK) profile was consistent with a mAb with a mean elimination half-life approximately 9 days. Although anticipated changes in PD markers such as serum VEGF, bFGF and mRNA expression of SMAD7 were observed in whole-blood, suggesting activity of TβM1 on the targeted pathway, these changes were not consistent to represent a PD effect. Additionally, despite the presence of an activated TGF-β1 expression signature in patients’ whole blood, the short dosing duration did not translate into significant antitumor effect in the small number of patients investigated in this study PMID:25270361

  20. Mesonic Form Factors

    SciTech Connect

    Frederic D. R. Bonnet; Robert G. Edwards; George T. Fleming; Randal Lewis; David Richards

    2003-07-22

    We have started a program to compute the electromagnetic form factors of mesons. We discuss the techniques used to compute the pion form factor and present preliminary results computed with domain wall valence fermions on MILC asqtad lattices, as well as Wilson fermions on quenched lattices. These methods can easily be extended to rho-to-gamma-pi transition form factors.

  1. Multilevel Mixture Factor Models

    ERIC Educational Resources Information Center

    Varriale, Roberta; Vermunt, Jeroen K.

    2012-01-01

    Factor analysis is a statistical method for describing the associations among sets of observed variables in terms of a small number of underlying continuous latent variables. Various authors have proposed multilevel extensions of the factor model for the analysis of data sets with a hierarchical structure. These Multilevel Factor Models (MFMs)…

  2. Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival

    PubMed Central

    Giatromanolaki, A; Koukourakis, M I; Sivridis, E; Turley, H; Talks, K; Pezzella, F; Gatter, K C; Harris, A L

    2001-01-01

    Hypoxia inducible factors HIF1α and HIF2α are important proteins involved in the regulation of the transcription of a variety of genes related to erythropoiesis, glycolysis and angiogenesis. Hypoxic stimulation results in rapid increase of the HIF1α and 2α protein levels, as a consequence of a redox-sensitive stabilization. The HIFαs enter the nucleus, heterodimerize with the HIF1β protein, and bind to DNA at the hypoxia response elements (HREs) of target genes. In this study we evaluated the immunohistochemical expression of these proteins in 108 tissue samples from non-small-cell lung cancer (NSCLC) and in normal lung tissues. Both proteins showed a mixed cytoplasmic/nuclear pattern of expression in cancer cells, tumoural vessels and tumour-infiltrating macrophages, as well as in areas of metaplasia, while normal lung components showed negative or very weak cytoplasmic staining. Positive HIF1α and HIF2α expression was noted in 68/108 (62%) and in 54/108 (50%) of cases respectively. Correlation analysis of HIF2α expression with HIF1α expression showed a significant association (P < 0.0001, r = 0.44). A strong association of the expression of both proteins with the angiogenic factors VEGF (P < 0.004), PD-ECGF (P < 0.003) and bFGF (P < 0.04) was noted. HIF1α correlated with the expression of bek-bFGF receptor expression (P = 0.01), while HIF2α was associated with intense VEGF/KDR-activated vascularization (P = 0.002). HIF2α protein was less frequently expressed in cases with a medium microvessel density (MVD); a high rate of expression was noted in cases with both low and high MVD (P = 0.006). Analysis of overall survival showed that HIF2α expression was related to poor outcome (P = 0.008), even in the group of patients with low MVD (P = 0.009). HIF1α expression was marginally associated with poor prognosis (P = 0.08). In multivariate analysis HIF2α expression was an independent prognostic indicator (P = 0.006, t-ratio 2.7). We conclude that HIF1

  3. Bayesian Exploratory Factor Analysis

    PubMed Central

    Conti, Gabriella; Frühwirth-Schnatter, Sylvia; Heckman, James J.; Piatek, Rémi

    2014-01-01

    This paper develops and applies a Bayesian approach to Exploratory Factor Analysis that improves on ad hoc classical approaches. Our framework relies on dedicated factor models and simultaneously determines the number of factors, the allocation of each measurement to a unique factor, and the corresponding factor loadings. Classical identification criteria are applied and integrated into our Bayesian procedure to generate models that are stable and clearly interpretable. A Monte Carlo study confirms the validity of the approach. The method is used to produce interpretable low dimensional aggregates from a high dimensional set of psychological measurements. PMID:25431517

  4. Aerostructural safety factor criteria

    NASA Technical Reports Server (NTRS)

    Verderaime, V.

    1992-01-01

    The present modification of the conventional safety factor method for aircraft structures evaluation involves the expression of deterministic safety factors in probabilistic tolerance limit ratios; these are found to involve a total of three factors that control the interference of applied and resistive stress distributions. The deterministic expression is extended so that it may furnish a 'relative ultimate safety' index that encompasses all three distribution factors. Operational reliability is developed on the basis of the applied and the yield stress distribution interferences. Industry standards are suggested to be derivable from factor selections that are based on the consequences of failure.

  5. Vulnerability and adaptation to climate change in the Comoe River Basin (West Africa).

    PubMed

    Yéo, Wonnan Eugène; Goula, Bi Tié Albert; Diekkrüger, Bernd; Afouda, Abel

    2016-01-01

    Climate change is impacting water users in many sectors: water supply, farming, industry, hydropower, fishing, housing, navigation and health. Existing situations, like population growth, movement of populations from rural to urban areas, poverty and pollution can aggravate the impacts of climate change. The aim of the study is to evaluate the vulnerability of different water user groups to climate change and define communities' adaptation strategies in the Comoe River Basin. Information was collected on communities' concerns and perception on changes in climate and potential adaptation measures and strategies. Results show that 95 % of the sample in the study communities had heard of it and are aware that climate change is occurring. They have been experiencing changes in economic activity and cropping pattern, reduced water level in rivers, crop failure, delay in cropping season, new pests and diseases, food insecurity, drop in income and decline in crop yield. Results also show that communities employ various adaptation strategies including crops diversification, substitution and calendar redefinition, agroforestry, borrowing from friends and money lenders and increasing fertilizer application. PMID:27386296

  6. Factor VIII and glomerulonephritis.

    PubMed

    Ekberg, M; Nilsson, I M

    1975-05-17

    To find out if determination of factor VIII,which most probably is synthetised in the intima of blood-vessesls, is of value for predicting the severity of vessel damge in glomerulonephritis, factor-VIII activity, factor-VIII-related antigen, and glomerular filtration-ratewere esto,ated om 85 patients with early glomerulonephritis on admission, and in 70 of these at follow-up for up to 4 years. The levels of factor-VIII activity and factor-VIII-related antigen on admission were normal in those patients who recovered. Where renal function was impaired on admission or becaome so during follow-up, factor VIII was high. Determination of factor VIII might thus be of prognostic value in early glomerulonephritis. PMID:49471

  7. Basic FGF and PDGF-BB synergistically stimulate hyaluronan and IL-6 production by orbital fibroblasts.

    PubMed

    Virakul, Sita; Heutz, Judith W; Dalm, Virgil A S H; Peeters, Robin P; Paridaens, Dion; van den Bosch, Willem A; Hirankarn, Nattiya; van Hagen, P Martin; Dik, Willem A

    2016-09-15

    Orbital fibroblast activation is a central pathologic feature of Graves' Ophthalmopathy (GO). Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have been proposed to contribute to GO, but their effects on orbital fibroblasts are largely unknown. We found that bFGF stimulated proliferation and hyaluronan production, but not IL-6 production by orbital fibroblasts, while VEGF hardly affected orbital fibroblast activity. Remarkably, co-stimulation of orbital fibroblasts with bFGF and PDGF-BB synergistically enhanced IL-6 and hyaluronan production and displayed an additive effect on proliferation compared to either bFGF or PDGF-BB stimulation. Nintedanib, a FGF- and PDGF-receptor targeting drug, more efficiently blocked bFGF + PDGF-BB-induced IL-6 and hyaluronan production than dasatinib that only targets PDGF-receptor. In conclusion, bFGF may contribute to orbital inflammation and tissue remodeling in GO, especially through synergistic interaction with PDGF-BB. Multi-target therapy directed at the bFGF and PDGF pathways may potentially be of interest for the treatment of GO. PMID:27267669

  8. New scale factor measure

    NASA Astrophysics Data System (ADS)

    Bousso, Raphael

    2012-07-01

    The computation of probabilities in an eternally inflating universe requires a regulator or “measure.” The scale factor time measure truncates the Universe when a congruence of timelike geodesics has expanded by a fixed volume factor. This definition breaks down if the generating congruence is contracting—a serious limitation that excludes from consideration gravitationally bound regions such as our own. Here we propose a closely related regulator which is well defined in the entire spacetime. The new scale factor cutoff restricts to events with a scale factor below a given value. Since the scale factor vanishes at caustics and crunches, this cutoff always includes an infinite number of disconnected future regions. We show that this does not lead to divergences. The resulting measure combines desirable features of the old scale factor cutoff and of the light-cone time cutoff, while eliminating some of the disadvantages of each.

  9. Analytic Couple Modeling Introducing Device Design Factor, Fin Factor, Thermal Diffusivity Factor, and Inductance Factor

    NASA Technical Reports Server (NTRS)

    Mackey, Jon; Sehirlioglu, Alp; Dynys, Fred

    2014-01-01

    A set of convenient thermoelectric device solutions have been derived in order to capture a number of factors which are previously only resolved with numerical techniques. The concise conversion efficiency equations derived from governing equations provide intuitive and straight-forward design guidelines. These guidelines allow for better device design without requiring detailed numerical modeling. The analytical modeling accounts for factors such as i) variable temperature boundary conditions, ii) lateral heat transfer, iii) temperature variable material properties, and iv) transient operation. New dimensionless parameters, similar to the figure of merit, are introduced including the device design factor, fin factor, thermal diffusivity factor, and inductance factor. These new device factors allow for the straight-forward description of phenomenon generally only captured with numerical work otherwise. As an example a device design factor of 0.38, which accounts for thermal resistance of the hot and cold shoes, can be used to calculate a conversion efficiency of 2.28 while the ideal conversion efficiency based on figure of merit alone would be 6.15. Likewise an ideal couple with efficiency of 6.15 will be reduced to 5.33 when lateral heat is accounted for with a fin factor of 1.0.

  10. Exploratory Bi-Factor Analysis

    ERIC Educational Resources Information Center

    Jennrich, Robert I.; Bentler, Peter M.

    2011-01-01

    Bi-factor analysis is a form of confirmatory factor analysis originally introduced by Holzinger. The bi-factor model has a general factor and a number of group factors. The purpose of this article is to introduce an exploratory form of bi-factor analysis. An advantage of using exploratory bi-factor analysis is that one need not provide a specific…

  11. FACTORS AFFECTING PITCH DISCRIMINATION.

    ERIC Educational Resources Information Center

    BERGAN, JOHN R.

    EFFECTS OF TONAL MEMORY OF TWO KINDS OF FACTORS WERE STUDIED. THE FACTORS WERE (1) THE CHARACTERISTICS OF STIMULI PRESENTED TO THE SUBJECT IN A PITCH IDENTIFICATION TASK, AND (2) THOSE EFFECTING THE RESPONSE THAT THE SUBJECT MAKES IN SUCH A TASK. FIVE HYPOTHESES WERE ADVANCED FOR STUDY. THE UNDERLYING ASSUMPTION WAS THAT THERE ARE IMPORTANT…

  12. Plant transcription factors.

    PubMed

    Meshi, T; Iwabuchi, M

    1995-12-01

    Transcriptional regulation of gene expression relies on the recognition of promoter elements by transcription factors. In the past several years, a considerable number of (putative) transcription factors have been identified in plants. Some genes coding for these factors were isolated by south-western screening with oligonucleotides as a probe or by homology-based screening, and others were initially isolated by genetic means and subsequently identified as the genes for transcription factors. These transcription factors often form families of structurally related proteins with similar DNA-binding specificities and in addition, they are sometimes involved in related phenomena. Some groups of factors homo- and/or heterodimerize to increase the length and variability of the target sequences. Transcriptional activators, in general, comprise a modular activation domain. The activities of the transcription factors are controlled by post-translational modification, like phosphorylation and glycosylation, as well as at the levels of nuclear transport, oligomerization, etc. In this review, we will summarize the current knowledge of plant transcription factors to help understand the mechanistic aspects of the transcriptional regulation of genes. PMID:8589926

  13. Factorizing RSA Keys

    NASA Astrophysics Data System (ADS)

    Blakey, Ed

    Factorization is notoriously difficult. Though the problem is not known to be NP-hard, neither efficient, algorithmic solution nor technologically practicable, quantum-computer solution has been found. This apparent complexity, which renders infeasible the factorization of sufficiently large values, makes secure the RSA cryptographic system.

  14. Block LU factorization

    NASA Technical Reports Server (NTRS)

    Demmel, James W.; Higham, Nicholas J.; Schreiber, Robert S.

    1992-01-01

    Many of the currently popular 'block algorithms' are scalar algorithms in which the operations have been grouped and reordered into matrix operations. One genuine block algorithm in practical use is block LU factorization, and this has recently been shown by Demmel and Higham to be unstable in general. It is shown here that block LU factorization is stable if A is block diagonally dominant by columns. Moreover, for a general matrix the level of instability in block LU factorization can be founded in terms of the condition number kappa(A) and the growth factor for Gaussian elimination without pivoting. A consequence is that block LU factorization is stable for a matrix A that is symmetric positive definite or point diagonally dominant by rows or columns as long as A is well-conditioned.

  15. Catalytic functionalities of supported sulfides. I. Effect of support and additives on the CoMo catalyst

    SciTech Connect

    Muralidhar, G.; Massoth, F.E.; Shabtai, J.

    1984-01-01

    C-S hydrogenolysis (HDS) of thiophene, hydrogenation (HYD) of 1-hexene, and hydrocracking (HCG) of 2,4,4-trimethyl-1-pentene, were used as separate model test reactions to differentiate and assess the catalytic functionalities of sulfided CoMo catalysts, and their dependence on the nature of the support and incorporation of additives. Rate constants and relative catalyst activities for these three reaction types were determined. HDS and HYD activities of CoMo supported on different types of Al/sub 2/O/sub 3/ were higher, while the HCG activity was lower compared with CoMo supported on SiO/sub 2/-Al/sub 2/O/sub 3/, SiO/sub 2/-MgO, or TiO/sub 2/. For SiO/sub 2/-Al/sub 2/O/sub 3/ supports both HDS and HYD activities decreased with increase in SiO/sub 2/ content from 10 to 75%, while HCG activity showed the opposite trend. Additives to a finished CoMo catalyst at 0.5% level caused variations in HDS and HCG activities, while HYD was essentially unaffected. HDS was promoted by NH/sub 4/HF/sub 2/ and NH/sub 4/Cl, but depressed by NaNO/sub 3/, Ca(NO/sub 3/)/sub 2/, and H/sub 3/BO/sub 3/. HCG was promoted by NH/sub 4/HF/sub 2/, NH/sub 4/Cl, and H/sub 3/BO/sub 3/. Additives at 5% level, prior to or after CoMo impregnation, showed a strong depressing effect on HDS and a lesser effect on HYD, while HCG was strongly promoted by NH/sub 4/HF/sub 2/, Ti isopropoxide, and H/sub 3/BO/sub 3/. The changes in catalytic functionalities are rationalized in terms of different interactions between CoMo phase, support, and additives. 3 tables, 1 figure.

  16. Growth factors in haemopoiesis.

    PubMed

    Jones, A L; Millar, J L

    1989-01-01

    Haemopoietic growth factors have for over two decades allowed experimentalists to grow haemopoietic bone marrow cells in vitro. With refinements in technique and the discovery of novel growth factors, all of the known haemopoietic lineages can now be grown in vitro. This has allowed a much greater understanding of the complex process of haemopoiesis from the haemopoietic stem cell to the mature, functioning end-cell. The in vivo action of these growth factors has been harder to investigate. Although recombinant technology has afforded us the much greater quantities necessary for in vivo work, problems remain with administration because of effects on other tissues. Interpretation of results is difficult because of the complex inter-relationships which exist between factors. Some of these have been defined in vitro and it appears likely that they also operate in vivo. Erythropoietin is a physiological regulator of erythropoiesis. It has been detected in vivo with levels responding appropriately to stress (i.e. elevated in anaemia) and, when administered in pharmacological doses, has been shown to correct anaemia. Granulocyte/macrophage colony-stimulating factor (GM-CSF) has been detected in vivo and may influence the production and function of granulocytes and macrophages, although how it is regulated is unknown. Granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor are ore lineage-specific. Interleukin 3 (IL-3), although it has not been detected in vivo, may act on a primitive marrow precursor by expanding the population and making these cells more susceptible to other growth factors, such as GM-CSF. Interleukin 1 (IL-1) has been detected in vivo, does not appear to have any isolated action on bone marrow (except possibly radioprotection) but probably acts synergistically with other growth factors, such as G-CSF. Interleukins 2, 4, 5 and 6 have not been detected in vivo. All have effects on B-cells. In addition IL-2 is an essential

  17. Risk Factors for Tuberculosis

    PubMed Central

    Narasimhan, Padmanesan; Wood, James; MacIntyre, Chandini Raina; Mathai, Dilip

    2013-01-01

    The risk of progression from exposure to the tuberculosis bacilli to the development of active disease is a two-stage process governed by both exogenous and endogenous risk factors. Exogenous factors play a key role in accentuating the progression from exposure to infection among which the bacillary load in the sputum and the proximity of an individual to an infectious TB case are key factors. Similarly endogenous factors lead in progression from infection to active TB disease. Along with well-established risk factors (such as human immunodeficiency virus (HIV), malnutrition, and young age), emerging variables such as diabetes, indoor air pollution, alcohol, use of immunosuppressive drugs, and tobacco smoke play a significant role at both the individual and population level. Socioeconomic and behavioral factors are also shown to increase the susceptibility to infection. Specific groups such as health care workers and indigenous population are also at an increased risk of TB infection and disease. This paper summarizes these factors along with health system issues such as the effects of delay in diagnosis of TB in the transmission of the bacilli. PMID:23476764

  18. Environmental Factors in Autism

    PubMed Central

    Grabrucker, Andreas M.

    2013-01-01

    Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed. PMID:23346059

  19. Precipitating factors of insomnia.

    PubMed

    Bastien, Célyne H; Vallières, Annie; Morin, Charles M

    2004-01-01

    Insomnia is a prevalent health complaint whose onset is precipitated by a variety of factors. There is an important need to identify and describe these factors to improve our understanding of risk factors and the natural history of insomnia. This article is aimed at identifying and describing the types of precipitating factors related to the onset of insomnia. A total of 345 patients evaluated for insomnia at a sleep-disorders clinic completed a sleep survey and underwent a semistructured clinical interview. As part of the evaluation, the specific precipitating events related to the onset of insomnia were identified. Subsequently, these factors were categorized (work-school, family, physical or psychological health, or indeterminate), and their affective valence (negative, positive, or indeterminate) was coded. The most common precipitating factors of insomnia were related to family, health, and work-school events. Sixty-five percent of precipitating events had a negative valence. These events differed with the age of onset of insomnia but not with the gender of participants. These findings are useful to identify potential risk factors for insomnia and improve our understanding of the natural history of insomnia. PMID:15600224

  20. Conundrums with uncertainty factors.

    PubMed

    Cooke, Roger

    2010-03-01

    The practice of uncertainty factors as applied to noncancer endpoints in the IRIS database harkens back to traditional safety factors. In the era before risk quantification, these were used to build in a "margin of safety." As risk quantification takes hold, the safety factor methods yield to quantitative risk calculations to guarantee safety. Many authors believe that uncertainty factors can be given a probabilistic interpretation as ratios of response rates, and that the reference values computed according to the IRIS methodology can thus be converted to random variables whose distributions can be computed with Monte Carlo methods, based on the distributions of the uncertainty factors. Recent proposals from the National Research Council echo this view. Based on probabilistic arguments, several authors claim that the current practice of uncertainty factors is overprotective. When interpreted probabilistically, uncertainty factors entail very strong assumptions on the underlying response rates. For example, the factor for extrapolating from animal to human is the same whether the dosage is chronic or subchronic. Together with independence assumptions, these assumptions entail that the covariance matrix of the logged response rates is singular. In other words, the accumulated assumptions entail a log-linear dependence between the response rates. This in turn means that any uncertainty analysis based on these assumptions is ill-conditioned; it effectively computes uncertainty conditional on a set of zero probability. The practice of uncertainty factors is due for a thorough review. Two directions are briefly sketched, one based on standard regression models, and one based on nonparametric continuous Bayesian belief nets. PMID:20030767

  1. Rheumatoid factor (RF)

    MedlinePlus

    Rheumatoid factor (RF) is a blood test that measures the amount of the RF antibody in the blood. ... these conditions still have a "normal" or low RF. Normal value ranges may vary slightly among different ...

  2. Aerospace Human Factors

    NASA Technical Reports Server (NTRS)

    Jordan, Kevin

    1999-01-01

    The following contains the final report on the activities related to the Cooperative Agreement between the human factors research group at NASA Ames Research Center and the Psychology Department at San Jose State University. The participating NASA Ames division has been, as the organization has changed, the Aerospace Human Factors Research Division (ASHFRD and Code FL), the Flight Management and Human Factors Research Division (Code AF), and the Human Factors Research and Technology Division (Code IH). The inclusive dates for the report are November 1, 1984 to January 31, 1999. Throughout the years, approximately 170 persons worked on the cooperative agreements in one capacity or another. The Cooperative Agreement provided for research personnel to collaborate with senior scientists in ongoing NASA ARC research. Finally, many post-MA/MS and post-doctoral personnel contributed to the projects. It is worth noting that 10 former cooperative agreement personnel were hired into civil service positions directly from the agreements.

  3. von Willebrand Factor Test

    MedlinePlus

    ... Platelet Count , Platelet Function Tests , Complete Blood Count , Coagulation Factor VIII , PT , PTT At a Glance Test ... a protein , one of several components of the coagulation system that work together to stop bleeding and ...

  4. Factor II deficiency

    MedlinePlus

    ... blood. It leads to problems with blood clotting (coagulation). Factor II is also known as prothrombin. ... blood clots form. This process is called the coagulation cascade. It involves special proteins called coagulation, or ...

  5. Factors Affecting Wound Healing

    PubMed Central

    Guo, S.; DiPietro, L.A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

  6. New microbial growth factor

    NASA Technical Reports Server (NTRS)

    Bok, S. H.; Casida, L. E., Jr.

    1977-01-01

    A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

  7. Automated Factor Slice Sampling.

    PubMed

    Tibbits, Matthew M; Groendyke, Chris; Haran, Murali; Liechty, John C

    2014-01-01

    Markov chain Monte Carlo (MCMC) algorithms offer a very general approach for sampling from arbitrary distributions. However, designing and tuning MCMC algorithms for each new distribution, can be challenging and time consuming. It is particularly difficult to create an efficient sampler when there is strong dependence among the variables in a multivariate distribution. We describe a two-pronged approach for constructing efficient, automated MCMC algorithms: (1) we propose the "factor slice sampler", a generalization of the univariate slice sampler where we treat the selection of a coordinate basis (factors) as an additional tuning parameter, and (2) we develop an approach for automatically selecting tuning parameters in order to construct an efficient factor slice sampler. In addition to automating the factor slice sampler, our tuning approach also applies to the standard univariate slice samplers. We demonstrate the efficiency and general applicability of our automated MCMC algorithm with a number of illustrative examples. PMID:24955002

  8. Automated Factor Slice Sampling

    PubMed Central

    Tibbits, Matthew M.; Groendyke, Chris; Haran, Murali; Liechty, John C.

    2013-01-01

    Markov chain Monte Carlo (MCMC) algorithms offer a very general approach for sampling from arbitrary distributions. However, designing and tuning MCMC algorithms for each new distribution, can be challenging and time consuming. It is particularly difficult to create an efficient sampler when there is strong dependence among the variables in a multivariate distribution. We describe a two-pronged approach for constructing efficient, automated MCMC algorithms: (1) we propose the “factor slice sampler”, a generalization of the univariate slice sampler where we treat the selection of a coordinate basis (factors) as an additional tuning parameter, and (2) we develop an approach for automatically selecting tuning parameters in order to construct an efficient factor slice sampler. In addition to automating the factor slice sampler, our tuning approach also applies to the standard univariate slice samplers. We demonstrate the efficiency and general applicability of our automated MCMC algorithm with a number of illustrative examples. PMID:24955002

  9. FGF growth factor analogs

    DOEpatents

    Zamora, Paul O.; Pena, Louis A.; Lin, Xinhua; Takahashi, Kazuyuki

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  10. Preparative two-step purification of recombinant human basic fibroblast growth factor from high-cell-density cultivation of Escherichia coli.

    PubMed

    Garke, G; Deckwer, W D; Anspach, F B

    2000-01-14

    Aggregation and precipitation are major pitfalls during bioprocessing and purification of recombinant human basic fibroblast growth factor (rh-bFGF). In order to gain high yields of the soluble protein monomer with high biological activity, an efficient downstream process was developed, focussing on the combination of expanded bed adsorption (EBA) and heparin chromatography. After expression in E. coli TG1:plambdaFGFB, cells were harvested and washed; then the rh-bFGF was released via high pressure homogenization. The high viscosity of the feedstock of about 40 mPa s, showing non-newtonian behaviour, was reduced to 2 mPa s by the addition of DNase. The homogenate (5.6 l) was loaded directly on an expanded bed column (C-50) packed with the strong cation-exchanger Streamline SP. In the eluates, histone-like (HU) protein was identified as the main protein contaminant by sequence analysis. The thermodynamics and kinetics of rh-bFGF adsorption from the whole broth protein mixture were determined in view of competition and displacement effects with host-derived proteins. Optimal binding and elution conditions were developed with knowledge of the dependence of rh-bFGF adsorption isotherms on the salt concentration to allow direct application of eluates onto Heparin HyperD. This affinity support maintained selectivity and efficiency under CIP and over a wide range of flow-rates; both is advantageous for the flexibility of the purification protocol in view of a scalable process. Remaining DNA and HU protein were separated by Heparin HyperD. The endotoxin level decreased from approximately 1,000,000 EU/ml in the whole broth to 10 EU in 3 mg bFGF per ml. The final purification protocol yields >99% pure rh-bFGF as judged from SDS-PAGE and MALDI-TOF mass spectrometry with high mitogenic activity (ED50=1-1.5 ng/ml) of the lyophilized sample. In comparison to the conventional process, the overall protein recovery rose by 15% to 65% with saving time and costs. PMID:10681038

  11. A load factor formula

    NASA Technical Reports Server (NTRS)

    Miller, Roy G

    1927-01-01

    The ultimate test of a load factor formula is experience. The chief advantages of a semi rational formula over arbitrary factors are that it fairs in between points of experience and it differentiates according to variables within a type. Structural failure of an airplane apparently safe according to the formula would call for a specific change in the formula. The best class of airplanes with which to check a load factor formula seems to be those which have experienced structural failure. Table I comprises a list of the airplanes which have experienced failure in flight traceable to the wing structure. The load factor by formula is observed to be greater than the designed strength in each case, without a single exception. Table II comprises the load factor by formula with the designed strength of a number of well-known service types. The formula indicates that by far the majority of these have ample structural strength. One case considered here in deriving a suitable formula is that of a heavy load carrier of large size and practically no reserve power.

  12. Power Factor Controller Study.

    SciTech Connect

    Knudson Engineers, Inc.

    1989-08-01

    The complete report is divided into three parts as follows: (1) This report combines a historical perspective with a current assessment of the use of power factor controllers for three-phase ac motor energy savings. The power factor controller (PFC) is a power electronics device that reduces voltage to a motor during periods of reduced motor torque requirements. (2) A power factor controller (PFC) is a power electronics device that reduces voltage to a motor during periods of reduced motor torque requirements. This report is the DEMONSTRATION phase of the PFC study. The phase report consists of three task reports -- Site Selection, Demonstration Preparation, and Demonstration. The reports explain how three sites were selected for demonstration, describe what was measured at each site and the method of measurement, and compare measured energy savings with calculated predictions of energy savings. The report concludes that PFCs can save energy on carefully selected motor applications. (3) The results of the demonstration task are described in this report. A power factor controller (PFC) is a power electronics device that reduces voltage to a motor during periods of reduced motor torque requirements. The demonstration phase of this study calculates projected energy savings with the use of a PFC and compares measured performance with the calculations. The effect of the PFC on motor power requirements, power factor and energy consumption shall be measured.

  13. Breast cancer risk factors

    PubMed Central

    Ciszewski, Tomasz; Łopacka-Szatan, Karolina; Miotła, Paweł; Starosławska, Elżbieta

    2015-01-01

    Breast cancer is the most frequently diagnosed neoplastic disease in women around menopause often leading to a significant reduction of these women's ability to function normally in everyday life. The increased breast cancer incidence observed in epidemiological studies in a group of women actively participating in social and professional life implicates the necessity of conducting multidirectional studies in order to identify risk factors associated with the occurrence of this type of neoplasm. Taking the possibility of influencing the neoplastic transformation process in individuals as a criterion, all the risk factors initiating the process can be divided into two groups. The first group would include inherent factors such as age, sex, race, genetic makeup promoting familial occurrence of the neoplastic disease or the occurrence of benign proliferative lesions of the mammary gland. They all constitute independent parameters and do not undergo simple modification in the course of an individual's life. The second group would include extrinsic factors conditioned by lifestyle, diet or long-term medical intervention such as using oral hormonal contraceptives or hormonal replacement therapy and their influence on the neoplastic process may be modified to a certain degree. Identification of modifiable factors may contribute to development of prevention strategies decreasing breast cancer incidence. PMID:26528110

  14. Electromagnetic nucleon form factors

    SciTech Connect

    Bender, A.; Roberts, C.D.; Frank, M.R.

    1995-08-01

    The Dyson-Schwinger equation framework is employed to obtain expressions for the electromagnetic nucleon form factor. In generalized impulse approximation the form factor depends on the dressed quark propagator, the dressed quark-photon vertex, which is crucial to ensuring current conservation, and the nucleon Faddeev amplitude. The approach manifestly incorporates the large space-like-q{sup 2} renormalization group properties of QCD and allows a realistic extrapolation to small space-like-q{sup 2}. This extrapolation allows one to relate experimental data to the form of the quark-quark interaction at small space-like-q{sup 2}, which is presently unknown. The approach provides a means of unifying, within a single framework, the treatment of the perturbative and nonperturbative regimes of QCD. The wealth of experimental nucleon form factor data, over a large range of q{sup 2}, ensures that this application will provide an excellent environment to test, improve and extend our approach.

  15. Geothermal Plant Capacity Factors

    SciTech Connect

    Greg Mines; Jay Nathwani; Christopher Richard; Hillary Hanson; Rachel Wood

    2015-01-01

    The capacity factors recently provided by the Energy Information Administration (EIA) indicated this plant performance metric had declined for geothermal power plants since 2008. Though capacity factor is a term commonly used by geothermal stakeholders to express the ability of a plant to produce power, it is a term frequently misunderstood and in some instances incorrectly used. In this paper we discuss how this capacity factor is defined and utilized by the EIA, including discussion on the information that the EIA requests from operations in their 923 and 860 forms that are submitted both monthly and annually by geothermal operators. A discussion is also provided regarding the entities utilizing the information in the EIA reports, and how those entities can misinterpret the data being supplied by the operators. The intent of the paper is to inform the facility operators as the importance of the accuracy of the data that they provide, and the implications of not providing the correct information.

  16. Psychological Factors in Asthma

    PubMed Central

    2008-01-01

    Asthma has long been considered a condition in which psychological factors have a role. As in many illnesses, psychological variables may affect outcome in asthma via their effects on treatment adherence and symptom reporting. Emerging evidence suggests that the relation between asthma and psychological factors may be more complex than that, however. Central cognitive processes may influence not only the interpretation of asthma symptoms but also the manifestation of measurable changes in immune and physiologic markers of asthma. Furthermore, asthma and major depressive disorder share several risk factors and have similar patterns of dysregulation in key biologic systems, including the neuroendocrine stress response, cytokines, and neuropeptides. Despite the evidence that depression is common in people with asthma and exerts a negative impact on outcome, few treatment studies have examined whether improving symptoms of depression do, in fact, result in better control of asthma symptoms or improved quality of life in patients with asthma. PMID:20525122

  17. DSN human factors project

    NASA Technical Reports Server (NTRS)

    Chafin, R. L.; Martin, T. H.

    1980-01-01

    The project plan was to hold focus groups to identify the factors influencing the ease of use characteristics of software and to bond the problem. A questionnaire survey was conducted to evaluate those factors which were more appropriately measured with that method. The performance oriented factors were analyzed and relationships hypothesized. The hypotheses were put to test in the experimental phase of the project. In summary, the initial analysis indicates that there is an initial performance effect favoring computer controlled dialogue but the advantage fades fast as operators become experienced. The user documentation style is seen to have a significant effect on performance. The menu and prompt command formats are preferred by inexperienced operators. The short form mnemonic is least favored. There is no clear best command format but the short form mnemonic is clearly the worst.

  18. Multi-factor authentication

    SciTech Connect

    Hamlet, Jason R; Pierson, Lyndon G

    2014-10-21

    Detection and deterrence of spoofing of user authentication may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a user of the hardware device. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generates a PUF value. Combining logic is coupled to receive the PUF value, combines the PUF value with one or more other authentication factors to generate a multi-factor authentication value. A key generator is coupled to generate a private key and a public key based on the multi-factor authentication value while a decryptor is coupled to receive an authentication challenge posed to the hardware device and encrypted with the public key and coupled to output a response to the authentication challenge decrypted with the private key.

  19. WRKY transcription factors

    PubMed Central

    Bakshi, Madhunita; Oelmüller, Ralf

    2014-01-01

    WRKY transcription factors are one of the largest families of transcriptional regulators found exclusively in plants. They have diverse biological functions in plant disease resistance, abiotic stress responses, nutrient deprivation, senescence, seed and trichome development, embryogenesis, as well as additional developmental and hormone-controlled processes. WRKYs can act as transcriptional activators or repressors, in various homo- and heterodimer combinations. Here we review recent progress on the function of WRKY transcription factors in Arabidopsis and other plant species such as rice, potato, and parsley, with a special focus on abiotic, developmental, and hormone-regulated processes. PMID:24492469

  20. Anti-nutritional Factors.

    PubMed

    2016-01-01

    Anti-nutritional factors such as trypsin inhibitor, phytic acid and cyanogen are as important as nutritional content of any edible plant part. The anti-nutritional factors can be defined as those substances generated in natural food substances by the normal metabolism of species and by different mechanisms (e.g. inactivation of some nutrients, diminution of the digestive process or metabolic utilization of feed) which exert effects contrary to optimum nutrition. Hence, trypsin inhibitor, phytic acid and cyanogens present in edibles with the methods in the chapter would be helpful. PMID:26939264

  1. Factor D Enzyme

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The trauma caused by the open heart surgery often triggers massive inflammation because the immune system overreacts. Factor D, the protein which plays a key role in the biological steps that activate this immune response prevents the imune system from inappropriately rurning out of control, allowing the patient to recover more rapidly. Factor D blockers, with their great potential to alleviate the complication of inflammation associated with heart surgery, are now being developed for clinical trials. These new drugs, developed from space research, should be commercially available as soon as year 2001.

  2. The Transcription Factor Encyclopedia

    PubMed Central

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe. PMID:22458515

  3. Radiative Gaunt factors

    NASA Astrophysics Data System (ADS)

    Burgess, Alan; Summers, Hugh P.

    1987-05-01

    Numerical methods for the evaluation of radiative Gaunt factors for complex ions, and for the calculation of the principal integrals over the Gaunt factors relevant to plasma spectroscopy, are presented. The present techniques are suitable for the computation of intermediate accuracy results for large numbers of ions over extended parameter ranges, and they cover bound-bound, bound-free, and free-free cases in both hydrogenic and nonhydrogenic approximations. The results demonstrate the reliability of the numerical methods and their advantages over the methods of Peach (1965, 1967) and Burgess and Seaton (1960). Significant differences from hydrogenic results at low and moderate z values are pointed out.

  4. The transcription factor encyclopedia.

    PubMed

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I; Bolotin, Eugene; Ticoll, Amy; Cheung, Warren A; Zhang, Xiao Yu Cindy; Dickman, Christopher T D; Fulton, Debra L; Lim, Jonathan S; Schnabl, Jake M; Ramos, Oscar H P; Vasseur-Cognet, Mireille; de Leeuw, Charles N; Simpson, Elizabeth M; Ryffel, Gerhart U; Lam, Eric W-F; Kist, Ralf; Wilson, Miranda S C; Marco-Ferreres, Raquel; Brosens, Jan J; Beccari, Leonardo L; Bovolenta, Paola; Benayoun, Bérénice A; Monteiro, Lara J; Schwenen, Helma D C; Grontved, Lars; Wederell, Elizabeth; Mandrup, Susanne; Veitia, Reiner A; Chakravarthy, Harini; Hoodless, Pamela A; Mancarelli, M Michela; Torbett, Bruce E; Banham, Alison H; Reddy, Sekhar P; Cullum, Rebecca L; Liedtke, Michaela; Tschan, Mario P; Vaz, Michelle; Rizzino, Angie; Zannini, Mariastella; Frietze, Seth; Farnham, Peggy J; Eijkelenboom, Astrid; Brown, Philip J; Laperrière, David; Leprince, Dominique; de Cristofaro, Tiziana; Prince, Kelly L; Putker, Marrit; del Peso, Luis; Camenisch, Gieri; Wenger, Roland H; Mikula, Michal; Rozendaal, Marieke; Mader, Sylvie; Ostrowski, Jerzy; Rhodes, Simon J; Van Rechem, Capucine; Boulay, Gaylor; Olechnowicz, Sam W Z; Breslin, Mary B; Lan, Michael S; Nanan, Kyster K; Wegner, Michael; Hou, Juan; Mullen, Rachel D; Colvin, Stephanie C; Noy, Peter John; Webb, Carol F; Witek, Matthew E; Ferrell, Scott; Daniel, Juliet M; Park, Jason; Waldman, Scott A; Peet, Daniel J; Taggart, Michael; Jayaraman, Padma-Sheela; Karrich, Julien J; Blom, Bianca; Vesuna, Farhad; O'Geen, Henriette; Sun, Yunfu; Gronostajski, Richard M; Woodcroft, Mark W; Hough, Margaret R; Chen, Edwin; Europe-Finner, G Nicholas; Karolczak-Bayatti, Magdalena; Bailey, Jarrod; Hankinson, Oliver; Raman, Venu; LeBrun, David P; Biswal, Shyam; Harvey, Christopher J; DeBruyne, Jason P; Hogenesch, John B; Hevner, Robert F; Héligon, Christophe; Luo, Xin M; Blank, Marissa Cathleen; Millen, Kathleen Joyce; Sharlin, David S; Forrest, Douglas; Dahlman-Wright, Karin; Zhao, Chunyan; Mishima, Yuriko; Sinha, Satrajit; Chakrabarti, Rumela; Portales-Casamar, Elodie; Sladek, Frances M; Bradley, Philip H; Wasserman, Wyeth W

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe. PMID:22458515

  5. Radiation View Factor With Shadowing

    Energy Science and Technology Software Center (ESTSC)

    1992-02-24

    FACET calculates the radiation geometric view factor (alternatively called shape factor, angle factor, or configuration factor) between surfaces for axisymmetric, two-dimensional planar and three-dimensional geometries with interposed third surface obstructions. FACET was developed to calculate view factors as input data to finite element heat transfer analysis codes.

  6. Factor Analysis and Counseling Research

    ERIC Educational Resources Information Center

    Weiss, David J.

    1970-01-01

    Topics discussed include factor analysis versus cluster analysis, analysis of Q correlation matrices, ipsativity and factor analysis, and tests for the significance of a correlation matrix prior to application of factor analytic techniques. Techniques for factor extraction discussed include principal components, canonical factor analysis, alpha…

  7. Affective Factors: Anxiety

    ERIC Educational Resources Information Center

    Tasnimi, Mahshad

    2009-01-01

    Affective factors seem to play a crucial role in success or failure in second language acquisition. Negative attitudes can reduce learners' motivation and harm language learning, while positive attitudes can do the reverse. Discovering students' attitudes about language will help both teacher and student in teaching learning process. Anxiety is…

  8. Assessment of Human Factors

    NASA Technical Reports Server (NTRS)

    Mount, Frances; Foley, Tico

    1999-01-01

    Human Factors Engineering, often referred to as Ergonomics, is a science that applies a detailed understanding of human characteristics, capabilities, and limitations to the design, evaluation, and operation of environments, tools, and systems for work and daily living. Human Factors is the investigation, design, and evaluation of equipment, techniques, procedures, facilities, and human interfaces, and encompasses all aspects of human activity from manual labor to mental processing and leisure time enjoyments. In spaceflight applications, human factors engineering seeks to: (1) ensure that a task can be accomplished, (2) maintain productivity during spaceflight, and (3) ensure the habitability of the pressurized living areas. DSO 904 served as a vehicle for the verification and elucidation of human factors principles and tools in the microgravity environment. Over six flights, twelve topics were investigated. This study documented the strengths and limitations of human operators in a complex, multifaceted, and unique environment. By focusing on the man-machine interface in space flight activities, it was determined which designs allow astronauts to be optimally productive during valuable and costly space flights. Among the most promising areas of inquiry were procedures, tools, habitat, environmental conditions, tasking, work load, flexibility, and individual control over work.

  9. Introduction to human factors

    SciTech Connect

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  10. ERYTHROPOIETIC FACTOR PURIFICATION

    DOEpatents

    White, W.F.; Schlueter, R.J.

    1962-05-01

    A method is given for purifying and concentrating the blood plasma erythropoietic factor. Anemic sheep plasma is contacted three times successively with ion exchange resins: an anion exchange resin, a cation exchange resin at a pH of about 5, and a cation exchange resin at a pH of about 6. (AEC)

  11. Thyroid Cancer Risk Factors

    MedlinePlus

    ... and radiation fallout from power plant accidents or nuclear weapons. Having had head or neck radiation treatments in childhood is a risk factor for ... should be done using the lowest dose of radiation that still provides a clear ... from nuclear weapons or power plant accidents. For instance, thyroid ...

  12. Common conversion factors.

    PubMed

    2001-05-01

    This appendix presents tables of some of the more common conversion factors for units of measure used throughout Current Protocols manuals, as well as prefixes indicating powers of ten for SI units. Another table gives conversions between temperatures on the Celsius (Centigrade) and Fahrenheit scales. PMID:18770653

  13. Inelastic Scattering Form Factors

    Energy Science and Technology Software Center (ESTSC)

    1992-01-01

    ATHENA-IV computes form factors for inelastic scattering calculations, using single-particle wave functions that are eigenstates of motion in either a Woods-Saxon potential well or a harmonic oscillator well. Two-body forces of Gauss, Coulomb, Yukawa, and a sum of cut-off Yukawa radial dependences are available.

  14. Recombinant factor VIIa.

    PubMed

    Aitken, Michael G

    2004-01-01

    Human coagulation factor (F) VII is a single chain protease that circulates in the blood as a weakly active zymogen at concentrations of approximately 10 nmol/L. When converted to the active 2 chain form (FVIIa), it is a powerful initiator of haemostasis. Recombinant factor VIIa (rFVIIa, eptacog alfa, NovoSeven) is a genetically engineered product that was first introduced in 1988 for the treatment of patients with haemophilia A and B with high inhibitory antibody titres to factors VIII and IX. Recent reports in the form of case studies and series, and early trial data, have suggested a role for rFVIIa across a diverse range of indications including bleeding associated with trauma, surgery, thrombocytopaenia, liver disease and oral anticoagulant toxicity. This review describes the physiology of the coagulation pathway and in particular the role of recombinant factor VIIa. It will also focus on the emerging role of rFVIIa in both trauma and non-trauma bleeding and its potential use in the ED. PMID:15537408

  15. Co/Mo bimetallic addition to electrolytic manganese dioxide for oxygen generation in acid medium.

    PubMed

    Delgado, Dario; Minakshi, Manickam; McGinnity, Justin; Kim, Dong-Jin

    2015-01-01

    An efficient electrocatalyst comprising inexpensive and earth-abundant materials for the oxygen evolution reaction (OER) is crucial for the development of water electrolysis. In this work, in-situ addition of cobalt/molybdenum ions to the electrolytic manganese dioxide has been shown to be beneficial for the OER in acid solution as its overpotential performed better (305 mV) than that of the commercial DSA(®) (341 mV) at 100 mA cm(-2). The OER was investigated at ambient temperature in 2 M H2SO4 solution on the modified EMD (MnMoCoO) electrodes. The energy efficiency of the MnMoCoO electrodes improved significantly with the amount of Co in the plating solution. For the electrodeposited catalysts, physico-chemical and electrochemical measurements were conducted including static overpotentials. The better performance of the modified EMD was attributed to an improved charge transfer resistance (Rct; 0.290 Ω cm(2)), average roughness factor (rf; 429) and decrease in water content in the electrodeposited catalysts. The kinetic parameters obtained on MnMoCoO catalysts were compared and discussed according to the cobalt concentration. PMID:26469204

  16. Co/Mo bimetallic addition to electrolytic manganese dioxide for oxygen generation in acid medium

    PubMed Central

    Delgado, Dario; Minakshi, Manickam; McGinnity, Justin; Kim, Dong-Jin

    2015-01-01

    An efficient electrocatalyst comprising inexpensive and earth-abundant materials for the oxygen evolution reaction (OER) is crucial for the development of water electrolysis. In this work, in-situ addition of cobalt/molybdenum ions to the electrolytic manganese dioxide has been shown to be beneficial for the OER in acid solution as its overpotential performed better (305 mV) than that of the commercial DSA® (341 mV) at 100 mA cm−2. The OER was investigated at ambient temperature in 2 M H2SO4 solution on the modified EMD (MnMoCoO) electrodes. The energy efficiency of the MnMoCoO electrodes improved significantly with the amount of Co in the plating solution. For the electrodeposited catalysts, physico-chemical and electrochemical measurements were conducted including static overpotentials. The better performance of the modified EMD was attributed to an improved charge transfer resistance (Rct; 0.290 Ω cm2), average roughness factor (rf; 429) and decrease in water content in the electrodeposited catalysts. The kinetic parameters obtained on MnMoCoO catalysts were compared and discussed according to the cobalt concentration. PMID:26469204

  17. Co/Mo bimetallic addition to electrolytic manganese dioxide for oxygen generation in acid medium

    NASA Astrophysics Data System (ADS)

    Delgado, Dario; Minakshi, Manickam; McGinnity, Justin; Kim, Dong-Jin

    2015-10-01

    An efficient electrocatalyst comprising inexpensive and earth-abundant materials for the oxygen evolution reaction (OER) is crucial for the development of water electrolysis. In this work, in-situ addition of cobalt/molybdenum ions to the electrolytic manganese dioxide has been shown to be beneficial for the OER in acid solution as its overpotential performed better (305 mV) than that of the commercial DSA® (341 mV) at 100 mA cm-2. The OER was investigated at ambient temperature in 2 M H2SO4 solution on the modified EMD (MnMoCoO) electrodes. The energy efficiency of the MnMoCoO electrodes improved significantly with the amount of Co in the plating solution. For the electrodeposited catalysts, physico-chemical and electrochemical measurements were conducted including static overpotentials. The better performance of the modified EMD was attributed to an improved charge transfer resistance (Rct; 0.290 Ω cm2), average roughness factor (rf; 429) and decrease in water content in the electrodeposited catalysts. The kinetic parameters obtained on MnMoCoO catalysts were compared and discussed according to the cobalt concentration.

  18. Peptide growth factors, part B

    SciTech Connect

    Barnes, D.; Sirbasku, D.A.

    1987-01-01

    This book discusses the following topics: Platelet-Derived Growth Factor;Nerve and Glial Growth Factors;PC12 Pheochromocytoma Cells;Techniques for the Study of Growth Factor Activity;Genetic Approaches and Biological Effects.

  19. Factor structure of nonverbal cognition.

    PubMed

    Ardil, A; Pineda, D A

    2000-01-01

    In order to define the factor structure of nonverbal cognitive processes, 156 twenty to sixty year-old participants were selected in Medellin (Colombia). A neuropsychological test battery for assessing different nonverbal cognitive domains (attention, memory, visuoperceptual and visuoconstructive abilities. executive functions, praxis abilities, and written calculation abilities) was administered. Initially, independent factor analyses were carried out for each domain. Three attention factors (Sustained Attention, Divided Attention, and Processing Speed, 73.1% of the variance); two memory factors (Categorical and Non-Categorical Memory, 59.7% of the variance): two visuoperceptual and visuoconstructive factors (Sequential and Simultaneous, 54.0% of the variance); and two executive function factors (Categorization and Trial Error, 82.0% of the variance) were found. Further, several sequential factor analyses using Varimax orthogonal rotations for noncorrelated variables were performed. The 32 test variables were included, but progressively some variables were removed. This procedure finally selected 13 variables corresponding to five factors accounting for 72.6% of variance. Factor I was an Executive Function factor (30% of variance). Factor 2 corresponded to a Sequential Constructional factor (14.7%). Factor 3 represented a Processing Speed factor and accounted for 10.6% of the variance. Factor 4 was Visuoperceptual factor (9.5% of the variance). Finally, Factor 5 (7.8% of the variance) was a Nonverbal Memory factor. It was concluded that several, different cognitive dimensions are included in nonverbal cognition. PMID:11011978

  20. Hydrotreatment of Athabasca bitumen derived gas oil over Ni-Mo, Ni-W, and Co-Mo catalysts

    SciTech Connect

    Diaz-Real, R.A.; Mann, R.S.; Sambi, I.S. . Dept. of Chemical Engineering)

    1993-07-01

    The hydrotreatment of Athabasca bitumen derived heavy gas oil containing 4.08% S and 0.49% N was carried out in a trickle bed reactor over Ni-W, Ni-Mo, and Co-Mo catalysts supported on zeolite-alumina-silica at 623-698 K, LHSV of 1-4, gas flow rate 890 m[sup 3][sub H2]/m[sup 3][sub oil] (5,000 sef/bbl), and pressure of 6.89 MPa. Analyses for viscosity, density, aniline point, ASTM mid boiling point distillation, C/H ratio, and percentage of N and S in the final product were carried out to characterize the product oil. The amounts of N and S removed indicated the hydrodenitrogenation and hydrodesulfurization activity of the catalysts. Results of zeolite-alumina-silica-supported catalysts are compared to those obtained with commercially available Ni-Mo, Ni-W, and Co-Mo on [gamma]-alumina. Ni-Mo supported on zeolite-alumina-silica was most active and could remove as much as 99 % S and 89% N present in the oil at 698 K. The data for HDN and HDS fitted the pseudo first order model. The kinetic model is described in detail.

  1. Ab initio study of energetics and magnetism of sigma phase in Co-Mo and Fe-Mo systems

    NASA Astrophysics Data System (ADS)

    Pavlů, J.; Vřešťál, J.; Šob, M.

    2016-02-01

    We analyse, from first-principles, the energetics and magnetic ordering of sigma phases in Co-Mo and Fe-Mo systems. Total energy differences between the sigma phase and Standard Element Reference (SER) structures are calculated in the whole concentration range at equilibrium volumes by means of the linear muffin-tin orbitals method in the atomic-sphere approximation (LMTO-ASA), the full-potential linearised augmented-plane waves (FLAPW) method and the pseudopotential approach. They are compared with the enthalpy of formation of sigma phase obtained from the phase equilibria calculations at higher temperature based on the semiempirical CALPHAD (CALculation of PHAse Diagram) method. It turns out that the binary sigma phases are more stable than the weighted average of the sigma phase of elemental constituents and that this stability for Fe-Mo is higher than for Co-Mo. On the other hand it was found that the binary sigma phases do not exhibit any stability with respect to the weighted average of the SER structures. The magnetic configurations in all systems are investigated and the stabilizing effect of magnetic order in sigma phase at 0 K is presented. It turns out that the atomic magnetic moment strongly depends on the type of occupied sublattice and total composition of the alloy.

  2. Alejarse como proceso social: niños y ancianos «abandonados» en Ayacucho1

    PubMed Central

    Leinaweaver, Jessaca

    2013-01-01

    En investigaciones previas sobre el acogimiento familiar y la adopción en Ayacucho, se ha podido descubrir cómo los ayacuchanos adquieren y producen relaciones sociales. Mientras negocian creativamente los discursos y espacios construidos simultáneamente por instituciones, comunidades, y estructuras sociales, van adquiriendo nuevas formas de relacionarse. Este artículo discute el proceso opuesto: el deshacerse de relaciones de parentesco, y el proceso social del abandono o alejamiento. Cuando se aleja a una persona de su familia o su comunidad, los que se quedan en ella llegan a entenderse como ciertos tipos de personas. En los estudios de caso discutidos aquí, recopilados a través de una detallada y cuidadosa observación participante y de entrevistas etnográficas grabadas entre 2001 y 2007, se puede ver cómo, después de un alejamiento social, los individuos que alejan se reinterpretan como sujetos que se encuentran superándose o volviéndose modernos, o bien sacrificándose. PMID:25177044

  3. Human factors workplace considerations

    NASA Technical Reports Server (NTRS)

    Haines, Richard F.

    1988-01-01

    Computer workstations assume many different forms and play different functions today. In order for them to assume the effective interface role which they should play they must be properly designed to take into account the ubiguitous human factor. In addition, the entire workplace in which they are used should be properly configured so as to enhance the operational features of the individual workstation where possible. A number of general human factors workplace considerations are presented. This ongoing series of notes covers such topics as achieving comfort and good screen visibility, hardware issues (e.g., mouse maintenance), screen symbology features (e.g., labels, cursors, prompts), and various miscellaneous subjects. These notes are presented here in order to: (1) illustrate how one's workstation can be used to support telescience activities of many other people working within an organization, and (2) provide a single complete set of considerations for future reference.

  4. Helicopter human factors

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.

    1988-01-01

    The state-of-the-art helicopter and its pilot are examined using the tools of human-factors analysis. The significant role of human error in helicopter accidents is discussed; the history of human-factors research on helicopters is briefly traced; the typical flight tasks are described; and the noise, vibration, and temperature conditions typical of modern military helicopters are characterized. Also considered are helicopter controls, cockpit instruments and displays, and the impact of cockpit design on pilot workload. Particular attention is given to possible advanced-technology improvements, such as control stabilization and augmentation, FBW and fly-by-light systems, multifunction displays, night-vision goggles, pilot night-vision systems, night-vision displays with superimposed symbols, target acquisition and designation systems, and aural displays. Diagrams, drawings, and photographs are provided.

  5. [Streptococcus pyogenes pathogenic factors].

    PubMed

    Bidet, Ph; Bonacorsi, S

    2014-11-01

    The pathogenicity of ß-hemolytic group A streptococcus (GAS) is particularly diverse, ranging from mild infections, such as pharyngitis or impetigo, to potentially debilitating poststreptococcal diseases, and up to severe invasive infections such as necrotizing fasciitis or the dreaded streptococcal toxic shock syndrome. This variety of clinical expressions, often radically different in individuals infected with the same strain, results from a complex interaction between the bacterial virulence factors, the mode of infection and the immune system of the host. Advances in comparative genomics have led to a better understanding of how, following this confrontation, GAS adapts to the immune system's pressure, either peacefully by reducing the expression of certain virulence factors to achieve an asymptomatic carriage, or on the contrary, by overexpressing them disproportionately, resulting in the most severe forms of invasive infection. PMID:25456681

  6. Factors regulating microglia activation

    PubMed Central

    Kierdorf, Katrin; Prinz, Marco

    2013-01-01

    Microglia are resident macrophages of the central nervous system (CNS) that display high functional similarities to other tissue macrophages. However, it is especially important to create and maintain an intact tissue homeostasis to support the neuronal cells, which are very sensitive even to minor changes in their environment. The transition from the “resting” but surveying microglial phenotype to an activated stage is tightly regulated by several intrinsic (e.g., Runx-1, Irf8, and Pu.1) and extrinsic factors (e.g., CD200, CX3CR1, and TREM2). Under physiological conditions, minor changes of those factors are sufficient to cause fatal dysregulation of microglial cell homeostasis and result in severe CNS pathologies. In this review, we discuss recent achievements that gave new insights into mechanisms that ensure microglia quiescence. PMID:23630462

  7. Risk Factors in Stroke

    PubMed Central

    Mustacchi, Piero

    1985-01-01

    In the United States, stroke accounts for 160,000 annual deaths; only 16% of the 1.8 million stroke survivors are fully independent. The incidence of stroke increases with age. Hemorrhagic strokes outnumber ischemic strokes before age 15. Japanese men in this country have a lower stroke mortality than their age peers in Japan. Excessive stroke mortality for US nonwhites may not be entirely due to the greater prevalence of hypertension among blacks. Hypertension emerges as the single most powerful and reversible risk factor in stroke and for survival after stroke. Impaired cardiac function is the second most important precursor of stroke. The recurrence of stroke in survivors is high. The frequency of completed stroke is high in persons with transient ischemic attacks, but not in those with asymptomatic carotid bruits. Other reversible risk factors are smoking, the use of oral contraceptives, alcoholic excess, a low level of physical activity, blood hyperviscosity and drug abuse. PMID:3898597

  8. Growth factors for nanobacteria

    NASA Astrophysics Data System (ADS)

    Ciftcioglu, Neva; Kajander, E. Olavi

    1999-12-01

    Nanobacteria are novel microorganisms recently isolated from fetal bovine serum and blood of cows and humans. These coccoid, gram negative bacteria in alpha-2 subgroup of Proteobacteria grow slowly under mammalian cell culture conditions but not in common media for microbes. Now we have found two different kinds of culture supplement preparations that improve their growth and make them culturable in the classical sense. These are supernatant fractions of conditioned media obtained from 1 - 3 months old nanobacteria cultures and from about a 2 weeks old Bacillus species culture. Both improved multiplication and particle yields and the latter increased their resistance to gentamicin. Nanobacteria cultured with any of the methods shared similar immunological property, structure and protein pattern. The growth supporting factors were heat-stabile and nondialyzable, and dialysis improved the growth promoting action. Nanobacteria formed stony colonies in a bacteriological medium supplemented with the growth factors. This is an implication that nanobacterial growth is influenced by pre-existing bacterial flora.

  9. Power Factor Controller

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Frank Nola invented the Power Factor Controller (PFC) at Marshall Space Flight Center more than a decade ago. Nola came up with a way to curb power wastage in AC induction motors. The PFC matches voltage with the motor's actual need by continuously sensing shifts between voltage and current. When it senses a light load it cuts the voltage to the minimum needed. Potential energy savings range from 8 to 65 percent.

  10. Factorization of simulations

    SciTech Connect

    Barrett, C. L.; Mortveit, H. S.; Reidys, C. M.

    2001-01-01

    A simulation is collection of agents that, according to some schedule, are making decisions based on information about other agents in that collection. In this paper we present a class of dynamical systems called Sequential Dynamical Systems (SDS) that was developed to capture these key features of computer simulations. Here, as an example of the use of SDS, we demonstrate how one can obtain information about a simulation by a factorization into smaller simulations.

  11. Nucleon Electromagnetic Form Factors

    SciTech Connect

    Kees de Jager

    2004-08-01

    Although nucleons account for nearly all the visible mass in the universe, they have a complicated structure that is still incompletely understood. The first indication that nucleons have an internal structure, was the measurement of the proton magnetic moment by Frisch and Stern (1933) which revealed a large deviation from the value expected for a point-like Dirac particle. The investigation of the spatial structure of the nucleon, resulting in the first quantitative measurement of the proton charge radius, was initiated by the HEPL (Stanford) experiments in the 1950s, for which Hofstadter was awarded the 1961 Nobel prize. The first indication of a non-zero neutron charge distribution was obtained by scattering thermal neutrons off atomic electrons. The recent revival of its experimental study through the operational implementation of novel instrumentation has instigated a strong theoretical interest. Nucleon electro-magnetic form factors (EMFFs) are optimally studied through the exchange of a virtual photon, in elastic electron-nucleon scattering. The momentum transferred to the nucleon by the virtual photon can be selected to probe different scales of the nucleon, from integral properties such as the charge radius to scaling properties of its internal constituents. Polarization instrumentation, polarized beams and targets, and the measurement of the polarization of the recoiling nucleon have been essential in the accurate separation of the charge and magnetic form factors and in studies of the elusive neutron charge form factor.

  12. Fano factor estimation.

    PubMed

    Rajdl, Kamil; Lansky, Petr

    2014-02-01

    Fano factor is one of the most widely used measures of variability of spike trains. Its standard estimator is the ratio of sample variance to sample mean of spike counts observed in a time window and the quality of the estimator strongly depends on the length of the window. We investigate this dependence under the assumption that the spike train behaves as an equilibrium renewal process. It is shown what characteristics of the spike train have large effect on the estimator bias. Namely, the effect of refractory period is analytically evaluated. Next, we create an approximate asymptotic formula for the mean square error of the estimator, which can also be used to find minimum of the error in estimation from single spike trains. The accuracy of the Fano factor estimator is compared with the accuracy of the estimator based on the squared coefficient of variation. All the results are illustrated for spike trains with gamma and inverse Gaussian probability distributions of interspike intervals. Finally, we discuss possibilities of how to select a suitable observation window for the Fano factor estimation. PMID:24245675

  13. Human Factors Review Plan

    SciTech Connect

    Paramore, B.; Peterson, L.R.

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  14. FACTORS INFLUENCING THE DESIGN OF BIOACCUMULATION FACTOR AND BIOTA-SEDIMENT ACCUMULATION FACTOR FIELD STUDIES

    EPA Science Inventory

    General guidance for designing field studies to measure bioaccumulation factors (BAFs) and biota-sediment accumulation factors (BSAFs) is not available. To develop such guidance, a series of modeling simulations were performed to evaluate the underlying factors and principles th...

  15. Risk Factors for Eating Disorders

    ERIC Educational Resources Information Center

    Striegel-Moore, Ruth H.; Bulik, Cynthia M.

    2007-01-01

    The authors review research on risk factors for eating disorders, restricting their focus to studies in which clear precedence of the hypothesized risk factor over onset of the disorder is established. They illustrate how studies of sociocultural risk factors and biological factors have progressed on parallel tracks and propose that major advances…

  16. Activation of human factor V by factor Xa and thrombin

    SciTech Connect

    Monkovic, D.D.; Tracy, P.B. )

    1990-02-06

    The activation of human factor V by factor Xa and thrombin was studied by functional assessment of cofactor activity and sodium dodecyl sulfate-polycarylamide gel electrophoresis followed by either autoradiography of {sup 125}I-labeled factor V activation products or Western blot analyses of unlabeled factor V activation products. Cofactor activity was measured by the ability of the factor V/Va peptides to support the activation of prothrombin. The factor Xa catalyzed cleavage of factor V was observed to be time, phospholipid, and calcium ion dependent, yielding a cofactor with activity equal to that of thrombin-activated factor V (factor Va). The cleavage pattern differed markedly from the one observed in the bovine system. The factor Xa activated factor V subunits expressing cofactor activity were isolated and found to consist of peptides of M{sub r} 220,000 and 105,000. Although thrombin cleaved the M{sub r} 220,000 peptide to yield peptides previously shown to be products of thrombin activation, cofactor activity did not increase. N-Terminal sequence analysis confirmed that both factor Xa and thrombin cleave factor V at the same bond to generate the M{sub r} 220,000 peptide. The factor Xa dependent functional assessment of {sup 125}I-labeled factor V coupled with densitometric analyses of the cleavage products indicated that the cofactor activity of factor Xa activated factor V closely paralleled the appearance of the M{sub r} 220,000 peptide. The data indicate that factor Xa is as efficient an enzyme toward factor V as thrombin.

  17. Milestones and Impact Factors

    PubMed Central

    2010-01-01

    Environmental Health has just received its first Impact Factor by Thomson ISI. At a level of 2.48, this achievement is quite satisfactory and places Environmental Health in the top 25% of environmental science journals. When the journal was launched in 2002, it was still unclear whether the Open Access publishing model could be made into a viable commercial enterprise within the biomedical field. During the past eight years, Open Access journals have become widely available, although still covering only about 15% of journal titles. Major funding agencies and institutions, including prominent US universities, now require that researchers publish in Open Access journals. Because of the profound role of scientific journals for the sharing of results and communication between researchers, the advent of Open Access may be of as much significance as the transition from handwriting to printing via moveable type. As Environmental Health is an electronic Open Access journal, the numbers of downloads at the journal website can be retrieved. The top-20 list of articles most frequently accessed shows that all of them have been downloaded over 10,000 times. Back in 2002, the first article published was accessed only 49 times during the following month. A year later, the server had over 1,000 downloads per month, and now the total number of monthly downloads approaches 50,000. These statistics complement the Impact Factor and confirm the viability of Open Access in our field of research. The advent of digital media and its decentralized mode of distribution - the internet - have dramatically changed the control and financing of scientific information dissemination, while facilitating peer review, accelerating editorial handling, and supporting much needed transparency. Both the meaning and means of "having an impact" are therefore changing, as will the degree and way in which scientific journals remain "factors" in that impact. PMID:20615249

  18. Neutron quality factor

    SciTech Connect

    1995-06-01

    Both the International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurements (NCRP) have recommended that the radiation quality weighting factor for neutrons (Q{sub n}, or the corresponding new modifying factor, w{sub R}) be increased by a value of two for most radiation protection practices. This means an increase in the recommended value for Q{sub n} from a nominal value of 10 to a nominal value of 20. This increase may be interpreted to mean that the biological effectiveness of neutrons is two times greater than previously thought. A decision to increase the value of Q{sub n} will have a major impact on the regulations and radiation protection programs of Federal agencies responsible for the protection of radiation workers. Therefore, the purposes of this report are: (1) to examine the general concept of {open_quotes}quality factor{close_quotes} (Q) in radiation protection and the rationale for the selection of specific values of Q{sub n}; and (2) to make such recommendations to the Federal agencies, as appropriate. This report is not intended to be an exhaustive review of the scientific literature on the biological effects of neutrons, with the aim of defending a particular value for Q{sub n}. Rather, the working group examined the technical issues surrounding the current recommendations of scientific advisory bodies on this matter, with the aim of determining if these recommendations should be adopted by the Federal agencies. Ultimately, the group concluded that there was no compelling basis for a change in Q{sub n}. The report was prepared by Federal scientists working under the auspices of the Science Panel of the Committee on Interagency Radiation Research and Policy Coordination (CIRRPC).

  19. Nucleon elastic form factors

    SciTech Connect

    D. Day

    2007-03-01

    The nucleon form factors are still the subject of active investigation even after an experimental effort spanning 50 years. This is because they are of critical importance to our understanding of the electromagnetic properties of nuclei and provide a unique testing ground for QCD motivated models of nucleon structure. Progress in polarized beams, polarized targets and recoil polarimetry have allowed an important and precise set of data to be collected over the last decade. I will review the experimental status of elastic electron scattering from the nucleon along with an outlook for future progress.

  20. Psychosocial factors in obesity.

    PubMed

    Mustajoki, P

    1987-01-01

    Obese people as a group have similar mental health as normal weight people, and there are no psychiatric features characteristic of obesity in general. However, small subgroups of obese individuals may have psychiatric abnormalities which are specific for obesity, such as body image disturbance or periodic compulsive overeating (bulimia). Obesity is strongly related to sociocultural factors. In western countries obesity is commoner in lower than in higher social classes. Thus, the development of obesity is influenced by social status. However, also the converse is true: recent observations suggest that obese people lose social status. This is probably due to prejudice and discrimination against obese persons in the modern western society. PMID:3477994

  1. Human Factors Model

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  2. Stress intensity factors

    SciTech Connect

    Erdogan, F.

    1983-12-01

    In this work the concept of the stress intensity factor, the underlying mechanics problem leading to its emergence, and its physical relevance, particularly its relation to fracture mechanics are discussed. The reasons as to why it has become nearly an indispensable tool for studying such important phenomena as brittle fracture and fatigue or corrosion fatigue crack propagation in structural solids are considered. A brief discussion of some of the important methods of solution of elastic crack problems is given. Also, a number of related special mechanics problems are described. 24 references.

  3. Electromagnetic pion form factor

    SciTech Connect

    Roberts, C.D.

    1995-08-01

    A phenomenological Dyson-Schwinger/Bethe-Salpeter equation approach to QCD, formalized in terms of a QCD-based model field theory, the Global Color-symmetry Model (GCM), was used to calculate the generalized impulse approximation contribution to the electromagnetic pion form factor at space-like q{sup 2} on the domain [0,10] GeV{sup 2}. In effective field theories this form factor is sometimes understood as simply being due to Vector Meson Dominance (VMD) but this does not allow for a simple connection with QCD where the VMD contribution is of higher order than that of the quark core. In the GCM the pion is treated as a composite bound state of a confined quark and antiquark interacting via the exchange of colored vector-bosons. A direct study of the quark core contribution is made, using a quark propagator that manifests the large space-like-q{sup 2} properties of QCD, parameterizes the infrared behavior and incorporates confinement. It is shown that the few parameters which characterize the infrared form of the quark propagator may be chosen so as to yield excellent agreement with the available data. In doing this one directly relates experimental observables to properties of QCD at small space-like-q{sup 2}. The incorporation of confinement eliminates endpoint and pinch singularities in the calculation of F{sub {pi}}(q{sup 2}). With asymptotic freedom manifest in the dressed quark propagator the calculation yields q{sup 4}F{sub {pi}}(q{sup 2}) = constant, up to [q{sup 2}]- corrections, for space-like-q{sup 2} {approx_gt} 35 GeV{sup 2}, which indicates that soft, nonperturbative contributions dominate the form factor at presently accessible q{sup 2}. This means that the often-used factorization Ansatz fails in this exclusive process. A paper describing this work was submitted for publication. In addition, these results formed the basis for an invited presentation at a workshop on chiral dynamics and will be published in the proceedings.

  4. From compatible factorization to near-compatible factorization

    NASA Astrophysics Data System (ADS)

    Aldiabat, Raja'i.; Ibrahim, Haslinda

    2014-12-01

    A compatible factorization of order ν, is an ν× ν-1/2 array in which the entries in row i form a near-one-factor with focus i, and the triples associated with the rows contain no repetitions. In this paper, we aim to amend this compatible factorization so that we can display ν(ν-1)/2 - 2ν/3 triples with the minimum repeated triples. Throughout this paper we propose a new type of factorization called near-compatible factorization. First, we present the compatible factorization towards developing a near-compatible factorization. Second, we discuss briefly the necessary and sufficient conditions for the existence of near-compatible factorization. Then, we exemplify the construction for case ν = 9 as a groundwork in developing near-compatible factorization.

  5. Leukemia inhibitory factor (LIF).

    PubMed

    Nicola, Nicos A; Babon, Jeffrey J

    2015-10-01

    Leukemia inhibitory factor (LIF) is the most pleiotropic member of the interleukin-6 family of cytokines. It utilises a receptor that consists of the LIF receptor β and gp130 and this receptor complex is also used by ciliary neurotrophic growth factor (CNTF), oncostatin M, cardiotrophin1 (CT1) and cardiotrophin-like cytokine (CLC). Despite common signal transduction mechanisms (JAK/STAT, MAPK and PI3K) LIF can have paradoxically opposite effects in different cell types including stimulating or inhibiting each of cell proliferation, differentiation and survival. While LIF can act on a wide range of cell types, LIF knockout mice have revealed that many of these actions are not apparent during ordinary development and that they may be the result of induced LIF expression during tissue damage or injury. Nevertheless LIF does appear to have non-redundant actions in maternal receptivity to blastocyst implantation, placental formation and in the development of the nervous system. LIF has also found practical use in the maintenance of self-renewal and totipotency of embryonic stem cells and induced pluripotent stem cells. PMID:26187859

  6. Auxin response factors.

    PubMed

    Chandler, John William

    2016-05-01

    Auxin signalling involves the activation or repression of gene expression by a class of auxin response factor (ARF) proteins that bind to auxin response elements in auxin-responsive gene promoters. The release of ARF repression in the presence of auxin by the degradation of their cognate auxin/indole-3-acetic acid repressors forms a paradigm of transcriptional response to auxin. However, this mechanism only applies to activating ARFs, and further layers of complexity of ARF function and regulation are being revealed, which partly reflect their highly modular domain structure. This review summarizes our knowledge concerning ARF binding site specificity, homodimer and heterodimer multimeric ARF association and cooperative function and how activator ARFs activate target genes via chromatin remodelling and evolutionary information derived from phylogenetic comparisons from ARFs from diverse species. ARFs are regulated in diverse ways, and their importance in non-auxin-regulated pathways is becoming evident. They are also embedded within higher-order transcription factor complexes that integrate signalling pathways from other hormones and in response to the environment. The ways in which new information concerning ARFs on many levels is causing a revision of existing paradigms of auxin response are discussed. PMID:26487015

  7. SARSCEST (human factors)

    NASA Technical Reports Server (NTRS)

    Parsons, H. Mcilvaine

    1988-01-01

    People interact with the processes and products of contemporary technology. Individuals are affected by these in various ways and individuals shape them. Such interactions come under the label 'human factors'. To expand the understanding of those to whom the term is relatively unfamiliar, its domain includes both an applied science and applications of knowledge. It means both research and development, with implications of research both for basic science and for development. It encompasses not only design and testing but also training and personnel requirements, even though some unwisely try to split these apart both by name and institutionally. The territory includes more than performance at work, though concentration on that aspect, epitomized in the derivation of the term ergonomics, has overshadowed human factors interest in interactions between technology and the home, health, safety, consumers, children and later life, the handicapped, sports and recreation education, and travel. Two aspects of technology considered most significant for work performance, systems and automation, and several approaches to these, are discussed.

  8. Factors in risk perception

    PubMed

    Sjoberg

    2000-02-01

    Risk perception is a phenomenon in search of an explanation. Several approaches are discussed in this paper. Technical risk estimates are sometimes a potent factor in accounting for perceived risk, but in many important applications it is not. Heuristics and biases, mainly availability, account for only a minor portion of risk perception, and media contents have not been clearly implicated in risk perception. The psychometric model is probably the leading contender in the field, but its explanatory value is only around 20% of the variance of raw data. Adding a factor of "unnatural risk" considerably improves the psychometric model. Cultural Theory, on the other hand, has not been able to explain more than 5-10% of the variance of perceived risk, and other value scales have similarly failed. A model is proposed in which attitude, risk sensitivity, and specific fear are used as explanatory variables; this model seems to explain well over 30-40% of the variance and is thus more promising than previous approaches. The model offers a different type of psychological explanation of risk perception, and it has many implications, e.g., a different approach to the relationship between attitude and perceived risk, as compared with the usual cognitive analysis of attitude. PMID:10795334

  9. Enhanced target factor analysis.

    PubMed

    Rostami, Akram; Abdollahi, Hamid; Maeder, Marcel

    2016-03-10

    Target testing or target factor analysis, TFA, is a well-established soft analysis method. TFA answers the question whether an independent target test vector measured at the same wavelengths as the collection of spectra in a data matrix can be excluded as the spectrum of one of the components in the system under investigation. Essentially, TFA cannot positively prove that a particular test spectrum is the true spectrum of one of the components, it can, only reject a spectrum. However, TFA will not reject, or in other words TFA will accept, many spectra which cannot be component spectra. Enhanced Target Factor Analysis, ETFA addresses the above problem. Compared with traditional TFA, ETFA results in a significantly narrower range of positive results, i.e. the chance of a false positive test result is dramatically reduced. ETFA is based on feasibility testing as described in Refs. [16-19]. The method has been tested and validated with computer generated and real data sets. PMID:26893084

  10. The stucco decorations from St. Lorenzo in Laino (Como, Italy): The materials and the techniques employed by the "Magistri Comacini".

    PubMed

    Rampazzi, Laura; Rizzo, Biagio; Colombo, Chiara; Conti, Claudia; Realini, Marco; Bartolucci, Ugo; Colombini, Maria Perla; Spiriti, Andrea; Facchin, Laura

    2008-12-01

    The paper reports a cross-cutting and systematic approach to the analytical study of Baroque stucco decorations by Italian artists known as "Magistri Comacini". Samples from the Church of St. Lorenzo in Laino (Como, Italy) were analysed using chemical and mineralogical techniques and the results interpreted with the help of art historians in order to enlighten the artistic techniques. The characterisation of the binder, aggregate and organic fractions was carried out through optical microscopy, scanning electron microscopy with microprobe, X-ray powder diffraction, Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry and laser ablation mass spectrometry equipped with plasma source spectrometry. The results on major, minor and trace components ascertained various recipes. In particular, the investigation of the finishing layers corroborated hypotheses of attribution and chronology and stressed the different skills of the artists working in the building, shedding a light on details of the decoration technique. PMID:19068330

  11. A Utilização da Astronomia como Tema Interdisciplinar e Aplicações de Objetos de Aprendizagem

    NASA Astrophysics Data System (ADS)

    da Silva, L. A.; Voelzke, M. R.

    2008-09-01

    Este trabalho visa analisar a possibilidade de relacionar conteúdos aplicados no ensino fundamental e médio de forma interdisciplinar por intermédio da astronomia, com a intervenção de objetos de aprendizagem que possam integrar as disciplinas e a utilização de recursos tecnológicos. Em uma pesquisa prévia com 20 professores de uma escola estadual situada na cidade de Guarulhos foi observado que apenas 25% dos professores utilizam algum recurso tecnológico para o desenvolvimento de conteúdos pertinentes à sua disciplina, tais como sites e softwares educativos, sendo que a maioria absoluta continua ensinando apenas com livros didáticos. A maior parte dos professores apresenta dificuldades em trabalhar sua disciplina de forma interdisciplinar, ou seja, 75% dos professores preferem aplicar os conteúdos seguindo uma hierarquia linear de tópicos, evitando a discussão de temas que de alguma forma estão relacionados. A astronomia pode vir à fascinar o ser humano e despertar sua curiosidade promovendo um maior interesse no aprendizado, podendo favorecer análises interdisciplinares de forma lógica e objetiva, desta forma colocar a astronomia como tema motivador interdisciplinar, pode ser relevante no que se refere ao distanciamento da fragmentação dos conteúdos. No Estado de São Paulo, a implantação da proposta curricular no ensino fundamental e médio mostra claramente a inserção da astronomia na maior parte das séries, principalmente na 6ª série em que todo o bimestre se fala de astronomia.

  12. Design and application of chitosan/biphasic calcium phosphate porous scaffolds for bone tissue engineering

    NASA Astrophysics Data System (ADS)

    Sendemir-Urkmez, Aylin

    For the restoration of maxillofacial bone tissue, design of novel tissue engineering scaffolds capable of inducing bone remodeling through the delivery of mesenchymal stem cells (MSCs) and an angiogenic growth factor, directly at the site of the defect was investigated in order to replace autogenous cancellous bone grafts with synthetic materials. Porous, three dimensional scaffolds were fabricated by a freeze drying method. In culture media, biphasic calcium phosphate particles within chitosan produced a surface reprecipitate of a composition similar to natural apatite that led to a uniform distribution of cells and mineralized ECM through chemotaxis. Further, the reprecipitation regulated the differentiation pathway and phenotype commitment of stem cells by altering the initial cell attachment morphology and actin cytoskeleton organization. In order to induce neovascularization after implantation, constructs were designed to be loaded with gelatin microspheres that delivered basic fibroblast growth factor (bFGF), a potent angiogenic factor. In vitro proliferation tests performed on fibroblastic cells showed no detectible loss of bFGF activity when delivered through enzymatic degradation of gelatin. Laser scanning confocal microscopy was used to demonstrate that gelatin microspheres can be injected evenly into cell-scaffold constructs owing to the spongy characteristics of the scaffold. To examine the binding interactions of bFGF with surface bound gelatin, a label free biosensor system, Biomolecular INteraction Detection sensor (BIND) was used. Results confirm that the principal interaction that takes place between bFGF and gelatin is electrostatic. Cell loaded tissue engineered constructs were produced in vitro at clinically relevant sizes and implanted with and without bFGF into a porcine mandibular defect model. Tissue engineered constructs facilitated the healing of mandibular defects only if combined with delivery of bFGF via gelatin microspheres. bFGF

  13. Neurotrophic factors and neurologic disease.

    PubMed Central

    Holtzman, D M; Mobley, W C

    1994-01-01

    Discovered only 40 years ago, nerve growth factor is the prototypic neurotrophic factor. By binding to specific receptors on certain neurons in the peripheral nervous system and brain, nerve growth factor acts to enhance their survival, differentiation, and maintenance. In recent years, many additional neurotrophic factors have been discovered; some are structurally related to nerve growth factor while others are distinct from it. The robust actions of neurotrophic factors have suggested their use in preventing or lessening the dysfunction and death of neurons in neurologic disorders. We review the progress in defining neurotrophic factors and their receptors and in characterizing their actions. We also discuss some of the uses of neurotrophic factors in animal models of disease. Finally, we discuss how neurotrophic factors could be implicated in the pathogenesis of neurologic disorders. Images PMID:7975562

  14. The majority of early primordial germ cells acquire pluripotency by AKT activation.

    PubMed

    Matsui, Yasuhisa; Takehara, Asuka; Tokitake, Yuko; Ikeda, Makiko; Obara, Yuka; Morita-Fujimura, Yuiko; Kimura, Tohru; Nakano, Toru

    2014-12-01

    Primordial germ cells (PGCs) are undifferentiated germ cells in embryos, the fate of which is to become gametes; however, mouse PGCs can easily be reprogrammed into pluripotent embryonic germ cells (EGCs) in culture in the presence of particular extracellular factors, such as combinations of Steel factor (KITL), LIF and bFGF (FGF2). Early PGCs form EGCs more readily than do later PGCs, and PGCs lose the ability to form EGCs by embryonic day (E) 15.5. Here, we examined the effects of activation of the serine/threonine kinase AKT in PGCs during EGC formation; notably, AKT activation, in combination with LIF and bFGF, enhanced EGC formation and caused ∼60% of E10.5 PGCs to become EGCs. The results indicate that the majority of PGCs at E10.5 could acquire pluripotency with an activated AKT signaling pathway. Importantly, AKT activation did not fully substitute for bFGF and LIF, and AKT activation without both LIF and bFGF did not result in EGC formation. These findings indicate that AKT signal enhances and/or collaborates with signaling pathways of bFGF and of LIF in PGCs for the acquisition of pluripotency. PMID:25359722

  15. 125I-labeled anti-bFGF monoclonal antibody inhibits growth of hepatocellular carcinoma

    PubMed Central

    Hu, Peng-Hui; Pan, Lan-Hong; Wong, Patrick Ting-Yat; Chen, Wen-Hui; Yang, Yan-Qing; Wang, Hong; Xiang, Jun-Jian; Xu, Meng

    2016-01-01

    AIM: To investigate the inhibitory efficacy of 125I-labeled anti-basic fibroblast growth factor (bFGF) monoclonal antibody (mAb) in hepatocellular carcinoma (HCC). METHODS: bFGF mAb was prepared by using the 1G9B9 hybridoma cell line with hybridization technology and extracted from ascites fluid through a Protein G Sepharose affinity column. After labeling with 125I through the chloramine-T method, bFGF mAb was further purified by a Sephadex G-25 column. Gamma radiation counter GC-1200 detected radioactivity of 125I-bFGF mAb. The murine H22 HCC xenograft model was established and randomized to interventions with control (phosphate-buffered saline), 125I-bFGF mAb, 125I plus bFGF mAb, bFGF mAb, or 125I. The ratios of tumor inhibition were then calculated. Expression of bFGF, fibroblast growth factor receptor (FGFR), platelet-derived growth factor, and vascular endothelial growth factor (VEGF) mRNA was determined by quantitative reverse transcriptase real-time polymerase chain reaction. RESULTS: The purified bFGF mAb solution was 8.145 mg/mL with a titer of 1:2560000 and was stored at -20 °C. After coupling, 125I-bFGF mAb was used at a 1: 1280000 dilution, stored at 4 °C, and its specific radioactivity was 37 MBq/mg. The corresponding tumor weight in the control, 125I, bFGF mAb, 125I plus bFGF mAb, and 125I-bFGF mAb groups was 1.88 ± 0.25, 1.625 ± 0.21, 1.5 ± 0.18, 1.41 ± 0.16, and 0.98 ± 0.11 g, respectively. The tumor inhibition ratio in the 125I, bFGF mAb, 125I plus bFGF mAb, and 125I-bFGF mAb groups was 13.6%, 20.2%, 25.1%, and 47.9%, respectively. Growth of HCC xenografts was inhibited significantly more in the 125I-bFGF mAb group than in the other groups (P < 0.05). Expression of bFGF and FGFR mRNA in the 125I-bFGF mAb group was significantly decreased in comparison with other groups (P < 0.05). Groups under interventions revealed increased expression of VEGF mRNA (except for 125I group) compared with the control group. CONCLUSION: 125I-bFGF m

  16. Human factors in aviation

    NASA Technical Reports Server (NTRS)

    Wiener, Earl L. (Editor); Nagel, David C. (Editor)

    1988-01-01

    The fundamental principles of human-factors (HF) analysis for aviation applications are examined in a collection of reviews by leading experts, with an emphasis on recent developments. The aim is to provide information and guidance to the aviation community outside the HF field itself. Topics addressed include the systems approach to HF, system safety considerations, the human senses in flight, information processing, aviation workloads, group interaction and crew performance, flight training and simulation, human error in aviation operations, and aircrew fatigue and circadian rhythms. Also discussed are pilot control; aviation displays; cockpit automation; HF aspects of software interfaces; the design and integration of cockpit-crew systems; and HF issues for airline pilots, general aviation, helicopters, and ATC.

  17. Perioperative allergy: risk factors.

    PubMed

    Caffarelli, C; Stringari, G; Pajno, G B; Peroni, D G; Franceschini, F; Dello Iacono, I; Bernardini, R

    2011-01-01

    Perioperative anaphylactic as well as anaphylactoid reactions can be elicited by drugs, diagnostic agents, antiseptics, disinfectants and latex. In some individuals, allergic reactions occur in the absence of any evident risk factor. Previous history of specific safe exposure to a product does not permit to exclude the risk of having a reaction. We have systematically reviewed characteristics in the patient's history or clinical parameters that affect the risk of developing reactions during anesthesia. Evidence shows that patients with previous unexplained reaction during anesthesia are at risk for perioperative allergic reactions. An allergic reaction to an agent is associated with previous reaction to a product that is related with the culprit agent. Multiple surgery procedures, professional exposure to latex and allergy to fruit are associated with an increased frequency of latex allergy. It has been shown that in some instances, allergic perioperative reactions may be more common in atopic patients and in females. PMID:22014923

  18. Pion form factor

    SciTech Connect

    Ryong Ji, C.; Pang, A.; Szczepaniak, A.

    1994-04-01

    It is pointed out that the correct criterion to define the legal PQCD contribution to the exclusive processes in the lightcone perturbative expansion should be based on the large off-shellness of the lightcone energy in the intermediate states. In the lightcone perturbative QCD calculation of the pion form factor, the authors find that the legal PQCD contribution defined by the lightcone energy cut saturates in the smaller Q{sup 2} region compared to that defined by the gluon four-momentum square cut. This is due to the contribution by the highly off-energy-shell gluons in the end point regions of the phase space, indicating that the gluon four-momentum-square cut may have cut too much to define the legal PQCD.

  19. Nucleon Electromagnetic Form Factors

    SciTech Connect

    Marc Vanderhaeghen; Charles Perdrisat; Vina Punjabi

    2007-10-01

    There has been much activity in the measurement of the elastic electromagnetic proton and neutron form factors in the last decade, and the quality of the data has greatly improved by performing double polarization experiments, in comparison with previous unpolarized data. Here we review the experimental data base in view of the new results for the proton, and neutron, obtained at JLab, MAMI, and MIT-Bates. The rapid evolution of phenomenological models triggered by these high-precision experiments will be discussed, including the recent progress in the determination of the valence quark generalized parton distributions of the nucleon, as well as the steady rate of improvements made in the lattice QCD calculations.

  20. Unity power factor converter

    NASA Technical Reports Server (NTRS)

    Wester, Gene W. (Inventor)

    1980-01-01

    A unity power factor converter capable of effecting either inversion (dc-to-dc) or rectification (ac-to-dc), and capable of providing bilateral power control from a DC source (or load) through an AC transmission line to a DC load (or source) for power flow in either direction, is comprised of comparators for comparing the AC current i with an AC signal i.sub.ref (or its phase inversion) derived from the AC ports to generate control signals to operate a switch control circuit for high speed switching to shape the AC current waveform to a sine waveform, and synchronize it in phase and frequency with the AC voltage at the AC ports, by selectively switching the connections to a series inductor as required to increase or decrease the current i.

  1. Psychosomatic factors in pruritus

    PubMed Central

    Tey, Hong Liang; Wallengren, Joanna; Yosipovitch, Gil

    2013-01-01

    Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease). PMID:23245971

  2. Psychosomatic factors in pruritus.

    PubMed

    Tey, Hong Liang; Wallengren, Joanna; Yosipovitch, Gil

    2013-01-01

    Pruritus and psyche are intricately and reciprocally related, with psychophysiological evidence and psychopathological explanations helping us to understand their complex association. Their interaction may be conceptualized and classified into 3 groups: pruritic diseases with psychiatric sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Management of chronic pruritus is directed at treating the underlying causes and adopting a multidisciplinary approach to address the dermatologic, somatosensory, cognitive, and emotional aspects. Pharmcotherapeutic agents that are useful for chronic pruritus with comorbid depression and/or anxiety comprise selective serotonin reuptake inhibitors, mirtazapine, tricyclic antidepressants (amitriptyline and doxepin), and anticonvulsants (gabapentin, pregabalin); the role of neurokinin receptor-1 antagonists awaits verification. Antipsychotics are required for treating itch and formication associated with schizophrenia and delusion of parasitosis (including Morgellons disease). PMID:23245971

  3. Helicopter Human Factors

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control

  4. Factor Rotation and Standard Errors in Exploratory Factor Analysis

    ERIC Educational Resources Information Center

    Zhang, Guangjian; Preacher, Kristopher J.

    2015-01-01

    In this article, we report a surprising phenomenon: Oblique CF-varimax and oblique CF-quartimax rotation produced similar point estimates for rotated factor loadings and factor correlations but different standard error estimates in an empirical example. Influences of factor rotation on asymptotic standard errors are investigated using a numerical…

  5. Environmental factors and aggressive behavior

    SciTech Connect

    Anderson, A.C.

    1982-07-01

    This paper briefly reviews some of the research areas which indicate a correlation between environmental factors and initiation of aggressive behavior. Environmental factors including lunar influences, month of birth, climate and the effects of crowding and certain chemicals are discussed.

  6. Plasma factor XIII and platelet factor XIII in hyperlipaemia.

    PubMed

    Cucuianu, M P; Miloszewski, K; Porutiu, D; Losowsky, M S

    1976-12-31

    Plasma factor XIII activity measured by a quantitative assay was found to be significantly higher in hypertriglyceridaemic patients (type IV and combined hyperlipoproteinaemia), as compared to normolipaemic controls. No such elevation in plasma factor XIII activity was found in patients with type Ha hyperlipaemia. Plasma pseudocholinesterase was found to parallel the elevated factor XIII activity in hypertriglyceridaemic subjects. In contrast, platelet factor XIII activity was not raised in hyperlipaemic subjects, and plasma factor XIII was found to be normal in a normolipaemic subjects with thrombocythaemia. It was concluded that there is no significant contribution from platelets to plasma factor XIII activity, and that the observed increase in plasma factor XIII in hypertriglyceridaemia results from enhanced hepatic synthesis of the enzyme. PMID:1037152

  7. FACTOR FINDER CD-ROM

    EPA Science Inventory

    The Factor Finder CD-ROM is a user-friendly, searchable tool used to locate exposure factors and sociodemographic data for user-defined populations. Factor Finder improves the exposure assessors and risk assessors (etc.) ability to efficiently locate exposure-related informatio...

  8. Factor Analysis of Intern Effectiveness

    ERIC Educational Resources Information Center

    Womack, Sid T.; Hannah, Shellie Louise; Bell, Columbus David

    2012-01-01

    Four factors in teaching intern effectiveness, as measured by a Praxis III-similar instrument, were found among observational data of teaching interns during the 2010 spring semester. Those factors were lesson planning, teacher/student reflection, fairness & safe environment, and professionalism/efficacy. This factor analysis was as much of a…

  9. Phonological Awareness: Factors of Influence

    ERIC Educational Resources Information Center

    Frohlich, Linda Paulina; Petermann, Franz; Metz, Dorothee

    2013-01-01

    Early child development is influenced by various genetic and environmental factors. This study aims to identify factors that affect the phonological awareness of preschool and first grade children. Based on a sample of 330 German-speaking children (mean age = 6.2 years) the following domains were evaluated: Parent factors, birth and pregnancy,…

  10. Salivary Gland Cancer: Risk Factors

    MedlinePlus

    ... Factors Request Permissions Print to PDF Salivary Gland Cancer: Risk Factors Approved by the Cancer.Net Editorial Board , 08/ ... anything that increases a person’s chance of developing cancer. Although risk factors often influence the development of cancer, most do ...

  11. Quantification of Emission Factor Uncertainty

    EPA Science Inventory

    Emissions factors are important for estimating and characterizing emissions from sources of air pollution. There is no quantitative indication of uncertainty for these emission factors, most factors do not have an adequate data set to compute uncertainty, and it is very difficult...

  12. Risk Factor Assessment Branch (RFAB)

    Cancer.gov

    The Risk Factor Assessment Branch (RFAB) focuses on the development, evaluation, and dissemination of high-quality risk factor metrics, methods, tools, technologies, and resources for use across the cancer research continuum, and the assessment of cancer-related risk factors in the population.

  13. Factor Analysis via Components Analysis

    ERIC Educational Resources Information Center

    Bentler, Peter M.; de Leeuw, Jan

    2011-01-01

    When the factor analysis model holds, component loadings are linear combinations of factor loadings, and vice versa. This interrelation permits us to define new optimization criteria and estimation methods for exploratory factor analysis. Although this article is primarily conceptual in nature, an illustrative example and a small simulation show…

  14. [Environmental factors in ALS].

    PubMed

    Juntas-Morales, Raul; Pageot, Nicolas; Corcia, Philippe; Camu, William

    2014-05-01

    ALS is likely to be a disorder of multifactorial origin. Among all the factors that may increase the risk of ALS, environmental ones are being studied for many years, but in the recent years, several advances have pointed to a new interest in their potential involvement in the disease process, especially for the cyanotoxin BMAA. Food containing BMAA has been found on Guam, a well-known focus of ALS/parkinsonism/dementia and high levels of BMAA have been identified into the brain of these patients. The BMAA cyanotoxin is potentially ubiquitous and have also been found into the food of patients who died from ALS both in Europe and USA. BMAA can be wrongly integrated into the protein structure during mRNA traduction, competing with serine. This may induce abnormal protein folding and a subsequent cell death. Heavy metals, such as lead or mercury may be directly toxic for neuronal cells. Several works have suggested an increased risk of ALS in individuals chronically exposed to these metals. Exposure to pesticides has been suggested to be linked to an increased risk of developing ALS. The mechanism of their toxicity is likely to be mediated by paraoxonases. These proteins are in charge of detoxifying the organism from toxins, and particularly organophosphates. To date, there are insufficient scientific data to suggest that exposure to electromagnetic fields may increase the risk of having ALS. We are particularly missing longitudinal cohorts to demonstrate that risk. PMID:24703731

  15. Dietary factors and hyperuricaemia.

    PubMed

    Schlesinger, Naomi

    2005-01-01

    The connection of gout and hyperuricaemia with gluttony, overindulgence in food and alcohol and obesity dates from ancient times. Studies from different parts of the world suggest that the incidence and severity of hyperuricaemia and gout may be increasing. Uric acid (urate) is the end product of purine degradation. Although most uric acid is derived from the metabolism of endogenous purine, eating foods rich in purines contributes to the total pool of uric acid. Sustained hyperuricaemia is a risk factor for acute gouty arthritis, chronic tophaceous gout, renal stones and possibly cardiovascular events and mortality. Before starting lifelong urate-lowering drug therapy, it is important to identify and treat underlying disorders that may be contributing to hyperuricaemia. It is relevant to recognize the strong association of the insulin resistance syndrome (IRS) (abdominal obesity, dyslipidaemia, hypertension, raised serum insulin levels and glucose intolerance) with hyperuricaemia. Consumption of meat, seafood and alcoholic beverages in moderation and attention to food portion size is important. Moderation in the consumption of not only beer but also other forms of alcohol is essential. In the obese, controlled weight management has the potential to lower serum urate in a quantitatively similar way to relatively unpalatable "low purine" diets. Non-fat milk and low-fat yogurt have a variety of health benefits and dairy products may have clinically meaningful antihyperuricaemic effects. In addition, fruits, such as cherries and high intakes of vegetable protein diet may reduce serum urate levels. PMID:16375734

  16. Human Factors in Training

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Byrne, Vicky; Arsintescu, Lucia; Connell, Erin

    2010-01-01

    Future space missions will be significantly longer than current shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. By researching established training principles, examining future needs, and by using current practices in space flight training as test beds, both in Flight Controller and Crew Medical domains, this research project is mitigating program risks and generating templates and requirements to meet future training needs. Training efforts in Fiscal Year 09 (FY09) strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center (MCC) operations. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: 1) Risk associated with poor task design; 2) Risk of error due to inadequate information; and 3) Risk associated with reduced safety and efficiency due to poor human factors design.

  17. Human Factors in Training

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Byme, Vicky; Arsintescu, Lucia

    2008-01-01

    Future space missions will be significantly longer than current Shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. Training efforts in FY07 strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center operations. Beginning in January 2008, the training research effort will include team training prototypes and tools. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: 1) Risk associated with poor task design; 2) Risk of error due to inadequate information; 3) Risk associated with reduced safety and efficiency due to poor human factors design.

  18. Human Factors in Training

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Byrne, Vicky; Arsintescu, Lucia; Connell, Erin; Sandor, Aniko

    2009-01-01

    Future space missions will be significantly longer than current shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. By researching established training principles, examining future needs, and by using current practices in space flight training as test beds, both in Flight Controller and Crew Medical domains, this research project is mitigating program risks and generating templates and requirements to meet future training needs. Training efforts in Fiscal Year 08 (FY08) strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center (MCC) operations. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: (1) Risk associated with poor task design (2) Risk of error due to inadequate information (3) Risk associated with reduced safety and efficiency due to poor human factors design

  19. Las fulguraciones como manifestación de reconexión en el campo magnético solar

    NASA Astrophysics Data System (ADS)

    Bagalá, L. G.; Mandrini, M. C.; Rovira, M. G.; Démoulin, P.

    Las fulguraciones solares son fenómenos transitorios de liberación de energía que se desarrollan en las estructuras magnéticas de las regiones activas del Sol. Las fulguraciones pueden llegar a liberar hasta 1032 erg en 100 seg. en todo el rango electromagnético, y acelerar partículas. En este trabajo mostramos que la ubicación de los abrillantamientos en Hα de diversas fulguraciones está relacionado con las propiedades de las conexiones de las líneas del campo magnético de la región, como se espera por las teorías de reconexión en 3D recientemente desarrolladas (Démoulin et al, 1996a). El campo magnético coronal se extrapola del campo fotosférico observado suponiendo una configuración libre de fuerzas lineal. Por medio de un algoritmo se determinan las regiones donde existe un cambio drástico en la conectividad de las líneas de campo (límites ``cuasi-discontinuos'', o cuasi-separatrices CS). Las CS son bandas abiertas que identifican zonas donde el campo magnético se reconectará con más probabilidad y, siempre que las mismas sean lo suficientemente finas, se producirá allíla liberación de energía proveniente del campo magnético. Hemos encontrado que en todas las regiones fulgurantes estudiadas (Démoulin et al, 1996b) existen CS en los mismos lugares donde se observaron los abrillantamientos en Hα. Allídonde coinciden los abrillantamientos con las CS, éstas tienen un espesor menor que 1 Mm. Las líneas de campo coronales extrapoladas de nuestro modelo tienen sus orígenes fotosféricos a ambos lados de las CS, como se espera dados los recientes estudios de reconexión magnética en 3D. Estos resultados ponen a prueba los modelos presentes sobre fulguraciones solares.

  20. In-situ HRTEM study of the reactive carbide phase of Co/MoS2 catalyst.

    PubMed

    Ramos, Manuel; Ferrer, Domingo; Martinez-Soto, Eduan; Lopez-Lippmann, Hugo; Torres, Brenda; Berhault, Gilles; Chianelli, Russell R

    2013-04-01

    Hydrotreatment catalytic operations are commonly performed industrially by layered molybdenum sulfide promoted by cobalt or nickel in order to remove heteroelements (S, N, O) from fossil fuels and biofuels. Indeed, these heteroelements are responsible of the emission of pollutants when these fuels are used in vehicles. In this respect, previous studies made by our research group have shown that the active phase under steady state conditions is partially carbided while strong bending effects of MoS2 slabs were also observed. However, up to now, the morphology of the resulting Co/MoSxCy carbided catalyst has not been fully characterized. In the present study, for the first time, a chemical reaction between the carbon content of a TEM Cu/C grid and a freshly sulfide Co/MoS2 catalyst was in situ observed at 300 °C and 450 °C by HRTEM experimental techniques at ~10 nm of resolution. Results indicate that bending of MoS2 layers occurred due to carbon addition on MoS2 edge sites, as observed in stabilized catalysts after HDS reaction. Using a silicon grid, only cracks of MoS2 slabs were observed without bending effect confirming the role of structural-carbon in this change of morphology. PMID:22925737

  1. Growth factors in ischemic stroke

    PubMed Central

    Lanfranconi, S; Locatelli, F; Corti, S; Candelise, L; Comi, G P; Baron, P L; Strazzer, S; Bresolin, N; Bersano, A

    2011-01-01

    Abstract Data from pre-clinical and clinical studies provide evidence that colony-stimulating factors (CSFs) and other growth factors (GFs) can improve stroke outcome by reducing stroke damage through their anti-apoptotic and anti-inflammatory effects, and by promoting angiogenesis and neurogenesis. This review provides a critical and up-to-date literature review on CSF use in stroke. We searched for experimental and clinical studies on haemopoietic GFs such as granulocyte CSF, erythropoietin, granulocyte-macrophage colony-stimulating factor, stem cell factor (SCF), vascular endothelial GF, stromal cell-derived factor-1α and SCF in ischemic stroke. We also considered studies on insulin-like growth factor-1 and neurotrophins. Despite promising results from animal models, the lack of data in human beings hampers efficacy assessments of GFs on stroke outcome. We provide a comprehensive and critical view of the present knowledge about GFs and stroke, and an overview of ongoing and future prospects. PMID:20015202

  2. Approximate factorization with source terms

    NASA Technical Reports Server (NTRS)

    Shih, T. I.-P.; Chyu, W. J.

    1991-01-01

    A comparative evaluation is made of three methodologies with a view to that which offers the best approximate factorization error. While two of these methods are found to lead to more efficient algorithms in cases where factors which do not contain source terms can be diagonalized, the third method used generates the lowest approximate factorization error. This method may be preferred when the norms of source terms are large, and transient solutions are of interest.

  3. Women's Career Success: A Factor Analytic Study of Contributing Factors.

    ERIC Educational Resources Information Center

    Gaskill, LuAnn Ricketts

    1991-01-01

    A survey of 466 women employed in retailing received 205 responses identifying (1) factors influencing the success and advancement of women in retailing and (2) how those factors differ for women in upper versus middle positions. Upper-level executives placed more importance on ambition and abilities; midlevel executives credited opportunity and…

  4. Five Describing Factors of Dyslexia.

    PubMed

    Tamboer, Peter; Vorst, Harrie C M; Oort, Frans J

    2016-09-01

    Two subtypes of dyslexia (phonological, visual) have been under debate in various studies. However, the number of symptoms of dyslexia described in the literature exceeds the number of subtypes, and underlying relations remain unclear. We investigated underlying cognitive features of dyslexia with exploratory and confirmatory factor analyses. A sample of 446 students (63 with dyslexia) completed a large test battery and a large questionnaire. Five factors were found in both the test battery and the questionnaire. These 10 factors loaded on 5 latent factors (spelling, phonology, short-term memory, rhyme/confusion, and whole-word processing/complexity), which explained 60% of total variance. Three analyses supported the validity of these factors. A confirmatory factor analysis fit with a solution of five factors (RMSEA = .03). Those with dyslexia differed from those without dyslexia on all factors. A combination of five factors provided reliable predictions of dyslexia and nondyslexia (accuracy >90%). We also looked for factorial deficits on an individual level to construct subtypes of dyslexia, but found varying profiles. We concluded that a multiple cognitive deficit model of dyslexia is supported, whereas the existence of subtypes remains unclear. We discussed the results in relation to advanced compensation strategies of students, measures of intelligence, and various correlations within groups of those with and without dyslexia. PMID:25398549

  5. Factorized molecular wave functions: Analysis of the nuclear factor

    SciTech Connect

    Lefebvre, R.

    2015-06-07

    The exact factorization of molecular wave functions leads to nuclear factors which should be nodeless functions. We reconsider the case of vibrational perturbations in a diatomic species, a situation usually treated by combining Born-Oppenheimer products. It was shown [R. Lefebvre, J. Chem. Phys. 142, 074106 (2015)] that it is possible to derive, from the solutions of coupled equations, the form of the factorized function. By increasing artificially the interstate coupling in the usual approach, the adiabatic regime can be reached, whereby the wave function can be reduced to a single product. The nuclear factor of this product is determined by the lowest of the two potentials obtained by diagonalization of the potential matrix. By comparison with the nuclear wave function of the factorized scheme, it is shown that by a simple rectification, an agreement is obtained between the modified nodeless function and that of the adiabatic scheme.

  6. [Host factors and viral factors in hepatitis C treatment].

    PubMed

    Sakamoto, Minoru; Enomoto, Nobuyuki

    2015-02-01

    In the interferon-based therapy for hepatitis C, host factors such as age, gender, liver fibrosis and steatosis are important as a therapeutic effect predictor, and viral factors such as HCV genotype, HCV viral load, HCV gene (IL28B, ITPA) are also important. In addition in genotype 1b, ISDR/IRRDR and core amino acid substitution are important. Also in the DAA treatment, viral factors are also important at the view of therapeutic effect and difficulty of acquisition of drug resistance mutation. In addition, the goal of treatment of hepatitis C are suppression of liver fibrosis progression and liver cancer and improvement of quality of life due to this (quality of life: QOL) and life prognosis, it is important to understand the host factors and HCV viral factors. PMID:25764672

  7. Peripheral nerve regeneration through a silicone chamber implanted with negative carbon ions: Possibility to clinical application

    NASA Astrophysics Data System (ADS)

    Ikeguchi, Ryosuke; Kakinoki, Ryosuke; Tsuji, Hiroshi; Yasuda, Tadashi; Matsuda, Shuichi

    2014-08-01

    We investigated whether a tube with its inner surface implanted with negative-charged carbon ions (C- ions) would enable axons to extend over a distance greater than 10 mm. The tube was found to support nerves regenerating across a 15-mm-long inter-stump gap. We also investigated whether a C- ion-implanted tube pretreated with basic fibroblast growth factor (bFGF) promotes peripheral nerve regeneration. The C- ion implanted tube accelerated nerve regeneration, and this effect was enhanced by bFGF. Silicone treated with C- ions showed increased hydrophilic properties and cellular affinity, and axon regeneration was promoted with this increased biocompatibility.

  8. Factors That Influence Teacher Attrition.

    ERIC Educational Resources Information Center

    Gonzalez, Patricia

    1995-01-01

    External, employment, and personal factors which influence teacher decisions to stay, leave, or transfer from teaching assignments are discussed, with emphasis on special education teachers. Factors attributed to teacher attrition in urban and rural environments also are briefly reviewed, along with attrition of related services professionals.…

  9. Matrix factorizations and elliptic fibrations

    NASA Astrophysics Data System (ADS)

    Omer, Harun

    2016-09-01

    I use matrix factorizations to describe branes at simple singularities of elliptic fibrations. Each node of the corresponding Dynkin diagrams of the ADE-type singularities is associated with one indecomposable matrix factorization which can be deformed into one or more factorizations of lower rank. Branes with internal fluxes arise naturally as bound states of the indecomposable factorizations. Describing branes in such a way avoids the need to resolve singularities. This paper looks at gauge group breaking from E8 fibers down to SU (5) fibers due to the relevance of such fibrations for local F-theory GUT models. A purpose of this paper is to understand how the deformations of the singularity are understood in terms of its matrix factorizations. By systematically factorizing the elliptic fiber equation, this paper discusses geometries which are relevant for building semi-realistic local models. In the process it becomes evident that breaking patterns which are identical at the level of the Kodaira type of the fibers can be inequivalent at the level of matrix factorizations. Therefore the matrix factorization picture supplements information which the conventional less detailed descriptions lack.

  10. Risk Factors for Teenage Fatherhood.

    ERIC Educational Resources Information Center

    Thornberry, Terence P.; Smith, Carolyn A.; Howard, Gregory J.

    1997-01-01

    Uses data from the Rochester Youth Development Study of urban youth (N=615) to identify early risk factors for the likelihood of becoming a teen father. Results show that teen fatherhood is related to a variety of risk factors, such as social class, educational performance, precocious sexual activity, and drug use. (RJM)

  11. Stroke prevention: modifying risk factors

    PubMed Central

    Romero, José Rafael; Morris, Jane; Pikula, Aleksandra

    2009-01-01

    Risk factor modification remains as the principal aspect of care for stroke prevention. Understanding of risk factors has advanced and several options are now available to treat modifiable risk factors. However, effective treatment remains a challenging task in clinical practice. Prevention begins with awareness of risk factors by patients and clinicians. Risk factor assessment along with overall stroke risk estimation should be part of evaluation of patients with stroke, and used with careful clinical judgment. In this review we discuss the impact of modifiable traditional vascular risk factors on ischemic stroke, interventions for stroke prevention, and evidence for early treatment of risk factors where available as well as areas of research progress. Emphasis should be paid in education of patients, the community and medical personnel. Future research in the field of genetic determinants of vascular risk factors and stroke will increase our understanding of the underlying mechanisms of cerebrovascular disease and likely result in development of new therapies and individualized programs for stroke prevention. PMID:19124428

  12. About the Exposure Factors Program

    EPA Science Inventory

    The development of the latest version of the Exposure Factors Handbook (EFH): 2011 Edition (EPA/600/R-09/052F) has maintained the need for a more comprehensive program that addresses issues related to exposure factors. Since the first version of the EFH was r...

  13. Factorization with genus 2 curves

    NASA Astrophysics Data System (ADS)

    Cosset, Romain

    2010-04-01

    The elliptic curve method (ECM) is one of the best factorization methods available. It is possible to use hyperelliptic curves instead of elliptic curves but it is in theory slower. We use special hyperelliptic curves and Kummer surfaces to reduce the complexity of the algorithm. Our implementation GMP-HECM is faster than GMP-ECM for factoring large numbers.

  14. Statistical Factors in Complexation Reactions.

    ERIC Educational Resources Information Center

    Chung, Chung-Sun

    1985-01-01

    Four cases which illustrate statistical factors in complexation reactions (where two of the reactants are monodentate ligands) are presented. Included are tables showing statistical factors for the reactions of: (1) square-planar complexes; (2) tetrahedral complexes; and (3) octahedral complexes. (JN)

  15. Activity factors of the Korean exposure factors handbook.

    PubMed

    Jang, Jae-Yeon; Jo, Soo-Nam; Kim, So-Yeon; Lee, Kyung-Eun; Choi, Kyung-Ho; Kim, Young-Hee

    2014-01-01

    Exposure factors based on the Korean population are required for making appropriate risk assessment. It is expected that handbooks for exposure factors will be applied in many fields, as well as by health department risk assessors. The present article describes the development of an exposure factors handbook that specifically focuses on human activities in situations involving the possible risk of exposure to environmental contaminants. We define majour exposure factors that represent behavioral patterns for risk assessment, including time spent on routine activities, in different places, on using transportation, and engaged in activities related to water contact including swimming, bathing and washing. Duration of residence and employment are also defined. National survey data were used to identify recommended levels of exposure factors in terms of time spent on routine activities and period of residence and employment. An online survey was conducted with 2073 subjects who were selected using a stratified random sampling method in order to develop a list of exposure factors for the time spent in different places and in performing water-related activities. We provide the statistical distribution of the variables, and report reference levels of average exposure based on the reliable data in our exposure factors handbook. PMID:24570804

  16. Optimizing human factors in dentistry

    PubMed Central

    Gupta, Arpit; Ankola, Anil V.; Hebbal, Mamata

    2013-01-01

    Occupational health hazards among dental professionals are on a continuous rise and they have a significant negative overall impact on daily life. This review is intended to provide the information regarding risk factors and to highlight the prevention strategies for optimizing human factors in dentistry. Risk factors among dentists are multifactorial, which can be categorized into biomechanical and psychosocial. To achieve a realistic target of safety and health at work, prevention is clearly the best approach; therefore, musculoskeletal disorders can be reduced through proper positioning of dental worker and patient, regular rest breaks, general good health, using ergonomic equipment, and exercises designed to counteract the particular risk factors for the dental occupation. However, substantial evidences are still required to elucidate the potential risk factors and to formulate effective prevention programs. PMID:23946745

  17. Mitotic bookmarking by transcription factors

    PubMed Central

    2013-01-01

    Mitosis is accompanied by dramatic changes in chromatin organization and nuclear architecture. Transcription halts globally and most sequence-specific transcription factors and co-factors are ejected from mitotic chromatin. How then does the cell maintain its transcriptional identity throughout the cell division cycle? It has become clear that not all traces of active transcription and gene repression are erased within mitotic chromatin. Many histone modifications are stable or only partially diminished throughout mitosis. In addition, some sequence-specific DNA binding factors have emerged that remain bound to select sites within mitotic chromatin, raising the possibility that they function to transmit regulatory information through the transcriptionally silent mitotic phase, a concept that has been termed “mitotic bookmarking.” Here we review recent approaches to studying potential bookmarking factors with regards to their mitotic partitioning, and summarize emerging ideas concerning the in vivo functions of mitotically bound nuclear factors. PMID:23547918

  18. Factoring in Factor VIII With Acute Ischemic Stroke

    PubMed Central

    Siegler, James E.; Samai, Alyana; Albright, Karen C.; Boehme, Amelia K.; Martin-Schild, Sheryl

    2016-01-01

    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. PMID:25669199

  19. Inhibition of Hageman factor (factor XII) by popcorn inhibitor.

    PubMed

    Kambhu, S A; Ratnoff, O D; Everson, B

    1985-05-01

    A protein derived from sweet corn or popcorn inhibits the enzymatic activity of the carboxy-terminal fragment of Hageman factor (HFf) and of ellagic acid-activated Hageman factor (HF, factor XII). Not clarified is whether the inhibitor is directed at the active site of HF. Filtration of normal plasma or purified HF through columns of popcorn inhibitor bound to agarose gels demonstrated that HF was bound to these gels and could then be eluted by buffers containing 2.0 mol/L sodium chloride. The eluted HF was in the precursor form. Thus, popcorn inhibitor appeared to attach to a point on the carboxy-terminal HFf that was distinct from the enzymatically active site of this clotting factor. PMID:3989356

  20. Using Bayes factors for multi-factor, biometric authentication

    NASA Astrophysics Data System (ADS)

    Giffin, A.; Skufca, J. D.; Lao, P. A.

    2015-01-01

    Multi-factor/multi-modal authentication systems are becoming the de facto industry standard. Traditional methods typically use rates that are point estimates and lack a good measure of uncertainty. Additionally, multiple factors are typically fused together in an ad hoc manner. To be consistent, as well as to establish and make proper use of uncertainties, we use a Bayesian method that will update our estimates and uncertainties as new information presents itself. Our algorithm compares competing classes (such as genuine vs. imposter) using Bayes Factors (BF). The importance of this approach is that we not only accept or reject one model (class), but compare it to others to make a decision. We show using a Receiver Operating Characteristic (ROC) curve that using BF for determining class will always perform at least as well as the traditional combining of factors, such as a voting algorithm. As the uncertainty decreases, the BF result continues to exceed the traditional methods result.

  1. Development of stress intensification factors

    SciTech Connect

    Minichiello, J.C.; Rodabaugh, E.C.

    1995-12-01

    B31.1 Equation 13A, B31.3 Equation 18, and Section 3 Paragraphs NC/ND-3653 EQS. (10), (10a), and 11 all use i-factors (SIFs) to compute stresses in piping due to displacement induced loadings. Appendix D of the B31 Standards and Figure NC/ND-3673.2(b)-1 of Section 3 give values of i-factors for commonly used piping components. A need occasionally arises to establish i-factors for other components (e.g., a branch connection in an elbow). In order to provide guidance on the development of these factors, a new draft Appendix has been prepared to assure that the experimental procedures and interpretation of the test results leading to new i-factors are consistent with the basis for existing i-factors. This paper discusses the background to the proposed Appendix, using the Section 3 version as a model, and also provides the authors` opinions an the need for experimental verification (vs purely analytical computation) of i-factors. The Appendix proposed is to be part of Appendix 2 of Section 3.

  2. GATA Transcription Factors and Cancer

    PubMed Central

    Zheng, Rena; Blobel, Gerd A.

    2010-01-01

    It has been almost a quarter century since it was first appreciated that a class of oncogenes contained in rapidly transforming avian retroviruses encoded DNA-binding transcription factors. As with other oncogenes, genetic recombination with the viral genome led to their overexpression or functional alteration. In the years that followed, alterations of numerous transcription factors were shown to be causatively involved in various cancers in human patients and model organisms. Depending on their normal cellular functions, these factors were subsequently categorized as proto-oncogenes or tumor suppressor genes. This review focuses on the role of GATA transcription factors in carcinogenesis. GATA factors are zinc finger DNA binding proteins that control the development of diverse tissues by activating or repressing transcription. GATA factors thus coordinate cellular maturation with proliferation arrest and cell survival. Therefore, a role of this family of genes in human cancers is not surprising. Prominent examples include structural mutations in GATA1 that are found in almost all megakaryoblastic leukemias in patients with Down syndrome; loss of GATA3 expression in aggressive, dedifferentiated breast cancers; and silencing of GATA4 and GATA5 expression in colorectal and lung cancers. Here, we discuss possible mechanisms of carcinogenesis vis-à-vis the normal functions of GATA factors as they pertain to human patients and mouse models of cancer. PMID:21779441

  3. Risk Factors For Chronic Rhinosinusitis

    PubMed Central

    Min, Jin-Young; Tan, Bruce K.

    2015-01-01

    Purpose of review To review the recent literature on risk factors for chronic rhinosinusitis (CRS) with an emphasis on genetic, comorbid diseases and environmental factors associated with CRS. Through identifying potential risk factors for CRS, we glean insights into the underlying pathogenic mechanisms and essential for developing effective therapeutic strategies. Recent findings Recent findings demonstrate that genetics, comorbid medical conditions including airway diseases, gastroesophageal reflux disease, inflammatory and autoimmune diseases and various demographic and environmental factors are associated with having a CRS diagnosis. Limitations of current studies include, variable application of disease definitions, lack of prospective longitudinal studies and a disproportionate focus on tertiary care populations. Summary CRS has a broad spectrum of associations ranging from genetics to comorbid diseases and environmental factors. These predisposing factors provide valuable information for possible designing therapeutic and preventive interventions. However, to better understand whether these associations cause CRS, further studies are needed to independently replicate findings, establish temporal relationships between exposure and disease onset, evaluate the influence of exposure dose on disease severity, and to understand the biological effects of these risk factors in the context of CRS. PMID:25479315

  4. Corrosion effects on friction factors

    SciTech Connect

    Magleby, H.L.; Shaffer, S.J.

    1996-03-01

    This paper presents the results of NRC-sponsored material specimen tests that were performed to determine if corrosion increases the friction factors of sliding surfaces of motor-operated gate valves, which could require higher forces to close and open safety-related valves when subjected to their design basis differential pressures. Friction tests were performed with uncorroded specimens and specimens subjected to accelerated corrosion. Preliminary tests at ambient conditions showed that corrosion increased the friction factors, indicating the need for additional tests duplicating valve operating parameters at hot conditions. The additional tests showed friction factors of corroded specimens were 0.1 to 0.2 higher than for uncorroded specimens, and that the friction factors of the corroded specimens were not very dependent on contact stress or corrosion film thickness. The measured values of friction factors for the three corrosion films tested (simulating three operating times) were in the range of 0.3 to 0.4. The friction factor for even the shortest simulated operating time was essentially the same as the others, indicating that the friction factors appear to reach a plateau and that the plateau is reached quickly.

  5. Factors Affecting Medical Service Quality

    PubMed Central

    MOSADEGHRAD, Ali Mohammad

    2014-01-01

    Abstract Background A better understanding of factors influencing quality of medical service can pinpoint better strategies for quality assurance in medical services. This study aimed to identify factors affecting the quality of medical services provided by Iranian physicians. Methods Exploratory in-depth individual interviews were conducted with sixty-four physicians working in various medical institutions in Iran. Results Individual, organizational and environmental factors enhance or inhibit the quality of medical services. Quality of medical services depends on the personal factors of the physician and patient, and factors pertaining to the healthcare setting and the broader environment. Conclusion Differences in internal and external factors such as availability of resources, patient cooperation and collaboration among providers affect the quality of medical services and patient outcomes. Supportive leadership, proper planning, education and training and effective management of resources and processes improve the quality of medical services. This article contributes to healthcare theory and practice by developing a conceptual framework for understanding factors that influence medical services quality. PMID:26060745

  6. Sequence Factorization with Multiple References

    PubMed Central

    Wandelt, Sebastian; Leser, Ulf

    2015-01-01

    The success of high-throughput sequencing has lead to an increasing number of projects which sequence large populations of a species. Storage and analysis of sequence data is a key challenge in these projects, because of the sheer size of the datasets. Compression is one simple technology to deal with this challenge. Referential factorization and compression schemes, which store only the differences between input sequence and a reference sequence, gained lots of interest in this field. Highly-similar sequences, e.g., Human genomes, can be compressed with a compression ratio of 1,000:1 and more, up to two orders of magnitude better than with standard compression techniques. Recently, it was shown that the compression against multiple references from the same species can boost the compression ratio up to 4,000:1. However, a detailed analysis of using multiple references is lacking, e.g., for main memory consumption and optimality. In this paper, we describe one key technique for the referential compression against multiple references: The factorization of sequences. Based on the notion of an optimal factorization, we propose optimization heuristics and identify parameter settings which greatly influence 1) the size of the factorization, 2) the time for factorization, and 3) the required amount of main memory. We evaluate a total of 30 setups with a varying number of references on data from three different species. Our results show a wide range of factorization sizes (optimal to an overhead of up to 300%), factorization speed (0.01 MB/s to more than 600 MB/s), and main memory usage (few dozen MB to dozens of GB). Based on our evaluation, we identify the best configurations for common use cases. Our evaluation shows that multi-reference factorization is much better than single-reference factorization. PMID:26422374

  7. Topical application of Cleome viscosa increases the expression of basic fibroblast growth factor and type III collagen in rat cutaneous wound.

    PubMed

    Upadhyay, Aadesh; Chattopadhyay, Pronobesh; Goyary, Danswrang; Mazumder, Papiya M; Veer, Vijay

    2014-01-01

    Cleome viscosa L. (Cleomaceae) is an important traditional medicine of the Indian-Ayurvedic and Chinese-medicine system documented for rheumatic arthritis, hypertension, malaria, neurasthenia, and wound healing. The plant is also known as Asian spider flower and is distributed throughout the greater part of India. The present study explored the wound healing property of C. viscosa methanol extract (CvME) and its related mechanism using Wistar rat cutaneous excision wound model. Wound contraction rate, hydroxyproline quantification, and histopathological examination of wound granulation tissue were performed. The healing potential was comparatively assessed with a reference gentamicin sulfate hydrogel (0.01% w/w). Western blot for COL3A1, bFGF, and Smad-2, Smad-3, Smad-4, and Smad-7 was performed with 7-day postoperative granulation tissue. Results revealed that the topical application of CvME (2.5% w/w) significantly accelerated the wound contraction rate (95.14%, 24 postoperative days), increased the hydroxyproline content (3.947 mg/100 mg tissue), and improved histopathology of wound tissue as compared to control groups. Western blot analysis revealed that CvME significantly upregulated the expression of COL3A1 and bFGF and increased the Smad-mediated collagen production in granulation tissue. These findings suggest that C. viscosa promoted the wound repair process by attenuating the Smad-mediated collagen production in wound granulation tissue. PMID:24864253

  8. Human Factors In Aircraft Automation

    NASA Technical Reports Server (NTRS)

    Billings, Charles

    1995-01-01

    Report presents survey of state of art in human factors in automation of aircraft operation. Presents examination of aircraft automation and effects on flight crews in relation to human error and aircraft accidents.

  9. Radiant-interchange Configuration Factors

    NASA Technical Reports Server (NTRS)

    Hamilton, D C :; Morgan, W R

    1952-01-01

    A study is presented of the geometric configuration factors required for computing radiant heat transfer between opaque surfaces separated by a nonabsorbing medium and various methods of determining the configuration factors are discussed. Configuration-factor solutions available in the literature have been checked and the more complicated equations are presented as families of curves. Cases for point, line, and finite-area sources are worked out over a wide range of geometric proportions. These cases include several new configurations involving rectangles, triangles, and cylinders of finite length which are integrated and tabulated. An analysis is presented, in which configuration factors are employed of the radiant heat transfer to the rotor blades of a typical gas turbine under different conditions of temperature and pressure. (author)

  10. Chemical Specific Adjustment Factors Workshop

    EPA Science Inventory

    The World Health Organization, through the International Programme on Chemical Safety (IPCS), has established guidance on the use of mechanistic data to replace default uncertainty factors for interspecies extrapolation and intraspecies variability in deriving risk values such as...

  11. Factorization-based texture segmentation

    DOE PAGESBeta

    Yuan, Jiangye; Wang, Deliang; Cheriyadat, Anil M.

    2015-06-17

    This study introduces a factorization-based approach that efficiently segments textured images. We use local spectral histograms as features, and construct an M × N feature matrix using M-dimensional feature vectors in an N-pixel image. Based on the observation that each feature can be approximated by a linear combination of several representative features, we factor the feature matrix into two matrices-one consisting of the representative features and the other containing the weights of representative features at each pixel used for linear combination. The factorization method is based on singular value decomposition and nonnegative matrix factorization. The method uses local spectral histogramsmore » to discriminate region appearances in a computationally efficient way and at the same time accurately localizes region boundaries. Finally, the experiments conducted on public segmentation data sets show the promise of this simple yet powerful approach.« less

  12. Factorization-based texture segmentation

    SciTech Connect

    Yuan, Jiangye; Wang, Deliang; Cheriyadat, Anil M.

    2015-06-17

    This study introduces a factorization-based approach that efficiently segments textured images. We use local spectral histograms as features, and construct an M × N feature matrix using M-dimensional feature vectors in an N-pixel image. Based on the observation that each feature can be approximated by a linear combination of several representative features, we factor the feature matrix into two matrices-one consisting of the representative features and the other containing the weights of representative features at each pixel used for linear combination. The factorization method is based on singular value decomposition and nonnegative matrix factorization. The method uses local spectral histograms to discriminate region appearances in a computationally efficient way and at the same time accurately localizes region boundaries. Finally, the experiments conducted on public segmentation data sets show the promise of this simple yet powerful approach.

  13. Formulas for Image Factor Scores

    ERIC Educational Resources Information Center

    Hakstian, A. Ralph

    1973-01-01

    Formulas are presented in this paper for computing scores associated with factors of G, the image covariance matrix, under three conditions. The subject of the paper is restricted to "pure" image analysis. (Author/NE)

  14. Stroke Risk Factors and Symptoms

    MedlinePlus

    ... effective if given quickly. Every minute counts! "Stroke Risk Factors and Symptoms", NINDS. June 1, 2008. Prepared by: Office of Communications and Public Liaison National Institute of Neurological Disorders ...

  15. Predisposition Factors in Anorexia Nervosa.

    ERIC Educational Resources Information Center

    Nagel, K. L.; Jones, Karen H.

    1992-01-01

    Reviews literature concerned with investigating psychiatric disturbances and genetic variables hypothesized as predisposing factors in etiology of anorexia nervosa. Gives particular emphasis to research which discusses association between anorexia nervosa and depression. Reviews psychopharmacological evidence and family genetics studies. Offers…

  16. Factors That Impair Wound Healing

    PubMed Central

    Anderson, Kristin; Hamm, Rose L.

    2014-01-01

    The body's response to tissue injury in a healthy individual is an intricate, sequential physiologic process that results in timely healing with full re-epithelialization, resolution of drainage, and return of function to the affected tissue. Chronic wounds, however, do not follow this sequence of events and can challenge the most experienced clinician if the underlying factors that are impairing wound healing are not identified. The purpose of this article is to present recent information about factors that impair wound healing with the underlying pathophysiological mechanism that interferes with the response to tissue injury. These factors include co-morbidities (diabetes, obesity, protein energy malnutrition), medications (steroids, non-steroidal anti-inflammatory drugs or NSAIDs, anti-rejection medications), oncology interventions (radiation, chemotherapy), and life style habits (smoking, alcohol abuse). Successful treatment of any chronic wound depends upon identification and management of the factors for each individual. PMID:26199879

  17. Environmental Factors Inducing Human Cancers

    PubMed Central

    Parsa, N

    2012-01-01

    Background An explosion of research has been done in discovering how human health is affected by environmental factors. I will discuss the impacts of environmental cancer causing factors and how they continue to cause multiple disruptions in cellular networking. Some risk factors may not cause cancer. Other factors initiate consecutive genetic mutations that would eventually alter the normal pathway of cellular proliferations and differentiation. Genetic mutations in four groups of genes; (Oncogenes, Tumor suppressor genes, Apoptosis genes and DNA repairing genes) play a vital role in altering the normal cell division. In recent years, molecular genetics have greatly increased our understanding of the basic mechanisms in cancer development and utilizing these molecular techniques for cancer screening, diagnosis, prognosis and therapies. Inhibition of carcinogenic exposures wherever possible should be the goal of cancer prevention programs to reduce exposures from all environmental carcinogens. PMID:23304670

  18. Hidden Risk Factors for Women

    MedlinePlus

    ... high cholesterol. “Those are the most common risk factors,” according to Steven J. Kittner, M.D., director of the Maryland Stroke Center at the University of Maryland School of Medicine in Baltimore. “But ...

  19. Factors influencing dust suppressant effectiveness

    SciTech Connect

    Copeland, C.R.; Eisele, T.C.; Chesney, D.J.; Kawatra, S.K.

    2008-11-15

    Water sprays are a common method used to reduce particulate matter (PM) emissions. Various factors such as wettability, surface area coverage, fine particle engulfment rates, interparticle adhesion forces, suppressant penetration and suppressant longevity have all been suggested as critical factors in achieving effective PM control. However, it has not been established which of these factors are the most important. Experimental work indicated that suppressant penetration is the most critical of these factors. The length of time after application that suppressants were effective was also improved by using hygroscopic reagents that retained moisture to prevent evaporation. Maximizing suppressant penetration and improving suppressant longevity led to an average 86% reduction in PM10 concentrations in laboratory dust tower tests.

  20. Genetic factors and systemic sclerosis.

    PubMed

    Murdaca, Giuseppe; Contatore, Miriam; Gulli, Rossella; Mandich, Paola; Puppo, Francesco

    2016-05-01

    Systemic sclerosis (SSc) is a rare connective tissue disease of unknown etiology characterized by chronic inflammation and fibrosis of the skin, vascular abnormalities, and variable involvement of organs including kidneys, gastrointestinal tract, heart, and lungs. SSc shows a complex etiology in which both environmental and genetic factors seem to influence the onset and outcome of the disease. We provide an extensive overview of the genetic factors and epigenetic modifications and what their knowledge has revealed in terms of etiopathogenesis of SSc. PMID:26826434

  1. Factors influencing dental decision making.

    PubMed

    Grembowski, D; Milgrom, P; Fiset, L

    1988-01-01

    In clinical decision making, dentists routinely choose between alternative treatments such as crown vs amalgam/composite buildup, root canal vs extraction, fixed bridge vs removable partial denture, and prophylaxis vs subgingival curettage or periodontal scaling. A number of technical and patient factors can influence dentists' choice of treatment in these situations; however, little is known about their relative importance. To address this issue, a list of technical (e.g., periodontal status and caries rate) and patient (e.g., cost and patient preference) factors possibly influencing choice of treatment was developed for each pair of services. Responding to a mail questionnaire, 156 general dentists in Washington State listed the top three factors influencing their choice of service in each pair. Results revealed that dentists took different factors into account in choosing among alternative treatments. Technical factors dominated over patient concerns; only about 33 percent of the dentists considered patient factors important in choosing alternative therapies. The latter group was less preventively oriented, were solo practitioners, worked longer hours, and had lower prices. Results suggest patients may have little influence on prescriptions of therapy among experienced general dentists. PMID:3045303

  2. Interstitial fibrosis and growth factors.

    PubMed Central

    Lasky, J A; Brody, A R

    2000-01-01

    Interstitial pulmonary fibrosis (IPF) is scarring of the lung caused by a variety of inhaled agents including mineral particles, organic dusts, and oxidant gases. The disease afflicts millions of individuals worldwide, and there are no effective therapeutic approaches. A major reason for this lack of useful treatments is that few of the molecular mechanisms of disease have been defined sufficiently to design appropriate targets for therapy. Our laboratory has focused on the molecular mechanisms through which three selected peptide growth factors could play a role in the development of IPF. Hundreds of growth factors and cytokines could be involved in the complex disease process. We are studying platelet-derived growth factor because it is the most potent mesenchymal cell mitogen yet described, transforming growth factor beta because it is a powerful inducer of extracellular matrix (scar tissue) components by mesenchymal cells, and tumor necrosis factor alpha because it is a pleiotropic cytokine that we and others have shown is essential for the development of IPF in animal models. This review describes some of the evidence from studies in humans, in animal models, and in vitro, that supports the growth factor hypothesis. The use of modern molecular and transgenic technologies could elucidate those targets that will allow effective therapeutic approaches. Images Figure 1 Figure 2 PMID:10931794

  3. Industrial Power Factor Analysis Guidebook.

    SciTech Connect

    Electrotek Concepts.

    1995-03-01

    Power factor is a way of measuring the percentage of reactive power in an electrical system. Reactive power represents wasted energy--electricity that does no useful work because the electrical current is out of phase with the voltage. Reactive power is used by inductive loads (such as, motors, transformers, fluorescent lights, arc welders and induction furnaces) to sustain their magnetic fields. Electric systems with many motors exhibit low power factors, increased conductor and transformer losses, and lower voltages. Utilities must supply both active and reactive power and compensate for these losses. Power factor can be improved by the addition of shunt capacitors. Capacitors act in opposition to inductive loads, thereby minimizing the reactive power required to serve them. In raising the power factor, shunt capacitors release energy to the system, reduce system losses, and ultimately decrease power costs. Improving system power factor can reduce reactive and active power losses for both industry and utilities through the addition of shunt capacitors. This Guide Book gives electric utility technical staff, industrial end-users, consultants and BPA employees a step-by-step method for evaluating the cost effectiveness of installing power factor correction capacitors in an industrial plant.

  4. Sexual harassment: identifying risk factors.

    PubMed

    O'Hare, E A; O'Donohue, W

    1998-12-01

    A new model of the etiology of sexual harassment, the four-factor model, is presented and compared with several models of sexual harassment including the biological model, the organizational model, the sociocultural model, and the sex role spillover model. A number of risk factors associated with sexually harassing behavior are examined within the framework of the four-factor model of sexual harassment. These include characteristics of the work environment (e.g., sexist attitudes among co-workers, unprofessional work environment, skewed sex ratios in the workplace, knowledge of grievance procedures for sexual harassment incidents) as well as personal characteristics of the subject (e.g., physical attractiveness, job status, sex-role). Subjects were 266 university female faculty, staff, and students who completed the Sexual Experience Questionnaire to assess the experience of sexual harassment and a questionnaire designed to assess the risk factors stated above. Results indicated that the four-factor model is a better predictor of sexual harassment than the alternative models. The risk factors most strongly associated with sexual harassment were an unprofessional environment in the workplace, sexist atmosphere, and lack of knowledge about the organization's formal grievance procedures. PMID:9883305

  5. Sparse Bayesian infinite factor models

    PubMed Central

    Bhattacharya, A.; Dunson, D. B.

    2011-01-01

    We focus on sparse modelling of high-dimensional covariance matrices using Bayesian latent factor models. We propose a multiplicative gamma process shrinkage prior on the factor loadings which allows introduction of infinitely many factors, with the loadings increasingly shrunk towards zero as the column index increases. We use our prior on a parameter-expanded loading matrix to avoid the order dependence typical in factor analysis models and develop an efficient Gibbs sampler that scales well as data dimensionality increases. The gain in efficiency is achieved by the joint conjugacy property of the proposed prior, which allows block updating of the loadings matrix. We propose an adaptive Gibbs sampler for automatically truncating the infinite loading matrix through selection of the number of important factors. Theoretical results are provided on the support of the prior and truncation approximation bounds. A fast algorithm is proposed to produce approximate Bayes estimates. Latent factor regression methods are developed for prediction and variable selection in applications with high-dimensional correlated predictors. Operating characteristics are assessed through simulation studies, and the approach is applied to predict survival times from gene expression data. PMID:23049129

  6. Microfluidic analysis of extracellular matrix-bFGF crosstalk on primary human myoblast chemoproliferation, chemokinesis, and chemotaxis

    PubMed Central

    Ferreira, Meghaan M.; Dewi, Ruby E.; Heilshorn, Sarah C.

    2015-01-01

    Exposing myoblasts to basic fibroblast growth factor (bFGF), which is released after muscle injury, results in receptor phosphorylation, faster migration, and increased proliferation. These effects occur on time scales that extend across three orders of magnitude (100 – 103 minutes). Finite element modeling of Transwell assays, which are traditionally used to assess chemotaxis, revealed that the bFGF gradient formed across the membrane pore is short-lived and diminishes 45% within the first minute. Thus, to evaluate bFGF-induced migration over 102 minutes, we employed a microfluidic assay capable of producing a stable, linear concentration gradient to perform single-cell analyses of chemokinesis and chemotaxis. We hypothesized that the composition of the underlying extracellular matrix (ECM) may affect the behavioral response of myoblasts to soluble bFGF, as previous work with other cell types has suggested crosstalk between integrin and fibroblast growth factor (FGF) receptors. Consistent with this notion, we found that bFGF significantly reduced the doubling time of myoblasts cultured on laminin but not fibronectin or collagen. Laminin also promoted significantly faster migration speeds (13.4 μm/h) than either fibronectin (10.6 μm/h) or collagen (7.6 μm/h) without bFGF stimulation. Chemokinesis driven by bFGF further increased migration speed in a strictly additive manner, resulting in an average increase of 2.3 μm/h across all ECMs tested. We observed relatively mild chemoattraction (~ 67% of myoblast population) in response to bFGF gradients of 3.2 ng/mL/mm regardless of ECM identity. Thus, while ECM-bFGF crosstalk did impact chemoproliferation, it did not have a significant effect on chemokinesis or chemotaxis. These data suggest that the main physiological effect of bFGF on myoblast migration is chemokinesis and that changes in the surrounding ECM, resulting from aging and/or disease may impact muscle regeneration by altering myoblast migration and

  7. Factors influencing healthcare service quality

    PubMed Central

    Mosadeghrad, Ali Mohammad

    2014-01-01

    Background: The main purpose of this study was to identify factors that influence healthcare quality in the Iranian context. Methods: Exploratory in-depth individual and focus group interviews were conducted with 222 healthcare stakeholders including healthcare providers, managers, policy-makers, and payers to identify factors affecting the quality of healthcare services provided in Iranian healthcare organisations. Results: Quality in healthcare is a production of cooperation between the patient and the healthcare provider in a supportive environment. Personal factors of the provider and the patient, and factors pertaining to the healthcare organisation, healthcare system, and the broader environment affect healthcare service quality. Healthcare quality can be improved by supportive visionary leadership, proper planning, education and training, availability of resources, effective management of resources, employees and processes, and collaboration and cooperation among providers. Conclusion: This article contributes to healthcare theory and practice by developing a conceptual framework that provides policy-makers and managers a practical understanding of factors that affect healthcare service quality. PMID:25114946

  8. General factors of the Korean exposure factors handbook.

    PubMed

    Jang, Jae-Yeon; Kim, So-Yeon; Kim, Sun-Ja; Lee, Kyung-Eun; Cheong, Hae-Kwan; Kim, Eun-Hye; Choi, Kyung-Ho; Kim, Young-Hee

    2014-01-01

    Risk assessment considers the situations and characteristics of the exposure environment and host. Various physiological variables of the human body reflects the characteristics of the population that can directly influence risk exposure. Therefore, identification of exposure factors based on the Korean population is required for appropriate risk assessment. It is expected that a handbook about general exposure factors will be used by professionals in many fields as well as the risk assessors of the health department. The process of developing the exposure factors handbook for the Korean population will be introduced in this article, with a specific focus on the general exposure factors including life expectancy, body weight, surface area, inhalation rates, amount of water intake, and soil ingestion targeting the Korean population. The researchers used national databases including the Life Table and the 2005 Time Use Survey from the National Statistical Office. The anthropometric study of size in Korea used the resources provided by the Korean Agency for Technology and Standards. In addition, direct measurement and questionnaire surveys of representative samples were performed to calculate the inhalation rate, drinking water intake, and soil ingestion. PMID:24570802

  9. [Success factors in hospital management].

    PubMed

    Heberer, M

    1998-12-01

    The hospital environment of most Western countries is currently undergoing dramatic changes. Competition among hospitals is increasing, and economic issues have become decisive factors for the allocation of medical care. Hospitals therefore require management tools to respond to these changes adequately. The balanced scorecard is a method of enabling development and implementation of a business strategy that equally respects the financial requirements, the needs of the customers, process development, and organizational learning. This method was used to derive generally valid success factors for hospital management based on an analysis of an academic hospital in Switzerland. Strategic management, the focus of medical services, customer orientation, and integration of professional groups across the hospital value chain were identified as success factors for hospital management. PMID:10023551

  10. Environmental risk factors for osteoporosis

    SciTech Connect

    Goyer, R.A.; Korach, K.S. ); Epstein, S. ); Bhattacharyya, M. ); Pounds, J. )

    1994-04-01

    Environmental risk factors for osteoporosis were reviewed at a conference held at the National Institute for Environmental Health Sciences 8-9 November 1993. The conference was co-sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Disease and the NIH Office of Research in Women's Health. The objective of the conference was to review what is known about risk factors for osteoporosis and to identify gaps in the present state of knowledge that might be addressed by future research. The conference was divided into two broad themes. The first session focused on current knowledge regarding etiology, risk factors, and approaches to clinical and laboratory diagnosis. This was followed by three sessions in which various environmental pollutants were discussed. Topics selected for review included environmental agents that interfere with bone and calcium metabolism, such as the toxic metals lead, cadmium, aluminum, and fluoride, natural and antiestrogens, calcium, and vitamin D.

  11. Success factors in technology development

    NASA Astrophysics Data System (ADS)

    Preston, John T.

    1995-01-01

    Universities in the U.S. have a significant impact on business through the transfer of technology. This paper describes goals and philosophy of the Technology Licensing Office at the Massachusetts Institute of Technology. This paper also relates the critical factors for susscessful technology transfer, particularly relating to new business formation. These critical factors include the quality of the technology, the quality of the management, the quality of the investor, the passion for success, and the image of the company. Descriptions of three different levels of investment are also given and the most successful level of investment for starting a new company is reviewed. Licensing to large companies is also briefly reviewed, as this type of licensing requires some different strategies than that of licensing to start-up companies. High quality critical factors and intelligent investment create rewards for the parties and successful ventures.

  12. Vascular growth factors in neuropsychiatry

    PubMed Central

    Newton, Samuel S.; Fournier, Neil M.; Duman, Ronald S.

    2014-01-01

    Recent advances in understanding the cellular and molecular basis of psychiatric illnesses have shed light on the important role played by trophic factors in modulating functional parameters associated with disease causality and drug action. Disease mechanisms are now thought to involve multiple cell types, including neurons and endothelial cells. These functionally distinct but interactively coupled cell types engage in cellular cross talk via shared and common signaling molecules. Dysregulation in their cellular signaling pathways influences brain function and alters behavioral performance. Multifunctional trophic factors such as VEGF and EPO that possess both neurotrophic and angiogenic actions are of particular interest due to their ability to rescue structural and plasticity deficits in neurons and vasculature. Obtaining insight into the behavioral, cellular and molecular actions of multi-functional trophic factors has the potential to open new and transformative therapeutic approaches. PMID:23475069

  13. Dnmt1/Transcription Factor Interactions

    PubMed Central

    Hervouet, Eric; Vallette, François M.; Cartron, Pierre-François

    2010-01-01

    DNA methylation inheritance is the process of copying, via the DNA methyltransferase 1 (Dnmt1), the pre-existing methylation patterns onto the new DNA strand during DNA replication. Experiments of chromatin immunoprecipitation, measurement of maintenance methyltransferase activity, proximity ligation in situ assays (P-LISA, Duolink/Olink), and transcription factor arrays demonstrate that Dnmt1 interacts with transcription factors to promote site-specific DNA methylation inheritance, while the Dnmt1-PCNA-UHRF1 complex promotes the DNA methylation inheritance without site preference. We also show that the Dnmt1-PCNA-UHRF1 and Dnmt1/transcription factor complexes methylate DNA by acting as a single player or in cooperation. Thus, our data establish that the copying of the pre-existing methylation pattern is governed by the orchestration of the untargeted and the targeted mechanisms of DNA methylation inheritance, which are themselves dictated by the partners of Dnmt1. PMID:21779454

  14. Isospectral potentials from modified factorization

    NASA Astrophysics Data System (ADS)

    Berger, Micheal S.; Ussembayev, Nail S.

    2010-08-01

    Factorization of quantum-mechanical potentials has a long history extending back to the earliest days of the subject. In the present article, the nonuniqueness of the factorization is exploited to derive new isospectral nonsingular potentials. Many one-parameter families of potentials can be generated from known potentials using a factorization that involves superpotentials defined in terms of excited states of a potential. For these cases an operator representation is available. If ladder operators are known for the original potential, then a straightforward procedure exists for defining such operators for its isospectral partners. The generality of the method is illustrated with a number of examples which may have many possible applications in atomic and molecular physics.

  15. Risk Factors in Adolescent Hypertension.

    PubMed

    Ewald, D Rose; Haldeman PhD, Lauren A

    2016-01-01

    Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

  16. Risk Factors in Adolescent Hypertension

    PubMed Central

    Ewald, D. Rose; Haldeman, Lauren A.

    2016-01-01

    Hypertension is a complex and multifaceted disease, with many contributing factors. While diet and nutrition are important influences, the confounding effects of overweight and obesity, metabolic and genetic factors, racial and ethnic predispositions, socioeconomic status, cultural influences, growth rate, and pubertal stage have even more influence and make diagnosis quite challenging. The prevalence of hypertension in adolescents far exceeds the numbers who have been diagnosed; studies have found that 75% or more go undiagnosed. This literature review summarizes the challenges of blood pressure classification in adolescents, discusses the impact of these confounding influences, and identifies actions that will improve diagnosis and treatment outcomes. PMID:27335997

  17. Bayes factors and multimodel inference

    USGS Publications Warehouse

    Link, W.A.; Barker, R.J.

    2009-01-01

    Multimodel inference has two main themes: model selection, and model averaging. Model averaging is a means of making inference conditional on a model set, rather than on a selected model, allowing formal recognition of the uncertainty associated with model choice. The Bayesian paradigm provides a natural framework for model averaging, and provides a context for evaluation of the commonly used AIC weights. We review Bayesian multimodel inference, noting the importance of Bayes factors. Noting the sensitivity of Bayes factors to the choice of priors on parameters, we define and propose nonpreferential priors as offering a reasonable standard for objective multimodel inference.

  18. [Environmental Risk Factors for Dementia].

    PubMed

    Tashiro, Yoshitaka; Kinoshita, Ayae

    2016-07-01

    Owing to recent advancements in imaging techniques and biomarker research, the natural history of Alzheimer's disease (AD) has become clear from the very first preclinical stage. According to the study, more than 20 years before the onset of AD, Aβ starts to accumulate in the brain. This induces neurofibrillary tangle formation in the cerebral isocortex, leading to cognitive decline. If this process is suppressed, disease activity can be controlled. However, at this point, the best and most realistic way to deal with AD is to target the environmental factors that have been identified as risk factors by epidemiological studies. PMID:27395468

  19. Growth factors in orthopedic surgery

    PubMed Central

    Zaharia, C; Despa, N; Simionescu, M; Jinga, V; Fleseriu, I

    2010-01-01

    Growth factors have represented an essential issue of interest for the researchers and clinicians in orthopedics and trauma over the last 40 years. In the last 10 to 15 years, the advances registered in this field have permitted the identification of the most active cellular and humoral factors as well as the improvement of their use in the orthopedic and trauma surgery. Their domain of application has been continuously enlarged and the results have been visible from the beginning. The authors present their appreciation on the actual state of this subject as well as their experience with results and related conclusions. PMID:20302195

  20. Factors associated with caffeine consumption.

    PubMed

    Brice, Carolyn F; Smith, Andrew P

    2002-01-01

    The main aim of this research was to identify factors that were related to caffeine consumption. From this investigation it can be concluded that coffee is the main source of caffeine and that consumption varies with time of day. Individuals may be utilising the arousing effects of caffeine by consuming it at times when arousal is low for instance to counteract sleep inertia or a post-lunch dip in alertness. There is, however, very little evidence to suggest that psychological characteristics such as personality traits or psychosocial factors are important in influencing caffeine consumption, although smoking was found to be related to the amount of caffeine consumed. PMID:11820098

  1. Human factors and risk assessment

    SciTech Connect

    Al-Minhali, A.

    1996-11-01

    A case study was presented in the 1994 Abu Dhabi International Exhibition and Conference (ADIPEC, 94) which discussed the importance of investigating human factors in the design of a high integrity protection system (HIPS) to be installed on an offshore high pressure gas platform, (SPE reference ADSPE 80). This paper will follow up on the design changes, installation and operation of the HIPS with emphasis on practical implications as a result of improper integration of human factors in the system reliability and risk assessment studies.

  2. Prognostic factors in lupus nephritis.

    PubMed

    Mok, C C

    2005-01-01

    Systemic lupus erythematosus (SLE) is a heterogeneous disorder and its renal manifestations are protean. The course and prognosis of lupus nephritis is dependent on a large number of demographic, histopathological, serological, racial, socioeconomic and time dependent factors. Moreover, the initial and maintenance therapeutic regimens may also influence the long term renal outcome. This article reviews the important prognostic factors that have been reported in literature. The management strategy of lupus nephritis should be individualized and based on a composite of these parameters. PMID:15732286

  3. Environmental factors associated with asthma.

    PubMed Central

    Walker, Bailus; Stokes, Lynette D.; Warren, Rueben

    2003-01-01

    Asthma, a disease of attacks and remission, continues to account for substantial morbidity and direct economic costs. Numerous studies--epidemiologic, toxicologic and clinical--present evidence for a broad spectrum of environmental risk factors associated with asthma. This review summarizes current thinking on a subset of these factors. Knowledge of potential environmental determinants of asthma is important to both the patient and healthcare professional in the application of multiple modalities of medical and environmental intervention for management of the development, and exacerbation of this chronic inflammatory disorder of the airways. PMID:12760611

  4. Deregulated transcription factors in leukemia.

    PubMed

    Shima, Yutaka; Kitabayashi, Issay

    2011-08-01

    Specific chromosomal translocations and other mutations associated with acute myeloblastic leukemia (AML) often involve transcription factors and transcriptional coactivators. Such target genes include AML1, C/EBPα, RARα, MOZ, p300/CBP, and MLL, all of which are important in the regulation of hematopoiesis. The resultant fusion or mutant proteins deregulate the transcription of the affected genes and disrupt their essential role in hematopoiesis, causing differentiation block and abnormal proliferation and/or survival. This review focuses on such transcription factors and coactivators, and describes their roles in leukemogenesis and hematopoiesis. PMID:21823042

  5. Psychological factors in the antarctic.

    PubMed

    Rothblum, E D

    1990-05-01

    For the people who live and work in the Antarctic, isolation and extreme physical conditions cause considerable stress. This article reviews psychological research on Antarctic residents, focusing on factors related to the isolation (effective personnel selection, positive adjustment, conflict, and reintegration into the home environment) and factors related to the physical environment (the extreme cold, high altitude, increased radiation, sensory deprivation, and seasonal changes in activity level). Finally, Antarctic research has been applied to the study of future space travel and space station habitation. PMID:2189993

  6. Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons

    PubMed Central

    Tang, Jin Bo; Wu, Ya Fang; Cao, Yi; Chen, Chuan Hao; Zhou, You Lang; Avanessian, Bella; Shimada, Masaru; Wang, Xiao Tian; Liu, Paul Y.

    2016-01-01

    Tendon injury during limb motion is common. Damaged tendons heal poorly and frequently undergo unpredictable ruptures or impaired motion due to insufficient innate healing capacity. By basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) gene therapy via adeno-associated viral type-2 (AAV2) vector to produce supernormal amount of bFGF or VEGF intrinsically in the tendon, we effectively corrected the insufficiency of the tendon healing capacity. This therapeutic approach (1) resulted in substantial amelioration of the low growth factor activity with significant increases in bFGF or VEGF from weeks 4 to 6 in the treated tendons (p < 0.05 or p < 0.01), (2) significantly promoted production of type I collagen and other extracellular molecules (p < 0.01) and accelerated cellular proliferation, and (3) significantly increased tendon strength by 68–91% from week 2 after AAV2-bFGF treatment and by 82–210% from week 3 after AAV2-VEGF compared with that of the controls (p < 0.05 or p < 0.01). Moreover, the transgene expression dissipated after healing was complete. These findings show that the gene transfers provide an optimistic solution to the insufficiencies of the intrinsic healing capacity of the tendon and offers an effective therapeutic possibility for patients with tendon disunion. PMID:26865366

  7. Basic FGF or VEGF gene therapy corrects insufficiency in the intrinsic healing capacity of tendons.

    PubMed

    Tang, Jin Bo; Wu, Ya Fang; Cao, Yi; Chen, Chuan Hao; Zhou, You Lang; Avanessian, Bella; Shimada, Masaru; Wang, Xiao Tian; Liu, Paul Y

    2016-01-01

    Tendon injury during limb motion is common. Damaged tendons heal poorly and frequently undergo unpredictable ruptures or impaired motion due to insufficient innate healing capacity. By basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) gene therapy via adeno-associated viral type-2 (AAV2) vector to produce supernormal amount of bFGF or VEGF intrinsically in the tendon, we effectively corrected the insufficiency of the tendon healing capacity. This therapeutic approach (1) resulted in substantial amelioration of the low growth factor activity with significant increases in bFGF or VEGF from weeks 4 to 6 in the treated tendons (p < 0.05 or p < 0.01), (2) significantly promoted production of type I collagen and other extracellular molecules (p < 0.01) and accelerated cellular proliferation, and (3) significantly increased tendon strength by 68-91% from week 2 after AAV2-bFGF treatment and by 82-210% from week 3 after AAV2-VEGF compared with that of the controls (p < 0.05 or p < 0.01). Moreover, the transgene expression dissipated after healing was complete. These findings show that the gene transfers provide an optimistic solution to the insufficiencies of the intrinsic healing capacity of the tendon and offers an effective therapeutic possibility for patients with tendon disunion. PMID:26865366

  8. Synthetic Division and Matrix Factorization

    ERIC Educational Resources Information Center

    Barabe, Samuel; Dubeau, Franc

    2007-01-01

    Synthetic division is viewed as a change of basis for polynomials written under the Newton form. Then, the transition matrices obtained from a sequence of changes of basis are used to factorize the inverse of a bidiagonal matrix or a block bidiagonal matrix.

  9. Neurophysiological Factors in Spatial Development.

    ERIC Educational Resources Information Center

    Harris, Lauren Jay

    Some of the major lines of investigation that point to neurophysiological factors in spatial skill are presented. These lines include: the two hemispheres of the brain, recent studies, tachistoscopic studies, morphological differences between the cerebral hemispheres, Geschwind and Levitsky's discovery, cerebral dominance re-examined, sex…

  10. Employability Development Teams: Cohesion Factors

    ERIC Educational Resources Information Center

    Johnson, Douglas W.; Munger, Paul F.

    1972-01-01

    In this study the researchers attempted to analyze the factors of age, sex, racial-ethnic background, operational life of the team, educational status, leader status, team size, caseload size, and the location of program site in terms of their potential effects upon team cohesion. (Author)

  11. Time dependent view factor methods

    SciTech Connect

    Kirkpatrick, R.C.

    1998-03-01

    View factors have been used for treating radiation transport between opaque surfaces bounding a transparent medium for several decades. However, in recent years they have been applied to problems involving intense bursts of radiation in enclosed volumes such as in the laser fusion hohlraums. In these problems, several aspects require treatment of time dependence.

  12. On Techniques of Prime Factorization

    ERIC Educational Resources Information Center

    Cohen, David B.

    1977-01-01

    This article gives two methods of resolving natural numbers into prime factors. Depending upon the number that is being resolved, one method may be better to use than the other. However, it is difficult to tell beforehand which is the better method to employ. Examples are given. (Author/MA)

  13. Factors Affecting the Tutoring Process.

    ERIC Educational Resources Information Center

    Hartman, Hope J.

    1990-01-01

    Analyzes factors internal to the tutor and tutee (i.e., cognition, metacognition, and affect) and external to them (e.g., teacher/tutor background knowledge, educational environment, content to be learned, socioeconomic status, family background, and cultural forces) that influence the tutoring process. Suggests a theoretical framework for…

  14. Factors Influencing College Science Success

    ERIC Educational Resources Information Center

    Tai, Robert H.; Sadler, Philip M.; Mintzes, Joel J.

    2006-01-01

    In this paper, the authors report some of the salient findings of a large-scale, four-year national study, conducted at the Harvard-Smithsonian Center for Astrophysics, entitled "Factors Influencing College Science Success" (FICSS), which surveyed college students who enrolled in first-year biology, chemistry, and physics courses throughout the…

  15. Heredity Factors in Spatial Visualization.

    ERIC Educational Resources Information Center

    Vandenberg, S. G.

    Spatial visualization is not yet clearly understood. Some researchers have concluded that two factors or abilities are involved, spatial orientation and spatial visualization. Different definitions and different tests have been proposed for these two abilities. Several studies indicate that women generally perform more poorly on spatial tests than…

  16. [Psoriasis and cardiovascular risk factors].

    PubMed

    Tal, Roy; Pavlovsky, Lev; David, Michael

    2012-10-01

    Psoriasis is a common inflammatory skin disease which may dramatically affect patients' lives. This chronic disease is characterized by a protracted course of alternating remissions and relapses. In recent years, the attention of researchers has focused on the association between psoriasis and cardiovascular disease risk factors. This review summarizes the literature on this topic with an emphasis on research conducted in Israel. PMID:23316664

  17. Entropy algebras and Birkhoff factorization

    NASA Astrophysics Data System (ADS)

    Marcolli, Matilde; Tedeschi, Nicolas

    2015-11-01

    We develop notions of Rota-Baxter structures and associated Birkhoff factorizations, in the context of min-plus semirings and their thermodynamic deformations, including deformations arising from quantum information measures such as the von Neumann entropy. We consider examples related to Manin's renormalization and computation program, to Markov random fields and to counting functions and zeta functions of algebraic varieties.

  18. R factors from Serratia marcescens.

    PubMed

    Hedges, R W; Rodriguez-Lemoine, V; Datta, N

    1975-01-01

    In recent years, Serratia marcescens has become established in certain localities as an agent of hospital infection and cross-infection (Clayton & von Graevenitz, 1966; Wilfert, Barrett & Kass, 1968; Davis, Foltz & Blakemore, 1970; Wilkowske, Washington, Martin & Ritts, 1970). In general, strains of S. marcescens isolated from infective lesions differ from those from other sources in being non-pigmented and antibiotic resistant (Ewing, Johnson & David, 1962; Clayton & von Graevenitz, 1966). Medeiros & O'Brien (1969) and Schaefler et al. (1971) described strains of S. marcescens, isolated from hospital patients, which were able to transfer R factors to Escherichia coli. Transfer of resistance to E. coli has also been reported from strains of S. marcescens isolated in France (Grimont & Dulong de Rosnay, 1972; Scavizzi, 1972; Lemosquet-Villemon, Morel & Freymuth, 1973)9 We have collected strains of S. marcescens, most, but not all, clinical isolates, from widely separate geographical areas; each strain was tested for antibiotic resistance and for R factors transmissible to E. coli K129 The R factors were classified by compatibility in K12 (Datta, 1974). Our purpose was to find out how much of the antibiotic resistance observed in S. marcescens is characteristic of that genus and to what extent it is shared with other bacterial genera (Coetzee, Datta & Hedges, 1972; Datta & Hedges, 1972a; Hedges, 1974). The R factors described by Medeiros & O'Brien (1969) and Lemosquet-Villemon et al. (1973) were included in this study. PMID:1089756

  19. Stress Factors among College Educators.

    ERIC Educational Resources Information Center

    Grant, George Farid

    Stress factors affecting community college educators in Ontario were determined using a questionnaire survey. The effect of demographic variables (campus location, program types and specialization, gender, age, and years taught at the college) on perceived stress levels were evaluated. Participants rated their present stress levels on a…

  20. 2012 Critical Success Factors Report

    ERIC Educational Resources Information Center

    North Carolina Community College System (NJ1), 2012

    2012-01-01

    The Critical Success Factors Report is the North Carolina Community College System's major accountability document. This annual performance report is based on data compiled from the previous year and serves to inform colleges and the public on the performance of North Carolina's 58 community colleges. In 1993, the State Board of Community Colleges…

  1. 2011 Critical Success Factors Report

    ERIC Educational Resources Information Center

    North Carolina Community College System (NJ1), 2011

    2011-01-01

    The Critical Success Factors Report is the North Carolina Community College System's major accountability document. This annual performance report serves to inform colleges and the public on the performance of North Carolina's 58 community colleges. In 1993, the State Board of Community Colleges began monitoring performance data on specific…

  2. Human factors in underwater systems.

    PubMed

    Crosson, D

    1993-10-01

    Applications of human factors to undersea engineering and the relationship to aerospace science are explored. Cooperative ventures include the TEKTITE underwater habitat and development of better procedures to prevent decompression sickness. Other research involved the use of alternate gases in diving systems, remote-operation vehicles, and diving system tests. PMID:11541030

  3. Inner City Human Factors Evaluation.

    ERIC Educational Resources Information Center

    Griffith, Albert R.

    This evaluation examines the degree to which human factors support, relate to, or impede the successful achievements of Polaroid's Inner City mission to provide on-the-job training for the career development of disadvantaged workers. The program is cited as a model for industry-based career education. Background information is provided on the…

  4. Transcription factor-based biosensor

    SciTech Connect

    Dietrich, Jeffrey A; Keasling, Jay D

    2013-10-08

    The present invention provides for a system comprising a BmoR transcription factor, a .sigma..sup.54-RNA polymerase, and a pBMO promoter operatively linked to a reporter gene, wherein the pBMO promoter is capable of expression of the reporter gene with an activated form of the BmoR and the .sigma..sup.54-RNA polymerase.

  5. Soft Factors Influence College Enrollment

    ERIC Educational Resources Information Center

    Fogg, Neeta P.; Harrington, Paul E.

    2010-01-01

    Evidence about the role that "soft factors" like student engagement and school environment play in influencing whether high school students go on to enroll in college is hard to come by. Over the past two years, the Center for Labor Market Studies (CLMS) of Northeastern University, with support from the Nellie Mae Education Foundation and the…

  6. Highly parallel sparse Cholesky factorization

    NASA Technical Reports Server (NTRS)

    Gilbert, John R.; Schreiber, Robert

    1990-01-01

    Several fine grained parallel algorithms were developed and compared to compute the Cholesky factorization of a sparse matrix. The experimental implementations are on the Connection Machine, a distributed memory SIMD machine whose programming model conceptually supplies one processor per data element. In contrast to special purpose algorithms in which the matrix structure conforms to the connection structure of the machine, the focus is on matrices with arbitrary sparsity structure. The most promising algorithm is one whose inner loop performs several dense factorizations simultaneously on a 2-D grid of processors. Virtually any massively parallel dense factorization algorithm can be used as the key subroutine. The sparse code attains execution rates comparable to those of the dense subroutine. Although at present architectural limitations prevent the dense factorization from realizing its potential efficiency, it is concluded that a regular data parallel architecture can be used efficiently to solve arbitrarily structured sparse problems. A performance model is also presented and it is used to analyze the algorithms.

  7. Cognitive Factors in Academic Achievement.

    ERIC Educational Resources Information Center

    Cuasay, Peter

    1992-01-01

    This review explores the factors of cognitive processing, style, and metacognitive organization as they contribute to academic success. Specific discussions consider aspects of short- and long-term memory, including how these affect learning and academic performance, and the keys to attaining long-term memory capability by involving redundancy,…

  8. Risk factors for postoperative ileus

    PubMed Central

    Kutun, Suat; Ulucanlar, Haluk; Tarcan, Oguz; Demir, Abdullah; Cetin, Abdullah

    2011-01-01

    Purpose This study aimed to examine extended postoperative ileus and its risk factors in patients who have undergone abdominal surgery, and discuss the techniques of prevention and management thereof the light of related risk factors connected with our study. Methods This prospective study involved 103 patients who had undergone abdominal surgery. The effects of age, gender, diagnosis, surgical operation conducted, excessive small intestine manipulation, opioid analgesic usage time, and systemic inflammation on the time required for the restoration of intestinal motility were investigated. The parameters were investigated prospectively. Results Regarding the factors that affected the restoration of gastrointestinal motility, resection operation type, longer operation period, longer opioid analgesics use period, longer nasogastric catheter use period, and the presence of systemic inflammation were shown to retard bowel motility for 3 days or more. Conclusion Our study confirmed that unnecessary analgesics use in patients with pain tolerance with non-steroid anti-inflammatory drugs, excessive small bowel manipulation, prolonged nasogastric catheter use have a direct negative effect on gastrointestinal motility. Considering that an exact treatment for postoperative ileus has not yet been established, and in light of the risk factors mentioned above, we regard that prevention of postoperative ileus is the most effective way of coping with intestinal dysmotility. PMID:22111079

  9. Efficient networks for quantum factoring

    SciTech Connect

    Beckman, D.; Chari, A.N.; Devabhaktuni, S.; Preskill, J.

    1996-08-01

    We consider how to optimize memory use and computation time in operating a quantum computer. In particular, we estimate the number of memory quantum bits (qubits) and the number of operations required to perform factorization, using the algorithm suggested by Shor [in {ital Proceedings} {ital of} {ital the} 35{ital th} {ital Annual} {ital Symposium} {ital on} {ital Foundations} {ital of} {ital Computer} {ital Science}, edited by S. Goldwasser (IEEE Computer Society, Los Alamitos, CA, 1994), p. 124]. A {ital K}-bit number can be factored in time of order {ital K}{sup 3} using a machine capable of storing 5{ital K}+1 qubits. Evaluation of the modular exponential function (the bottleneck of Shor{close_quote}s algorithm) could be achieved with about 72{ital K}{sup 3} elementary quantum gates; implementation using a linear ion trap would require about 396{ital K}{sup 3} laser pulses. A proof-of-principle demonstration of quantum factoring (factorization of 15) could be performed with only 6 trapped ions and 38 laser pulses. Though the ion trap may never be a useful computer, it will be a powerful device for exploring experimentally the properties of entangled quantum states. {copyright} {ital 1996 The American Physical Society.}

  10. NASA Space Human Factors Program

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This booklet briefly and succinctly treats 23 topics of particular interest to the NASA Space Human Factors Program. Most articles are by different authors who are mainly NASA Johnson or NASA Ames personnel. Representative topics covered include mental workload and performance in space, light effects on Circadian rhythms, human sleep, human reasoning, microgravity effects and automation and crew performance.

  11. The Environmental Factors Influencing Attrition.

    ERIC Educational Resources Information Center

    Villella, Edward F.

    1986-01-01

    Offers an economics/business-management perspective on student attrition, focusing on the external macro-environment (including such factors as government funding of education, changing enrollment patterns, and the increased number of postsecondary institutions) and the internal micro-environment (exhibiting characteristics of intangibility,…

  12. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  13. Transforming Rubrics Using Factor Analysis

    ERIC Educational Resources Information Center

    Baryla, Ed; Shelley, Gary; Trainor, William

    2012-01-01

    Student learning and program effectiveness is often assessed using rubrics. While much time and effort may go into their creation, it is equally important to assess how effective and efficient the rubrics actually are in terms of measuring competencies over a number of criteria. This study demonstrates the use of common factor analysis to identify…

  14. Nutritional factors in human cancers.

    PubMed

    Giovannucci, E

    1999-01-01

    A variety of external factors interacting with genetic susceptibility influence the carcinogenesis process. External factors including oxidative compounds, electrophilic agents, and chronic infections may enhance genetic damage. In addition, various hormonal factors which influence growth and differentiation are critically important in the carcinogenic process. Diet and nutrition can influence these processes directly in the gastrointestinal tract by providing bioactive compounds to specific tissues via the circulatory system, or by modulating hormone levels. Differences in certain dietary patterns among populations explain a substantial proportion of cancers of the colon, prostate and breast. These malignancies are largely influenced by a combination of factors related to diet and nutrition. Their causes are multifactorial and complex, but a major influence is the widespread availability of energy-dense, highly processed and refined foods that are also deplete in fiber. These dietary patterns in combination with physical inactivity contribute to obesity and metabolic consequences such as increased levels of IGF-1, insulin, estrogen, and possibly testosterone. These hormones tend to promote cellular growth. For prostate cancer, epidemiologic studies consistently show a positive association with high consumption of milk, dairy products, and meats. These dietary factors tend to decrease 1.25(OH)2 vitamin D, a cell differentiator, and low levels of this hormone may enhance prostate carcinogenesis. While the nutritional modulation of growth-enhancing and differentiating hormones is likely to contribute to the high prevalence of breast, colorectal, prostate, and several other cancers in the Western world, these cancers are relatively rare in less economically developed countries, where malignancies of the upper gastrointestinal tract are quite common. The major causes of upper gastrointestinal tract cancers are likely related to various food practices or preservation

  15. Motivating factors among Iranian nurses

    PubMed Central

    Negarandeh, Reza; Dehghan-Nayeri, Nahid; Ghasemi, Elham

    2015-01-01

    Background: One of the most important challenges of Iranian health care system is “quality of care,” and it is assumed that motivated nurses are more ready to provide better care. There are limited studies investigating Iranian nurses’ motivations; however, factors which motivate them have not been studied yet. Identifying the motivating factors enables nurse managers to inspire nurses for continuous quality improvement. The aim of this study was to identify motivating factors for Iranian hospital nurses. Materials and Methods: This is a cross-sectional descriptive study in which 310 nurses working at 14 hospitals of Tehran University of Medical Sciences were selected by proportionate stratified random sampling. Data were collected in 2010 by a researcher-developed questionnaire. Descriptive statistics and independent t-test, analysis of variance, Tukey post-hoc test, Chi-Square and Fisher's exact test were used for statistical analysis by Statistical Package for Social Sciences (SPSS) version 16. Results: The mean score of motivation was 90.53 ± 10.76 (range: 59–121). Four motivating factors including “career development” (22.63 ± 5.66), “job characteristics” (34.29 ± 4), “job authority” (18.48 ± 2.79), and “recognition” (15.12 ± 2.5) were recognized. The least mean of the motivation score, considering the number of items, was 3.23 for career development, while the highest mean was 3.81 for job characteristics. Conclusions: The findings showed that motivation of nurses was at a medium level, which calls for improvement. The factors that have the greatest potential to motivate nurses were identified in this study and they can help managers to achieve the goal of continuous quality improvement. PMID:26257797

  16. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  17. Factors influencing permanent teeth eruption. Part one--general factors.

    PubMed

    Almonaitiene, Ruta; Balciuniene, Irena; Tutkuviene, Janina

    2010-01-01

    Variation in the normal eruption of teeth is a common finding, but significant deviation from established norms should alert the clinician to take some diagnostic procedures in order to evaluate patient health and development. Disturbance in tooth eruption time could be a symptom of general condition or indication of altered physiology and craniofacial development. The aim of this review is to analyze general factors that could influence permanent teeth eruption. The articles from 1965 to 2009 in English related to topic were identified. 84 articles were selected for data collection. Although permanent teeth eruption is under significant genetic control, various general factors such as gender, socioeconomic status, craniofacial morphology, body composition can influence this process. Most significant disturbance in teeth emergence is caused by systemic diseases and syndromes. PMID:21063135

  18. Food ingestion factors of the Korean exposure factors handbook.

    PubMed

    Jang, Jae-Yeon; Jo, Soo-Nam; Kim, Sun-Ja; Myung, Hyung-Nam; Kim, Cho-Il

    2014-01-01

    The purpose of this study was to establish food ingestion factors needed to assess exposure to contaminants through food ingestion. The study reclassified the raw data of the Korean National Health and Nutrition Examination Survey in 2001 into 12 subcategories including grain products, meat products, fish and shellfish, and vegetables for international comparability of exposure evaluation. The criteria for food intake calculation were unified according to the characteristics of food groups, and recommended values for food ingestion factors were calculated through moisture correction and recategorization of cooked, processed, and mixed foods for each group. The average intake rate for grain and grain products was 6.25 g/kg-d per capita and the men's intake rate was approximately 8% higher than that of the women. The average intake rate of meat and meat products was 1.62 g/kg-d per capita and the men's intake rate was 30% higher than that of the women, on average. The average intake rate of fish and shellfish was 1.53 g/kg-d per capita, and the age groups of 1 to 2 and 3 to 6 recorded higher capita intake rates than other age groups, 2.62 g/kg-d and 2.25 g/kg-d, respectively. The average intake rate of vegetables was 6.47 g/kg-d per capita, with the age group of 1 to 2 recording the highest per capita intake rate of 9.79 g/kg-d and that of 13 to 19 recording the lowest mean. The study also offers recommended values for food ingestion factors of other food groups by gender, age, and region. The food ingestion exposure factors will need future updates in consideration of ongoing changes in food consumption behavior. PMID:24570803

  19. Sequential coagulation factor VIIa domain binding to tissue factor

    SciTech Connect

    Oesterlund, Maria; Persson, Egon; Freskgard, Per-Ola . E-mail: msv@ifm.liu.se

    2005-12-02

    Vessel wall tissue factor (TF) is exposed to blood upon vascular damage which enables association with factor VIIa (FVIIa). This leads to initiation of the blood coagulation cascade through localization and allosteric induction of FVIIa procoagulant activity. To examine the docking pathway of the FVIIa-TF complex, various residues in the extracellular part of TF (sTF) that are known to interact with FVIIa were replaced with cysteines labelled with a fluorescent probe. By using stopped-flow fluorescence kinetic measurements in combination with surface plasmon resonance analysis, we studied the association of the resulting sTF variants with FVIIa. We found the docking trajectory to be a sequence of events in which the protease domain of FVIIa initiates contact with sTF. Thereafter, the two proteins are tethered via the first epidermal growth factor-like and finally the {gamma}-carboxyglutamic acid (Gla) domain. The two labelled sTF residues interacting with the protease domain of FVIIa bind or become eventually ordered at different rates, revealing kinetic details pertinent to the allosteric activation of FVIIa by sTF. Moreover, when the Gla domain of FVIIa is removed the difference in the rate of association for the remaining domains is much more pronounced.

  20. About Alzheimer's Disease: Risk Factors and Prevention

    MedlinePlus

    ... About ADEAR About Alzheimer's Disease: Risk Factors and Prevention We can’t control some risk factors for ... as well. NIA Information on Risk Factors and Prevention 2014-2015 Alzheimer's Disease Progress Report: Advancing Research ...

  1. Genetics Home Reference: factor V deficiency

    MedlinePlus

    ... Genetics Home Health Conditions factor V deficiency factor V deficiency Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Factor V deficiency is a rare bleeding disorder. The signs ...

  2. XAS Study at Mo and Co K-Edges of the Sulfidation of a CoMo / Al2O3 Hydrotreating Catalyst

    NASA Astrophysics Data System (ADS)

    Pichon, C.; Gandubert, A. D.; Legens, C.; Guillaume, D.

    2007-02-01

    Because of its impact on environment, the removal of sulfur is an indispensable step, called hydrotreatment, in the refining of petroleum. One of the most commonly used hydrotreating catalysts is CoMo-type catalyst which is composed of molybdenum disulfide slabs promoted by cobalt atoms (CoMoS phase) and well dispersed on a high specific area alumina. As far as the highest sulfur content allowed in gasoline and diesel is continually decreasing, more and more efficient and active hydrotreating catalysts are required. In order to optimize the reactivity of the CoMo-type catalyst in hydrotreatment, a better understanding of the processes used to produce the active phase (CoMoS slabs) of the catalyst is necessary. The study reported here deals with the sulfiding mechanism of the slabs and the influence of temperature on the phenomenon. Ex situ X-ray absorption spectroscopy (XANES and EXAFS) was used to study the evolution of the structure of CoMo-type catalyst sulfided at various temperatures (from 293 to 873 K). XAS analysis was performed at both molybdenum and cobalt K-edges to obtain a cross-characterization of the sulfidation of the slabs. It evidenced the formation of various compounds, including two molybdenum oxides, MoS3 (or MoS3-like compound) and Co9S8, at specific steps of the sulfiding process. It showed the role of intermediate played by MoS3 (or MoS3-like compound) during the formation of the slabs and the competition between the appearance of promoted slabs (CoMoS phase) and Co9S8. At last, it leaded to the proposal of a mechanism for the sulfidation of the catalyst.

  3. XAS Study at Mo and Co K-Edges of the Sulfidation of a CoMo / Al2O3 Hydrotreating Catalyst

    SciTech Connect

    Pichon, C.; Gandubert, A. D.; Legens, C.; Guillaume, D.

    2007-02-02

    Because of its impact on environment, the removal of sulfur is an indispensable step, called hydrotreatment, in the refining of petroleum. One of the most commonly used hydrotreating catalysts is CoMo-type catalyst which is composed of molybdenum disulfide slabs promoted by cobalt atoms (CoMoS phase) and well dispersed on a high specific area alumina. As far as the highest sulfur content allowed in gasoline and diesel is continually decreasing, more and more efficient and active hydrotreating catalysts are required. In order to optimize the reactivity of the CoMo-type catalyst in hydrotreatment, a better understanding of the processes used to produce the active phase (CoMoS slabs) of the catalyst is necessary. The study reported here deals with the sulfiding mechanism of the slabs and the influence of temperature on the phenomenon. Ex situ X-ray absorption spectroscopy (XANES and EXAFS) was used to study the evolution of the structure of CoMo-type catalyst sulfided at various temperatures (from 293 to 873 K). XAS analysis was performed at both molybdenum and cobalt K-edges to obtain a cross-characterization of the sulfidation of the slabs. It evidenced the formation of various compounds, including two molybdenum oxides, MoS3 (or MoS3-like compound) and Co9S8, at specific steps of the sulfiding process. It showed the role of intermediate played by MoS3 (or MoS3-like compound) during the formation of the slabs and the competition between the appearance of promoted slabs (CoMoS phase) and Co9S8. At last, it leaded to the proposal of a mechanism for the sulfidation of the catalyst.

  4. Shot-noise Fano factor

    NASA Astrophysics Data System (ADS)

    Rajdl, Kamil; Lansky, Petr

    2015-11-01

    A variability measure of the times of uniform events based on a shot-noise process is proposed and studied. The measure is inspired by the Fano factor, which we generalize by considering the time-weighted influence of the events given by a shot-noise response function. The sequence of events is assumed to be an equilibrium renewal process, and based on this assumption we present formulas describing the behavior of the variability measure. The formulas are derived for a general response function, restricted only by some natural conditions, but the main focus is given to the shot noise with exponential decrease. The proposed measure is analyzed and compared with the Fano factor.

  5. Nutritional Factors Affecting Mental Health.

    PubMed

    Lim, So Young; Kim, Eun Jin; Kim, Arang; Lee, Hee Jae; Choi, Hyun Jin; Yang, Soo Jin

    2016-07-01

    Dietary intake and nutritional status of individuals are important factors affecting mental health and the development of psychiatric disorders. Majority of scientific evidence relating to mental health focuses on depression, cognitive function, and dementia, and limited evidence is available about other psychiatric disorders including schizophrenia. As life span of human being is increasing, the more the prevalence of mental disorders is, the more attention rises. Lists of suggested nutritional components that may be beneficial for mental health are omega-3 fatty acids, phospholipids, cholesterol, niacin, folate, vitamin B6, and vitamin B12. Saturated fat and simple sugar are considered detrimental to cognitive function. Evidence on the effect of cholesterol is conflicting; however, in general, blood cholesterol levels are negatively associated with the risk of depression. Collectively, the aims of this review are to introduce known nutritional factors for mental health, and to discuss recent issues of the nutritional impact on cognitive function and healthy brain aging. PMID:27482518

  6. Endometriosis, Angiogenesis and Tissue Factor

    PubMed Central

    Krikun, Graciela

    2012-01-01

    Tissue factor (TF), is a cellular receptor that binds the factor VII/VIIa to initiate the blood coagulation cascade. In addition to its role as the initiator of the hemostatic cascade, TF is known to be involved in angiogenesis via intracellular signaling that utilizes the protease activated receptor-2 (PAR-2). We now review the physiologic expression of TF in the endometrium and its altered expression in multiple cell types derived from eutopic and ectopic endometrium from women with endometriosis compared with normal endometrium. Our findings suggest that TF might be an ideal target for therapeutic intervention in endometriosis. We have employed a novel immunoconjugate molecule known as Icon and were able to eradicate endometrial lesions in a mouse model of endometriosis without affecting fertility. These findings have major implications for potential treatment in humans. PMID:24278684

  7. Human factors and quality improvement.

    PubMed

    Handyside, James; Suresh, Gautham

    2010-03-01

    Human factors analysis (HFE) presents a formidable contribution to quality improvement (QI) in the neonatal intensive care unit (NICU). The science behind the fundamental principles concerning the design of work systems that match the needs of the people who work in them is sound and is applied widely in other safety critical situations. Early application of HFE in NICUs has shown the usefulness of these methods for frontline teams working to improve quality, reliability, and safety. The inclusion of human factors considerations in the design of structure and process has the potential to improve outcomes for patients and families and to improve the comfort and usability of work systems for providers who work in them. New technologies and continual change must be informed and designed through the application of HFE methods and principles to realize the full potential of QI. PMID:20363451

  8. [Epidemiologic factors in ovarian cancer].

    PubMed

    Curie, P; Sussmann, M; Treisser, A; Renaud, R

    1985-05-01

    Ovarian carcinoma is the most severe gynecological cancer with an overall incidence of 12 per 1000 Americans or Europeans developing it over 40 years of age. Only 3 of the 12 cases will receive efficient care because the diagnosis will be made too late. This study reveals the principal risk factors i.e. upper socioeconomic echelon, ovarian function uninterrupted by a pregnancy or usage of oral contraceptives, anamnestic evidence of ovarian carcinoma in the family, some hereditary disorders, external insults (talcum powder). The synthesis of these various risk factors permits a comprehensive review of the hypotheses of pathogenesis concerning recurrence of tumors. But corollary epidemiologic studies are still needed to try to define better the high risk groups whose follow-up systematic detection and testing is a priority. PMID:4023542

  9. Prognostic factors in histiocytosis X.

    PubMed

    Lahey, M E

    1981-01-01

    It is now clear that the prognosis in children with histiocytosis X has improved considerable over the past few years. To be sure, patients with solitary lesions have an excellent prognosis. Whereas the outlook for patients with significant visceral involvement is not as good as those with bone lesions only, the outlook is by no means hopeless, as was once thought. A number of prognostic factors have been reviewed here. The most significant of these factors at the present time would appear to be age of onset of the disease, extent of involvement, the rapidity of progression of the disease, and, in particular, the presence or absence of dysfunction of such crucial organ systems as liver, lung, and hemopoietic system. Further studies of the significance of histologic features and immunologic findings are clearly needed to further our understanding of this disorder. PMID:6972178

  10. Shot-noise Fano factor.

    PubMed

    Rajdl, Kamil; Lansky, Petr

    2015-11-01

    A variability measure of the times of uniform events based on a shot-noise process is proposed and studied. The measure is inspired by the Fano factor, which we generalize by considering the time-weighted influence of the events given by a shot-noise response function. The sequence of events is assumed to be an equilibrium renewal process, and based on this assumption we present formulas describing the behavior of the variability measure. The formulas are derived for a general response function, restricted only by some natural conditions, but the main focus is given to the shot noise with exponential decrease. The proposed measure is analyzed and compared with the Fano factor. PMID:26651674

  11. Nutritional Factors Affecting Mental Health

    PubMed Central

    Lim, So Young; Kim, Eun Jin; Kim, Arang; Lee, Hee Jae; Choi, Hyun Jin

    2016-01-01

    Dietary intake and nutritional status of individuals are important factors affecting mental health and the development of psychiatric disorders. Majority of scientific evidence relating to mental health focuses on depression, cognitive function, and dementia, and limited evidence is available about other psychiatric disorders including schizophrenia. As life span of human being is increasing, the more the prevalence of mental disorders is, the more attention rises. Lists of suggested nutritional components that may be beneficial for mental health are omega-3 fatty acids, phospholipids, cholesterol, niacin, folate, vitamin B6, and vitamin B12. Saturated fat and simple sugar are considered detrimental to cognitive function. Evidence on the effect of cholesterol is conflicting; however, in general, blood cholesterol levels are negatively associated with the risk of depression. Collectively, the aims of this review are to introduce known nutritional factors for mental health, and to discuss recent issues of the nutritional impact on cognitive function and healthy brain aging. PMID:27482518

  12. Factors influencing pacing in triathlon

    PubMed Central

    Wu, Sam SX; Peiffer, Jeremiah J; Brisswalter, Jeanick; Nosaka, Kazunori; Abbiss, Chris R

    2014-01-01

    Triathlon is a multisport event consisting of sequential swim, cycle, and run disciplines performed over a variety of distances. This complex and unique sport requires athletes to appropriately distribute their speed or energy expenditure (ie, pacing) within each discipline as well as over the entire event. As with most physical activity, the regulation of pacing in triathlon may be influenced by a multitude of intrinsic and extrinsic factors. The majority of current research focuses mainly on the Olympic distance, whilst much less literature is available on other triathlon distances such as the sprint, half-Ironman, and Ironman distances. Furthermore, little is understood regarding the specific physiological, environmental, and interdisciplinary effects on pacing. Therefore, this article discusses the pacing strategies observed in triathlon across different distances, and elucidates the possible factors influencing pacing within the three specific disciplines of a triathlon. PMID:25258562

  13. [Suicide - background, epidemiology, risk factors].

    PubMed

    Ajdacic-Gross, Vladeta

    2015-10-01

    Suicide research, in particular epidemiology, comprises a huge amount of data. However, the theoretical understanding clearly lags behind the empirical knowledge. Suicide, suicide attempts and other suicidal behaviors are more heterogeneous than most explanatory approaches would assume. The most important recent contributions to a better understanding have come from selected epidemiological findings and, interestingly, prevention. This article provides an overview of epidemiological findings, the most relevant risk factors and conclusions related to successful preventive efforts. PMID:26423878

  14. Human factors in incident reporting

    NASA Technical Reports Server (NTRS)

    Jones, S. G.

    1993-01-01

    The paper proposes a cooperative research effort be undertaken by academic institutions and industry organizations toward the compilation of a human factors data base in conjunction with technical information. Team members in any discipline can benefit and learn from observing positive examples of decision making and performance by crews under stressful or less than optimal circumstances. The opportunity to note trends in interpersonal and interactive behaviors and to categorize them is terms of more or less desirable outcomes should not be missed.

  15. Human Factors in Space Exploration

    NASA Technical Reports Server (NTRS)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    The exploration of space is one of the most fascinating domains to study from a human factors perspective. Like other complex work domains such as aviation (Pritchett and Kim, 2008), air traffic management (Durso and Manning, 2008), health care (Morrow, North, and Wickens, 2006), homeland security (Cooke and Winner, 2008), and vehicle control (Lee, 2006), space exploration is a large-scale sociotechnical work domain characterized by complexity, dynamism, uncertainty, and risk in real-time operational contexts (Perrow, 1999; Woods et ai, 1994). Nearly the entire gamut of human factors issues - for example, human-automation interaction (Sheridan and Parasuraman, 2006), telerobotics, display and control design (Smith, Bennett, and Stone, 2006), usability, anthropometry (Chaffin, 2008), biomechanics (Marras and Radwin, 2006), safety engineering, emergency operations, maintenance human factors, situation awareness (Tenney and Pew, 2006), crew resource management (Salas et aI., 2006), methods for cognitive work analysis (Bisantz and Roth, 2008) and the like -- are applicable to astronauts, mission control, operational medicine, Space Shuttle manufacturing and assembly operations, and space suit designers as they are in other work domains (e.g., Bloomberg, 2003; Bos et al, 2006; Brooks and Ince, 1992; Casler and Cook, 1999; Jones, 1994; McCurdy et ai, 2006; Neerincx et aI., 2006; Olofinboba and Dorneich, 2005; Patterson, Watts-Perotti and Woods, 1999; Patterson and Woods, 2001; Seagull et ai, 2007; Sierhuis, Clancey and Sims, 2002). The human exploration of space also has unique challenges of particular interest to human factors research and practice. This chapter provides an overview of those issues and reports on sorne of the latest research results as well as the latest challenges still facing the field.

  16. Nutritional factors and hair loss.

    PubMed

    Rushton, D H

    2002-07-01

    The literature reveals what little is known about nutritional factors and hair loss. What we do know emanates from studies in protein-energy malnutrition, starvation, and eating disorders. In otherwise healthy individuals, nutritional factors appear to play a role in subjects with persistent increased hair shedding. Hård, 40 years ago, demonstrated the importance of iron supplements in nonanaemic, iron-deficient women with hair loss. Serum ferritin concentrations provide a good assessment of an individual's iron status. Rushton et al. first published data showing that serum ferritin concentrations were a factor in female hair loss and, 10 years later, Kantor et al. confirmed this association. What level of serum ferritin to employ in subjects with increased hair shedding is yet to be definitively established but 70 micro g/L, with a normal erythrocyte sedimentation rate (< 10 mm/h), is recommended. The role of the essential amino acid, l-lysine in hair loss also appears to be important. Double-blind data confirmed the findings of an open study in women with increased hair shedding, where a significant proportion responded to l-lysine and iron therapy. There is no evidence to support the popular view that low serum zinc concentrations cause hair loss. Excessive intakes of nutritional supplements may actually cause hair loss and are not recommended in the absence of a proven deficiency. While nutritional factors affect the hair directly, one should not forget that they also affect the skin. In the management of subjects with hair loss, eliminating scaling problems is important as is good hair care advice and the need to explain fully the hair cycle. Many individuals reduced their shampooing frequency due to fear of losing more hair but this increases the amount seen in subsequent shampoos fuelling their fear of going bald and adversely affecting their quality of life. PMID:12190640

  17. Factor weighting in DRASTIC modeling.

    PubMed

    Pacheco, F A L; Pires, L M G R; Santos, R M B; Sanches Fernandes, L F

    2015-02-01

    Evaluation of aquifer vulnerability comprehends the integration of very diverse data, including soil characteristics (texture), hydrologic settings (recharge), aquifer properties (hydraulic conductivity), environmental parameters (relief), and ground water quality (nitrate contamination). It is therefore a multi-geosphere problem to be handled by a multidisciplinary team. The DRASTIC model remains the most popular technique in use for aquifer vulnerability assessments. The algorithm calculates an intrinsic vulnerability index based on a weighted addition of seven factors. In many studies, the method is subject to adjustments, especially in the factor weights, to meet the particularities of the studied regions. However, adjustments made by different techniques may lead to markedly different vulnerabilities and hence to insecurity in the selection of an appropriate technique. This paper reports the comparison of 5 weighting techniques, an enterprise not attempted before. The studied area comprises 26 aquifer systems located in Portugal. The tested approaches include: the Delphi consensus (original DRASTIC, used as reference), Sensitivity Analysis, Spearman correlations, Logistic Regression and Correspondence Analysis (used as adjustment techniques). In all cases but Sensitivity Analysis, adjustment techniques have privileged the factors representing soil characteristics, hydrologic settings, aquifer properties and environmental parameters, by leveling their weights to ≈4.4, and have subordinated the factors describing the aquifer media by downgrading their weights to ≈1.5. Logistic Regression predicts the highest and Sensitivity Analysis the lowest vulnerabilities. Overall, the vulnerability indices may be separated by a maximum value of 51 points. This represents an uncertainty of 2.5 vulnerability classes, because they are 20 points wide. Given this ambiguity, the selection of a weighting technique to integrate a vulnerability index may require additional

  18. Factors affecting maximal acid secretion

    PubMed Central

    Desai, H. G.

    1969-01-01

    The mechanisms by which different factors affect the maximal acid secretion of the stomach are discussed with particular reference to nationality, sex, age, body weight or lean body mass, procedural details, mode of calculation, the nature, dose and route of administration of a stimulus, the synergistic action of another stimulus, drugs, hormones, electrolyte levels, anaemia or deficiency of the iron-dependent enzyme system, vagal continuity and parietal cell mass. PMID:4898322

  19. [Nutritional factors in preventing osteoporosis].

    PubMed

    Martín Jiménez, Juan Antonio; Consuegra Moya, Belkis; Martín Jiménez, María Teresa

    2015-01-01

    Osteoporosis, main risk factor for suffering fragility fractures, is an important public health problem which has undoubted social, health and economic impact; but mainly causes pain, functional limitation and severe alterations in the patient's quality of life. Its current prevalence is very high and a further increase is expected due to a higher life expectancy and the progressive ageing of the population. In the prevention of osteoporosis, the main goal is to prevent fragility fractures; for this reason, it is necessary to: 1) promote bone formation in youth, to get sufficient bone mass peak, 2) reduce bone loss in adulthood, especially after menopause, 3) maintain bone health throughout life, and 4) prevent falls. There is enough evidence that multifactorial strategies (assessment of risk factors, healthy lifestyle habits, smoking cessation, moderation in alcohol consumption, physical exercise, outdoor activity with prudent exposure to sunlight, and a varied and balanced diet), are effective in the population at risk. Regarding factors for the prevention of osteoporosis, current recommendations are: increased consumption of calcium, phosphorus, magnesium and fluoride; provide adequate vitamin D (even with fortified food if necessary); consumption of foods rich in omega-3 acids; reduction of salt and prepared ready meals; sufficient but moderate intake of protein and, in the absence of intolerance, promote the consumption of milk and dairy products, especially yogurt and fermented milk products. PMID:26267775

  20. Human Factors in Financial Trading

    PubMed Central

    Leaver, Meghan; Reader, Tom W.

    2016-01-01

    Objective This study tests the reliability of a system (FINANS) to collect and analyze incident reports in the financial trading domain and is guided by a human factors taxonomy used to describe error in the trading domain. Background Research indicates the utility of applying human factors theory to understand error in finance, yet empirical research is lacking. We report on the development of the first system for capturing and analyzing human factors–related issues in operational trading incidents. Method In the first study, 20 incidents are analyzed by an expert user group against a referent standard to establish the reliability of FINANS. In the second study, 750 incidents are analyzed using distribution, mean, pathway, and associative analysis to describe the data. Results Kappa scores indicate that categories within FINANS can be reliably used to identify and extract data on human factors–related problems underlying trading incidents. Approximately 1% of trades (n = 750) lead to an incident. Slip/lapse (61%), situation awareness (51%), and teamwork (40%) were found to be the most common problems underlying incidents. For the most serious incidents, problems in situation awareness and teamwork were most common. Conclusion We show that (a) experts in the trading domain can reliably and accurately code human factors in incidents, (b) 1% of trades incur error, and (c) poor teamwork skills and situation awareness underpin the most critical incidents. Application This research provides data crucial for ameliorating risk within financial trading organizations, with implications for regulation and policy. PMID:27142394

  1. Environmental factors in multiple sclerosis.

    PubMed

    Pantazou, Vasiliki; Schluep, Myriam; Du Pasquier, Renaud

    2015-04-01

    Although multiple sclerosis (MS) is recognized as a disorder involving the immune system, the interplay of environmental factors and individual genetic susceptibility seems to influence MS onset and clinical expression, as well as therapeutic responsiveness. Multiple human epidemiological and animal model studies have evaluated the effect of different environmental factors, such as viral infections, vitamin intake, sun exposure, or still dietary and life habits on MS prevalence. Previous Epstein-Barr virus infection, especially if this infection occurs in late childhood, and lack of vitamin D (VitD) currently appear to be the most robust environmental factors for the risk of MS, at least from an epidemiological standpoint. Ultraviolet radiation (UVR) activates VitD production but there are also some elements supporting the fact that insufficient UVR exposure during childhood may represent a VitD-independent risk factor of MS development, as well as negative effect on the clinical and radiological course of MS. Recently, there has been a growing interest in the gut-brain axis, a bidirectional neuro-hormonal communication system between the intestinal microbiota and the central nervous system (CNS). Indeed, components of the intestinal microbiota may be pro-inflammatory, promote the migration of immune cells into the CNS, and thus be a key parameter for the development of autoimmune disorders such as MS. Interestingly most environmental factors seem to play a role during childhood. Thus, if childhood is the most fragile period to develop MS later in life, preventive measures should be applied early in life. For example, adopting a diet enriched in VitD, playing outdoor and avoiding passive smoking would be extremely simple measures of primary prevention for public health strategies. However, these hypotheses need to be confirmed by prospective evaluations, which are obviously difficult to conduct. In addition, it remains to be determined whether and how Vit

  2. Cardiac risk factors: environmental, sociodemographic, and behavioral cardiovascular risk factors.

    PubMed

    Anthony, David; George, Paul; Eaton, Charles B

    2014-06-01

    Several environmental exposures are associated with increased risk of coronary heart disease (CHD). Exposure to secondhand smoke may increase the risk by as much as 25% to 30%. Exposure to third hand smoke, residual components of tobacco smoke that remain in the environment after a cigarette is extinguished, also appears to increase risk. These residual components can remain in rooms and automobiles for up to 30 years and enter the body through the skin or via inhalation or ingestion. Exposure to particulate matter air pollution from automobile emissions, power plants, and other sources is yet another environmental risk factor for CHD, resulting in tens of thousands of deaths annually in the United States. Exposure to other environmental toxins, particularly bisphenol A and phthalates, also has been linked to CHD. There are sociodemographic risks for CHD, with numerous studies showing that lower socioeconomic status is associated with higher risk. Behavioral risk factors include poor diet, such as frequent consumption of fast food and processed meals; sleep disturbance; and psychological stress, particularly related to marital or work issues. Finally, although high alcohol consumption is associated with increased CHD risk, moderate alcohol consumption (ie, less than 1 to 2 drinks/day), particularly of wine and possibly beer, appears to reduce the risk. PMID:24936715

  3. Scene kinetics mitigation using factor analysis with derivative factors.

    SciTech Connect

    Larson, Kurt W.; Melgaard, David Kennett; Scholand, Andrew Joseph

    2010-07-01

    Line of sight jitter in staring sensor data combined with scene information can obscure critical information for change analysis or target detection. Consequently before the data analysis, the jitter effects must be significantly reduced. Conventional principal component analysis (PCA) has been used to obtain basis vectors for background estimation; however PCA requires image frames that contain the jitter variation that is to be modeled. Since jitter is usually chaotic and asymmetric, a data set containing all the variation without the changes to be detected is typically not available. An alternative approach, Scene Kinetics Mitigation, first obtains an image of the scene. Then it computes derivatives of that image in the horizontal and vertical directions. The basis set for estimation of the background and the jitter consists of the image and its derivative factors. This approach has several advantages including: (1) only a small number of images are required to develop the model, (2) the model can estimate backgrounds with jitter different from the input training images, (3) the method is particularly effective for sub-pixel jitter, and (4) the model can be developed from images before the change detection process. In addition the scores from projecting the factors on the background provide estimates of the jitter magnitude and direction for registration of the images. In this paper we will present a discussion of the theoretical basis for this technique, provide examples of its application, and discuss its limitations.

  4. Dopamine receptor regulating factor, DRRF: a zinc finger transcription factor.

    PubMed

    Hwang, C K; D'Souza, U M; Eisch, A J; Yajima, S; Lammers, C H; Yang, Y; Lee, S H; Kim, Y M; Nestler, E J; Mouradian, M M

    2001-06-19

    Dopamine receptor genes are under complex transcription control, determining their unique regional distribution in the brain. We describe here a zinc finger type transcription factor, designated dopamine receptor regulating factor (DRRF), which binds to GC and GT boxes in the D1A and D2 dopamine receptor promoters and effectively displaces Sp1 and Sp3 from these sequences. Consequently, DRRF can modulate the activity of these dopamine receptor promoters. Highest DRRF mRNA levels are found in brain with a specific regional distribution including olfactory bulb and tubercle, nucleus accumbens, striatum, hippocampus, amygdala, and frontal cortex. Many of these brain regions also express abundant levels of various dopamine receptors. In vivo, DRRF itself can be regulated by manipulations of dopaminergic transmission. Mice treated with drugs that increase extracellular striatal dopamine levels (cocaine), block dopamine receptors (haloperidol), or destroy dopamine terminals (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) show significant alterations in DRRF mRNA. The latter observations provide a basis for dopamine receptor regulation after these manipulations. We conclude that DRRF is important for modulating dopaminergic transmission in the brain. PMID:11390978

  5. Academic Success Factors: An IT Student Perspective

    ERIC Educational Resources Information Center

    Zhang, Aimao; Aasheim, Cheryl L.

    2011-01-01

    Numerous studies have identified causal factors for academic success. Factors vary from personal factors, such as cognitive style (McKenzie & Schweitzer, 2001), to social factors, such as culture differences (Aysan, Tanriogen, & Tanriogen, 1996). However, in these studies it is re-searchers who theorized the causal dimensions and hypothesized the…

  6. Factor Analysis of Law School Grades.

    ERIC Educational Resources Information Center

    Boldt, Robert F.

    Grades of 116 law school students were obtained from transcripts, along with LSAT, Writing Ability and Background scores. The grades were factored, and an analysis of the goodness of fit of one- through four-factor systems indicated that the system of grades was essentially one factor in nature. A plot of factor loadings for the various courses…

  7. Remarks on KERMA Factors in ACE files

    NASA Astrophysics Data System (ADS)

    Konno, C.; Ochiai, K.; Takakura, K.; Sato, S.

    2014-04-01

    Some neutron KERMA factors in ACE files are negative and extremely large if nuclear data libraries do not keep energy-balance. The status of neutron KERMA factors in the official ACE file of ENDF/B-VII.1 is examined. As a result, it is found out that neutron KERMA factors of nuclei more than 200 in ENDF/B-VII.1 have some problems. Effects of the inadequate KERMA factor are also investigated, which are large for neutron heat while those are small for total (neutron + gamma) heat. Users who use only neutron KERMA factors should check if the factors are adequate or not before they use the factors.

  8. Understanding adverse events: human factors.

    PubMed Central

    Reason, J

    1995-01-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  9. Modifications of Coronary Risk Factors

    PubMed Central

    Albu, Jeanine; Gottlieb, Sheldon H.; August, Phyllis; Nesto, Richard W.; Orchard, Trevor J.

    2009-01-01

    In addition to the revascularization and glycemic management interventions assigned at random, the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) design includes the uniform control of major coronary artery disease risk factors, including dyslipidemia, hypertension, smoking, central obesity, and sedentary lifestyle. Target levels for risk factors were adjusted throughout the trial to comply with changes in recommended clinical practice guidelines. At present, the goals are low-density lipoprotein cholesterol <2.59 mmol/L (<100 mg/dL) with an optional goal of <1.81 mmol/L (<70 mg/dL); plasma triglyceride level <1.70 mmol/L (<150 mg/dL); blood pressure level <130 mm Hg systolic and <80 mm Hg diastolic; and smoking cessation treatment for all active smokers. Algorithms were developed for the pharmacologic management of dyslipidemia and hypertension. Dietary prescriptions for the management of glycemia, plasma lipid profiles, and blood pressure levels were adapted from existing clinical practice guidelines. Patients with a body mass index >25 were prescribed moderate caloric restriction; after the trial was under way, a lifestyle weight-management program was instituted. All patients were formally prescribed both endurance and resistance/flexibility exercises, individually adapted to their level of disability and fitness. Pedometers were distributed as a biofeedback strategy. Strategies to achieve the goals for risk factors were designed by BARI 2D working groups (lipid, cardiovascular and hypertension, and nonpharmacologic intervention) and the ongoing implementation of the strategies is monitored by lipid, hypertension, and lifestyle intervention management centers. PMID:16813737

  10. Small Peptides Blocking Inhibition of Factor Xa and Tissue Factor-Factor VIIa by Tissue Factor Pathway Inhibitor (TFPI)*

    PubMed Central

    Dockal, Michael; Hartmann, Rudolf; Fries, Markus; Thomassen, M. Christella L. G. D.; Heinzmann, Alexandra; Ehrlich, Hartmut; Rosing, Jan; Osterkamp, Frank; Polakowski, Thomas; Reineke, Ulrich; Griessner, Andreas; Brandstetter, Hans; Scheiflinger, Friedrich

    2014-01-01

    Tissue factor pathway inhibitor (TFPI) is a Kunitz-type protease inhibitor that inhibits activated factor X (FXa) via a slow-tight binding mechanism and tissue factor-activated FVII (TF-FVIIa) via formation of a quaternary FXa-TFPI-TF-FVIIa complex. Inhibition of TFPI enhances coagulation in hemophilia models. Using a library approach, we selected and subsequently optimized peptides that bind TFPI and block its anticoagulant activity. One peptide (termed compound 3), bound with high affinity to the Kunitz-1 (K1) domain of TFPI (Kd ∼1 nm). We solved the crystal structure of this peptide in complex with the K1 of TFPI at 2.55-Å resolution. The structure of compound 3 can be segmented into a N-terminal anchor; an Ω-shaped loop; an intermediate segment; a tight glycine-loop; and a C-terminal α-helix that is anchored to K1 at its reactive center loop and two-stranded β-sheet. The contact surface has an overall hydrophobic character with some charged hot spots. In a model system, compound 3 blocked FXa inhibition by TFPI (EC50 = 11 nm) and inhibition of TF-FVIIa-catalyzed FX activation by TFPI (EC50 = 2 nm). The peptide prevented transition from the loose to the tight FXa-TFPI complex, but did not affect formation of the loose FXa-TFPI complex. The K1 domain of TFPI binds and inhibits FVIIa and the K2 domain similarly inhibits FXa. Because compound 3 binds to K1, our data show that K1 is not only important for FVIIa inhibition but also for FXa inhibition, i.e. for the transition of the loose to the tight FXa-TFPI complex. This mode of action translates into normalization of coagulation of hemophilia plasmas. Compound 3 thus bears potential to prevent bleeding in hemophilia patients. PMID:24275667

  11. Human Factors in Space Flight

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara J.; Mount, Frances

    2005-01-01

    After forty years of experience with human space flight (Table 1), the current emphasis is on the design of space vehicles, habitats, and missions to ensure mission success. What lessons have we learned that will affect the design of spacecraft for future space exploration, leading up to exploring Mars? This chapter addresses this issue in four sections: Anthropometry and Biomechanics; Environmental Factors; Habitability and Architecture; and Crew Personal Sustenance. This introductory section introduces factors unique to space flight. A unique consideration for design of a habitable volume in a space vehicle is the lack of gravity during a space flight, referred to as microgravity. This affects all aspects of life, and drives special features in the habitat, equipment, tools, and procedures. The difference in gravity during a space mission requires designing for posture and motion differences. In Earth s gravity, or even with partial gravity, orientation is not a variable because the direction in which gravity acts defines up and down. In a microgravity environment the working position is arbitrary; there is no gravity cue. Orientation is defined primarily through visual cues. The orientation within a particular crew station or work area is referred to as local vertical, and should be consistent within a module to increase crew productivity. Equipment was intentionally arranged in various orientations in one module on Skylab to assess the efficiency in use of space versus the effects of inconsistent layout. The effects of that arrangement were confusion on entering the module, time spent in re-orientation, and conflicts in crew space requirements when multiple crew members were in the module. Design of a space vehicle is constrained by the three major mission drivers: mass, volume and power. Each of these factors drives the cost of a mission. Mass and volume determine the size of the launch vehicle directly; they can limit consumables such as air, water, and

  12. Psychological factors in emergency medicine.

    PubMed

    Gutenstein, Marc

    2014-06-01

    Human psychology, neuroscience and behavioural economics study the human mind, brain and behaviour. Scientific research has discovered a great deal about the factors that influence human perception, judgment and activity in the real world. In this article, I aim to provide an outline of the relationship between decision-making, cognition, emotion and behaviour. I propose that meta-cognition, or thinking-about-thinking, has the potential to inform how we practice emergency medicine. By accommodating human traits rather than trying to defy them, we can ultimately benefit our patients. PMID:24712897

  13. [Environmental factors in Asperger syndrome].

    PubMed

    Abe, Takaaki; Kato, Satoshi

    2007-03-01

    This paper reviews what is currently known about the environmental factors in Asperger syndrome that is a neurodevelopmental disorder of genetic origins. Its characteristics tend to occur in families of those with the syndrome. The rate of complications during pregnancy or the neonatal period in the patients with Asperger syndrome was about the same as that in the control group. It is true that their involvement in their outer world could not influence the core social deficits very much. But it might facilitate the appearance of the second symptoms such as dissociation, anxiety, depression, persecutory delusion as well as antisocial behavior including serious criminal acts. PMID:17354554

  14. Human factors in spacecraft design

    NASA Technical Reports Server (NTRS)

    Harrison, Albert A.; Connors, Mary M.

    1990-01-01

    This paper describes some of the salient implications of evolving mission parameters for spacecraft design. Among the requirements for future spacecraft are new, higher standards of living, increased support of human productivity, and greater accommodation of physical and cultural variability. Design issues include volumetric allowances, architecture and layouts, closed life support systems, health maintenance systems, recreational facilities, automation, privacy, and decor. An understanding of behavioral responses to design elements is a precondition for critical design decisions. Human factors research results must be taken into account early in the course of the design process.

  15. Targeting Transcription Factors in Cancer

    PubMed Central

    Bhagwat, Anand S.; Vakoc, Christopher R.

    2015-01-01

    Transcription factors (TFs) are commonly deregulated in the pathogenesis of human cancer and are a major class of cancer cell dependencies. Consequently, targeting of TFs can be highly effective in treating particular malignancies, as highlighted by the clinical efficacy of agents that target nuclear hormone receptors. In this review we discuss recent advances in our understanding of TFs as drug targets in oncology, with an emphasis on the emerging chemical approaches to modulate TF function. The remarkable diversity and potency of TFs as drivers of cell transformation justifies a continued pursuit of TFs as therapeutic targets for drug discovery. PMID:26645049

  16. Biographical factors of occupational independence.

    PubMed

    Müller, G F

    2001-10-01

    The present study examined biographical factors of occupational independence including any kind of nonemployed profession. Participants were 59 occupationally independent and 58 employed persons of different age (M = 36.3 yr.), sex, and profession. They were interviewed on variables like family influence, educational background, occupational role models, and critical events for choosing a particular type of occupational career. The obtained results show that occupationally independent people reported stronger family ties, experienced fewer restrictions of formal education, and remembered fewer negative role models than the employed people. Implications of these results are discussed. PMID:11783553

  17. Human factors in spacecraft design.

    PubMed

    Harrison, A A; Connors, M M

    1990-01-01

    This paper describes some of the salient implications of evolving mission parameters for spacecraft design. Among the requirements for future spacecraft are new, higher standards of living, increased support of human productivity, and greater accommodation of physical and cultural variability. Design issues include volumetric allowances, architecture and layouts, closed life support systems, health maintenance systems, recreational facilities, automation, privacy, and decor. An understanding of behavioral responses to design elements is a precondition for critical design decisions. Human factors research results must be taken into account early in the course of the design process. PMID:11537619

  18. Weak-shock reflection factors

    SciTech Connect

    Reichenbach, H.; Kuhl, A.L.

    1993-09-07

    The purpose of this paper is to compare reflection factors for weak shocks from various surfaces, and to focus attention on some unsolved questions. Three different cases are considered: square-wave planar shock reflection from wedges; square-wave planar shock reflection from cylinders; and spherical blast wave reflection from a planar surface. We restrict ourselves to weak shocks. Shocks with a Mach number of M{sub O} < 1.56 in air or with an overpressure of {Delta}{sub PI} < 25 psi (1.66 bar) under normal ambient conditions are called weak.

  19. Human factors in space telepresence

    NASA Technical Reports Server (NTRS)

    Akin, D. L.; Howard, R. D.; Oliveria, J. S.

    1983-01-01

    The problems of interfacing a human with a teleoperation system, for work in space are discussed. Much of the information presented here is the result of experience gained by the M.I.T. Space Systems Laboratory during the past two years of work on the ARAMIS (Automation, Robotics, and Machine Intelligence Systems) project. Many factors impact the design of the man-machine interface for a teleoperator. The effects of each are described in turn. An annotated bibliography gives the key references that were used. No conclusions are presented as a best design, since much depends on the particular application desired, and the relevant technology is swiftly changing.

  20. Factorization of the tenth Fermat number

    NASA Astrophysics Data System (ADS)

    Brent, Richard P.

    We describe the complete factorization of the tenth Fermat number F_{10} by the elliptic curve method (ECM). F_{10} is a product of four prime factors with 8, 10, 40 and 252 decimal digits. The 40-digit factor was found after about 140 Mflop-years of computation. We also discuss the complete factorization of other Fermat numbers by ECM, and summarize the factorizations of F_5, ..., F_{11}.

  1. Human Factors Checklist: Think Human Factors - Focus on the People

    NASA Technical Reports Server (NTRS)

    Miller, Darcy; Stelges, Katrine; Barth, Timothy; Stambolian, Damon; Henderson, Gena; Dischinger, Charles; Kanki, Barbara; Kramer, Ian

    2016-01-01

    A quick-look Human Factors (HF) Checklist condenses industry and NASA Agency standards consisting of thousands of requirements into 14 main categories. With support from contractor HF and Safety Practitioners, NASA developed a means to share key HF messages with Design, Engineering, Safety, Project Management, and others. It is often difficult to complete timely assessments due to the large volume of HF information. The HF Checklist evolved over time into a simple way to consider the most important concepts. A wide audience can apply the checklist early in design or through planning phases, even before hardware or processes are finalized or implemented. The checklist is a good place to start to supplement formal HF evaluation. The HF Checklist was based on many Space Shuttle processing experiences and lessons learned. It is now being applied to ground processing of new space vehicles and adjusted for new facilities and systems.

  2. Factor VIII/factor IX prophylaxis for severe hemophilia.

    PubMed

    Carcao, Manuel; Srivastava, Alok

    2016-01-01

    Experience with clotting factor concentrate (CFC) replacement products over several decades has shown that regular replacement (prophylaxis) is the only way to prevent musculoskeletal damage in hemophilia and impact the natural history of hemophilia. Yet there is a lack of data on the optimal age to start such replacement therapy and the regimens to be used. While very early administration of high doses is certainly more effective in preventing bleeding, cost and compliance are major constraints all over the world. Starting prophylaxis with even lower doses comparable to that used in episodic therapies leads to major reduction in bleeding. Recognition of the clinical heterogeneity of hemophilia even among patients with a label of severe hemophilia in terms of their spontaneous bleeding has led to efforts aimed at individualizing CFC replacement, based on clinical responses or pharmacokinetic data of the CFC. The importance of long-term outcome assessment being combined with CFC replacement therapy cannot be overemphasized. PMID:26805901

  3. Cardiovascular risk factors among Chamorros

    PubMed Central

    Chiem, Binh; Nguyen, Victoria; Wu, Phillis L; Ko, Celine M; Cruz, Lee Ann; Sadler, Georgia Robins

    2006-01-01

    Background Little is known regarding the cardiovascular disease risk factors among Chamorros residing in the United States. Methods The Chamorro Directory International and the CDC's Behavioral Risk Factor Surveillance System Questionnaire (BRFSS) were used to assess the health related practices and needs of a random sample of 228 Chamorros. Results Inactivity, hypertension, elevated cholesterol and diabetes mellitus were more prevalent in this Chamorro sample compared to the US average. Participants who were 50-and-older or unemployed were more likely to report hypertension, diabetes and inactivity, but they were also more likely to consume more fruits and vegetables than their younger and employed counterparts. Women were more likely to report hypertension and diabetes, whereas men were more likely to have elevated BMI and to have never had their blood cholesterol checked. Conclusion The study provides data that will help healthcare providers, public health workers and community leaders identify where to focus their health improvement efforts for Chamorros and create culturally competent programs to promote health in this community. PMID:17156462

  4. Hadamard Factorization of Stable Polynomials

    NASA Astrophysics Data System (ADS)

    Loredo-Villalobos, Carlos Arturo; Aguirre-Hernández, Baltazar

    2011-11-01

    The stable (Hurwitz) polynomials are important in the study of differential equations systems and control theory (see [7] and [19]). A property of these polynomials is related to Hadamard product. Consider two polynomials p,q ∈ R[x]:p(x) = anxn+an-1xn-1+...+a1x+a0q(x) = bmx m+bm-1xm-1+...+b1x+b0the Hadamard product (p × q) is defined as (p×q)(x) = akbkxk+ak-1bk-1xk-1+...+a1b1x+a0b0where k = min(m,n). Some results (see [16]) shows that if p,q ∈R[x] are stable polynomials then (p×q) is stable, also, i.e. the Hadamard product is closed; however, the reciprocal is not always true, that is, not all stable polynomial has a factorization into two stable polynomials the same degree n, if n> 4 (see [15]).In this work we will give some conditions to Hadamard factorization existence for stable polynomials.

  5. Factors affecting outcomes in colonoscopy.

    PubMed

    Selehi, Seema; Leung, Edmund; Wong, Ling

    2008-01-01

    There are many factors that influence successful outcomes in colonoscopy. The aims of this study were to evaluate these factors and determine ways to improve outcomes. All participants (N=229) who underwent planned colonoscopy between July and September 2004 were retrospectively included. Participants included 118 men and 111 women with a mean age of 59 years. Completion rate was 92%. Reasons of failure included poor bowel preparation (2.2%, p< .025), bowel looping (2.2%, p< .025), participant discomfort (1.3%), and obstructing lesion (1.3%). Mean midazolam dose was 3.8 mg. Three participants (1.3%) had midazolam alone, and all had complete colonoscopy. One hundred thirty-three participants (60.7%) had additional meperidine, with a completion rate of 94%. Eighty three participants (37.9%) had additional meperidine and Buscopan, with a completion rate reduced to 89.2%. There was no correlation between sedatives used and completion rate. Completion rate of colonoscopy in our unit was acceptable at 92%. A combination of midazolam and meperidine gave the best completion rates (94%). The two main reasons for incompletion were poor bowel preparation and excessive bowel looping. PMID:18300826

  6. Salmonella-secreted Virulence Factors

    SciTech Connect

    Heffron, Fred; Niemann, George; Yoon, Hyunjin; Kidwai, Afshan S.; Brown, Roslyn N.; McDermott, Jason E.; Smith, Richard D.; Adkins, Joshua N.

    2011-05-01

    In this short review we discuss secreted virulence factors of Salmonella, which directly affect Salmonella interaction with its host. Salmonella secretes protein to subvert host defenses but also, as discussed, to reduce virulence thereby permitting the bacteria to persist longer and more successfully disperse. The type III secretion system (TTSS) is the best known and well studied of the mechanisms that enable secretion from the bacterial cytoplasm to the host cell cytoplasm. Other secretion systems include outer membrane vesicles, which are present in all Gram-negative bacteria examined to date, two-partner secretion, and type VI secretion will also be addressed. Excellent reviews of Salmonella secreted effectors have focused on themes such as actin rearrangements, vesicular trafficking, ubiquitination, and the activities of the virulence factors themselves. This short review is based on S. Typhimurium infection of mice because it is a model of typhoid like disease in humans. We have organized effectors in terms of events that happen during the infection cycle and how secreted effectors may be involved.

  7. Dissecting soft radiation with factorization.

    PubMed

    Stewart, Iain W; Tackmann, Frank J; Waalewijn, Wouter J

    2015-03-01

    An essential part of high-energy hadronic collisions is the soft hadronic activity that underlies the primary hard interaction. It includes soft radiation from the primary hard partons, secondary multiple parton interactions (MPI), and factorization-violating effects. The invariant mass spectrum of the leading jet in Z+jet and H+jet events is directly sensitive to these effects, and we use a QCD factorization theorem to predict its dependence on the jet radius R, jet p_{T}, jet rapidity, and partonic process for both the perturbative and nonperturbative components of primary soft radiation. We prove that the nonperturbative contributions involve only odd powers of R, and the linear R term is universal for quark and gluon jets. The hadronization model in Pythia8 agrees well with these properties. The perturbative soft initial state radiation (ISR) has a contribution that depends on the jet area in the same way as the underlying event, but this degeneracy is broken by dependence on the jet p_{T}. The size of this soft ISR contribution is proportional to the color state of the initial partons, yielding the same positive contribution for gg→Hg and gq→Zq, but a negative interference contribution for qq[over ¯]→Zg. Hence, measuring these dependencies allows one to separate hadronization, soft ISR, and MPI contributions in the data. PMID:25793802

  8. Environmental factors in cardiovascular disease.

    PubMed

    Cosselman, Kristen E; Navas-Acien, Ana; Kaufman, Joel D

    2015-11-01

    Environmental exposure is an important but underappreciated risk factor contributing to the development and severity of cardiovascular disease (CVD). The heart and vascular system are highly vulnerable to a number of environmental agents--ambient air pollution and the metals arsenic, cadmium, and lead are widespread and the most-extensively studied. Like traditional risk factors, such as smoking and diabetes mellitus, these exposures advance disease and mortality via augmentation or initiation of pathophysiological processes associated with CVD, including blood-pressure control, carbohydrate and lipid metabolism, vascular function, and atherogenesis. Although residence in highly polluted areas is associated with high levels of cardiovascular risk, adverse effects on cardiovascular health also occur at exposure levels below current regulatory standards. Considering the widespread prevalence of exposure, even modest contributions to CVD risk can have a substantial effect on population health. Evidence-based clinical and public-health strategies aimed at reducing environmental exposures from current levels could substantially lower the burden of CVD-related death and disability worldwide. PMID:26461967

  9. Environmental factors influencing blackfly populations

    PubMed Central

    Carlsson, G.

    1967-01-01

    Much more information is required on the distribution of blackflies in various parts of the world, and in many cases an adequate methodology for obtaining such information still has to be worked out. A detailed methodology for the collection of information about blackflies is given, which was developed for investigations mainly in the Holarctic regions but is basically applicable to other parts of the world. A brief survey of the population dynamics of various species of blackflies in various parts of the Holarctic regions is given, and the main factors influencing the population dynamics are discussed. Interspecific and intraspecific fluctuations in natural blackfly populations are attributed chiefly to abiotic environmental factors rather than to competition. Larval competition in a given microhabitat is mainly individual, though specimens belonging to a given species may have a slightly more favourable position than others. The use of parasites and in particular the replacement of one species by another are promising methods of blackfly control. Predators are not generally likely to prove useful for this purpose. PMID:5300046

  10. Factors identified for negative appendicectomies.

    PubMed

    Mirza, M R; Habib, L; Jaleel, F

    2009-07-01

    The study was done, to determine the factors for negative appendicectomies. This prospective descriptive study includes patients managed at four non teaching and a teaching hospital of Karachi from March 2006 to February 2008. One hundred and sixty eight patients underwent appendicectomy during the study period. Details of clinical presentations, investigations, operative findings and histopathology were entered and analyzed. Literature search was aimed to see the negative appendicectomy rate (NAR) in last ten years despite using diagnostic tools (clinical scoring, diagnostic imaging and laparoscopy). In this study a total number of 168 patients under went appendicectomy. Normal appendices were found in 31 patients (negative appendicectomy rate was 18.45%) and associated pathology was seen in 13 patients, an incidental finding of Meckel's diverticulum in 5 patients and no other pathology was seen in 13 patients. The different factors which we identified for negative appendicectomies in our practice were non teaching hospitals where diagnostic scoring system was difficult to apply, female gender, selective use of imaging modality, other pathologies presenting with pain in right lower quadrant (RLQ) and requiring surgical intervention, and non-availability of CT scan and laparoscopy. Despite many advances in diagnostic system, acute appendicitis is still a diagnostic dilemma at times. Although there is no substitute for clinical judgment but in sub groups of patients in whom the possibility of negative appendicectomy is high, diagnostic modalities should be used judiciously to decrease the negative exploration. PMID:19623147

  11. Factors Affecting Aerosol Radiative Forcing

    NASA Astrophysics Data System (ADS)

    Wang, Jingxu; Lin, Jintai; Ni, Ruijing

    2016-04-01

    Rapid industrial and economic growth has meant a large amount of aerosols in the atmosphere with strong radiative forcing (RF) upon the climate system. Over parts of the globe, the negative forcing of aerosols has overcompensated for the positive forcing of greenhouse gases. Aerosol RF is determined by emissions and various chemical-transport-radiative processes in the atmosphere, a multi-factor problem whose individual contributors have not been well quantified. In this study, we analyze the major factors affecting RF of secondary inorganic aerosols (SIOAs, including sulfate, nitrate and ammonium), primary organic aerosol (POA), and black carbon (BC). We analyze the RF of aerosols produced by 11 major regions across the globe, including but not limited to East Asia, Southeast Asia, South Asia, North America, and Western Europe. Factors analyzed include population size, per capita gross domestic production (GDP), emission intensity (i.e., emissions per unit GDP), chemical efficiency (i.e., mass per unit emissions) and radiative efficiency (i.e., RF per unit mass). We find that among the 11 regions, East Asia produces the largest emissions and aerosol RF, due to relatively high emission intensity and a tremendous population size. South Asia produce the second largest RF of SIOA and BC and the highest RF of POA, in part due to its highest chemical efficiency among all regions. Although Southeast Asia also has large emissions, its aerosol RF is alleviated by its lowest chemical efficiency. The chemical efficiency and radiative efficiency of BC produced by the Middle East-North Africa are the highest across the regions, whereas its RF is lowered by a small per capita GDP. Both North America and Western Europe have low emission intensity, compensating for the effects on RF of large population sizes and per capita GDP. There has been a momentum to transfer industries to Southeast Asia and South Asia, and such transition is expected to continue in the coming years. The

  12. Dental pulp tissue engineering with bFGF-incorporated silk fibroin scaffolds.

    PubMed

    Yang, Jing-Wen; Zhang, Yu-Feng; Sun, Zhe-Yi; Song, Guang-Tai; Chen, Zhi

    2015-08-01

    The clinical translation of regenerative endodontics demands further development of suitable scaffolds. Here, we assessed the possibility of using silk fibroin scaffold for pulp regeneration with dental pulp stem cells (DPSCs) and basic fibroblast growth factor (bFGF) in ectopic root canal transplantation model. Porous silk fibroin scaffolds were fabricated using freeze-drying technique (with or without bFGF incorporation), and characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy. DPSCs were isolated, characterized, seeded onto scaffolds, and inserted into the tooth root fragments. Cell viability and morphology were tested in the 3D model in vitro using CCK8 assay and SEM. Furthermore, the ectopic transplantation model was used to verify the generation of pulp-like tissue in DPSCs seeded silk fibroin scaffold with bFGF, as examined by histological analysis. DPSCs seeded in silk fibroin scaffold survived, exhibited cytoplasmic elongation in scaffolds at least 4 weeks in culture. bFGF promoted DPSCs viability in tooth fragments/scaffolds (TSS) between 7 and 28 days. Pulp-like tissue was generated in the bFGF-incorporated TSS with DPSCs. Histologically, the generated tissue was shown to be with well vascularity, have new matrix deposition and dentin-like tissue formation, and consist of both the transplanted and host-derived cells. Collectively, these data support the use of bFGF-incorporated silk fibroin scaffold as a highly promising scaffold candidate for future treatment concepts in regenerative endodontics to save teeth. PMID:25791684

  13. Multi-protein Delivery by Nanodiamonds Promotes Bone Formation

    PubMed Central

    Moore, L.; Gatica, M.; Kim, H.; Osawa, E.; Ho, D.

    2013-01-01

    Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE® for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation. PMID:24045646

  14. Crosstalk between platelets and PBMC: New evidence in wound healing.

    PubMed

    Nami, Niccolò; Feci, Luca; Napoliello, Luca; Giordano, Antonio; Lorenzini, Sauro; Galeazzi, Mauro; Rubegni, Pietro; Fimiani, Michele

    2016-01-01

    Platelet-derived products have proven useful in accelerating healing processes and tissue regeneration. However, despite their widespread use in clinical practice, the cellular and molecular mechanisms involved have not yet been completely clarified. Recent studies show that interaction between platelet gel (PG) and peripheral blood mononuclear cells (PBMC) can result in activation of PBMC and production of several cytokines involved in wound healing and tissue repair. The aim of our study was to analyze whether crosstalk between platelets and PBMC can influence wound healing by modulating release of VEGF, bFGF and IL-10 by PBMC. Cultures of PBMC alone and co-cultures with autologous PG of 24 healthy volunteers were incubated under normoxia for 24 h. VEGF, bFGF and IL-10 concentration and expression were then analyzed in supernatants by ELISA and by real-time RT-PCR. We observed a down-regulation of VEGF and bFGF release and an up-regulation of IL-10 release in co-cultures of PBMC and PG. Platelets are not only important in the early stages of the healing process (clot formation, direct release of growth factors), but also can influence the whole process of tissue regeneration by modulating synthesis and release of VEGF, bFGF and IL-10 by PBMC. These effects could give platelets a new key role in the control of healing processes and provide insights into the clinical success of platelet-derived products in many medical fields. PMID:26030799

  15. Multi-protein delivery by nanodiamonds promotes bone formation.

    PubMed

    Moore, L; Gatica, M; Kim, H; Osawa, E; Ho, D

    2013-11-01

    Bone morphogenetic proteins (BMPs) are well-studied regulators of cartilage and bone development that have been Food and Drug Administration (FDA)-approved for the promotion of bone formation in certain procedures. BMPs are seeing more use in oral and maxillofacial surgeries because of recent FDA approval of InFUSE(®) for sinus augmentation and localized alveolar ridge augmentation. However, the utility of BMPs in medical and dental applications is limited by the delivery method. Currently, BMPs are delivered to the surgical site by the implantation of bulky collagen sponges. Here we evaluate the potential of detonation nanodiamonds (NDs) as a delivery vehicle for BMP-2 and basic fibroblast growth factor (bFGF). Nanodiamonds are biocompatible, 4- to 5-nm carbon nanoparticles that have previously been used to deliver a wide variety of molecules, including proteins and peptides. We find that both BMP-2 and bFGF are readily loaded onto NDs by physisorption, forming a stable colloidal solution, and are triggered to release in slightly acidic conditions. Simultaneous delivery of BMP-2 and bFGF by ND induces differentiation and proliferation in osteoblast progenitor cells. Overall, we find that NDs provide an effective injectable alternative for the delivery of BMP-2 and bFGF to promote bone formation. PMID:24045646

  16. A Comparison of Conventional Collagen Sponge and Collagen-Gelatin Sponge in Wound Healing

    PubMed Central

    Jinno, Chizuru; Morimoto, Naoki; Ito, Ran; Sakamoto, Michiharu; Ogino, Shuichi; Taira, Tsuguyoshi; Suzuki, Shigehiko

    2016-01-01

    The objective of this study was to compare the effectiveness of the collagen-gelatin sponge (CGS) with that of the collagen sponge (CS) in dermis-like tissue regeneration. CGS, which achieves the sustained release of basic fibroblast growth factor (bFGF), is a promising material in wound healing. In the present study, we evaluated and compared CGSs and conventional CSs. We prepared 8 mm full-thickness skin defects on the backs of rats. Either CGSs or CSs were impregnated with normal saline solution (NSS) or 7 μg/cm2 of bFGF solution and implanted into the defects. At 1 and 2 weeks after implantation, tissue specimens were obtained from the rats of each group (n = 3, total n = 24). The wound area, neoepithelial length, dermis-like tissue area, and the number and area of capillaries were evaluated at 1 and 2 weeks after implantation. There were no significant differences in the CGS without bFGF and CS groups. Significant improvements were observed in the neoepithelial length, the dermis-like tissue area, and the number of newly formed capillaries in the group of rats that received CGSs impregnated with bFGF. The effects on epithelialization, granulation, and vascularization of wound healing demonstrated that, as a scaffold, CGSs are equal or superior to conventional CSs. PMID:27218103

  17. Long-term Angiogenesis Efficacy Using a Heparin-Conjugated Fibrin (HCF) Delivery System with HBM-MSCs

    PubMed Central

    Kim, Ae-Kyeong; Kim, Min-Hee; Kim, Byung-Soo; Kim, Dong-Ik

    2012-01-01

    Background and Objectives: Heparin-conjugated fibrin (HCF) is suitable for the release and localization of bFGF. We analyzed the effects of a bFGF delivery system using HCF with human bone marrow-derived mesenchymal stem cells (HBM- MSCs) in a dog ischemic limb model. Methods and Results: Animals were divided into HBM-MSCs, HBM-MSCs+HCF, bFGF-HCF, and HBM-MSCs+ bFGF-HCF groups. A total of 1×107 HBM-MSCs were injected per animal, and the amount of bFGF was 1 mg per dog. Ischemic muscles were harvested at eight weeks and six months after injection of cells. The HBM-MSCs+ bFGF-HCF group exhibited decreased proportions of capillaries and arterioles six months after transplantation. However, there were more cells positive for the angiogenic factors, VEGF and PDGF, in the eight-week specimens compared with those harvested six months after transplantation. Conclusions: Our results demonstrated that a single injection of HBM-MSCs did not have significant long-term angiogenic effects; however, a bFGF delivery system using HCF exerted prolonged angiogenic effects when combined with HBM-MSCs. PMID:24298352

  18. Intramuscular Injection of Angiogenic Gene with Bubble Liposomes Followed by Ultrasound Exposure to Improve Angiogenesis

    NASA Astrophysics Data System (ADS)

    Negishi, Yoichi; Matsuo, Keiko; Endo-Takahashi, Yoko; Suzuki, Kentaro; Matsuki, Yuuki; Takagi, Norio; Suzuki, Ryo; Maruyama, Kazuo; Aramaki, Yukihiko

    2011-09-01

    Ultrasound (US) in combination with microbubbles has recently engendered much attention as a safe method of gene delivery. Previously, we have developed polyethyleneglycol (PEG)-modified liposomes entrapping echo-contrast gas. We have called the liposomes "Bubble liposomes" (BLs). In this study, to assess the feasibility and the effectiveness of BLs for angiogenic gene delivery in clinical use, we tried to deliver bFGF (an angiogenic factor) expressing plasmid DNA into a mouse hindlimb ischemia model by the combination of BLs and US exposure. After femoral artery ligation, the hindlimb of ischemic mice were treated with BLs and US-mediated intramuscular gene transfer of bFGF expressing plasmid DNA. After the treatment, blood flow was determined over 2 weeks using laser doppler blood flow meter. As a result, the blood flow in the treated groups with BLs and US-mediated the gene transfer was quickly measured, and compared to other treatment groups (non-treated, bFGF alone, or bFGF+US). Furthermore, the number of CD31 positive cells was higher in the treatment groups with BLs and US-mediated the gene transfer than in other treatment groups. These results suggest that intramuscular injection of bFGF as an angiogenic gene with Bubble liposomes followed by ultrasound exposure improved angiogenesis in the ischemic muscle. Thus, gene transfer into the ischemic muscle by the combination of BLs and US exposure is an effective means of angiogenic gene therapy.

  19. Forced expression of Sox2 or Nanog in human bone marrow derived mesenchymal stem cells maintains their expansion and differentiation capabilities

    SciTech Connect

    Go, Masahiro J. Takenaka, Chiemi; Ohgushi, Hajime

    2008-03-10

    Mesenchymal stem cells (MSCs) derived from human bone marrow have capability to differentiate into cells of mesenchymal lineage. The cells have already been applied in various clinical situations because of their expansion and differentiation capabilities. The cells lose their capabilities after several passages, however. With the aim of conferring higher capability on human bone marrow MSCs, we introduced the Sox2 or Nanog gene into the cells. Sox2 and Nanog are not only essential for pluripotency and self-renewal of embryonic stem cells, but also expressed in somatic stem cells that have superior expansion and differentiation potentials. We found that Sox2-expressing MSCs showed consistent proliferation and osteogenic capability in culture media containing basic fibroblast growth factor (bFGF) compared to control cells. Significantly, in the presence of bFGF in culture media, most of the Sox2-expressing cells were small, whereas the control cells were elongated in shape. We also found that Nanog-expressing cells even in the absence of bFGF had much higher capabilities for expansion and osteogenesis than control cells. These results demonstrate not only an effective way to maintain proliferation and differentiation potentials of MSCs but also an important implication about the function of bFGF for self-renewal of stem cells including MSCs.

  20. Telescópio de pequeno porte como suporte ao ensino em cidades com intensa poluição luminosa II

    NASA Astrophysics Data System (ADS)

    Pereira, P. C. R.; Santos-Júnior, J. M.; Cruz, W. S.

    2003-08-01

    Para a maioria dos estudantes, sua passagem pelo ensino formal fundamental envolve a transmissão de fatos que devem ser guardados para um exame, a habilidade para lembrar fórmulas e, eventualmente, a repetição de experimentos que devem produzir resultados exigidos pelo professor. O resultado deste modelo de ensino, ao longo dos anos, é conhecido por todos: desconhecimento e descontentamento, por parte dos estudantes, de temas relativos ao papel e aos processos da ciência. Acreditamos que a Astronomia, pelo seu caráter observacional, é uma das áreas do conhecimento que pode contribuir neste cenário. A Fundação Planetário da Cidade do Rio de Janeiro possui um telescópio Meade LX-200 (25cm) que, juntamente com as câmeras CCD ST-7E e ST8E, tem sido utilizado em projetos voltados aos estudantes do ensino médio desde o ano 2000. Tais projetos envolvem a condução de um projeto de pesquisa observacional num nível apropriado, e possibilitam o contato com técnicas e novas tecnologias: computador, software para manipulação de dados e gráficos, programas de tratamento e redução de dados, uso de equipamentos óptico-eletrônicos (telescópio e CCD), bem como o processo de aquisição de conhecimento. Dentro da proposta dos anos anteriores, priorizamos projetos de uma noite, ou seja, procuramos trabalhar com fenômenos que apresentem variabilidade com intervalo de recorrência relativamente curto. Em todos os casos, optamos pela fotometria diferencial, que tem se mostrado bastante eficiente para o céu luminoso como o da cidade do Rio de Janeiro. Neste painel, apresentamos alguns dos projetos desenvolvidos no último ano, com 25 estudantes. Apresentamos os resultados da observação da variável pulsante AI Vel (V = 6,6) e da variável cataclísmica FO Aqr (V = 13,5), e do monitoramento do trânsito da lua de Júpiter, Europa, ocorrido em 30 de abril de 2003. As curvas de luz produzidas para as primeiras estão concordantes com as da literatura, assim