How do different types of community commitment influence brand commitment? The mediation of brand attachment.

PubMed

Zhang, Ning; Zhou, Zhi-min; Su, Chen-ting; Zhou, Nan

2013-11-01

Although previous research indicates that participation in a brand community may foster consumer loyalty to the brand in question, research has seldom examined the mediating effect of community commitment on brand commitment. Drawing from the typologies of organizational commitment, we divide community commitment into three components: continuance community commitment (continuance CC), affective community commitment (affective CC), and normative community commitment (normative CC). We then assess the mediating role of brand attachment in the relationship between these three components and brand commitment. We test the hypotheses using a sample of online mobile phone brand communities in China. The empirical results reveal that brand attachment exerts an indirect (but not mediated) effect on the relationship between continuance CC and brand commitment and on the relationship between normative CC and brand commitment. We also find that it exerts a partial mediating effect on the relationship between affective CC and brand commitment. The findings contribute to the branding literature and have important implications for brand community management.

How Do Different Types of Community Commitment Influence Brand Commitment? The Mediation of Brand Attachment

PubMed Central

Zhang, Ning; Su, Chen-ting; Zhou, Nan

2013-01-01

Abstract Although previous research indicates that participation in a brand community may foster consumer loyalty to the brand in question, research has seldom examined the mediating effect of community commitment on brand commitment. Drawing from the typologies of organizational commitment, we divide community commitment into three components: continuance community commitment (continuance CC), affective community commitment (affective CC), and normative community commitment (normative CC). We then assess the mediating role of brand attachment in the relationship between these three components and brand commitment. We test the hypotheses using a sample of online mobile phone brand communities in China. The empirical results reveal that brand attachment exerts an indirect (but not mediated) effect on the relationship between continuance CC and brand commitment and on the relationship between normative CC and brand commitment. We also find that it exerts a partial mediating effect on the relationship between affective CC and brand commitment. The findings contribute to the branding literature and have important implications for brand community management. PMID:23768073

Innate immunity and HIV-1 infection.

PubMed

Lehner, T; Wang, Y; Whittall, T; Seidl, T

2011-04-01

HIV-1 is predominantly transmitted through mucosal tissues, targeting CD4(+)CCR5(+) T cells, 50% of which are destroyed within 2 weeks of infection. Conventional vaccination strategies have so far failed to prevent HIV-1 infection. Neither antibodies nor cytotoxic lymphocytes are capable of mounting a sufficiently rapid immune response to prevent early destruction of these cells. However, innate immunity is an early-response system, largely independent of prior encounter with a pathogen. Innate immunity can be classified into cellular, extracellular, and intracellular components, each of which is exemplified in this review by γδ T cells, CC chemokines, and APOBEC3G, respectively. First, γδ T cells are found predominantly in mucosal tissues and produce cytokines, CC chemokines, and antiviral factors. Second, the CC chemokines CCL-3, CCL-4, and CCL-5 can be upregulated by immunization of macaques with SIVgp120 and gag p27, and these can bind and downmodulate CCR5, thereby inhibiting HIV-1 entry into the host cells. Third, APOBEC3G is generated and maintained following rectal mucosal immunization in rhesus macaques for over 17 weeks, and the innate anti-SIV factor is generated by CD4(+)CD95(+)CCR7(-) effector memory T cells. Thus, innate anti-HIV-1 or SIV immunity can be linked with immune memory, mediated by CD4(+) T cells generating APOBEC3G. The multiple innate functions may mount an early anti-HIV-1 response and either prevent viral transmission or contain the virus until an effective adaptive immune response develops.

GSTM3 and GSTP1: novel players driving tumor progression in cervical cancer

PubMed Central

Checa-Rojas, Alberto; Delgadillo-Silva, Luis Fernando; Velasco-Herrera, Martín del Castillo; Andrade-Domínguez, Andrés; Gil, Jeovanis; Santillán, Orlando; Lozano, Luis; Toledo-Leyva, Alfredo; Ramírez-Torres, Alberto; Talamas-Rohana, Patricia; Encarnación-Guevara, Sergio

2018-01-01

The molecular processes and proteomic markers leading to tumor progression (TP) in cervical cancer (CC) are either unknown or only partially understood. TP affects metabolic and regulatory mechanisms that can be identified as proteomic changes. To identify which proteins are differentially expressed and to understand the mechanisms of cancer progression, we analyzed the dynamics of the tumor proteome in CC cell lines. This analysis revealed two proteins that are up-regulated during TP, GSTM3 and GSTP1. These proteins are involved in cell maintenance, cell survival and the cellular stress response via the NF-κB and MAP kinase pathways during TP. Furthermore, GSTM3 and GSTP1 knockdown showed that evasion of apoptosis was affected, and tumor proliferation was significantly reduced. Our data indicate the critical role of GST proteins in the regulation and progression of cervical cancer cells. Hence, we suggest GSTM3 and GSTP1 as novel biomarkers and potential therapeutic targets for treating cervical cancer. Significance CC is particularly hazardous in the advanced stages, and there are few therapeutic strategies specifically targeting these stages. We performed analyses on CC tumor proteome dynamics and identified GSTM3 and GSTP1 as novel potential therapeutic targets. Knockdown of these proteins showed that they are involved in cell survival, cell proliferation and cellular evasion of apoptosis. PMID:29774096

Centchroman inhibits proliferation of head and neck cancer cells through the modulation of PI3K/mTOR Pathway

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

Srivastava, Vikas Kumar; Gara, Rishi Kumar; Bhatt, M.L.B.

Research highlights: {yields} Centchroman (CC) inhibits cellular proliferation in HNSCC cells through the dual inhibition of PI3/mTOR pathway. {yields} CC treatment also inhibits STAT3 activation and alters expression of proteins involved in cell cycle regulation and DNA repair response in HNSCC cells. {yields} CC exhibits anti-proliferative activity in a variety of non-HNSCC cancer cell lines and is devoid of cytotoxicity to normal cell types of diverse origins. -- Abstract: Centchroman (CC; 67/20; INN: Ormeloxifene) is a non-steroidal antiestrogen extensively used as a female contraceptive in India. In the present study, we report the anti-proliferative effect of CC in head andmore » neck squamous cell carcinoma (HNSCC) cells. CC inhibited cell proliferation in a dose dependent manner at 24 h of treatment. Further studies showed that CC treatment induced apoptosis, inhibited Akt/mTOR and signal transducers and activators of transcription protein 3 (STAT3) signaling, altered proteins associated with cell cycle regulation and DNA damage and inhibited colony forming efficiency of HNSCC cells. In addition, CC displayed anti-proliferative activity against a variety of non-HNSCC cell lines of diverse origin. The ability of CC to serve as a dual-inhibitor of Akt/mTOR and STAT3 signaling warrants further studies into its role as a therapeutic strategy against HNSCC.« less

Can dendritic cells improve whole cancer cell vaccines based on immunogenically killed cancer cells?

PubMed Central

Cicchelero, Laetitia; Denies, Sofie; Devriendt, Bert; de Rooster, Hilde; Sanders, Niek N

2015-01-01

Immunogenic cell death (ICD) offers interesting opportunities in cancer cell (CC) vaccine manufacture, as it increases the immunogenicity of the dead CC. Furthermore, fusion of CCs with dendritic cells (DCs) is considered a superior method for generating whole CC vaccines. Therefore, in this work, we determined in naive mice whether immunogenically killed CCs per se (CC vaccine) elicit an antitumoral immune response different from the response observed when immunogenically killed CCs are associated with DCs through fusion (fusion vaccine) or through co-incubation (co-incubation vaccine). After tumor inoculation, the type of immune response in the prophylactically vaccinated mice differed between the groups. In more detail, fusion vaccines elicited a humoral anticancer response, whereas the co-incubation and CC vaccine mainly induced a cellular response. Despite these differences, all three approaches offered a prophylactic protection against tumor development in the murine mammary carcinoma model. In summary, it can be concluded that whole CC vaccines based on immunogenically killed CCs may not necessarily require association with DCs to elicit a protective anticancer immune response. If this finding can be endorsed in other cancer models, the manufacture of CC vaccines would greatly benefit from this new insight, as production of DC-based vaccines is laborious, time-consuming and expensive. PMID:26587315

Deregulation of the miRNAs Expression in Cervical Cancer: Human Papillomavirus Implications

PubMed Central

Gómez-Gómez, Yazmín; Organista-Nava, Jorge; Gariglio, Patricio

2013-01-01

MicroRNAs (miRNAs) are a class of small non coding RNAs of 18–25 nucleotides in length. The temporal or short-lived expression of the miRNAs modulates gene expression post transcriptionally. Studies have revealed that miRNAs deregulation correlates and is involved with the initiation and progression of human tumors. Cervical cancer (CC) displays notably increased or decreased expression of a large number of cellular oncogenic or tumor suppressive miRNAs, respectively. However, understanding the potential role of miRNAs in CC is still limited. In CC, the high-risk human papillomaviruses (HR-HPVs) infection can affect the miRNAs expression through oncoprotein E6 and E7 that contribute to viral pathogenesis, although other viral proteins might also be involved. This deregulation in the miRNAs expression has an important role in the hallmarks of CC. Interestingly, the miRNA expression profile in CC can discriminate between normal and tumor tissue and the extraordinary stability of miRNAs makes it suitable to serve as diagnostic and prognostic biomarkers of cancer. In this review, we will summarize the role of the HR-HPVs in miRNA expression, the role of miRNAs in the hallmarks of CC, and the use of miRNAs as potential prognostic biomarkers in CC. PMID:24490161

75 FR 31791 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-04

... reveal the genetic processes occurring in ccRCC tissues that may contribute to advanced disease. Positive... transformed into blood brain barrier permeable forms by the coupling of an Inter-Cellular Adhesion Molecule-1...

The effect of a physical activity intervention on preschoolers' fundamental motor skills - A cluster RCT.

PubMed

Wasenius, Niko S; Grattan, Kimberly P; Harvey, Alysha L J; Naylor, Patti-Jean; Goldfield, Gary S; Adamo, Kristi B

2018-07-01

To assess the effect of a physical activity intervention delivered in the childcare centres (CC), with or without a parent-driven home physical activity component, on children's fundamental motor skills (FMS). Six-month 3-arm cluster randomized controlled trial. Preschoolers were recruited from 18 licensed CC. CC were randomly assigned to a typical curriculum comparison group (COM), childcare intervention alone (CC), or childcare intervention with parental component (CC+HOME). FMS was measured with the Test of Gross Motor Development-2. Linear mixed models were performed at the level of the individual while accounting for clustering. Raw locomotor skills score increased significantly in the CC group (mean difference=2.5 units, 95% Confidence Intervals, CI, 1.0-4.1, p<0.001) and the CC+HOME group (mean difference=2.4 units, 95% CI, 0.8-4.0, p<0.001) compared to the COM group. No significant (p>0.05) between group differences were observed in the raw object control skills, sum of raw scores, or gross motor quotient. No significant sex differences were found in any of the measured outcomes. A physical activity intervention delivered in childcare with or without parents' involvement was effective in increasing locomotor skills in preschoolers. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Centralized Command, Distributed Control, and Decentralized Execution - a Command and Control Solution to US Air Force A2/AD Challenges

DTIC Science & Technology

2017-04-28

Regional Air Component Commander (the Leader) 5 CC-DC- DE Solution to A2/AD – Distributed Theater Air Control System (the System) 9 CC-DC- DE ... Control , Decentralized Execution” to a new framework of “Centralized Command, Distributed Control , and Decentralized Execution” (CC-DC- DE ).4 5 This...USAF C2 challenges in A2/AD environments describes a three-part Centralized Command, Distributed Control , and Decentralized Execution (CC-DC- DE

Histological heterogeneity in primary and metastatic classic combined hepatocellular-cholangiocarcinoma: a case series.

PubMed

De Vito, Claudio; Sarker, Debashis; Ross, Paul; Heaton, Nigel; Quaglia, Alberto

2017-11-01

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare and aggressive primary liver cancer with both hepatocellular and cholangiocellular differentiation. Due to its bi-phenotypic component, cHCC-CC is a heterogeneous tumour and histopathological analysis of metastatic deposits is poorly characterized. In this retrospective study, we describe four patients in whom the histology from resected specimens of both primary and recurrent and/or metastatic tumour was available for comparison and immunohistochemical characterization. Our study shows that recurrent or metastatic deposits replicate the heterogeneity of the primary cHCC-CC, that even originally small foci of divergent differentiation can become predominant later on and that hepatocellular and cholangiocellular components can show different tropism in distant organs. In our experience, the behaviour of recurrent/metastatic cHCC-CC is unpredictable and histological examination is necessary to guide treatment options at present.

Cinnamomum cassia Essential Oil Inhibits α-MSH-Induced Melanin Production and Oxidative Stress in Murine B16 Melanoma Cells

PubMed Central

Chou, Su-Tze; Chang, Wen-Lun; Chang, Chen-Tien; Hsu, Shih-Lan; Lin, Yu-Che; Shih, Ying

2013-01-01

Essential oils extracted from aromatic plants exhibit important biological activities and have become increasingly important for the development of aromatherapy for complementary and alternative medicine. The essential oil extracted from Cinnamomum cassia Presl (CC-EO) has various functional properties; however, little information is available regarding its anti-tyrosinase and anti-melanogenic activities. In this study, 16 compounds in the CC-EO have been identified; the major components of this oil are cis-2-methoxycinnamic acid (43.06%) and cinnamaldehyde (42.37%). CC-EO and cinnamaldehyde exhibited anti-tyrosinase activities; however, cis-2-methoxycinnamic acid did not demonstrate tyrosinase inhibitory activity. In murine B16 melanoma cells stimulated with α-melanocyte-stimulating hormone (α-MSH), CC-EO and cinnamaldehyde not only reduced the melanin content and tyrosinase activity of the cells but also down-regulated tyrosinase expression without exhibiting cytotoxicity. Moreover, CC-EO and cinnamaldehyde decreased thiobarbituric acid-reactive substance (TBARS) levels and restored glutathione (GSH) and catalase activity in the α-MSH-stimulated B16 cells. These results demonstrate that CC-EO and its major component, cinnamaldehyde, possess potent anti-tyrosinase and anti-melanogenic activities that are coupled with antioxidant properties. Therefore, CC-EO may be a good source of skin-whitening agents and may have potential as an antioxidant in the future development of complementary and alternative medicine-based aromatherapy. PMID:24051402

Microbacterium agarici sp. nov., Microbacterium humi sp. nov. and Microbacterium pseudoresistens sp. nov., isolated from the base of the mushroom Agaricus blazei.

PubMed

Young, C-C; Busse, H-J; Langer, S; Chu, Jiunn-Nan; Schumann, P; Arun, A B; Shen, Fo-Ting; Rekha, P D; Kämpfer, P

2010-04-01

Three Gram-positive, rod-shaped bacteria (strains CC-SBCK-209( T), CC-12309(T) and CC-5209(T)) were isolated from the stalk of the edible mushroom Agaricus blazei grown in the laboratory. 16S rRNA gene sequence analysis indicated that all three isolates clearly belonged to the genus Microbacterium. Strains CC-SBCK-209( T) and CC-12309(T) were most related closely to the type strain of Microbacterium halotolerans (95.9 and 96.1 % 16S rRNA gene sequence similarity, respectively). These two novel strains shared 97.9 % 16S rRNA gene sequence similarity. Levels of similarity to the type strains of all other recognized Microbacterium species were lower than 95.5 %. The third strain (CC-5209( T)) showed the highest 16S rRNA gene sequence similarity to the type strain of Microbacterium resistens (97.6 %); levels of similarity to the type strains of all other recognized Microbacterium species were lower than 96 %. The quinone systems of strains CC-SBCK-209(T), CC-12309(T) and CC-5209(T) consisted of MK-11/MK-12, MK-11/MK-10 and MK-13 as major compounds, respectively. All three strains contained ornithine in their peptidoglycan. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and an unknown glycolipid. The polyamine pattern consisted of spermidine and spermine as predominant components. Fatty acid profiles (anteiso-C(15 : 0), iso-C(16 : 0) and anteiso-C(17 : 0 ) as major components) supported the affiliation of all three strains to the genus Microbacterium. The results of physiological and biochemical tests and DNA-DNA hybridization experiments allowed the clear phenotypic and genotypic differentiation of strains CC-SBCK-209(T) and CC-12309( T) from M. halotolerans and other closely related Microbacterium species. Strain CC-5209(T) could be differentiated clearly from M. resistens both genotypically and phenotypically. Based on these data, the novel strains are considered to represent three novel species of the genus Microbacterium. The names proposed for these organisms are Microbacterium agarici sp. nov. [type strain CC-SBCK-209( T) (=DSM 21798(T)=CCM 7686(T))], Microbacterium humi sp. nov. [type strain CC-12309(T) (=DSM 21799(T)=CCM 7687(T))] and Microbacterium pseudoresistens sp. nov. [type strain CC-5209(T) (=DSM 22185(T)=CCM 7688(T))].

Investigating implicit statistical learning mechanisms through contextual cueing.

PubMed

Goujon, Annabelle; Didierjean, André; Thorpe, Simon

2015-09-01

Since its inception, the contextual cueing (CC) paradigm has generated considerable interest in various fields of cognitive sciences because it constitutes an elegant approach to understanding how statistical learning (SL) mechanisms can detect contextual regularities during a visual search. In this article we review and discuss five aspects of CC: (i) the implicit nature of learning, (ii) the mechanisms involved in CC, (iii) the mediating factors affecting CC, (iv) the generalization of CC phenomena, and (v) the dissociation between implicit and explicit CC phenomena. The findings suggest that implicit SL is an inherent component of ongoing processing which operates through clustering, associative, and reinforcement processes at various levels of sensory-motor processing, and might result from simple spike-timing-dependent plasticity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lightweight, Ultra-High-Temperature, CMC-Lined Carbon/Carbon Structures

NASA Technical Reports Server (NTRS)

Wright, Matthew J.; Ramachandran, Gautham; Williams, Brian E.

2011-01-01

Carbon/carbon (C/C) is an established engineering material used extensively in aerospace. The beneficial properties of C/C include high strength, low density, and toughness. Its shortcoming is its limited usability at temperatures higher than the oxidation temperature of carbon . approximately 400 C. Ceramic matrix composites (CMCs) are used instead, but carry a weight penalty. Combining a thin laminate of CMC to a bulk structure of C/C retains all of the benefits of C/C with the high temperature oxidizing environment usability of CMCs. Ultramet demonstrated the feasibility of combining the light weight of C/C composites with the oxidation resistance of zirconium carbide (ZrC) and zirconium- silicon carbide (Zr-Si-C) CMCs in a unique system composed of a C/C primary structure with an integral CMC liner with temperature capability up to 4,200 F (.2,315 C). The system effectively bridged the gap in weight and performance between coated C/C and bulk CMCs. Fabrication was demonstrated through an innovative variant of Ultramet fs rapid, pressureless melt infiltration processing technology. The fully developed material system has strength that is comparable with that of C/C, lower density than Cf/SiC, and ultra-high-temperature oxidation stability. Application of the reinforced ceramic casing to a predominantly C/C structure creates a highly innovative material with the potential to achieve the long-sought goal of long-term, cyclic high-temperature use of C/C in an oxidizing environment. The C/C substructure provided most of the mechanical integrity, and the CMC strengths achieved appeared to be sufficient to allow the CMC to perform its primary function of protecting the C/C. Nozzle extension components were fabricated and successfully hot-fire tested. Test results showed good thermochemical and thermomechanical stability of the CMC, as well as excellent interfacial bonding between the CMC liner and the underlying C/C structure. In particular, hafnium-containing CMCs on C/C were shown to perform well at temperatures exceeding 3,500 F (.1,925 C). The melt-infiltrated CMC-lined C/C composites offered a lower density than Cf/SiC. The melt-infiltrated composites offer greater use temperature than Cf/SiC because of the more refractory ceramic matrices and the C/C substructure provides greater high-temperature strength. The progress made in this work will allow multiple high-temperature components used in oxidizing environments to take advantage of the low density and high strength of C/C combined with the high-temperature oxidation resistance of melt-infiltrated CMCs.

Recombinant Human T-Cell Leukemia Virus Types 1 and 2 Tax Proteins Induce High Levels of CC-Chemokines and Downregulate CCR5 in Human Peripheral Blood Mononuclear Cells

PubMed Central

Barrios, Christy S.; Abuerreish, Muna; Lairmore, Michael D.; Castillo, Laura; Giam, Chou-Zen

2011-01-01

Abstract Human T-cell leukemia viruses types 1 (HTLV-1) and 2 (HTLV-2) produce key transcriptional regulatory gene products, known as Tax1 and Tax2, respectively. Tax1 and Tax2 transactivate multiple host genes involved in cellular immune responses within the cellular microenvironment, including induction of genes encoding expression of CC-chemokines. It is speculated that HTLV Tax proteins may act as immune modulators. In this study, recombinant Tax1 and Tax2 proteins were tested for their effects on the viability of cultured peripheral blood mononuclear cells (PBMCs), and their ability to induce expression of CC-chemokines and to downregulate the level of CCR5 expression in PBMCs. PBMCs obtained from uninfected donors were cultured in a range of Tax1 and Tax2 concentrations (10–100 pM), and supernatant fluids were harvested at multiple time points for quantitative determinations of MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5. Treatment of PBMCs with Tax1 and Tax2 proteins (100 pM) resulted in a significant increase in viability over a 7-d period compared to controls (p<0.01). Both Tax1 and Tax2 induced high levels of all three CC-chemokines over the dosing range compared to mock-treated controls (p<0.05). The gated population of lymphocytes treated with Tax2, as well as lymphocytes from HTLV-2-infected donors, showed a significantly lower percentage of CCR5-positive cells compared to those of uninfected donors and from mock-treated lymphocytes, respectively (p<0.05). These results suggest that Tax1 and Tax2 could promote innate immunity in the extracellular environment during HTLV-1 and HTLV-2 infections via CC-chemokine ligands and receptors. PMID:22111594

Immunohistochemical localization of Clara cell secretory proteins (CC10-CC26) and Annexin-1 protein in rat major salivary glands

PubMed Central

Cecchini, Maria Paola; Merigo, Flavia; Cristofoletti, Mirko; Osculati, Francesco; Sbarbati, Andrea

2009-01-01

The oral cavity is continuously bathed by saliva secreted by the major and minor salivary glands. Saliva is the first biological medium to confront external materials that are taken into the body as part of food or drink or inhaled volatile substances, and it contributes to the first line of oral defence. In humans, it has been shown that sputum and a variety of biological fluids contain Clara cell secretory proteins (CC10–CC26). Various studies of the respiratory apparatus have suggested their protective effect against inflammatory response and oxidative stress. Recently, CC10 deficiency has been related to the protein Annexin-1 (ANXA1), which has immunomodulatory and anti-inflammatory properties. Considering the defensive role of both Clara cell secretory proteins and ANXA1 in the respiratory apparatus, and the importance of salivary gland secretion in the first line of oral defence, we decided to evaluate the expression of CC10, CC26 and ANXA1 proteins in rat major salivary glands using immunohistochemistry. CC10 expression was found only in the ductal component of the sublingual gland. Parotid and submandibular glands consistently lacked CC10 immunoreactivity. In the parotid gland, both acinar and ductal cells were always CC26-negative, whereas in the submandibular gland, immunostaining was localized in the ductal component and in the periodic acid Schiff (PAS)-positive area. In the sublingual gland, ductal cells were always positive. Acinar cells were not immunostained at all. ANXA1 was expressed in ductal cells in all three major glands. In parotid and sublingual glands, acinar cells were negative. In submandibular glands, immunostaining was present in the mucous PAS-positive portion, whereas serous acinar cells were consistently negative. The existence of some CC10-CC26–ANXA1-positive cells in rat salivary glandular tissue is an interesting preliminary finding which could support the hypothesis, suggested for airway tissue, that these proteins have a defensive and protective role. Protein expression heterogeneity in the different portions of the glands could be an important clue in further investigations of their role. PMID:19438769

The coiled-coil domain of MURC/cavin-4 is involved in membrane trafficking of caveolin-3 in cardiomyocytes.

PubMed

Naito, Daisuke; Ogata, Takehiro; Hamaoka, Tetsuro; Nakanishi, Naohiko; Miyagawa, Kotaro; Maruyama, Naoki; Kasahara, Takeru; Taniguchi, Takuya; Nishi, Masahiro; Matoba, Satoaki; Ueyama, Tomomi

2015-12-15

Muscle-restricted coiled-coil protein (MURC), also referred to as cavin-4, is a member of the cavin family that works cooperatively with caveolins in caveola formation and function. Cavins are cytoplasmic proteins with coiled-coil domains and form heteromeric complexes, which are recruited to caveolae in cells expressing caveolins. Among caveolins, caveolin-3 (Cav3) is exclusively expressed in muscle cells, similar to MURC/cavin-4. In the heart, Cav3 overexpression contributes to cardiac protection, and its deficiency leads to progressive cardiomyopathy. Mutations in the MURC/cavin-4 gene have been identified in patients with dilated cardiomyopathy. In the present study, we show the role of MURC/cavin-4 as a caveolar component in the heart. In H9c2 cells, MURC/cavin-4 was localized at the plasma membrane, whereas a MURC/cavin-4 mutant lacking the coiled-coil domain (ΔCC) was primarily localized to the cytoplasm. ΔCC bound to Cav3 and impaired membrane localization of Cav3 in cardiomyocytes. Additionally, although ΔCC did not alter Cav3 mRNA expression, ΔCC decreased the Cav3 protein level. MURC/cavin-4 and ΔCC similarly induced cardiomyocyte hypertrophy; however, ΔCC showed higher hypertrophy-related fetal gene expression than MURC/cavin-4. ΔCC induced ERK activation in cardiomyocytes. Transgenic mice expressing ΔCC in the heart (ΔCC-Tg mice) showed impaired cardiac function accompanied by cardiomyocyte hypertrophy and marked interstitial fibrosis. Hearts from ΔCC-Tg mice showed a reduction of the Cav3 protein level and activation of ERK. These results suggest that MURC/cavin-4 requires its coiled-coil domain to target the plasma membrane and to stabilize Cav3 at the plasma membrane of cardiomyocytes and that MURC/cavin-4 functions as a crucial caveolar component to regulate cardiac function. Copyright © 2015 the American Physiological Society.

An Overview of Cultural Competency Curricula in ACGME-accredited General Surgery Residency Programs.

PubMed

Shah, Sagar S; Sapigao, Francisco B; Chun, Maria B J

Cultural competency(CC) in surgical residency curricula is not the novel idea it was fourteen years ago when the ACGME challenged program directors to teach and assess six core competencies. CC is recognized as a component of "patient care", "professionalism", and "interpersonal and communication skills." The results of five programs (2004-2012) with CC curricula were identified in a 2013 paper by Ly and Chun. The primary objective of this paper is to provide the current status of CC curricula in general surgery residency programs. Three sources were used for this study. First, a four question survey on the current status of CC education was sent to program directors of ACGME-accredited surgery residency programs. Second, the lead authors from five programs previously reported in the 2013 paper were interviewed. Third, the survey mentioned above was resent to 52 residency programs who implemented New York University's (NYU) SPICE program, which has a CC component. Participants for the survey consisted of program directors of ACGME-accredited surgery residency programs. The interviews were conducted with the corresponding authors from the previous study by Ly and Chun. Of the 256 surveyed, nine responded; seven stated that CC is not taught formally at their institution while four stated that they do not feel any part of CC curricula is missing from their program. Due to the low response rate, we identified and conducted interviews with general surgery residency programs with CC curricula. Of the five programs contacted, only three remain active and utilize Objective Structured Clinical Examinations (OSCEs) to teach cultural competency. One of the three, the SPICE program at NYU, has expanded to 52 other residency programs in the US. Although the importance of CC has been identified in general surgery, formal curricula and documentation of implementation remains elusive. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

International Symposiun on Biological Reactive Intermediates: Molecular and Cellular Effects and Their Impact on Human Health (4th) Held in Tucson, Arizona on 14-17 January 1990

DTIC Science & Technology

1991-04-03

477 Robert A. Roth, and James F. Reindel Reactive Oxygen Species in the Progression of CC14-1nduced Liver Injury ...COMMUNICATIONS CCl4 -Induced Cytochrome P-4S0 Loss and Lipid Peroxldation In Rat Liver Slices ........................... 669 Shana Azri, Heriberto P. Mata, A...VII. Cellular Consequences of BRI Session VIII. Interactions Between Liver and Other Celis by BR! Session IX. Messenger Mediated Intraorgan Effects

Optical implementation of (3, 3, 2) regular rectangular CC-Banyan optical network

NASA Astrophysics Data System (ADS)

Yang, Junbo; Su, Xianyu

2007-07-01

CC-Banyan network plays an important role in the optical interconnection network. Based on previous reports of (2, 2, 3) the CC-Banyan network, another rectangular-Banyan network, i.e. (3, 3, 2) rectangular CC-Banyan network, has been discussed. First, according to its construction principle, the topological graph and the routing rule of (3, 3, 2) rectangular CC-Banyan network have been proposed. Then, the optically experimental setup of (3, 3, 2) rectangular CC-Banyan network has been designed and achieved. Each stage of node switch consists of phase spatial light modulator (PSLM) and polarizing beam-splitter (PBS), and fiber has been used to perform connection between adjacent stages. PBS features that s-component (perpendicular to the incident plane) of the incident light beam is reflected, and p-component (parallel to the incident plane) passes through it. According to switching logic, under the control of external electrical signals, PSLM functions to control routing paths of the signal beams, i.e. the polarization of each optical signal is rotated or not rotated 90° by a programmable PSLM. Finally, the discussion and analysis show that the experimental setup designed here can realize many functions such as optical signal switch and permutation. It has advantages of large number of input/output-ports, compact in structure, and low energy loss. Hence, the experimental setup can be used in optical communication and optical information processing.

Inhibition of JNK Sensitizes Hypoxic Colon Cancer Cells to DNA Damaging Agents

PubMed Central

Vasilevskaya, Irina A.; Selvakumaran, Muthu; Hierro, Lucia Cabal; Goldstein, Sara R.; Winkler, Jeffrey D.; O'Dwyer, Peter J.

2015-01-01

Purpose We showed previously that in HT29 colon cancer cells, modulation of hypoxia-induced stress signaling affects oxaliplatin cytotoxicity. To further study the significance of hypoxia-induced signaling through JNK, we set out to investigate how modulation of kinase activities influences cellular responses of hypoxic colon cancer cells to cytotoxic drugs. Experimental design In a panel of cell lines we investigated effects of pharmacological and molecular inhibition of JNK on sensitivity to oxaliplatin, SN-38 and 5-FU. Combination studies for the drugs and JNK inhibitor CC-401 were carried out in vitro and in vivo. Results Hypoxia-induced JNK activation was associated with resistance to oxaliplatin. CC-401 in combination with chemotherapy demonstrates synergism in colon cancer cell lines, though synergy is not always hypoxia-specific. A more detailed analysis focused on HT29 and SW620 (responsive), and HCT116 (non-responsive) lines. In HT29 and SW620 cells CC-401 treatment results in greater DNA damage in the sensitive cells. In vivo, potentiation of bevacizumab, oxaliplatin, and the combination by JNK inhibition was confirmed in HT29-derived mouse xenografts, where tumor growth delay was greater in the presence of CC-401. Finally, stable introduction of a dominant negative JNK1, but not JNK2, construct into HT29 cells rendered them more sensitive to oxaliplatin under hypoxia, suggesting differing input of JNK isoforms in cellular responses to chemotherapy. Conclusions These findings demonstrate that signaling through JNK is a determinant of response to therapy in colon cancer models, and support the testing of JNK inhibition to sensitize colon tumors in the clinic. PMID:26023085

Association between polymorphisms in the promoter region of miR-17-92 cluster and systemic lupus erythematosus in a Chinese population.

PubMed

Wang, Rong; Wang, Chun-Fang; Qin, Hai-Mei; Lu, Yu-Lan; Wei, Gui-Jiang; Huang, Hua-Tuo; Xiang, Yang; Wang, Jun-Li; Lan, Yan; Wei, Ye-Sheng

2018-05-16

The aim of this study was to investigate the association of genetic polymorphisms in the promoter region of miR-17-92 with systemic lupus erythematosus (SLE). The gene polymorphism was analysed using SNaPshot in 312 SLE patients and 396 controls. Relative expression of miR-17-92 was measured by quantitative real-time PCR. Association was found between rs9515692 and a decreased risk of SLE (CT vs CC: OR = 0.65, 95%CI, 0.46-0.92, P = .014; CT+TT vs CC: OR = 0.64, 95%CI, 0.46-0.90, P = .009; T vs C: OR = 0.69, 95%CI, 0.52-0.92, P = .010, respectively). Haplotype analysis showed that C-G-G, C-A-A haplotypes were associated with an increased SLE risk (OR=4.46, 95%CI, 2.17-9.17, P < 0.001; OR=2.33, 95%CI, 1.44-3.76, P < 0.001, respectively). T allele and CT+TT genotypes in rs9515692 were associated with decreased risk of anti-dsDNA in SLE (CT+TT vs CC: OR = 0.42, 95%CI = 0.24-0.72, P = .002; T vs A: OR = 0.49, 95%CI = 0.31-0.79, P = .003). Moreover, rs9515692 CT+TT genotypes had a higher level of miR-17 as compared to CC genotype (P = .017). These findings suggest that the rs9515692 CT+TT genotypes were a protective factor for the susceptibility of SLE, probably by increasing the expression of miR-17. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

CC chemokine receptor 4 is required for experimental autoimmune encephalomyelitis by regulating GM-CSF and IL-23 production in dendritic cells

PubMed Central

Poppensieker, Karola; Otte, David-Marian; Schürmann, Britta; Limmer, Andreas; Dresing, Philipp; Drews, Eva; Schumak, Beatrix; Klotz, Luisa; Raasch, Jennifer; Mildner, Alexander; Waisman, Ari; Scheu, Stefanie; Knolle, Percy; Förster, Irmgard; Prinz, Marco; Maier, Wolfgang; Zimmer, Andreas; Alferink, Judith

2012-01-01

Dendritic cells (DCs) are pivotal for the development of experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which they control disease remain to be determined. This study demonstrates that expression of CC chemokine receptor 4 (CCR4) by DCs is required for EAE induction. CCR4−/− mice presented enhanced resistance to EAE associated with a reduction in IL-23 and GM-CSF expression in the CNS. Restoring CCR4 on myeloid cells in bone marrow chimeras or intracerebral microinjection of CCR4-competent DCs, but not macrophages, restored EAE in CCR4−/− mice, indicating that CCR4+ DCs are cellular mediators of EAE development. Mechanistically, CCR4−/− DCs were less efficient in GM-CSF and IL-23 production and also TH-17 maintenance. Intraspinal IL-23 reconstitution restored EAE in CCR4−/− mice, whereas intracerebral inoculation using IL-23−/− DCs or GM-CSF−/− DCs failed to induce disease. Thus, CCR4-dependent GM-CSF production in DCs required for IL-23 release in these cells is a major component in the development of EAE. Our study identified a unique role for CCR4 in regulating DC function in EAE, harboring therapeutic potential for the treatment of CNS autoimmunity by targeting CCR4 on this specific cell type. PMID:22355103

Small cell carcinoma with concomitant adenocarcinoma arising in a Barrett's oesophagus: report of a case with a favourable behaviour.

PubMed

Bibeau, Frédéric; Chateau, Marie-Christine; Guiu, Michel; Assenat, Eric; Azria, David; Lavaill, Rosy; Ychou, Marc; Boissière-Michot, Florence

2008-01-01

Most Barrett's oesophagus-associated cancers are adenocarcinomas which occur in a pure form. They are rarely combined with another type of malignancy, such as endocrine tumours. Within the endocrine spectrum, small cell carcinomas (SmCC) usually have a highly aggressive behaviour with a poor prognosis. We report a case of composite SmCC and adenocarcinoma in the setting of a Barrett's oesophagus, in a 54-year-old man. This tumour was identified on a surgical specimen after neoadjuvant treatment with radiotherapy and 5-FU-Cis-platin based chemotherapy. The SmCC component was positive for chromogranin A, synaptophysin, neural cell adhesion molecule and neuron-specific enolase and negative for high molecular weight cytokeratin. The adenocarcinoma component showed a converse phenotype. In our case, the origin of the SmCC component could be explained by the numerous chromogranin A-positive cells observed in the Barrett's oesophagus or by the potential progenitor cells that may be located in the submucosal oesophageal gland ducts and the Barrett's metaplasia. Our report is thus indicative of the high and totipotential risk of Barrett's oesophagus. Moreover, it is particular because of its favourable behaviour, with a 6-year disease-free survival, after neoadjuvant chemoradiation, surgery and postoperative chemotherapy.

Factor IX assay

MedlinePlus

... factor assay; Serum factor IX; Hemophilic factor B; Plasma thromboplastin component; PTC ... BJ. Factor IX (Christmas factor, hemophilic factor B, plasma thromboplastin component, PTC) - blood. In: Chernecky CC, Berger ...

Bacillus anthracis Edema Toxin Inhibits Staphylococcus aureus Enterotoxin B Effects in Vitro: A Potential Protein Therapeutic?

DTIC Science & Technology

2005-10-01

5). Inherent characteristics of edema toxin and other procaryotic adenylate cyclases from Bordetella pertussis, Pseudomonas aeruginosa, and Yersinia...by mouse peritoneal macrophages: the role of cellular cyclic AMP. Immunology 64:719–724. 12. Krakauer, T. 1999. Induction of CC chemokines in human

LDPE/PHB blends filled with castor oil cake

NASA Astrophysics Data System (ADS)

Burlein, Gustavo A.; Rocha, Marisa C. G.

2015-05-01

The response surface methodology (RSM) is a collection of mathematical techniques useful for developing, improving and optimizing process. In this study, RSM technique was applied to evaluate the effect of the components proportion on the mechanical properties of low density polyethylene (LDPE)/ poly (3-hydroxy-butyrate) (PHB) blends filled with castor oil cake (CC). The blends were prepared by melt mixing in a twin screw extruder. Low density polyethylene, poly (3-hydroxy-butyrate) and castor oil pressed cake were represented by the input variables designated as LDPE, PHB and CC, respectively. As it was desirable to consider the largest LDPE content in the ternary system, the components of the mixture were subjected to the following constraints: 0.7 ≤ LDPE ≤ 1.0, 0≤ PHB≤0.3 e 0 ≤ CC ≤0.3. The mechanical properties of the different mixtures were determined by conventional ASTM tests and were evaluated through analysis of variance performed by the Minitab software. Some polynomial equations were tested in order to describe the mechanical behavior of the samples. The quadratic model in pseudo components was selected for describing the tensile behavior because it was the most efficient from a statistical point of view (p-value ≤ 0.05; coefficient of determination (r2) close to 1 and variation inflation factor (VIF) values < 5). The results showed that the LDPE Young's modulus increases but the other tensile properties and impact resistance deteriorate with the addition of PHB or CC. The tensile strength values of binary mixtures of LDPE lie in the range from 8.9 to 10 MPa. As some commercial grades of LDPE have mechanical strength in this range, it may be inferred that the addition of a certain amount of PHB or CC to LDPE may be considered as a possibility for obtaining LDPE based materials with increased susceptibility to biodegradation. The cubic model in pseudo components was selected for describe the flexural strength of the samples because it was the most adequate from a statistical point of view. However, the linear model in pseudo components was the most efficient to describe the flexural modulus of the samples. The results obtained show that superior LDPE flexural properties may be obtained by the addition of PHB or castor oil cake to LDPE. The morphological study of the materials obtained showed that LDPE/PHB blends are immiscible and form morphological structures with well distinguished phase boundaries between dispersed phase and matrix. Biodegradation was evaluated burying the samples in simulated soil for different periods of time. The LDPE/PHB/CC mixtures with higher content of PHB showed more pronounced degradation. Under the experimental conditions studied the LDPE/CC compositions presented no degradation. However, the loss of mass of the LDPE/PHB/CC mixtures was higher than the loss of mass of the corresponding LDPE/PHB binary blend. This result suggests that the castor oil cake accelerates the degradation of the LDPE/PHB blends.

Intraspecies cellular fatty acids heterogeneity of Lactobacillus plantarum strains isolated from fermented foods in Ukraine.

PubMed

Garmasheva, I; Vasyliuk, O; Kovalenko, N; Ostapchuk, A; Oleschenko, L

2015-09-01

The intraspecies heterogeneity of cellular fatty acids composition of Lactobacillus plantarum strains isolated from Ukrainian traditional fermented foods was examined. Seven cellular fatty acids were identified. All Lact. plantarum strains investigated contained C16:0 (from 7·54 to 49·83% of total fatty acids), cC18:1 (3·23-38·67% of total fatty acids) and cycC19:0 acids (9·03-67·68% of total fatty acids) as the major fatty acids. The tC18:1 acid made up 1·47-22·0% of the total fatty acids. The C14:0 and C16:1 acids were present in small amounts (0·22-6·96% and 0·66-7·42% respectively) in most Lact. plantarum strains. Differences in relative contents of some fatty acids between Lact. plantarum strains depending on the source isolation were found. Isolates of dairy origin contained slightly greater levels of the C16:0 and tC18:1 fatty acids and lower levels of the cC18:1 than strains obtained from fermented vegetables. The origin of Lact. plantarum strains affects their fatty acids composition, which in turn, appears to be related to their ability to growth under stress factors. Cellular fatty acids composition is an important chemotaxonomic characteristic of bacterial cells. At the same time cellular fatty acids play a key role in maintaining the viability of micro-organisms in different environmental conditions. In this study, intraspecies heterogeneity of cellular fatty acids composition of Lactobacillus plantarum strains was examined. This work provides novel and important information about a relationship between cellular fatty acids composition of Lact. plantarum strains and source of isolation or stress resistance profile. Our results showed that cellular fatty acids composition is quite diverse among Lact. plantarum strains derived from different sources and may reflect previous cell's history. Our findings should be considered in chemotaxonomic studies of lactic acid bacteria and its ecology. © 2015 The Society for Applied Microbiology.

Chemical analysis and giardicidal effectiveness of the aqueous extract of Cymbopogon citratus Stapf.

PubMed

Méabed, Eman M H; Abou-Sreea, Alaa I B; Roby, Mohamed H H

2018-06-01

Searching for new effective and safe treatment of Giardia lamblia (G. lamblia) parasite is mandatory. The aim was to evaluate the in vitro and in vivo effectiveness of an aqueous extract prepared from the leaves of Cymbagogon citratus (CcAE) against G. lamblia and to reveal the phenolic and antioxidant properties of CcAE. CcAE (25, 50, 100, 200, 400, and 500 μg/ml) was in vitro incubated with G. lamblia trophozoites in comparison with metronidazole (MTZ 10 and 25 μg/ml). Growth inhibition was evaluated after 3, 24, and 48 h of drug exposure. Infected groups of mice were orally treated for 7 days with CcAE at 125, 250, and 500 mg/kg/day/mouse, in comparison with a group treated with 15 mg/kg/day/mouse MTZ for the same period. The total phenolic components (TPC), the total flavonoid components (TFC), the 2,2,diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, and the high-performance liquid chromatography (HPLC) for quantitative and qualitative phenolic content were chemically estimated. After 24 and 48 h of in vitro incubation, the estimated minimal inhibitory concentrations (MIC) were 500 and 400 μg/ml, respectively, and the concentrations that induced 50% growth inhibition (IC 50 ) were 93.8 and 60.4 μg/ml, respectively (P < 0.001). Mice given 500 mg/kg CcAE showed 100% stool clearance of G. lamblia stages, similar to MTZ-treated control group (P < 0.001). The TPC was 10.7 ± 0.2 mg GAE/g and the TFC was 23.9 ± 0.3 mg quercetin/g, and the estimated IC 50 for DPPH free radical scavenging was 16.4 ± 0.1 mg/ml. HPLC revealed the major phenolic components of CcAE to be carnosic acid, p-coumaric acid, cinnamiac acid, quercetin, rutin, and chlorogenic acid. In conclusion, CcAE is significantly effective against G. lamblia in vitro and in vivo, and has considerable phenolic and antioxidant properties.

Lung Basal Stem Cells Rapidly Repair DNA Damage Using the Error-Prone Nonhomologous End-Joining Pathway

PubMed Central

Weeden, Clare E.; Chen, Yunshun; Ma, Stephen B.; Hu, Yifang; Ramm, Georg; Sutherland, Kate D.; Smyth, Gordon K.

2017-01-01

Lung squamous cell carcinoma (SqCC), the second most common subtype of lung cancer, is strongly associated with tobacco smoking and exhibits genomic instability. The cellular origins and molecular processes that contribute to SqCC formation are largely unexplored. Here we show that human basal stem cells (BSCs) isolated from heavy smokers proliferate extensively, whereas their alveolar progenitor cell counterparts have limited colony-forming capacity. We demonstrate that this difference arises in part because of the ability of BSCs to repair their DNA more efficiently than alveolar cells following ionizing radiation or chemical-induced DNA damage. Analysis of mice harbouring a mutation in the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key enzyme in DNA damage repair by nonhomologous end joining (NHEJ), indicated that BSCs preferentially repair their DNA by this error-prone process. Interestingly, polyploidy, a phenomenon associated with genetically unstable cells, was only observed in the human BSC subset. Expression signature analysis indicated that BSCs are the likely cells of origin of human SqCC and that high levels of NHEJ genes in SqCC are correlated with increasing genomic instability. Hence, our results favour a model in which heavy smoking promotes proliferation of BSCs, and their predilection for error-prone NHEJ could lead to the high mutagenic burden that culminates in SqCC. Targeting DNA repair processes may therefore have a role in the prevention and therapy of SqCC. PMID:28125611

High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion.

PubMed

Li, Caixia; Culver, Silas A; Quadri, Syed; Ledford, Kelly L; Al-Share, Qusai Y; Ghadieh, Hilda E; Najjar, Sonia M; Siragy, Helmy M

2015-11-01

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis. Copyright © 2015 the American Physiological Society.

Extensive Aspartoacylase Expression in the Rat Central Nervous System

DTIC Science & Technology

2011-01-01

pathways are shown in panel (A) including the corpus callosum (cc), anterior com- missure (see also C; aco), and fornix ( fx ). The subfornical organ (sfo...14 MOFFETT ET AL. GLIA protein. That antibody and the one used in the current study both stained the same cellular elements. Astro - cytes were the

DNA Methylation of Cellular Retinoic Acid-Binding Proteins in Cervical Cancer.

PubMed

Arellano-Ortiz, Ana L; Salcedo-Vargas, Mauricio; Vargas-Requena, Claudia L; López-Díaz, José A; De la Mora-Covarrubias, Antonio; Silva-Espinoza, Juan C; Jiménez-Vega, Florinda

2016-01-01

This study determined the methylation status of cellular retinoic acid-binding protein ( CRABP ) gene promoters and associated them with demographic characteristics, habits, and the presence of human papilloma virus (HPV) in patients with cervical cancer (CC), low and high squamous intraepithelial lesions, and no intraepithelial lesion. Women (n = 158) were selected from the Colposcopy Clinic of Sanitary Jurisdiction II in Ciudad Juarez, Chihuahua, Mexico. Demographic characteristics and habit information were collected. Cervical biopsy and endocervical scraping were used to determine methylation in promoter regions by methylation-specific polymerase chain reaction technique. We found hemi-methylation patterns in the promoter regions of CRABP1 and CRABP2 ; there was 28.5% hemi-methylation in CRABP1 and 7.0% in that of CRABP2 . Methylation in CRABP1 was associated with age (≥35 years, P = 0.002), family history of cancer ( P = 0.032), the presence of HPV-16 ( P = 0.013), and no alcohol intake ( P = 0.035). These epigenetic changes could be involved in the CC process, and CRABP1 has the potential to be a predictive molecular marker of retinoid therapy response.

DNA Methylation of Cellular Retinoic Acid-Binding Proteins in Cervical Cancer

PubMed Central

Arellano-Ortiz, Ana L.; Salcedo-Vargas, Mauricio; Vargas-Requena, Claudia L.; López-Díaz, José A.; De la Mora-Covarrubias, Antonio; Silva-Espinoza, Juan C.; Jiménez-Vega, Florinda

2016-01-01

This study determined the methylation status of cellular retinoic acid-binding protein (CRABP) gene promoters and associated them with demographic characteristics, habits, and the presence of human papilloma virus (HPV) in patients with cervical cancer (CC), low and high squamous intraepithelial lesions, and no intraepithelial lesion. Women (n = 158) were selected from the Colposcopy Clinic of Sanitary Jurisdiction II in Ciudad Juarez, Chihuahua, Mexico. Demographic characteristics and habit information were collected. Cervical biopsy and endocervical scraping were used to determine methylation in promoter regions by methylation-specific polymerase chain reaction technique. We found hemi-methylation patterns in the promoter regions of CRABP1 and CRABP2; there was 28.5% hemi-methylation in CRABP1 and 7.0% in that of CRABP2. Methylation in CRABP1 was associated with age (≥35 years, P = 0.002), family history of cancer (P = 0.032), the presence of HPV-16 (P = 0.013), and no alcohol intake (P = 0.035). These epigenetic changes could be involved in the CC process, and CRABP1 has the potential to be a predictive molecular marker of retinoid therapy response. PMID:27867303

Concholepas concholepas Ferritin H-like subunit (CcFer): Molecular characterization and single nucleotide polymorphism associated to innate immune response.

PubMed

Chávez-Mardones, Jacqueline; Valenzuela-Muñoz, Valentina; Núñez-Acuña, Gustavo; Maldonado-Aguayo, Waleska; Gallardo-Escárate, Cristian

2013-09-01

Ferritin has been identified as the principal protein of iron storage and iron detoxification, playing a pivotal role for the cellular homeostasis in living organisms. However, recent studies in marine invertebrates have suggested its association with innate immune system. In the present study, one Ferritin subunit was identified from the gastropod Concholepas concholepas (CcFer), which was fully characterized by Rapid Amplification of cDNA Ends technique. Simultaneously, a challenge test was performed to evaluate the immune response against Vibrio anguillarum. The full length of cDNA Ccfer was 1030 bp, containing 513 bp of open reading frame that encodes to 170 amino acid peptide, which was similar to the Ferritin H subunit described in vertebrates. Untranslated Regions (UTRs) were identified with a 5'UTR of 244 bp that contains iron responsive element (IRE), and a 3'UTR of 273 bp. The predicted molecular mass of deduced amino acid of CcFer was 19.66 kDa and isoelectric point of 4.92. Gene transcription analysis revealed that CcFer increases against infections with V. anguillarum, showing a peak expression at 6 h post-infection. Moreover, a single nucleotide polymorphism was detected at -64 downstream 5'UTR sequence (SNP-64). Quantitative real time analysis showed that homozygous mutant allele (TT) was significantly associated with higher expression levels of the challenged group compared to wild (CC) and heterozygous (CT) variants. Our findings suggest that CcFer is associated to innate immune response in C. concholepas and that the presence of SNPs may involve differential transcriptional expression of CcFer. Copyright © 2013 Elsevier Ltd. All rights reserved.

Estimating genetic and phenotypic parameters of cellular immune-associated traits in dairy cows.

PubMed

Denholm, Scott J; McNeilly, Tom N; Banos, Georgios; Coffey, Mike P; Russell, George C; Bagnall, Ainsley; Mitchell, Mairi C; Wall, Eileen

2017-04-01

Data collected from an experimental Holstein-Friesian research herd were used to determine genetic and phenotypic parameters of innate and adaptive cellular immune-associated traits. Relationships between immune-associated traits and production, health, and fertility traits were also investigated. Repeated blood leukocyte records were analyzed in 546 cows for 9 cellular immune-associated traits, including percent T cell subsets, B cells, NK cells, and granulocytes. Variance components were estimated by univariate analysis. Heritability estimates were obtained for all 9 traits, the highest of which were observed in the T cell subsets percent CD4 + , percent CD8 + , CD4 + :CD8 + ratio, and percent NKp46 + cells (0.46, 0.41, 0.43 and 0.42, respectively), with between-individual variation accounting for 59 to 81% of total phenotypic variance. Associations between immune-associated traits and production, health, and fertility traits were investigated with bivariate analyses. Strong genetic correlations were observed between percent NKp46 + and stillbirth rate (0.61), and lameness episodes and percent CD8 + (-0.51). Regarding production traits, the strongest relationships were between CD4 + :CD8 + ratio and weight phenotypes (-0.52 for live weight; -0.51 for empty body weight). Associations between feed conversion traits and immune-associated traits were also observed. Our results provide evidence that cellular immune-associated traits are heritable and repeatable, and the noticeable variation between animals would permit selection for altered trait values, particularly in the case of the T cell subsets. The associations we observed between immune-associated, health, fertility, and production traits suggest that genetic selection for cellular immune-associated traits could provide a useful tool in improving animal health, fitness, and fertility. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY 2.0 license (http://creativecommons.org/licenses/by/2.0/).

Identification of immunity related genes to study the Physalis peruviana--Fusarium oxysporum pathosystem.

PubMed

Enciso-Rodríguez, Felix E; González, Carolina; Rodríguez, Edwin A; López, Camilo E; Landsman, David; Barrero, Luz Stella; Mariño-Ramírez, Leonardo

2013-01-01

The Cape gooseberry (Physalisperuviana L) is an Andean exotic fruit with high nutritional value and appealing medicinal properties. However, its cultivation faces important phytosanitary problems mainly due to pathogens like Fusarium oxysporum, Cercosporaphysalidis and Alternaria spp. Here we used the Cape gooseberry foliar transcriptome to search for proteins that encode conserved domains related to plant immunity including: NBS (Nucleotide Binding Site), CC (Coiled-Coil), TIR (Toll/Interleukin-1 Receptor). We identified 74 immunity related gene candidates in P. peruviana which have the typical resistance gene (R-gene) architecture, 17 Receptor like kinase (RLKs) candidates related to PAMP-Triggered Immunity (PTI), eight (TIR-NBS-LRR, or TNL) and nine (CC-NBS-LRR, or CNL) candidates related to Effector-Triggered Immunity (ETI) genes among others. These candidate genes were categorized by molecular function (98%), biological process (85%) and cellular component (79%) using gene ontology. Some of the most interesting predicted roles were those associated with binding and transferase activity. We designed 94 primers pairs from the 74 immunity-related genes (IRGs) to amplify the corresponding genomic regions on six genotypes that included resistant and susceptible materials. From these, we selected 17 single band amplicons and sequenced them in 14 F. oxysporum resistant and susceptible genotypes. Sequence polymorphisms were analyzed through preliminary candidate gene association, which allowed the detection of one SNP at the PpIRG-63 marker revealing a nonsynonymous mutation in the predicted LRR domain suggesting functional roles for resistance.

Crambescin C1 Exerts a Cytoprotective Effect on HepG2 Cells through Metallothionein Induction

PubMed Central

Roel, María; Rubiolo, Juan A.; Ternon, Eva; Thomas, Olivier P.; Vieytes, Mercedes R.; Botana, Luis M.

2015-01-01

The Mediterranean marine sponge Crambe crambe is the source of two families of guanidine alkaloids known as crambescins and crambescidins. Some of the biological effects of crambescidins have been previously reported while crambescins have undergone little study. Taking this into account, we performed comparative transcriptome analysis to examine the effect of crambescin-C1 (CC1) on human tumor hepatocarcinoma cells HepG2 followed by validation experiments to confirm its predicted biological activities. We report herein that, while crambescin-A1 has a minor effect on these cells, CC1 protects them against oxidative injury by means of metallothionein induction even at low concentrations. Additionally, at high doses, CC1 arrests the HepG2 cell cycle in G0/G1 and thus inhibits tumor cell proliferation. The findings presented here provide the first detailed approach regarding the different effects of crambescins on tumor cells and provide a basis for future studies on other possible cellular mechanisms related to these bioactivities. PMID:26225985

Primary clear cell renal carcinoma cells display minimal mitochondrial respiratory capacity resulting in pronounced sensitivity to glycolytic inhibition by 3-Bromopyruvate

PubMed Central

Nilsson, H; Lindgren, D; Mandahl Forsberg, A; Mulder, H; Axelson, H; Johansson, M E

2015-01-01

Changes of cellular metabolism are an integral property of the malignant potential of most cancer cells. Already in the 1930s, Otto Warburg observed that tumor cells preferably utilize glycolysis and lactate fermentation for energy production, rather than the mitochondrial oxidative phosphorylation dominating in normal cells, a phenomenon today known as the Warburg effect. Even though many tumor types display a high degree of aerobic glycolysis, they still retain the activity of other energy-producing metabolic pathways. One exception seems to be the clear cell variant of renal cell carcinoma, ccRCC, where the activity of most other pathways than that of glycolysis has been shown to be reduced. This makes ccRCC a promising candidate for the use of glycolytic inhibitors in treatment of the disease. However, few studies have so far addressed this issue. In this report, we show a strikingly reduced mitochondrial respiratory capacity of primary human ccRCC cells, resulting in enhanced sensitivity to glycolytic inhibition by 3-Bromopyruvate (3BrPA). This effect was largely absent in established ccRCC cell lines, a finding that highlights the importance of using biologically relevant models in the search for new candidate cancer therapies. 3BrPA markedly reduced ATP production in primary ccRCC cells, followed by cell death. Our data suggest that glycolytic inhibitors such as 3BrPA, that has been shown to be well tolerated in vivo, should be further analyzed for the possible development of selective treatment strategies for patients with ccRCC. PMID:25569102

Primary clear cell renal carcinoma cells display minimal mitochondrial respiratory capacity resulting in pronounced sensitivity to glycolytic inhibition by 3-Bromopyruvate.

PubMed

Nilsson, H; Lindgren, D; Mandahl Forsberg, A; Mulder, H; Axelson, H; Johansson, M E

2015-01-08

Changes of cellular metabolism are an integral property of the malignant potential of most cancer cells. Already in the 1930s, Otto Warburg observed that tumor cells preferably utilize glycolysis and lactate fermentation for energy production, rather than the mitochondrial oxidative phosphorylation dominating in normal cells, a phenomenon today known as the Warburg effect. Even though many tumor types display a high degree of aerobic glycolysis, they still retain the activity of other energy-producing metabolic pathways. One exception seems to be the clear cell variant of renal cell carcinoma, ccRCC, where the activity of most other pathways than that of glycolysis has been shown to be reduced. This makes ccRCC a promising candidate for the use of glycolytic inhibitors in treatment of the disease. However, few studies have so far addressed this issue. In this report, we show a strikingly reduced mitochondrial respiratory capacity of primary human ccRCC cells, resulting in enhanced sensitivity to glycolytic inhibition by 3-Bromopyruvate (3BrPA). This effect was largely absent in established ccRCC cell lines, a finding that highlights the importance of using biologically relevant models in the search for new candidate cancer therapies. 3BrPA markedly reduced ATP production in primary ccRCC cells, followed by cell death. Our data suggest that glycolytic inhibitors such as 3BrPA, that has been shown to be well tolerated in vivo, should be further analyzed for the possible development of selective treatment strategies for patients with ccRCC.

Effect of perineoplasm perinephric adipose tissues on migration of clear cell renal cell carcinoma cells: a potential role of WNT signaling.

PubMed

Zi, Xiaolin; Lusch, Achim; Blair, Christopher A; Okhunov, Zhamshid; Yokoyama, Noriko N; Liu, Shuman; Baker, Molly; Huynh, Victor; Landman, Jaime

2016-08-16

To investigate the cellular and molecular interactions between clear-cell renal cell carcinoma (ccRCC) and perinephric adipose tissue (PAT), perineoplasm PAT, PAT away from the neoplasm, renal sinus and subcutaneous adipose tissues were collected at the time of renal surgery for renal masses and conditioned medium (CM) was generated from 62 patients. Perineoplasm PAT CMs from 44 out of 62 (about 71%) of patients with ccRCC or benign renal diseases (e.g. oncocytomas, angiomyolipomas, multicystic kidney, interstitial fibrosis, etc.) enhanced the migration of CaKi-2 cells. Perineoplasm PAT CMs from ccRCC significantly increased migration of ACHN and CaKi-2 cells by ~8.2 and ~2.4 folds, respectively, relative to those from benign renal diseases, whereas there is no significant difference in migration between ccRCC and benign renal diseases in CMs collected from culturing PAT away from neoplasm, renal sinus and subcutaneous adipose tissues. High Fuhrman Grade was associated with increased migration of Caki-2 cells by perineoplasm PAT CMs. Perineoplasm PATs from pT3 RCCs overexpressed multiple WNTs and their CMs exhibited higher WNT/ß-catenin activity and increased the migration of Caki-2 cells compared to CMs from benign neoplasms. Addition of secreted WNT inhibitory factor-1 recombinant protein into perineoplasm PAT CMs completely blocked the cell migration. These results indicate that WNT related factors from perineoplasm PAT may promote progression of local ccRCC to locally advanced (pT3) disease by increasing ccRCC cell mobility.

The C2238/αANP variant is a negative modulator of both viability and function of coronary artery smooth muscle cells.

PubMed

Rubattu, Speranza; Marchitti, Simona; Bianchi, Franca; Di Castro, Sara; Stanzione, Rosita; Cotugno, Maria; Bozzao, Cristina; Sciarretta, Sebastiano; Volpe, Massimo

2014-01-01

Abnormalities of vascular smooth muscle cells (VSMCs) contribute to development of vascular disease. Atrial natriuretic peptide (ANP) exerts important effects on VSMCs. A common ANP molecular variant (T2238C/αANP) has recently emerged as a novel vascular risk factor. We aimed at identifying effects of CC2238/αANP on viability, migration and motility in coronary artery SMCs, and the underlying signaling pathways. Cells were exposed to either TT2238/αANP or CC2238/αANP. At the end of treatment, cell viability, migration and motility were evaluated, along with changes in oxidative stress pathway (ROS levels, NADPH and eNOS expression), on Akt phosphorylation and miR21 expression levels. CC2238/αANP reduced cell vitality, increased apoptosis and necrosis, increased oxidative stress levels, suppressed miR21 expression along with consistent changes of its molecular targets (PDCD4, PTEN, Bcl2) and of phosphorylated Akt levels. As a result of increased oxidative stress, CC2238/αANP markedly stimulated cell migration and increased cell contraction. NPR-C gene silencing with specific siRNAs restored cell viability, miR21 expression, and reduced oxidative stress induced by CC2238/αANP. The cAMP/PKA/CREB pathway, driven by NPR-C activation, significantly contributed to both miR21 and phosphoAkt reduction upon CC2238/αANP. miR21 overexpression by mimic-hsa-miR21 rescued the cellular damage dependent on CC2238/αANP. CC2238/αANP negatively modulates viability through NPR-C/cAMP/PKA/CREB/miR21 signaling pathway, and it augments oxidative stress leading to increased migratory and vasoconstrictor effects in coronary artery SMCs. These novel findings further support a damaging role of this common αANP variant on vessel wall and its potential contribution to acute coronary events.

Unusual recurrent tongue spindle cell carcinoma with marked anaplasia occurring at the site of glossectomy for a well-differentiated squamous cell carcinoma: A case report.

PubMed

Okuyama, Kohei; Fujita, Shuichi; Yanamoto, Souichi; Naruse, Tomofumi; Sakamoto, Yuki; Kawakita, Akiko; Omori, Keisuke; Tsuchihashi, Hiroki; Umeda, Masahiro

2017-09-01

Spindle cell carcinoma (SpCC), which predominantly arises in the oral, pharyngeal and laryngeal mucosal tissues, is composed of a mixture of squamous and sarcomatoid components. The present study describes the case of a 62-year-old woman with SpCC recurrence 4 years after an initial surgery to remove a well-differentiated primary squamous cell carcinoma (SCC) of the tongue. The recurrent tumor was spherical and located deep within the tongue tissue, which differs from the typical manifestation of ulcerated masses of the mucosa. The majority of cases of recurrence involving SpCC are associated with radiotherapeutic treatment of the primary malignancy; however, the patient in the present study had not received postoperative radiotherapy for SCC. Furthermore, the recurrent tumor in the present case exhibited marked anaplasia and sarcomatoid features, and the absence of SCC elements upon biopsy rendered histological diagnosis difficult. In summary, the present findings suggest that immunohistochemical examination and identification of SCC components are essential for ensuring the accuracy of the histological diagnosis of recurrent SpCC following a primary epithelial malignancy.

Unusual recurrent tongue spindle cell carcinoma with marked anaplasia occurring at the site of glossectomy for a well-differentiated squamous cell carcinoma: A case report

PubMed Central

Okuyama, Kohei; Fujita, Shuichi; Yanamoto, Souichi; Naruse, Tomofumi; Sakamoto, Yuki; Kawakita, Akiko; Omori, Keisuke; Tsuchihashi, Hiroki; Umeda, Masahiro

2017-01-01

Spindle cell carcinoma (SpCC), which predominantly arises in the oral, pharyngeal and laryngeal mucosal tissues, is composed of a mixture of squamous and sarcomatoid components. The present study describes the case of a 62-year-old woman with SpCC recurrence 4 years after an initial surgery to remove a well-differentiated primary squamous cell carcinoma (SCC) of the tongue. The recurrent tumor was spherical and located deep within the tongue tissue, which differs from the typical manifestation of ulcerated masses of the mucosa. The majority of cases of recurrence involving SpCC are associated with radiotherapeutic treatment of the primary malignancy; however, the patient in the present study had not received postoperative radiotherapy for SCC. Furthermore, the recurrent tumor in the present case exhibited marked anaplasia and sarcomatoid features, and the absence of SCC elements upon biopsy rendered histological diagnosis difficult. In summary, the present findings suggest that immunohistochemical examination and identification of SCC components are essential for ensuring the accuracy of the histological diagnosis of recurrent SpCC following a primary epithelial malignancy. PMID:28781811

Raman spectroscopy combined with principle component analysis to investigate the aging of high energy materials

NASA Astrophysics Data System (ADS)

Farhadian, A. H.; Kavosh Tehrani, M.; Keshavarz, M. H.; Darbani, S. M. R.

2017-07-01

This paper attempts to investigate the possibility of using Raman spectroscopy for aged solid composite propellants. Propellant samples was prepared and aged by an accelerated mechanism in three different temperatures (50, 60 and 70 °C) and times. In the Raman spectrum of the unaged sample, vibrational modes of all structural substances consisting of hydroxyl-terminated polybutadiene as a binder, ammonium perchlorate (AP) as an oxidizer and aluminum as a metal fuel were observed. Comparison of the spectra of the aged samples shows the changes of several peaks with increasing aging times. The important changes are the elimination of NH3+ mode and intensity reduction of CH2 modes, which can be attributed to oxidative cross linking phenomena due to AP decomposition in the chemical structure. Intensity ratios of C-C, C=C and CH2 have been changed with aging and cross linking so that C=C bonds are converted into C-C bonds, as well as the intensity of CH2 modes, was decreased. A principle component analysis method is implemented in order to use all ranges of the spectrum and better discrimination of the samples, which show good results.

Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations.

PubMed

Song, Pu; Li, Kai; Liu, Ling; Wang, Xiaowen; Jian, Zhe; Zhang, Weigang; Wang, Gang; Li, Chunying; Gao, Tianwen

2016-10-01

The nuclear factor erythroid-derived two-like 2-antioxidant response element (Nrf2-ARE) pathway and its downstream antioxidant enzyme heme oxygenase-1 (HMOX1 or HO-1) play essential roles in H2 O2 -induced oxidative damage in human melanocytes. However, the link between Nrf2 promoter polymorphisms and susceptibility to oxidative stress-related diseases such as vitiligo is unknown. This study evaluated the association of the Nrf2 and HO-1 genes polymorphisms with vitiligo susceptibility. In this case-control study of 1136 Han Chinese vitiligo patients and 1200 controls, Nrf2 (rs35652124 and rs6721961) and HO-1 (rs2071746) genes were genotyped by PCR-restriction fragment length polymorphism analysis. Overall, a significantly decreased risk of vitiligo was found to be associated with Nrf2 rs35652124 CC and combined (CT+CC) genotypes [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.50-0.83 and OR, 0.84, 95% CI 0.71-0.99, respectively], as well as among subgroups: female, onset age ≤20 and never smoker. We subsequently found that Nrf2 rs35652124 C allele had higher transcriptional activity in the luciferase reporter assay compared with Nrf2 rs35652124 T allele. Furthermore, we investigated serum HO-1 activity was associated with the rs35652124 CT+CC genotype and lower in patients than in controls (P = 0.024). Logistic regression analysis showed a dose-response relationship between lower vitiligo risk and increased HO-1 activity in rs35652124 CT+CC genotype carriers (Ptrend < 0.05). These findings indicate that the C allele of rs35652124 located in the promoter region of Nrf2 gene is associated with protective effect on vitiligo in a Han Chinese population. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

A case of cervical cancer expressed three mRNA variant of Hyaluronan-mediated motility receptor

PubMed Central

Villegas-Ruíz, Vanessa; Salcedo, Mauricio; Zentella-Dehesa, Alejandro; de Oca, Edén V Montes; Román-Basaure, Edgar; Mantilla-Morales, Alejandra; Dávila-Borja, Víctor M; Juárez-Méndez, Sergio

2014-01-01

Cervical cancer is the second malignancy in Mexico, little is known about the prognostic factors associated with this disease. Several cellular components are important in their transformation and progression. Alternative mRNA splice is an important mechanism for generating protein diversity, nevertheless, in cancer unknown mRNA diversity is expressed. Hyaluronan-mediated motility receptor (HMMR, RHAMM, CD168) is a family member of proteins, hyaluronan acid dependent, and has been associated with different malignant processes such as: angiogenesis, cell invasiveness, proliferation, metastasis and poor outcome in some tumors. In the present study we identified expression of HMMR in cervical cancer by means of RT-PCR and sequencing. Our results indicate co-expression of two HMMR variants in all samples, and one case expressed three alternative HMMR splice transcripts. These results showed the heterogeneity of mRNA transcripts of HMMR that could express in cancer and the expression of HMMR could be marker of malignancy in CC. PMID:24966934

Large-scale image-based profiling of single-cell phenotypes in arrayed CRISPR-Cas9 gene perturbation screens.

PubMed

de Groot, Reinoud; Lüthi, Joel; Lindsay, Helen; Holtackers, René; Pelkmans, Lucas

2018-01-23

High-content imaging using automated microscopy and computer vision allows multivariate profiling of single-cell phenotypes. Here, we present methods for the application of the CISPR-Cas9 system in large-scale, image-based, gene perturbation experiments. We show that CRISPR-Cas9-mediated gene perturbation can be achieved in human tissue culture cells in a timeframe that is compatible with image-based phenotyping. We developed a pipeline to construct a large-scale arrayed library of 2,281 sequence-verified CRISPR-Cas9 targeting plasmids and profiled this library for genes affecting cellular morphology and the subcellular localization of components of the nuclear pore complex (NPC). We conceived a machine-learning method that harnesses genetic heterogeneity to score gene perturbations and identify phenotypically perturbed cells for in-depth characterization of gene perturbation effects. This approach enables genome-scale image-based multivariate gene perturbation profiling using CRISPR-Cas9. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

Nested variant of the method of moments of coupled cluster equations for vertical excitation energies and excited-state potential energy surfaces.

PubMed

Kowalski, Karol

2009-05-21

In this article we discuss the problem of proper balancing of the noniterative corrections to the ground- and excited-state energies obtained with approximate coupled cluster (CC) and equation-of-motion CC (EOMCC) approaches. It is demonstrated that for a class of excited states dominated by single excitations and for states with medium doubly excited component, the newly introduced nested variant of the method of moments of CC equations provides mathematically rigorous way of balancing the ground- and excited-state correlation effects. The resulting noniterative methodology accounting for the effect of triples is tested using its parallel implementation on the systems, for which iterative CC/EOMCC calculations with full inclusion of triply excited configurations or their most important subset are numerically feasible.

The Gene Ontology (GO) Cellular Component Ontology: integration with SAO (Subcellular Anatomy Ontology) and other recent developments

PubMed Central

2013-01-01

Background The Gene Ontology (GO) (http://www.geneontology.org/) contains a set of terms for describing the activity and actions of gene products across all kingdoms of life. Each of these activities is executed in a location within a cell or in the vicinity of a cell. In order to capture this context, the GO includes a sub-ontology called the Cellular Component (CC) ontology (GO-CCO). The primary use of this ontology is for GO annotation, but it has also been used for phenotype annotation, and for the annotation of images. Another ontology with similar scope to the GO-CCO is the Subcellular Anatomy Ontology (SAO), part of the Neuroscience Information Framework Standard (NIFSTD) suite of ontologies. The SAO also covers cell components, but in the domain of neuroscience. Description Recently, the GO-CCO was enriched in content and links to the Biological Process and Molecular Function branches of GO as well as to other ontologies. This was achieved in several ways. We carried out an amalgamation of SAO terms with GO-CCO ones; as a result, nearly 100 new neuroscience-related terms were added to the GO. The GO-CCO also contains relationships to GO Biological Process and Molecular Function terms, as well as connecting to external ontologies such as the Cell Ontology (CL). Terms representing protein complexes in the Protein Ontology (PRO) reference GO-CCO terms for their species-generic counterparts. GO-CCO terms can also be used to search a variety of databases. Conclusions In this publication we provide an overview of the GO-CCO, its overall design, and some recent extensions that make use of additional spatial information. One of the most recent developments of the GO-CCO was the merging in of the SAO, resulting in a single unified ontology designed to serve the needs of GO annotators as well as the specific needs of the neuroscience community. PMID:24093723

Hemispheric connectivity and the visual-spatial divergent-thinking component of creativity.

PubMed

Moore, Dana W; Bhadelia, Rafeeque A; Billings, Rebecca L; Fulwiler, Carl; Heilman, Kenneth M; Rood, Kenneth M J; Gansler, David A

2009-08-01

Divergent thinking is an important measurable component of creativity. This study tested the postulate that divergent thinking depends on large distributed inter- and intra-hemispheric networks. Although preliminary evidence supports increased brain connectivity during divergent thinking, the neural correlates of this characteristic have not been entirely specified. It was predicted that visuospatial divergent thinking would correlate with right hemisphere white matter volume (WMV) and with the size of the corpus callosum (CC). Volumetric magnetic resonance imaging (MRI) analyses and the Torrance Tests of Creative Thinking (TTCT) were completed among 21 normal right-handed adult males. TTCT scores correlated negatively with the size of the CC and were not correlated with right or, incidentally, left WMV. Although these results were not predicted, perhaps, as suggested by Bogen and Bogen (1988), decreased callosal connectivity enhances hemispheric specialization, which benefits the incubation of ideas that are critical for the divergent-thinking component of creativity, and it is the momentary inhibition of this hemispheric independence that accounts for the illumination that is part of the innovative stage of creativity. Alternatively, decreased CC size may reflect more selective developmental pruning, thereby facilitating efficient functional connectivity.

JAK/STAT signaling in Drosophila muscles controls the cellular immune response against parasitoid infection.

PubMed

Yang, Hairu; Kronhamn, Jesper; Ekström, Jens-Ola; Korkut, Gül Gizem; Hultmark, Dan

2015-12-01

The role of JAK/STAT signaling in the cellular immune response of Drosophila is not well understood. Here, we show that parasitoid wasp infection activates JAK/STAT signaling in somatic muscles of the Drosophila larva, triggered by secretion of the cytokines Upd2 and Upd3 from circulating hemocytes. Deletion of upd2 or upd3, but not the related os (upd1) gene, reduced the cellular immune response, and suppression of the JAK/STAT pathway in muscle cells reduced the encapsulation of wasp eggs and the number of circulating lamellocyte effector cells. These results suggest that JAK/STAT signaling in muscles participates in a systemic immune defense against wasp infection. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

A Method for Accurate Group Difference Detection by Constraining the Mixing Coefficients in an ICA Framework

PubMed Central

Sui, Jing; Adali, Tülay; Pearlson, Godfrey D.; Clark, Vincent P.; Calhoun, Vince D.

2009-01-01

Independent component analysis (ICA) is a promising method that is increasingly used to analyze brain imaging data such as functional magnetic resonance imaging (fMRI), structural MRI, and electroencephalography and has also proved useful for group comparison, e.g., differentiating healthy controls from patients. An advantage of ICA is its ability to identify components that are mixed in an unknown manner. However, ICA is not necessarily robust and optimal in identifying between-group effects, especially in highly noisy situations. Here, we propose a modified ICA framework for multi-group data analysis that incorporates prior information regarding group membership as a constraint into the mixing coefficients. Our approach, called coefficient-constrained ICA (CC-ICA), prioritizes identification of components that show a significant group difference. The performance of CC-ICA via synthetic and hybrid data simulations is evaluated under different hypothesis testing assumptions and signal to noise ratios (SNRs). Group analysis is also conducted on real multitask fMRI data. Results show that CC-ICA improves the estimation accuracy of the independent components greatly, especially those that have different patterns for different groups (e.g., patients vs. controls); In addition, it enhances the data extraction sensitivity to group differences by ranking components with P value or J-divergence more consistently with the ground truth. The proposed algorithm performs quite well for both group-difference detection and multitask fMRI data fusion, which may prove especially important for the identification of relevant disease biomarkers. PMID:19172631

Glutamine Addiction in Kidney Cancer Suppresses Oxidative Stress and Can Be Exploited for Real-Time Imaging

DOE PAGES

Abu Aboud, Omran; Habib, Samy L.; Trott, Josephine; ...

2017-10-11

Many cancers appear to activate intrinsic antioxidant systems as a means to counteract oxidative stress. Some cancers, such as clear cell renal cell carcinoma (ccRCC), require exogenous glutamine for growth and exhibit reprogrammed glutamine metabolism, at least in part due to the glutathione pathway, an efficient cellular buffering system that counteracts reactive oxygen species (ROS) and other oxidants. We show here that ccRCC xenograft tumors under the renal capsule exhibit enhanced oxidative stress compared to adjacent normal tissue and the contralateral kidney. Upon glutaminase inhibition with CB-839 or BPTES, the RCC cell lines SN12PM-6-1 (SN12) and 786-O exhibited decreased survivalmore » and pronounced apoptosis associated with a decreased GSH/GSSG ratio, augmented nuclear factor erythroid related factor 2 (NRF2), and increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of DNA damage. SN12 tumor xenografts showed decreased growth when treated with CB-839. Furthermore, PET imaging confirmed that ccRCC tumors exhibited increased tumoral uptake of 18F-(2S,4R)4- fluoroglutamine (18F-FGln) compared to the kidney in the orthotopic mouse model. This technique can be utilized to follow changes in ccRCC metabolism in vivo. Further development of these paradigms will lead to new treatment options with glutaminase inhibitors and the utility of PET to identify and manage ccRCC patients who are likely to respond to glutaminase inhibitors in the clinic.« less

Glutamine Addiction in Kidney Cancer Suppresses Oxidative Stress and Can Be Exploited for Real-Time Imaging

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

Abu Aboud, Omran; Habib, Samy L.; Trott, Josephine

Many cancers appear to activate intrinsic antioxidant systems as a means to counteract oxidative stress. Some cancers, such as clear cell renal cell carcinoma (ccRCC), require exogenous glutamine for growth and exhibit reprogrammed glutamine metabolism, at least in part due to the glutathione pathway, an efficient cellular buffering system that counteracts reactive oxygen species (ROS) and other oxidants. We show here that ccRCC xenograft tumors under the renal capsule exhibit enhanced oxidative stress compared to adjacent normal tissue and the contralateral kidney. Upon glutaminase inhibition with CB-839 or BPTES, the RCC cell lines SN12PM-6-1 (SN12) and 786-O exhibited decreased survivalmore » and pronounced apoptosis associated with a decreased GSH/GSSG ratio, augmented nuclear factor erythroid related factor 2 (NRF2), and increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of DNA damage. SN12 tumor xenografts showed decreased growth when treated with CB-839. Furthermore, PET imaging confirmed that ccRCC tumors exhibited increased tumoral uptake of 18F-(2S,4R)4- fluoroglutamine (18F-FGln) compared to the kidney in the orthotopic mouse model. This technique can be utilized to follow changes in ccRCC metabolism in vivo. Further development of these paradigms will lead to new treatment options with glutaminase inhibitors and the utility of PET to identify and manage ccRCC patients who are likely to respond to glutaminase inhibitors in the clinic.« less

Agent-Based Computational Modeling of Cell Culture: Understanding Dosimetry In Vitro as Part of In Vitro to In Vivo Extrapolation

EPA Science Inventory

Quantitative characterization of cellular dose in vitro is needed for alignment of doses in vitro and in vivo. We used the agent-based software, CompuCell3D (CC3D), to provide a stochastic description of cell growth in culture. The model was configured so that isolated cells assu...

Mouse Hepatitis Virus Strain A59 and Blocking Antireceptor Monoclonal Antibody Bind to the N-Terminal Domain of Cellular Receptor

NASA Astrophysics Data System (ADS)

Dveksler, Gabriela S.; Pensiero, Michael N.; Dieffenbach, Carl W.; Cardellichio, Christine B.; Basile, Alexis A.; Elia, Patrick E.; Holmes, Kathryn V.

1993-03-01

Mouse hepatitis virus (MHV) strain A59 uses as cellular receptors members of the carcinoembryonic antigen family in the immunoglobulin superfamily. Recombinant receptor proteins with deletions of whole or partial immunoglobulin domains were used to identify the regions of receptor glycoprotein recognized by virus and by antireceptor monoclonal antibody CC1, which blocks infection of murine cells. Monoclonal antibody CC1 and MHV-A59 virions bound only to recombinant proteins containing the entire first domain of MHV receptor. To determine which of the proteins could serve as functional virus receptors, receptor-negative hamster cells were transfected with recombinant deletion clones and then challenged with MHV-A59 virions. Receptor activity required the entire N-terminal domain with either the second or the fourth domain and the transmembrane and cytoplasmic domains. Recombinant proteins lacking the first domain or its C-terminal portion did not serve as viral receptors. Thus, like other virus receptors in the immunoglobulin superfamily, including CD4, poliovirus receptor, and intercellular adhesion molecule 1, the N-terminal domain of MHV receptor is recognized by the virus and the blocking monoclonal antibody.

COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

PubMed Central

2013-01-01

Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (e.g. VHL) and the maintenance of chromatin states (e.g. PBRM1). We surveyed more than 400 tumors using different genomic platforms and identified 19 significantly mutated genes. The PI3K/Akt pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodeling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving down-regulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, up-regulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 and GRB10. Remodeling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumor stage and severity and offers new views on the opportunities for disease treatment. PMID:23792563

Effects of modified FOLFOX-6 chemotherapy on cellular immune function in patients with gastric cancer

PubMed Central

Wang, Liang; Zhou, Donger; Ren, Haitao; Chen, Yan

2018-01-01

Tumor immunosuppression serves an important role in the occurrence and development of gastric cancer. However, the effect of chemotherapy on the immune function of patients remains unclear. The present study aimed to investigate changes in cellular immune function and regulatory T cells (Tregs) in patients with gastric cancer prior to and following chemotherapy. In the peripheral blood of patients with gastric cancer, the percentage of CD4+ T cells was substantially decreased compared with that of healthy controls (11.39±5.91 vs. 22.34±3.37%, respectively; P<0.05). High frequencies of CD8+ T cells and Tregs were also observed in the peripheral blood of patients. Although the number of T cells decreased following chemotherapy (the proportions of CD4+ and CD8+ cells were 8.99±7.31 and 16.00±4.51%, respectively), the ratio of CD4+/CD8+ T cells increased (0.31±0.17 vs. 0.56±0.22; P<0.05). Furthermore, the level of C-C motif chemokine ligand 20 (CCL20) was increased in patients prior to chemotherapy compared with healthy controls. As the sole receptor for CCL20, a high level of expression of C-C motif chemokine receptor 6 on circulating Tregs was also identified in the patients, which decreased following chemotherapy. These results suggest that chemotherapy may efficiently promote cellular immune function and inhibit immunosuppression in patients with gastric cancer.

Insights from fumarole gas geochemistry on the origin of hydrothermal fluids on the Yellowstone Plateau

USGS Publications Warehouse

Chiodini, Giovanni; Caliro, Stefano; Lowenstern, Jacob B.; Evans, William C.; Bergfeld, D.; Tassi, Franco; Tedesco, Dario

2012-01-01

The chemistry of Yellowstone fumarole gases shows the existence of two component waters, type MC, influenced by the addition of deep mantle fluid, and type CC, influenced by crustal interactions (CC). MC is high in 3He/4He (22 Ra) and low in 4He/40Ar (~1), reflecting input of deep mantle components. The other water is characterized by 4He concentrations 3-4 orders of magnitude higher than air-saturated meteoric water (ASW). These high He concentrations originate through circulation in Pleistocene volcanic rocks, as well as outgassing of Tertiary and older (including Archean) basement, some of which could be particularly rich in uranium, a major 4He source. Consideration of CO2-CH4-CO-H2O-H2 gas equilibrium reactions indicates equilibration temperatures from 170 °C to 310 °C. The estimated temperatures highly correlate with noble-gas variations, suggesting that the two waters differ in temperature. Type CC is ~170 °C whereas the MC is hotter, at 340 °C. This result is similar to models proposed by previous studies of thermal water chemistry. However, instead of mixing the deep hot component simply with cold, meteoric waters we argue that addition of a 4He-rich component, equilibrated at temperatures around 170 °C, is necessary to explain the range in fumarole gas chemistry.

The glutathione redox system is essential to prevent ferroptosis caused by impaired lipid metabolism in clear cell renal cell carcinoma.

PubMed

Miess, Heike; Dankworth, Beatrice; Gouw, Arvin M; Rosenfeldt, Mathias; Schmitz, Werner; Jiang, Ming; Saunders, Becky; Howell, Michael; Downward, Julian; Felsher, Dean W; Peck, Barrie; Schulze, Almut

2018-06-05

Metabolic reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Here we investigated metabolic dependencies in a panel of ccRCC cell lines using nutrient depletion, functional RNAi screening and inhibitor treatment. We found that ccRCC cells are highly sensitive to the depletion of glutamine or cystine, two amino acids required for glutathione (GSH) synthesis. Moreover, silencing of enzymes of the GSH biosynthesis pathway or glutathione peroxidases, which depend on GSH for the removal of cellular hydroperoxides, selectively reduced viability of ccRCC cells but did not affect the growth of non-malignant renal epithelial cells. Inhibition of GSH synthesis triggered ferroptosis, an iron-dependent form of cell death associated with enhanced lipid peroxidation. VHL is a major tumour suppressor in ccRCC and loss of VHL leads to stabilisation of hypoxia inducible factors HIF-1α and HIF-2α. Restoration of functional VHL via exogenous expression of pVHL reverted ccRCC cells to an oxidative metabolism and rendered them insensitive to the induction of ferroptosis. VHL reconstituted cells also exhibited reduced lipid storage and higher expression of genes associated with oxidiative phosphorylation and fatty acid metabolism. Importantly, inhibition of β-oxidation or mitochondrial ATP-synthesis restored ferroptosis sensitivity in VHL reconstituted cells. We also found that inhibition of GSH synthesis blocked tumour growth in a MYC-dependent mouse model of renal cancer. Together, our data suggest that reduced fatty acid metabolism due to inhibition of β-oxidation renders renal cancer cells highly dependent on the GSH/GPX pathway to prevent lipid peroxidation and ferroptotic cell death.

Oil accumulation in the model green alga Chlamydomonas reinhardtii: characterization, variability between common laboratory strains and relationship with starch reserves.

PubMed

Siaut, Magali; Cuiné, Stéphan; Cagnon, Caroline; Fessler, Boris; Nguyen, Mai; Carrier, Patrick; Beyly, Audrey; Beisson, Fred; Triantaphylidès, Christian; Li-Beisson, Yonghua; Peltier, Gilles

2011-01-21

When cultivated under stress conditions, many microalgae species accumulate both starch and oil (triacylglycerols). The model green microalga Chlamydomonas reinhardtii has recently emerged as a model to test genetic engineering or cultivation strategies aiming at increasing lipid yields for biodiesel production. Blocking starch synthesis has been suggested as a way to boost oil accumulation. Here, we characterize the triacylglycerol (TAG) accumulation process in Chlamydomonas and quantify TAGs in various wild-type and starchless strains. In response to nitrogen deficiency, Chlamydomonas reinhardtii produced TAGs enriched in palmitic, oleic and linoleic acids that accumulated in oil-bodies. Oil synthesis was maximal between 2 and 3 days following nitrogen depletion and reached a plateau around day 5. In the first 48 hours of oil deposition, a ~80% reduction in the major plastidial membrane lipids occurred. Upon nitrogen re-supply, mobilization of TAGs started after starch degradation but was completed within 24 hours. Comparison of oil content in five common laboratory strains (CC124, CC125, cw15, CC1690 and 11-32A) revealed a high variability, from 2 μg TAG per million cell in CC124 to 11 μg in 11-32A. Quantification of TAGs on a cell basis in three mutants affected in starch synthesis (cw15sta1-2, cw15sta6 and cw15sta7-1) showed that blocking starch synthesis did not result in TAG over-accumulation compared to their direct progenitor, the arginine auxotroph strain 330. Moreover, no significant correlation was found between cellular oil and starch levels among the twenty wild-type, mutants and complemented strains tested. By contrast, cellular oil content was found to increase steeply with salt concentration in the growth medium. At 100 mM NaCl, oil level similar to nitrogen depletion conditions could be reached in CC124 strain. A reference basis for future genetic studies of oil metabolism in Chlamydomonas is provided. Results highlight the importance of using direct progenitors as control strains when assessing the effect of mutations on oil content. They also suggest the existence in Chlamydomonas of complex interplays between oil synthesis, genetic background and stress conditions. Optimization of such interactions is an alternative to targeted metabolic engineering strategies in the search for high oil yields.

Oil accumulation in the model green alga Chlamydomonas reinhardtii: characterization, variability between common laboratory strains and relationship with starch reserves

PubMed Central

2011-01-01

Background When cultivated under stress conditions, many microalgae species accumulate both starch and oil (triacylglycerols). The model green microalga Chlamydomonas reinhardtii has recently emerged as a model to test genetic engineering or cultivation strategies aiming at increasing lipid yields for biodiesel production. Blocking starch synthesis has been suggested as a way to boost oil accumulation. Here, we characterize the triacylglycerol (TAG) accumulation process in Chlamydomonas and quantify TAGs in various wild-type and starchless strains. Results In response to nitrogen deficiency, Chlamydomonas reinhardtii produced TAGs enriched in palmitic, oleic and linoleic acids that accumulated in oil-bodies. Oil synthesis was maximal between 2 and 3 days following nitrogen depletion and reached a plateau around day 5. In the first 48 hours of oil deposition, a ~80% reduction in the major plastidial membrane lipids occurred. Upon nitrogen re-supply, mobilization of TAGs started after starch degradation but was completed within 24 hours. Comparison of oil content in five common laboratory strains (CC124, CC125, cw15, CC1690 and 11-32A) revealed a high variability, from 2 μg TAG per million cell in CC124 to 11 μg in 11-32A. Quantification of TAGs on a cell basis in three mutants affected in starch synthesis (cw15sta1-2, cw15sta6 and cw15sta7-1) showed that blocking starch synthesis did not result in TAG over-accumulation compared to their direct progenitor, the arginine auxotroph strain 330. Moreover, no significant correlation was found between cellular oil and starch levels among the twenty wild-type, mutants and complemented strains tested. By contrast, cellular oil content was found to increase steeply with salt concentration in the growth medium. At 100 mM NaCl, oil level similar to nitrogen depletion conditions could be reached in CC124 strain. Conclusion A reference basis for future genetic studies of oil metabolism in Chlamydomonas is provided. Results highlight the importance of using direct progenitors as control strains when assessing the effect of mutations on oil content. They also suggest the existence in Chlamydomonas of complex interplays between oil synthesis, genetic background and stress conditions. Optimization of such interactions is an alternative to targeted metabolic engineering strategies in the search for high oil yields. PMID:21255402

Deregulation of energetic metabolism in the clear cell renal cell carcinoma: A multiple pathway analysis based on microarray profiling.

PubMed

Soltysova, Andrea; Breza, Jan; Takacova, Martina; Feruszova, Jana; Hudecova, Sona; Novotna, Barbora; Rozborilova, Eva; Pastorekova, Silvia; Kadasi, Ludevit; Krizanova, Olga

2015-07-01

Clear cell renal cell carcinoma (ccRCC) is the most frequent type of kidney cancer. In order to better understand the biology of ccRCC, we accomplished the gene profiling of fresh tissue specimens from 11 patients with the renal tumors (9 ccRCCs, 1 oncocytoma and 1 renal B-lymphoma), in which the tumor-related data were compared to the paired healthy kidney tissues from the same patients. All ccRCCs exhibited a considerably elevated transcription of the gene coding for carbonic anhydrase IX (CAIX). Moreover, the ccRCC tumors consistently displayed increased expression of genes encoding the glycolytic pathway enzymes, e.g. hexokinase II (HK2) and lactate dehydrogenase A (LDHA) and a decreased expression of genes for the mitochondrial electron transport chain components, indicating an overall reprogramming of the energetic metabolism in this tumor type. This appears to be accompanied by altered expression of the genes of the pH regulating machinery, including ion and lactate transporters. Immunohistochemical staining of tumor tissue sections confirmed the increased expression of CAIX, HK2 and LDHA in ccRCC, validating the microarray data and supporting their potential as the energetic metabolism-related biomarkers of the ccRCC.

Study of high-energy neutrino neutral-current interactions

NASA Astrophysics Data System (ADS)

Aderholz, M.; Aggarwal, M. M.; Akbari, H.; Allport, P. P.; Badyal, S. K.; Ballagh, H. C.; Barth, M.; Baton, J. P.; Bingham, H. H.; Brucker, E. B.; Burnstein, R. A.; Campbell, J. R.; Cence, R. J.; Chatterjee, T. K.; Clayton, E. F.; Corrigan, G.; Coutures, C.; Deprospo, D.; Devanand; de Wolf, E. A.; Faulkner, P. J.; Foeth, H.; Fretter, W. B.; Gupta, V. K.; Hanlon, J.; Harigel, G.; Harris, F. A.; Jabiol, M. A.; Jacques, P.; Jain, V.; Jones, G. T.; Jones, M. D.; Kafka, T.; Kalelkar, M.; Kasper, P.; Kohli, J. M.; Koller, E. L.; Krawiec, R. J.; Lauko, M.; Lys, J. E.; Marage, P.; Milburn, R. H.; Miller, D. B.; Mittra, I. S.; Mobayyen, M. M.; Moreels, J.; Morrison, D. R.; Myatt, G.; Nailor, P.; Naon, R.; Napier, A.; Neveu, M.; Passmore, D.; Peters, M. W.; Peterson, V. Z.; Plano, R.; Rao, N. K.; Rubin, H. A.; Sacton, J.; Sambyal, S. S.; Schmitz, N.; Schneps, J.; Singh, J. B.; Smart, W.; Stamer, P.; Varvell, K. E.; Verluyten, L.; Wachsmuth, H.; Wainstein, S.; Willocq, S.; Yost, G. P.

1992-04-01

From an exposure of the Fermilab 15-foot bubble chamber to the Tevatron quadrupole triplet neutrino beam, we have determined the ratio of neutral-current (NC) to charged-current (CC) interactions to be 0.288+/-0.032 for events with visible hadron momentum above 10 GeV/c. The mean ν(ν¯) event energy is 150 (110) GeV, which is higher than that for any previous beam. This result agrees with those from previous experiments at lower energies. The NC/CC ratio is derived for a combined sample of ν and ν¯ events. A value of 0.274+/-0.038 is obtained for the dominant ν component assuming ν¯ NC/CC=0.39+/-0.08. For events with visible hadron momentum above 25 GeV/c, where the neutral hadron contamination remaining in the NC sample is assumed to be negligible, the combined NC/CC is 0.323+/-0.025 and the K0 production rates are 0.375+/-0.064 per CC and 0.322+/-0.073 per NC event. The corresponding Λ rates are 0.161+/-0.030 per CC and 0.113+/-0.030 per NC event. The K0 and Λ distributions of the fractional hadron energy variable z in NC events are consistent with those in CC events.

Pyridine group assisted addition of diazo-compounds to imines in the 3-CC reaction of 2-aminopyridines, aldehydes, and diazo-compounds.

PubMed

Gulevich, Anton V; Helan, Victoria; Wink, Donald J; Gevorgyan, Vladimir

2013-02-15

A novel three-component coupling (3-CC) reaction of 2-aminoazines, aromatic aldehydes, and diazo-compounds producing polyfunctional β-amino-α-diazo-compounds has been developed. The reaction features an unprecedented heterocycle-assisted addition of a diazo-compound to an imine. The obtained diazoesters were efficiently converted into valuable heterocycles as well as β-amino acid derivatives.

Corneal coupling of astigmatism applied to incisional and ablative surgery.

PubMed

Alpins, Noel; Ong, James K Y; Stamatelatos, George

2014-11-01

To redefine measures of corneal coupling for use with incisional and ablation procedures for astigmatism. Private clinics, Melbourne, Victoria, Australia. Retrospective nonrandomized study. The measures known as the coupling ratio (CR) and coupling constant (CC) were redefined to ensure validity in most cases of incisional procedures and laser vision correction procedures. In addition, a new measure--the coupling adjustment (CAdj)--was developed to quantify the amount of spherical adjustment that must be applied to compensate for coupling that occurs as a result of astigmatism treatment. These quantitative measures of coupling were applied to retrospective data to show their applicability. Pure myopic, compound myopic, and compound hyperopic astigmatism excimer laser treatments showed a CR close to zero, a CC close to 0.5, and a CAdj close to zero. Incision LRIs showed a CR close to 1.0 and a CC close to zero. In all cases, the coupling measures were consistent for treatments with a larger astigmatic component (>1.0 diopter) but variable when the astigmatic component of the treatment was smaller. The revised definitions of CR and CC can be used with incisional and ablative surgery. Incorporating the CAdj into the planning of spherocylindrical treatments allows one to factor in the effect of the astigmatic treatment on the spherical component and thus to more accurately target the desired spherical equivalent. Dr. Alpins and Mr. Stamatelatos have a financial interest in the Assort software program. Dr. Ong is an employee of Assort. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Cellular and soluble components decrease the viable pathogen counts in milk from dairy cows with subclinical mastitis.

PubMed

Koshiishi, Tomoko; Watanabe, Masako; Miyake, Hajime; Hisaeda, Keiichi; Isobe, Naoki

2017-08-10

The present study was undertaken to clarify the factors that reduce the viable pathogen count in milk collected from the udders of subclinical mastitic cows during preservation. Milk was centrifuged to divide somatic cells (cellular components, precipitates) and antimicrobial peptides (soluble components, supernatants without fat layer); each fraction was cultured with bacteria, and the number of viable bacteria was assessed prior to and after culture. In 28.8% of milk samples, we noted no viable bacteria immediately after collection; this value increased significantly after a 5-hr incubation of milk with cellular components but not with soluble components (48.1 and 28.8%, respectively). After culture with cellular components, the numbers of bacteria (excluding Staphylococcus aureus and Streptococcus uberis) and yeast decreased dramatically, although the differences were not statistically significant. After cultivation with soluble components, only yeasts showed a tendency toward decreased mean viability, whereas the mean bacterial counts of S. uberis and T. pyogenes tended to increase after 5-hr preservation with soluble components. These results suggest that most pathogens in high somatic cell count (SCC) milk decreased during preservation at 15 to 25°C, due to both the cellular components and antimicrobial components in the milk. Particularly, the cellular components more potently reduced bacterial counts during preservation.

The Experiment and Numerical Simulation of Composite Countersunk-head Fasteners Pull-through Mechanical Behavior

NASA Astrophysics Data System (ADS)

Mu, Junwu; Guan, Zhidong; Bian, Tianya; Li, Zengshan; Wang, Kailun; Liu, Sui

2014-10-01

Fasteners made of the anisotropic carbon/carbon (C/C) composite material have been developed for joining C/C composite material components in the high-temperature environment. The fastener specimens are fabricated from the C/C composites which are made from laminated carbon cloths with Z-direction carbon fibers being punctured as perform. Densification process cycles such as the thermal gradient chemical vapor infiltration (CVI) technology were repeated to obtain high density C/C composites fastener. The fasteners were machined parallel to the carbon cloths (X-Y direction). A method was proposed to test pull-through mechanical behavior of the countersunk-head C/C composite material fasteners. The damage morphologies of the fasteners were observed through the charge coupled device (CCD) and the scanning electron microscope (SEM). The internal micro-structure were observed through the high-resolution Mirco-CT systems. Finally, an excellent simulation of the C/C composite countersunk-head fasteners were performed with the finite element method (FEM), in which the damage evolution model of the fastener was established based on continuum damage mechanics. The simulation is correspond well with the test result . The damage evolution process and the relation between the countersunk depth and the ultimate load was investigated.

Pathological aspects of so called "hilar cholangiocarcinoma".

PubMed

Castellano-Megías, Víctor M; Ibarrola-de Andrés, Carolina; Colina-Ruizdelgado, Francisco

2013-07-15

Cholangiocarcinoma (CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group. However, "hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or, more commonly, the extrahepatic hilar CC. Grossly, a major distinction can be made between papillary and non-papillary tumors. Histologically, most hilar CCs are well to moderately differentiated conventional type (biliary) carcinomas. Immunohistochemically, CK7, CK20, CEA and MUC1 are normally expressed, being MUC2 positive in less than 50% of cases. Two main premalignant lesions are known: biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the biliary tract (IPNB). IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma. A series of 29 resected hilar CC from our archives is reviewed. Most (82.8%) were conventional type adenocarcinomas, mostly well to moderately differentiated, although with a broad morphological spectrum; three cases exhibited a poorly differentiated cell component resembling signet ring cells. IPNB was observed in 5 (17.2%), four of them with an associated invasive carcinoma. A clear cell type carcinoma, an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.

Endometrial Carcinomas With Clear Cells: A Study of a Heterogeneous Group of Tumors Including Interobserver Variability, Mutation Analysis, and Immunohistochemistry With HNF-1β.

PubMed

Han, Guangming; Soslow, Robert A; Wethington, Stephanie; Levine, Douglas A; Bogomolniy, Faina; Clement, Philip B; Köbel, Martin; Gilks, Blake; DeLair, Deborah

2015-07-01

Endometrial clear cell carcinoma (CC) is an uncommon tumor and often carries a poor prognosis. It has histologic features that overlap with other endometrial carcinomas and is frequently misclassified. Accurate classification is crucial, however, to improve treatment options. The objectives of this study were (1) to assess diagnostic interobserver variability among 5 gynecologic pathologists for tumors originally diagnosed as CC or with a component of CC (n=44); (2) to determine the utility of immunohistochemical markers estrogen receptor and HNF-1β; and (3) to detect mutations in select genes. Clinical data and morphologic features were also recorded. Agreement among reviewers was only moderate: only 46% of the original CC remained classified as such. After reclassification, estrogen receptor was positive in 8% of CC, 67% of endometrioid carcinomas (EC), and 47% of serous carcinomas (SC). Sensitivities of HNF-1β in CC, SC, and EC were 62%, 27%, and 17%, respectively, whereas specificity for CC versus EC or SC was 78%. Mutations in PIK3CA, PIK3R1, PTEN, KRAS, and NRAS were detected in 41% of 37 cases that had adequate material for study. At least 1 mutation was identified in 33% of CC, 67% of EC, and 33% of SC. This group of patients had poor outcomes: 72% of the patients with follow-up information had died of disease. In summary, this study suggests that the current pool of CC is a heterogeneous group of tumors from the morphologic, immunophenotypic, and molecular point of views and that only a percentage of them represent true CC.

[Characterization and transcriptional analysis of a new CC chemokine associated with innate imimune response in cobia (Rachycentron canadum)].

PubMed

Su, Y; Feng, J; Sun, X; Guo, Z; Xu, L; Jiang, J

2013-01-01

Chemokines are small, secreted cytokine peptides, known principally for their ability to induce migration and activation of leukocyte populations under both pathological and physiological conditions. On the basis of previously constructed express sequence tags (ESTs) of the head kidney and spleen cDNA library of the perciform marine fish Rachycentron canadum (common name cobia). We used bi-directional rapid amplification of cDNA ends (RACE) and obtained a full-length cDNA of a new CC chemokine gene (designated RcCC3). The RcCC3 putative peptide exhibits sequence similarity to the group of CCL19/21/25 CC chemokines. The reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used in transcript expression studies of RcCC3. We examined the constitutive expression of the transcripts in 12 tissues of non-stressed cobia; RcCC3 transcripts were detected in all tissues examined, with the highest expression in gill and liver, following by head kidney, kidney, spleen, skin, intestine, muscle, stomach, heart, blood and brain. Transcript expression of RcCC3 was examined in immune-related organs, including head kidney, spleen and liver, following intraperitoneal injection of phosphate-buffered saline control, polyriboinosinic polyribocytidylic acid (poly(I:C)) and formalin-killed Vibrio carchariae (bacterial vaccine). The transcripts in these tissues were quickly up-regulated by the injection of poly(I:C) and bacterial vaccine at early time points, although with different expression profiles. These results indicate RcCC3 represents an important component of innate immunity in cobia.

Pyridine Group-Assisted Addition of Diazo-Compounds to Imines in the 3-CC Reaction of 2-Aminopyridines, Aldehydes, and Diazo-Compounds

PubMed Central

Gulevich, Anton V.; Helan, Victoria; Wink, Donald J.

2013-01-01

A novel three-component (3-CC) coupling reaction of 2-aminoazines, aromatic aldehydes and diazo-compounds producing polyfunctional β-amino-α-diazo-compounds has been developed. The reaction features an unprecedented heterocycle-assisted addition of a diazo-compound to an imine. The obtained diazoesters were efficiently converted into valuable heterocycles, as well as to β-amino acid derivatives. PMID:23373731

T-type calcium channels cause bursts of spikes in motor but not sensory thalamic neurons during mimicry of natural patterns of synaptic input.

PubMed

Kim, Haram R; Hong, Su Z; Fiorillo, Christopher D

2015-01-01

Although neurons within intact nervous systems can be classified as 'sensory' or 'motor,' it is not known whether there is any general distinction between sensory and motor neurons at the cellular or molecular levels. Here, we extend and test a theory according to which activation of certain subtypes of voltage-gated ion channel (VGC) generate patterns of spikes in neurons of motor systems, whereas VGC are proposed to counteract patterns in sensory neurons. We previously reported experimental evidence for the theory from visual thalamus, where we found that T-type calcium channels (TtCCs) did not cause bursts of spikes but instead served the function of 'predictive homeostasis' to maximize the causal and informational link between retinogeniculate excitation and spike output. Here, we have recorded neurons in brain slices from eight sensory and motor regions of rat thalamus while mimicking key features of natural excitatory and inhibitory post-synaptic potentials. As predicted by theory, TtCC did cause bursts of spikes in motor thalamus. TtCC-mediated responses in motor thalamus were activated at more hyperpolarized potentials and caused larger depolarizations with more spikes than in visual and auditory thalamus. Somatosensory thalamus is known to be more closely connected to motor regions relative to auditory and visual thalamus, and likewise the strength of its TtCC responses was intermediate between these regions and motor thalamus. We also observed lower input resistance, as well as limited evidence of stronger hyperpolarization-induced ('H-type') depolarization, in nuclei closer to motor output. These findings support our theory of a specific difference between sensory and motor neurons at the cellular level.

The interplay of T1- and T2-relaxation on T1-weighted MRI of hMSCs induced by Gd-DOTA-peptides.

PubMed

Cao, Limin; Li, Binbin; Yi, Peiwei; Zhang, Hailu; Dai, Jianwu; Tan, Bo; Deng, Zongwu

2014-04-01

Three Gd-DOTA-peptide complexes with different peptide sequence are synthesized and used as T1 contrast agent to label human mesenchymal stem cells (hMSCs) for magnetic resonance imaging study. The peptides include a universal cell penetrating peptide TAT, a linear MSC-specific peptide EM7, and a cyclic MSC-specific peptide CC9. A significant difference in labeling efficacy is observed between the Gd-DOTA-peptides as well as a control Dotarem. All Gd-DOTA-peptides as well as Dotarem induce significant increase in T1 relaxation rate which is in favor of T1-weighted MR imaging. Gd-DOTA-CC9 yields the maximum labeling efficacy but poor T1 contrast enhancement. Gd-DOTA-EM7 yields the minimum labeling efficacy but better T1 contrast enhancement. Gd-DOTA-TAT yields a similar labeling efficacy as Gd-DOTA-CC9 and similar T1 contrast enhancement as Gd-DOTA-EM7. The underlying mechanism that governs T1 contrast enhancement effect is discussed. Our results suggest that T1 contrast enhancement induced by Gd-DOTA-peptides depends not only on the introduced cellular Gd content, but more importantly on the effect that Gd-DOTA-peptides exert on the T1-relaxation and T2-relaxation processes/rates. Both T1 and particularly T2 relaxation rate have to be taken into account to interpret T1 contrast enhancement. In addition, the interpretation has to be based on cellular instead of aqueous longitudinal and transverse relaxivities of Gd-DOTA-peptides. Copyright © 2014 Elsevier Ltd. All rights reserved.

Is the Chronic Care Model Integrated Into Research Examining Culturally Competent Interventions for Ethnically Diverse Adults With Type 2 Diabetes Mellitus? A Review.

PubMed

Dauvrin, Marie; Lorant, Vincent; d'Hoore, William

2015-12-01

The chronic care model (CCM) concerns both the medical and the cultural and linguistic needs of patients through the inclusion of cultural competence in the delivery system design. This literature review attempted to@@ identify the domains of the CCM culturally competent (CC) interventions that the adults from ethnic minorities suffering from type 2 diabetes mellitus report. We identified the CCM and the CC components in the relevant studies published between 2005 and 2014. Thirty-two studies were included. Thirty-one articles focused on self-management and 20 on community resources. Twenty-three interventions integrated cultural norms from the patients' backgrounds. CC interventions reported the CCM at the individual level but need to address the organizational level more effectively. The scope of CC interventions should be expanded to transform health care organizations and systems. © The Author(s) 2015.

An experimental study of adsorption interference in binary mixtures flowing through activated carbon

NASA Technical Reports Server (NTRS)

Madey, R.; Photinos, P. J.

1983-01-01

The isothermal transmission through activated carbon adsorber beds at 25 C of acetaldehyde-propane and acetylene-ethane mixtures in a helium carrier gas was measured. The inlet concentration of each component was in the range between 10 ppm and 500 ppm. The constant inlet volumetric flow rate was controlled at 200 cc (STP)/min in the acetaldehyde-propane experiments and at 50 cc (STP)/min in the acetaldehyde-ethane experiments. Comparison of experimental results with the corresponding single-component experiments under similar conditions reveals interference phenomena between the components of the mixtures as evidenced by changes in both the adsorption capacity and the dispersion number. Propane was found to displace acetaldehyde from the adsorbed state. The outlet concentration profiles of propane in the binary mixtures tend to become more diffuse than the corresponding concentration profiles of the one-component experiments. Similar features were observed with mixtures of acetylene and ethane; however, the displacement of acetylene by ethane is less pronounced.

miR-3156-3p is downregulated in HPV-positive cervical cancer and performs as a tumor-suppressive miRNA.

PubMed

Xia, Yu-Fang; Pei, Gui-Hua; Wang, Ning; Che, Yan-Ci; Yu, Feng-Sheng; Yin, Fu-Fen; Liu, Hai-Xia; Luo, Bing; Wang, Yan-Kui

2017-02-04

Cervical cancer (CC) is the second most common cancer in females in developing countries. The two viral oncoproteins E6 and E7 mediate the oncogenic activities of high-risk human papillomavirus (HR-HPV), and HR-HPV, especially HPV16 or/and HPV18 (HPV16/18) play critical roles in CC through different pathways. microRNAs (miRNAs) may be associated with CC pathogenesis. Researches have indicated that human papillomavirus (HPV) may regulate cellular miRNA expression through viral E6 and E7. Herein, the purposes of this study were to identify the relationship between HPV infection and aberrantly expressed miRNAs and to investigate their pathogenic roles in CC. miRNA expression was assessed using a microRNAs microarray in HPV16 E6- and E7-integrated HPV-negative HT-3 cell lines and mock vector-transfected HT-3 cells. The microarray results were validated, and the expression of miR-3156-3p was identified in HPV-positive and -negative CC cell lines as well as primary CC and normal cervical epithelium tissues using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK8), flow cytometry, transwell analysis, tube formation, and Western blotting were used to identify the functional role of miR-3156-3p in CaSki, SiHa, and HeLa cell lines. Six underexpressed microRNAs (miR-3156-3p, 6779-3p, 4779-3p, 6841-3p, 454-5p and 656-5p) were consistently identified in HPV16 E6- and E7-integrated HT-3 cells. Further investigation confirmed a significant decrease of miR-3156-3p in HPV16/18 positive CC lesions. CCK8, flow cytometry, transwell analysis, tube formation assays, and Western blotting of the CC cell lines with miR-3156-3p over/under-expression in vitro showed that miR-3156-3p was involved in cell proliferation, apoptosis, migration, neovascularization, and SLC6A6 regulation. Our findings indicate that miR-3156-3p plays a suppressor-miRNA role in CC and that its expression is associated with HR-HPV infection.

A new approach to the human muscle model.

PubMed

Baildon, R W; Chapman, A E

1983-01-01

Hill's (1938) two component muscle model is used as basis for digital computer simulation of human muscular contraction by means of an iterative process. The contractile (CC) and series elastic (SEC) components are lumped components of structures which produce and transmit torque to the external environment. The CC is described in angular terms along four dimensions as a series of non-planar torque-angle-angular velocity surfaces stacked on top of each other, each surface being appropriate to a given level of muscular activation. The SEC is described similarly along dimensions of torque, angular stretch, overall muscle angular displacement and activation. The iterative process introduces negligible error and allows the mechanical outcome of a variety of normal muscular contractions to be evaluated parsimoniously. The model allows analysis of many aspects of muscle behaviour as well as optimization studies. Definition of relevant relations should also allow reproduction and prediction of the outcome of contractions in individuals.

Foreshock search over a long duration using a method of setting appropriate criteria

NASA Astrophysics Data System (ADS)

Toyomoto, Y.; Kawakata, H.; Hirano, S.; Doi, I.

2016-12-01

Recently, small foreshocks have been detected using cross-correlation techniques (e.g., Bouchon et al., 2011) in which the foreshocks are identified when the cross-correlation coefficient (CC) exceeded a certain threshold. For some shallow intraplate earthquakes, foreshocks whose hypocenters were estimated to be adjacent to the main shock hypocenter were detected from several tens of minutes before the main shock occurrence (Doi and Kawakata, 2012; 2013). At least two problems remain in the cross-correlation techniques employed. First, previous studies on foreshocks used data whose durations are at most a month (Kato et al., 2013); this is insufficient to check if such events occurred only before the main shock occurrence or not. Second, CC is used for detection criteria without considering validity of the threshold. In this study, we search for foreshocks of an M 5.4 earthquake in central Nagano prefecture in Japan on June 30, 2011 with a vertical-component waveform at N.MWDH (Hi-net) station due to one of the cataloged foreshocks (M 1) as a template to calculate CC. We calculate CC between the template and continuous waveforms of the same component at the same station for two years before the main shock occurrence, and we try to overcome the problems mentioned above. We find that histogram of CC is well modeled with the normal distribution, which is similar to previous studies on tremors (e.g., Ohta and Ide, 2008). According to the model, the expected number of misdetection is less than 1 when CC > 0.63. Therefore, we regard that the waveform is due to a foreshock when CC > 0.63. As a result, foreshocks are detected only within thirteen hours immediately before the main shock occurrence for the two years. By setting an appropriate threshold, we conclude that foreshocks just before the main shock occurrence are not stationary events. Acknowledgments: We use continuous waveform records of NIED high sensitivity seismograph network in Japan (Hi-net) and the JMA unified hypocenter catalogs. This work is supported by MEXT of Japan, under its Earthquake and Volcano Hazards Observation and Research Program.

Two-Component System RgfA/C Activates the fbsB Gene Encoding Major Fibrinogen-Binding Protein in Highly Virulent CC17 Clone Group B Streptococcus

PubMed Central

Safadi, Rim Al; Mereghetti, Laurent; Salloum, Mazen; Lartigue, Marie-Frédérique; Virlogeux-Payant, Isabelle; Quentin, Roland; Rosenau, Agnès

2011-01-01

Group B streptococcus (GBS) strains with the highest ability to bind to human fibrinogen belong to the highly invasive clonal complex (CC) 17. To investigate the fibrinogen-binding mechanisms of CC17 strains, we determined the prevalence of fibrinogen-binding genes (fbsA and fbsB), and fbs regulator genes (rogB encoding an fbsA activator, rovS encoding an fbsA repressor and rgf encoding a two-component system [TCS] whose role on fbs genes was not determined yet) in a collection of 134 strains representing the major CCs of the species. We showed that specific gene combinations were related to particular CCs; only CC17 strains contained the fbsA, fbsB, and rgf genes combination. Non polar rgfAC deletion mutants of three CC17 serotype III strains were constructed. They showed a 3.2- to 5.1-fold increase of fbsA transcripts, a 4.8- to 6.7-fold decrease of fbsB transcripts, and a 52% to 68% decreased fibrinogen-binding ability, demonstrating that the RgfA/RgfC TCS inhibits the fbsA gene and activates the fbsB gene. The relative contribution of the two fbs genes in fibrinogen-binding ability was determined by constructing isogenic fbsA, fbsB, deletion mutants of the three CC17 strains. The ability to bind to fibrinogen was reduced by 49% to 57% in ΔfbsA mutants, and by 78% to 80% in ΔfbsB mutants, suggesting that FbsB protein plays a greater role in the fibrinogen-binding ability of CC17 strains. Moreover, the relative transcription level of fbsB gene was 9.2- to 12.7-fold higher than that of fbsA gene for the three wild type strains. Fibrinogen-binding ability could be restored by plasmid-mediated expression of rgfAC, fbsA, and fbsB genes in the corresponding deletion mutants. Thus, our results demonstrate that a specific combination of fbs genes and fbs regulator genes account for the high fibrinogen-binding ability of CC17 strains that may participate to their enhanced invasiveness for neonates as compared to strains of other CCs. PMID:21326613

JMS Proxy and C/C++ Client SDK

NASA Technical Reports Server (NTRS)

Wolgast, Paul; Pechkam, Paul

2007-01-01

JMS Proxy and C/C++ Client SDK (JMS signifies "Java messaging service" and "SDK" signifies "software development kit") is a software package for developing interfaces that enable legacy programs (here denoted "clients") written in the C and C++ languages to communicate with each other via a JMS broker. This package consists of two main components: the JMS proxy server component and the client C library SDK component. The JMS proxy server component implements a native Java process that receives and responds to requests from clients. This component can run on any computer that supports Java and a JMS client. The client C library SDK component is used to develop a JMS client program running in each affected C or C++ environment, without need for running a Java virtual machine in the affected computer. A C client program developed by use of this SDK has most of the quality-of-service characteristics of standard Java-based client programs, including the following: Durable subscriptions; Asynchronous message receipt; Such standard JMS message qualities as "TimeToLive," "Message Properties," and "DeliveryMode" (as the quoted terms are defined in previously published JMS documentation); and Automatic reconnection of a JMS proxy to a restarted JMS broker.

Laue Crystal Structure of Shewanella oneidensis Cytochrome c Nitrite Reductase from a High-yield Expression System

PubMed Central

Youngblut, Matthew; Judd, Evan T.; Srajer, Vukica; Sayyed, Bilal; Goelzer, Tyler; Elliott, Sean J.; Schmidt, Marius; Pacheco, A. Andrew

2012-01-01

The high-yield expression and purification of Shewanella oneidensis cytochrome c nitrite reductase (ccNiR), and its characterization by a variety of methods, notably Laue crystallography, is reported. A key component of the expression system is an artificial ccNiR gene in which the N-terminal signal peptide from the highly expressed S. oneidensis protein “Small Tetra-heme c” replaces the wild-type signal peptide. This gene, inserted into the plasmid pHSG298 and expressed in S. oneidensis TSP-1 strain, generated ~20 mg crude ccNiR/L culture, compared with 0.5–1 mg/L for untransformed cells. Purified ccNiR has nitrite and hydroxylamine reductase activities comparable to those previously reported for E. coli ccNiR, and is stable for over two weeks in pH 7 solution at 4° C. UV/Vis spectropotentiometric titrations and protein film voltammetry identified 5 independent 1-electron reduction processes. Global analysis of the spectropotentiometric data also allowed determination of the extinction coefficient spectra for the 5 reduced ccNiR species. The characteristics of the individual extinction coefficient spectra suggest that, within each reduced species, the electrons are distributed amongst the various hemes, rather than being localized on specific heme centers. The purified ccNiR yielded good quality crystals, with which the 2.59 Å resolution structure was solved at room temperature using the Laue diffraction method. The structure is similar to that of E. coli ccNiR, except in the region where the enzyme interacts with its physiological electron donor (CymA in the case of S. oneidensis ccNiR, NrfB in the case of the E. coli protein). PMID:22382353

The effectiveness of holistic diabetic management between Siriraj Continuity of Care clinic and medical out-patient department.

PubMed

Chalermsri, Chalobol; Paisansudhi, Supalerg; Kantachuvesiri, Pitchaporn; Pramyothin, Pornpoj; Washirasaksiri, Chaiwat; Srivanichakorn, Weerachai; Nopmaneejumruslers, Cherdchai; Chouriyagune, Charoen; Pandejpong, Denla; Phisalprapa, Pochamana

2014-03-01

Diabetes mellitus is one of the most common diseases in the Thai population, and it is well known that diabetic complications could be prevented with appropriate management. Despite published guidelines, most Thai patients with diabetes do not achieve treatment goals. Siriraj Continuity of Care clinic (CC clinic) was recently established in order to provide training for medical students and internal medicine residents. It is possible that the training component in the CC clinic may contribute to better overall outcomes in type 2 diabetes mellitus (type 2 DM) patients when compared with usual care at the medical out-patient department (OPD). To compare the effectiveness of diabetic management in type 2 diabetes mellitus patients who attended the CC clinic and the medical OPD. Retrospective chart review was performed in type 2 diabetes mellitus patients who were treated at either clinic at Siriraj Hospital in 2007-2011. Baseline demographics, treatment strategies and outcomes, and participation in an appropriate health maintenance program were assessed in both groups. Seven hundred and fifty seven medical records were reviewed, including 383 patients in the CC clinic group and 374 in the OPD group. Mean HbA1c was significantly lower in the CC clinic group compared with the OPD group (7.3 +/- 0.9% and 7.8 +/- 1.3%, respectively, < 0.001). The number of patients who achieved goal HbA1c of less than 7% in CC clinic group was 123 (32.1%) compared with 91 (24.3%) in the OPD group (p = 0.039). More patients were screened for diabetic complications in the CC clinic group compared with the OPD group, including screening for diabetic neuropathy (57.4% vs. 2.1%, p < 0.001), diabetic retinopathy (56.7% vs. 36.6%, p < 0.001), and diabetic nephropathy (80.9% vs. 36.9%, p < 0.001). Patients in the CC clinic group had a higher rate of age-appropriate cancer screening than those in the OPD group (54.2% vs. 13.3%, p < 0.001 for breast cancer; 24.0% vs. 0.9%, p < 0.001 for cervical cancer; and 23.0% vs. 7.4%, p < 0.001 for colon cancer). Moreover, significantly more patients in the CC clinic group received recommended immunization (influenza, diphtheria tetanus and pneumococcal vaccine) compared with the control group (p < or = 0.001). Diabetic patients treated at the CC clinic had better clinical outcomes and healthcare maintenance compared with those who received usual care at the medical OPD. Continuity of care and integrated training component may have contributed to the improved outcomes.

Imaging Prostate Cancer Microenvironment by Collagen Hybridization

DTIC Science & Technology

2013-10-01

There is an emerging concept of using non-cellular solid state compartment as a source for therapeutic targets and for selective imaging of micro ... using second harmonic generation and two-photon micros - copy. J. Biomed. Opt. 14, 044013. Bioconjugate Chemistry Communication dx.doi.org/10.1021...Chiu WC, Lai CC, Liou GG, Li HC, Chou MY: Production of multivalent protein binders using a self- trimerizing collagen-like peptide scaffold. FASEB J

Orai1 and STIM1 are critical for cell migration and proliferation of clear cell renal cell carcinoma

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

Kim, Ji-Hee; Lkhagvadorj, Sayamaa; Lee, Mi-Ra

2014-05-23

Highlights: • Orai1 channel is highly expressed in clear cell renal cell carcinoma (ccRCC) tissues. • Orai1 and STIM1 constitute a native store-operated Ca{sup 2+} entry in ccRCC cells. • Orai1 and STIM1 promote cell migration and proliferation of ccRCC cells. - Abstract: The intracellular Ca{sup 2+} regulation has been implicated in tumorigenesis and tumor progression. Notably, store-operated Ca{sup 2+} entry (SOCE) is a major Ca{sup 2+} entry mechanism in non-excitable cells, being involved in cell proliferation and migration in several types of cancer. However, the expression and biological role of SOCE have not been investigated in clear cell renalmore » cell carcinoma (ccRCC). Here, we demonstrate that Orai1 and STIM1, not Orai3, are crucial components of SOCE in the progression of ccRCC. The expression levels of Orai1 in tumor tissues were significantly higher than those in the adjacent normal parenchymal tissues. In addition, native SOCE was blunted by inhibiting SOCE or by silencing Orai1 and STIM1. Pharmacological blockade or knockdown of Orai1 or STIM1 also significantly inhibited RCC cell migration and proliferative capability. Taken together, Orai1 is highly expressed in ccRCC tissues illuminating that Orai1-mediated SOCE may play an important role in ccRCC development. Indeed, Orai1 and STIM1 constitute a native SOCE pathway in ccRCC by promoting cell proliferation and migration.« less

Analysis of Students' Aptitude to Provide Meaning to Images that Represent Cellular Components at the Molecular Level

ERIC Educational Resources Information Center

Dahmani, Hassen-Reda; Schneeberger, Patricia; Kramer, IJsbrand M.

2009-01-01

The number of experimentally derived structures of cellular components is rapidly expanding, and this phenomenon is accompanied by the development of a new semiotic system for teaching. The infographic approach is shifting from a schematic toward a more realistic representation of cellular components. By realistic we mean artist-prepared or…

Emerging role of chemokine CC motif ligand 4 related mechanisms in diabetes mellitus and cardiovascular disease: friends or foes?

PubMed

Chang, Ting-Ting; Chen, Jaw-Wen

2016-08-24

Chemokines are critical components in pathology. The roles of chemokine CC motif ligand 4 (CCL4) and its receptor are associated with diabetes mellitus (DM) and atherosclerosis cardiovascular diseases. However, due to the complexity of these diseases, the specific effects of CCL4 remain unclear, although recent reports have suggested that multiple pathways are related to CCL4. In this review, we provide an overview of the role and potential mechanisms of CCL4 and one of its major receptors, fifth CC chemokine receptor (CCR5), in DM and cardiovascular diseases. CCL4-related mechanisms, including CCL4 and CCR5, might provide potential therapeutic targets in DM and/or atherosclerosis cardiovascular diseases.

Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites.

PubMed

Di Mattia, Thomas; Wilhelm, Léa P; Ikhlef, Souade; Wendling, Corinne; Spehner, Danièle; Nominé, Yves; Giordano, Francesca; Mathelin, Carole; Drin, Guillaume; Tomasetto, Catherine; Alpy, Fabien

2018-06-01

Membrane contact sites are cellular structures that mediate interorganelle exchange and communication. The two major tether proteins of the endoplasmic reticulum (ER), VAP-A and VAP-B, interact with proteins from other organelles that possess a small VAP-interacting motif, named FFAT [two phenylalanines (FF) in an acidic track (AT)]. In this study, using an unbiased proteomic approach, we identify a novel ER tether named motile sperm domain-containing protein 2 (MOSPD2). We show that MOSPD2 possesses a Major Sperm Protein (MSP) domain which binds FFAT motifs and consequently allows membrane tethering in vitro MOSPD2 is an ER-anchored protein, and it interacts with several FFAT-containing tether proteins from endosomes, mitochondria, or Golgi. Consequently, MOSPD2 and these organelle-bound proteins mediate the formation of contact sites between the ER and endosomes, mitochondria, or Golgi. Thus, we characterized here MOSPD2, a novel tethering component related to VAP proteins, bridging the ER with a variety of distinct organelles. © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Organizational readiness for knowledge translation in chronic care: a review of theoretical components

PubMed Central

2013-01-01

Background With the persistent gaps between research and practice in healthcare systems, knowledge translation (KT) has gained significance and importance. Also, in most industrialized countries, there is an increasing emphasis on managing chronic health conditions with the best available evidence. Yet, organizations aiming to improve chronic care (CC) require an adequate level of organizational readiness (OR) for KT. Objectives: The purpose of this study is to review and synthesize the existing evidence on conceptual models/frameworks of Organizational Readiness for Change (ORC) in healthcare as the basis for the development of a comprehensive framework of OR for KT in the context of CC. Data sources We conducted a systematic review of the literature on OR for KT in CC using Pubmed, Embase, CINAHL, PsychINFO, Web of Sciences (SCI and SSCI), and others. Search terms included readiness; commitment and change; preparedness; willing to change; organization and administration; and health and social services. Study selection: The search was limited to studies that had been published between the starting date of each bibliographic database (e.g., 1964 for PubMed) and November 1, 2012. Only papers that refer to a theory, a theoretical component from any framework or model on OR that were applicable to the healthcare domain were considered. We analyzed data using conceptual mapping. Data extraction: Pairs of authors independently screened the published literature by reviewing their titles and abstracts. Then, the two same reviewers appraised the full text of each study independently. Results Overall, we found and synthesized 10 theories, theoretical models and conceptual frameworks relevant to ORC in healthcare described in 38 publications. We identified five core concepts, namely organizational dynamics, change process, innovation readiness, institutional readiness, and personal readiness. We extracted 17 dimensions and 59 sub-dimensions related to these 5 concepts. Conclusion Our findings provide a useful overview for researchers interested in ORC and aims to create a consensus on the core theoretical components of ORC in general and of OR for KT in CC in particular. However, more work is needed to define and validate the core elements of a framework that could help to assess OR for KT in CC. PMID:24283365

Mitosis Is a Source of Potential Markers for Screening and Survival and Therapeutic Targets in Cervical Cancer

PubMed Central

Espinosa, Ana María; Alfaro, Ana; Roman-Basaure, Edgar; Guardado-Estrada, Mariano; Palma, Ícela; Serralde, Cyntia; Medina, Ingrid; Juárez, Eligia; Bermúdez, Miriam; Márquez, Edna; Borges-Ibáñez, Manuel; Muñoz-Cortez, Sergio; Alcántara-Vázquez, Avissai; Alonso, Patricia; Curiel-Valdez, José; Kofman, Susana; Villegas, Nicolas; Berumen, Jaime

2013-01-01

The effect of preventive human papillomavirus (HPV) vaccination on the reduction of the cervical cancer (CC) burden will not be known for 30 years. Therefore, it’s still necessary to improve the procedures for CC screening and treatment. The objective of this study was to identify and characterize cellular targets that could be considered potential markers for screening or therapeutic targets. A pyramidal strategy was used. Initially the expression of 8,638 genes was compared between 43 HPV16-positive CCs and 12 healthy cervical epitheliums using microarrays. A total of 997 genes were deregulated, and 21 genes that showed the greatest deregulation were validated using qRT-PCR. The 6 most upregulated genes (CCNB2, CDC20, PRC1, SYCP2, NUSAP1, CDKN3) belong to the mitosis pathway. They were further explored in 29 low-grade cervical intraepithelial neoplasias (CIN1) and 21 high-grade CIN (CIN2/3) to investigate whether they could differentiate CC and CIN2/3 (CIN2+) from CIN1 and controls. CCNB2, PRC1, and SYCP2 were mostly associated with CC and CDC20, NUSAP1, and CDKN3 were also associated with CIN2/3. The sensitivity and specificity of CDKN3 and NUSAP1 to detect CIN2+ was approximately 90%. The proteins encoded by all 6 genes were shown upregulated in CC by immunohistochemistry. The association of these markers with survival was investigated in 42 CC patients followed up for at least 42 months. Only CDKN3 was associated with poor survival and it was independent from clinical stage (HR = 5.9, 95%CI = 1.4–23.8, p = 0.01). CDKN3 and NUSAP1 may be potential targets for the development of screening methods. Nevertheless, further studies with larger samples are needed to define the optimal sensitivity and specificity. Inhibition of mitosis is a well-known strategy to combat cancers. Therefore, CDKN3 may be not only a screening and survival marker but a potential therapeutic target in CC. However, whether it’s indispensable for tumor growth remains to be demonstrated. PMID:23405241

Epigallocatechin-3-gallate induces oxidative phosphorylation by activating cytochrome c oxidase in human cultured neurons and astrocytes

PubMed Central

Castellano-González, Gloria; Pichaud, Nicolas; Ballard, J. William O.; Bessede, Alban; Marcal, Helder; Guillemin, Gilles J.

2016-01-01

Mitochondrial dysfunction and resulting energy impairment have been identified as features of many neurodegenerative diseases. Whether this energy impairment is the cause of the disease or the consequence of preceding impairment(s) is still under discussion, however a recovery of cellular bioenergetics would plausibly prevent or improve the pathology. In this study, we screened different natural molecules for their ability to increase intracellular adenine triphosphate purine (ATP). Among them, epigallocatechin-3-gallate (EGCG), a polyphenol from green tea, presented the most striking results. We found that it increases ATP production in both human cultured astrocytes and neurons with different kinetic parameters and without toxicity. Specifically, we showed that oxidative phosphorylation in human cultured astrocytes and neurons increased at the level of the routine respiration on the cells pre-treated with the natural molecule. Furthermore, EGCG-induced ATP production was only blocked by sodium azide (NaN3) and oligomycin, inhibitors of cytochrome c oxidase (CcO; complex IV) and ATP synthase (complex V) respectively. These findings suggest that the EGCG modulates CcO activity, as confirmed by its enzymatic activity. CcO is known to be regulated differently in neurons and astrocytes. Accordingly, EGCG treatment is acting differently on the kinetic parameters of the two cell types. To our knowledge, this is the first study showing that EGCG promotes CcO activity in human cultured neurons and astrocytes. Considering that CcO dysfunction has been reported in patients having neurodegenerative diseases such as Alzheimer's disease (AD), we therefore suggest that EGCG could restore mitochondrial function and prevent subsequent loss of synaptic function. PMID:26760769

Krüppel Like Factors Family Expression in Cervical Cancer Cells.

PubMed

Marrero-Rodríguez, Daniel; la Cruz, Hugo Arreola-De; Taniguchi-Ponciano, Keiko; Gomez-Virgilio, Laura; Huerta-Padilla, Victor; Ponce-Navarrete, Gustavo; Andonegui-Elguera, Sergio; Jimenez-Vega, Florinda; Romero-Morelos, Pablo; Rodriguez-Esquivel, Miriam; Meraz-Rios, Marco; Figueroa-Corona, Ma Del Pilar; Monroy, Alberto; Pérez-González, Oscar; Salcedo, Mauricio

2017-05-01

Krüppel Like Factors (KLF) refers to a family of seventeen members of transcription factors. Involved in several cellular processes. As other cancer types, Cervical Cancer (CC) presents molecular deregulations in transcription factors, but especially Human Papilloma Virus (HPV) sequences. Here in this work we analyzed the mRNA expression of all KLF family members in CC-derived cell lines and CC tissues. The cell lines used were HeLa, INBL, RoVa, C4-I, Ms751, ViPa, CaLo, SiHa, CaSki, C33a and ViBo and the non-tumorigenic HaCaT. mRNA expression was analyzed by means of expression microarray and RT-PCR, and KLF5 protein by immunofluorescence. The cell lines were grouped according to HPV genotype as HPV16, HPV18 positive or HPV negative cells. Heterogeneous expression was observed among the cell lines. Despite the heterogeneous expression profile, KLF3, -5, -12, -15 and -16 transcripts were present in all cell lines, KLF4 and -10 which were not expressed in CaSki; KLF11 and 13 were not expressed by Vipa and C4-I, and KLF7 was not expressed by C4-I and Rova. The CC tissue analysis shows expression of most of the KLF members, such as KLF5. KLF5 immunosignal was positive in the three cell lines analyzed. We suggest that KLF expression could not be related to HPV presence/genotype, at least at transcriptional level, and the expression of KLF family members may be necessary in the biology of the CC cells. Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.

FwWebViewPlus: integration of web technologies into WinCC OA based Human-Machine Interfaces at CERN

NASA Astrophysics Data System (ADS)

Golonka, Piotr; Fabian, Wojciech; Gonzalez-Berges, Manuel; Jasiun, Piotr; Varela-Rodriguez, Fernando

2014-06-01

The rapid growth in popularity of web applications gives rise to a plethora of reusable graphical components, such as Google Chart Tools and JQuery Sparklines, implemented in JavaScript and run inside a web browser. In the paper we describe the tool that allows for seamless integration of web-based widgets into WinCC Open Architecture, the SCADA system used commonly at CERN to build complex Human-Machine Interfaces. Reuse of widely available widget libraries and pushing the development efforts to a higher abstraction layer based on a scripting language allow for significant reduction in maintenance of the code in multi-platform environments compared to those currently used in C++ visualization plugins. Adequately designed interfaces allow for rapid integration of new web widgets into WinCC OA. At the same time, the mechanisms familiar to HMI developers are preserved, making the use of new widgets "native". Perspectives for further integration between the realms of WinCC OA and Web development are also discussed.

Numerical Simulation of Thermal Response and Ablation Behavior of a Hybrid Carbon/Carbon Composite

NASA Astrophysics Data System (ADS)

Zhang, Bai; Li, Xudong

2017-09-01

The thermal response and ablation behavior of a hybrid carbon/carbon (C/C) composite are studied herein by using a numerical model. This model is based on the energy- and mass-conservation principles as well as on the calculation of the thermophysical properties of materials. The thermal response and ablation behavior are simulated from the perspective of the matrix and fiber components of a hybrid C/C composite. The thermophysical properties during ablation are calculated, and a moving boundary is implemented to consider the recession of the ablation surface. The temperature distribution, thermophysical properties, char layer thickness, linear ablation rate, mass flow rate of the pyrolysis gases, and mass loss of the hybrid C/C composite are quantitatively predicted. This numerical study describing the thermal response and ablation behavior provides a fundamental understanding of the ablative mechanism of a hybrid C/C composite, serving as a reference and basis for further designs and optimizations of thermoprotective materials.

Numerical Simulation of Thermal Response and Ablation Behavior of a Hybrid Carbon/Carbon Composite

NASA Astrophysics Data System (ADS)

Zhang, Bai; Li, Xudong

2018-06-01

The thermal response and ablation behavior of a hybrid carbon/carbon (C/C) composite are studied herein by using a numerical model. This model is based on the energy- and mass-conservation principles as well as on the calculation of the thermophysical properties of materials. The thermal response and ablation behavior are simulated from the perspective of the matrix and fiber components of a hybrid C/C composite. The thermophysical properties during ablation are calculated, and a moving boundary is implemented to consider the recession of the ablation surface. The temperature distribution, thermophysical properties, char layer thickness, linear ablation rate, mass flow rate of the pyrolysis gases, and mass loss of the hybrid C/C composite are quantitatively predicted. This numerical study describing the thermal response and ablation behavior provides a fundamental understanding of the ablative mechanism of a hybrid C/C composite, serving as a reference and basis for further designs and optimizations of thermoprotective materials.

Computationally-Guided Synthetic Control over Pore Size in Isostructural Porous Organic Cages

DOE PAGES

Slater, Anna G.; Reiss, Paul S.; Pulido, Angeles; ...

2017-06-20

The physical properties of 3-D porous solids are defined by their molecular geometry. Hence, precise control of pore size, pore shape, and pore connectivity are needed to tailor them for specific applications. However, for porous molecular crystals, the modification of pore size by adding pore-blocking groups can also affect crystal packing in an unpredictable way. This precludes strategies adopted for isoreticular metal-organic frameworks, where addition of a small group, such as a methyl group, does not affect the basic framework topology. Here, we narrow the pore size of a cage molecule, CC3, in a systematic way by introducing methyl groupsmore » into the cage windows. Computational crystal structure prediction was used to anticipate the packing preferences of two homochiral methylated cages, CC14-R and CC15-R, and to assess the structure-energy landscape of a CC15-R/CC3-S cocrystal, designed such that both component cages could be directed to pack with a 3-D, interconnected pore structure. The experimental gas sorption properties of these three cage systems agree well with physical properties predicted by computational energy-structure-function maps.« less

Pathological aspects of so called "hilar cholangiocarcinoma"

PubMed Central

Castellano-Megías, Víctor M; Ibarrola-de Andrés, Carolina; Colina-Ruizdelgado, Francisco

2013-01-01

Cholangiocarcinoma (CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group. However, “hilar and perihilar CC” are also used to refer exclusively to the intrahepatic hilar type CC or, more commonly, the extrahepatic hilar CC. Grossly, a major distinction can be made between papillary and non-papillary tumors. Histologically, most hilar CCs are well to moderately differentiated conventional type (biliary) carcinomas. Immunohistochemically, CK7, CK20, CEA and MUC1 are normally expressed, being MUC2 positive in less than 50% of cases. Two main premalignant lesions are known: biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the biliary tract (IPNB). IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma. A series of 29 resected hilar CC from our archives is reviewed. Most (82.8%) were conventional type adenocarcinomas, mostly well to moderately differentiated, although with a broad morphological spectrum; three cases exhibited a poorly differentiated cell component resembling signet ring cells. IPNB was observed in 5 (17.2%), four of them with an associated invasive carcinoma. A clear cell type carcinoma, an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed. PMID:23919110

Computationally-Guided Synthetic Control over Pore Size in Isostructural Porous Organic Cages

PubMed Central

2017-01-01

The physical properties of 3-D porous solids are defined by their molecular geometry. Hence, precise control of pore size, pore shape, and pore connectivity are needed to tailor them for specific applications. However, for porous molecular crystals, the modification of pore size by adding pore-blocking groups can also affect crystal packing in an unpredictable way. This precludes strategies adopted for isoreticular metal–organic frameworks, where addition of a small group, such as a methyl group, does not affect the basic framework topology. Here, we narrow the pore size of a cage molecule, CC3, in a systematic way by introducing methyl groups into the cage windows. Computational crystal structure prediction was used to anticipate the packing preferences of two homochiral methylated cages, CC14-R and CC15-R, and to assess the structure–energy landscape of a CC15-R/CC3-S cocrystal, designed such that both component cages could be directed to pack with a 3-D, interconnected pore structure. The experimental gas sorption properties of these three cage systems agree well with physical properties predicted by computational energy–structure–function maps. PMID:28776015

Expression of WNT genes in cervical cancer-derived cells: Implication of WNT7A in cell proliferation and migration.

PubMed

Ramos-Solano, Moisés; Meza-Canales, Ivan D; Torres-Reyes, Luis A; Alvarez-Zavala, Monserrat; Alvarado-Ruíz, Liliana; Rincon-Orozco, Bladimiro; Garcia-Chagollan, Mariel; Ochoa-Hernández, Alejandra B; Ortiz-Lazareno, Pablo C; Rösl, Frank; Gariglio, Patricio; Jave-Suárez, Luis F; Aguilar-Lemarroy, Adriana

2015-07-01

According to the multifactorial model of cervical cancer (CC) causation, it is now recognized that other modifications, in addition to Human papillomavirus (HPV) infection, are necessary for the development of this neoplasia. Among these, it has been proposed that a dysregulation of the WNT pathway might favor malignant progression of HPV-immortalized keratinocytes. The aim of this study was to identify components of the WNT pathway differentially expressed in CC vs. non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A expression was found strongly downregulated in cell lines and biopsies derived from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviral gene delivery system or after adding a recombinant human protein decreases cell proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly accelerates proliferation. Decreased WNT7A expression was due to hypermethylation at particular CpG sites. To our knowledge, this is the first study reporting reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration. Copyright © 2015 Elsevier Inc. All rights reserved.

Computationally-Guided Synthetic Control over Pore Size in Isostructural Porous Organic Cages

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

Slater, Anna G.; Reiss, Paul S.; Pulido, Angeles

The physical properties of 3-D porous solids are defined by their molecular geometry. Hence, precise control of pore size, pore shape, and pore connectivity are needed to tailor them for specific applications. However, for porous molecular crystals, the modification of pore size by adding pore-blocking groups can also affect crystal packing in an unpredictable way. This precludes strategies adopted for isoreticular metal-organic frameworks, where addition of a small group, such as a methyl group, does not affect the basic framework topology. Here, we narrow the pore size of a cage molecule, CC3, in a systematic way by introducing methyl groupsmore » into the cage windows. Computational crystal structure prediction was used to anticipate the packing preferences of two homochiral methylated cages, CC14-R and CC15-R, and to assess the structure-energy landscape of a CC15-R/CC3-S cocrystal, designed such that both component cages could be directed to pack with a 3-D, interconnected pore structure. The experimental gas sorption properties of these three cage systems agree well with physical properties predicted by computational energy-structure-function maps.« less

Dynamic transcriptomic analysis in hircine longissimus dorsi muscle from fetal to neonatal development stages.

PubMed

Zhan, Siyuan; Zhao, Wei; Song, Tianzeng; Dong, Yao; Guo, Jiazhong; Cao, Jiaxue; Zhong, Tao; Wang, Linjie; Li, Li; Zhang, Hongping

2018-01-01

Muscle growth and development from fetal to neonatal stages consist of a series of delicately regulated and orchestrated changes in expression of genes. In this study, we performed whole transcriptome profiling based on RNA-Seq of caprine longissimus dorsi muscle tissue obtained from prenatal stages (days 45, 60, and 105 of gestation) and neonatal stage (the 3-day-old newborn) to identify genes that are differentially expressed and investigate their temporal expression profiles. A total of 3276 differentially expressed genes (DEGs) were identified (Q value < 0.01). Time-series expression profile clustering analysis indicated that DEGs were significantly clustered into eight clusters which can be divided into two classes (Q value < 0.05), class I profiles with downregulated patterns and class II profiles with upregulated patterns. Based on cluster analysis, GO enrichment analysis found that 75, 25, and 8 terms to be significantly enriched in biological process (BP), cellular component (CC), and molecular function (MF) categories in class I profiles, while 35, 21, and 8 terms to be significantly enriched in BP, CC, and MF in class II profiles. KEGG pathway analysis revealed that DEGs from class I profiles were significantly enriched in 22 pathways and the most enriched pathway was Rap1 signaling pathway. DEGs from class II profiles were significantly enriched in 17 pathways and the mainly enriched pathway was AMPK signaling pathway. Finally, six selected DEGs from our sequencing results were confirmed by qPCR. Our study provides a comprehensive understanding of the molecular mechanisms during goat skeletal muscle development from fetal to neonatal stages and valuable information for future studies of muscle development in goats.

Rapid transport of CCL11 across the blood-brain barrier: regional variation and importance of blood cells.

PubMed

Erickson, Michelle A; Morofuji, Yoichi; Owen, Joshua B; Banks, William A

2014-06-01

Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine.

Rapid Transport of CCL11 across the Blood-Brain Barrier: Regional Variation and Importance of Blood Cells

PubMed Central

Erickson, Michelle A.; Morofuji, Yoichi; Owen, Joshua B.

2014-01-01

Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine. PMID:24706984

Cultural competence education for health professionals from pre-graduation to licensure delivered using facebook: Twelve-month follow-up on a randomized control trial.

PubMed

Chang, Li-Chun; Guo, Jong Long; Lin, Hui-Ling

2017-12-01

Cultural competence (CC) training is widely recognized as a crucial component of the professional development of healthcare providers. There is no study on the effect of Facebook (FB) as a strategy to promote continual learning to enhance CC among students in health professions. To test the effects of cultural competence education using FB as a delivery platform on knowledge, awareness, self-efficacy, and skill related to CC in health students from pre-graduation to licensed professional stages. A randomized controlled trial. We recruited students from professional nursing, pharmacy, and nutrition programs at six medical universities and randomly assigned them to study groups. Between T1 and T2 (months 1-3), the intervention group (IG) received pre-graduation education in CC while the control group (CG) received their regular educational program. Between T2 and T3 (months 6-9), IG received on-the-job education in CC while CG received the regular program. An online self-report questionnaire assessing CC knowledge, awareness, self-efficacy, and skill was analyzed at baseline, 6months, and 12months. Of 180 participants who completed the pretest, 120 (65 IG and 55 CG) completed both follow-ups. Changes over time were mixed; the only statistical difference between groups was an improvement in awareness in IG but not in CG. At 12months, intervention and control participants had different levels of awareness of CC (β=2.56, p<0.001), but other outcomes did not differ between groups. Health profession educators can adopt Facebook as an education delivery platform to offer personalized, social learning incorporating cultural competency curricula into ongoing education and training in rising awareness on CC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Longitudinal changes in corneal curvature and its relationship to axial length in the Correction of Myopia Evaluation Trial (COMET) cohort.

PubMed

Scheiman, Mitchell; Gwiazda, Jane; Zhang, Qinghua; Deng, Li; Fern, Karen; Manny, Ruth E; Weissberg, Erik; Hyman, Leslie

2016-01-01

To describe longitudinal changes in corneal curvature (CC) and axial length (AL) over 14 years, and to explore the relationship between AL and CC, and the axial length/corneal radius (AL/CR) ratio. In total 469, 6 to <12-year-old, children were enrolled in COMET. Measurements of refractive error, CC (D), CR (mm), and ocular component dimensions including AL were gathered annually. Linear mixed models were used to evaluate longitudinal changes adjusting for covariates (gender, ethnicity, lens type, baseline age and baseline refraction). The Pearson correlation coefficient between AL and CC was computed at each visit. There was a slight but significant (p<0.0001) flattening in CC over 14 years. At all visits females had significantly steeper CC than males (overall difference=0.53 D, p<0.0001). Caucasians had the steepest CC, and Hispanics the flattest (p=0.001). The correlation between AL and CC was -0.70 (p<0.0001) at baseline (mean age=9.3 years) and decreased to -0.53 (p<0.0001) at the 14-year visit (mean age=24.1 years). The average AL/CR ratio was 3.15 at baseline and increased to 3.31 at the 14-year visit. The correlation between the magnitude of myopia and AL/CR ratio was significantly higher (p<0.0001) at each visit than the correlation between myopia and AL alone. Differences in average corneal curvature by age, gender, and ethnicity observed in early childhood remain consistent as myopia progresses and stabilizes. This study also demonstrates increases in the AL/CR ratio as myopia progresses and then stabilizes, supporting observations from previous cross-sectional data. Copyright © 2015 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

CMPK1 and RBP3 are associated with corneal curvature in Asian populations.

PubMed

Chen, Peng; Miyake, Masahiro; Fan, Qiao; Liao, Jiemin; Yamashiro, Kenji; Ikram, Mohammad K; Chew, Merywn; Vithana, Eranga N; Khor, Chiea-Chuen; Aung, Tin; Tai, E-Shyong; Wong, Tien-Yin; Teo, Yik-Ying; Yoshimura, Nagahisa; Saw, Seang-Mei; Cheng, Ching-Yu

2014-11-15

Corneal curvature (CC) measures the steepness of the cornea and is an important parameter for clinically diseases such as astigmatism and myopia. Despite the high heritability of CC, only two associated genes have been discovered to date. We performed a three-stage genome-wide association study meta-analysis in 12 660 Asian individuals. Our Stage 1 was done in multiethnic cohorts comprising 7440 individuals, followed by a Stage 2 replication in 2473 Chinese and Stage 3 in 2747 Japanese. The SNP array genotype data were imputed up to the 1000 Genomes Project Phase 1 cosmopolitan panel. The SNP association with the radii of CC was investigated in the linear regression model with the adjustment of age, gender and principal components. In addition to the known genes, MTOR (also known as FRAP1) and PDGFRA, we discovered two novel genes associated with CC: CMPK1 (rs17103186, P = 3.3 × 10(-12)) and RBP3 (rs11204213 [Val884Met], P = 1.1 × 10(-13)). The missense RBP3 SNP, rs11204213, was also associated with axial length (AL) (P = 4.2 × 10(-6)) and had larger effects on both CC and AL compared with other SNPs. The index SNPs at the four indicated loci explained 1.9% of CC variance across the Stages 1 and 2 cohorts, while 33.8% of CC variance was explained by the genome-wide imputation data. We identified two novel genes influencing CC, which are related to either corneal shape or eye size. This study provides additional insights into genetic architecture of corneal shape. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Campbell Creek Research Homes FY 2012 Annual Performance Report

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

Gehl, Anthony C; Munk, Jeffrey D; Jackson, Roderick K

The Campbell Creek project is funded and managed by the Tennessee Valley Authority (TVA) Technology Innovation, Energy Efficiency, Power Delivery & and Utilization Office. Technical support is provided under contract by the Oak Ridge National Laboratory (ORNL) and the Electric Power Research Institute.The project was designed to determine the relative energy efficiency of typical new home construction, energy efficiency retrofitting of existing homes, and high -performance new homes built from the ground up for energy efficiency. This project will compare three houses that represented the current construction practice as a base case (Builder House CC1); a modified house that couldmore » represent a major energy- efficient retrofit (Retrofit House CC2); and a house constructed from the ground up to be a high- performance home (High Performance House CC3). In order tTo enablehave a valid comparison, it was necessary to simulate occupancy in all three houses and heavily monitor the structural components and the energy usage by component. All three houses are two story, slab on grade, framed construction. CC1 and CC2 are approximately 2,400 square feet2. CC3 has a pantry option, that is primarily used as a mechanical equipment room, that adds approximately 100 square feet2. All three houses are all-electric (with the exception of a gas log fireplace that is not used during the testing), and use air-source heat pumps for heating and cooling. The three homes are located in Knoxville in the Campbell Creek Subdivision. CC1 and CC2 are next door to each other and CC3 is across the street and a couple of houses down. The energy data collected will be used to determine the benefits of retrofit packages and high -performance new home packages. There are over 300 channels of continuous energy performance and thermal comfort data collection in the houses (100 for each house). The data will also be used to evaluate the impact of energy -efficient upgrades ton the envelope, mechanical equipment, or demand -response options. Each retrofit will be evaluated incrementally, by both short -term measurements and computer modeling, using a calibrated model. This report is intended to document the comprehensive testing, data analysis, research, and findings within the January 2011 through October 2012 timeframe at the Campbell Creek research houses. The following sections will provide an in-depth assessment of the technology progression in each of the three research houses. A detailed assessment and evaluation of the energy performance of technologies tested will also be provided. Finally, lessons learned and concluding remarks will be highlighted.« less

Low molecular weight hyaluronan induces migration of human choriocarcinoma JEG-3 cells mediated by RHAMM as well as by PI3K and MAPK pathways.

PubMed

Mascaró, Marilina; Pibuel, Matías A; Lompardía, Silvina L; Díaz, Mariangeles; Zotta, Elsa; Bianconi, Maria I; Lago, Néstor; Otero, Silvina; Jankilevich, Gustavo; Alvarez, Elida; Hajos, Silvia E

2017-08-01

Hyaluronan (HA) is the major glycosaminoglycan present in the extracellular matrix. It is produced by some tumours and promotes proliferation, differentiation and migration among others cellular processes. Gestational trophoblastic disease (GTD) is composed by non-tumour entities, such as hydatidiform mole (HM), which is the most common type of GTD and also malignant entities such as choriocarcinoma (CC) and placental site trophoblastic tumour (PSTT), being CC the most aggressive tumour. Although there is a growing understanding of GTD biology, the role of HA in the pathogenesis of this group of diseases remains largely unknown. The aim of this work was to study the role of HA in the pathogenesis of GTD by defining the expression pattern of HA and its receptors CD44 and RHAMM, as well as to determine if HA can modulate proliferation, differentiation and migration of CC cells. Receptors and signalling pathways involved were also analyzed. We demonstrated that HA and RHAMM are differently expressed among GTD entities and even among trophoblast subtypes. We also showed that HA is able to enhance the expression of extravillous trophoblast markers and also to induce migration of JEG-3 cells, the latter mediated by RHAMM as well as PI3K and MAPK pathways. These findings indicate a novel regulatory mechanism for CC cell biology and also contribute to the understanding of GTD pathophysiology.

Effect of a pH Gradient on the Protonation States of Cytochrome c Oxidase: A Continuum Electrostatics Study.

PubMed

Magalhães, Pedro R; Oliveira, A Sofia F; Campos, Sara R R; Soares, Cláudio M; Baptista, António M

2017-02-27

Cytochrome c oxidase (CcO) couples the reduction of dioxygen to water with transmembrane proton pumping, which leads to the generation of an electrochemical gradient. In this study we analyze how one of the components of the electrochemical gradient, the difference in pH across the membrane, or ΔpH, influences the protonation states of residues in CcO. We modified our continuum electrostatics/Monte Carlo (CE/MC) method in order to include the ΔpH and applied it to the study of CcO, in what is, to our best knowledge, the first CE/MC study of CcO in the presence of a pH gradient. The inclusion of a transmembrane pH gradient allows for the identification of residues whose titration behavior depends on the pH on both sides of the membrane. Among the several residues with unusual titration profiles, three are well-known key residues in the proton transfer process of CcO: E286 I , Y288 I , and K362 I . All three residues have been previously identified as being critical for the catalytic or proton pumping functions of CcO. Our results suggest that when the pH gradient increases, these residues may be part of a regulatory mechanism to stem the proton flow.

Selective enrichment of Eicosapentaenoic acid (20:5n-3) in N. oceanica CASA CC201 by natural auxin supplementation.

PubMed

Udayan, Aswathy; Arumugam, Muthu

2017-10-01

The present study aims to evaluate the effect of different concentration of natural auxin, Indole-3 acetic acid (IAA) on growth, lipid yield, PUFA and EPA accumulation in Nannochloropsis oceanica CASA CC201. It was observed that the, treatment with 10ppm concentration of IAA resulted in high cell number 579.5×10 6 cells/ml than the control (215.5×10 6 cells/ml). Treatment with IAA at a concentration of 40ppm gives the highest cellular lipid accumulation of 60.9% DCW than the control 31.05% DCW). Lipid yield is also found to be increased by the addition of 40ppm IAA (319.5mg/L) compared with the control (121.5mg/L). EPA percentage is increased to 10.76% by the addition of 40ppm IAA compared to the control (1.87%). Copyright © 2017 Elsevier Ltd. All rights reserved.

At a glance: cellular biology for engineers.

PubMed

Khoshmanesh, K; Kouzani, A Z; Nahavandi, S; Baratchi, S; Kanwar, J R

2008-10-01

Engineering contributions have played an important role in the rise and evolution of cellular biology. Engineering technologies have helped biologists to explore the living organisms at cellular and molecular levels, and have created new opportunities to tackle the unsolved biological problems. There is now a growing demand to further expand the role of engineering in cellular biology research. For an engineer to play an effective role in cellular biology, the first essential step is to understand the cells and their components. However, the stumbling block of this step is to comprehend the information given in the cellular biology literature because it best suits the readers with a biological background. This paper aims to overcome this bottleneck by describing the human cell components as micro-plants that form cells as micro-bio-factories. This concept can accelerate the engineers' comprehension of the subject. In this paper, first the structure and function of different cell components are described. In addition, the engineering attempts to mimic various cell components through numerical modelling or physical implementation are highlighted. Next, the interaction of different cell components that facilitate complicated chemical processes, such as energy generation and protein synthesis, are described. These complex interactions are translated into simple flow diagrams, generally used by engineers to represent multi-component processes.

Do the Particles of an Ideal Gas Collide?

ERIC Educational Resources Information Center

Lesk, Arthur M.

1974-01-01

Describes the collisional properties as a logically essential component of the ideal gas model since an actual intraparticle process cannot support observable anisotropic velocity distributions without collisions taken into account. (CC)

Abnormalities of laboratory coagulation tests versus clinically evident coagulopathic bleeding: results from the prehospital resuscitation on helicopters study (PROHS).

PubMed

Chang, Ronald; Fox, Erin E; Greene, Thomas J; Swartz, Michael D; DeSantis, Stacia M; Stein, Deborah M; Bulger, Eileen M; Melton, Sherry M; Goodman, Michael D; Schreiber, Martin A; Zielinski, Martin D; O'Keeffe, Terence; Inaba, Kenji; Tomasek, Jeffrey S; Podbielski, Jeanette M; Appana, Savitri; Yi, Misung; Johansson, Pär I; Henriksen, Hanne H; Stensballe, Jakob; Steinmetz, Jacob; Wade, Charles E; Holcomb, John B

2018-04-01

Laboratory-based evidence of coagulopathy (LC) is observed in 25-35% of trauma patients, but clinically-evident coagulopathy (CC) is not well described. Prospective observational study of adult trauma patients transported by helicopter from the scene to nine Level 1 trauma centers in 2015. Patients meeting predefined highest-risk criteria were divided into CC+ (predefined as surgeon-confirmed bleeding from uninjured sites or injured sites not controllable by sutures) or CC-. We used a mixed-effects, Poisson regression with robust error variance to test the hypothesis that abnormalities on rapid thrombelastography (r-TEG) and international normalized ratio (INR) were independently associated with CC+. Of 1,019 highest-risk patients, CC+ (n=41, 4%) were more severely injured (median ISS 32 vs 17), had evidence of LC on r-TEG and INR, received more transfused blood products at 4 hours (37 vs 0 units), and had greater 30-day mortality (59% vs 12%) than CC- (n=978, 96%). The overall incidence of LC was 39%. 30-day mortality was 22% vs 9% in those with and without LC. In two separate models, r-TEG K-time >2.5 min (RR 1.3, 95% CI 1.1-1.7), r-TEG mA <55 mm (RR 2.5, 95% CI 2.0-3.2), platelet count <150 x 10 9 /L (RR 1.2, 95% CI 1.1-1.3), and INR >1.5 (RR 5.4, 95% CI 1.8-16.3) were independently associated with CC+. A combined regression model was not generated because too few patients underwent both r-TEG and INR. CC was rare compared to LC. CC was associated with poor outcomes and impairment of both clotting factor and platelet-mediated coagulation components. Copyright © 2017 Elsevier Inc. All rights reserved.

The rhodium catalyzed three-component reaction of diazoacetates, titanium(IV) alkoxides and aldehydes.

PubMed

Lu, Chong-Dao; Liu, Hui; Chen, Zhi-Yong; Hu, Wen-Hao; Mi, Ai-Qiao

2005-05-28

The rhodium(II)-catalyzed three-component reaction of diazoacetates, titanium alkoxides and aldehydes is shown to give alpha-alkoxyl-beta-hydroxyl acid derivatives; the novel C-C bond formation reaction is proposed to occur through oxonium ylides derived from diazo compounds and titanium alkoxides, and followed by intermolecular trapping by aldehydes.

26 CFR 1.23-5 - Certification procedures.

Code of Federal Regulations, 2013 CFR

2013-04-01

... definition of an energy-conserving component or renewable energy source property. Upon the request of a...)(1)). (2) The item meets the definition of an other energy-conserving component specified in section 23(c)(4) or former section 44C(c)(4) see (§ 1.23-2(d)(4)). (3) The item meets the definition of solar...

26 CFR 1.23-5 - Certification procedures.

Code of Federal Regulations, 2012 CFR

2012-04-01

... definition of an energy-conserving component or renewable energy source property. Upon the request of a...)(1)). (2) The item meets the definition of an other energy-conserving component specified in section 23(c)(4) or former section 44C(c)(4) see (§ 1.23-2(d)(4)). (3) The item meets the definition of solar...

26 CFR 1.23-5 - Certification procedures.

Code of Federal Regulations, 2014 CFR

2014-04-01

... definition of an energy-conserving component or renewable energy source property. Upon the request of a...)(1)). (2) The item meets the definition of an other energy-conserving component specified in section 23(c)(4) or former section 44C(c)(4) see (§ 1.23-2(d)(4)). (3) The item meets the definition of solar...

Enantioselective Copper-Catalyzed Carboetherification of Unactivated Alkenes**

PubMed Central

Bovino, Michael T.; Liwosz, Timothy W.; Kendel, Nicole E.; Miller, Yan; Tyminska, Nina

2014-01-01

Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein is reported a highly efficient copper-catalyzed cyclization of γ-unsaturated pentenols that terminates in C-C bond formation, a net alkene carboetherification. Both intra- and intermolecular C-C bond formations are demonstrated, yielding functionalized chiral tetrahydrofurans as well as fused-ring and bridged-ring oxabicyclic products. Transition state calculations support a cis-oxycupration stereochemistry-determining step. PMID:24798697

The influence of different sub-bandage pressure values on venous leg ulcers healing when treated with compression therapy.

PubMed

Milic, Dragan J; Zivic, Sasa S; Bogdanovic, Dragan C; Jovanovic, Milan M; Jankovic, Radmilo J; Milosevic, Zoran D; Stamenkovic, Dragan M; Trenkic, Marija S

2010-03-01

Venous leg ulcers (VLU) have a huge social and economic impact. An estimated 1.5% of European adults will suffer a venous ulcer at some point in their lives. Despite the widespread use of bandaging with high pressure in the treatment of this condition, recurrence rates range between 25% to 70%. Numerous studies have suggested that the compression system should provide sub-bandage pressure values in the range from 35 mm Hg to 45 mm Hg in order to achieve the best possible healing results. An open, randomized, prospective, single-center study was performed in order to determine the healing rates of VLU when treated with different compression systems and different sub-bandage pressure values. One hundred thirty-one patients (72 women, 59 men; mean age, 59-years-old) with VLU (ulcer surface >3 cm(2); duration >3 months) were randomized into three groups: group A - 42 patients who were treated using an open-toed, elastic, class III compression device knitted in tubular form (Tubulcus, Laboratoires Innothera, Arcueil, France); group B - 46 patients treated with the multi-component bandaging system comprised of Tubulcus and one elastic bandage (15 cm wide and 5 cm long with 200% stretch, Niva, Novi Sad, Serbia); and group C - forty-three patients treated with the multi-component bandaging system comprised of Tubulcus and two elastic bandages. Pressure measurements were taken with the Kikuhime device (TT MediTrade, Soro, Denmark) at the B1 measuring point in the supine, sitting, and standing positions under the three different compression systems. The median resting values in the supine and standing positions in examined study groups were as follows: group A - 36.2 mm Hg and 43.9 mm Hg; group B - 53.9 mm Hg and 68.2 mm Hg; group C - 74.0 mm Hg and 87.4 mm Hg. The healing rate during the 26-week treatment period was 25% (13/42) in group A, 67.4% (31/46) in group B, and 74.4% (32/43) in group C. The success of compression treatment in group A was strongly associated with the small ulcer surface (<5 cm(2)) and smaller calf circumference (CC; <38 cm). On the other hand, compliance in group A was good. In groups B and C, compliance was poor in patients with small CC, but the healing rate was high, especially in patients with large ulcers and a large CC (>43 cm). The results obtained in this study indicate that better healing results are achieved with two or multi-component compression systems than with single-component compression systems and that a compression system should be individually determined for each patient according to individual characteristics of the leg and CC. Target sub-bandage pressure value (B1 measuring point in the sitting position) of the compression system needed for the ulcer healing could be determined according to a simple formula, CC + CC/2.

Flexible distributed architecture for semiconductor process control and experimentation

NASA Astrophysics Data System (ADS)

Gower, Aaron E.; Boning, Duane S.; McIlrath, Michael B.

1997-01-01

Semiconductor fabrication requires an increasingly expensive and integrated set of tightly controlled processes, driving the need for a fabrication facility with fully computerized, networked processing equipment. We describe an integrated, open system architecture enabling distributed experimentation and process control for plasma etching. The system was developed at MIT's Microsystems Technology Laboratories and employs in-situ CCD interferometry based analysis in the sensor-feedback control of an Applied Materials Precision 5000 Plasma Etcher (AME5000). Our system supports accelerated, advanced research involving feedback control algorithms, and includes a distributed interface that utilizes the internet to make these fabrication capabilities available to remote users. The system architecture is both distributed and modular: specific implementation of any one task does not restrict the implementation of another. The low level architectural components include a host controller that communicates with the AME5000 equipment via SECS-II, and a host controller for the acquisition and analysis of the CCD sensor images. A cell controller (CC) manages communications between these equipment and sensor controllers. The CC is also responsible for process control decisions; algorithmic controllers may be integrated locally or via remote communications. Finally, a system server images connections from internet/intranet (web) based clients and uses a direct link with the CC to access the system. Each component communicates via a predefined set of TCP/IP socket based messages. This flexible architecture makes integration easier and more robust, and enables separate software components to run on the same or different computers independent of hardware or software platform.

Composition of three essential oils, and their mammalian cell toxicity and antimycobacterial activity against drug resistant-tuberculosis and nontuberculous mycobacteria strains.

PubMed

Bueno, Juan; Escobar, Patricia; Martínez, Jairo René; Leal, Sandra Milena; Stashenko, Elena E

2011-11-01

Tuberculosis (TB) is the most ancient epidemic disease in the world and a serious opportunistic disease in HIV/AIDS patients. The increase in multidrug resistant Mycobacterium tuberculosis (MDR-TB, XDR-TB) demands the search for novel antimycobacterial drugs. Essential oils (EOs) have been widely used in medicine and some EOs and their major components have been shown to be active against M. tuberculosis. The aim of this work was to evaluate the antimycobacterial and cell toxicity activities of three EOs derived from Salvia aratocensis, Turnera diffusa and Lippia americana, aromatics plants collected in Colombia. The EOs were isolated by hydrodistillation and analyzed by GC/MS techniques. The EOs were tested against 15 Mycobacterium spp using a colorimetric macrodilution method and against mammalian Vero and THP-1 cells by MTT. The activity was expressed as minimal concentration in microg/mL that inhibits growth, and the concentration that is cytotoxic for 50 or 90% of the cells (CC50 and CC90). The major components were epi-alpha-cadinol (20.1%) and 1,10-di-epi-cubenol (14.2%) for Salvia aratocensis; drima-7,9(11)-diene (22.9%) and viridiflorene (6.6%) for Turnera diffusa; and germacrene D (15.4%) and trans-beta- caryophyllene (11.3%) for Lippia americana. The most active EO was obtained from S. aratocensis, with MIC values below 125 microg mL(-1) for M. tuberculosis Beijing genotype strains, and 200 to 500 microg mL(-1) for nontuberculous mycobacterial strains. The EOs were either partially or non toxic to Vero and THP-1 mammalian cells with CC50 values from 30 to > 100 microg mL(-1), and a CC90 > 100 microg mL(-1). The EOs obtained from the three aromatic Colombian plants are an important source of potential compounds against TB. Future studies using the major EO components are recommended.

Processing the Bouguer anomaly map of Biga and the surrounding area by the cellular neural network: application to the southwestern Marmara region

NASA Astrophysics Data System (ADS)

Aydogan, D.

2007-04-01

An image processing technique called the cellular neural network (CNN) approach is used in this study to locate geological features giving rise to gravity anomalies such as faults or the boundary of two geologic zones. CNN is a stochastic image processing technique based on template optimization using the neighborhood relationships of cells. These cells can be characterized by a functional block diagram that is typical of neural network theory. The functionality of CNN is described in its entirety by a number of small matrices (A, B and I) called the cloning template. CNN can also be considered to be a nonlinear convolution of these matrices. This template describes the strength of the nearest neighbor interconnections in the network. The recurrent perceptron learning algorithm (RPLA) is used in optimization of cloning template. The CNN and standard Canny algorithms were first tested on two sets of synthetic gravity data with the aim of checking the reliability of the proposed approach. The CNN method was compared with classical derivative techniques by applying the cross-correlation method (CC) to the same anomaly map as this latter approach can detect some features that are difficult to identify on the Bouguer anomaly maps. This approach was then applied to the Bouguer anomaly map of Biga and its surrounding area, in Turkey. Structural features in the area between Bandirma, Biga, Yenice and Gonen in the southwest Marmara region are investigated by applying the CNN and CC to the Bouguer anomaly map. Faults identified by these algorithms are generally in accordance with previously mapped surface faults. These examples show that the geologic boundaries can be detected from Bouguer anomaly maps using the cloning template approach. A visual evaluation of the outputs of the CNN and CC approaches is carried out, and the results are compared with each other. This approach provides quantitative solutions based on just a few assumptions, which makes the method more powerful than the classical methods.

Biorthogonal moment expansions in coupled-cluster theory: Review of key concepts and merging the renormalized and active-space coupled-cluster methods

NASA Astrophysics Data System (ADS)

Shen, Jun; Piecuch, Piotr

2012-06-01

After reviewing recent progress in the area of the development of coupled-cluster (CC) methods for quasi-degenerate electronic states that are characterized by stronger non-dynamical correlation effects, including new generations of single- and multi-reference approaches that can handle bond breaking and excited states dominated by many-electron transitions, and after discussing the key elements of the left-eigenstate completely renormalized (CR) CC and equation-of-motion (EOM) CC methods, and the underlying biorthogonal method of moments of CC (MMCC) equations [P. Piecuch, M. Włoch, J. Chem. Phys. 123 (2005) 224105; P. Piecuch, M. Włoch, J.R. Gour, A. Kinal, Chem. Phys. Lett. 418 (2006) 467; M. Włoch, M.D. Lodriguito, P. Piecuch, J.R. Gour, Mol. Phys. 104 (2006) 2149], it is argued that it is beneficial to merge the CR-CC/EOMCC and active-space CC/EOMCC [P. Piecuch, Mol. Phys. 108 (2010) 2987, and references therein] theories into a single formalism. In order to accomplish this goal, the biorthogonal MMCC theory, which provides compact many-body expansions for the differences between the full configuration interaction and CC or, in the case of excited states, EOMCC energies, obtained using conventional truncation schemes in the cluster operator T and excitation operator Rμ, is generalized, so that one can correct the CC/EOMCC energies obtained with arbitrary truncations in T and Rμ for the selected many-electron correlation effects of interest. The resulting moment expansions, defining the new, Flexible MMCC (Flex-MMCC) formalism, and the ensuing CC(P; Q) hierarchy, proposed in the present work, enable one to correct energies obtained in the active-space CC and EOMCC calculations, in which one selects higher many-body components of T and Rμ via active orbitals and which recover much of the relevant non-dynamical and some dynamical electron correlation effects in applications involving potential energy surfaces (PESs) along bond breaking coordinates, for the effects of higher-order, primarily dynamical, correlations missing in the active-space CC/EOMCC considerations. The Flex-MMCC corrections to the active-space CC/EOMCC energies are mathematically similar to the non-iterative energy corrections defining the existing left-eigenstate CR-CC and CR-EOMCC methods, such as CR-CC(2, 3) and CR-EOMCC(2, 3). The potential advantages of the Flex-MMCC and CC(P; Q) formalisms are illustrated by describing the initial implementation and numerical tests of the novel CC hybrid scheme, abbreviated as CC(t; 3), in which one corrects the results of the CC calculations with singles, doubles, and active-space triples, termed CCSDt, for the remaining effects due to connected triple excitations that are missing in the CCSDt considerations, but are present in the MMCC-based CR-CC(2, 3) approach. By examining bond breaking in the HF, F2, and F2+ molecules, it is demonstrated that the CC(t; 3) method improves the CCSDt and CR-CC(2, 3) results, providing PESs that agree with those obtained with the full CC theory with singles, doubles, and triples (CCSDT) to within small fractions of a millihartree, at the fraction of the computer costs of the CCSDT calculations. Different strategies for defining active-space triples within the CC(t; 3) scheme and the underlying CCSDt method are discussed. When limited to the ground-state problem, the CC(t; 3) approach can be regarded as an improved and rigorously derived extension of the recently proposed CCSD(T)-h method [J. Shen, E. Xu, Z. Kou, S. Li, J. Chem. Phys. 132 (2010) 114115], in which triples corrections of the CCSD(T) type are replaced by their more robust CR-CC(2, 3)-style analogs.

Inter-Cellular Exchange of Cellular Components via VE-Cadherin-Dependent Trans-Endocytosis

PubMed Central

Sakurai, Takashi; Woolls, Melissa J.; Jin, Suk-Won

2014-01-01

Cell-cell communications typically involve receptor-mediated signaling initiated by soluble or cell-bound ligands. Here, we report a unique mode of endocytosis: proteins originating from cell-cell junctions and cytosolic cellular components from the neighboring cell are internalized, leading to direct exchange of cellular components between two adjacent endothelial cells. VE-cadherins form transcellular bridges between two endothelial cells that are the basis of adherence junctions. At such adherens junction sites, we observed the movement of the entire VE-cadherin molecule from one endothelial cell into the other with junctional and cytoplasmic components. This phenomenon, here termed trans-endocytosis, requires the establishment of a VE-cadherin homodimer in trans with internalization proceeding in a Rac1-, and actomyosin-dependent manner. Importantly, the trans-endocytosis is not dependent on any known endocytic pathway including clathrin-dependent endocytosis, macropinocytosis or phagocytosis. This novel form of cell-cell communications, leading to a direct exchange of cellular components, was observed in 2D and 3D-cultured endothelial cells as well as in the developing zebrafish vasculature. PMID:24603875

A Modified Double Monte Carlo Technique to Approximate Reliability Confidence Limits of Systems with Components Characterized by the Weibull Distribution.

DTIC Science & Technology

1980-12-01

m ~ 1O ,-4 - 0 r-- o4 0 0 0 0) 0 0) 0 C) 0 0 0 o 0 0 0 0 0 0 0 0 0 0 0 N~ t- 10 m ~ m v t - 0 t...8217- 10 00 m ~ o 0 m ~ w r-l m ~ (D wcc C’ O1 q1I t - t- wc mD t- 0 10 N’ r- 0 1-1 o- 0 0 0 0 0 r-A 0 0 0 0 0 o 0 0C) 0 0 0 0 C) 0 0 0 - ~ t- t- m ~ cc wc N m m ...10 0 mc m ’- C 0 0 r-i 0 C) r-I 0 0 0 0 0 4-4) 0 0 0 0 0 0 0 0 C 0 C)H -qc)cic) o 0 D 00 4- a)mNC0 ( ) - O c Y 0 0 cc C’] cc 00 r4 LO CD) cc 0 cq

Extracellular cystatin SN and cathepsin B prevent cellular senescence by inhibiting abnormal glycogen accumulation.

PubMed

Oh, Sang-Seok; Park, Soojong; Lee, Ki-Won; Madhi, Hamadi; Park, Sae Gwang; Lee, Hee Gu; Cho, Yong-Yeon; Yoo, Jiyun; Dong Kim, Kwang

2017-04-06

Cystatin SN (CST1), a known inhibitor of cathepsin B (CatB), has important roles in tumor development. Paradoxically, CatB is a member of the cysteine cathepsin family that acts in cellular processes, such as tumor development and invasion. However, the relationship between CST1 and CatB, and their roles in tumor development are poorly understood. In this study, we observed that the knockdown of CST1 induced the activity of senescence-associated β-galactosidase, a marker of cellular senescence, and expression of senescence-associated secretory phenotype genes, including interleukin-6 and chemokine (C-C motif) ligand 20, in MDA-MB-231 and SW480 cancer cells. Furthermore, CST1 knockdown decreased extracellular CatB activity, and direct CatB inhibition, using specific inhibitors or shCatB, induced cellular senescence. Reconstitution of CST1 restored CatB activity and inhibited cellular senescence in CST1 knockdown cells. CST1 knockdown or CatB inhibition increased glycogen synthase (GS) kinase 3β phosphorylation at serine 9, resulting in the activation of GS and the induction of glycogen accumulation associated with cellular senescence. Importantly, CST1 knockdown suppressed cancer cell proliferation, soft agar colony growth and tumor growth in a xenograft model. These results indicate that CST1-mediated extracellular CatB activity enhances tumor development by preventing cellular senescence. Our findings suggest that antagonists of CST1 or inhibitors of CatB are potential anticancer agents.

Cyanide Antidotes for Mass Casualties: Comparison of Intramuscular Injector by Autoinjector, Intraosseous Injection, and Inhalational Delivery

DTIC Science & Technology

2015-12-01

oxygen consump- tion,46,47 we studied the effects of cyanide on cellular oxygen consumption using an XF extracellular flux analyzer (Seahorse...baseline values during whole blood resuscitation (−0.24 0.14 μM at the end of resuscita- tion). Figure 2 also shows the effect of inspired oxygen concen...during respiratory challenges. This composite effect demonstrates uncoupling of the hemo- globin oxygen signal changes from CcO redox state signals

Campbell Creek Research Homes: FY2013 Annual Performance Report OCT.1, 2012 SEP. 30, 2013

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

Jackson, Roderick K; Boudreaux, Philip R; Munk, Jeffrey D

1.INTRODUCTION AND PROJECT OVERVIEW The Campbell Creek project is funded and managed by the Tennessee Valley Authority (TVA) Technology Innovation, Energy Efficiency, Power Delivery and Utilization Office. Technical support is provided under contract by the Oak Ridge National Laboratory (ORNL) and the Electric Power Research Institute (EPRI). The project was designed to determine the relative energy efficiency of typical new home construction, of retrofitting of existing homes, and of high-performance new homes built from the ground up for energy efficiency. This project was designed to compare three houses that represent current construction practices: a base case (Builder House CC1); amore » modified house that could represent a major energy-efficient retrofit (Retrofit House CC2); and a house constructed from the ground up to be a high-performance home (High Performance House CC3). To enable a valid comparison, it was necessary to simulate occupancy in all three houses and extensively monitor the structural components and the energy usage by component. In October 2013, the base case was also modified by replacing the builder-grade heating, ventilation, and air-conditioning (HVAC) system with a high-efficiency variable-speed unit. All three houses are two-story, slab-on-grade, framed construction. CC1 and CC2 are approximately 2,400 ft2. CC3 has a pantry option, used primarily as a mechanical equipment room, that adds approximately 100 ft2. All three houses are all-electric (with the exception of a gas log fireplace that is not used during the testing) and use air-source heat pumps for heating and cooling. The three homes are located in Knoxville in the Campbell Creek Subdivision. CC1 and CC2 are next door to each other with a south-facing orientation; CC3 has a north-facing orientation and is located across the street and a couple of houses down. The energy data collected will be used to determine the benefits of retrofit packages and high-performance new home packages. There are more than 300 channels of continuous energy performance and thermal comfort data collection in the houses (100 for each house). The data will be used to evaluate the impact of energy-efficiency upgrades on the envelope, mechanical equipment, and demand-response options. Each retrofit will be evaluated incrementally, by both short-term measurements and computer modeling, using a calibrated model. This report is intended to document the comprehensive testing, data analysis, research, and findings within the October 2012 through September 2013 (FY 2013) timeframe at the Campbell Creek research houses. The following sections will provide an in-depth assessment of the technology progression in each of the three research houses. A detailed assessment and evaluation of the energy performance of technologies tested will also be provided. Finally, lessons learned and concluding remarks will be highlighted.« less

NMR insight into myosin-binding subunit coiled-coil structure reveals binding interface with protein kinase G-Iα leucine zipper in vascular function.

PubMed

Sharma, Alok K; Birrane, Gabriel; Anklin, Clemens; Rigby, Alan C; Alper, Seth L

2017-04-28

Nitrovasodilators relax vascular smooth-muscle cells in part by modulating the interaction of the C-terminal coiled-coil domain (CC) and/or the leucine zipper (LZ) domain of the myosin light-chain phosphatase component, myosin-binding subunit (MBS), with the N-terminal LZ domain of protein kinase G (PKG)-Iα. Despite the importance of vasodilation in cardiovascular homeostasis and therapy, our structural understanding of the MBS CC interaction with LZ PKG-1α has remained limited. Here, we report the 3D NMR solution structure of homodimeric CC MBS in which amino acids 932-967 form a coiled-coil of two monomeric α-helices in parallel orientation. We found that the structure is stabilized by non-covalent interactions, with dominant contributions from hydrophobic residues at a and d heptad positions. Using NMR chemical-shift perturbation (CSP) analysis, we identified a subset of hydrophobic and charged residues of CC MBS (localized within and adjacent to the C-terminal region) contributing to the dimer-dimer interaction interface between homodimeric CC MBS and homodimeric LZ PKG-Iα. 15 N backbone relaxation NMR revealed the dynamic features of the CC MBS interface residues identified by NMR CSP. Paramagnetic relaxation enhancement- and CSP-NMR-guided HADDOCK modeling of the dimer-dimer interface of the heterotetrameric complex exhibits the involvement of non-covalent intermolecular interactions that are localized within and adjacent to the C-terminal regions of each homodimer. These results deepen our understanding of the binding restraints of this CC MBS·LZ PKG-Iα low-affinity heterotetrameric complex and allow reevaluation of the role(s) of myosin light-chain phosphatase partner polypeptides in regulation of vascular smooth-muscle cell contractility. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Utilizing a Modified Care Coordination Measurement Tool to Capture Value for a Pediatric Outpatient Parenteral and Prolonged Oral Antibiotic Therapy Program.

PubMed

Vaz, Louise E; Farnstrom, Cindi L; Felder, Kimberly K; Guzman-Cottrill, Judith; Rosenberg, Hannah; Antonelli, Richard C

2017-04-17

Outpatient parenteral or prolonged oral antibiotic therapy (OPAT) programs reduce inpatient healthcare costs by shifting care to outpatient settings. Care coordination (CC) is a necessary component to successfully transition patients. Our objective was to assess outcomes of provider time spent on nonreimbursable CC activities in a pediatric OPAT program. We used a qualitative feasibility pilot design and modified the Care Coordination Measurement Tool. We captured nonreimbursable CC activity and associated outcome(s) among pediatric patients enrolled in OPAT from March 1 to April 30, 2015 (44 work days) at Doernbecher Children's Hospital. We generated summary statistics for this institutional review board-waived QI project. There were 154 nonreimbursable CC encounters conducted by 2 infectious diseases (ID) providers for 29 patients, ages 17 months-15 years, with complex infections. Total estimated time spent on CC was 54 hours, equivalent to at least 6 workdays. Five patients with complex social issues used 37% of total CC time. Of 129 phone events, 38% involved direct contact with families, pharmacies (13%), primary care providers (13%), and home health nursing (11%). Care coordination prevented 10 emergency room (ER) visits and 2 readmissions. Care coordination led to 16 additional, not previously scheduled subspecialist and 13 primary care visits. The OPAT providers billed for 32 clinic visits during the study period. Nonreimbursable CC work by OPAT providers prevented readmissions and ER visits and helped facilitate appropriate healthcare use. The value of pediatric OPAT involvement in patient care would have been underestimated based on reimbursable ID consultations and clinic visits alone. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Impact of bacteriophage Saint3 carriage on the immune evasion capacity and hemolytic potential of Staphylococcus aureus CC398.

PubMed

Jung, Philipp; Abdelbary, Mohamed M H; Kraushaar, Britta; Fetsch, Alexandra; Geisel, Jürgen; Herrmann, Mathias; Witte, Wolfgang; Cuny, Christiane; Bischoff, Markus

2017-02-01

Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates of clonal complex 398 (CC398) are frequently found in Europe, and recent studies highlighted the importance of mobile genetic element (MGE) exchange for host adaptation of this lineage. Of note, one of the MGEs commonly found in human S. aureus isolates, the immune evasion cluster (IEC) harboring bacteriophage Saint3, is very rarely found in LA-MRSA CC398 isolates obtained from farm animals, but more frequently found in LA-MRSA CC398 that were retransmitted to humans. Here, we analyzed with a set of S. aureus CC398 isolates harboring/lacking φSaint3 how this MGE affects (i) phagocytosis of CC398 isolates by polymorphonuclear neutrophils (PMNs), and (ii) hemolysis of human and livestock-derived erythrocytes. Isolates lacking φSaint3 were more efficiently phagocytosed by human PMNs in whole blood phagocytosis assays than isolates harboring this bacteriophage, irrespective of their origin. Notably, a similar effect was observed when equine blood was utilized, but not detected with porcine blood. Integration of φSaint3 into LA-MRSA CC398 strains lacking this MGE confirmed these findings, as φSaint3-harboring recipients were again less efficiently ingested by PMNs in equine and human blood than their parental strains. Integration of φSaint3 strongly reduced the hemolytic potential of the culture supernatants against human-derived erythrocytes, and to a smaller extent also against porcine-derived erythrocytes, while φSaint3 integration only slightly affected the hemolytic capacities against equine-derived red blood cells. The significant protective effect of φSaint3 against phagocytosis by equine PMNs suggests that the host specificity of the IEC components might be broader than currently assumed. Copyright © 2016 Elsevier B.V. All rights reserved.

Impaired viscosity of gastric secretion and its mucin content as potential contributing factors to the development of chronic constipation.

PubMed

Castro-Combs, Juan; Garcia, Cesar J; Majewski, Marek; Wallner, Grzegorz; Sarosiek, Jerzy

2014-11-01

The alimentary tract mucosa continuously releases mucus-rich secretion. Mucin, the major component of mucus, determines its viscosity and provides lubrication for the luminal content of indigestible food particles. To measure mucin secretion rate and its viscosity in patients with chronic constipation (CC) and in asymptomatic volunteers. Nineteen patients with symptoms of CC and 19 controls were included in the study. Mucin secretion and viscosity were assessed in aspirated gastric juice in basal conditions and after stimulation with pentagastrin (1 h each). Mucin content was tested by PAS methodology. Viscosity was measured using cone/plate digital viscometer. Mucin secretion rates in basal and stimulated conditions in controls were 65 and 42 % higher than in patients with CC (P < 0.05 and P < 0.001, respectively). Basal viscosity in controls was 48 % higher than in CC (P < 0.05) at the lowest and 55 % higher (P < 0.05) at the middle velocities. Viscosity in pentagastrin-stimulated conditions in controls was 71 % higher than in CC (P < 0.01) at the lowest and 35 % higher (P < 0.05) at the middle velocities. (1) The significantly lower rate of soluble mucin secretion in patients with CC than in normal volunteers may reflect impairment in mucin-related lubrication. (2) Significantly lower viscosity of gastric secretion in patients with CC may result from the lower rate of mucin secretion and may also diminish lubrication within the alimentary tract. (3) This may potentially set the stage for the development of symptoms related to chronic constipation and open a new therapeutic avenue for this patient population.

CC-Chemokine Ligand 2 (CCL2) Suppresses High Density Lipoprotein (HDL) Internalization and Cholesterol Efflux via CC-Chemokine Receptor 2 (CCR2) Induction and p42/44 Mitogen-activated Protein Kinase (MAPK) Activation in Human Endothelial Cells *

PubMed Central

Sun, Run-Lu; Huang, Can-Xia; Bao, Jin-Lan; Jiang, Jie-Yu; Zhang, Bo; Zhou, Shu-Xian; Cai, Wei-Bin; Wang, Hong; Wang, Jing-Feng; Zhang, Yu-Ling

2016-01-01

High density lipoprotein (HDL) has been proposed to be internalized and to promote reverse cholesterol transport in endothelial cells (ECs). However, the mechanism underlying these processes has not been studied. In this study, we aim to characterize HDL internalization and cholesterol efflux in ECs and regulatory mechanisms. We found mature HDL particles were reduced in patients with coronary artery disease (CAD), which was associated with an increase in CC-chemokine ligand 2 (CCL2). In cultured primary human coronary artery endothelial cells and human umbilical vein endothelial cells, we determined that CCL2 suppressed the binding (4 °C) and association (37 °C) of HDL to/with ECs and HDL cellular internalization. Furthermore, CCL2 inhibited [3H]cholesterol efflux to HDL/apoA1 in ECs. We further found that CCL2 induced CC-chemokine receptor 2 (CCR2) expression and siRNA-CCR2 reversed CCL2 suppression on HDL binding, association, internalization, and on cholesterol efflux in ECs. Moreover, CCL2 induced p42/44 mitogen-activated protein kinase (MAPK) phosphorylation via CCR2, and p42/44 MAPK inhibition reversed the suppression of CCL2 on HDL metabolism in ECs. Our study suggests that CCL2 was elevated in CAD patients. CCL2 suppressed HDL internalization and cholesterol efflux via CCR2 induction and p42/44 MAPK activation in ECs. CCL2 induction may contribute to impair HDL function and form atherosclerosis in CAD. PMID:27458015

Extracorporeal shock wave markedly alleviates radiation-induced chronic cystitis in rat

PubMed Central

Chen, Yen-Ta; Chen, Kuan-Hung; Sung, Pei-Hsun; Yang, Chih-Chao; Cheng, Ben-Chung; Chen, Chih-Hung; Chang, Chia-Lo; Sheu, Jiunn-Jye; Lee, Fan-Yen; Shao, Pei-Lin; Sun, Cheuk-Kwan; Yip, Hon-Kan

2018-01-01

This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can effectively inhibit radiation-induced chronic cystitis (CC). Adult male Sprague-Dawley (SD) rats (n = 24) were randomly divided into group 1 (normal control), group 2 (CC induced by radiation with 300 cGy twice with a four-hour interval to the urinary bladder), group 3 [CC with ECSW treatment (0.2 mJ/mm2/120 impulses/at days 1, 7, and 14 after radiation)]. Bladder specimens were harvested by day 28 after radiation. By day 28 after radiation, the degree of detrusor contraction impairment was significantly higher in group 2 than that in groups 1 and 3, and significantly higher in group 3 than that in group 1 (P<0.0001). The urine albumin concentration expressed an opposite pattern compared to that of detrusor function among the three groups (P<0.0001). The bladder protein expressions of inflammatory (TLR-2/TLR-4/IL-6/IL-12/MMP-9/TNF-α/NF-κB/RANTES/iNOS) and oxidative-stress (NOX-1/NOX-2/oxidized protein) biomarkers exhibited a pattern identical to that of urine albumin in all groups (all P<0.0001). The cellular expressions of inflammatory (CD14+/CD68+/CD74+/COX-2/MIF+/substance P+) and cytokeratin (CK13+/HMW CK+/CK+17/CK+18/CK+19) biomarkers, and collagen-deposition/fibrotic areas as well as epithelial-damaged score displayed an identical pattern compared to that of urine albumin among the three groups (all P<0.0001). In conclusion, ECSW treatment effectively protected urinary bladder from radiation-induced CC. PMID:29636892

A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

ERIC Educational Resources Information Center

Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

2015-01-01

Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do…

Hypersonic Composites Resist Extreme Heat and Stress

NASA Technical Reports Server (NTRS)

2007-01-01

Through research contracts with NASA, Materials and Electrochemical Research Corporation (MER), of Tucson, Arizona, contributed a number of technologies to record-breaking hypersonic flights. Through this research, MER developed a coating that successfully passed testing to simulate Mach 10 conditions, as well as provide several additional carbon-carbon (C-C) composite components for the flights. MER created all of the leading edges for the X-43A test vehicles at Dryden-considered the most critical parts of this experimental craft. In addition to being very heat resistant, the coating had to be very lightweight and thin, as the aircraft was designed to very precise specifications and could not afford to have a bulky coating. MER patented its carbon-carbon (C-C) composite process and then formed a spinoff company, Frontier Materials Corporation (FMC), also based in Tucson. FMC is using the patent in conjunction with low-cost PAN (polyacrylonitrile)-based fibers to introduce these materials to the commercial markets. The C-C composites are very lightweight and exceptionally strong and stiff, even at very high temperatures. The composites have been used in industrial heating applications, the automotive and aerospace industries, as well as in glass manufacturing and on semiconductors. Applications also include transfer components for glass manufacturing and structural members for carrier support in semiconductor processing.

Effects of a clear-cut harvest on soil respiration in a jack pine - Lichen woodland

USGS Publications Warehouse

Striegl, Robert G.; Wickland, K.P.

1998-01-01

Quantification of the components of ecosystem respiration is essential to understanding carbon (C) cycling of natural and disturbed landscapes. Soil respiration, which includes autotrophic and heterotrophic respiration from throughout the soil profile, is the second largest flux in the global carbon cycle. We measured soil respiration (soil CO2 emission) at an undisturbed mature jack pine (Pinus banksiana Lamb.) stand in Saskatchewan (old jack pine, OJP), and at a formerly continuous portion of the stand that was clear-cut during the previous winter (clear-cut, CC). Tree harvesting reduced soil CO2 emission from ???22.5 to ???9.1 mol CO2??m2 for the 1994 growing season. OJP was a small net sink of atmospheric CO2, while CC was a net source of CO2. Winter emissions were similar at both sites. Reduction of soil respiration was attributed to disruption of the soil surface and to the death of tree roots. Flux simulations for CC and OJP identify 40% of CO2 emission at the undisturbed OJP site as near-surface respiration, 25% as deep-soil respiration, and 35% as tree-root respiration. The near-surface component was larger than the estimated annual C input to soil, suggesting fast C turnover and no net C accumulation in these boreal uplands in 1994.

A Suboptimal Power-Saving Transmission Scheme in Multiple Component Carrier Networks

NASA Astrophysics Data System (ADS)

Chung, Yao-Liang; Tsai, Zsehong

Power consumption due to transmissions in base stations (BSs) has been a major contributor to communication-related CO2 emissions. A power optimization model is developed in this study with respect to radio resource allocation and activation in a multiple Component Carrier (CC) environment. We formulate and solve the power-minimization problem of the BS transceivers for multiple-CC networks with carrier aggregation, while maintaining the overall system and respective users' utilities above minimum levels. The optimized power consumption based on this model can be viewed as a lower bound of that of other algorithms employed in practice. A suboptimal scheme with low computation complexity is proposed. Numerical results show that the power consumption of our scheme is much better than that of the conventional one in which all CCs are always active, if both schemes maintain the same required utilities.

Enantioselective copper-catalyzed carboetherification of unactivated alkenes.

PubMed

Bovino, Michael T; Liwosz, Timothy W; Kendel, Nicole E; Miller, Yan; Tyminska, Nina; Zurek, Eva; Chemler, Sherry R

2014-06-16

Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein reported is a highly efficient copper-catalyzed cyclization of γ-unsaturated pentenols which terminates in C-C bond formation, a net alkene carboetherification. Both intra- and intermolecular C-C bond formations are demonstrated, thus yielding functionalized chiral tetrahydrofurans as well as fused-ring and bridged-ring oxabicyclic products. Transition-state calculations support a cis-oxycupration stereochemistry-determining step. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Extracellular matrix controls neuronal features that mediate the persistence of fear.

PubMed

Pignataro, Annabella; Pagano, Roberto; Guarneri, Giorgia; Middei, Silvia; Ammassari-Teule, Martine

2017-12-01

Degradation of the chondroitin sulfate proteoglycans of the extracellular matrix (ECM) by injections of the bacterial enzyme chondroitinase ABC (ChABC) in the basolateral amygdala (BLA) does not impair fear memory formation but accelerates its extinction and disrupts its reactivation. These observations suggest that the treatment might selectively interfere with the post-extinction features of neurons that mediate the reinstatement of fear. Here, we report that ChABC mice show regular fear memory and memory-driven c-fos activation and dendritic spine formation in the BLA. These mice then rapidly extinguish their fear response and exhibit a post-extinction concurrent reduction in c-fos activation and large dendritic spines that extends to the anterior cingulate cortex 7 days later. At this remote time point, fear renewal and fear retrieval are impaired. These findings show that a non-cellular component of the brain tissue controls post-extinction levels of neuronal activity and spine enlargement in the regions sequentially remodelled during the formation of recent and remote fear memory. By preventing BLA and aCC neurons to retain neuronal features that serve to reactivate an extinguished fear memory, ECM digestion might offer a therapeutic strategy for durable attenuation of traumatic memories.

CoQ deficiency causes disruption of mitochondrial sulfide oxidation, a new pathomechanism associated with this syndrome.

PubMed

Luna-Sánchez, Marta; Hidalgo-Gutiérrez, Agustín; Hildebrandt, Tatjana M; Chaves-Serrano, Julio; Barriocanal-Casado, Eliana; Santos-Fandila, Ángela; Romero, Miguel; Sayed, Ramy Ka; Duarte, Juan; Prokisch, Holger; Schuelke, Markus; Distelmaier, Felix; Escames, Germaine; Acuña-Castroviejo, Darío; López, Luis C

2017-01-01

Coenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain, but it also has several other functions in the cellular metabolism. One of them is to function as an electron carrier in the reaction catalyzed by sulfide:quinone oxidoreductase (SQR), which catalyzes the first reaction in the hydrogen sulfide oxidation pathway. Therefore, SQR may be affected by CoQ deficiency. Using human skin fibroblasts and two mouse models with primary CoQ deficiency, we demonstrate that severe CoQ deficiency causes a reduction in SQR levels and activity, which leads to an alteration of mitochondrial sulfide metabolism. In cerebrum of Coq9 R239X mice, the deficit in SQR induces an increase in thiosulfate sulfurtransferase and sulfite oxidase, as well as modifications in the levels of thiols. As a result, biosynthetic pathways of glutamate, serotonin, and catecholamines were altered in the cerebrum, and the blood pressure was reduced. Therefore, this study reveals the reduction in SQR activity as one of the pathomechanisms associated with CoQ deficiency syndrome. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Hubble Space Telescope Ultraviolet Light Curves Reveal Interesting Properties of CC Sculptoris and RZ Leonis

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

Szkody, Paula; Mukadam, Anjum S.; Toloza, Odette

2017-03-01

Time-tag ultraviolet data obtained on the Hubble Space Telescope in 2013 reveal interesting variability related to the white dwarf spin in the two cataclysmic variables RZ Leo and CC Scl. RZ Leo shows a period at 220 s and its harmonic at 110 s, thus identifying it as a likely Intermediate Polar (IP). The spin signal is not visible in a short single night of ground-based data in 2016, but the shorter exposures in that data set indicate a possible partial eclipse. The much larger UV amplitude of the spin signal in the known IP CC Scl allows the spinmore » of 389 s, previously only seen at outburst, to be visible at quiescence. Spectra created from the peaks and troughs of the spin times indicate a hotter temperature of several thousand degrees during the peak phases, with multiple components contributing to the UV light.« less

Critical consciousness: current status and future directions.

PubMed

Watts, Roderick J; Diemer, Matthew A; Voight, Adam M

2011-01-01

In this chapter, the authors consider Paulo Freire's construct of critical consciousness (CC) and why it deserves more attention in research and discourse on youth political and civic development. His approach to education and similar ideas by other scholars of liberation aims to foster a critical analysis of society--and one's status within it--using egalitarian, empowering, and interactive methods. The aim is social change as well as learning, which makes these ideas especially relevant to the structural injustice faced by marginalized youth. From their review of these ideas, the authors derive three core CC components: critical reflection, political efficacy, and critical action. They highlight promising research related to these constructs and innovative applied work including youth action-research methodology. Their conclusion offers ideas for closing some of the critical gaps in CC theory and research. Copyright © 2011 Wiley Periodicals, Inc., A Wiley Company.

Effect of External Pressure Drop on Loop Heat Pipe Operating Temperature

NASA Technical Reports Server (NTRS)

Jentung, Ku; Ottenstein, Laura; Rogers, Paul; Cheung, Kwok; Obenschain, Arthur F. (Technical Monitor)

2002-01-01

This paper discusses the effect of the pressure drop on the operating temperature in a loop heat pipe (LHP). Because the evaporator and the compensation chamber (CC) both contain two-phase fluid, a thermodynamic constraint exists between the temperature difference and the pressure drop for these two components. As the pressure drop increases, so will the temperature difference. The temperature difference in turn causes an increase of the heat leak from the evaporator to the CC, resulting in a higher CC temperature. Furthermore, the heat leak strongly depends on the vapor void fraction inside the evaporator core. Tests were conducted by installing a valve on the vapor line so as to vary the pressure drop, and by charging the LHP with various amounts of fluid. Test results verify that the LHP operating temperature increases with an increasing differential pressure, and the temperature increase is a strong function of the fluid inventory in the loop.

Permeability-diffusivity modeling vs. fractional anisotropy on white matter integrity assessment and application in schizophrenia.

PubMed

Kochunov, P; Chiappelli, J; Hong, L E

2013-01-01

Diffusion tensor imaging (DTI) assumes a single pool of anisotropically diffusing water to calculate fractional anisotropy (FA) and is commonly used to ascertain white matter (WM) deficits in schizophrenia. At higher b-values, diffusion-signal decay becomes bi-exponential, suggesting the presence of two, unrestricted and restricted, water pools. Theoretical work suggests that semi-permeable cellular membrane rather than the presence of two physical compartments is the cause. The permeability-diffusivity (PD) parameters measured from bi-exponential modeling may offer advantages, over traditional DTI-FA, in identifying WM deficits in schizophrenia. Imaging was performed in N = 26/26 patients/controls (age = 20-61 years, average age = 40.5 ± 12.6). Imaging consisted of fifteen b-shells: b = 250-3800 s/mm(2) with 30 directions/shell, covering seven slices of mid-sagittal corpus callosum (CC) at 1.7 × 1.7 × 4.6 mm. 64-direction DTI was also collected. Permeability-diffusivity-index (PDI), the ratio of restricted to unrestricted apparent diffusion coefficients, and the fraction of unrestricted compartment (Mu) were calculated for CC and cingulate gray matter (GM). FA values for CC were calculated using tract-based-spatial-statistics. Patients had significantly reduced PDI in CC (p ≅ 10(- 4)) and cingulate GM (p = 0.002), while differences in CC FA were modest (p ≅ .03). There was no group-related difference in Mu. Additional theoretical-modeling analysis suggested that reduced PDI in patients may be caused by reduced cross-membrane water molecule exchanges. PDI measurements for cerebral WM and GM yielded more robust patient-control differences than DTI-FA. Theoretical work offers an explanation that patient-control PDI differences should implicate abnormal active membrane permeability. This would implicate abnormal activities in ion-channels that use water as substrate for ion exchange, in cerebral tissues of schizophrenia patients.

Biochemical characterization of Gram-positive and Gram-negative plant-associated bacteria with micro-Raman spectroscopy.

PubMed

Paret, Mathews L; Sharma, Shiv K; Green, Lisa M; Alvarez, Anne M

2010-04-01

Raman spectra of Gram-positive and Gram-negative plant bacteria have been measured with micro-Raman spectrometers equipped with 785 and 514.5 nm lasers. The Gram-positive bacteria Microbacterium testaceum, Paenibacillus validus, and Clavibacter michiganensis subsp. michiganensis have strong carotenoid bands in the regions 1155-1157 cm(-1) and 1516-1522 cm(-1) that differentiate them from other tested Gram-negative bacteria. In the Raman spectrum of Gram-positive bacteria Bacillus megaterium excited with 785 nm laser, the Raman bands at 1157 and 1521 cm(-1) are weak in intensity compared to other Gram-positive bacteria, and these bands did not show significant resonance Raman enhancement in the spectrum recorded with 514.5 nm laser excitation. The Gram-positive bacteria could be separated from each other based on the bands associated with the in-phase C=C (v(1)) vibrations of the polyene chain of carotenoids. None of the Gram-negative bacteria tested had carotenoid bands. The bacteria in the genus Xanthomonas have a carotenoid-like pigment, xanthomonadin, identified in Xanthomonas axonopodis pv. dieffenbachiae, and it is a unique Raman marker for the bacteria. The representative bands for xanthomonadin were the C-C stretching (v(2)) vibrations of the polyene chain at 1135-1136 cm(-1) and the in-phase C=C (v(1)) vibrations of the polyene chain at 1529-1531 cm(-1), which were distinct from the carotenoid bands of other tested bacteria. The tyrosine peak in the region 1170-1175 cm(-1) was the only other marker present in Gram-negative bacteria that was absent in all tested Gram-positives. A strong-intensity exopolysaccharide-associated marker at 1551 cm(-1) is a distinguishable feature of Enterobacter cloacae. The Gram-negative Agrobacterium rhizogenes and Ralstonia solanacearum were differentiated from each other and other tested bacteria on the basis of presence or absence and relative intensities of peaks. The principal components analysis (PCA) of the spectra excited with 785 nm laser differentiated the various strains of bacteria based on the unique pigments these bacteria do or do not possess. Raman spectroscopy of diverse plant bacteria that are pathogenic and non-pathogenic to plants, and isolated from plants and soil, indicates the possibilities of using the method in understanding plant-bacterial interactions at the cellular level.

Effectiveness of a Core-Competency-based Program on Residents' Learning and Experience.

PubMed

Charles, Lesley; Triscott, Jean; Dobbs, Bonnie; Tian, Peter George; Babenko, Oksana

2016-06-01

The Care of the Elderly (COE) Diploma Program is a six-to-twelve-month enhanced skills program taken after two years of core residency training in Family Medicine. In 2010, we developed and implemented a core-competency-based COE Diploma program (CC), in lieu of one based on learning objectives (LO). This study assessed the effectiveness of the core-competency-based program on residents' learning and their training experience as compared to residents trained using learning objectives. The data from the 2007-2013 COE residents were used in the study, with nine and eight residents trained in the LO and CC programs, respectively. Residents' learning was measured using preceptors' evaluations of residents' skills/abilities throughout the program (118 evaluations in total). Residents' rating of training experience was measured using the Graduate's Questionnaire which residents completed after graduation. For residents' learning, overall, there was no significant difference between the two programs. However, when examined as a function of the four CanMEDS roles, there were significant increases in the CC residents' scores for two of the CanMEDS roles: Communicator/Collaborator/Manager and Scholar compared to residents in the LO program. With respect to residents' training experience, seven out of ten program components were rated by the CC residents higher than by the LO residents. The implementation of a COE CC program appears to facilitate resident learning and training experience.

Effects of pretension on work and power output of the muscle-tendon complex in dynamic elbow flexion.

PubMed

Wakayama, Akinobu; Nagano, Akinori; Hay, Dean; Fukashiro, Senshi

2005-06-01

The purpose of the present study was to investigate the effects of pretension on work and power output of the muscle-tendon complex during dynamic elbow flexion under several submaximal and maximal conditions. The subjects were 10 healthy female students. Randomized trials from 0% to 100% maximal voluntary contraction (MVC) pretension (PT) at 60 degrees elbow flexion were conducted. After about 3 s of static PT, subjects maximally flexed the elbow joint to 90 degrees using a quick release method. The weight was individually selected for each subject to provide an optimal load for the development of maximal power. A Hill-type model was utilized to analyze the performance of the elbow muscle-tendon complex (MTC). PT 0, 30, 60 and 90% MVC data were used for comparison, and all data were expressed as the mean and standard deviation. Multiple paired comparisons between the value of PT 0% MVC and that of the other PT levels were performed post-hoc using Dunnett's method. The work of the series elastic component (SEC) increased gradually with the PT level because elastic energy was stored in the PT phase. However, the work of the contractile component (CC) decreased gradually with an increase in PT level. Moreover, the work of the MTC also decreased, closely related to the CC work decrement. The phenomenon of CC work decrement was caused by force depression and was not related to either the force-length or force-velocity relationships of the CC. EMG activity (agonist and antagonist) showed no significant differences. Muscle geometry changes or intracellular chemical shifts may have occurred in the PT phase.

Cross-correlation Doppler global velocimetry (CC-DGV)

NASA Astrophysics Data System (ADS)

Cadel, Daniel R.; Lowe, K. Todd

2015-08-01

A flow velocimetry method, cross-correlation Doppler global velocimetry (CC-DGV), is presented as a robust, simplified, and high dynamic range implementation of the Doppler global/planar Doppler velocimetry technique. A sweep of several gigahertz of the vapor absorption spectrum is used for each velocity sample, with signals acquired from both Doppler-shifted scattered light within the flow and a non-Doppler shifted reference beam. Cross-correlation of these signals yields the Doppler shift between them, averaged over the duration of the scan. With presently available equipment, velocities from 0 ms-1 to over 3000 ms-1 can notionally be measured simultaneously, making the technique ideal for high speed flows. The processing routine is shown to be robust against large changes in the vapor pressure of the iodine cell, benefiting performance of the system in facilities where ambient conditions cannot be easily regulated. Validation of the system was performed with measurements of a model wind turbine blade boundary layer made in a 1.83 m by 1.83 m subsonic wind tunnel for which laser Doppler velocimetry (LDV) measurements were acquired alongside the CC-DGV results. CC-DGV uncertainties of ±1.30 ms-1, ±0.64 ms-1, and ±1.11 ms-1 were determined for the orthogonal stream-wise, transverse-horizontal, and transverse-vertical velocity components, and root-mean-square deviations of 2.77 ms-1 and 1.34 ms-1 from the LDV validation results were observed for Reynolds numbers of 1.5 million and 2 million, respectively. Volumetric mean velocity measurements are also presented for a supersonic jet, with velocity uncertainties of ±4.48 ms-1, ±16.93 ms-1, and ±0.50 ms-1 for the orthogonal components, and self-validation done by collapsing the data with a physical scaling.

The Lawrence D. Dorr Surgical Techniques & Technologies Award: "Running Two Rooms" Does Not Compromise Outcomes or Patient Safety in Joint Arthroplasty.

PubMed

Hamilton, William G; Ho, Henry; Parks, Nancy L; Strait, Alexander V; Hopper, Robert H; McDonald, James F; Goyal, Nitin; Fricka, Kevin B; Engh, C Anderson

2018-07-01

Scrutiny from the federal government and the media regarding the safety of 1 surgeon doing cases in 2 operating rooms (ORs) on the same day, prompted us to examine our own institutional data. Over the past 11 years, surgeons at our facility have operated consecutively in 1 OR on a given day or used 2 alternating ORs. This study compares these cases with a focus on revisions and complications in both groups. Six surgeons performed a total of 16,916 primary hip and knee arthroplasties from 2006-2016. 7002 cases (41%) were consecutive cases (CCs) and 9914 cases (59%) were overlapping cases (OCs). Intraoperative complications, component revisions, and postoperative complications within 90 days of surgery were compared between the CC and OC groups. There was no difference in intraoperative complication rates between the two groups (CC 1.6% vs. OC 1.7%, relative risk 1.082, 95% confidence interval 0.852 to 1.375, P = .52). There was no difference in 90-day component revision rates among the CC and OC groups (0.66% vs. 0.85% respectively, relative risk = 1.290, 95% confidence interval 0.901 to 1.845, P = .19). There was also no difference in 90-day complication rates among the CC and OC groups (1.33% vs. 1.45% respectively, relative risk = 1.094, 95% confidence interval 0.844 to 1.417, P = .54). This large study of a single institution with multiple surgeons over an 11-year period shows no compromise in patient safety or outcomes when comparing cases done in either consecutive or overlapping rooms. Copyright © 2018 Elsevier Inc. All rights reserved.

Initial activation of STIM1, the regulator of store-operated calcium entry

PubMed Central

Zhou, Yubin; Srinivasan, Prasanna; Razavi, Shiva; Seymour, Sam; Meraner, Paul; Gudlur, Aparna; Stathopulos, Peter B; Ikura, Mitsuhiko; Rao, Anjana; Hogan, Patrick G

2013-01-01

Physiological Ca2+ signalling in T lymphocytes and other cells depends on the STIM-ORAI pathway of store-operated Ca2+ entry. STIM1 and STIM2 are Ca2+ sensors located in the endoplasmic reticulum (ER) membrane, with ER-luminal domains that monitor cellular Ca2+ stores and cytoplasmic domains that gate ORAI channels in the plasma membrane. The STIM ER-luminal domain dimerizes or oligomerizes upon dissociation of Ca2+, but the mechanism transmitting activation to the STIM cytoplasmic domain has not been defined. Here we demonstrate, using Tb3+–acceptor energy transfer, that dimerization of STIM1 ER-luminal domains can initiate an extensive conformational change in murine STIM1 cytoplasmic domains. The conformational change, triggered by apposition of the predicted coiled-coil 1 (CC1) regions, releases the ORAI-activating domains from their interaction with the CC1 regions and allows physical extension of the STIM1 cytoplasmic domain across the gap between ER and plasma membrane to communicate with ORAI channels. PMID:23851458

Carbon-Carbon Composite Radiator Development for the EO-1 Spacecraft

NASA Technical Reports Server (NTRS)

Vaughn, Wallace; Shinn, Elizabeth; Rawal, Suraj; Wright, Joe

2004-01-01

The Carbon-Carbon Space Radiator Partnership (CSRP), an informal partnership of Government and industrial personnel, was formed to promote the use of Carbon-carbon composites (C-C) as engineering materials for spacecraft thermal management applications . As a part of this effort the partnership has built a structural radiator for the Earth Orbiter - 1 (EO-1) spacecraft. This radiator, using C-C face-sheets with an aluminum honeycomb core, will demonstrate both the thermal and structural properties of C-C under actual service conditions as well as provide performance data from space flight. This paper will present results from the design of the radiator, the thermal/mechanical tests of the facesheet materials, and sub-component test results on the C-C/Al honeycomb sandwich material. The 29- by 28-inch radiator was designed to support two electronics boxes with a combined heat output of 60 watts maximum and a weight of 58 lbs. The analysis of the radiator design shows that the radiator constructed with 20-mil-thick facesheets of a P30-fiber-reinforced C-C from BFGoodrich is able to meet or exceed all the required thermal and mechanical requirements.

Atmospheric CO2 enrichment alters energy assimilation, investment and allocation in Xanthium strumarium.

PubMed

Nagel, Jennifer M; Wang, Xianzhong; Lewis, James D; Fung, Howard A; Tissue, David T; Griffin, Kevin L

2005-05-01

Energy-use efficiency and energy assimilation, investment and allocation patterns are likely to influence plant growth responses to increasing atmospheric CO2 concentration ([CO2]). Here, we describe the influence of elevated [CO2] on energetic properties as a mechanism of growth responses in Xanthium strumarium. Individuals of X. strumarium were grown at ambient or elevated [CO2] and harvested. Total biomass and energetic construction costs (CC) of leaves, stems, roots and fruits and percentage of total biomass and energy allocated to these components were determined. Photosynthetic energy-use efficiency (PEUE) was calculated as the ratio of total energy gained via photosynthetic activity (Atotal) to leaf CC. Elevated [CO2] increased leaf Atotal, but decreased CC per unit mass of leaves and roots. Consequently, X. strumarium individuals produced more leaf and root biomass at elevated [CO2] without increasing total energy investment in these structures (CCtotal). Whole-plant biomass was associated positively with PEUE. Whole-plant construction required 16.1% less energy than modeled whole-plant energy investment had CC not responded to increased [CO2]. As a physiological mechanism affecting growth, altered energetic properties could positively influence productivity of X. strumarium, and potentially other species, at elevated [CO2].

Massive close binaries with early-type components

NASA Astrophysics Data System (ADS)

Polushina, T. S.

A brief review of the study of massive close binaries system with the hot components carried out in Kourovka astronomical observatory is presented including such systems as CC Cas, SZ Cam, UU Cas, V368 Cas, BH Cen, SV Cen, LY Aur, V701 Sco. An attempt to explain the results of observations by the presence of circumstellar matter has been made. Some estimates of the circumstellar matter parameters are obtained.

Reducing Air Force Fighter Pilot Shortages

DTIC Science & Technology

2015-12-31

that active-component fighter pilot requirements (particularly nonflying staff requirements) exceed its capacity to train and provide initial...pilots in the reserve components. This research was sponsored by four elements of the U.S. Air Force: the Deputy Chief of Staff for Operations (AF/A3...the Deputy Chief of Staff for Manpower, Personnel and Services (AF/A1); the Commander, Air Force Reserve Command (AFRC/CC); and the Director, Air

Creating Age Asymmetry: Consequences of Inheriting Damaged Goods in Mammalian Cells.

PubMed

Moore, Darcie L; Jessberger, Sebastian

2017-01-01

Accumulating evidence suggests that mammalian cells asymmetrically segregate cellular components ranging from genomic DNA to organelles and damaged proteins during cell division. Asymmetric inheritance upon mammalian cell division may be specifically important to ensure cellular fitness and propagate cellular potency to individual progeny, for example in the context of somatic stem cell division. We review here recent advances in the field and discuss potential effects and underlying mechanisms that mediate asymmetric segregation of cellular components during mammalian cell division. Copyright © 2016 Elsevier Ltd. All rights reserved.

CC-Chemokine Ligand 2 (CCL2) Suppresses High Density Lipoprotein (HDL) Internalization and Cholesterol Efflux via CC-Chemokine Receptor 2 (CCR2) Induction and p42/44 Mitogen-activated Protein Kinase (MAPK) Activation in Human Endothelial Cells.

PubMed

Sun, Run-Lu; Huang, Can-Xia; Bao, Jin-Lan; Jiang, Jie-Yu; Zhang, Bo; Zhou, Shu-Xian; Cai, Wei-Bin; Wang, Hong; Wang, Jing-Feng; Zhang, Yu-Ling

2016-09-09

High density lipoprotein (HDL) has been proposed to be internalized and to promote reverse cholesterol transport in endothelial cells (ECs). However, the mechanism underlying these processes has not been studied. In this study, we aim to characterize HDL internalization and cholesterol efflux in ECs and regulatory mechanisms. We found mature HDL particles were reduced in patients with coronary artery disease (CAD), which was associated with an increase in CC-chemokine ligand 2 (CCL2). In cultured primary human coronary artery endothelial cells and human umbilical vein endothelial cells, we determined that CCL2 suppressed the binding (4 °C) and association (37 °C) of HDL to/with ECs and HDL cellular internalization. Furthermore, CCL2 inhibited [(3)H]cholesterol efflux to HDL/apoA1 in ECs. We further found that CCL2 induced CC-chemokine receptor 2 (CCR2) expression and siRNA-CCR2 reversed CCL2 suppression on HDL binding, association, internalization, and on cholesterol efflux in ECs. Moreover, CCL2 induced p42/44 mitogen-activated protein kinase (MAPK) phosphorylation via CCR2, and p42/44 MAPK inhibition reversed the suppression of CCL2 on HDL metabolism in ECs. Our study suggests that CCL2 was elevated in CAD patients. CCL2 suppressed HDL internalization and cholesterol efflux via CCR2 induction and p42/44 MAPK activation in ECs. CCL2 induction may contribute to impair HDL function and form atherosclerosis in CAD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Integrating Intracellular Dynamics Using CompuCell3D and Bionetsolver: Applications to Multiscale Modelling of Cancer Cell Growth and Invasion

PubMed Central

Andasari, Vivi; Roper, Ryan T.; Swat, Maciej H.; Chaplain, Mark A. J.

2012-01-01

In this paper we present a multiscale, individual-based simulation environment that integrates CompuCell3D for lattice-based modelling on the cellular level and Bionetsolver for intracellular modelling. CompuCell3D or CC3D provides an implementation of the lattice-based Cellular Potts Model or CPM (also known as the Glazier-Graner-Hogeweg or GGH model) and a Monte Carlo method based on the metropolis algorithm for system evolution. The integration of CC3D for cellular systems with Bionetsolver for subcellular systems enables us to develop a multiscale mathematical model and to study the evolution of cell behaviour due to the dynamics inside of the cells, capturing aspects of cell behaviour and interaction that is not possible using continuum approaches. We then apply this multiscale modelling technique to a model of cancer growth and invasion, based on a previously published model of Ramis-Conde et al. (2008) where individual cell behaviour is driven by a molecular network describing the dynamics of E-cadherin and -catenin. In this model, which we refer to as the centre-based model, an alternative individual-based modelling technique was used, namely, a lattice-free approach. In many respects, the GGH or CPM methodology and the approach of the centre-based model have the same overall goal, that is to mimic behaviours and interactions of biological cells. Although the mathematical foundations and computational implementations of the two approaches are very different, the results of the presented simulations are compatible with each other, suggesting that by using individual-based approaches we can formulate a natural way of describing complex multi-cell, multiscale models. The ability to easily reproduce results of one modelling approach using an alternative approach is also essential from a model cross-validation standpoint and also helps to identify any modelling artefacts specific to a given computational approach. PMID:22461894

Independent cellular effects of cold ischemia and reperfusion: experimental molecular study.

PubMed

Lledó-García, E; Humanes-Sánchez, B; Mojena-Sánchez, M; Rodrígez, J C J; Hernández-Fernández, C; Tejedor-Jorge, A; Fernández, A L

2013-04-01

There is less information available on cell cultures on the exclusive effects of either duration of cold ischemia (CI) or rewarming-reperfusion in the kidney subjected to initial warm ischemia (WI). Therefore, the goals of our work were: (1) to evaluate the consequences on tubular cellular viability of different durations of CI on a kidney after an initial period of WI, and (2) to analyze the additional effect on tubular cell viability of rewarming of the same kidney. Sixteen mini-pig were used. All the animals were performed a right nephrectomy after 45-minute occlusion of the vascular pedicle. The kidneys were then divided into 2 groups (phase 1): cold storage in university of wisconsin (UW) solution for 3 hours (group A, n = 8) at 4°C, or cold storage in UW for 12 hours (group B, n = 8) at 4°C. Four organs of group A and four organs of group B were autotrasplanted (AT) and reperfused for 1 hour (phase 2). Nephrectomy was finally done. Biopsies were taken from all groups to perform cultures of proximal tubule epithelium cells. The biopsies were subjected to studies of cellular morphological viability (contrast phase microscopy [CPM]) and quantitative (confluence cell [CC]) parameters. Phase of pure CI effects (phase 1): Both CC rate and CPM parameters were significantly lower in group B compared with group A, where cell activity reached almost normal results. Phase of CI + AT (phase 2): At produced additional harmful effects in cell cultures compared with those obtained in phase 1, more evident in group B cells. The presence of cold storage followed by rewarming-reperfusion induces independent and cumulative detrimental effects in viability of renal proximal tubule cells. CI periods ≤ 3 hours may ameliorate the injuries secondary to reperfusion in comparison with longer CI periods. Copyright © 2013 Elsevier Inc. All rights reserved.

Net shape fabrication of Alpha Silicon Carbide turbine components

NASA Technical Reports Server (NTRS)

Storm, R. S.

1982-01-01

Development of Alpha Silicon Carbide components by net shape fabrication techniques has continued in conjunction with several turbine engine programs. Progress in injection molding of simple parts has been extended to much larger components. Turbine rotors fabricated by a one piece molding have been successfully spin tested above design speeds. Static components weighing up to 4.5 kg and 33 cc in diameter have also been produced using this technique. Use of sintering fixtures significantly improves dimensional control. A new Si-SiC composite material has also been developed with average strengths up to 1000 MPa (150 ksi) at 1200 C.

Cardiac Stem Cell Hybrids Enhance Myocardial Repair

PubMed Central

Quijada, Pearl; Salunga, Hazel T.; Hariharan, Nirmala; Cubillo, Jonathan D.; El-Sayed, Farid G.; Moshref, Maryam; Bala, Kristin M.; Emathinger, Jacqueline M.; La Torre, Andrea De; Ormachea, Lucia; Alvarez, Roberto; Gude, Natalie A.; Sussman, Mark A.

2015-01-01

Rationale Dual cell transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction improves myocardial repair and performance in large animal models relative to delivery of either cell population. Objective To demonstrate that CardioChimeras (CCs) formed by fusion between CPCs and MSCs have enhanced reparative potential in a mouse model of myocardial infarction relative to individual stem cells or combined cell delivery. Methods and Results Two distinct and clonally derived CCs, CC1 and CC2 were utilized for this study. CCs improved left ventricular anterior wall thickness (AWT) at 4 weeks post injury, but only CC1 treatment preserved AWT at 18 weeks. Ejection fraction was enhanced at 6 weeks in CCs, and functional improvements were maintained in CCs and CPC + MSC groups at 18 weeks. Infarct size was decreased in CCs, whereas CPC + MSC and CPC parent groups remained unchanged at 12 weeks. CCs exhibited increased persistence, engraftment, and expression of early commitment markers within the border zone relative to combinatorial and individual cell population-injected groups. CCs increased capillary density and preserved cardiomyocyte size in the infarcted regions suggesting CCs role in protective paracrine secretion. Conclusions CCs merge the application of distinct cells into a single entity for cellular therapeutic intervention in the progression of heart failure. CCs are a novel cell therapy that improves upon combinatorial cell approaches to support myocardial regeneration. PMID:26228030

Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells.

PubMed

Mármol, Inés; Virumbrales-Muñoz, María; Quero, Javier; Sánchez-de-Diego, Cristina; Fernández, Luis; Ochoa, Ignacio; Cerrada, Elena; Yoldi, Mª Jesús Rodríguez

2017-11-01

Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NC 5 H 4 )(PTA)] whose anticancer effect was tested on the colorectal adenocarcinoma Caco-2 cell line. With regard to its mechanism of action, this gold complex enters the mitochondria and disrupts its normal function, leading to an increase in ROS production, which triggers necroptosis. Necroptosis induction has been found dependent of TNF-α (Tumor necrosisfactor α) and TNFR1(Tumor necrosisfactor receptor 1) binding, RIP1(Receptor-Interacting Protein 1) activation and NF-κB (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells) signaling. Moreover, the antitumor potential of [Au(CC-2-NC 5 H 4 )(PTA)] has also been confirmed on the 3D cancer model spheroid. Overall, the obtained data show firstly that gold complexes might have the ability of inducing necroptosis, and secondarily that our compound [Au(CC-2-NC 5 H 4 )(PTA)] is an interesting alternative to current chemotherapy drugs in cases of apoptosis resistance. Copyright © 2017. Published by Elsevier Inc.

Immunohistochemical expression of apoptosis-related biomarkers in normal tissues of camel (Camelus dromedarius): A survey in a desert-dwelling mammalian model.

PubMed

Osman, Abdel-Hamid K; Caceci, Thomas; Shintani, Mitchiko

2018-05-01

Programmed cell death is a fundamental event that takes place during organ development and plays an important role in cellular homeostasis. Since various body organs of the camel are under high ecological and physiological stress during food and water deprivation, desiccation, and the long exposure to solar radiation in these desert nomads, we aimed to examine the immunohistochemical expression of apoptosis-related biomarkers in some of its normal body organs to illustrate a basic track for further pathological investigation. Regarding apoptosis, the present study has revealed that the higher expression of cleaved caspase-9 (CC9) [initiator of the intrinsic pathway] and CC3 (effector caspase), and the scanty expression of CC8 (initiator of the extrinsic pathway), highlight the role of the caspase-dependent, intrinsic apoptotic pathway particularly in the intestines and lymphoid organs. The apoptosis- inducing factor (AIF)-immunoexpression was completely missing in the cell nuclei of the examined tissues, indicating the absence of the caspase-independent pathway. The nuclear overexpression of the phospho-histone H2AX (γ H2AX) and the occasional expression of single-stranded DNA, particularly among the CNS neurons, suggest an efficient, protective DNA-repair mechanism in such cells. Thus, despite efficient anti-apoptotic mechanisms intrinsic apoptotic pathways exists in brain, intestine and lymph organs of adult desert camels. Copyright © 2018 Elsevier GmbH. All rights reserved.

Effect of a cocoa-enriched diet on immune response and anaphylaxis in a food allergy model in Brown Norway rats.

PubMed

Abril-Gil, Mar; Pérez-Cano, Francisco J; Franch, Àngels; Castell, Margarida

2016-01-01

Previous studies have demonstrated that cocoa intake decreased Th2 immune-related antibodies in rats. In consequence, we aimed to study in depth this cocoa action, particularly assessing its effect on a rat model of food allergy (FA) and also on an anaphylactic response. The involvement of the intestinal immune system was analyzed to allow the action mechanisms to be investigated. The role of cocoa flavonoids in the antiallergic properties of cocoa was also established. Brown Norway rats were fed either a reference diet or diets containing conventional cocoa (CC) or nonfermented cocoa (NFC). FA to ovalbumin (OVA) was induced and, later, an anaphylactic response was provoked. As expected, the synthesis of anti-OVA IgE and other Th2-related antibodies was inhibited by CC diet. In addition, the release of mast cell protease II after anaphylaxis was partially prevented by CC, although other variables were not modified. The CC diet also attenuated the increase of some Th2-related cytokines released from mesenteric lymph node and spleen cells, and modulated the intestinal gene expression of molecules involved in allergic response. These results demonstrated the local and systemic influence of CC diet. The effects of the NFC diet were weaker than those of CC, suggesting that cocoa components other than flavonoids play a role in cocoa's action. In conclusion, by acting on intestinal and systemic immune functions, a cocoa-enriched diet in rats exhibited a protective effect against FA and partially against anaphylaxis, making this a food of high interest to the fields of health and immunonutrition. Copyright © 2015 Elsevier Inc. All rights reserved.

The MNS glycophorin variant GP.Mur affects differential erythroid expression of Rh/RhAG transcripts.

PubMed

Hsu, K; Kuo, M-S; Yao, C-C; Cheng, H-C; Lin, H-J; Chan, Y-S; Lin, M

2017-10-01

The band 3 macrocomplex (also known as the ankyrin-associated complex) on the red cell membrane comprises two interacting subcomplexes: a band 3/glycophorin A subcomplex, and a Rh/RhAG subcomplex. Glycophorin B (GPB) is a component of the Rh/RhAG subcomplex that is also structurally associated with glycophorin A (GPA). Expression of glycophorin B-A-B hybrid GP.Mur enhances band 3 expression and is associated with lower levels of Rh-associated glycoprotein (RhAG) and Rh polypeptides. The goal of this study was to determine whether GP.Mur influenced erythroid Rh/RhAG expression at the transcript level. GP.Mur was serologically determined in healthy participants from Taitung County, Taiwan. RNA was extracted from the reticulocyte-enriched fraction of peripheral blood, followed by reverse transcription and quantitative PCR for RhAG, RhD and RhCcEe. Quantification by real-time PCR revealed significantly fewer RhAG and RhCcEe transcripts in the reticulocytes from subjects with homozygous GYP*Mur. Independent from GYP.Mur, both RhAG and RhD transcript levels were threefold or higher than that of RhCcEe. Also, in GYP.Mur and the control samples alike, direct quantitative associations were observed between the transcript levels of RhAG and RhD, but not between that of RhAG and RhCcEe. Erythroid RhD and RhCcEe were differentially expressed at the transcript levels, which could be related to their different degrees of interaction or sensitivity to RhAG. Further, the reduction or absence of glycophorin B in GYP.Mur erythroid cells affected transcript expressions of RhAG and RhCcEe. Thus, GPB and GP.Mur differentially influenced Rh/RhAG expressions prior to protein translation. © 2017 International Society of Blood Transfusion.

Different cellular effects of four anti-inflammatory eye drops on human corneal epithelial cells: independent in active components.

PubMed

Qu, Mingli; Wang, Yao; Yang, Lingling; Zhou, Qingjun

2011-01-01

To evaluate and compare the cellular effects of four commercially available anti-inflammatory eye drops and their active components on human corneal epithelial cells (HCECs) in vitro. The cellular effects of four eye drops (Bromfenac Sodium Hydrate Eye Drops, Pranoprofen Eye Drops, Diclofenac Sodium Eye Drops, and Tobramycin & Dex Eye Drops) and their corresponding active components were evaluated in an HCEC line with five in vitro assays. Cell proliferation and migration were measured using 3-(4,5)-dimethylthiahiazo (-z-y1)-3 5-di-phenytetrazoliumromide (MTT) assay and transwell migration assay. Cell damage was determined with the lactate dehydrogenase (LDH) assay. Cell viability and median lethal time (LT₅₀) were measured by 7-amino-actinomycin D (7-AAD) staining and flow cytometry analysis. Cellular effects after exposure of HCECs to the four anti-inflammatory eye drops were concentration dependent. The differences of cellular toxicity on cell proliferation became significant at lower concentrations (<0.002%). Diclofenac Sodium Eye Drops showed significant increasing effects on cell damage and viability when compared with the other three solutions. Tobramycin & Dex Eye Drops inhibited the migration of HCECs significantly. Tobramycin & Dex Eye Drops showed the quickest effect on cell viability: the LT₅₀ was 3.28, 9.23, 10.38, and 23.80 min for Tobramycin & Dex Eye Drops, Diclofenac Sodium Eye Drops, Pranoprofen Eye Drops, and Bromfenac Sodium Hydrate Eye Drops, respectively. However, the comparisons of cellular toxicity revealed significant differences between the eye drops and their active components under the same concentration. The corneal epithelial toxicity differences among the active components of the four eye drops became significant as higher concentration (>0.020%). The four anti-inflammatory eye drops showed different cellular effects on HCECs, and the toxicity was not related with their active components, which provides new reference for the clinical application and drug research and development.

Unexpected formation of (E)-4-alkene 1,3-diketones from the three-component reaction of lithium selenolates with 1-(1-alkynyl)cyclopropyl ketones and aldehydes.

PubMed

Xu, Jianfeng; Wu, Luling; Huang, Xian

2011-07-15

A novel three-component stereoselective synthesis of (E)-4-alkene 1,3-diketones from lithium selenolates, 1-(1-alkynyl)cyclopropyl ketones, and aldehydes is reported. This reaction afforded the products in moderate to good yields with the formation of a new C-Se single bond, a new C-C double bond, and a new C-O double bond.

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

Ramos-Solano, Moisés, E-mail: mrsolano84@gmail.com; Programa de Doctorado en Ciencias Biomédica, Centro Universitario de Ciencias de la Salud; Meza-Canales, Ivan D., E-mail: imezacanales@ice.mpg.de

According to the multifactorial model of cervical cancer (CC) causation, it is now recognized that other modifications, in addition to Human papillomavirus (HPV) infection, are necessary for the development of this neoplasia. Among these, it has been proposed that a dysregulation of the WNT pathway might favor malignant progression of HPV-immortalized keratinocytes. The aim of this study was to identify components of the WNT pathway differentially expressed in CC vs. non-tumorigenic, but immortalized human keratinocytes. Interestingly, WNT7A expression was found strongly downregulated in cell lines and biopsies derived from CC. Restoration of WNT7A in CC-derived cell lines using a lentiviralmore » gene delivery system or after adding a recombinant human protein decreases cell proliferation. Likewise, WNT7A silencing in non-tumorigenic cells markedly accelerates proliferation. Decreased WNT7A expression was due to hypermethylation at particular CpG sites. To our knowledge, this is the first study reporting reduced WNT7A levels in CC-derived cells and that ectopic WNT7A restoration negatively affects cell proliferation and migration. - Highlights: • WNT7A is expressed in normal keratinocytes or cervical cells without lesion. • WNT7A is significantly reduced in cervical cancer-derived cells. • Restoration of WNT7A expression in HeLa decreases proliferation and cell migration. • Silencing of WNT7A in HaCaT induces an increased proliferation and migration rate. • Decreased WNT7A expression in this model is due to hypermethylation.« less

Inhibition deficit in the spatial tendency of the response in multiple-domain amnestic mild cognitive impairment. An event-related potential study

PubMed Central

Cespón, Jesús; Galdo-Álvarez, Santiago; Díaz, Fernando

2015-01-01

Longitudinal studies have shown that a high percentage of people with amnestic mild cognitive impairment (MCI) develop Alzheimer’s disease (AD). Prodromal AD is known to involve deficits in executive control processes. In the present study, we examined such deficits by recording EEG in 13 single-domain amnestic MCI (sdaMCI), 12 multiple-domain amnestic MCI (mdaMCI) and 18 healthy elderly (control group, CG) participants while they performed a Simon task. The Simon task demands deployment of executive processes because participants have to respond to non-spatial features of a lateralized stimulus and inhibit the more automatic spatial tendency of the response. We specifically focused on the negativity central contralateral (N2cc), an event-related potential (ERP) component related to brain activity that prevents the cross-talk between direction of spatial attention and manual response preparation. The reaction time (RT) was not significantly different among the three groups of participants. The percentage of errors (PE) was higher in mdaMCI than in CG and sdaMCI participants. In addition, N2cc latency was delayed in mdaMCI (i.e., delayed implementation of mechanisms for controlling the spatial tendency of the response). The N2cc latency clearly distinguished among mdaMCI and CG/sdaMCI participants (area under curve: 0.91). Longer N2cc was therefore associated with executive control deficits, which suggests that N2cc latency is a correlate of mdaMCI. PMID:25999853

NiFe-Layered Double Hydroxide Nanosheet Arrays Supported on Carbon Cloth for Highly Sensitive Detection of Nitrite.

PubMed

Ma, Yue; Wang, Yongchuang; Xie, Donghua; Gu, Yue; Zhang, Haimin; Wang, Guozhong; Zhang, Yunxia; Zhao, Huijun; Wong, Po Keung

2018-02-21

Excessive uptake of nitrite has been proven to be detrimental to the ecological system and human health. Hence, there is a rising requirement for constructing effective electrochemical sensors to precisely monitor the level of nitrite. In this work, NiFe-layered double hydroxide nanosheet arrays (NiFe-LDH NSAs) have been successfully fabricated on a carbon cloth (CC) substrate via a facile one-pot hydrothermal route. By integrating the collective merits of macroporous CC and NiFe-LDH NSAs such as superior electrical conductivity, striking synergistic effect between the dual active components, enlarged electrochemically active surface area, unique three-dimensional hierarchical porous network characteristics, and fast charge transport and ion diffusion, the proposed NiFe-LDH NSAs/CC architecture can be served as a self-supporting sensor toward nitrite detection. As a consequence, the resulting NiFe-LDH NSAs/CC electrode demonstrates superior nitrite sensing characteristics, accompanied by broad linear range (5-1000 μM), quick response rate (ca. 3 s), ultralow detection limit (0.02 μM), and high sensitivity (803.6 μA·mM -1 ·cm -2 ). Meanwhile, the electrochemical sensor possesses timeless stability, good reproducibility, and strong anti-interference feature. Importantly, the resulting sensor can determine nitrite level in tap and lake water with high recoveries, suggesting its feasibility for practical applications. These findings show that the obtained NiFe-LDH NSAs/CC electrode holds great prospect in highly sensitive and specific detection of nitrite.

Effectiveness of a Core-Competency–based Program on Residents’ Learning and Experience

PubMed Central

Charles, Lesley; Triscott, Jean; Dobbs, Bonnie; Tian, Peter George; Babenko, Oksana

2016-01-01

Background The Care of the Elderly (COE) Diploma Program is a six-to-twelve-month enhanced skills program taken after two years of core residency training in Family Medicine. In 2010, we developed and implemented a core-competency–based COE Diploma program (CC), in lieu of one based on learning objectives (LO). This study assessed the effectiveness of the core-competency–based program on residents’ learning and their training experience as compared to residents trained using learning objectives. Methods The data from the 2007–2013 COE residents were used in the study, with nine and eight residents trained in the LO and CC programs, respectively. Residents’ learning was measured using preceptors’ evaluations of residents’ skills/abilities throughout the program (118 evaluations in total). Residents’ rating of training experience was measured using the Graduate’s Questionnaire which residents completed after graduation. Results For residents’ learning, overall, there was no significant difference between the two programs. However, when examined as a function of the four CanMEDS roles, there were significant increases in the CC residents’ scores for two of the CanMEDS roles: Communicator/Collaborator/Manager and Scholar compared to residents in the LO program. With respect to residents’ training experience, seven out of ten program components were rated by the CC residents higher than by the LO residents. Conclusion The implementation of a COE CC program appears to facilitate resident learning and training experience. PMID:27403213

Cross-Talk Limits of Highly Segmented Semiconductor Detectors

NASA Astrophysics Data System (ADS)

Pullia, Alberto; Weisshaar, Dirk; Zocca, Francesca; Bazzacco, Dino

2011-06-01

Cross-talk limits of monolithic highly-segmented semiconductor detectors for high-resolution X-gamma spectrometry are investigated. Cross-talk causes false signal components yielding amplitude losses and fold-dependent shifts of the spectral lines, which partially spoil the spectroscopic performance of the detector. Two complementary electrical models are developed, which describe quantitatively the inter-channel cross-talk of monolithic segmented detectors whose electrodes are read out by charge-sensitive preamplifiers. The first is here designated as Cross-Capacitance (CC) model, the second as Split-Charge (SC) model. The CC model builds around the parasitic capacitances Cij linking the preamplifier outputs and the neighbor channel inputs. The SC model builds around the finite-value of the decoupling capacitance CC used to read out the high-voltage detector electrode. The key parameters of the models are individuated and ideas are shown to minimize their impact. Using a quasi-coaxial germanium segmented detector it is found that the SC cross-talk becomes negligible for decoupling capacitances larger than 1 nF, where instead the CC cross-talk tends to dominate. The residual cross-talk may be reduced by minimization of stray capacitances Cij, through a careful design of the layout of the Printed Circuit Board (PCB) where the input transistors are mounted. Cij can be made as low as 5 fF, but it is shown that even in such case the impact of the CC cross-talk on the detector performance is not negligible. Finally, an algorithm for cross-talk correction is presented and elaborated.

Cellular angiofibroma with atypia or sarcomatous transformation: clinicopathologic analysis of 13 cases.

PubMed

Chen, Eleanor; Fletcher, Christopher D M

2010-05-01

Cellular angiofibroma is a mesenchymal neoplasm that is characterized by a bland spindle cell component, morphologically reminiscent of spindle cell lipoma, and thick-walled vessels. The tumor occurs equally in men and women and usually arises in the inguino-scrotal or vulvovaginal regions. An earlier study of 51 cases from our group showed that the tumor follows a benign course without any tendency for recurrence. In 1 case, an intralesional microscopic nodule of pleomorphic liposarcoma was observed. The biologic significance of atypia or sarcomatous transformation in cellular angiofibroma remains uncertain. In this study, we characterized clinicopathologic features in 13 cases of cellular angiofibroma with morphologic atypia or sarcomatous transformation. Thirteen cases with atypia or sarcomatous transformation among 154 usual cellular angiofibromas identified between 1993 and 2009 were retrieved from consultation files. There were 12 females and 1 male ranging in age from 39 to 71 years (median age, 46 y). Tumor size ranged from 1.2 to 7.5 cm. In 11 cases, the tumors occurred in the vulva. One case each occurred in the paratesticular and hip regions. Most tumors were located in subcutaneous tissue. There were 4 cases of cellular angiofibroma with atypia. Three showed severely atypical cells as scattered foci within the cellular angiofibroma. One case showed a discrete nodule of atypical cells. There were 9 cases of cellular angiofibroma with morphologic features of sarcomatous transformation. In each case, abrupt transition to a discrete sarcomatous component was seen. Of these 9 cases, the sarcomatous component in 2 cases showed features of pleomorphic liposarcoma with multivacuolated lipoblasts readily identified. Three of these 9 cases showed discrete nodule(s) closely resembling atypical lipomatous tumor within usual cellular angiofibroma. In the remaining 4 cases, the sarcomatous component was composed of pleomorphic spindle cells arranged in various patterns. By immunohistochemistry, atypical cells and sarcomatous areas showed either multifocal or more diffuse p16 expression compared with either scattered or negative expression in the conventional cellular angiofibroma. The 3 cases with atypical lipomatous tumor-like areas were negative for MDM-2 and CDK4. Follow-up information was available for 7 patients (range from 2 to 75 mo; median: 14 mo). Six patients did not develop recurrence or metastasis. One patient died of metastatic carcinoma of unknown primary site 27 months after the diagnosis of cellular angiofibroma with sarcomatous transformation. Cellular angiofibroma with atypia or morphologic sarcomatous transformation occurs predominantly in the subcutaneous tissue of the vulva and, as yet, shows no evident tendency to recur based on limited clinical follow-up available for 7 cases. The sarcomatous component can show variable features including atypical lipomatous tumor, pleomorphic liposarcoma, and pleomorphic sarcoma NOS. Overexpression of p16 in the atypical cells and sarcomatous component suggests a possible underlying molecular mechanism.

Responses of the Housefly, Musca domestica, to the Hytrosavirus Replication: Impacts on Host's Vitellogenesis and Immunity

PubMed Central

Kariithi, Henry M.; Yao, Xu; Yu, Fahong; Teal, Peter E.; Verhoeven, Chelsea P.; Boucias, Drion G.

2017-01-01

Hytrosaviridae family members replicate in the salivary glands (SGs) of their adult dipteran hosts and are transmitted to uninfected hosts via saliva during feeding. Despite inducing similar gross symptoms (SG hypertrophy; SGH), hytrosaviruses (SGHVs) have distinct pathobiologies, including sex-ratio distortions in tsetse flies and refusal of infected housefly females to copulate. Via unknown mechanism(s), SGHV replication in other tissues results in reduced fecundity in tsetse flies and total shutdown of vitellogenesis and sterility in housefly females. We hypothesized that vitellogenesis shutdown was caused by virus-induced modulation of hormonal titers. Here, we used RNA-Seq to investigate virus-induced modulation of host genes/pathways in healthy and virus-infected houseflies, and we validated expression of modulated genes (n = 23) by RT-qPCR. We also evaluated the levels and activities of hemolymph AMPs, levels of endogenous sesquiterpenoids, and impacts of exogenous hormones on ovarian development in viremic females. Of the 973 housefly unigenes that were significantly modulated (padj ≤ 0.01, log2FC ≤ −2.0 or ≥ 2.0), 446 and 527 genes were downregulated and upregulated, respectively. While the most downregulated genes were related to reproduction (embryogenesis/oogenesis), the repertoire of upregulated genes was overrepresented by genes related to non-self recognition, ubiquitin-protease system, cytoskeletal traffic, cellular proliferation, development and movement, and snRNA processing. Overall, the virus, Musca domestica salivary gland hytrosavirus (MdSGHV), induced the upregulation of various components of the siRNA, innate antimicrobial immune, and autophagy pathways. We show that MdSGHV undergo limited morphogenesis in the corpora allata/corpora cardiaca (CA/CC) complex of M. domestica. MdSGHV replication in CA/CC potentially explains the significant reduction of hemolymph sesquiterpenoids levels, the refusal to mate, and the complete shutdown of egg development in viremic females. Notably, hormonal rescue of vitellogenesis did not result in egg production. The mechanism underlying MdSGHV-induced sterility has yet to be resolved. PMID:28424677

Herpes Simplex Virus Selectively Induces Expression of the CC Chemokine RANTES/CCL5 in Macrophages through a Mechanism Dependent on PKR and ICP0

PubMed Central

Melchjorsen, Jesper; Pedersen, Finn S.; Mogensen, Søren C.; Paludan, Søren R.

2002-01-01

Recruitment of leukocytes is essential for eventual control of virus infections. Macrophages represent a leukocyte population involved in the first line of defense against many infections, including herpes simplex virus (HSV) infection. Through presentation of antigens to T cells and production of cytokines and chemokines, macrophages also constitute an important link between the innate and adaptive immune systems. Here, we have investigated the chemokine expression profile of macrophages after HSV infection and the virus-cell interactions involved. By reverse transcription-PCR and cDNA arrays, we found that HSV type 1 (HSV-1) and HSV-2 induced expression of the CC chemokine RANTES/CCL5 in murine macrophage cell lines and peritoneal cells. The CXC chemokine BCA-1/CXCL13 was also induced in peritoneal cells. Twenty-six other chemokines tested were not affected. Accumulation of RANTES mRNA was detectable after 5 h of infection, was sensitive to UV irradiation of the virus, and was preceded by accumulation of viral immediate-early mRNA and proteins. The viral components responsible for initiation of RANTES expression were examined with virus mutants and RAW 264.7 macrophage-like cells expressing a dominant negative mutant of the double-stranded-RNA-activated protein kinase (PKR). The PKR mutant cell line displayed reduced constitutive and HSV-inducible RANTES expression compared to the control cell line. HSV-1 mutants deficient in genes encoding the immediate-early proteins ICP4, ICP22, and ICP27 remained fully capable of inducing RANTES expression in macrophages. By contrast, the ability of an ICP0-deficient HSV-1 mutant to induce RANTES expression was compromised. Thus, HSV selectively induces expression of RANTES in macrophages through a mechanism dependent on cellular PKR and viral ICP0. PMID:11861845

Cellular Entry of Clostridium perfringens Iota-Toxin and Clostridium botulinum C2 Toxin

PubMed Central

Takehara, Masaya; Takagishi, Teruhisa; Seike, Soshi; Oda, Masataka; Sakaguchi, Yoshihiko; Hisatsune, Junzo; Ochi, Sadayuki; Kobayashi, Keiko; Nagahama, Masahiro

2017-01-01

Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins. PMID:28800062

Cellular Entry of Clostridium perfringens Iota-Toxin and Clostridium botulinum C2 Toxin.

PubMed

Takehara, Masaya; Takagishi, Teruhisa; Seike, Soshi; Oda, Masataka; Sakaguchi, Yoshihiko; Hisatsune, Junzo; Ochi, Sadayuki; Kobayashi, Keiko; Nagahama, Masahiro

2017-08-11

Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin are composed of two non-linked proteins, one being the enzymatic component and the other being the binding/translocation component. These latter components recognize specific receptors and oligomerize in plasma membrane lipid-rafts, mediating the uptake of the enzymatic component into the cytosol. Enzymatic components induce actin cytoskeleton disorganization through the ADP-ribosylation of actin and are responsible for cell rounding and death. This review focuses upon the recent advances in cellular internalization of clostridial binary toxins.

Composition and chemical variability of Corsican Pinus halepensis cone oil.

PubMed

Nam, Anne-Marie; Casanova, Joseph; Tomi, Félix; Bighelli, Ange

2014-09-01

The composition of the essential oil isolated from cones of Pinus halepensis grown in Corsica has been investigated by a combination of chromatographic (CC, GC) and spectroscopic (MS, 13C NMR) techniques. In total, 48 compounds that accounted for 95.5% of the whole composition have been identified. α-Pinene (47.5%) was the major component followed by myrcene (11.0%), (E)-β-caryophyllene (8.3%) and caryophyllene oxide (5.9%). Various diterpenes have been identified by 13C NMR in the fractions of CC. Fifteen oil samples isolated from cones harvested in three forests have been analyzed and two groups of similar importance have been differentiated within the 15 compositions. Oil samples of the first group contained α-pinene (mean 45.0 g/100 g, SD = 5.5) as the major component. The composition of samples of the second group was dominated by myrcene (mean 30.3 g/100g, SD = 9.0) and α-pinene (mean 24.6 g/100 g, SD = 3.1).

Photometric and Spectroscopic Study of the Delta Scuti Stars FH Cam, CU CVn and CC Lyn

NASA Astrophysics Data System (ADS)

Conidis, G. J.; Gazeas, K. D.; Capobianco, C. C.; Ogloza, W.

2010-06-01

Three short period (P ˜ 1 day) variable stars from the Hipparcos catalogue targets were observed after suspected misclassification as Beta Lyr eclipsing systems (Perryman et al. 1997), as no secondary component had been noticed in the inspection of their Broadening Functions (BFs) (Rucinski 2002). FH Cam is found to be a multiple star system with a member exhibiting Delta Scuti behaviour. The dominant pulsation frequency is found to be 7.3411 ± 0.0002 c/d, which corresponds to a pulsation mode of l ≤ 1. We confirmed the pulsations of CU CVn using photometric observations and found a pulsation frequency of 14.7626 ± 0.0250 c/d, which is in agreement with the period given in literature. CC Lyn is a non-eclipsing visual binary (CCDM J07359+4302AB), the brighter component (A) is found to be a multi-mode Delta Scuti pulsator, with pulsation frequencies of 5.6402 ± 0.0004 c/d and 7.3368 ± 0.0005 c/d.

Equation-of-motion coupled cluster method for the description of the high spin excited states

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

Musiał, Monika, E-mail: musial@ich.us.edu.pl; Lupa, Łukasz; Kucharski, Stanisław A.

2016-04-21

The equation-of-motion (EOM) coupled cluster (CC) approach in the version applicable for the excitation energy (EE) calculations has been formulated for high spin components. The EE-EOM-CC scheme based on the restricted Hartree-Fock reference and standard amplitude equations as used in the Davidson diagonalization procedure yields the singlet states. The triplet and higher spin components require separate amplitude equations. In the case of quintets, the relevant equations are much simpler and easier to solve. Out of 26 diagrammatic terms contributing to the R{sub 1} and R{sub 2} singlet equations in the case of quintets, only R{sub 2} operator survives with 5more » diagrammatic terms present. In addition all terms engaging three body elements of the similarity transformed Hamiltonian disappear. This indicates a substantial simplification of the theory. The implemented method has been applied to the pilot study of the excited states of the C{sub 2} molecule and quintet states of C and Si atoms.« less

Isolation and characterization of an anti-leishmanial disintegrin from Cerastes cerastes venom.

PubMed

Allane, Dihia; Oussedik-Oumehdi, Habiba; Harrat, Zoubir; Seve, Michel; Laraba-Djebari, Fatima

2018-02-01

Investigating new antimicrobial and antiparasitic components from Viperidae venoms represents an alternative therapeutic strategy. In this study, we report the characterization of a disintegrin isolated from Cerastes cerastes venom, exhibiting antiparasitic activity on Leishmania infantum promastigotes. Indeed, isolated disintegrin, referred to Disintegrin_Cc, induced 84.75% of parasiticidal activity and deep morphological alterations on the parasites. SDS-PAGE analysis indicated that this disintegrin was homogenous. This dimeric disintegrin of 14,193.97 Da contains an RGD domain and four intramolecular disulfide bridges. It presents a high percentage of identity with other related snake disintegrins. Predicted 3D structure indicated that this peptide shares partial homology with well-known active antimicrobial peptides. Disintegrin_Cc inhibited 80% of arachidonic acid-induced platelet aggregation. The obtained results suggest that the isolated molecule plays a dual role as a disintegrin and as an anti-leishmanial compound. This component could be useful as a drug in the treatment of leishmaniasis. © 2017 Wiley Periodicals, Inc.

Deep learning for computational biology.

PubMed

Angermueller, Christof; Pärnamaa, Tanel; Parts, Leopold; Stegle, Oliver

2016-07-29

Technological advances in genomics and imaging have led to an explosion of molecular and cellular profiling data from large numbers of samples. This rapid increase in biological data dimension and acquisition rate is challenging conventional analysis strategies. Modern machine learning methods, such as deep learning, promise to leverage very large data sets for finding hidden structure within them, and for making accurate predictions. In this review, we discuss applications of this new breed of analysis approaches in regulatory genomics and cellular imaging. We provide background of what deep learning is, and the settings in which it can be successfully applied to derive biological insights. In addition to presenting specific applications and providing tips for practical use, we also highlight possible pitfalls and limitations to guide computational biologists when and how to make the most use of this new technology. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Sub-inhibitory concentrations of oxacillin modify the expression of agr locus in Staphylococcus aureus clinical strains belonging to different clonal complexes.

PubMed

Viedma, Esther; Pérez-Montarelo, Dafne; Villa, Jennifer; Muñoz-Gallego, Irene; Larrosa, Nieves; Fernández-Hidalgo, Nuria; Gavaldà, Joan; Almirante, Benito; Chaves, Fernando

2018-04-16

The ability of Staphylococcus aureus to invade tissues and cause an infectious disease is the result of a multi-factorial process supported by the huge number of virulence factors inherent to this microorganism tightly regulated by the accessory gene regulator (agr). During antimicrobial therapy bacteria may be exposed to sub-inhibitory concentrations (subMICs) of antibiotics that may trigger transcriptional changes that may have an impact on the pathogenesis of infection. The objective of this study was to investigate the effect of oxacillin sub-MICs on agr system expression as the key component in the regulation of virulence in methicillin-susceptible (MSSA) and -resistant S. aureus (MRSA) strains. Furthermore, we studied the genetic basis of the agr locus and their potential association with the expression levels. We have examined the expression of RNAIII and agrA mRNA as biomarkers for agr expression in the presence and absence of oxacillin subMICs in 10 MSSA and 4 MRSA clinical strains belonging to 5 clonal complexes (CC45-agrI, CC8-agrI, CC5-agrII, CC15-agrII and CC30-agrIII) causing endovascular complications. The DNA sequences of agr locus were obtained by whole genome sequencing. Our results revealed that exposure to subMICs of oxacillin had an impact on agr locus expression modifying the relative levels of expression with increases in 11 strains and with decreases in 3 strains. Thereby, the exposure to subMICs of oxacillin resulted in higher levels of expression of agr in CC15 and CC45 and lower levels in CC30. We also observed the presence of mutations in agrC and agrA in 13/14 strains with similar mutation profiles among strains within individual CCs except for strains of CC5. Although, agr expression levels differed among strains within CCs, the presence of these mutations was associated with differences in agr expression levels in most cases. Changes in agr expression induced by exposure to oxacillin subMICs should be considered because they could lead to changes in the virulence modulation and have an adverse effect on the course of infection, especially in certain clonal complexes.

[Cell signaling pathways interaction in cellular proliferation: Potential target for therapeutic interventionism].

PubMed

Valdespino-Gómez, Víctor Manuel; Valdespino-Castillo, Patricia Margarita; Valdespino-Castillo, Víctor Edmundo

2015-01-01

Nowadays, cellular physiology is best understood by analysing their interacting molecular components. Proteins are the major components of the cells. Different proteins are organised in the form of functional clusters, pathways or networks. These molecules are ordered in clusters of receptor molecules of extracellular signals, transducers, sensors and biological response effectors. The identification of these intracellular signaling pathways in different cellular types has required a long journey of experimental work. More than 300 intracellular signaling pathways have been identified in human cells. They participate in cell homeostasis processes for structural and functional maintenance. Some of them participate simultaneously or in a nearly-consecutive progression to generate a cellular phenotypic change. In this review, an analysis is performed on the main intracellular signaling pathways that take part in the cellular proliferation process, and the potential use of some components of these pathways as target for therapeutic interventionism are also underlined. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Multiple cognitive capabilities/deficits in children with an autism spectrum disorder: "weak" central coherence and its relationship to theory of mind and executive control.

PubMed

Pellicano, Elizabeth; Maybery, Murray; Durkin, Kevin; Maley, Alana

2006-01-01

This study examined the validity of "weak" central coherence (CC) in the context of multiple cognitive capabilities/deficits in autism. Children with an autism spectrum disorder (ASD) and matched typically developing children were administered tasks tapping visuospatial coherence, false-belief understanding and aspects of executive control. Significant group differences were found in all three cognitive domains. Evidence of local processing on coherence tasks was widespread in the ASD group, but difficulties in attributing false beliefs and in components of executive functioning were present in fewer of the children with ASD. This cognitive profile was generally similar for younger and older children with ASD. Furthermore, weak CC was unrelated to false-belief understanding, but aspects of coherence (related to integration) were associated with aspects of executive control. Few associations were found between cognitive variables and indices of autistic symptomatology. Implications for CC theory are discussed.

Hydrogen production from algal biomass via steam gasification.

PubMed

Duman, Gozde; Uddin, Md Azhar; Yanik, Jale

2014-08-01

Algal biomasses were tested as feedstock for steam gasification in a dual-bed microreactor in a two-stage process. Gasification experiments were carried out in absence and presence of catalyst. The catalysts used were 10% Fe₂O₃-90% CeO₂ and red mud (activated and natural forms). Effects of catalysts on tar formation and gasification efficiencies were comparatively investigated. It was observed that the characteristic of algae gasification was dependent on its components and the catalysts used. The main role of the catalyst was reforming of the tar derived from algae pyrolysis, besides enhancing water gas shift reaction. The tar reduction levels were in the range of 80-100% for seaweeds and of 53-70% for microalgae. Fe₂O₃-CeO₂ was found to be the most effective catalyst. The maximum hydrogen yields obtained were 1036 cc/g algae for Fucus serratus, 937 cc/g algae for Laminaria digitata and 413 cc/g algae for Nannochloropsis oculata. Copyright © 2014 Elsevier Ltd. All rights reserved.

Two-Phase chief complaint mapping to the UMLS metathesaurus in Korean electronic medical records.

PubMed

Kang, Bo-Yeong; Kim, Dae-Won; Kim, Hong-Gee

2009-01-01

The task of automatically determining the concepts referred to in chief complaint (CC) data from electronic medical records (EMRs) is an essential component of many EMR applications aimed at biosurveillance for disease outbreaks. Previous approaches that have been used for this concept mapping have mainly relied on term-level matching, whereby the medical terms in the raw text and their synonyms are matched with concepts in a terminology database. These previous approaches, however, have shortcomings that limit their efficacy in CC concept mapping, where the concepts for CC data are often represented by associative terms rather than by synonyms. Therefore, herein we propose a concept mapping scheme based on a two-phase matching approach, especially for application to Korean CCs, which uses term-level complete matching in the first phase and concept-level matching based on concept learning in the second phase. The proposed concept-level matching suggests the method to learn all the terms (associative terms as well as synonyms) that represent the concept and predict the most probable concept for a CC based on the learned terms. Experiments on 1204 CCs extracted from 15,618 discharge summaries of Korean EMRs showed that the proposed method gave significantly improved F-measure values compared to the baseline system, with improvements of up to 73.57%.

Analysis of independent components of cognitive event related potentials in a group of ADHD adults.

PubMed

Markovska-Simoska, Silvana; Pop-Jordanova, Nada; Pop-Jordanov, Jordan

In the last decade, many studies have tried to define the neural correlates of attention deficit hyperactivity disorder (ADHD). The main aim of this study is the comparison of the ERPs independent components in the four QEEG subtypes in a group of ADHD adults as a basis for defining the corresponding endophenotypes among ADHD population. Sixty-seven adults diagnosed as ADHD according to the DSM-IV criteria and 50 age-matched control subjects participated in the study. The brain activity of the subjects was recorded by 19 channel quantitative electroencephalography (QEEG) system in two neuropsychological tasks (visual and emotional continuous performance tests). The ICA method was applied for separation of the independent ERPs components. The components were associated with distinct psychological operations, such as engagement operations (P3bP component), comparison (vcomTL and vcom TR), motor inhibition (P3supF) and monitoring (P4monCC) operations. The ERPs results point out that there is disturbance in executive functioning in investigated ADHD group obtained by the significantly lower amplitude and longer latency for the engagement (P3bP), motor inhibition (P3supF) and monitoring (P4monCC) components. Particularly, the QEEG subtype IV was with the most significant ERPs differences comparing to the other subtypes. In particular, the most prominent difference in the ERPs independent components for the QEEG subtype IV in comparison to other three subtypes, rise many questions and becomes the subject for future research. This study aims to advance and facilitate the use of neurophysiological procedures (QEEG and ERPs) in clinical practice as objective measures of ADHD for better assessment, subtyping and treatment of ADHD.

Coastal Changes in Temperature and Salinity Observed during Hurricane Isaac Recorded and Downloaded by NASA DRIFTERs Moored in Heron Bay and at Half Moon Island, Louisiana

NASA Technical Reports Server (NTRS)

Kalcic, Maria; Iturriaga, Rodolfo H.; Kuper, Philip D.; O'Neal, Stanford Duane; Underwood, Lauren; Fletcher, Rose

2012-01-01

Major changes in salinity (approx.14 ppt.) and temperature (approx.40C) were continuously registered by two prototype NASA DRIFTERs, surface moored floaters, that NASA's Applied Science and Technology Project Office (ASTPO) has developed. The DRIFTER floating sensor module is equipped with an Arduino open-source electronics prototyping platform and programming language (http://www.arduino.cc), a GPS (Global Positioning System) module with antenna, a cell phone SIM (Subscriber Identity Module) card and a cellular antenna which is used to transmit data, and a probe to measure temperature and conductivity (from which salinity can be derived). The DRIFTER is powered by a solar cell panel and all the electronic components are mounted and sealed in [ waterproof encasement. Position and measurement data are transmitted via short message service (SMS) messaging to a Twitter site (DRIFTER 002@NASADRIFTER_002 and DRIFTER 004@NASADRIFTER_004), which provides a live feed. These data are the imported into a Google spreadsheet where conductivity is converted to salinity, and graphed in real-time. The spreadsheet data will be imported into a webpage maintained by ASTPO, where it will be displayed available for dO\\\\1lload.

Stressing the Need for Safety in Technical Education

ERIC Educational Resources Information Center

Defore, Jesse j.

1974-01-01

Discusses the importance of a safety orientation program in technical education and major components of a safety-conscious working enviroment. Suggests every institution take such measures as appointment of a safety officer, maintenance of a safety posture, inclusion of safety in curricula, and application of good safety practices. (CC)

A deep look at the nuclear region of UGC 5101 through high angular resolution mid-IR data with GTC/CanariCam

NASA Astrophysics Data System (ADS)

Martínez-Paredes, M.; Alonso-Herrero, A.; Aretxaga, I.; Ramos Almeida, C.; Hernán-Caballero, A.; González-Martín, O.; Pereira-Santaella, M.; Packham, C.; Asensio Ramos, A.; Díaz-Santos, T.; Elitzur, M.; Esquej, P.; García-Bernete, I.; Imanishi, M.; Levenson, N. A.; Rodríguez Espinosa, J. M.

2015-12-01

We present an analysis of the nuclear infrared (IR, 1.6-18 μm) emission of the ultraluminous IR galaxy UGC 5101 to derive the properties of its active galactic nucleus (AGN) and its obscuring material. We use new mid-IR high angular resolution (0.3-0.5 arcsec) imaging using the Si-2 filter (λC = 8.7 μm) and 7.5-13 μm spectroscopy taken with CanariCam (CC) on the 10.4 m Gran Telescopio CANARIAS. We also use archival Hubble Space Telescope/NICMOS and Subaru/COMICS imaging and Spitzer/IRS spectroscopy. We estimate the near- and mid-IR unresolved nuclear emission by modelling the imaging data with GALFIT. We decompose the Spitzer/IRS and CC spectra using a power-law component, which represents the emission due to dust heated by the AGN, and a starburst component, both affected by foreground extinction. We model the resulting unresolved near- and mid-IR, and the starburst subtracted CC spectrum with the CLUMPY torus models of Nenkova et al. The derived geometrical properties of the torus, including the large covering factor and the high foreground extinction needed to reproduce the deep 9.7 μm silicate feature, are consistent with the lack of strong AGN signatures in the optical. We derive an AGN bolometric luminosity Lbol ˜ 1.9 × 1045 erg s-1 that is in good agreement with other estimates in the literature.

Solitary waves in the nonlinear Dirac equation in the presence of external driving forces

DOE PAGES

Mertens, Franz G.; Cooper, Fred; Quintero, Niurka R.; ...

2016-01-05

In this paper, we consider the nonlinear Dirac (NLD) equation in (1 + 1) dimensions with scalar–scalar self interaction g 2/κ + 1 (Ψ¯Ψ) κ + 1 in the presence of external forces as well as damping of the form f(x) - iμγ 0Ψ, where both f and Ψ are two-component spinors. We develop an approximate variational approach using collective coordinates (CC) for studying the time dependent response of the solitary waves to these external forces. This approach predicts intrinsic oscillations of the solitary waves, i.e. the amplitude, width and phase all oscillate with the same frequency. The translational motionmore » is also affected, because the soliton position oscillates around a mean trajectory. For κ = 1 we solve explicitly the CC equations of the variational approximation for slow moving solitary waves in a constant external force without damping and find reasonable agreement with solving numerically the CC equations. Finally, we then compare the results of the variational approximation with no damping with numerical simulations of the NLD equation for κ = 1, when the components of the external force are of the form f j = r j exp(–iΚx) and again find agreement if we take into account a certain linear excitation with specific wavenumber that is excited together with the intrinsic oscillations such that the momentum in a transformed NLD equation is conserved.« less

[The role of developmental HOX genes in cervical cancer].

PubMed

López-Romero, Ricardo; Marrero-Rodríguez, Daniel; Romero-Morelos, Pablo; Villegas, Vanessa; Valdivia, Alejandra; Arreola, Hugo; Huerta-Padilla, Víctor; Salcedo, Mauricio

2015-01-01

Cervical cancer (CC) is a multifactorial disease associated to genetic, environmental and epigenetic factors, being the infection by human papillomavirus the main etiologic agent. Additionally, the alteration in the expression of transcription factors has been considered of importance for the development of this tumor. HOX genes encode a group of transcription factors involved in cellular proliferation and differentiation processes during the development of embryonic structures in vertebrates; their aberrant expression is associated with tumorigenesis and metastasis. A range of evidence suggests a role for HOX genes in the development of cervical neoplastic cell. Studies in CC cell lines, primary tumors and premalignant lesions have suggested the involvement of HOXA1, HOXC5, C6, C8 and C10, HOXD9 and HOXD13 in the process of cervical carcinogenesis. Also, the de novo expression of genes HOXB2, B4, B13 and HOXC11-C13 appears to be involved in the process of malignant transformation of cervical epithelial cell. These data would allow to open a field in search of new molecular markers in cervical cancer and the development of new therapeutic strategies for this malignancy.

Neuropathological Consequences of Gestational Exposure to Concentrated Ambient Fine and Ultrafine Particles in the Mouse.

PubMed

Klocke, Carolyn; Allen, Joshua L; Sobolewski, Marissa; Mayer-Pröschel, Margot; Blum, Jason L; Lauterstein, Dana; Zelikoff, Judith T; Cory-Slechta, Deborah A

2017-04-01

Increasing evidence indicates that the central nervous system (CNS) is a target of air pollution. We previously reported that postnatal exposure of mice to concentrated ambient ultrafine particles (UFP; ≤100 nm) via the University of Rochester HUCAPS system during a critical developmental window of CNS development, equivalent to human 3rd trimester, produced male-predominant neuropathological and behavioral characteristics common to multiple neurodevelopmental disorders, including autism spectrum disorder (ASD), in humans. The current study sought to determine whether vulnerability to fine (≤2.5 μm) and UFP air pollution exposure extends to embryonic periods of brain development in mice, equivalent to human 1st and 2nd trimesters. Pregnant mice were exposed 6 h/day from gestational days (GDs) 0.5-16.5 using the New York University VACES system to concentrated ambient fine/ultrafine particles at an average concentration of 92.69 μg/m3 over the course of the exposure period. At postnatal days (PNDs) 11-15, neuropathological consequences were characterized. Gestational air pollution exposures produced ventriculomegaly, increased corpus callosum (CC) area and reduced hippocampal area in both sexes. Both sexes demonstrated CC hypermyelination and increased microglial activation and reduced total CC microglia number. Analyses of iron deposition as a critical component of myelination revealed increased iron deposition in the CC of exposed female offspring, but not in males. These findings demonstrate that vulnerability of the brain to air pollution extends to gestation and produces features of several neurodevelopmental disorders in both sexes. Further, they highlight the importance of the commonalities of components of particulate matter exposures as a source of neurotoxicity and common CNS alterations. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hybrid Correlation Energy (HyCE): An Approach Based on Separate Evaluations of Internal and External Components.

PubMed

Ivanic, Joseph; Schmidt, Michael W

2018-06-04

A novel hybrid correlation energy (HyCE) approach is proposed that determines the total correlation energy via distinct computation of its internal and external components. This approach evolved from two related studies. First, rigorous assessment of the accuracies and size extensivities of a number of electron correlation methods, that include perturbation theory (PT2), coupled-cluster (CC), configuration interaction (CI), and coupled electron pair approximation (CEPA), shows that the CEPA(0) variant of the latter and triples-corrected CC methods consistently perform very similarly. These findings were obtained by comparison to near full CI results for four small molecules and by charting recovered correlation energies for six steadily growing chain systems. Second, by generating valence virtual orbitals (VVOs) and utilizing the CEPA(0) method, we were able to partition total correlation energies into internal (or nondynamic) and external (or dynamic) parts for the aforementioned six chain systems and a benchmark test bed of 36 molecules. When using triple-ζ basis sets it was found that per orbital internal correlation energies were appreciably larger than per orbital external energies and that the former showed far more chemical variation than the latter. Additionally, accumulations of external correlation energies were seen to proceed smoothly, and somewhat linearly, as the virtual space is gradually increased. Combination of these two studies led to development of the HyCE approach, whereby the internal and external correlation energies are determined separately by CEPA(0)/VVO and PT2/external calculations, respectively. When applied to the six chain systems and the 36-molecule benchmark test set it was found that HyCE energies followed closely those of triples-corrected CC and CEPA(0) while easily outperforming MP2 and CCSD. The success of the HyCE approach is more notable when considering that its cost is only slightly more than MP2 and significantly cheaper than the CC approaches.

An investigation of evapotranspiration rates within mid-western agricultural systems in response to elevated carbon dioxide and ozone concentrations and climate change

NASA Astrophysics Data System (ADS)

Abdullah, W. F.; Lombardozzi, D.; Levis, S.; Bonan, G. B.

2013-12-01

Warith Featherstone Abdullah, Danica Lombardozzi, Samuel Levis and Gordon Bonan Jackson State University Dept. of Physics, Atmospheric Sciences & Geosciences National Center for Atmospheric Research Climate & Global Dynamics Because the human population is expected to surpass 8 billion by the year 2050, food security is a pressing issue. In the face of elevated temperatures associated with climate change (CC), elevated carbon dioxide (CO2) and elevated ozone (O3) concentrations, food productivity is uncertain. Plant stomata must be open to gain carbon which simultaneously causes water loss. Research suggests rising temperatures, elevated CO2 and elevated O3 in the future may impact plant stomata and change the rate plants lose water and take up carbon, affecting plant productivity and crop yields. Evapotranspiration (ET), latent heat fluxes, leaf carbon and net primary productivity (NPP) were analyzed in U.S Mid-west where crop density is greatest. Four simulations were run using the National Center for Atmospheric Research (NCAR) Community Land Model version 4 (CLM4) component of the Community Earth System Model (CESM) with an extended carbon-nitrogen model (CN). Analyses were based on June-July-August seasonal averages through 2080-2100 to compare the individual effects of CC, elevated CO2 and O3, and combined effects of all drivers. Results from model projections show increased ET with CC and all drivers combined, but only small changes from O3 or CO2 alone. Further results show that NPP was reduced with CC and O3 alone, but increased with CO2 alone and only slightly reduced with interacting components. The combined driver simulation, which most accurately represents future global change, suggests deteriorating water usage efficiency, thus potentially decreasing carbon uptake and crop production. However, further research is needed for verification. Midwest seasonal summation estimates for net primary productivity calculated by CLM4CN model. Climate change, CO2 and O3 levels are predicted using IPCC RCP8.5 scenarios.

The expression of MUC mucin in cholangiocarcinoma.

PubMed

Mall, Anwar S; Tyler, Marilyn G; Ho, Sam B; Krige, Jake E J; Kahn, Delawir; Spearman, Wendy; Myer, Landon; Govender, Dhirendra

2010-12-15

Cholangiocarcinoma (CC) is a highly malignant epithelial cancer of the biliary tract, the cellular and molecular pathogenesis of which remains unclear. Malignant transformation of glandular epithelial cells is associated with the altered expression of mucin. We investigated the type of mucins expressed in CC. Twenty-six patients with histologically confirmed CC were included in this study. The expression of mucin was studied by immunohistochemistry using antibodies to MUC1, MUC1 core, MUC2, MUC3, MUC4, MUC5AC, and MUC6. There was extensive (>50%) expression of mucin, mainly MUC1 in 11/25 and MUC5AC in 12/26 cases. In the case of MUC3, 6/26 cases expressed mucin extensively, whilst only 1/26 had MUC2, MUC4, and MUC6 expression. Well-differentiated tumors significantly expressed MUC3 extensively compared to poor or moderately differentiated tumors (p=0.003). Fifteen of 25 cases had metastatic disease. MUC1 was extensively expressed in 9/15 cases with metastatic disease. In contrast, MUC1 expression was present in 2/10 cases where metastases were absent. Hilar lesions were less likely to express MUC1, but this was not statistically significant. Fifteen of 25 cases had metastatic disease. Extensive MUC3 expression was significantly associated with well-differentiated tumors, whilst there was an approaching significance between the extensive expression of MUC1 and metastasis in cholangiocarcinoma. Copyright © 2010 Elsevier GmbH. All rights reserved.

Microwave components for cellular portable radiotelephone

NASA Astrophysics Data System (ADS)

Muraguchi, Masahiro; Aikawa, Masayoshi

1995-09-01

Mobile and personal communication systems are expected to represent a huge market for microwave components in the coming years. A number of components in silicon bipolar, silicon Bi-CMOS, GaAs MESFET, HBT and HEMT are now becoming available for system application. There are tradeoffs among the competing technologies with regard to performance, cost, reliability and time-to-market. This paper describes process selection and requirements of cost and r.f. performances to microwave semiconductor components for digital cellular and cordless telephones. Furthermore, new circuit techniques which were developed by NTT are presented.

43. Cognitive Functioning in First-Episode Psychosis:_x000B_ Comparison of a 2-Year Coordinated Specialty Care Program to Community Care

PubMed Central

Schooler, Nina; Khan, Anzalee; Keefe, Richard; Robinson, Delbert; Kane, John

2017-01-01

Abstract Background: Significant cognitive impairment is already seen in first-episode psychosis (FEP) and degree of impairment is a moderator of long-term outcomes. Does specialized FEP treatment improve cognitive functioning? The NIMH sponsored RAISE-ETP study allows comparison of NAVIGATE, a coordinated specialty care intervention designed for FEP, to Community Care (CC) in a randomized clinical trial. (RCT) Methods: The RCT was conducted at 34 sites in the United States. Seventeen sites were randomly assigned to provide NAVIGATE and 17 to provide CC. Four hundred four consenting participants age 15 to 45 years old, experiencing an FEP and had not received more than 6 months of antipsychotic medication entered the study. Treatment and assessment continued for up to two years. The Brief Assessment of Cognition in Schizophrenia (BACS) was administered at baseline, one and two years. Age and sex adjusted T-scores for the BACS Composite and six sub-tests (Verbal Memory, Digit Sequencing, Verbal Fluency, Token Motor, Symbol Coding and Tower of London) were calculated. Generalized estimating equations (GEEs) were applied to compare change in treatments between baseline, months 12 and 24 adjusting for within and between site variation. Results: The NAVIGATE and CC groups included 221 and 181 participants. The Group X Visit interactions was a statistically significant predictor of change in: Verbal Memory, Verbal Fluency, Symbol Coding, Tower of London and the Composite (P < .001 for all). For the NAVIGATE group, there was significant improvement at Month 12 and Month 24 for Verbal Memory, Digit Sequencing, Tower of London, and the Composite. For the CC group, there was a significant improvement at Month 12 and Month 24 for the Composite; and only at month 24 for the Tower of London. Conclusion: The results of this analysis suggest that NAVIGATE resulted in greater improvement in cognitive functioning in both an overall score and for specific components than did CC. NAVIGATE is a multi-component intervention, guided by manuals and supervision by a central team. NAVIGATE includes psychopharmacological treatment with antipsychotics and other psychotropic medications using an internet based decision support system, an individual psychotherapy called Individual Resiliency Training, family psychoeducation and supported employment and education. The role of individual components cannot be readily determined and further analyses will evaluate the effect of moderator variables such as duration of untreated psychosis, symptomatology and functioning at study entry. To date, pharmacologic treatments to improve cognition have not demonstrated efficacy. Cognitive remediation strategies, notably Cognitive Enhancement Therapy pioneered by Gerard Hogarty, has shown efficacy in FEP patients but to the best of our knowledge, this is the first RCT to show an effect of a broad FEP focused intervention on cognitive functioning.

Correlation consistent basis sets for actinides. II. The atoms Ac and Np-Lr

NASA Astrophysics Data System (ADS)

Feng, Rulin; Peterson, Kirk A.

2017-08-01

New correlation consistent basis sets optimized using the all-electron third-order Douglas-Kroll-Hess (DKH3) scalar relativistic Hamiltonian are reported for the actinide elements Ac and Np through Lr. These complete the series of sets reported previously for Th-U [K. A. Peterson, J. Chem. Phys. 142, 074105 (2015); M. Vasiliu et al., J. Phys. Chem. A 119, 11422 (2015)]. The new sets range in size from double- to quadruple-zeta and encompass both those optimized for valence (6s6p5f7s6d) and outer-core electron correlations (valence + 5s5p5d). The final sets have been contracted for both the DKH3 and eXact 2-component (X2C) Hamiltonians, yielding cc-pVnZ-DK3/cc-pVnZ-X2C sets for valence correlation and cc-pwCVnZ-DK3/cc-pwCVnZ-X2C sets for outer-core correlation (n = D, T, Q in each case). In order to test the effectiveness of the new basis sets, both atomic and molecular benchmark calculations have been carried out. In the first case, the first three atomic ionization potentials (IPs) of all the actinide elements Ac-Lr have been calculated using the Feller-Peterson-Dixon (FPD) composite approach, primarily with the multireference configuration interaction (MRCI) method. Excellent convergence towards the respective complete basis set (CBS) limits is achieved with the new sets, leading to good agreement with experiment, where these exist, after accurately accounting for spin-orbit effects using the 4-component Dirac-Hartree-Fock method. For a molecular test, the IP and atomization energy (AE) of PuO2 have been calculated also using the FPD method but using a coupled cluster approach with spin-orbit coupling accounted for using the 4-component MRCI. The present calculations yield an IP0 for PuO2 of 159.8 kcal/mol, which is in excellent agreement with the experimental electron transfer bracketing value of 162 ± 3 kcal/mol. Likewise, the calculated 0 K AE of 305.6 kcal/mol is in very good agreement with the currently accepted experimental value of 303.1 ± 5 kcal/mol. The ground state of PuO2 is predicted to be the 0 g +5Σ state.

Correlation consistent basis sets for actinides. II. The atoms Ac and Np-Lr.

PubMed

Feng, Rulin; Peterson, Kirk A

2017-08-28

New correlation consistent basis sets optimized using the all-electron third-order Douglas-Kroll-Hess (DKH3) scalar relativistic Hamiltonian are reported for the actinide elements Ac and Np through Lr. These complete the series of sets reported previously for Th-U [K. A. Peterson, J. Chem. Phys. 142, 074105 (2015); M. Vasiliu et al., J. Phys. Chem. A 119, 11422 (2015)]. The new sets range in size from double- to quadruple-zeta and encompass both those optimized for valence (6s6p5f7s6d) and outer-core electron correlations (valence + 5s5p5d). The final sets have been contracted for both the DKH3 and eXact 2-component (X2C) Hamiltonians, yielding cc-pVnZ-DK3/cc-pVnZ-X2C sets for valence correlation and cc-pwCVnZ-DK3/cc-pwCVnZ-X2C sets for outer-core correlation (n = D, T, Q in each case). In order to test the effectiveness of the new basis sets, both atomic and molecular benchmark calculations have been carried out. In the first case, the first three atomic ionization potentials (IPs) of all the actinide elements Ac-Lr have been calculated using the Feller-Peterson-Dixon (FPD) composite approach, primarily with the multireference configuration interaction (MRCI) method. Excellent convergence towards the respective complete basis set (CBS) limits is achieved with the new sets, leading to good agreement with experiment, where these exist, after accurately accounting for spin-orbit effects using the 4-component Dirac-Hartree-Fock method. For a molecular test, the IP and atomization energy (AE) of PuO 2 have been calculated also using the FPD method but using a coupled cluster approach with spin-orbit coupling accounted for using the 4-component MRCI. The present calculations yield an IP 0 for PuO 2 of 159.8 kcal/mol, which is in excellent agreement with the experimental electron transfer bracketing value of 162 ± 3 kcal/mol. Likewise, the calculated 0 K AE of 305.6 kcal/mol is in very good agreement with the currently accepted experimental value of 303.1 ± 5 kcal/mol. The ground state of PuO 2 is predicted to be the Σ0g+5 state.

Global change impact on oxidative potential and toxicity of atmospheric particles from the East Mediterranean basin: the ARCHIMEDES initiative

NASA Astrophysics Data System (ADS)

Alleman, Laurent; Anthérieu, Sébastien; Baeza-Squiban, Armelle; Garçon, Guillaume; Lo Guidice, Jean-Marc; Hamonou, Eric; Öztürk, Fatma; Perdrix, Esperanza; Rudich, Yinon; Sciare, Jean; Sauvage, Stéphane

2017-04-01

Climate change (CC) has important social, economical and health implications, notably in accordance with variation in air pollution or microbiome modification and its related toxicity mechanisms. CC will have a strong influence on meteorology, inducing dryer and warmer conditions in some regions. The Mediterranean basin is foreseen as a hotspot for regional climate warming, favoring larger dust episodes, wild fire events, vegetation emissions and changes in air pollution physic-chemical characteristics due to enhanced photochemical reactivity. Increasing concentrations of biogenic volatile organic compounds (VOCs), ozone, and radicals will be associated with rising concentrations of secondary organic aerosols (SOA) and other oxidized aerosols. These expected changes in aerosol composition are currently studied within the international ChArMEx (Chemistry-aerosol Mediterranean Experiment) program, part of the interdisciplinary MISTRALS metaprogramme (Mediterranean Integrated STudies at Regional And Local Scales). According to the LIFE/MED-PARTICLES (LIFE) project, this might result in more adverse effects on health. However, toxicologists are far from having a detailed mechanistic knowledge of the quantitative causal relations between particles (PM) and health effects suggested by epidemiological evidences. Detailed toxicological studies looking at contrasted PM origins and chemical compositions are highly needed, particularly on strongly aged SOA suspected to increase the oxidative potential (OP) and to enhance the toxicity of airborne particles. Intensive researches onto the underlying mechanisms of inflammation started to describe the outlines of the intricate relationship between oxidative stress and inflammation. It is therefore, of great importance to better determine the OP of PM from contrasted surroundings, its relationship with CC through PM's physical, chemical and microbial characteristics, and its toxicological consequences within the lungs. Recently, several projects under the ARCHIMEDES (Envi-MED funded) initiative including various research groups from Eastern Mediterranean countries have been submitted to French research calls. Their objectives are to develop an integrated testing strategy (ITS) through a combination of high throughput screening (HTS) methods based on acellular and lung cellular systems evaluating the respective OP (DTT, ascorbic acid and GSH depletion, DCFH oxidation) of various PM samples according to their origins in terms of sources and CC forecast. In order to ensure significant variability in ageing of the size segregated PM (fine, coarse) tested, samples from both northern (France) and southern countries (Cyprus, Israel, Turkey) should be collected at different seasons and site typologies, searching for various compositions and mixing states in SOA (biogenic, anthropogenic), metals and PAHs. These projects will combine relevant chemical, microbiological (DNA extract) and toxicological experiments (transcriptome, epigenome and secretome). A joint toxicological analysis related to their harmful effects on relevant oxidative (ATP, TAS, GSH/GSSG, gammaH2AX), inflammatory, genetic, and epigenetic endpoints within novel tissue-engineering tools will help in recapturing the native lung environment ex vivo. In the CC context, such projects will help to (1) better understand the cellular and molecular mechanisms of PM toxicity, (2) detect and predict their respiratory effects, (3) better comprehend the relationship between the physicochemical characteristics and the toxicological effects of PM, (4) provide innovative biomarkers that could be subsequently validated in humans and thereby contribute to the predictive toxicology.

Multicomponent Calibration and Quantitation Methods.

DTIC Science & Technology

1984-11-01

liquid chromatographic peaks (45). Applying rank annihilation to LC /UV data requires that the elution profiles of each individual component in the...measurements, e.g. LC /UV, CC/MS, or GC/FTIR analyses. The response of a single component can be described as M = a x y’ (45) 0 where M contains the...in the second dimension. For example, a GC/MS peak consisting - 3 of 50 mass spectra each composed of 20 distinct m/e ratios would result in a matrix

Preliminary Airworthiness Evaluation OH-58C Helicopter Configured with a Mast Mounted Sight

DTIC Science & Technology

1980-05-01

r’assemnbled on tlhc bench and measured for component allirnment. It was found tlait the nonrotating platform had a 0.026 inch radial runout and a 0(020 face... runout with respect to the mast axis of rotation. The contractor determined that this runout was sufficient to cause a I,’rev vibration at the MMS cc...mast to nonrotating platform allignment. By selectively matching the above components, the final configuration resulted in a face runout of 0.002

Body composition analysis: Cellular level modeling of body component ratios.

PubMed

Wang, Z; Heymsfield, S B; Pi-Sunyer, F X; Gallagher, D; Pierson, R N

2008-01-01

During the past two decades, a major outgrowth of efforts by our research group at St. Luke's-Roosevelt Hospital is the development of body composition models that include cellular level models, models based on body component ratios, total body potassium models, multi-component models, and resting energy expenditure-body composition models. This review summarizes these models with emphasis on component ratios that we believe are fundamental to understanding human body composition during growth and development and in response to disease and treatments. In-vivo measurements reveal that in healthy adults some component ratios show minimal variability and are relatively 'stable', for example total body water/fat-free mass and fat-free mass density. These ratios can be effectively applied for developing body composition methods. In contrast, other ratios, such as total body potassium/fat-free mass, are highly variable in vivo and therefore are less useful for developing body composition models. In order to understand the mechanisms governing the variability of these component ratios, we have developed eight cellular level ratio models and from them we derived simplified models that share as a major determining factor the ratio of extracellular to intracellular water ratio (E/I). The E/I value varies widely among adults. Model analysis reveals that the magnitude and variability of each body component ratio can be predicted by correlating the cellular level model with the E/I value. Our approach thus provides new insights into and improved understanding of body composition ratios in adults.

Quantitative proteomics identifies 38 proteins that are differentially expressed in cucumber in response to cucumber green mottle mosaic virus infection.

PubMed

Liu, Hua-Wei; Liang, Chao-Qiong; Liu, Peng-Fei; Luo, Lai-Xin; Li, Jian-Qiang

2015-12-15

Since it was first reported in 1935, Cucumber green mottle mosaic virus (CGMMV) has become a serious pathogen in a range of cucurbit crops. The virus is generally transmitted by propagation materials, and to date no effective chemical or cultural methods of control have been developed to combat its spread. The current study presents a preliminary analysis of the pathogenic mechanisms from the perspective of protein expression levels in an infected cucumber host, with the objective of elucidating the infection process and potential strategies to reduce both the economic and yield losses associated with CGMMV. Isobaric tags for relative and absolute quantitation (iTRAQ) technology coupled with liquid chromatography-tandem mass spectrometric (LC-MS/MS) were used to identify the differentially expressed proteins in cucumber plants infected with CGMMV compared with mock-inoculated plants. The functions of the proteins were deduced by functional annotation and their involvement in metabolic processes explored by KEGG pathway analysis to identify their interactions during CGMMV infection, while their in vivo expression was further verified by qPCR. Infection by CGMMV altered both the expression level and absolute quantity of 38 proteins (fold change >0.6) in cucumber hosts. Of these, 23 were found to be up-regulated, while 15 were down-regulated. Gene ontology (GO) analysis revealed that 22 of the proteins had a combined function and were associated with molecular function (MF), biological process (BP) and cellular component (CC). Several other proteins had a dual function with 1, 7, and 2 proteins being associated with BP/CC, BP/MF, CC/MF, respectively. The remaining 3 proteins were only involved in MF. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified 18 proteins that were involved in 13 separate metabolic pathways. These pathways were subsequently merged to generate three network diagrams illustrating the interactions between the different pathways, while qPCR was used to track the changes in expression levels of the proteins identified at 3 time points during CGMMV infection. Taken together these results greatly expand our understanding of the relationships between CGMMV and cucumber hosts. The results of the study indicate that CGMMV infection significantly changes the physiology of cucumbers, affecting the expression levels of individual proteins as well as entire metabolic pathways. The bioinformatic analysis also identified several pathogenesis-related (PR) proteins that could be useful in the development of disease-resistant plants.

Gelation-driven selection in dynamic covalent C 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 1111111111111111111111111111111111 1111111111111111111111111111111111 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 0000000000000000000000000000000000 C/CN exchange.

PubMed

Liang, Chunshuang; Kulchat, Sirinan; Jiang, Shimei; Lehn, Jean-Marie

2017-10-01

Knoevenagel barbiturate derivatives bearing long alkyl chains were proven to form organogels in suitable solvents based on supramolecular interactions. Their reaction with imines allows for component exchange through CC/CN recombination. The effect of various parameters (solvents, chain length, and temperature) on the CC/CN exchange reaction has been studied. Mixing Knoevenagel compound K and imine I-16 in a 1 : 1 ratio generated a constitutional dynamic library containing the four constituents K , I-16 , K'-16 , and I' . The reversible exchange reaction was monitored by 1 H-NMR, showing marked changes in the fractions of the four constituents on sol-gel interconversion as a function of temperature. The library composition changed from statistical distribution of the four constituents in the sol state to selective amplification of the gel forming K'-16 constituent together with that of its agonist I' . The process amounts to self-organization driven component selection in a constitutional dynamic organogel system undergoing gelation. This process displays up-regulation of the gel-forming constituent by component redistribution through reversible covalent connections.

Collaborative care for depression and anxiety disorders in patients with recent cardiac events: the Management of Sadness and Anxiety in Cardiology (MOSAIC) randomized clinical trial.

PubMed

Huffman, Jeff C; Mastromauro, Carol A; Beach, Scott R; Celano, Christopher M; DuBois, Christina M; Healy, Brian C; Suarez, Laura; Rollman, Bruce L; Januzzi, James L

2014-06-01

Depression and anxiety are associated with adverse cardiovascular outcomes in patients with recent acute cardiac events. There has been minimal study of collaborative care (CC) management models for mental health disorders in high-risk cardiac inpatients, and no prior CC intervention has simultaneously managed depression and anxiety disorders. To determine the impact of a low-intensity CC intervention for depression, generalized anxiety disorder, and panic disorder among patients hospitalized for an acute cardiac illness. Single-blind randomized clinical trial, with study assessors blind to group assignment, from September 2010 through July 2013 of 183 patients admitted to inpatient cardiac units in an urban academic general hospital for acute coronary syndrome, arrhythmia, or heart failure and found to have clinical depression, generalized anxiety disorder, or panic disorder on structured assessment. Participants were randomized to 24 weeks of a low-intensity telephone-based multicomponent CC intervention targeting depression and anxiety disorders (n = 92) or to enhanced usual care (serial notification of primary medical providers; n = 91). The CC intervention used a social work care manager to coordinate assessment and stepped care of psychiatric conditions and to provide support and therapeutic interventions as appropriate. Improvement in mental health-related quality of life (Short Form-12 Mental Component Score [SF-12 MCS]) at 24 weeks, compared between groups using a random-effects model in an intent-to-treat analysis. Patients randomized to CC had significantly greater estimated mean improvements in SF-12 MCS at 24 weeks (11.21 points [from 34.21 to 45.42] in the CC group vs 5.53 points [from 36.30 to 41.83] in the control group; estimated mean difference, 5.68 points [95% CI, 2.14-9.22]; P = .002; effect size, 0.61). Patients receiving CC also had significant improvements in depressive symptoms and general functioning, and higher rates of treatment of a mental health disorder; anxiety scores, rates of disorder response, and adherence did not differ between groups. A novel telephone-based, low-intensity model to concurrently manage cardiac patients with depression and/or anxiety disorders was effective for improving mental health-related quality of life in a 24-week trial. clinicaltrials.gov Identifier: NCT01201967.

The aconitate hydratase family from Citrus

PubMed Central

2010-01-01

Background Research on citrus fruit ripening has received considerable attention because of the importance of citrus fruits for the human diet. Organic acids are among the main determinants of taste and organoleptic quality of fruits and hence the control of fruit acidity loss has a strong economical relevance. In citrus, organic acids accumulate in the juice sac cells of developing fruits and are catabolized thereafter during ripening. Aconitase, that transforms citrate to isocitrate, is the first step of citric acid catabolism and a major component of the citrate utilization machinery. In this work, the citrus aconitase gene family was first characterized and a phylogenetic analysis was then carried out in order to understand the evolutionary history of this family in plants. Gene expression analyses of the citrus aconitase family were subsequently performed in several acidic and acidless genotypes to elucidate their involvement in acid homeostasis. Results Analysis of 460,000 citrus ESTs, followed by sequencing of complete cDNA clones, identified in citrus 3 transcription units coding for putatively active aconitate hydratase proteins, named as CcAco1, CcAco2 and CcAco3. A phylogenetic study carried on the Aco family in 14 plant species, shows the presence of 5 Aco subfamilies, and that the ancestor of monocot and dicot species shared at least one Aco gene. Real-time RT-PCR expression analyses of the three aconitase citrus genes were performed in pulp tissues along fruit development in acidic and acidless citrus varieties such as mandarins, oranges and lemons. While CcAco3 expression was always low, CcAco1 and CcAco2 genes were generally induced during the rapid phase of fruit growth along with the maximum in acidity and the beginning of the acid reduction. Two exceptions to this general pattern were found: 1) Clemenules mandarin failed inducing CcAco2 although acid levels were rapidly reduced; and 2) the acidless "Sucreña" orange showed unusually high levels of expression of both aconitases, an observation correlating with the acidless phenotype. However, in the acidless "Dulce" lemon aconitase expression was normal suggesting that the acidless trait in this variety is not dependent upon aconitases. Conclusions Phylogenetic studies showed the occurrence of five different subfamilies of aconitate hydratase in plants and sequence analyses indentified three active genes in citrus. The pattern of expression of two of these genes, CcAco1 and CcAco2, was normally associated with the timing of acid content reduction in most genotypes. Two exceptions to this general observation suggest the occurrence of additional regulatory steps of citrate homeostasis in citrus. PMID:20958971

Case Study: The Mystery of the Seven Deaths--A Case Study in Cellular Respiration

ERIC Educational Resources Information Center

Gazdik, Michaela

2014-01-01

Cellular respiration, the central component of cellular metabolism, can be a difficult concept for many students to fully understand. In this interrupted, problem-based case study, students explore the purpose of cellular respiration as they play the role of medical examiner, analyzing autopsy evidence to determine the mysterious cause of death…

Cytochrome c oxidase inhibition by calcium at physiological ionic composition of the medium: Implications for physiological significance of the effect.

PubMed

Vygodina, Tatiana V; Mukhaleva, Elizaveta; Azarkina, Natalia V; Konstantinov, Alexander A

2017-12-01

Cytochrome c oxidase (CcO) from mammalian mitochondria binds Ca 2+ and Na + in a special cation binding site. Binding of Ca 2+ brings about partial inhibition of the enzyme while Na + competes with Ca 2+ for the binding site and protects the enzyme from the inhibition [Vygodina, T., Kirichenko, A. and Konstantinov, A.A. (2013). Direct Regulation of Cytochrome c oxidase by Calcium Ions. PLoS One 8(9): e74436]. In the original studies, the inhibition was found to depend significantly on the ionic composition of the buffer. Here we describe inhibition of CcO by Ca 2+ in media containing the main ionic components of cytoplasm (150mM KCl, 12mM NaCl and 1mM MgCl 2 ). Under these conditions, Ca 2+ inhibits CcO with effective K i of 20-26μM, that is an order of magnitude higher than determined earlier in the absence of Na + . At physiological value of ionic strength, the inhibition can be observed at any turnover number of CcO, rather than only at low TN (<10s -1 ) as found previously. The inhibition requires partially oxidized state of cytochrome c and is favored by high ionic strength with a sharp transition at 0.1-0.2M. The high K i =20-26μM found for CcO inhibition by calcium matches closely the known value of "K m " for Ca 2+ -induced activation of the mitochondrial calcium uniporter. The inhibition of CcO by Ca 2+ is proposed to modulate mitochondrial Ca 2+ -uptake via the mitochondrial calcium uniporter, promote permeability transition pore opening and induce reduction of Mia40 in the mitochondrial intermembrane space. Copyright © 2017 Elsevier B.V. All rights reserved.

Why does MP2 work?

PubMed

Fink, Reinhold F

2016-11-14

We show analytically and numerically that the performance of second order Møller-Plesset (MP) perturbation theory (PT), coupled-cluster (CC) theory, and other perturbation theory approaches can be rationalized by analyzing the wavefunctions of these methods. While rather large deviations for the individual contributions of configurations to the electron correlation energy are found for MP wavefunctions, they profit from an advantageous and robust error cancellation: The absolute contribution to the correlation energy is generally underestimated for the critical excitations with small energy denominators and all other doubly excited configurations where the two excited electrons are coupled to a singlet. This is balanced by an overestimation of the contribution of triplet-coupled double excitations to the correlation energy. The even better performance of spin-component-scaled-MP2 theory is explained by a similar error compensation effect. The wavefunction analysis for the lowest singlet states of H 2 O, CH 2 , CO, and Cu + shows the predicted trends for MP methods, rapid but biased convergence of CC theory as well as the substantial potential of linearized CC, or retaining the excitation-degree (RE)-PT.

29 CFR 1926.500 - Scope, application, and definitions applicable to this subpart.

Code of Federal Regulations, 2014 CFR

2014-07-01

... CC of this part. (iii) Fall protection requirements for employees performing steel erection work... for training in the installation and use of fall protection systems, except in relation to steel... component parts. Load refusal is the point where the ultimate strength is exceeded. Free fall means the act...

Measurement of the neutrino component of an antineutrino beam observed by a nonmagnetized detector

NASA Astrophysics Data System (ADS)

Aguilar-Arevalo, A. A.; Anderson, C. E.; Brice, S. J.; Brown, B. C.; Bugel, L.; Conrad, J. M.; Dharmapalan, R.; Djurcic, Z.; Fleming, B. T.; Ford, R.; Garcia, F. G.; Garvey, G. T.; Grange, J.; Green, J. A.; Imlay, R.; Johnson, R. A.; Karagiorgi, G.; Katori, T.; Kobilarcik, T.; Linden, S. K.; Louis, W. C.; Mahn, K. B. M.; Marsh, W.; Mauger, C.; Metcalf, W.; Mills, G. B.; Mirabal, J.; Moore, C. D.; Mousseau, J.; Nelson, R. H.; Nguyen, V.; Nienaber, P.; Nowak, J. A.; Osmanov, B.; Patch, A.; Pavlovic, Z.; Perevalov, D.; Polly, C. C.; Ray, H.; Roe, B. P.; Russell, A. D.; Shaevitz, M. H.; Sorel, M.; Spitz, J.; Stancu, I.; Stefanski, R. J.; Tayloe, R.; Tzanov, M.; van de Water, R. G.; Wascko, M. O.; White, D. H.; Wilking, M. J.; Zeller, G. P.; Zimmerman, E. D.

2011-10-01

Two methods are employed to measure the neutrino flux of the antineutrino-mode beam observed by the MiniBooNE detector. The first method compares data to simulated event rates in a high-purity νμ-induced charged-current single π+ (CC1π+) sample while the second exploits the difference between the angular distributions of muons created in νμ and ν¯μ charged-current quasielastic (CCQE) interactions. The results from both analyses indicate the prediction of the neutrino flux component of the predominately antineutrino beam is overestimated—the CC1π+ analysis indicates the predicted νμ flux should be scaled by 0.76±0.11, while the CCQE angular fit yields 0.65±0.23. The energy spectrum of the flux prediction is checked by repeating the analyses in bins of reconstructed neutrino energy, and the results show that the spectral shape is well-modeled. These analyses are a demonstration of techniques for measuring the neutrino contamination of antineutrino beams observed by future nonmagnetized detectors.

Ternary electrocatalysts for oxidizing ethanol to carbon dioxide: making ir capable of splitting C-C bond.

PubMed

Li, Meng; Cullen, David A; Sasaki, Kotaro; Marinkovic, Nebojsa S; More, Karren; Adzic, Radoslav R

2013-01-09

Splitting the C-C bond is the main obstacle to electrooxidation of ethanol (EOR) to CO(2). We recently demonstrated that the ternary PtRhSnO(2) electrocatalyst can accomplish that reaction at room temperature with Rh having a unique capability to split the C-C bond. In this article, we report the finding that Ir can be induced to split the C-C bond as a component of the ternary catalyst. We characterized and compared the properties of several carbon-supported nanoparticle (NP) electrocatalysts comprising a SnO(2) NP core decorated with multimetallic nanoislands (MM' = PtIr, PtRh, IrRh, PtIrRh) prepared using a seeded growth approach. An array of characterization techniques were employed to establish the composition and architecture of the synthesized MM'/SnO(2) NPs, while electrochemical and in situ infrared reflection absorption spectroscopy studies elucidated trends in activity and the nature of the reaction intermediates and products. Both EOR reactivity and selectivity toward CO(2) formation of several of these MM'/SnO(2)/C electrocatalysts are significantly higher compared to conventional Pt/C and Pt/SnO(2)/C catalysts. We demonstrate that the PtIr/SnO(2)/C catalyst with high Ir content shows outstanding catalytic properties with the most negative EOR onset potential and reasonably good selectivity toward ethanol complete oxidation to CO(2).

Discovery of Novel Hepatitis C Virus NS5B Polymerase Inhibitors by Combining Random Forest, Multiple e-Pharmacophore Modeling and Docking

PubMed Central

Wei, Yu; Li, Jinlong; Qing, Jie; Huang, Mingjie; Wu, Ming; Gao, Fenghua; Li, Dongmei; Hong, Zhangyong; Kong, Lingbao; Huang, Weiqiang; Lin, Jianping

2016-01-01

The NS5B polymerase is one of the most attractive targets for developing new drugs to block Hepatitis C virus (HCV) infection. We describe the discovery of novel potent HCV NS5B polymerase inhibitors by employing a virtual screening (VS) approach, which is based on random forest (RB-VS), e-pharmacophore (PB-VS), and docking (DB-VS) methods. In the RB-VS stage, after feature selection, a model with 16 descriptors was used. In the PB-VS stage, six energy-based pharmacophore (e-pharmacophore) models from different crystal structures of the NS5B polymerase with ligands binding at the palm I, thumb I and thumb II regions were used. In the DB-VS stage, the Glide SP and XP docking protocols with default parameters were employed. In the virtual screening approach, the RB-VS, PB-VS and DB-VS methods were applied in increasing order of complexity to screen the InterBioScreen database. From the final hits, we selected 5 compounds for further anti-HCV activity and cellular cytotoxicity assay. All 5 compounds were found to inhibit NS5B polymerase with IC50 values of 2.01–23.84 μM and displayed anti-HCV activities with EC50 values ranging from 1.61 to 21.88 μM, and all compounds displayed no cellular cytotoxicity (CC50 > 100 μM) except compound N2, which displayed weak cytotoxicity with a CC50 value of 51.3 μM. The hit compound N2 had the best antiviral activity against HCV, with a selective index of 32.1. The 5 hit compounds with new scaffolds could potentially serve as NS5B polymerase inhibitors through further optimization and development. PMID:26845440

Integration of Proteomic, Transcriptional, and Interactome Data Reveals Hidden Signaling Components

PubMed Central

Huang, Shao-shan Carol; Fraenkel, Ernest

2009-01-01

Cellular signaling and regulatory networks underlie fundamental biological processes such as growth, differentiation, and response to the environment. Although there are now various high-throughput methods for studying these processes, knowledge of them remains fragmentary. Typically, the vast majority of hits identified by transcriptional, proteomic, and genetic assays lie outside of the expected pathways. These unexpected components of the cellular response are often the most interesting, because they can provide new insights into biological processes and potentially reveal new therapeutic approaches. However, they are also the most difficult to interpret. We present a technique, based on the Steiner tree problem, that uses previously reported protein-protein and protein-DNA interactions to determine how these hits are organized into functionally coherent pathways, revealing many components of the cellular response that are not readily apparent in the original data. Applied simultaneously to phosphoproteomic and transcriptional data for the yeast pheromone response, it identifies changes in diverse cellular processes that extend far beyond the expected pathways. PMID:19638617

Regulation of cellular senescence by the essential caveolar component PTRF/Cavin-1

PubMed Central

Bai, Lin; Deng, Xiaoli; Li, Juanjuan; Wang, Miao; Li, Qian; An, Wei; A, Deli; Cong, Yu-Sheng

2011-01-01

Polymerase I and transcript release factor (PTRF, also known as Cavin-1) is an essential component in the biogenesis and function of caveolae. Here, we show that PTRF expression is increased in senescent human fibroblasts. Importantly, overexpression of PTRF induced features characteristic of cellular senescence, whereas reduced PTRF expression extended the cellular replicative lifespan. Interestingly, we found that PTRF localized primarily to the nuclei of young and quiescent WI-38 human fibroblasts, but translocated to the cytosol and plasma membrane during cellular senescence. Furthermore, electron microscopic analysis demonstrated an increased number of caveolar structures in senescent and PTRF-transfected WI-38 cells. Our data suggest that the role of PTRF in cellular senescence is dependent on its targeting to caveolae and its interaction with caveolin-1, which appeared to be regulated by the phosphorylation of PTRF. Taken together, our findings identify PTRF as a novel regulator of cellular senescence that acts through the p53/p21 and caveolar pathways. PMID:21445100

Analysis of Students' Aptitude to Provide Meaning to Images that Represent Cellular Components at the Molecular Level

PubMed Central

Dahmani, Hassen-Reda; Schneeberger, Patricia

2009-01-01

The number of experimentally derived structures of cellular components is rapidly expanding, and this phenomenon is accompanied by the development of a new semiotic system for teaching. The infographic approach is shifting from a schematic toward a more realistic representation of cellular components. By realistic we mean artist-prepared or computer graphic images that closely resemble experimentally derived structures and are characterized by a low level of styling and simplification. This change brings about a new challenge for teachers: designing course instructions that allow students to interpret these images in a meaningful way. To determine how students deal with this change, we designed several image-based, in-course assessments. The images were highly relevant for the cell biology course but did not resemble any of the images in the teaching documents. We asked students to label the cellular components, describe their function, or both. What we learned from these tests is that realistic images, with a higher apparent level of complexity, do not deter students from investigating their meaning. When given a choice, the students do not necessarily choose the most simplified representation, and they were sensitive to functional indications embedded in realistic images. PMID:19723817

Implementation and validation of collapsed cone superposition for radiopharmaceutical dosimetry of photon emitters

NASA Astrophysics Data System (ADS)

Sanchez-Garcia, Manuel; Gardin, Isabelle; Lebtahi, Rachida; Dieudonné, Arnaud

2015-10-01

Two collapsed cone (CC) superposition algorithms have been implemented for radiopharmaceutical dosimetry of photon emitters. The straight CC (SCC) superposition method uses a water energy deposition kernel (EDKw) for each electron, positron and photon components, while the primary and scatter CC (PSCC) superposition method uses different EDKw for primary and once-scattered photons. PSCC was implemented only for photons originating from the nucleus, precluding its application to positron emitters. EDKw are linearly scaled by radiological distance, taking into account tissue density heterogeneities. The implementation was tested on 100, 300 and 600 keV mono-energetic photons and 18F, 99mTc, 131I and 177Lu. The kernels were generated using the Monte Carlo codes MCNP and EGSnrc. The validation was performed on 6 phantoms representing interfaces between soft-tissues, lung and bone. The figures of merit were γ (3%, 3 mm) and γ (5%, 5 mm) criterions corresponding to the computation comparison on 80 absorbed doses (AD) points per phantom between Monte Carlo simulations and CC algorithms. PSCC gave better results than SCC for the lowest photon energy (100 keV). For the 3 isotopes computed with PSCC, the percentage of AD points satisfying the γ (5%, 5 mm) criterion was always over 99%. A still good but worse result was found with SCC, since at least 97% of AD-values verified the γ (5%, 5 mm) criterion, except a value of 57% for the 99mTc with the lung/bone interface. The CC superposition method for radiopharmaceutical dosimetry is a good alternative to Monte Carlo simulations while reducing computation complexity.

Implementation and validation of collapsed cone superposition for radiopharmaceutical dosimetry of photon emitters.

PubMed

Sanchez-Garcia, Manuel; Gardin, Isabelle; Lebtahi, Rachida; Dieudonné, Arnaud

2015-10-21

Two collapsed cone (CC) superposition algorithms have been implemented for radiopharmaceutical dosimetry of photon emitters. The straight CC (SCC) superposition method uses a water energy deposition kernel (EDKw) for each electron, positron and photon components, while the primary and scatter CC (PSCC) superposition method uses different EDKw for primary and once-scattered photons. PSCC was implemented only for photons originating from the nucleus, precluding its application to positron emitters. EDKw are linearly scaled by radiological distance, taking into account tissue density heterogeneities. The implementation was tested on 100, 300 and 600 keV mono-energetic photons and (18)F, (99m)Tc, (131)I and (177)Lu. The kernels were generated using the Monte Carlo codes MCNP and EGSnrc. The validation was performed on 6 phantoms representing interfaces between soft-tissues, lung and bone. The figures of merit were γ (3%, 3 mm) and γ (5%, 5 mm) criterions corresponding to the computation comparison on 80 absorbed doses (AD) points per phantom between Monte Carlo simulations and CC algorithms. PSCC gave better results than SCC for the lowest photon energy (100 keV). For the 3 isotopes computed with PSCC, the percentage of AD points satisfying the γ (5%, 5 mm) criterion was always over 99%. A still good but worse result was found with SCC, since at least 97% of AD-values verified the γ (5%, 5 mm) criterion, except a value of 57% for the (99m)Tc with the lung/bone interface. The CC superposition method for radiopharmaceutical dosimetry is a good alternative to Monte Carlo simulations while reducing computation complexity.

Electron correlation in the interacting quantum atoms partition via coupled-cluster lagrangian densities.

PubMed

Holguín-Gallego, Fernando José; Chávez-Calvillo, Rodrigo; García-Revilla, Marco; Francisco, Evelio; Pendás, Ángel Martín; Rocha-Rinza, Tomás

2016-07-15

The electronic energy partition established by the Interacting Quantum Atoms (IQA) approach is an important method of wavefunction analyses which has yielded valuable insights about different phenomena in physical chemistry. Most of the IQA applications have relied upon approximations, which do not include either dynamical correlation (DC) such as Hartree-Fock (HF) or external DC like CASSCF theory. Recently, DC was included in the IQA method by means of HF/Coupled-Cluster (CC) transition densities (Chávez-Calvillo et al., Comput. Theory Chem. 2015, 1053, 90). Despite the potential utility of this approach, it has a few drawbacks, for example, it is not consistent with the calculation of CC properties different from the total electronic energy. To improve this situation, we have implemented the IQA energy partition based on CC Lagrangian one- and two-electron orbital density matrices. The development presented in this article is tested and illustrated with the H2 , LiH, H2 O, H2 S, N2 , and CO molecules for which the IQA results obtained under the consideration of (i) the CC Lagrangian, (ii) HF/CC transition densities, and (iii) HF are critically analyzed and compared. Additionally, the effect of the DC in the different components of the electronic energy in the formation of the T-shaped (H2 )2 van der Waals cluster and the bimolecular nucleophilic substitution between F(-) and CH3 F is examined. We anticipate that the approach put forward in this article will provide new understandings on subjects in physical chemistry wherein DC plays a crucial role like molecular interactions along with chemical bonding and reactivity. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Reproducibility of data-driven dietary patterns in two groups of adult Spanish women from different studies.

PubMed

Castelló, Adela; Lope, Virginia; Vioque, Jesús; Santamariña, Carmen; Pedraz-Pingarrón, Carmen; Abad, Soledad; Ederra, Maria; Salas-Trejo, Dolores; Vidal, Carmen; Sánchez-Contador, Carmen; Aragonés, Nuria; Pérez-Gómez, Beatriz; Pollán, Marina

2016-08-01

The objective of the present study was to assess the reproducibility of data-driven dietary patterns in different samples extracted from similar populations. Dietary patterns were extracted by applying principal component analyses to the dietary information collected from a sample of 3550 women recruited from seven screening centres belonging to the Spanish breast cancer (BC) screening network (Determinants of Mammographic Density in Spain (DDM-Spain) study). The resulting patterns were compared with three dietary patterns obtained from a previous Spanish case-control study on female BC (Epidemiological study of the Spanish group for breast cancer research (GEICAM: grupo Español de investigación en cáncer de mama)) using the dietary intake data of 973 healthy participants. The level of agreement between patterns was determined using both the congruence coefficient (CC) between the pattern loadings (considering patterns with a CC≥0·85 as fairly similar) and the linear correlation between patterns scores (considering as fairly similar those patterns with a statistically significant correlation). The conclusions reached with both methods were compared. This is the first study exploring the reproducibility of data-driven patterns from two studies and the first using the CC to determine pattern similarity. We were able to reproduce the EpiGEICAM Western pattern in the DDM-Spain sample (CC=0·90). However, the reproducibility of the Prudent (CC=0·76) and Mediterranean (CC=0·77) patterns was not as good. The linear correlation between pattern scores was statistically significant in all cases, highlighting its arbitrariness for determining pattern similarity. We conclude that the reproducibility of widely prevalent dietary patterns is better than the reproducibility of more population-specific patterns. More methodological studies are needed to establish an objective measurement and threshold to determine pattern similarity.

Profiling planktonic biomass using element-specific, multicomponent nuclear magnetic resonance spectroscopy.

PubMed

Komatsu, Takanori; Kobayashi, Toshiya; Hatanaka, Minoru; Kikuchi, Jun

2015-06-02

Planktonic metabolism plays crucial roles in Earth's elemental cycles. Chemical speciation as well as elemental stoichiometry is important for advancing our understanding of planktonic roles in biogeochemical cycles. In this study, a multicomponent solid-state nuclear magnetic resonance (NMR) approach is proposed for chemical speciation of cellular components, using several advanced NMR techniques. Measurements by ssNMR were performed on (13)C and (15)N-labeled Euglena gracilis, a flagellated protist. 3D dipolar-assisted rotational resonance, double-cross-polarization (1)H-(13)C correlation spectroscopy, and (1)H-(13)C solid-state heteronuclear single quantum correlation spectroscopy successively allowed characterization of cellular components. These techniques were then applied to E. gracilis cultured in high and low ammonium media to demonstrate the power of this method for profiling and comparing cellular components. Cellular NMR spectra indicated that ammonium induced both paramylon degradation and amination. Arginine was stored as a nitrogen reserve and ammonium replaced by arginine catabolism via the arginine dihydrolase pathway. (15)N and (31)P cellular ssNMR indicated arginine and polyphosphate accumulation in E. gracilis, respectively. This chemical speciation technique will contribute to environmental research by providing detailed information on environmental chemical properties.

Role of atypical chemokine receptor ACKR2 in experimental oral squamous cell carcinogenesis.

PubMed

da Silva, Janine Mayra; Dos Santos, Tálita Pollyanna Moreira; Saraiva, Adriana Machado; Fernandes de Oliveira, Ana Laura; Garlet, Gustavo Pompermaier; Batista, Aline Carvalho; de Mesquita, Ricardo Alves; Russo, Remo Castro; da Silva, Tarcília Aparecida

2018-03-14

Chemokines and chemokine receptors are critical in oral tumourigenesis. The atypical chemokine receptor ACKR2 is a scavenger of CC chemokines controlling the availability of these molecules at tumour sites, but the role of ACKR2 in the context of oral carcinogenesis is unexplored. In this study, wild-type (WT) and ACKR2 deficient mice (ACKR2 -/- ) were treated with chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) for induction of oral carcinogenesis. Tongues were collected for macro and microscopic analysis and to evaluate the expression of ACKRs, CC chemokines and its receptors, inflammatory cytokines, angiogenic factors, adhesion molecules and extracellular matrix components. An increased expression of ACKR2 in squamous cell carcinoma (SCC) lesions of 4NQO-treated WT mice was observed. No significant differences were seen in the ACKR1, ACKR3 and ACKR4 mRNA expression comparing SCC lesions from WT and ACKR2 -/- treated mice. Significantly higher expression of CCL2, IL-6 and IL-17 was detected in ACKR2 -/- treated mice. In contrast, the expression of other CC-chemokines, and receptors, angiogenic factors, adhesion molecules and extracellular matrix components were similarly increased in SCC lesions of both groups. Clinical and histopathological analysis revealed no differences in inflammatory cell recruitment and in the SCC incidence comparing WT and ACKR2 -/- treated mice. The results suggest that ACKR2 expression regulates inflammation in tumour-microenvironment but the absence of ACKR2 does not impact chemically-induced oral carcinogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Regulation of alternative splicing at the single-cell level.

PubMed

Faigenbloom, Lior; Rubinstein, Nimrod D; Kloog, Yoel; Mayrose, Itay; Pupko, Tal; Stein, Reuven

2015-12-28

Alternative splicing is a key cellular mechanism for generating distinct isoforms, whose relative abundances regulate critical cellular processes. It is therefore essential that inclusion levels of alternative exons be tightly regulated. However, how the precision of inclusion levels among individual cells is governed is poorly understood. Using single-cell gene expression, we show that the precision of inclusion levels of alternative exons is determined by the degree of evolutionary conservation at their flanking intronic regions. Moreover, the inclusion levels of alternative exons, as well as the expression levels of the transcripts harboring them, also contribute to this precision. We further show that alternative exons whose inclusion levels are considerably changed during stem cell differentiation are also subject to this regulation. Our results imply that alternative splicing is coordinately regulated to achieve accuracy in relative isoform abundances and that such accuracy may be important in determining cell fate. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

Changes in the topography of cellular components in pea root statocytes exposed to high gradient magnetic fields

NASA Astrophysics Data System (ADS)

Belyavskaya, Ninel A.; Polishchuk, Olexandr V.; Kondrachuk, Alexander V.

2005-08-01

High-gradient magnetic field (HGMF) is one of methods, by which gravitropism in plants is studied. The aim of our study was elucidation of HGMF effects on topography of cellular components in root statocytes of 4- day Pisum sativum L. seedlings in comparison to gravistimulation. Under gravistimulation during 5, 30 and 60 min seedlings were rotated 45o; magnetostimulation was carried out along gap between two NdFeB magnets (0.7 T). Morphometric measurements were made from images of whole statocytes, for upper, middle and lower thirds of cells, and proximal and distal halves of cells. Morphometric analysis revealed that HGMF resulted in the redistribution of all cellular components in statocytes. The correlation in the amyloplast distribution between gravistimulation and magnetostimulation was established.

Mesoporous carbons and polymers

DOEpatents

Bell, William; Dietz, Steven

2004-05-18

A polymer is prepared by polymerizing a polymerizable component from a mixture containing the polymerizable component and a surfactant, the surfactant and the polymerizable component being present in the mixture in a molar ratio of at least 0.2:1, having an average pore size greater than 4 nm and a density greater than 0.1 g/cc. The polymerizable component can comprise a resorcinol/formaldehyde system and the mixture can comprise an aqueous solution or the polymerizable component can comprise a divinylbenzene/styrene system and the mixture can comprise an organic solution. Alternatively, the polymerizable component can comprise vinylidene chloride or a vinylidene chloride/divinylbenzene system. The polymer may be monolithic, have a BET surface area of at least about 50 m.sup.2 /g., include a quantity of at least one metal powder, or have an electrical conductivity greater than 10 Scm.sup.-1.

Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI

PubMed Central

Zhang, Yue; Udayakumar, Durga; Cai, Ling; Hu, Zeping; Kapur, Payal; Kho, Eun-Young; Pavía-Jiménez, Andrea; Fulkerson, Michael; de Leon, Alberto Diaz; Yuan, Qing; Dimitrov, Ivan E.; Ye, Jin; Mitsche, Matthew A.; Kim, Hyeonwoo; McDonald, Jeffrey G.; Madhuranthakam, Ananth J.; Dwivedi, Durgesh K.; Lenkinski, Robert E.; Cadeddu, Jeffrey A.; Margulis, Vitaly; Brugarolas, James; DeBerardinis, Ralph J.

2017-01-01

BACKGROUND. Dysregulated lipid and glucose metabolism in clear cell renal cell carcinoma (ccRCC) has been implicated in disease progression, and whole tumor tissue–based assessment of these changes is challenged by the tumor heterogeneity. We studied a noninvasive quantitative MRI method that predicts metabolic alterations in the whole tumor. METHODS. We applied Dixon-based MRI for in vivo quantification of lipid accumulation (fat fraction [FF]) in targeted regions of interest of 45 primary ccRCCs and correlated these MRI measures to mass spectrometry–based lipidomics and metabolomics of anatomically colocalized tissue samples isolated from the same tumor after surgery. RESULTS. In vivo tumor FF showed statistically significant (P < 0.0001) positive correlation with histologic fat content (Spearman correlation coefficient, ρ = 0.79), spectrometric triglycerides (ρ = 0.56) and cholesterol (ρ = 0.47); it showed negative correlation with free fatty acids (ρ = –0.44) and phospholipids (ρ = –0.65). We observed both inter- and intratumoral heterogeneity in lipid accumulation within the same tumor grade, whereas most aggressive tumors (International Society of Urological Pathology [ISUP] grade 4) exhibited reduced lipid accumulation. Cellular metabolites in tumors were altered compared with adjacent renal parenchyma. CONCLUSION. Our results support the use of noninvasive quantitative Dixon-based MRI as a biomarker of reprogrammed lipid metabolism in ccRCC, which may serve as a predictor of tumor aggressiveness before surgical intervention. FUNDING. NIH R01CA154475 (YZ, MF, PK, IP), NIH P50CA196516 (IP, JB, RJD, JAC, PK), Welch Foundation I-1832 (JY), and NIH P01HL020948 (JGM). PMID:28768909

Instabilities in rapid solidification of multi-component alloys

NASA Astrophysics Data System (ADS)

Altieri, Anthony L.; Davis, Stephen H.

2017-10-01

Rapid solidification of multi-component liquids occurs in many modern applications such as additive manufacturing. In the present work the interface departures from equilibrium consist of the segregation coefficient and liquidus slope depending on front speed, the one-sided, frozen-temperature approximation, and the alloy behaving as the superposition of individual components. Linear-stability theory is applied, showing that the cellular and oscillatory instabilities of the binary case are modified. The addition of components tends to destabilize the interface while the addition of a single large-diffusivity material can entirely suppress the oscillatory mode. Multiple minima in the neutral curve for the cellular mode occur.

ERCC2/XPD Lys751Gln alter DNA repair efficiency of platinum-induced DNA damage through P53 pathway.

PubMed

Zhang, Guopei; Guan, Yangyang; Zhao, Yuejiao; van der Straaten, Tahar; Xiao, Sha; Xue, Ping; Zhu, Guolian; Liu, Qiufang; Cai, Yuan; Jin, Cuihong; Yang, Jinghua; Wu, Shengwen; Lu, Xiaobo

2017-02-01

Platinum-based treatment causes Pt-DNA adducts which lead to cell death. The platinum-induced DNA damage is recognized and repaired by the nucleotide excision repair (NER) system of which ERCC2/XPD is a critical enzyme. Single nucleotide polymorphisms in ERCC2/XPD have been found to be associated with platinum resistance. The aim of the present study was to investigate whether ERCC2/XPD Lys751Gln (rs13181) polymorphism is causally related to DNA repair capacity of platinum-induced DNA damage. First, cDNA clones expressing different genotypes of the polymorphism was transfected to an ERCC2/XPD defective CHO cell line (UV5). Second, all cells were treated with cisplatin. Cellular survival rate were investigated by MTT growth inhibition assay, DNA damage levels were investigated by comet assay and RAD51 staining. The distribution of cell cycle and the change of apoptosis rates were detected by a flow cytometric method (FCM). Finally, P53mRNA and phospho-P53 protein levels were further investigated in order to explore a possible explanation. As expected, there was a significantly increased in viability of UV5 ERCC2 (AA) as compared to UV5 ERCC2 (CC) after cisplatin treatment. The DNA damage level of UV5 ERCC2 (AA) was significant decreased compared to UV5 ERCC2 (CC) at 24 h of treatment. Mutation of ERCC2rs13181 AA to CC causes a prolonged S phase in cell cycle. UV5 ERCC2 (AA) alleviated the apoptosis compared to UV5 ERCC2 (CC) , meanwhile P53mRNA levels in UV ERCC2 (AA) was also lower when compared UV5 ERCC2 (CC) . It co-incides with a prolonged high expression of phospho-P53, which is relevant for cell cycle regulation, apoptosis, and the DNA damage response (DDR). We concluded that ERCC2/XPD rs13181 polymorphism is possibly related to the DNA repair capacity of platinum-induced DNA damage. This functional study provides some clues to clarify the relationship between cisplatin resistance and ERCC2/XPDrs13181 polymorphism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

PhosphoregDB: The tissue and sub-cellular distribution of mammalian protein kinases and phosphatases

PubMed Central

Forrest, Alistair RR; Taylor, Darrin F; Fink, J Lynn; Gongora, M Milena; Flegg, Cameron; Teasdale, Rohan D; Suzuki, Harukazu; Kanamori, Mutsumi; Kai, Chikatoshi; Hayashizaki, Yoshihide; Grimmond, Sean M

2006-01-01

Background Protein kinases and protein phosphatases are the fundamental components of phosphorylation dependent protein regulatory systems. We have created a database for the protein kinase-like and phosphatase-like loci of mouse that integrates protein sequence, interaction, classification and pathway information with the results of a systematic screen of their sub-cellular localization and tissue specific expression data mined from the GNF tissue atlas of mouse. Results The database lets users query where a specific kinase or phosphatase is expressed at both the tissue and sub-cellular levels. Similarly the interface allows the user to query by tissue, pathway or sub-cellular localization, to reveal which components are co-expressed or co-localized. A review of their expression reveals 30% of these components are detected in all tissues tested while 70% show some level of tissue restriction. Hierarchical clustering of the expression data reveals that expression of these genes can be used to separate the samples into tissues of related lineage, including 3 larger clusters of nervous tissue, developing embryo and cells of the immune system. By overlaying the expression, sub-cellular localization and classification data we examine correlations between class, specificity and tissue restriction and show that tyrosine kinases are more generally expressed in fewer tissues than serine/threonine kinases. Conclusion Together these data demonstrate that cell type specific systems exist to regulate protein phosphorylation and that for accurate modelling and for determination of enzyme substrate relationships the co-location of components needs to be considered. PMID:16504016

An ICA-based method for the identification of optimal FMRI features and components using combined group-discriminative techniques

PubMed Central

Sui, Jing; Adali, Tülay; Pearlson, Godfrey D.; Calhoun, Vince D.

2013-01-01

Extraction of relevant features from multitask functional MRI (fMRI) data in order to identify potential biomarkers for disease, is an attractive goal. In this paper, we introduce a novel feature-based framework, which is sensitive and accurate in detecting group differences (e.g. controls vs. patients) by proposing three key ideas. First, we integrate two goal-directed techniques: coefficient-constrained independent component analysis (CC-ICA) and principal component analysis with reference (PCA-R), both of which improve sensitivity to group differences. Secondly, an automated artifact-removal method is developed for selecting components of interest derived from CC-ICA, with an average accuracy of 91%. Finally, we propose a strategy for optimal feature/component selection, aiming to identify optimal group-discriminative brain networks as well as the tasks within which these circuits are engaged. The group-discriminating performance is evaluated on 15 fMRI feature combinations (5 single features and 10 joint features) collected from 28 healthy control subjects and 25 schizophrenia patients. Results show that a feature from a sensorimotor task and a joint feature from a Sternberg working memory (probe) task and an auditory oddball (target) task are the top two feature combinations distinguishing groups. We identified three optimal features that best separate patients from controls, including brain networks consisting of temporal lobe, default mode and occipital lobe circuits, which when grouped together provide improved capability in classifying group membership. The proposed framework provides a general approach for selecting optimal brain networks which may serve as potential biomarkers of several brain diseases and thus has wide applicability in the neuroimaging research community. PMID:19457398

Two overlapping domains of a lyssavirus matrix protein that acts on different cell death pathways.

PubMed

Larrous, Florence; Gholami, Alireza; Mouhamad, Shahul; Estaquier, Jérôme; Bourhy, Hervé

2010-10-01

The lyssavirus matrix (M) protein induces apoptosis. The regions of the M protein that are essential for triggering cell death pathways are not yet clearly defined. We therefore compared the M proteins from two viruses that have contrasting characteristics in terms of cellular apoptosis: a genotype 3 lyssavirus, Mokola virus (MOK), and a genotype 1 rabies virus isolated from a dog from Thailand (THA). We identified a 20-amino-acid fragment (corresponding to positions 67 to 86) that retained the cell death activities of the full-length M protein from MOK via both the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and inhibition of cytochrome c oxidase (CcO) activity. We found that the amino acids at positions 77 and 81 have an essential role in triggering these two cell death pathways. Directed mutagenesis demonstrated that the amino acid at position 77 affects CcO activity, whereas the amino acid at position 81 affects TRAIL-dependent apoptosis. Mutations in the full-length M protein that compromised induction of either of these two pathways resulted in delayed apoptosis compared with the time to apoptosis for the nonmutated control.

Two Overlapping Domains of a Lyssavirus Matrix Protein That Acts on Different Cell Death Pathways ▿

PubMed Central

Larrous, Florence; Gholami, Alireza; Mouhamad, Shahul; Estaquier, Jérôme; Bourhy, Hervé

2010-01-01

The lyssavirus matrix (M) protein induces apoptosis. The regions of the M protein that are essential for triggering cell death pathways are not yet clearly defined. We therefore compared the M proteins from two viruses that have contrasting characteristics in terms of cellular apoptosis: a genotype 3 lyssavirus, Mokola virus (MOK), and a genotype 1 rabies virus isolated from a dog from Thailand (THA). We identified a 20-amino-acid fragment (corresponding to positions 67 to 86) that retained the cell death activities of the full-length M protein from MOK via both the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and inhibition of cytochrome c oxidase (CcO) activity. We found that the amino acids at positions 77 and 81 have an essential role in triggering these two cell death pathways. Directed mutagenesis demonstrated that the amino acid at position 77 affects CcO activity, whereas the amino acid at position 81 affects TRAIL-dependent apoptosis. Mutations in the full-length M protein that compromised induction of either of these two pathways resulted in delayed apoptosis compared with the time to apoptosis for the nonmutated control. PMID:20631119

A Single Nucleotide Polymorphism in the Phospholipase D1 Gene is Associated with Risk of Non-Small Cell Lung Cancer

PubMed Central

Ahn, Myung-Ju; Park, Shin-Young; Kim, Won Kyu; Cho, Ju Hwan; Chang, Brian Junho; Kim, Dong Jo; Ahn, Jin Seok; Park, Keunchil; Han, Joong-Soo

2012-01-01

Phospholipase D (PLD) has an important role in various biological functions including vesicular transport, endocytosis, exocytosis, cell migration, and mitosis. These cellular biological processes are deregulated in the development of various human tumors. In order to explore the relationship between the PLD1 gene and risk of non-small cell lung cancer (NSCLC), single nucleotide polymorphisms (SNP) in the PLD1 exon region were surveyed in 211 NSCLC patients and 205 normal controls. In this study, we identified six SNPs at exon 23 in the PLD1 gene. Among the six SNPs, the most notable was a heterozygous A to C transition at nucleotide 2698 (A2698C, p<0.001). In addition, the genotype frequencies of A2744C (AC+CC) and A2756C (AC+CC) were associated with gender (female, A2744C and A2756C: p=0.071) in NSCLC patients. Interestingly, although the SNP A2698C did not cause change in amino acid, correlation between odd ratio of NSCLC patients and the SNP A2698C was observed to be statistically significant. PMID:23675264

The origin of the two-electron/four-centers C--C bond in pi-TCNE(2)2- dimers: electrostatic or dispersion?

PubMed

García-Yoldi, Iñigo; Mota, Fernando; Novoa, Juan J

2007-01-15

The structure and stability of the pi-TCNE(2)2- dimers in K2TCNE2 aggregates is revisited trying to find if the origin of their two-electron/four-centers C--C bond are the electrostatic K+-TCNE- interactions or the dispersion interactions between the anions. The study is done at the HF, B3LYP, CASSCF (2,2), and MCQDPT/CASSCF (2,2) levels using the 6-31+G(d) basis set. Our results show that the only minima of this aggregate that preserves the pi-TCNE(2)2- structure has the two K+ atoms placed in equatorial positions in between the two TCNE- planes. When the K+ atoms are placed along the D2h axis of the anions the structure is not a minimum. The main energetic component responsible for the stability of these aggregates comes from the cation-anion interactions. However, a proper accounting of the dispersion component (as done in the MCQDPT/CASSCF (2,2) calculations) is needed to make the closed-shell singlet more stable than the open-shell singlet. Thus, the bond results from the combination of the electrostatic and dispersion components, being the first the dominant one. The optimum geometry of the closed-shell singlet is very similar to the experimental one found in crystals. Copyright (c) 2006 Wiley Periodicals, Inc.

Electrophysiological Evidence for a Sensory Recruitment Model of Somatosensory Working Memory.

PubMed

Katus, Tobias; Grubert, Anna; Eimer, Martin

2015-12-01

Sensory recruitment models of working memory assume that information storage is mediated by the same cortical areas that are responsible for the perceptual processing of sensory signals. To test this assumption, we measured somatosensory event-related brain potentials (ERPs) during a tactile delayed match-to-sample task. Participants memorized a tactile sample set at one task-relevant hand to compare it with a subsequent test set on the same hand. During the retention period, a sustained negativity (tactile contralateral delay activity, tCDA) was elicited over primary somatosensory cortex contralateral to the relevant hand. The amplitude of this component increased with memory load and was sensitive to individual limitations in memory capacity, suggesting that the tCDA reflects the maintenance of tactile information in somatosensory working memory. The tCDA was preceded by a transient negativity (N2cc component) with a similar contralateral scalp distribution, which is likely to reflect selection of task-relevant tactile stimuli at the encoding stage. The temporal sequence of N2cc and tCDA components mirrors previous observations from ERP studies of working memory in vision. The finding that the sustained somatosensory delay period activity varies as a function of memory load supports a sensory recruitment model for spatial working memory in touch. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Formalizing Knowledge in Multi-Scale Agent-Based Simulations

PubMed Central

Somogyi, Endre; Sluka, James P.; Glazier, James A.

2017-01-01

Multi-scale, agent-based simulations of cellular and tissue biology are increasingly common. These simulations combine and integrate a range of components from different domains. Simulations continuously create, destroy and reorganize constituent elements causing their interactions to dynamically change. For example, the multi-cellular tissue development process coordinates molecular, cellular and tissue scale objects with biochemical, biomechanical, spatial and behavioral processes to form a dynamic network. Different domain specific languages can describe these components in isolation, but cannot describe their interactions. No current programming language is designed to represent in human readable and reusable form the domain specific knowledge contained in these components and interactions. We present a new hybrid programming language paradigm that naturally expresses the complex multi-scale objects and dynamic interactions in a unified way and allows domain knowledge to be captured, searched, formalized, extracted and reused. PMID:29338063

Formalizing Knowledge in Multi-Scale Agent-Based Simulations.

PubMed

Somogyi, Endre; Sluka, James P; Glazier, James A

2016-10-01

Multi-scale, agent-based simulations of cellular and tissue biology are increasingly common. These simulations combine and integrate a range of components from different domains. Simulations continuously create, destroy and reorganize constituent elements causing their interactions to dynamically change. For example, the multi-cellular tissue development process coordinates molecular, cellular and tissue scale objects with biochemical, biomechanical, spatial and behavioral processes to form a dynamic network. Different domain specific languages can describe these components in isolation, but cannot describe their interactions. No current programming language is designed to represent in human readable and reusable form the domain specific knowledge contained in these components and interactions. We present a new hybrid programming language paradigm that naturally expresses the complex multi-scale objects and dynamic interactions in a unified way and allows domain knowledge to be captured, searched, formalized, extracted and reused.

Microwave-assisted cationic polymerization of palm olein and their urea inclusion products

NASA Astrophysics Data System (ADS)

Soegijono, Bambang; Farid, Muhamad; Alim Mas'ud, Zainal

2018-01-01

Cationic polymerization is affected by the relative amount of unsaturated bond (C=C) in the compound. The enrichment of an unsaturated triglyceride fraction from oils may be performed using urea inclusion techniques. In this study, palm olein was enriched-unsaturated fraction using urea-methanol system. The palm olein and its urea-inclusion products were cationic polymerized with ethereal boron trifluoride catalyst and followed by irradiation using a commercial microwave (microwave-assisted). The microwave irradiated products were cured at 110 °C for 24 hours. Fatty acid composition of the palm olein and its urea-inclusion products were analyzed by gas chromatography. Iodine numbers, functional groups, and ultraviolet absorption spectra of all palm olein origin, urea inclusion products and polymerization products were analyzed using titrimetric, ultraviolet spectrophotometric, and Fourier Transform infrared spectrophotometric methods. Differential scanning calorimetric (DSC) was used to observe the thermal characteristics of the polymer. Urea-inclusion process increased the unsaturated fatty acid components as indicated by the increased iodine number, intensity of alkene band absorptions in the infrared spectra, and the absorbance of the ultraviolet spectra. The polymer formation is converting the C=C group to C-C, which is indicated by the opposite of the urea inclusion process. The curing process results in reformation of new C=C bonds that were similar to that of the urea inclusion process. The DSC thermogram curve shows that the enrichment process improves the thermal stability of the polymer formed.

Autophagy mediates HIF2α degradation and suppresses renal tumorigenesis

PubMed Central

Liu, Xian-De; Yao, Jun; Tripathi, Durga Nand; Ding, Zhiyong; Xu, Yi; Sun, Mianen; Zhang, Jiangwei; Bai, Shanshan; German, Peter; Hoang, Anh; Zhou, Lijun; Jonasch, Darius; Zhang, Xuesong; Conti, Claudio J.; Efstathiou, Eleni; Tannir, Nizar M; Eissa, N. Tony; Mills, Gordon B.; Walker, Cheryl Lyn; Jonasch, Eric

2014-01-01

Autophagy is a conserved process involved in lysosomal degradation of protein aggregates and damaged organelles. The role of autophagy in cancer is a topic of intense debate, and the underlying mechanism is still not clear. The hypoxia inducible factor 2α (HIF2α), an oncogenic transcription factor implicated in renal tumorigenesis, is known to be degraded by the ubiquitin-proteasome system (UPS). Here we report that HIF2α is in part constitutively degraded by autophagy. HIF2α interacts with autophagy-lysosome system components. Inhibition of autophagy increases HIF2α, while induction of autophagy decreases HIF2α. The E3 ligase von Hippel Lindau (VHL) and autophagy receptor protein p62 are required for autophagic degradation of HIF2α. There is a compensatory interaction between the UPS and autophagy in HIF2α degradation. Autophagy inactivation redirects HIF2α to proteasomal degradation, while proteasome inhibition induces autophagy and increases the HIF2α-p62 interaction. Importantly, clear cell renal cell carcinoma (ccRCC) is frequently associated with mono-allelic loss and/or mutation of autophagy related gene ATG7, and low expression level of autophagy genes correlates with ccRCC progression. The protein levels of ATG7 and beclin 1 are also reduced in ccRCC tumors. This study indicates that autophagy plays an anticancer role in ccRCC tumorigenesis, and suggests that constitutive autophagic degradation of HIF2α is a novel tumor suppression mechanism. PMID:24998849

Gaussian basis sets for use in correlated molecular calculations. XI. Pseudopotential-based and all-electron relativistic basis sets for alkali metal (K-Fr) and alkaline earth (Ca-Ra) elements

NASA Astrophysics Data System (ADS)

Hill, J. Grant; Peterson, Kirk A.

2017-12-01

New correlation consistent basis sets based on pseudopotential (PP) Hamiltonians have been developed from double- to quintuple-zeta quality for the late alkali (K-Fr) and alkaline earth (Ca-Ra) metals. These are accompanied by new all-electron basis sets of double- to quadruple-zeta quality that have been contracted for use with both Douglas-Kroll-Hess (DKH) and eXact 2-Component (X2C) scalar relativistic Hamiltonians. Sets for valence correlation (ms), cc-pVnZ-PP and cc-pVnZ-(DK,DK3/X2C), in addition to outer-core correlation [valence + (m-1)sp], cc-p(w)CVnZ-PP and cc-pwCVnZ-(DK,DK3/X2C), are reported. The -PP sets have been developed for use with small-core PPs [I. S. Lim et al., J. Chem. Phys. 122, 104103 (2005) and I. S. Lim et al., J. Chem. Phys. 124, 034107 (2006)], while the all-electron sets utilized second-order DKH Hamiltonians for 4s and 5s elements and third-order DKH for 6s and 7s. The accuracy of the basis sets is assessed through benchmark calculations at the coupled-cluster level of theory for both atomic and molecular properties. Not surprisingly, it is found that outer-core correlation is vital for accurate calculation of the thermodynamic and spectroscopic properties of diatomic molecules containing these elements.

Cellular structures with interconnected microchannels

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

Shaefer, Robert Shahram; Ghoniem, Nasr M.; Williams, Brian

A method for fabricating a cellular tritium breeder component includes obtaining a reticulated carbon foam skeleton comprising a network of interconnected ligaments. The foam skeleton is then melt-infiltrated with a tritium breeder material, for example, lithium zirconate or lithium titanate. The foam skeleton is then removed to define a cellular breeder component having a network of interconnected tritium purge channels. In an embodiment the ligaments of the foam skeleton are enlarged by adding carbon using chemical vapor infiltration (CVI) prior to melt-infiltration. In an embodiment the foam skeleton is coated with a refractory material, for example, tungsten, prior to meltmore » infiltration.« less

Cellular fatty acids and aldehydes of oral Eubacterium.

PubMed

Itoh, U; Sato, M; Tsuchiya, H; Namikawa, I

1995-02-01

The cellular fatty acids and aldehydes of oral Eubacterium species were determined by gas chromatography-mass spectrometry. E. brachy and E. lentum contained mainly branched-chain fatty acids, whereas the others contained straight-chain acids. E. brachy, E. lentum, E. yurii ssp. yurii, E. yurii spp. margaretiae, E. limosum, E. plauti and E. aerofaciens also contained aldehydes with even carbon numbers. In addition to species-specific components, the compositional ratios of fatty acids and aldehydes characterized each individual species. The 10 species tested were divided into 5 groups by the principal component analysis. Cellular fatty acids and aldehydes would be chemical markers for interspecies differentiation of oral Eubacterium.

Development and validation of the Medical Home Care Coordination Survey for assessing care coordination in the primary care setting from the patient and provider perspectives.

PubMed

Zlateva, Ianita; Anderson, Daren; Coman, Emil; Khatri, Khushbu; Tian, Terrence; Fifield, Judith

2015-06-07

Community health centers are increasingly embracing the Patient Centered Medical Home (PCMH) model to improve quality, access to care, and patient experience while reducing healthcare costs. Care coordination (CC) is an important element of the PCMH model, but implementation and measurability of CC remains a problem within the outpatient setting. Assessing CC is an integral component of quality monitoring in health care systems. This study developed and validated the Medical Home Care Coordination Survey (MHCCS), to fill the gap in assessing CC in primary care from the perspectives of patients and their primary healthcare teams. We conducted a review of relevant literature and existing care coordination instruments identified by bibliographic search and contact with experts. After identifying all care coordination domains that could be assessed by primary healthcare team members and patients, we developed a conceptual model. Potentially appropriate items from existing published CC measures, along with newly developed items, were matched to each domain for inclusion. A modified Delphi approach was used to establish content validity. Primary survey data was collected from 232 patients with care transition and/or complex chronic illness needs from the Community Health Center, Inc. and from 164 staff members from 12 community health centers across the country via mail, phone and online survey. The MHCCS was validated for internal consistency, reliability, discriminant and convergent validity. This study was conducted at the Community Health Center, Inc. from January 15, 2012 to July 15, 2014. The 13-item MHCCS - Patient and the 32-item MHCCS - Healthcare Team were developed and validated. Exploratory Structural Equation Modeling was used to test the hypothesized domain structure. Four CC domains were confirmed from the patient group and eight were confirmed from the primary healthcare team group. All domains had high reliability (Cronbach's α scores were above 0.8). Patients experience the ultimate output of care coordination services, but primary healthcare staff members are best primed to perceive many of the structural elements of care coordination. The proactive measurement and monitoring of the core domains from both perspectives provides a richer body of information for the continuous improvement of care coordination services. The MHCCS shows promise as a valid and reliable assessment of these CC efforts.

Loss-of-function of the ciliopathy protein Cc2d2a disorganizes the vesicle fusion machinery at the periciliary membrane and indirectly affects Rab8-trafficking in zebrafish photoreceptors

PubMed Central

Gesemann, Matthias; Mateos, José M.; Barmettler, Gery; Forbes, Austin; Ziegler, Urs

2017-01-01

Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors. The link between the TZ and upstream vesicle trafficking has been little explored to date. Moreover, the role of the small GTPase Rab8 in opsin-carrier vesicle (OCV) trafficking has been recently questioned in a mouse model. Using correlative light and electron microscopy and live imaging in zebrafish photoreceptors, we provide the first live characterization of Rab8-mediated trafficking in photoreceptors in vivo. Our results support a possibly redundant role for both Rab8a/b paralogs in OCV trafficking, based on co-localization of Rab8 and opsins in vesicular structures, and joint movement of Rab8-tagged particles with opsin. We further investigate the role of the TZ protein Cc2d2a in Rab8-mediated trafficking using cc2d2a zebrafish mutants and identify a requirement for Cc2d2a in the latest step of OCV trafficking, namely vesicle fusion. Progressive accumulation of opsin-containing vesicles in the apical portion of photoreceptors lacking Cc2d2a is caused by disorganization of the vesicle fusion machinery at the periciliary membrane with mislocalization and loss of the t-SNAREs SNAP25 and Syntaxin3 and of the exocyst component Exoc4. We further observe secondary defects on upstream Rab8-trafficking with cytoplasmic accumulation of Rab8. Taken together, our results support participation of Rab8 in OCV trafficking and identify a novel role for the TZ protein Cc2d2a in fusion of incoming ciliary-directed vesicles, through organization of the vesicle fusion machinery at the periciliary membrane. PMID:29281629

Loss-of-function of the ciliopathy protein Cc2d2a disorganizes the vesicle fusion machinery at the periciliary membrane and indirectly affects Rab8-trafficking in zebrafish photoreceptors.

PubMed

Ojeda Naharros, Irene; Gesemann, Matthias; Mateos, José M; Barmettler, Gery; Forbes, Austin; Ziegler, Urs; Neuhauss, Stephan C F; Bachmann-Gagescu, Ruxandra

2017-12-01

Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction of environmental signals such as light sensation in photoreceptors. Concentration of signal detection proteins such as opsins in the ciliary membrane is achieved by RabGTPase-regulated polarized vesicle trafficking and by a selective barrier at the ciliary base, the transition zone (TZ). Dysfunction of the TZ protein CC2D2A causes Joubert/Meckel syndromes in humans and loss of ciliary protein localization in animal models, including opsins in retinal photoreceptors. The link between the TZ and upstream vesicle trafficking has been little explored to date. Moreover, the role of the small GTPase Rab8 in opsin-carrier vesicle (OCV) trafficking has been recently questioned in a mouse model. Using correlative light and electron microscopy and live imaging in zebrafish photoreceptors, we provide the first live characterization of Rab8-mediated trafficking in photoreceptors in vivo. Our results support a possibly redundant role for both Rab8a/b paralogs in OCV trafficking, based on co-localization of Rab8 and opsins in vesicular structures, and joint movement of Rab8-tagged particles with opsin. We further investigate the role of the TZ protein Cc2d2a in Rab8-mediated trafficking using cc2d2a zebrafish mutants and identify a requirement for Cc2d2a in the latest step of OCV trafficking, namely vesicle fusion. Progressive accumulation of opsin-containing vesicles in the apical portion of photoreceptors lacking Cc2d2a is caused by disorganization of the vesicle fusion machinery at the periciliary membrane with mislocalization and loss of the t-SNAREs SNAP25 and Syntaxin3 and of the exocyst component Exoc4. We further observe secondary defects on upstream Rab8-trafficking with cytoplasmic accumulation of Rab8. Taken together, our results support participation of Rab8 in OCV trafficking and identify a novel role for the TZ protein Cc2d2a in fusion of incoming ciliary-directed vesicles, through organization of the vesicle fusion machinery at the periciliary membrane.

Comparative tissue distribution profiles of five major bio-active components in normal and blood deficiency rats after oral administration of Danggui Buxue Decoction by UPLC-TQ/MS.

PubMed

Shi, Xuqin; Tang, Yuping; Zhu, Huaxu; Li, Weixia; Li, Zhenhao; Li, Wei; Duan, Jin-ao

2014-01-01

Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) were frequently combined and used in China as herbal pair called as Danggui Buxue Decoction (DBD) for treatment of blood deficiency syndrome, such as women's ailments. This study is to investigate the tissue distribution profiles of five major bio-active constituents (ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV) in DBD after oral administration of DBD in blood deficiency rats, and to compare the difference between normal and blood deficiency rats. The blood deficiency rats were induced by bleeding from orbit at the dosages of 5.0mLkg(-1) every day, and the experimental period was 12 days. At the finally day of experimental period, both normal and blood deficiency rats were orally administrated with DBD, and then the tissues samples were collected at different time points. Ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV in different tissues were detected simultaneously by UPLC-TQ/MS, and the histograms were drawn. The results showed that the overall trend was CLiver>CKidney>CHeart>CSpleen>CLung, CC-30min>CM-30min>CM-60min>CC-5min>CM-5min>CC-60min>CM-240min>CC-240min. The contents of the detected compounds in liver were more than that in other tissues no matter in normal or blood deficiency rats. Compared to normal rats, partial contents of the compounds in blood deficiency rats' tissues at different time points had significant difference (P<0.05). This study was the first report about tissue distribution investigation in blood deficiency animals which is conducted by bleeding. And the results demonstrated that the five DBD components in normal and blood deficiency rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in blood deficiency animals. Copyright © 2013 Elsevier B.V. All rights reserved.

X-37 C-Sic CMC Control Surface Components Development [Status of the NASA/Boeing/USAF Orbital Vehicle and Related Efforts

NASA Technical Reports Server (NTRS)

Valentine, Peter G; Rivers, H. Kevin; Chen, Victor L.

2004-01-01

Carbon/Silicon-Carbide (C-Sic) ceramic matrix composite (CMC) flaperon and ruddervator control surface components are being developed for the X-37 Orbital Vehicle (OV). The results of the prior NASA LaRC led work, aimed at developing C-Sic flaperon and ruddervator components for the X-37, will be reviewed. The status of several on-going and/or planned NASA, USAF, and Boeing programs that will support the development of control surface components for the X-37 OV will also be reviewed. The overall design and development philosophy being employed to assemble a team(s) to develop both: (a) C-Sic hot structure control surface components for the X-37 OV, and (b) carbon-carbon (C-C) hot structure components (a risk-reduction backup option for the OV), will be presented.

Integration of Mobil Satellite and Cellular Systems

NASA Technical Reports Server (NTRS)

Drucker, E. H.; Estabrook, P.; Pinck, D.; Ekroot, L.

1993-01-01

By integrating the ground based infrastructure component of a mobile satellite system with the infrastructure systems of terrestrial 800 MHz cellular service providers, a seamless network of universal coverage can be established.

Thermal Characterization of Carbon Fiber-Reinforced Carbon Composites

NASA Astrophysics Data System (ADS)

Macias, J. D.; Bante-Guerra, J.; Cervantes-Alvarez, F.; Rodrìguez-Gattorno, G.; Arés-Muzio, O.; Romero-Paredes, H.; Arancibia-Bulnes, C. A.; Ramos-Sánchez, V.; Villafán-Vidales, H. I.; Ordonez-Miranda, J.; Li Voti, R.; Alvarado-Gil, J. J.

2018-04-01

Carbon fiber-reinforced carbon (C/C) composites consist in a carbon matrix holding carbon or graphite fibers together, whose physical properties are determined not only by those of their individual components, but also by the layer buildup and the material preparation and processing. The complex structure of C/C composites along with the fiber orientation provide an effective means for tailoring their mechanical, electrical, and thermal properties. In this work, we use the Laser Flash Technique to measure the thermal diffusivity and thermal conductivity of C/C composites made up of laminates of weaved bundles of carbon fibers, forming a regular and repeated orthogonal pattern, embedded in a graphite matrix. Our experimental data show that: i) the cross-plane thermal conductivity remains practically constant around (5.3 ± 0.4) W·m-1 K-1, within the temperature range from 370 K to 1700 K. ii) The thermal diffusivity and thermal conductivity along the cross-plane direction to the fibers axis is about five times smaller than the corresponding ones in the laminates plane. iii) The measured cross-plane thermal conductivity is well described by a theoretical model that considers both the conductive and radiative thermal contributions of the effective thermal conductivity.

Notch3 drives development and progression of cholangiocarcinoma

PubMed Central

Guest, Rachel V.; Dwyer, Benjamin J.; Kendall, Timothy J.; Man, Tak-Yung; Minnis-Lyons, Sarah E.; Lu, Wei-Yu; Robson, Andrew J.; Gonzalez, Sofia Ferreira; Raven, Alexander; Wojtacha, Davina; Morton, Jennifer P.; Komuta, Mina; Roskams, Tania; Wigmore, Stephen J.; Sansom, Owen J.; Forbes, Stuart J.

2016-01-01

The prognosis of cholangiocarcinoma (CC) is dismal. Notch has been identified as a potential driver; forced exogenous overexpression of Notch1 in hepatocytes results in the formation of biliary tumors. In human disease, however, it is unknown which components of the endogenously signaling pathway are required for tumorigenesis, how these orchestrate cancer, and how they can be targeted for therapy. Here we characterize Notch in human-resected CC, a toxin-driven model in rats, and a transgenic mouse model in which p53 deletion is targeted to biliary epithelia and CC induced using the hepatocarcinogen thioacetamide. We find that across species, the atypical receptor NOTCH3 is differentially overexpressed; it is progressively up-regulated with disease development and promotes tumor cell survival via activation of PI3k-Akt. We use genetic KO studies to show that tumor growth significantly attenuates after Notch3 deletion and demonstrate signaling occurs via a noncanonical pathway independent of the mediator of classical Notch, Recombinant Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ). These data present an opportunity in this aggressive cancer to selectively target Notch, bypassing toxicities known to be RBPJ dependent. PMID:27791012

Diversity of Staphylococcus aureus Isolates in European Wildlife

PubMed Central

Monecke, Stefan; Gavier-Widén, Dolores; Hotzel, Helmut; Peters, Martin; Guenther, Sebastian; Lazaris, Alexandros; Loncaric, Igor; Müller, Elke; Reissig, Annett; Ruppelt-Lorz, Antje; Shore, Anna C.; Walter, Birgit; Coleman, David C.; Ehricht, Ralf

2016-01-01

Staphylococcus aureus is a well-known colonizer and cause of infection among animals and it has been described from numerous domestic and wild animal species. The aim of the present study was to investigate the molecular epidemiology of S. aureus in a convenience sample of European wildlife and to review what previously has been observed in the subject field. 124 S. aureus isolates were collected from wildlife in Germany, Austria and Sweden; they were characterized by DNA microarray hybridization and, for isolates with novel hybridization patterns, by multilocus sequence typing (MLST). The isolates were assigned to 29 clonal complexes and singleton sequence types (CC1, CC5, CC6, CC7, CC8, CC9, CC12, CC15, CC22, CC25, CC30, CC49, CC59, CC88, CC97, CC130, CC133, CC398, ST425, CC599, CC692, CC707, ST890, CC1956, ST2425, CC2671, ST2691, CC2767 and ST2963), some of which (ST2425, ST2691, ST2963) were not described previously. Resistance rates in wildlife strains were rather low and mecA-MRSA isolates were rare (n = 6). mecC-MRSA (n = 8) were identified from a fox, a fallow deer, hares and hedgehogs. The common cattle-associated lineages CC479 and CC705 were not detected in wildlife in the present study while, in contrast, a third common cattle lineage, CC97, was found to be common among cervids. No Staphylococcus argenteus or Staphylococcus schweitzeri-like isolates were found. Systematic studies are required to monitor the possible transmission of human- and livestock-associated S. aureus/MRSA to wildlife and vice versa as well as the possible transmission, by unprotected contact to animals. The prevalence of S. aureus/MRSA in wildlife as well as its population structures in different wildlife host species warrants further investigation. PMID:27992523

STEPS: efficient simulation of stochastic reaction-diffusion models in realistic morphologies.

PubMed

Hepburn, Iain; Chen, Weiliang; Wils, Stefan; De Schutter, Erik

2012-05-10

Models of cellular molecular systems are built from components such as biochemical reactions (including interactions between ligands and membrane-bound proteins), conformational changes and active and passive transport. A discrete, stochastic description of the kinetics is often essential to capture the behavior of the system accurately. Where spatial effects play a prominent role the complex morphology of cells may have to be represented, along with aspects such as chemical localization and diffusion. This high level of detail makes efficiency a particularly important consideration for software that is designed to simulate such systems. We describe STEPS, a stochastic reaction-diffusion simulator developed with an emphasis on simulating biochemical signaling pathways accurately and efficiently. STEPS supports all the above-mentioned features, and well-validated support for SBML allows many existing biochemical models to be imported reliably. Complex boundaries can be represented accurately in externally generated 3D tetrahedral meshes imported by STEPS. The powerful Python interface facilitates model construction and simulation control. STEPS implements the composition and rejection method, a variation of the Gillespie SSA, supporting diffusion between tetrahedral elements within an efficient search and update engine. Additional support for well-mixed conditions and for deterministic model solution is implemented. Solver accuracy is confirmed with an original and extensive validation set consisting of isolated reaction, diffusion and reaction-diffusion systems. Accuracy imposes upper and lower limits on tetrahedron sizes, which are described in detail. By comparing to Smoldyn, we show how the voxel-based approach in STEPS is often faster than particle-based methods, with increasing advantage in larger systems, and by comparing to MesoRD we show the efficiency of the STEPS implementation. STEPS simulates models of cellular reaction-diffusion systems with complex boundaries with high accuracy and high performance in C/C++, controlled by a powerful and user-friendly Python interface. STEPS is free for use and is available at http://steps.sourceforge.net/

STEPS: efficient simulation of stochastic reaction–diffusion models in realistic morphologies

PubMed Central

2012-01-01

Background Models of cellular molecular systems are built from components such as biochemical reactions (including interactions between ligands and membrane-bound proteins), conformational changes and active and passive transport. A discrete, stochastic description of the kinetics is often essential to capture the behavior of the system accurately. Where spatial effects play a prominent role the complex morphology of cells may have to be represented, along with aspects such as chemical localization and diffusion. This high level of detail makes efficiency a particularly important consideration for software that is designed to simulate such systems. Results We describe STEPS, a stochastic reaction–diffusion simulator developed with an emphasis on simulating biochemical signaling pathways accurately and efficiently. STEPS supports all the above-mentioned features, and well-validated support for SBML allows many existing biochemical models to be imported reliably. Complex boundaries can be represented accurately in externally generated 3D tetrahedral meshes imported by STEPS. The powerful Python interface facilitates model construction and simulation control. STEPS implements the composition and rejection method, a variation of the Gillespie SSA, supporting diffusion between tetrahedral elements within an efficient search and update engine. Additional support for well-mixed conditions and for deterministic model solution is implemented. Solver accuracy is confirmed with an original and extensive validation set consisting of isolated reaction, diffusion and reaction–diffusion systems. Accuracy imposes upper and lower limits on tetrahedron sizes, which are described in detail. By comparing to Smoldyn, we show how the voxel-based approach in STEPS is often faster than particle-based methods, with increasing advantage in larger systems, and by comparing to MesoRD we show the efficiency of the STEPS implementation. Conclusion STEPS simulates models of cellular reaction–diffusion systems with complex boundaries with high accuracy and high performance in C/C++, controlled by a powerful and user-friendly Python interface. STEPS is free for use and is available at http://steps.sourceforge.net/ PMID:22574658

Spectral transformation of ASTER and Landsat TM bands for lithological mapping of Soghan ophiolite complex, south Iran

NASA Astrophysics Data System (ADS)

Pournamdari, Mohsen; Hashim, Mazlan; Pour, Amin Beiranvand

2014-08-01

Spectral transformation methods, including correlation coefficient (CC) and Optimum Index Factor (OIF), band ratio (BR) and principal component analysis (PCA) were applied to ASTER and Landsat TM bands for lithological mapping of Soghan ophiolitic complex in south of Iran. The results indicated that the methods used evidently showed superior outputs for detecting lithological units in ophiolitic complexes. CC and OIF methods were used to establish enhanced Red-Green-Blue (RGB) color combination bands for discriminating lithological units. A specialized band ratio (4/1, 4/5, 4/7 in RGB) was developed using ASTER bands to differentiate lithological units in ophiolitic complexes. The band ratio effectively detected serpentinite dunite as host rock of chromite ore deposits from surrounding lithological units in the study area. Principal component images derived from first three bands of ASTER and Landsat TM produced well results for lithological mapping applications. ASTER bands contain improved spectral characteristics and higher spatial resolution for detecting serpentinite dunite in ophiolitic complexes. The developed approach used in this study offers great potential for lithological mapping using ASTER and Landsat TM bands, which contributes in economic geology for prospecting chromite ore deposits associated with ophiolitic complexes.

Drosophila Fip200 is an essential regulator of autophagy that attenuates both growth and aging.

PubMed

Kim, Myungjin; Park, Hae Li; Park, Hwan-Woo; Ro, Seung-Hyun; Nam, Samuel G; Reed, John M; Guan, Jun-Lin; Lee, Jun Hee

2013-08-01

Autophagy-related 1 (Atg1)/Unc-51-like protein kinases (ULKs) are evolutionarily conserved proteins that play critical physiological roles in controlling autophagy, cell growth and neurodevelopment. RB1-inducible coiled-coil 1 (RB1CC1), also known as PTK2/FAK family-interacting protein of 200 kDa (FIP200) is a recently discovered binding partner of ULK1. Here we isolated the Drosophila RB1CC1/FIP200 homolog (Fip200/CG1347) and showed that it mediates Atg1-induced autophagy as a genetically downstream component in diverse physiological contexts. Fip200 loss-of-function mutants experienced severe mobility loss associated with neuronal autophagy defects and neurodegeneration. The Fip200 mutants were also devoid of both developmental and starvation-induced autophagy in salivary gland and fat body, while having no defects in axonal transport and projection in developing neurons. Interestingly, moderate downregulation of Fip200 accelerated both developmental growth and aging, accompanied by target of rapamycin (Tor) signaling upregulation. These results suggest that Fip200 is a critical downstream component of Atg1 and specifically mediates Atg1's autophagy-, aging- and growth-regulating functions.

Drosophila Fip200 is an essential regulator of autophagy that attenuates both growth and aging

PubMed Central

Kim, Myungjin; Park, Hae Li; Park, Hwan-Woo; Ro, Seung-Hyun; Nam, Samuel G.; Reed, John M.; Guan, Jun-Lin; Lee, Jun Hee

2013-01-01

Autophagy-related 1 (Atg1)/Unc-51-like protein kinases (ULKs) are evolutionarily conserved proteins that play critical physiological roles in controlling autophagy, cell growth and neurodevelopment. RB1-inducible coiled-coil 1 (RB1CC1), also known as PTK2/FAK family-interacting protein of 200 kDa (FIP200) is a recently discovered binding partner of ULK1. Here we isolated the Drosophila RB1CC1/FIP200 homolog (Fip200/CG1347) and showed that it mediates Atg1-induced autophagy as a genetically downstream component in diverse physiological contexts. Fip200 loss-of-function mutants experienced severe mobility loss associated with neuronal autophagy defects and neurodegeneration. The Fip200 mutants were also devoid of both developmental and starvation-induced autophagy in salivary gland and fat body, while having no defects in axonal transport and projection in developing neurons. Interestingly, moderate downregulation of Fip200 accelerated both developmental growth and aging, accompanied by target of rapamycin (Tor) signaling upregulation. These results suggest that Fip200 is a critical downstream component of Atg1 and specifically mediates Atg1’s autophagy-, aging- and growth-regulating functions. PMID:23819996

Super-Resolution Microscopy: Shedding Light on the Cellular Plasma Membrane.

PubMed

Stone, Matthew B; Shelby, Sarah A; Veatch, Sarah L

2017-06-14

Lipids and the membranes they form are fundamental building blocks of cellular life, and their geometry and chemical properties distinguish membranes from other cellular environments. Collective processes occurring within membranes strongly impact cellular behavior and biochemistry, and understanding these processes presents unique challenges due to the often complex and myriad interactions between membrane components. Super-resolution microscopy offers a significant gain in resolution over traditional optical microscopy, enabling the localization of individual molecules even in densely labeled samples and in cellular and tissue environments. These microscopy techniques have been used to examine the organization and dynamics of plasma membrane components, providing insight into the fundamental interactions that determine membrane functions. Here, we broadly introduce the structure and organization of the mammalian plasma membrane and review recent applications of super-resolution microscopy to the study of membranes. We then highlight some inherent challenges faced when using super-resolution microscopy to study membranes, and we discuss recent technical advancements that promise further improvements to super-resolution microscopy and its application to the plasma membrane.

Characteristic vibration patterns of odor compounds from bread-baking volatiles upon protein binding: density functional and ONIOM study and principal component analysis.

PubMed

Treesuwan, Witcha; Hirao, Hajime; Morokuma, Keiji; Hannongbua, Supa

2012-05-01

As the mechanism underlying the sense of smell is unclear, different models have been used to rationalize structure-odor relationships. To gain insight into odorant molecules from bread baking, binding energies and vibration spectra in the gas phase and in the protein environment [7-transmembrane helices (7TMHs) of rhodopsin] were calculated using density functional theory [B3LYP/6-311++G(d,p)] and ONIOM [B3LYP/6-311++G(d,p):PM3] methods. It was found that acetaldehyde ("acid" category) binds strongly in the large cavity inside the receptor, whereas 2-ethyl-3-methylpyrazine ("roasted") binds weakly. Lys296, Tyr268, Thr118 and Ala117 were identified as key residues in the binding site. More emphasis was placed on how vibrational frequencies are shifted and intensities modified in the receptor protein environment. Principal component analysis (PCA) suggested that the frequency shifts of C-C stretching, CH(3) umbrella, C = O stretching and CH(3) stretching modes have a significant effect on odor quality. In fact, the frequency shifts of the C-C stretching and C = O stretching modes, as well as CH(3) umbrella and CH(3) symmetric stretching modes, exhibit different behaviors in the PCA loadings plot. A large frequency shift in the CH(3) symmetric stretching mode is associated with the sweet-roasted odor category and separates this from the acid odor category. A large frequency shift of the C-C stretching mode describes the roasted and oily-popcorn odor categories, and separates these from the buttery and acid odor categories.

Development of many-body polarizable force fields for Li-battery components: 1. Ether, alkane, and carbonate-based solvents.

PubMed

Borodin, Oleg; Smith, Grant D

2006-03-30

Classical many-body polarizable force fields were developed for n-alkanes, perflouroalkanes, polyethers, ketones, and linear and cyclic carbonates on the basis of quantum chemistry dimer energies of model compounds and empirical thermodynamic liquid-state properties. The dependence of the electron correlation contribution to the dimer binding energy on basis-set size and level of theory was investigated as a function of molecular separation for a number of alkane, ether, and ketone dimers. Molecular dynamics (MD) simulations of the force fields accurately predicted structural, dynamic, and transport properties of liquids and unentangled polymer melts. On average, gas-phase dimer binding energies predicted with the force field were between those from MP2/aug-cc-pvDz and MP2/aug-cc-pvTz quantum chemistry calculations.

Ectopic expression of the Coffea canephora SERK1 homolog-induced differential transcription of genes involved in auxin metabolism and in the developmental control of embryogenesis.

PubMed

Pérez-Pascual, Daniel; Jiménez-Guillen, Doribet; Villanueva-Alonzo, Hernán; Souza-Perera, Ramón; Godoy-Hernández, Gregorio; Zúñiga-Aguilar, José Juan

2018-04-01

Somatic embryogenesis receptor-like kinase 1 (SERK1) is a membrane receptor that might serve as common co-regulator of plant cell differentiation processes by forming heterodimers with specific receptor-like kinases. The Coffea canephora SERK1 homolog (CcSERK1) was cloned in this work, and its early function in the transcription of embryogenesis master genes and of genes encoding proteins involved in auxin metabolism was investigated by externally manipulating its expression in embryogenic leaf explants, before the appearance of embryogenic structures. Overexpression of CcSERK1 early during embryogenesis caused an increase in the number of somatic embryos when the 55-day process was completed. Suppression of CcSERK1 expression by RNA interference almost abolished somatic embryogenesis. Real time-PCR experiments revealed that the transcription of the CcAGL15, CcWUS, CcBBM, CcPKL, CcYUC1, CcPIN1 and CcPIN4 homologs was modified in direct proportion to the expression of CcSERK1 and that only CcLEC1 was inversely affected by the expression levels of CcSERK1. The expression of the CcYUC4 homolog was induced to more than 80-fold under CcSERK1 overexpression conditions, but it was also induced when CcSERK1 expression was silenced. The level of CcTIR1 was not affected by CcSERK1 overexpression but was almost abolished during CcSERK1 silencing. These results suggest that CcSERK1 co-regulates the induction of somatic embryogenesis in Coffea canephora by early activation of YUC-dependent auxin biosynthesis, auxin transport mediated by PIN1 and PIN4, and probably auxin perception by the TIR1 receptor, leading to the induction of early-stage homeotic genes (CcAGL15, CcWUS, CcPKL and CcBBM) and repression of late-stage homeotic genes (CcLec1). © 2018 Scandinavian Plant Physiology Society.

Invasion of Epithelial Cells and Proteolysis of Cellular Focal Adhesion Components by Distinct Types of Porphyromonas gingivalis Fimbriae

PubMed Central

Nakagawa, Ichiro; Inaba, Hiroaki; Yamamura, Taihei; Kato, Takahiro; Kawai, Shinji; Ooshima, Takashi; Amano, Atsuo

2006-01-01

Porphyromonas gingivalis fimbriae are classified into six types (types I to V and Ib) based on the fimA genes encoding FimA (a subunit of fimbriae), and they play a critical role in bacterial interactions with host tissues. In this study, we compared the efficiencies of P. gingivalis strains with distinct types of fimbriae for invasion of epithelial cells and for degradation of cellular focal adhesion components, paxillin, and focal adhesion kinase (FAK). Six representative strains with the different types of fimbriae were tested, and P. gingivalis with type II fimbriae (type II P. gingivalis) adhered to and invaded epithelial cells at significantly greater levels than the other strains. There were negligible differences in gingipain activities among the six strains; however, type II P. gingivalis apparently degraded intracellular paxillin in association with a loss of phosphorylation 30 min after infection. Degradation was blocked with cytochalasin D or in mutants with fimA disrupted. Paxillin was degraded by the mutant with Lys-gingipain disrupted, and this degradation was prevented by inhibition of Arg-gingipain activity by Nα-p-tosyl-l-lysine chloromethyl ketone. FAK was also degraded by type II P. gingivalis. Cellular focal adhesions with green fluorescent protein-paxillin macroaggregates were clearly destroyed, and this was associated with cellular morphological changes and microtubule disassembly. In an in vitro wound closure assay, type II P. gingivalis significantly inhibited cellular migration and proliferation compared to the cellular migration and proliferation observed with the other types. These results suggest that type II P. gingivalis efficiently invades epithelial cells and degrades focal adhesion components with Arg-gingipain, which results in cellular impairment during wound healing and periodontal tissue regeneration. PMID:16790749

Toward a W4-F12 approach: Can explicitly correlated and orbital-based ab initio CCSD(T) limits be reconciled?

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

Sylvetsky, Nitai, E-mail: gershom@weizmann.ac.il; Martin, Jan M. L., E-mail: gershom@weizmann.ac.il; Peterson, Kirk A., E-mail: kipeters@wsu.edu

2016-06-07

In the context of high-accuracy computational thermochemistry, the valence coupled cluster with all singles and doubles (CCSD) correlation component of molecular atomization energies presents the most severe basis set convergence problem, followed by the (T) component. In the present paper, we make a detailed comparison, for an expanded version of the W4-11 thermochemistry benchmark, between, on the one hand, orbital-based CCSD/AV{5,6}Z + d and CCSD/ACV{5,6}Z extrapolation, and on the other hand CCSD-F12b calculations with cc-pVQZ-F12 and cc-pV5Z-F12 basis sets. This latter basis set, now available for H–He, B–Ne, and Al–Ar, is shown to be very close to the basis setmore » limit. Apparent differences (which can reach 0.35 kcal/mol for systems like CCl{sub 4}) between orbital-based and CCSD-F12b basis set limits disappear if basis sets with additional radial flexibility, such as ACV{5,6}Z, are used for the orbital calculation. Counterpoise calculations reveal that, while total atomization energies with V5Z-F12 basis sets are nearly free of BSSE, orbital calculations have significant BSSE even with AV(6 + d)Z basis sets, leading to non-negligible differences between raw and counterpoise-corrected extrapolated limits. This latter problem is greatly reduced by switching to ACV{5,6}Z core-valence basis sets, or simply adding an additional zeta to just the valence orbitals. Previous reports that all-electron approaches like HEAT (high-accuracy extrapolated ab-initio thermochemistry) lead to different CCSD(T) limits than “valence limit + CV correction” approaches like Feller-Peterson-Dixon and Weizmann-4 (W4) theory can be rationalized in terms of the greater radial flexibility of core-valence basis sets. For (T) corrections, conventional CCSD(T)/AV{Q,5}Z + d calculations are found to be superior to scaled or extrapolated CCSD(T)-F12b calculations of similar cost. For a W4-F12 protocol, we recommend obtaining the Hartree-Fock and valence CCSD components from CCSD-F12b/cc-pV{Q,5}Z-F12 calculations, but the (T) component from conventional CCSD(T)/aug’-cc-pV{Q,5}Z + d calculations using Schwenke’s extrapolation; post-CCSD(T), core-valence, and relativistic corrections are to be obtained as in the original W4 theory. W4-F12 is found to agree slightly better than W4 with ATcT (active thermochemical tables) data, at a substantial saving in computation time and especially I/O overhead. A W4-F12 calculation on benzene is presented as a proof of concept.« less

Molecular characterization and expression of three preprosomatostatin genes and their association with growth in common carp (Cyprinus carpio).

PubMed

Feng, Xiu; Yu, Xiaomu; Pang, Meixia; Liu, Haiyang; Tong, Jingou

2015-04-01

Somatostatins (SSs) are a structurally diverse family of peptides that play important roles in the regulation of growth, development and metabolism in vertebrates. In this study, three preprosomatostatin genes (PSSs) in the common carp, Cyprinus carpio (Cc) were identified and characterized. Based on cloned sequences and genome BLAST, six isoforms of the PSS gene in C. carpio (CcPSS) were identified and included CcPSS1a and CcPSS1b, CcPSS2a and CcPSS2b, and finally, CcPSS3a and CcPSS3b. The open reading frames (ORF) of CcPSS1a, CcPSS2a and CcPSS3a consist of 345, 336 and 363 nucleotides. During embryonic development, the expressions of CcPSS2 and CcPSS3 were first observed at the stage of optic vesicle, and CcPSS1 mRNA was initially detected at the stage of muscular effect. The highest mRNA levels of CcPSS1, CcPSS2 and CcPSS3 were observed at 1-day post-hatch (dph), 2-dph and the stage of heart beating, respectively. In the adult brain, the distributions of three CcPSS mRNAs were differential but overlapping in the hypothalamus, telencephalon and medulla oblongata. For peripheral tissues, all three CcPSS mRNAs were detected in the mid-intestine, and CcPSS1 and CcPSS3 mRNAs were also expressed in the liver. Owing to the importance of somatostatins on regulating growth, functional mutations of CcPSSs were identified in a C. carpio population. A total of 23 polymorphic sites were detected in CcPSS1a and CcPSS3a. Of them, two SNPs (CcPSS1a-g.922C>T, and CcPSS3a-g.1125C>A) were significantly associated with growth traits, indicating their potential applications in gene (marker)-assisted selective breeding in C. carpio. Copyright © 2014 Elsevier Inc. All rights reserved.

Telomere Length, Oxidative Stress, Inflammation and BDNF Levels in Siblings of Patients with Bipolar Disorder: Implications for Accelerated Cellular Aging

PubMed Central

Vasconcelos-Moreno, Mirela Paiva; Fries, Gabriel Rodrigo; Gubert, Carolina; dos Santos, Bárbara Tietböhl Martins Quadros; Fijtman, Adam; Sartori, Juliana; Ferrari, Pamela; Grun, Lucas Kich; Parisi, Mariana Migliorini; Guma, Fátima Theresinha Costa Rodrigues; Barbé-Tuana, Florencia Maria; Kapczinski, Flávio; Rosa, Adriane Ribeiro; Yatham, Lakshmi N.

2017-01-01

Abstract Background: Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for bipolar disorder. The aim of this study was to examine potential differences in brain-derived neurotrophic factor, cytokines, oxidative stress, and telomere length markers between patients with bipolar disorder, their siblings, and healthy controls. Methods: Thirty-six patients with bipolar disorder type I, 39 siblings, and 44 healthy controls were assessed. Serum levels of brain-derived neurotrophic factor, interleukin-6, interleukin-10, tumor necrosis factor-α, C-C motif chemokine 11, C-C motif chemokine 24, and 3-nitrotyrosine were measured, as were the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Telomere length (T/S ratio) was measured using quantitative polymerase chain reaction. Results: Telomere length was different between the 3 groups (P = .041) with both patients and siblings showing a shorter T/S ratio compared with healthy controls. Patients showed increased levels of interleukin-6 (P = .005) and interleukin-10 (P = .002) compared with controls as well as increased levels of interleukin-6 (p = 0.014) and CCL24 (P = .016) compared with their siblings. C-C motif chemokine 11 levels were increased in siblings compared with controls (P = .015), and a similar tendency was found in patients compared with controls (P = .045). Glutathione peroxidase activity was decreased in patients compared with controls (P = .006) and siblings (P = .025). No differences were found for the other markers. Conclusions: The present results suggest that unaffected siblings may present accelerated aging features. These neurobiological findings may be considered as endophenotypic traits. Further prospective studies are warranted. PMID:28339618

How does information on the harms and benefits of cervical cancer screening alter the intention to be screened?: a randomized survey of Norwegian women.

PubMed

Iyer, Anita L; Bundorf, M Kate; Gyrd-Hansen, Dorte; Goldhaber-Fiebert, Jeremy D; Cyr, Pascale-Renée; Sønbø Kristiansen, Ivar

2018-03-27

Cervical cancer (CC) is the 13th most frequent cancer among women in Norway, but the third most common among women aged 25-49 years. The national screening program sends information letters to promote screening participation. We aimed to evaluate how women's stated intention to participate in screening and pursue treatment changed with the provision of additional information on harms associated with screening, and to assess women's preferences on the timing and source of such information. We administered a web-based questionnaire to a panel of Norwegian women aged 25-69 years and randomized into three groups on the basis of when in the screening process additional information was introduced: (i) invited for routine screening, (ii) recommended an additional test following detection of cellular abnormalities, and (iii) recommended precancer treatment. A fourth (control) group did not receive any additional information. Results show that among 1060 respondents, additional information did not significantly alter women's stated intentions to screen. However, it created decision uncertainty on when treatment was recommended (8.76-9.09 vs. 9.40; 10-point Likert scale; P=0.004). Over 80% of women favored receiving information on harms and 59% preferred that information come from a qualified public health authority. Nearly 90% of women in all groups overestimated women's lifetime risk of CC. In conclusion, additional information on harms did not alter Norwegian women's stated intention to screen for CC; yet, it resulted in greater decision uncertainty to undergo precancer treatment. Incorporating information on harms into invitation letters is warranted as it would increase women's ability to make informed choices.

Hydrogen-Bonded Network and Water Dynamics in the D-channel of Cytochrome c Oxidase.

PubMed

Ghane, Tahereh; Gorriz, Rene F; Wrzalek, Sandro; Volkenandt, Senta; Dalatieh, Ferand; Reidelbach, Marco; Imhof, Petra

2018-02-12

Proton transfer in cytochrome c oxidase (CcO) from the cellular inside to the binuclear redox centre as well as proton pumping through the membrane takes place through proton entrance via two distinct pathways, the D- and K-channel. Both channels show a dependence of their hydration level on the protonation states of their key residues, K362 for the K-channel, and E286 or D132 for the D-channel. In the oxidative half of CcO's catalytic cycle the D-channel is the proton-conducting path. For this channel, an interplay of protonation state of the D-channel residues with the water and hydrogen-bond dynamics has been observed in molecular dynamics simulations of the CcO protein, embedded in a lipid bi-layer, modelled in different protonation states. Protonation of residue E286 at the end of the D-channel results in a hydrogen-bonded network pointing from E286 to N139, that is against proton transport, and favouring N139 conformations which correspond to a closed asparagine gate (formed by residues N121 and N139). Consequently, the hydration level is lower than with unprotonated E286. In those models, the Asn gate is predominantly open, allowing water molecules to pass and thus increase the hydration level. The hydrogen-bonded network in these states exhibits longer life times of the Asn residues with water than other models and shows the D-channel to be traversable from the entrance, D132, to exit, E286. The D-channel can thus be regarded as auto-regulated with respect to proton transport, allowing proton passage only when required, that is the proton is located at the lower part of the D-channel (D132 to Asn gate) and not at the exit (E286).

Cellular Components, Including Stem-Like Cells, of Preterm Mother's Mature Milk as Compared with Those in Her Colostrum: A Pilot Study.

PubMed

Kaingade, Pankaj; Somasundaram, Indumathi; Sharma, Akshita; Patel, Darshan; Marappagounder, Dhanasekaran

2017-09-01

Whether the preterm mothers' mature milk retains the same cellular components as those in colostrum including stem-like cell, cell adhesion molecules, and immune cells. A total of five preterm mothers were recruited for the study having an average age of 30.2 years and gestational age of 29.8 weeks from the Pristine Women's Hospital, Kolhapur. Colostrum milk was collected within 2-5 days and matured milk was collected 20-30 days after delivery from the same mothers. Integral cellular components of 22 markers including stem cells, immune cells, and cell adhesion molecules were measured using flowcytometry. Preterm mature milk was found to possess higher expressions of hematopoietic stem cells, mesenchymal stem-like cells, immune cells, few cell adhesion molecules, and side population cells than colostrum. The increased level of these different cell components in mature milk may be important in the long-term preterm baby's health growth. Further similar research in a larger population of various gestational ages and lactation stages of preterm mothers is warranted to support these pilot findings.

Spine Radiosurgery: A Dosimetric Analysis in 124 Patients Who Received 18 Gy

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

Schipani, Stefano; Wen, Winston; Jin, Jain-Yue

2012-12-01

Purpose: To define the safely tolerated doses to organs at risk (OARs) adjacent to the target volume (TV) of spine radiosurgery (SRS) with 18-Gy in a single fraction. Methods and Materials: A total of 124 patient cases with 165 spine metastases were reviewed. An 18-Gy single-fraction regimen was prescribed to the 90% isodose line encompassing the TV. A constraint of 10 Gy to 10% of the spinal cord outlined 6 mm above and below the TV was used. Dosimetric data to OARs were analyzed. Results: A total of 124 patients (100%) were followed-up, and median follow-up time was 7 monthsmore » (1-50 months). Symptoms and local control were achieved in 114 patients (92%). Acute Radiation Therapy Oncology Group (RTOG) grade 1 oral mucositis occurred in 11 of 11 (100%) patients at risk for oropharyngeal toxicity after cervical spine treatment. There were no RTOG grade 2-4 acute or late complications. Median TV was 43.2 cc (5.3-175.4 cc) and 90% of the TV received median dose of 19 Gy (17-19.8 Gy). Median (range) of spinal cord maximum dose (Dmax), dose to spinal cord 0.35 cc (Dsc0.35), and cord volume receiving 10 Gy (Vsc10) were 13.8 Gy (5.4-21 Gy), 8.9 Gy (2.6-11.4 Gy) and 0.33 cc (0-1.6 cc), respectively. Other OARs were evaluated when in proximity to the TV. Esophagus (n=58), trachea (n=28), oropharynx (n=11), and kidneys (n=34) received median (range) V10 and V15 of 3.1 cc (0-5.8 cc) and 1.2 cc (0-2.9 cc), 2.8 cc (0-4.9 cc), and 0.8 cc (0-2.1 cc), 3.4 cc (0-6.2 cc) and 1.6 cc (0-3.2 cc), 0.3 cc (0-0.8 cc) and 0.08 cc (0-0.1 cc), respectively. Conclusions: Cord Dmax of 14 Gy and D0.35 of 10 Gy are safe dose constraints for 18-Gy single-fraction SRS. Esophagus V10 of 3 cc and V15 of 1 cc, trachea V10 of 3 cc, and V15 of 1 cc, oropharynx V10 of 3.5 cc and V15 of 1.5 cc, kidney V10 of 0.3 cc, and V15 of 0.1 cc are planning guidelines when these OARs are in proximity to the TV.« less

Data Link Test and Analysis System/ATCRBS Transponder Test System

DTIC Science & Technology

1990-05-01

cc pcinit() pcinit.cc plotdato( plotdat. cc plotmsgo( sumscrn *cc plotqueo( sumscrn. cc pmsg () pmsg.cc pr_head() prhead.cc Virt init() print.cc pw...The code data from the Decode Status word from hardware. 2 a data-> wind nm - The reply window that this data came from. mvarms) NAME mparms - Modify...character is entered. m5sg() NAME pmsg - Print error message. Source file - pmsg.cc. FUNCTION CALL pmsg (ecode, str) int ecode; /* Error code */ char

Teaching Experiment to Elucidate a Cation-Pi Effect in an Alkyne Cycloaddition Reaction and Illustrate Hypothesis-Driven Design of Experiments

ERIC Educational Resources Information Center

St.Germain, Elijah J.; Horowitz, Andrew S.; Rucco, Dominic; Rezler, Evonne M.; Lepore, Salvatore D.

2017-01-01

An organic chemistry experiment is described that is based on recent research to elucidate a novel cation-pi interaction between tetraalkammonium cations and propargyl hydrazines. This nonbonded interaction is a key component of the mechanism of ammonium-catalyzed intramolecular cycloaddition of nitrogen to the terminal carbon of a C-C triple bond…

The Development of Core Cognitive Skills in Autism: A 3-Year Prospective Study

ERIC Educational Resources Information Center

Pellicano, Elizabeth

2010-01-01

This longitudinal study tested the veracity of one candidate multiple-deficits account of autism by assessing 37 children with autism (M age = 67.9 months) and 31 typical children (M age = 65.2 months) on tasks tapping components of theory of mind (ToM), executive function (EF), and central coherence (CC) at intake and again 3 years later. As a…

Present and future of cervical cancer prevention in Spain: a cost-effectiveness analysis.

PubMed

Georgalis, Leonidas; de Sanjosé, Silvia; Esnaola, Mikel; Bosch, F Xavier; Diaz, Mireia

2016-09-01

Human papillomavirus (HPV) vaccination within a nonorganized setting creates a poor cost-effectiveness scenario. However, framed within an organized screening including primary HPV DNA testing with lengthening intervals may provide the best health value for invested money. To compare the effectiveness and cost-effectiveness of different cervical cancer (CC) prevention strategies, including current status and new proposed screening practices, to inform health decision-makers in Spain, a Markov model was developed to simulate the natural history of HPV and CC. Outcomes included cases averted, life expectancy, reduction in the lifetime risk of CC, life years saved, quality-adjusted life years (QALYs), net health benefits, lifetime costs, and incremental cost-effectiveness ratios. The willingness-to-pay threshold is defined at 20 000&OV0556;/QALY. Both costs and health outcomes were discounted at an annual rate of 3%. A strategy of 5-year organized HPV testing has similar effectiveness, but higher efficiency than 3-year cytology. Screening alone and vaccination combined with cytology are dominated by vaccination followed by 5-year HPV testing with cytology triage (12 214&OV0556;/QALY). The optimal age for both ending screening and switching age from cytology to HPV testing in older women is 5 years later for unvaccinated than for vaccinated women. Net health benefits decrease faster with diminishing vaccination coverage than screening coverage. Primary HPV DNA testing is more effective and cost-effective than current cytological screening. Vaccination uptake improvements and a gradual change toward an organized screening practice are critical components for achieving higher effectiveness and efficiency in the prevention of CC in Spain.

Enantiomer fractions of chlordane components in sediment from U.S. Geological Survey sites in lakes and rivers

USGS Publications Warehouse

Ulrich, E.M.; Foreman, W.T.; Van Metre, P.C.; Wilson, J.T.; Rounds, S.A.

2009-01-01

Spatial, temporal, and sediment-type trends in enantiomer signatures were evaluated for cis- and trans-chlordane (CC, TC) in archived core, suspended, and surficial-sediment samples from six lake, reservoir, and river sites across the United States. The enantiomer fractions (EFs) measured in these samples are in good agreement with those reported for sediment, soil, and air samples in previous studies. The chlordane EFs were generally close to the racemic value of 0.5, with CC values ranging from 0.493 to 0.527 (usually >0.5) and TC values from 0.463 to 0.53 (usually <0.5). EF changes with core depth were detected for TC and CC in some cores, with the most non-racemic values near the top of the core. Surficial and suspended sediments generally have EF values similar to the top core layers but are often more non-racemic, indicating that enantioselective degradation is occurring before soils are eroded and deposited into bottom sediments. We hypothesize that rapid losses (desorption or degradation) from suspended sediments of the more bioavailable chlordane fraction during transport and initial deposition could explain the apparent shift to more racemic EF values in surficial and top core sediments. Near racemic CC and TC in the core profiles suggest minimal alteration of chlordane from biotic degradation, unless it is via non-enantioselective processes. EF values for the heptachlor degradate, heptachlor epoxide (HEPX), determined in surficial sediments from one location only were always non-racemic (EF ??? 0.66), were indicative of substantial biotic processing, and followed reported EF trends.

Metal-organic cooperative catalysis in C-H and C-C bond activation and its concurrent recovery.

PubMed

Park, Young Jun; Park, Jung-Woo; Jun, Chul-Ho

2008-02-01

The development of an efficient catalytic activation (cleavage) system for C-H and C-C bonds is an important challenge in organic synthesis, because these bonds comprise a variety of organic molecules such as natural products, petroleum oils, and polymers on the earth. Among many elegant approaches utilizing transition metals to activate C-H and C-C bonds facilely, chelation-assisted protocols based on the coordinating ability of an organic moiety have attracted great attention, though they have often suffered from the need for an intact coordinating group in a substrate. In this Account, we describe our entire efforts to activate C-H or C-C bonds adjacent to carbonyl groups by employing a new concept of metal-organic cooperative catalysis (MOCC), which enables the temporal installation of a 2-aminopyridyl group into common aldehydes or ketones in a catalytic way. Consequently, a series of new catalytic reactions such as alcohol hydroacylation, oxo-ester synthesis, C-C triple bond cleavage, hydrative dimerization of alkynes, and skeletal rearrangements of cyclic ketones was realized through MOCC. In particular, in the quest for an optimized MOCC system composed of a Wilkinson's catalyst (Ph 3P) 3RhCl and an organic catalyst (2-amino-3-picoline), surprising efficiency enhancements could be achieved when benzoic acid and aniline were introduced as promoters for the aldimine formation process. Furthermore, a notable accomplishment of C-C bond activation has been made using 2-amino-3-picoline as a temporary chelating auxiliary in the reactions of unstrained ketones with various terminal olefins and Wilkinson's catalyst. In the case of seven-membered cyclic ketones, an interesting ring contraction to five- or six-membered ones takes place through skeletal rearrangements initiated by the C-C bond activation of MOCC. On the other hand, the fundamental advances of these catalytic systems into recyclable processes could be achieved by immobilizing both metal and organic components using a hydrogen-bonded self-assembled system as a catalyst support. This catalyst-recovery system provides a homogeneous phase at high temperature during the reaction and a heterogeneous phase at room temperature after the reaction. The product could be separated conveniently from the self-assembly support system by decanting the upper layer. The immobilized catalysts of both 2-aminopyridine and rhodium metal species sustained high catalytic activity for up to the eight catalytic reactions. In conclusion, the successful incorporation of an organocatalytic cycle into a transition metal catalyzed reaction led us to find MOCC for C-H and C-C bond activation. In addition, the hydrogen-bonded self-assembled support has been developed for an efficient and effective recovery system of homogeneous catalysts and could be successful in immobilizing both metal and organic catalysts.

Coexistence of diploid, triploid and tetraploid crucian carp (Carassius auratus) in natural waters

PubMed Central

2011-01-01

Background Crucian carp (abbreviated CC) belongs to the genus of Carassius within the family of Cyprinidae. It has been one of the most important freshwater species for Chinese aquaculture and is especially abundant in the Dongting water system of Hunan province. CC used to be considered as all diploid forms. However, coexistence of diploid (abbreviated 2nCC), triploid (abbreviated 3nCC) and tetraploid crucian carp (abbreviated 4nCC) population of the Dongting water system was first found by our recently researches. Results We examined the ploidy level and compared biological characteristics in different ploidy CC. In reproductive mode, 2nCC was bisexual generative and 4nCC generated all-female offspring by gynogenesis. However, 3nCC generated progenies in two different ways. 3nCC produced bisexual triploid offspring fertilized with 3nCC spermatozoa, while it produced all-female triploid offspring by gynogenesis when its ova were activated by heterogenous spermatozoa. The complete mitochondrial DNA of three different ploidy fishes was sequenced and analyzed, suggesting no significant differences. Interestingly, microchromosomes were found only in 3nCC, which were concluded to be the result of hybridization. Allogenetic DNA fragments of Sox genes were obtained in 3nCC and 4nCC, which were absent in 2nCC. Phylogenetics analysis based on Sox4 gene indicated 3nCC and 4nCC formed a separate group from 2nCC. Conclusions In summary, this is the first report of the co-existence of three types of different ploidy crucian carps in natural waters in China. It was proved that the coexistence of different ploidy CC was reproductively maintained. We further hypothesized that 3nCC and 4nCC were allopolyploids that resulted from hybridization. The different ploidy CC population we obtained in this study possesses great significance for the study of polyploidization and the evolution of vertebrates. PMID:21276259

High content cell-based assay for the inflammatory pathway

NASA Astrophysics Data System (ADS)

Mukherjee, Abhishek; Song, Joon Myong

2015-07-01

Cellular inflammation is a non-specific immune response to tissue injury that takes place via cytokine network orchestration to maintain normal tissue homeostasis. However chronic inflammation that lasts for a longer period, plays the key role in human diseases like neurodegenerative disorders and cancer development. Understanding the cellular and molecular mechanisms underlying the inflammatory pathways may be effective in targeting and modulating their outcome. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that effectively combines the pro-inflammatory features with the pro-apoptotic potential. Increased levels of TNF-α observed during acute and chronic inflammatory conditions are believed to induce adverse phenotypes like glucose intolerance and abnormal lipid profile. Natural products e. g., amygdalin, cinnamic acid, jasmonic acid and aspirin have proven efficacy in minimizing the TNF-α induced inflammation in vitro and in vivo. Cell lysis-free quantum dot (QDot) imaging is an emerging technique to identify the cellular mediators of a signaling cascade with a single assay in one run. In comparison to organic fluorophores, the inorganic QDots are bright, resistant to photobleaching and possess tunable optical properties that make them suitable for long term and multicolor imaging of various components in a cellular crosstalk. Hence we tested some components of the mitogen activated protein kinase (MAPK) pathway during TNF-α induced inflammation and the effects of aspirin in HepG2 cells by QDot multicolor imaging technique. Results demonstrated that aspirin showed significant protective effects against TNF-α induced cellular inflammation. The developed cell based assay paves the platform for the analysis of cellular components in a smooth and reliable way.

Application of the CC(P;Q) Hierarchy of Coupled-Cluster Methods to the Beryllium Dimer.

PubMed

Magoulas, Ilias; Bauman, Nicholas P; Shen, Jun; Piecuch, Piotr

2018-02-08

The performance of coupled-cluster approaches with higher-than-doubly excited clusters, including the CCSD(T), CCSD(2) T , CR-CC(2,3), CCSD(TQ), and CR-CC(2,4) corrections to CCSD, the active-space CCSDt, CCSDtq, and CCSDTq methods, and the CC(t;3), CC(t,q;3), CC(t,q;3,4), and CC(q;4) corrections to CCSDt, CCSDtq, and CCSDTq resulting from the CC(P;Q) formalism, in reproducing the CCSDT and CCSDTQ potential energy curves and vibrational term values characterizing Be 2 in its electronic ground state is assessed. The correlation-consistent aug-cc-pVnZ and aug-cc-pCVnZ (n = T and Q) basis sets are employed. Among the CCSD-based corrections, the completely renormalized CR-CC(2,3) and CR-CC(2,4) approaches perform the best. The CC(t;3), CC(t,q;3), CC(t,q;3,4), and CC(q;4) methods, especially CC(t;3) and CC(q;4), outperform other employed approaches in reproducing the CCSDT and CCSDTQ data. Composite schemes combining the all-electron CCSDT calculations extrapolated to the complete basis set limit with the frozen-core CC(q;4) and CCSDTQ computations using the aug-cc-pVTZ basis to account for connected quadruple excitations reproduce the latest experimental vibrational spectrum of Be 2 to within 4-5 cm -1 , when the vibrational spacings are examined, with typical errors being below 1-2 cm -1 . The resulting binding energies and equilibrium bond lengths agree with their experimentally derived counterparts to within ∼10 cm -1 and 0.01 Å.

Generation of a Tet-On Expression System to Study Transactivation Ability of Tax-2.

PubMed

Bignami, Fabio; Sozzi, Riccardo Alessio; Pilotti, Elisabetta

2017-01-01

HTLV Tax proteins (Tax-1 and Tax-2) are known to be able to transactivate several host cellular genes involved in complex molecular pathways. Here, we describe a stable and regulated high-level expression model based on Tet-On system, to study the capacity of Tax-2 to transactivate host genes. In particular, the Jurkat Tet-On cell line suitable for evaluating the ability of Tax-2 to stimulate transactivation of a specific host gene, CCL3L1 (C-C motif chemokine ligand 3 like 1 gene), was selected. Then, a plasmid expressing tax-2 gene under control of a tetracycline-response element was constructed. To avoid the production of a fusion protein between the report gene and the inserted gene, a bidirectional plasmid was designed. Maximum expression and fast response time were achieved by using nucleofection technology as transfection method. After developing an optimized protocol for efficiently transferring tax-2 gene in Jurkat Tet-On cellular model and exposing transfected cells to Dox (doxycycline, a tetracycline derivate), a kinetics of tax-2 expression through TaqMan Real-time PCR assay was determined.

Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3.

PubMed

Khan, Nahid A; Auranen, Mari; Paetau, Ilse; Pirinen, Eija; Euro, Liliya; Forsström, Saara; Pasila, Lotta; Velagapudi, Vidya; Carroll, Christopher J; Auwerx, Johan; Suomalainen, Anu

2014-06-01

Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD(+) precursor, was previously shown to boost NAD(+) levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD(+) levels are a promising treatment strategy for mitochondrial myopathy. © 2014 The Authors. Published under the terms of the CC BY license.

Long-term outcome of patients undergoing liver transplantation for mixed hepatocellular carcinoma and cholangiocarcinoma: an analysis of the UNOS database.

PubMed

Vilchez, Valery; Shah, Malay B; Daily, Michael F; Pena, Luis; Tzeng, Ching-Wei D; Davenport, Daniel; Hosein, Peter J; Gedaly, Roberto; Maynard, Erin

2016-01-01

Mixed hepatocellular and cholangiocarcinoma (HCC-CC) have been associated with a poor prognosis after liver transplantation (LT). We aimed to evaluate long-term outcomes in patients undergoing LT for HCC-CC versus patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC). Retrospective analysis of the United Network for Organ Sharing (UNOS) database from 1994-2013. Overall survival (OS) in patients with HCC-CC, HCC, and CC, were compared. We identified 4049 patients transplanted for primary malignancy (94 HCC-CC; 3515 HCC; 440 CC). Mean age of patients with HCC-CC was 57 ± 10 years, and 77% were male. MELD score did not differ among the groups (p = 0.637). Hepatitis C virus was the most common secondary diagnosis within the HCC-CC (44%) and HCC (36%) cohorts, with primary sclerosing cholangitis in the CC (16%) cohort. OS rates at 1, 3 and 5 years for HCC-CC (82%, 47%, 40%) were similar to CC (79%, 58%, 47%), but significantly worse than HCC (86%, 72%, and 62% p = 0.002). Patients undergoing LT for HCC had significantly better survival compared to those transplanted for HCC-CC and CC. LT for mixed HCC-CC confers a survival rate similar to selected patients with CC. Efforts should be made to identify HCC-CC patients preoperatively. Copyright © 2015. Published by Elsevier Ltd.

Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort.

PubMed

Ryberg, C; Rostrup, E; Paulson, O B; Barkhof, F; Scheltens, P; van Straaten, E C W; van der Flier, W M; Fazekas, F; Schmidt, R; Ferro, J M; Baezner, H; Erkinjuntti, T; Jokinen, H; Wahlund, L-O; Poggesi, A; Pantoni, L; Inzitari, D; Waldemar, G

2011-08-15

The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly. Copyright © 2011 Elsevier B.V. All rights reserved.

Validation of electronic structure methods for isomerization reactions of large organic molecules.

PubMed

Luo, Sijie; Zhao, Yan; Truhlar, Donald G

2011-08-14

In this work the ISOL24 database of isomerization energies of large organic molecules presented by Huenerbein et al. [Phys. Chem. Chem. Phys., 2010, 12, 6940] is updated, resulting in the new benchmark database called ISOL24/11, and this database is used to test 50 electronic model chemistries. To accomplish the update, the very expensive and highly accurate CCSD(T)-F12a/aug-cc-pVDZ method is first exploited to investigate a six-reaction subset of the 24 reactions, and by comparison of various methods with the benchmark, MCQCISD-MPW is confirmed to be of high accuracy. The final ISOL24/11 database is composed of six reaction energies calculated by CCSD(T)-F12a/aug-cc-pVDZ and 18 calculated by MCQCISD-MPW. We then tested 40 single-component density functionals (both local and hybrid), eight doubly hybrid functionals, and two other methods against ISOL24/11. It is found that the SCS-MP3/CBS method, which is used as benchmark for the original ISOL24, has an MUE of 1.68 kcal mol(-1), which is close to or larger than some of the best tested DFT methods. Using the new benchmark, we find ωB97X-D and MC3MPWB to be the best single-component and doubly hybrid functionals respectively, with PBE0-D3 and MC3MPW performing almost as well. The best single-component density functionals without molecular mechanics dispersion-like terms are M08-SO, M08-HX, M05-2X, and M06-2X. The best single-component density functionals without Hartree-Fock exchange are M06-L-D3 when MM terms are included and M06-L when they are not.

Nano-casted Metal Oxide Aerogels as Dual Purpose Structural Components for Space Exploration

NASA Technical Reports Server (NTRS)

Vassilaras, Plousia E.

2004-01-01

NASA missions and space exploration rely on strong, ultra lightweight materials. Such materials are needed for building up past and present space vehicles such as the Sojourner Rover (1997) or the two MERs (2003), but also for a number of components and/or systems including thermal insulators, Solar Sails, Rigid Aeroshells, and Ballutes. The purpose of my internship here at Glenn Research Center is to make dual purpose materials; materials that in addition to being lightweight have electronic, photophysical and magnetic properties and, therefore, act as electronic components and sensors as well as structural components. One type of ultra lightweight material of great interest is aerogels, which have densities ranging from 0.003 g/cc to 0.8 g/cc . However, aerogels are extremely fragile and, as a result, have limited practical applications. Recently, Glenn Research Center has developed a process of nano-casting polymers onto the inorganic network of silica-based aerogels increasing the strength 300 fold while only increasing the density 3 fold. By combining the process of nano-casting polymers with inorganic oxide networks other than silica, we are actively pursuing lightweight dual purpose materials. To date, thirty different inorganic oxide aerogels have been prepared using either standard sol-gel chemistry or a non-alkoxide method involving metal chloride precursors and an epoxide; epichlorohydrin, propylene oxide or trimethylene oxide, as proton scavengers. More importantly, preliminary investigations show that the residual surface hydroxyl groups on each of these inorganic oxide aerogels can be successfully crosslinked with urethane. In addition to characterizing physical and mechanical properties such as density, strength and flexibility, each of these metal oxide aerogels are being characterized for thermal and electronic conductivity and magnetic and optical properties.

Characterization of CcSTOP1; a C2H2-type transcription factor regulates Al tolerance gene in pigeonpea.

PubMed

Daspute, Abhijit Arun; Kobayashi, Yuriko; Panda, Sanjib Kumar; Fakrudin, Bashasab; Kobayashi, Yasufumi; Tokizawa, Mutsutomo; Iuchi, Satoshi; Choudhary, Arbind Kumar; Yamamoto, Yoshiharu Y; Koyama, Hiroyuki

2018-01-01

Al-responsive citrate-transporting CcMATE1 function and its regulation by CcSTOP1 were analyzed using NtSTOP1 -KD tobacco- and pigeonpea hairy roots, respectively, CcSTOP1 binding sequence of CcMATE1 showed similarity with AtALMT1 promoter. The molecular mechanisms of Aluminum (Al) tolerance in pigeonpea (Cajanus cajan) were characterized to provide information for molecular breeding. Al-inducible citrate excretion was associated with the expression of MULTIDRUGS AND TOXIC COMPOUNDS EXCLUSION (CcMATE1), which encodes a citrate transporter. Ectopic expression of CcMATE1-conferred Al tolerance to hairy roots of transgenic tobacco with the STOP1 regulation system knocked down. This gain-of-function approach clearly showed CcMATE1 was involved in Al detoxification. The expression of CcMATE1 and another Al-tolerance gene, ALUMINUM SENSITIVE 3 (CcALS3), was regulated by SENSITIVE TO PROTON RHIZOTOXICITY1 (CcSTOP1) according to loss-of-function analysis of pigeonpea hairy roots in which CcSTOP1 was suppressed. An in vitro binding assay showed that the Al-responsive CcMATE1 promoter contained the GGNVS consensus bound by CcSTOP1. Mutation of GGNVS inactivated the Al-inducible expression of CcMATE1 in pigeonpea hairy roots. This indicated that CcSTOP1 binding to the promoter is critical for CcMATE1 expression. The STOP1 binding sites of both the CcMATE1 and AtALMT1 promoters contained GGNVS and a flanking 3' sequence. The GGNVS region was identical in both CcMATE1 and AtALMT1. By contrast, the 3' flanking sequence with binding affinity to STOP1 did not show similarity. Putative STOP1 binding sites with similar structures were also found in Al-inducible MATE and ALMT1 promoters in other plant species. The characterized Al-responsive CcSTOP1 and CcMATE1 genes will help in pigeonpea breeding in acid soil tolerance.

A model predictive current control of flux-switching permanent magnet machines for torque ripple minimization

NASA Astrophysics Data System (ADS)

Huang, Wentao; Hua, Wei; Yu, Feng

2017-05-01

Due to high airgap flux density generated by magnets and the special double salient structure, the cogging torque of the flux-switching permanent magnet (FSPM) machine is considerable, which limits the further applications. Based on the model predictive current control (MPCC) and the compensation control theory, a compensating-current MPCC (CC-MPCC) scheme is proposed and implemented to counteract the dominated components in cogging torque of an existing three-phase 12/10 FSPM prototyped machine, and thus to alleviate the influence of the cogging torque and improve the smoothness of electromagnetic torque as well as speed, where a comprehensive cost function is designed to evaluate the switching states. The simulated results indicate that the proposed CC-MPCC scheme can suppress the torque ripple significantly and offer satisfactory dynamic performances by comparisons with the conventional MPCC strategy. Finally, experimental results validate both the theoretical and simulated predictions.

Imidazole-based deep eutectic solvents for starch dissolution and plasticization.

PubMed

Zdanowicz, Magdalena; Spychaj, Tadeusz; Mąka, Honorata

2016-04-20

Potato starch and high-amylose starch were treated with imidazole-based deep eutectic solvents (DESs) as dissolution and plasticization media. Beside imidazole (IM) for two-component DESs preparation choline chloride (CC), glycerol (G) or carboxylic acids (citric or malic) were used. An influence of water content in starch (as well as an extra water in the starch/DES system) on polymer dissolution and plasticization processes was investigated. Dissolution and gelatinization of starch in DESs were followed via DSC and laser scanning microscopy. A rheometric characteristics revealed an influence of starch/DES system storage time on the plasticization process. The tendency to recrystallization of compression-molded-starch films was evaluated using XRD technique. High dissolution and plasticization effectiveness of CC/IM and G/IM and a low tendency to film retrogradation of thermoplasticized starch were noted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural Ecosystems Therapy for HIV+ African-American women and drug abuse relapse.

PubMed

Feaster, Daniel J; Burns, Myron J; Brincks, Ahnalee M; Prado, Guillermo; Mitrani, Victoria B; Mauer, Megaly H; Szapocznik, Jose

2010-06-01

This report examines the effect of Structural Ecosystems Therapy (SET) for (n=143) HIV+ African-American women on rate of relapse to substance use relative to both a person-centered approach (PCA) to therapy and a community control (CC) group. A prior report has shown SET to decrease psychological distress and family hassles relative to these 2 comparison groups. In new analyses, SET and CC had a significant protective effect against relapse as compared with PCA. There is evidence that SET's protective effect on relapse was related to reductions in family hassles, whereas there was not a direct impact of change in psychological distress on rates of relapse. Lower retention in PCA, perhaps caused by the lack of a directive component to PCA, may have put these women at greater risk for relapse. Whereas SET did not specifically address substance abuse, SET indirectly protected at-risk women from relapse through reductions in family hassles.

Oxidative 1,2-carboamination of alkenes with alkyl nitriles and amines toward γ-amino alkyl nitriles

NASA Astrophysics Data System (ADS)

Liu, Yan-Yun; Yang, Xu-Heng; Song, Ren-Jie; Luo, Shenglian; Li, Jin-Heng

2017-04-01

Difunctionalization of alkenes has become a powerful tool for quickly increasing molecular complexity in synthesis. Despite significant progress in the area of alkene difunctionalization involving the incorporation of a nitrogen atom across the C-C double bonds, approaches for the direct 1,2-carboamination of alkenes to produce linear N-containing molecules are scarce and remain a formidable challenge. Here we describe a radical-mediated oxidative intermolecular 1,2-alkylamination of alkenes with alkyl nitriles and amines involving C(sp3)-H oxidative functionalization catalysed by a combination of Ag2CO3 with iron Lewis acids. This three-component alkene 1,2-alkylamination method is initiated by the C(sp3)-H oxidative radical functionalization, which enables one-step formation of two new chemical bonds, a C-C bond and a C-N bond, to selectively produce γ-amino alkyl nitriles.

Approximations to complete basis set-extrapolated, highly correlated non-covalent interaction energies.

PubMed

Mackie, Iain D; DiLabio, Gino A

2011-10-07

The first-principles calculation of non-covalent (particularly dispersion) interactions between molecules is a considerable challenge. In this work we studied the binding energies for ten small non-covalently bonded dimers with several combinations of correlation methods (MP2, coupled-cluster single double, coupled-cluster single double (triple) (CCSD(T))), correlation-consistent basis sets (aug-cc-pVXZ, X = D, T, Q), two-point complete basis set energy extrapolations, and counterpoise corrections. For this work, complete basis set results were estimated from averaged counterpoise and non-counterpoise-corrected CCSD(T) binding energies obtained from extrapolations with aug-cc-pVQZ and aug-cc-pVTZ basis sets. It is demonstrated that, in almost all cases, binding energies converge more rapidly to the basis set limit by averaging the counterpoise and non-counterpoise corrected values than by using either counterpoise or non-counterpoise methods alone. Examination of the effect of basis set size and electron correlation shows that the triples contribution to the CCSD(T) binding energies is fairly constant with the basis set size, with a slight underestimation with CCSD(T)∕aug-cc-pVDZ compared to the value at the (estimated) complete basis set limit, and that contributions to the binding energies obtained by MP2 generally overestimate the analogous CCSD(T) contributions. Taking these factors together, we conclude that the binding energies for non-covalently bonded systems can be accurately determined using a composite method that combines CCSD(T)∕aug-cc-pVDZ with energy corrections obtained using basis set extrapolated MP2 (utilizing aug-cc-pVQZ and aug-cc-pVTZ basis sets), if all of the components are obtained by averaging the counterpoise and non-counterpoise energies. With such an approach, binding energies for the set of ten dimers are predicted with a mean absolute deviation of 0.02 kcal/mol, a maximum absolute deviation of 0.05 kcal/mol, and a mean percent absolute deviation of only 1.7%, relative to the (estimated) complete basis set CCSD(T) results. Use of this composite approach to an additional set of eight dimers gave binding energies to within 1% of previously published high-level data. It is also shown that binding within parallel and parallel-crossed conformations of naphthalene dimer is predicted by the composite approach to be 9% greater than that previously reported in the literature. The ability of some recently developed dispersion-corrected density-functional theory methods to predict the binding energies of the set of ten small dimers was also examined. © 2011 American Institute of Physics

In vivo evolution of HIV-1 co-receptor usage and sensitivity to chemokine-mediated suppression.

PubMed

Scarlatti, G; Tresoldi, E; Björndal, A; Fredriksson, R; Colognesi, C; Deng, H K; Malnati, M S; Plebani, A; Siccardi, A G; Littman, D R; Fenyö, E M; Lusso, P

1997-11-01

Following the identification of the C-C chemokines RANTES, MIP-1alpha and MIP-1beta as major human immunodeficiency virus (HIV)-suppressive factors produced by CD8+ T cells, several chemokine receptors were found to serve as membrane co-receptors for primate immunodeficiency lentiretroviruses. The two most widely used co-receptors thus far recognized, CCR5 and CXCR4, are expressed by both activated T lymphocytes and mononuclear phagocytes. CCR5, a specific RANTES, MIP-1alpha and MIP-1 receptor, is used preferentially by non-MT2-tropic HIV-1 and HIV-2 strains and by simian immunodeficiency virus (SIV), whereas CXCR4, a receptor for the C-X-C chemokine SDF-1, is used by MT2-tropic HIV-1 and HIV-2, but not by SIV. Other receptors with a more restricted cellular distribution, such as CCR2b, CCR3 and STRL33, can also function as co-receptors for selected viral isolates. The third variable region (V3) of the gp120 envelope glycoprotein of HIV-1 has been fingered as a critical determinant of the co-receptor choice. Here, we document a consistent pattern of evolution of viral co-receptor usage and sensitivity to chemokine-mediated suppression in a longitudinal follow-up of children with progressive HIV-1 infection. Viral isolates obtained during the asymptomatic stages generally used only CCR5 as a co-receptor and were inhibited by RANTES, MIP-1alpha and MIP-1beta, but not by SDF-1. By contrast, the majority of the isolates derived after the progression of the disease were resistant to C-C chemokines, having acquired the ability to use CXCR4 and, in some cases, CCR3, while gradually losing CCR5 usage. Surprisingly, most of these isolates were also insensitive to SDF-1, even when used in combination with RANTES. An early acquisition of CXCR4 usage predicted a poor prognosis. In children who progressed to AIDS without a shift to CXCR4 usage, all the sequential isolates were CCR5-dependent but showed a reduced sensitivity to C-C chemokines. Discrete changes in the V3 domain of gp120 were associated with the loss of sensitivity to C-C chemokines and the shift in co-receptor usage. These results suggest an adaptive evolution of HIV-1 in vivo, leading to escape from the control of the antiviral C-C chemokines.

NFAT Signaling and the Tumorigenic Microenvironment of the Prostate

DTIC Science & Technology

2017-12-01

ABSTRACT Although the importance of microenvironment in prostate cancer is widely recognized, the molecular and cellular processes leading from genetic ...non-invasive clinical tests. Second, the illustration of the main cellular and molecular components in the tumorigenic microenvironment provides new...potential of NFATc1 as a novel biomarker for prostate cancer diagnosis/prognosis. We will take advantage of the cellular precision, genetic manipulability

Deregulation of PAX2 expression in renal cell tumours: mechanisms and potential use in differential diagnosis.

PubMed

Patrício, Patrícia; Ramalho-Carvalho, João; Costa-Pinheiro, Pedro; Almeida, Mafalda; Barros-Silva, João Diogo; Vieira, Joana; Dias, Paula Cristina; Lobo, Francisco; Oliveira, Jorge; Teixeira, Manuel R; Henrique, Rui; Jeronimo, Carmen

2013-08-01

Expression of PAX2 (Paired-box 2) is suppressed through promoter methylation at the later stages of embryonic development, but eventually reactivated during carcinogenesis. Pax-2 is commonly expressed in the most prevalent renal cell tumour (RCT) subtypes-clear cell RCC (ccRCC), papillary RCC (pRCC) and oncocytoma--but not in chromophobe RCC (chrRCC), which frequently displays chromosome 10 loss (to which PAX2 is mapped). Herein, we assessed the epigenetic and/or genetic alterations affecting PAX2 expression in RCTs and evaluated its potential as biomarker. We tested 120 RCTs (30 of each main subtype) and four normal kidney tissues. Pax-2 expression was assessed by immunohistochemistry and PAX2 mRNA expression levels were determined by quantitative RT-PCR. PAX2 promoter methylation status was assessed by methylation-specific PCR and bisulfite sequencing. Chromosome 10 and PAX2 copy number alterations were determined by FISH. Pax-2 immunoexpression was significantly lower in chrRCC compared to other RCT subtypes. Using a 10% immunoexpression cut-off, Pax-2 immunoreactivity discriminated chrRCC from oncocytoma with 67% sensitivity and 90% specificity. PAX2 mRNA expression was significantly lower in chrRCC, compared to ccRCC, pRCC and oncocytoma, and transcript levels correlated with immunoexpression. Whereas no promoter methylation was found in RCTs or normal kidney, 69% of chrRCC displayed chromosome 10 monosomy, correlating with Pax-2 immunoexpression. We concluded that Pax-2 expression might be used as an ancillary tool to discriminate chrRCC from oncocytomas with overlapping morphological features. The biological rationale lies on the causal relation between Pax-2 expression and chromosome 10 monosomy, but not PAX2 promoter methylation, in chrRCC. © 2013 The Authors. Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

The Monocyte Chemoattractant Protein-1/Cognate CC Chemokine Receptor 2 System Affects Cell Motility in Cultured Human Podocytes

PubMed Central

Burt, Davina; Salvidio, Gennaro; Tarabra, Elena; Barutta, Federica; Pinach, Silvia; Dentelli, Patrizia; Camussi, Giovanni; Perin, Paolo Cavallo; Gruden, Gabriella

2007-01-01

In crescentic glomerulonephritis (GN), monocyte chemoattractant protein-1 (MCP-1) is overexpressed within the glomeruli, and MCP-1 blockade has renoprotective effects. Adult podocytes are in a quiescent state, but acquisition of a migratory/proliferative phenotype has been described in crescentic GN and implicated in crescent formation. The cognate CC chemokine receptor 2 (CCR2), the MCP-1 receptor, is expressed by other cell types besides monocytes and has been implicated in both cell proliferation and migration. We investigated whether MCP-1 binding to CCR2 can induce a migratory/proliferative response in cultured podocytes. MCP-1 binding to CCR2 enhanced podocyte chemotaxis/haptotaxis in a concentration-dependent manner and had a modest effect on cell proliferation. Closure of a wounded podocyte monolayer was delayed by CCR2 blockade, and CCR2 was overexpressed at the wound edge, suggesting a role for CCR2 in driving podocyte migration. Immunohistochemical analysis of kidney biopsies from patients with crescentic GN demonstrated CCR2 expression in both podocytes and cellular crescents, confirming the clinical relevance of our in vitro findings. In conclusion, the MCP-1/CCR2 system is functionally active in podocytes and may be implicated in the migratory events triggered by podocyte injury in crescentic GN and other glomerular diseases. PMID:18055544

Human Papillomavirus Infections and Cancer Stem Cells of Tumors from the Uterine Cervix

PubMed Central

López, Jacqueline; Ruíz, Graciela; Organista-Nava, Jorge; Gariglio, Patricio; García-Carrancá, Alejandro

2012-01-01

Different rate of development of productive infections (as low grade cervical intraepithelial neoplasias), or high grade lesions and cervical malignant tumors associated with infections of the Transformation zone (TZ) by High-Risk Human Papillomavirus (HR-HPV), could suggest that different epithelial host target cells could exist. If there is more than one target cell, their differential infection by HR-HPV may play a central role in the development of cervical cancer. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support in several solid tumors, including cervical cancer (CC). According to the cancer stem cell (CSC) hypothesis, CC can now be considered a disease in which stem cells of the TZ are converted to cervical cancer stem cells by the interplay between HR-HPV viral oncogenes and cellular alterations that are thought to be finally responsible for tumor initiation and maintenance. Current studies of CSC could provide novel insights regarding tumor initiation and progression, their relation with viral proteins and interplay with the tumor micro-environment. This review will focus on the biology of cervical cancer stem cells, which might contribute to our understanding of the mechanisms responsible for cervical tumor development. PMID:23341858

Identification of SNP in HSP90AB1 and its association with the relative thermotolerance and milk production traits in Indian dairy cattle.

PubMed

Sajjanar, Basavaraj; Deb, Rajib; Singh, Umesh; Kumar, Sushil; Brahmane, Manoj; Nirmale, Avinash; Bal, Santanu Kumar; Minhas, P S

2015-01-01

Heat shock proteins (Hsp) play crucial role in cellular thermotolerance and heat stress response. In the present work, Allele specific PCR (AS-PCR) was standardized to detect the nucleotide polymorphism within the HSP90AB1 gene (SNP g.4338T>C) in Indian breeds of dairy cattle. The identified genotypes were associated with relative thermotolerance in terms of physiological parameters and milk production traits. The results of the experiments revealed that the genotype frequency of CC, CT, and TT for Sahiwal were 0.05, 0.78, and 0.17, respectively, and in Frieswal, the frequencies were 0.20, 0.70, and 0.10, respectively. The average rectal temperature (ART) and average respiration rates (ARR) were recorded during peak summer stress and heat tolerance coefficient (HTC) was calculated. The association studies indicated that TT genotypes had significantly (P < 0.01) higher HTC and lower ARR values than CT and CC in both the breeds. The TT genotype animals also had better production parameter in terms of total milk yield (TMY) (P < 0.01). These findings may partly suggest the role of HSP90AB1 polymorphisms in the regulation of heat stress response and consequent effect on production traits. Nevertheless, involvement of other regulatory mechanisms cannot be overruled.

Inhibition of AMP-Activated Protein Kinase Signaling Alleviates Impairments in Hippocampal Synaptic Plasticity Induced by Amyloid β

PubMed Central

Ma, Tao; Chen, Yiran; Vingtdeux, Valerie; Zhao, Haitian; Viollet, Benoit; Marambaud, Philippe

2014-01-01

The AMP-activated protein kinase (AMPK) is a Ser/Thr kinase that is activated in response to low-energy states to coordinate multiple signaling pathways to maintain cellular energy homeostasis. Dysregulation of AMPK signaling has been observed in Alzheimer's disease (AD), which is associated with abnormal neuronal energy metabolism. In the current study we tested the hypothesis that aberrant AMPK signaling underlies AD-associated synaptic plasticity impairments by using pharmacological and genetic approaches. We found that amyloid β (Aβ)-induced inhibition of long-term potentiation (LTP) and enhancement of long-term depression were corrected by the AMPK inhibitor compound C (CC). Similarly, LTP impairments in APP/PS1 transgenic mice that model AD were improved by CC treatment. In addition, Aβ-induced LTP failure was prevented in mice with genetic deletion of the AMPK α2-subunit, the predominant AMPK catalytic subunit in the brain. Furthermore, we found that eukaryotic elongation factor 2 (eEF2) and its kinase eEF2K are key downstream effectors that mediate the detrimental effects of hyperactive AMPK in AD pathophysiology. Our findings describe a previously unrecognized role of aberrant AMPK signaling in AD-related synaptic pathophysiology and reveal a potential therapeutic target for AD. PMID:25186765

Inhibition of Ca2+-activated Cl- channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea.

PubMed

Namkung, Wan; Thiagarajah, Jay R; Phuan, Puay-Wah; Verkman, A S

2010-11-01

TMEM16A was found recently to be a calcium-activated Cl(-) channel (CaCC). CaCCs perform important functions in cell physiology, including regulation of epithelial secretion, cardiac and neuronal excitability, and smooth muscle contraction. CaCC modulators are of potential utility for treatment of hypertension, diarrhea, and cystic fibrosis. Screening of drug and natural product collections identified tannic acid as an inhibitor of TMEM16A, with IC(50) ∼ 6 μM and ∼100% inhibition at higher concentrations. Tannic acid inhibited CaCCs in multiple cell types but did not affect CFTR Cl(-) channels. Structure-activity analysis indicated the requirement of gallic or digallic acid substituents on a macromolecular scaffold (gallotannins), as are present in green tea and red wine. Other polyphenolic components of teas and wines, including epicatechin, catechin, and malvidin-3-glucoside, poorly inhibited CaCCs. Remarkably, a 1000-fold dilution of red wine and 100-fold dilution of green tea inhibited CaCCs by >50%. Tannic acid, red wine, and green tea inhibited arterial smooth muscle contraction and intestinal Cl(-) secretion. Gallotannins are thus potent CaCC inhibitors whose biological activity provides a potential molecular basis for the cardioprotective and antisecretory benefits of red wine and green tea.

Externally Heated Protostellar Cores in the Ophiuchus Star-Forming Region

NASA Technical Reports Server (NTRS)

Lindberg, Johan E.; Charnley, Steven B.; Jorgensen, Jes K.; Cordiner, Martin A.; Bjerkeli, Per

2017-01-01

We present APEX 218 GHz observations of molecular emission in a complete sample of embedded protostars in the Ophiuchus star-forming region. To study the physical properties of the cores, we calculate H2CO and c-C3H2 rotational temperatures, both of which are good tracers of the kinetic temperature of the molecular gas. We find that the H2CO temperatures range between 16K and 124K, with the highest H2CO temperatures toward the hot corino source IRAS 16293-2422 (69-124 K) and the sources in the rho Oph A cloud (23-49 K) located close to the luminous Herbig Be star S1, which externally irradiates the rho Oph A cores. On the other hand, the c-C3H2 rotational temperature is consistently low (7-17 K) in all sources. Our results indicate that the c-C3H2 emission is primarily tracing more shielded parts of the envelope whereas the H2CO emission (at the angular scale of the APEX beam; 3600 au in Ophiuchus) mainly traces the outer irradiated envelopes, apart from in IRAS?16293-2422, where the hot corino emission dominates. In some sources, a secondary velocity component is also seen, possibly tracing the molecular outflow.

Selective advantages of two major clones of carbapenem-resistant Pseudomonas aeruginosa isolates (CC235 and CC641) from Korea: antimicrobial resistance, virulence and biofilm-forming activity.

PubMed

Lee, Ji-Young; Peck, Kyong Ran; Ko, Kwan Soo

2013-07-01

The characteristics of carbapenem-resistant P. aeruginosa (CRPA) isolates from Korea were investigated. Two major clones, clonal complex (CC) 235 and CC641, were identified. CC235, an important international clone, might have been imported recently in Korea as this clone displayed a homogeneous genotype, oprD mutation and antimicrobial resistance profile. While 13 ST235 isolates harboured the blaIMP-6 gene, which conferred high-level meropenem resistance, CC641 isolates showed high biofilm-forming activity. CC235 and CC641 isolates showed distinct distribution of ferripyoverdine receptor type and virulence markers. While all CC235 isolates were of the fpvAIIb type and exoS(-)/exoU(+), CC641 isolates were exoS(+)/exoU(-), and all but one showed the fpvAIII type. CC235 and CC641 isolates were also characterized by different extracellular protease activity: staphylolysin and elastase activities in CC235 and CC641, respectively. Two major CRPA clones in Korea seem to be predominant, reflecting their selective advantage by virtue of antimicrobial resistance, virulence and biofilm-forming activity.

Light-dependent governance of cell shape dimensions in cyanobacteria.

PubMed

Montgomery, Beronda L

2015-01-01

The regulation of cellular dimension is important for the function and survival of cells. Cellular dimensions, such as size and shape, are regulated throughout the life cycle of bacteria and can be adapted in response to environmental changes to fine-tune cellular fitness. Cell size and shape are generally coordinated with cell growth and division. Cytoskeletal regulation of cell shape and cell wall biosynthesis and/or deposition occurs in a range of organisms. Photosynthetic organisms, such as cyanobacteria, particularly exhibit light-dependent regulation of morphogenes and generation of reactive oxygen species and other signals that can impact cellular dimensions. Environmental signals initiate adjustments of cellular dimensions, which may be vitally important for optimizing resource acquisition and utilization or for coupling the cellular dimensions with the regulation of subcellular organization to maintain optimal metabolism. Although the involvement of cytoskeletal components in the regulation of cell shape is widely accepted, the signaling factors that regulate cytoskeletal and other distinct components involved in cell shape control, particularly in response to changes in external light cues, remain to be fully elucidated. In this review, factors impacting the inter-coordination of growth and division, the relationship between the regulation of cellular dimensions and central carbon metabolism, and consideration of the effects of specific environment signals, primarily light, on cell dimensions in cyanobacteria will be discussed. Current knowledge about the molecular bases of the light-dependent regulation of cellular dimensions and cell shape in cyanobacteria will be highlighted.

77 FR 2776 - Dorel Juvenile Group, Receipt of Petition for Decision of Inconsequential Noncompliance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... 22790CGT Deluxe 3 in 1 CC033BMT Alpha Omega Elite CC043ANK Alpha Omega Elite CC043ANL Alpha Omega Elite CC043AQS Alpha Omega Elite CC046AAI Deluxe 3 in 1 CC046AAU Deluxe 3 in 1 CC046CTA Deluxe 3 in 1 CC046SNW... between July 20, 2010 and May 18, 2011: 22187ANL Alpha Omega Elite 22187REM Alpha Omega Elite 22187REMA...

Targeting inflammation in pancreatic cancer: Clinical translation

PubMed Central

Steele, Colin William; Kaur Gill, Nina Angharad; Jamieson, Nigel Balfour; Carter, Christopher Ross

2016-01-01

Preclinical modelling studies are beginning to aid development of therapies targeted against key regulators of pancreatic cancer progression. Pancreatic cancer is an aggressive, stromally-rich tumor, from which few people survive. Within the tumor microenvironment cellular and extracellular components exist, shielding tumor cells from immune cell clearance, and chemotherapy, enhancing progression of the disease. The cellular component of this microenvironment consists mainly of stellate cells and inflammatory cells. New findings suggest that manipulation of the cellular component of the tumor microenvironment is possible to promote immune cell killing of tumor cells. Here we explore possible immunogenic therapeutic strategies. Additionally extracellular stromal elements play a key role in protecting tumor cells from chemotherapies targeted at the pancreas. We describe the experimental findings and the pitfalls associated with translation of stromally targeted therapies to clinical trial. Finally, we discuss the key inflammatory signal transducers activated subsequent to driver mutations in oncogenic Kras in pancreatic cancer. We present the preclinical findings that have led to successful early trials of STAT3 inhibitors in pancreatic adenocarcinoma. PMID:27096033

Tri-Service Literacy and Readability: Workshop Proceedings.

DTIC Science & Technology

1980-03-01

LN zC t’ DC D -2l C CC U CC., r C CzC.C-.C, CC C ~ ., caCQ.. *’UC - -C CL UQC’CC Ci - CT 0 --. . C DJZDCU- CC C C. C C...8217 flCCD.- CC, CCC~4J o zC C-Ca C ,.-C,-.O ,-,- CC CC,.. -- r C C,- -z~~~~~~~~~~~~~~~ (U’~’ C- O’ ,.0 C CCC,.. D Ca D CCCO.C - 0.a l F--Ci E CC CC CDO C C...understanding in problem solving. In Catellan, N. J., Jr., Pisoni, D . B., & Potts G. R . (Eds.), Cognitive theory. Hillsdale, NJ: Lawrence Erlbaum

A High-Level Symbolic Representation for Intelligent Agents Across Multiple Architectures

DTIC Science & Technology

2004-07-01

components of Soar that map to these concepts (instantiation support, selected operator). Fik Ed" Vie Go Boolbmo .’ lookb Wind , Help 1B w ,’ F:ld 1.ý fie...AnswerSpeedRequest ((msg> isa RequestSpeedChange consider (sel’>. pmsg (msg> end 0 St=ndadd irttezf•cc fo1.1 goals . ~interface lGoal s l’n sa,,invq this goail Ys "rt

Model for the Formation and Evolution of Sand Ridges on the Continental Shelf

DTIC Science & Technology

1992-10-01

difficulties of conducting laboratory experiments involving liquid/sediment media (such as leveling the sediment bed after each trial, extracting gas...reflected component, the 54 55 bottom velocities to lowest order are Uob = uo+ 32’.uoxr = E’= 1 Cja(X, y)e(•k’x-W’t) + c.c. (3.3) Vob = VO + 02 2 h(3 Vb2 To

Connecting Photosynthesis and Cellular Respiration: Preservice Teachers' Conceptions

ERIC Educational Resources Information Center

Brown, Mary H.; Schwartz, Renee S.

2009-01-01

The biological processes of photosynthesis and plant cellular respiration include multiple biochemical steps, occur simultaneously within plant cells, and share common molecular components. Yet, learners often compartmentalize functions and specialization of cell organelles relevant to these two processes, without considering the interconnections…

Ovarian mucinous tumors arising from mature cystic teratomas--a molecular genetic approach for understanding the cellular origin.

PubMed

Fujii, Kaho; Yamashita, Yoriko; Yamamoto, Toshimichi; Takahashi, Koji; Hashimoto, Katsunori; Miyata, Tomoko; Kawai, Kumi; Kikkawa, Fumitaka; Toyokuni, Shinya; Nagasaka, Tetsuro

2014-04-01

Mucinous tumors of the ovary are frequently associated with mature cystic teratomas, and it has been speculated that the mucinous tumors arise from teratoma components. The cellular origins of mature cystic teratomas are believed to be post-meiotic ovarian germ cells, and the analysis of microsatellite markers such as short tandem repeats is suitable for determining the cellular origin of tumors. In this study, we analyzed 3 ovarian mature cystic teratomas, all of which were associated with simultaneous ovarian mucinous tumors within the same ovary. Two of the 3 mucinous tumors were intestinal-type and the other was endocervical type. A laser capture microdissection technique was used to separate the epithelial component of the mucinous tumor, the components of the mature cystic teratoma, and control ovarian somatic tissue. Using short tandem repeat analysis based on 6 markers (D20S480, D6S2439, D6S1056, D9S1118, D4S2639, and D17S1290), we could distinguish the germ cell (homozygous) or somatic (heterozygous) origin of a given component in each sample. The epithelial components of the intestinal-type mucinous tumors in cases 1 and 2 were homozygous, and the epithelial component in case 3 (endocervical type) was heterozygous. All teratomatous components were homozygous, and the control components were heterozygous. In addition, we analyzed 3 mature cystic teratomas without mucinous tumors, and all 3 were homozygous in the tumor component. Our data suggest that the origin of mucinous tumors in the ovary may differ among histological subtypes, and intestinal-type mucinous tumors may arise from mature cystic teratomas, although endocervical-type mucinous tumors may not. Copyright © 2014 Elsevier Inc. All rights reserved.

Dienogest inhibits C-C motif chemokine ligand 20 expression in human endometriotic epithelial cells.

PubMed

Mita, Shizuka; Nakakuki, Masanori; Ichioka, Masayuki; Shimizu, Yutaka; Hashiba, Masamichi; Miyazaki, Hiroyasu; Kyo, Satoru

2017-07-01

C-C motif chemokine ligand 20 is thought to contribute to the development of endometriosis by recruiting Th17 lymphocytes into endometriotic foci. The present study investigated the effects of dienogest, a progesterone receptor agonist used to treat endometriosis, on C-C motif chemokine ligand 20 expression by endometriotic cells. Effects of dienogest on mRNA expression and protein secretion of C-C motif chemokine ligand 20 induced by interleukin 1β were assessed in three immortalized endometriotic epithelial cell lines, parental cells (EMosis-CC/TERT1), and stably expressing human progesterone receptor isoform A (EMosis-CC/TERT1/PRA+) or isoform B (EMosis-CC/TERT1/PRA-/PRB+). Dienogest markedly inhibited interleukin 1β-stimulated C-C motif chemokine ligand 20 mRNA expression and protein secretion in EMosis-CC/TERT1/PRA-/PRB+, which was abrogated by the progesterone receptor antagonist RU486. In EMosis-CC/TERT1/PRA+, dienogest slightly inhibited C-C motif chemokine ligand 20 mRNA and protein. In EMosis-CC/TERT1, dienogest slightly inhibited C-C motif chemokine ligand 20 mRNA, but had no effect on C-C motif chemokine ligand 20 protein. Dienogest inhibited interleukin 1β-induced up-regulation of C-C motif chemokine ligand 20 in endometriotic epithelial cells, mainly mediated by progesterone receptor B. Copyright © 2017 Elsevier B.V. All rights reserved.

Addition by subtraction in coupled-cluster theory: a reconsideration of the CC and CI interface and the nCC hierarchy.

PubMed

Bartlett, Rodney J; Musiał, Monika

2006-11-28

The nCC hierarchy of coupled-cluster approximations, where n guarantees exactness for n electrons and all products of n electrons are derived and applied to several illustrative problems. The condition of exactness for n=2 defines nCCSD=2CC, with nCCSDT=3CC and nCCSDTQ=4CC being exact for three and four electrons. To achieve this, the minimum number of diagrams is evaluated, which is less than in the corresponding CC model. For all practical purposes, nCC is also the proper definition of a size-extensive CI. 2CC is also an orbitally invariant coupled electron pair approximation. The numerical results of nCC are close to those for the full CC variant, and in some cases are closer to the full CI reference result. As 2CC is exact for separated electron pairs, it is the natural zeroth-order approximation for the correlation problem in molecules with other effects introduced as these units start to interact. The nCC hierarchy of approximations has all the attractive features of CC including its size extensivity, orbital invariance, and orbital insensitivity, but in a conceptually appealing form suited to bond breaking, while being computationally less demanding. Excited states from the equation of motion (EOM-2CC) are also reported, which show results frequently approaching those of EOM-CCSDT.

Stimulation of Mucin, Mucus, and Viscosity during Lubiprostone in Patients with Chronic Constipation may Potentially Lead to Increase of Lubrication.

PubMed

Majewski, Marek; Sarosiek, Irene; Wallner, Grzegorz; Edlavitch, Stanley A; Sarosiek, Jerzy

2014-12-18

The purpose of this clinical trial was to explore whether lubiprostone increases the rate of mucus and mucin secretion and its viscosity in chronic constipation (CC) patients. The secretion of chloride (CS) into the gastrointestinal tract lumen is pivotal in the body's ability to process non-digestible food components. CS sets the optimal rate of hydration for non-digestible food components, their fluidity, and their adequate propulsion along the alimentary tract. Chloride is also instrumental in the secretion of alimentary tract mucus, and the formation of a gel-like, viscous mucus-buffer layer. This layer acts as the first line and vanguard of the mucosal barrier. This barrier is essential in mucosal lubrication and protection. Lubiprostone, a novel chloride channel stimulator ClC-2, is currently approved for the treatment of CC. Its impact on mucus, mucus secretion, and viscosity is not established. A double-blind, crossover trial was approved by the IRBs at the Kansas University Medical Center (Kansas City, KS) (study site) and at the Texas Tech University HSC (El Paso, TX) (analysis site). The study included 20 patients (17 females (F); mean age: 37 years) with symptoms of CC diagnosed according to the Rome III criteria. Patients were randomized to 1 week of therapy with lubiprostone or placebo followed by a 1 week washout and 1 week of the alternative therapy. Gastric juice was collected basally and during stimulation with pentagastrin (6 μg/kg body weight subcutaneously) at the end of weeks 1 and 3. Pentagastrin stimulation mimics food stimulation. The mucus content in gastric juice was assessed gravimetrically. The mucin content was measured after its purification using ultracentrifugation. The viscosity of the gastric secretion was measured using a digital viscometer. In comparison with placebo, the volume of gastric secretion in patients with CC during administration of lubiprostone increased significantly by 50% (86.3 vs. 57.5 ml/h) (P<0.001) in basal conditions and increased by 25% (210.0 vs. 167.6 ml/h) (P=0.024) during stimulation with pentagastrin. The rate of gastric mucus secretion during therapy with lubiprostone was 91% higher (257.3 vs. 135 mg/h) (P=0.001) in basal conditions and 28% higher (348.1 vs. 270.8 mg/h) (NS) in stimulated conditions, although the latter was not statistically significant. The rate of gastric mucin secretion during lubiprostone therapy was 85% higher (98.4 vs. 65.5 mg/h) (P=0.011) in basal conditions and 38% (98.3 vs. 71.7 mg/h) (NS) higher in stimulated conditions. In basal conditions, the viscosity of gastric secretion during administration of lubiprostone increased by 240% at the lowest (P<0.001) and by 106% at the highest shear rate (P<0.001). In stimulated conditions, it increased by 226% (P<0.01) at the lowest shear rate and by 67% (P<0.01) at the highest shear rate. The significantly higher content of gastric mucus and mucin during therapy in basal conditions with lubiprostone in patients with CC suggests and supports the potentially leading role of lubiprostone and ClC-2 stimulation in their secretion. This increased stimulation results in profoundly increased viscosity, which in turn facilitates and/or accelerates the transit and evacuation of non-digestible food components. Although increases in mucus and mucin were observed in stimulated conditions, neither increase was statistically significant. Based on this experiment, we hypothesize that, in CC patients, the significantly increased rate of mucus and its major component, mucin secretion, during lubiprostone administration may partially explain its clinical effectiveness and also have additional clinically important effects. We propose that since the increased mucus production enhances the protective quality of the mucosal barrier, it also boosts its potential to withstand luminal aggressive components such as acid/pepsin duet, Helicobacter pylori and/or nonsteroidal anti-inflammatory drugs/aspirin, or a combination of all. Further trials are needed to test this hypothesis. As this was crossover clinical trial, the patients serve as their own controls. No interaction was found with body mass index (BMI) and treatment. The observed relationships of BMI and mucus and mucin secretions and gastric juice volume are important considerations in the design of future trials, particularly if a crossover design is not used.

Stimulation of Mucin, Mucus, and Viscosity during Lubiprostone in Patients with Chronic Constipation may Potentially Lead to Increase of Lubrication

PubMed Central

Majewski, Marek; Sarosiek, Irene; Wallner, Grzegorz; Edlavitch, Stanley A; Sarosiek, Jerzy

2014-01-01

Objectives: The purpose of this clinical trial was to explore whether lubiprostone increases the rate of mucus and mucin secretion and its viscosity in chronic constipation (CC) patients. The secretion of chloride (CS) into the gastrointestinal tract lumen is pivotal in the body's ability to process non-digestible food components. CS sets the optimal rate of hydration for non-digestible food components, their fluidity, and their adequate propulsion along the alimentary tract. Chloride is also instrumental in the secretion of alimentary tract mucus, and the formation of a gel-like, viscous mucus-buffer layer. This layer acts as the first line and vanguard of the mucosal barrier. This barrier is essential in mucosal lubrication and protection. Lubiprostone, a novel chloride channel stimulator ClC-2, is currently approved for the treatment of CC. Its impact on mucus, mucus secretion, and viscosity is not established. Methods: A double-blind, crossover trial was approved by the IRBs at the Kansas University Medical Center (Kansas City, KS) (study site) and at the Texas Tech University HSC (El Paso, TX) (analysis site). The study included 20 patients (17 females (F); mean age: 37 years) with symptoms of CC diagnosed according to the Rome III criteria. Patients were randomized to 1 week of therapy with lubiprostone or placebo followed by a 1 week washout and 1 week of the alternative therapy. Gastric juice was collected basally and during stimulation with pentagastrin (6 μg/kg body weight subcutaneously) at the end of weeks 1 and 3. Pentagastrin stimulation mimics food stimulation. The mucus content in gastric juice was assessed gravimetrically. The mucin content was measured after its purification using ultracentrifugation. The viscosity of the gastric secretion was measured using a digital viscometer. Results: In comparison with placebo, the volume of gastric secretion in patients with CC during administration of lubiprostone increased significantly by 50% (86.3 vs. 57.5 ml/h) (P<0.001) in basal conditions and increased by 25% (210.0 vs. 167.6 ml/h) (P=0.024) during stimulation with pentagastrin. The rate of gastric mucus secretion during therapy with lubiprostone was 91% higher (257.3 vs. 135 mg/h) (P=0.001) in basal conditions and 28% higher (348.1 vs. 270.8 mg/h) (NS) in stimulated conditions, although the latter was not statistically significant. The rate of gastric mucin secretion during lubiprostone therapy was 85% higher (98.4 vs. 65.5 mg/h) (P=0.011) in basal conditions and 38% (98.3 vs. 71.7 mg/h) (NS) higher in stimulated conditions. In basal conditions, the viscosity of gastric secretion during administration of lubiprostone increased by 240% at the lowest (P<0.001) and by 106% at the highest shear rate (P<0.001). In stimulated conditions, it increased by 226% (P<0.01) at the lowest shear rate and by 67% (P<0.01) at the highest shear rate. Conclusions: The significantly higher content of gastric mucus and mucin during therapy in basal conditions with lubiprostone in patients with CC suggests and supports the potentially leading role of lubiprostone and ClC-2 stimulation in their secretion. This increased stimulation results in profoundly increased viscosity, which in turn facilitates and/or accelerates the transit and evacuation of non-digestible food components. Although increases in mucus and mucin were observed in stimulated conditions, neither increase was statistically significant. Based on this experiment, we hypothesize that, in CC patients, the significantly increased rate of mucus and its major component, mucin secretion, during lubiprostone administration may partially explain its clinical effectiveness and also have additional clinically important effects. We propose that since the increased mucus production enhances the protective quality of the mucosal barrier, it also boosts its potential to withstand luminal aggressive components such as acid/pepsin duet, Helicobacter pylori and/or nonsteroidal anti-inflammatory drugs/aspirin, or a combination of all. Further trials are needed to test this hypothesis. As this was crossover clinical trial, the patients serve as their own controls. No interaction was found with body mass index (BMI) and treatment. The observed relationships of BMI and mucus and mucin secretions and gastric juice volume are important considerations in the design of future trials, particularly if a crossover design is not used. PMID:25521039

Seasonal varability of the Canary Current

NASA Astrophysics Data System (ADS)

Vélez-Belchí, P.; Hernandez-Guerra, A.; Pérez-Hernández, M. D.

2016-02-01

The Atlantic meridional overturning circulation (AMOC) is recognized as an important component of the climate system, contributing to the relatively mild climate of northwest Europe. Due to its importance, the strength of the AMOC is continually monitored along 26ºN with several moorings, east of the Bahamas, in the Middle Atlantic Ridge and south of the Canary islands, known as the RAPID array. The measurements of the RAPID array show a 6 Sv seasonal cycle for the AMOC, and recent studies have pointed out the dynamics of the eastern Atlantic as the main driver for this seasonal cycle, specifically, rossby waves excited south of the Canary Islands.Due to the important role of the eastern Atlantic, in this study we describe the seasonal cycle of the Canary Current (CC) and the Canary Upwelling Current (CUC), using hydrographic data from two cruises carried out in a box around the Canary Islands, the region where the eastern component of the RAPID array is placed. CTD, VMADCP and LADCP data were combined with inverse modeling in order to determine absolute geostrophic transports in the Canary Islands region in fall and spring. During spring, the overall transport of Canary Current and the CUC was southward. In the Lanzarote Passage (LP), between the Canary Islands and Africa, the CUC transported 0.6±0.20 Sv southward, while the Canary Current transported 1.0±0.40 Sv in the oceanic waters of the Canary Islands Archipelago. During fall, the CUC transported 2.8±0.4Sv northward, while the CC transported 2.9±0.60 Sv southward in the oceanic waters of the Canary Islands Archipelago. The seasonal cycle observed has and amplitude of 3.4Sv for the CUC and 1.9Sv for the CC. Data from a mooring in the LP and the hydrographic data was used to calibrate geostrophic transport estimated using altimetry data. The amplitude of the seasonal cycle of the geostrophic transport obtained using the calibrated altimetry data (Figure 1) was quite similar to the seasonal cycle of the Eastern Atlantic contribution to the AMOC, as measured by the RAPID array. To understand the relationship between the seasonal cycle found in the CC and CUC, and the amplitude of the seasonal cycle of the AMOC transport associated with Rossby waves, a sensitivity study of the Rossby wave model is included.

Seasonal cycle of the Canary Current.

NASA Astrophysics Data System (ADS)

Vélez-Belchí, P.; Hernandez-Guerra, A.; Pérez-Hernández, M. D.

2015-12-01

The Atlantic meridional overturning circulation (AMOC) is recognized as an important component of the climate system, contributing to the relatively mild climate of northwest Europe. Due to its importance, the strength of the AMOC is continually monitored along 26ºN with several moorings east of the Bahamas, in the Middle Atlantic Ridge and south of the Canary islands, known as the RAPID array. The measurements of the RAPID array show a 6 Sv seasonal cycle for the AMOC, and recent studies have pointed out the dynamics of the eastern Atlantic as the main driver for this seasonal cycle, specifically, rossby waves excited south of the Canary Islands. Due to the important role of the eastern Atlantic, in this study we describe the seasonal cycle of the Canary Current (CC) and the Canary Upwelling Current (CUC) using hydrographic data from two cruises carried out in a box around the Canary Islands, the region where the eastern component of the RAPID array is placed. CTD, VMADCP and LADCP data were combined with inverse modeling in order to determine absolute geostrophic transports in the Canary Islands region in fall and spring. During spring, the overall transport of Canary Current and the CUC was southward. In the Lanzarote Passage (LP), between the Canary Islands and Africa, the CUC transported 0.6±0.20 Sv southward, while the Canary Current transported 1.0±0.40 Sv in the oceanic waters of the Canary Islands Archipelago. During fall, the CUC transported 2.8±0.4Sv northward, while the CC transported 2.9±0.60 Sv southward in the oceanic waters of the Canary Islands Archipelago. The seasonal cycle observed has an amplitude of 3.4Sv for the CUC and 1.9Sv for the CC. Data from a mooring in the LP and the hydrographic data was used to calibrate geostrophic transport estimated using altimetry data. The amplitude of the seasonal cycle of the geostrophic transport obtained using the calibrated altimetry data (Figure 1) was quite similar to the seasonal cycle of the Eastern Atlantic contribution to the AMOC, as measured by the RAPID array. To understand the relationship between the seasonal cycle found in the CC and CUC, and the amplitude of the seasonal cycle of the AMOC transport associated with Rossby waves, a sensitivity study of the Rossby wave model is included.

Combat Ration Network for Technology Implementation. Universal Benchtop Package Tester

DTIC Science & Technology

2006-10-01

of three years of shelf life, but this packaging is susceptible to tears and holes during the manufacturing process. To avoid package integrity...characteristics, cannot provide a measurement of container contents. April 2003 - Precision Automation and PTI-USA expressed interest in manufacturing systems to... Noodles (185cc) • 212cc(+14.6%) • 209cc(+13.0%) – Chicken Brst. (150cc) • 160cc(+6.3%) • 154cc(+2.6%) • Water Trays – Tray A4 (185cc) • 200cc(+8.1

Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery

PubMed Central

Van Duyne, Rachel; Guendel, Irene; Klase, Zachary; Narayanan, Aarthi; Coley, William; Jaworski, Elizabeth; Roman, Jessica; Popratiloff, Anastas; Mahieux, Renaud; Kehn-Hall, Kylene; Kashanchi, Fatah

2012-01-01

The innate ability of the human cell to silence endogenous retroviruses through RNA sequences encoding microRNAs, suggests that the cellular RNAi machinery is a major means by which the host mounts a defense response against present day retroviruses. Indeed, cellular miRNAs target and hybridize to specific sequences of both HTLV-1 and HIV-1 viral transcripts. However, much like the variety of host immune responses to retroviral infection, the virus itself contains mechanisms that assist in the evasion of viral inhibition through control of the cellular RNAi pathway. Retroviruses can hijack both the enzymatic and catalytic components of the RNAi pathway, in some cases to produce novel viral miRNAs that can either assist in active viral infection or promote a latent state. Here, we show that HTLV-1 Tax contributes to the dysregulation of the RNAi pathway by altering the expression of key components of this pathway. A survey of uninfected and HTLV-1 infected cells revealed that Drosha protein is present at lower levels in all HTLV-1 infected cell lines and in infected primary cells, while other components such as DGCR8 were not dramatically altered. We show colocalization of Tax and Drosha in the nucleus in vitro as well as coimmunoprecipitation in the presence of proteasome inhibitors, indicating that Tax interacts with Drosha and may target it to specific areas of the cell, namely, the proteasome. In the presence of Tax we observed a prevention of primary miRNA cleavage by Drosha. Finally, the changes in cellular miRNA expression in HTLV-1 infected cells can be mimicked by the add back of Drosha or the addition of antagomiRs against the cellular miRNAs which are downregulated by the virus. PMID:22808228

Cellular generators of the cortical auditory evoked potential initial component.

PubMed

Steinschneider, M; Tenke, C E; Schroeder, C E; Javitt, D C; Simpson, G V; Arezzo, J C; Vaughan, H G

1992-01-01

Cellular generators of the initial cortical auditory evoked potential (AEP) component were determined by analyzing laminar profiles of click-evoked AEPs, current source density, and multiple unit activity (MUA) in primary auditory cortex of awake monkeys. The initial AEP component is a surface-negative wave, N8, that peaks at 8-9 msec and inverts in polarity below lamina 4. N8 is generated by a lamina 4 current sink and a deeper current source. Simultaneous MUA is present from lower lamina 3 to the subjacent white matter. Findings indicate that thalamocortical afferents are a generator of N8 and support a role for lamina 4 stellate cells. Relationships to the human AEP are discussed.

Anthrax Toxin

DTIC Science & Technology

1984-10-26

focused initially on EF because it seemed possible that this component, like cholera toxin, might cause edema in skin through elevation of cellular cAMP...behavior differed from that seen in cells exposed to cholera toxin, where cellular cAMP levels remain elevated upon toxin removal. Studies in CHO cell...LF, the rat bioassay is not likely to be an appropriate system for studying the cellular and molecular mechanisms of action of LF. Therefore, a survey

Identification of Immunity Related Genes to Study the Physalis peruviana – Fusarium oxysporum Pathosystem

PubMed Central

Enciso-Rodríguez, Felix E.; González, Carolina; Rodríguez, Edwin A.; López, Camilo E.; Landsman, David; Barrero, Luz Stella; Mariño-Ramírez, Leonardo

2013-01-01

The Cape gooseberry ( Physalis peruviana L) is an Andean exotic fruit with high nutritional value and appealing medicinal properties. However, its cultivation faces important phytosanitary problems mainly due to pathogens like Fusarium oxysporum, Cercosporaphysalidis and Alternaria spp. Here we used the Cape gooseberry foliar transcriptome to search for proteins that encode conserved domains related to plant immunity including: NBS (Nucleotide Binding Site), CC (Coiled-Coil), TIR (Toll/Interleukin-1 Receptor). We identified 74 immunity related gene candidates in P . peruviana which have the typical resistance gene (R-gene) architecture, 17 Receptor like kinase (RLKs) candidates related to PAMP-Triggered Immunity (PTI), eight (TIR-NBS-LRR, or TNL) and nine (CC–NBS-LRR, or CNL) candidates related to Effector-Triggered Immunity (ETI) genes among others. These candidate genes were categorized by molecular function (98%), biological process (85%) and cellular component (79%) using gene ontology. Some of the most interesting predicted roles were those associated with binding and transferase activity. We designed 94 primers pairs from the 74 immunity-related genes (IRGs) to amplify the corresponding genomic regions on six genotypes that included resistant and susceptible materials. From these, we selected 17 single band amplicons and sequenced them in 14 F. oxysporum resistant and susceptible genotypes. Sequence polymorphisms were analyzed through preliminary candidate gene association, which allowed the detection of one SNP at the PpIRG-63 marker revealing a nonsynonymous mutation in the predicted LRR domain suggesting functional roles for resistance. PMID:23844210

Promising Mid-term Results With a Cup-cage Construct for Large Acetabular Defects and Pelvic Discontinuity.

PubMed

Amenabar, Tomas; Rahman, Wael A; Hetaimish, Bandar M; Kuzyk, Paul R; Safir, Oleg A; Gross, Allan E

2016-02-01

Restoring normal anatomy and achieving stable fixation of the acetabular component can be especially challenging when the surgeon must deal with severe acetabular defects and/or pelvic discontinuity. The cup-cage (CC) construct, where an ilioischial cage is cemented within a biologically fixed porous metal cup, has emerged as an excellent option to treat such challenges. We sought to determine (1) mid-term Kaplan-Meier survival; (2) clinical outcomes based on Merle d'Aubigné-Postel scores; (3) radiological outcomes based primarily on construct migration; and (4) the complication rate for a series of 67 CC procedures performed at our institution. All hip revision procedures between January 2003 and March 2012 where a CC was used (with the exception of tumor cases or acute fracture; four total cases) that had a minimum 2-year followup and that had been seen within the last 2 years were included in this retrospective review. Acetabular bone loss and presence of pelvic discontinuity were assessed according to the Gross classification. Sixty-seven CC procedures with an average followup of 74 months (range, 24-135 months; SD, 34.3) months were identified; 26 of 67 (39%) were Gross Type IV and 41 of 67 (61%) were Gross Type V (pelvic discontinuity). Postoperative clinical and radiological evaluation was done annually. Merle d'Aubigné-Postel scores were recorded and all radiographs were compared with the 6-week postoperative radiographs to evaluate for radiographic loosening or migration. Failure was defined as revision surgery for any cause, including infection. The 5-year Kaplan-Meier survival rate with revision for any cause representing failure was 93% (95% confidence interval [CI], 83.1-97.4), and the 10-year survival rate was 85% (95% CI, 67.2-93.8). The Merle d'Aubigné-Postel score improved significantly from a mean of 6 preoperatively to 13 postoperatively (p < 0.001). Four CC had nonprogressive radiological migration of the ischial flange and they remain stable. We believe that the CC construct is a suitable choice to treat chronic pelvic discontinuity; it also remains a reliable option for the treatment of severe acetabular bone defects if stable fixation cannot be obtained through the use of a trabecular metal cup with or without augments. Level IV, therapeutic study.

Absence of cellular hypersensitivity to muscle and thymic antigens in myasthenia gravis.

PubMed Central

Behan, W M; Behan, P O; Simpson, J A

1975-01-01

Humoral antibodies to skeletal muscle and its components and to thymus have been demonstrated in the sera of patients with myasthenia gravis. A role for cellular hypersensitivity to similar antigens in the pathogenesis of the disease has been suggested by some reports of the presence of cellular immunity. A detailed immunological study using muscle and thymic antigens, including those prepared from the patients' own tissues, failed to confirm these findings. It is suggested that previous reports of cellular hypersensitivity represent the demonstration of an epiphenomenon. PMID:1206412

Integration of mobile satellite and cellular systems

NASA Technical Reports Server (NTRS)

Drucker, Elliott H.; Estabrook, Polly; Pinck, Deborah; Ekroot, Laura

1993-01-01

By integrating the ground based infrastructure component of a mobile satellite system with the infrastructure systems of terrestrial 800 MHz cellular service providers, a seamless network of universal coverage can be established. Users equipped for both cellular and satellite service can take advantage of a number of features made possible by such integration, including seamless handoff and universal roaming. To provide maximum benefit at lowest posible cost, the means by which these systems are integrated must be carefully considered. Mobile satellite hub stations must be configured to efficiently interface with cellular Mobile Telephone Switching Offices (MTSO's), and cost effective mobile units that provide both cellular and satellite capability must be developed.

Integration of mobile satellite and cellular systems

NASA Astrophysics Data System (ADS)

Drucker, Elliott H.; Estabrook, Polly; Pinck, Deborah; Ekroot, Laura

By integrating the ground based infrastructure component of a mobile satellite system with the infrastructure systems of terrestrial 800 MHz cellular service providers, a seamless network of universal coverage can be established. Users equipped for both cellular and satellite service can take advantage of a number of features made possible by such integration, including seamless handoff and universal roaming. To provide maximum benefit at lowest posible cost, the means by which these systems are integrated must be carefully considered. Mobile satellite hub stations must be configured to efficiently interface with cellular Mobile Telephone Switching Offices (MTSO's), and cost effective mobile units that provide both cellular and satellite capability must be developed.

Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

USDA-ARS?s Scientific Manuscript database

Cancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate tha...

[Evaluation of Cellular Effects Caused by Lunar Regolith Simulant Including Fine Particles].

PubMed

Horie, Masanori; Miki, Takeo; Honma, Yoshiyuki; Aoki, Shigeru; Morimoto, Yasuo

2015-06-01

The National Aeronautics and Space Administration has announced a plan to establish a manned colony on the surface of the moon, and our country, Japan, has declared its participation. The surface of the moon is covered with soil called lunar regolith, which includes fine particles. It is possible that humans will inhale lunar regolith if it is brought into the spaceship. Therefore, an evaluation of the pulmonary effects caused by lunar regolith is important for exploration of the moon. In the present study, we examine the cellular effects of lunar regolith simulant, whose components are similar to those of lunar regolith. We focused on the chemical component and particle size in particular. The regolith simulant was fractionated to < 10 μm, < 25 μm and 10-25 μm by gravitational sedimentation in suspensions. We also examined the cellular effects of fine regolith simulant whose primary particle size is 5.10 μm. These regolith simulants were applied to human lung carcinoma A549 cells at concentrations of 0.1 and 1.0 mg/ml. Cytotoxicity, oxidative stress and immune response were examined after 24 h exposure. Cell membrane damage, mitochondrial dysfunction and induction of Interleukin-8 (IL-8) were observed at the concentration of 1.0 mg/ml. The cellular effects of the regolith simulant at the concentration of 0.1 mg/ml were small, as compared with crystalline silica as a positive control. Secretion of IL-1β and tumor necrosis factor-α (TNF-α) was observed at the concentration of 1.0 mg/ml, but induction of gene expression was not observed at 24 h after exposure. Induction of cellular oxidative stress was small. Although the cellular effects tended to be stronger in the < 10 μm particles, there was no remarkable difference. These results suggest that the chemical components and particle size have little relationship to the cellular effects of lunar regolith simulant such as cell membrane damage, induction of oxidative stress and proinflammatory effect.

The effect of growth phase and medium on the use of the firefly adenosine triphosphate (ATP) assay for the quantitation of bacteria

NASA Technical Reports Server (NTRS)

Bush, V. N.; Picciolo, G. L.; Chappelle, E. W.

1975-01-01

Luciferase assay for adenosine triphosphate (ATP) was used as a rapid method to determine the number of bacteria in a urine sample after nonbacterial components were removed. Accurate cellular ATP values, determined when bacteria were grown in an environment similar to that in which they were found, were necessary for the calculation of bacterial titer in urine. Cellular ATP values vary depending on the extraction method, the cell growth phase, and cell growth conditions. ATP per cell values of stationary E. coli grown in urine were two times greater than ATP per cell values of cells grown in trypticase soy broth. Glucose and urea were examined as possible components responsible for the cellular ATP variation.

Low thermal expansion seal ring support

DOEpatents

Dewis, David W.; Glezer, Boris

2000-01-01

Today, the trend is to increase the temperature of operation of gas turbine engines. To cool the components with compressor discharge air, robs air which could otherwise be used for combustion and creates a less efficient gas turbine engine. The present low thermal expansion sealing ring support system reduces the quantity of cooling air required while maintaining life and longevity of the components. Additionally, the low thermal expansion sealing ring reduces the clearance "C","C'" demanded between the interface between the sealing surface and the tip of the plurality of turbine blades. The sealing ring is supported by a plurality of support members in a manner in which the sealing ring and the plurality of support members independently expand and contract relative to each other and to other gas turbine engine components.

Peritumoral adipose tissue as a source of inflammatory and angiogenic factors in colorectal cancer.

PubMed

Amor, S; Iglesias-de la Cruz, M C; Ferrero, E; García-Villar, O; Barrios, V; Fernandez, N; Monge, L; García-Villalón, A L; Granado, M

2016-02-01

Obesity is a risk factor for the development of human colorectal cancer (CC). The aim of this work is to report the inflammatory and angiogenic scenario in lean (BMI < 25 kg/m2) and obese (BMI > 30 kg/m2) patients with and without CC and to assess the role of peritumoral adipose tissue in CC-induced inflammation. Patients were divided in four experimental groups: obese patients with CC (OB-CC), lean patients with CC (LEAN-CC), obese patients without CC (OB), and lean patients without CC (LEAN). Plasma levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-4, IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in OB-CC patients. Peritumoral adipose tissue (TF) explants and cultured mature adipocytes secreted higher amounts of nitrites and nitrates than did control and non-tumoral (NTF) adipose tissue both alone and in response to lipopolysaccharide (LPS). Nitrite and nitrate secretion was also increased in TF explants from OB-CC patients compared with that from LEAN-CC patients. Gene expression of adiponectin, tumor necrosis factor alpha (TNF-α), insulin-like growth factor type I (IGF-I), cyclooxygenase-2 (COX-2), and peroxisome proliferator-activated receptor γ (PPAR-γ) was increased in TF explants from CC patients. LPS increased the gene expression of IL-6, IL-10, TNF-α, vascular endothelial growth factor (VEGF), and COX-2 in OB and in TF explants from OB-CC patients. COX-2 and PPAR-γ inhibition further increased LPS-induced release of nitrites and nitrates in TF explants and adipocytes from OB-CC patients. In conclusion, OB-CC patients have increased plasma levels of pro-inflammatory and angiogenic factors. TF from OB-CC patients shows an increased secretion of inflammatory markers compared with both TF from LEAN-CC and non-tumoral adipose tissue (AT) through a COX-2- and PPAR-γ-independent mechanism.

Importance of CMR within the Task Force Criteria for the diagnosis of ARVC in children and adolescents.

PubMed

Etoom, Yousef; Govindapillai, Sindu; Hamilton, Robert; Manlhiot, Cedric; Yoo, Shi-Joon; Farhan, Maryam; Sarikouch, Samir; Peters, Brigitte; McCrindle, Brian W; Grosse-Wortmann, Lars

2015-03-17

Cardiac magnetic resonance (CMR) is a component of the revised Task Force Criteria (rTFC) for the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). However, its diagnostic value in a pediatric population is unknown. This study examined the contribution of CMR to diagnosing ARVC using the rTFC in a pediatric population. Clinical CMR studies of 142 pediatric patients evaluated for ARVC between 2005 and 2009 were reviewed. Patients were categorized into "definitive," "borderline," "possible," or "no" ARVC diagnostic groups based on the rTFC. The extent to which each element of the rTFC contributed to diagnosing ARVC was determined using a c-statistics model. A total of 23 (16%), 32 (23%), 37 (26%), and 50 (35%) patients had definite, borderline, possible, and no ARVC, respectively, applying the rTFC. The prevalence of regional wall motion abnormalities in these groups was 83%, 53%, 22%, and 16%, respectively (p < 0.001). By CMR, right ventricular end-diastolic volumes were 118 ± 31 cc/m², 108 ± 22 cc/m², 94 ± 14 cc/m², and 92 ± 18 cc/m², respectively (p < 0.001). Right ventricular fatty infiltration and fibrosis were detected in only 1 and 3 patients, respectively, all of whom had definitive ARVC. Of all rTFC major criteria, CMR had the largest c-statistic decline (c = -0.163). Eleven of the 23 patients (48%) with definite ARVC would not have been in this group if CMR had not been performed. CMR parameters are important contributors to a diagnosis of ARVC in children, using the rTFC. Fatty infiltration and myocardial fibrosis provide limited value in children and adolescents. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

A comparative overview of the sperm centriolar complex in mammals and birds: Variations on a theme.

PubMed

Soley, John T

2016-06-01

This paper presents an overview of the structure, function and anomalies of the sperm centriolar complex (CC) on a comparative basis between mammals and birds. The information is based on selected references from the literature supplemented by original observations on spermiogenesis and sperm structure in disparate mammalian (cheetah and cane rat) and avian (ostrich, rhea and emu) species. Whereas the basic structure of the CC (a diplosome surrounded by pericentriolar material) is similar in Aves and Mammalia, certain differences are apparent. Centriole reduction does not generally occur in birds, but when present as in oscines, involves the loss of the proximal centriole. In ratites, the distal centriole forms the core of the entire midpiece and incorporates the outer dense fibres in addition to initiating axoneme formation. The elements of the connecting piece are not segmented in birds and less complex in basic design than in mammals. The functions of the various components of the CC appear to be similar in birds and mammals. Despite obvious differences in sperm head shape, the centrosomal anomalies afflicting both vertebrate groups demonstrate structural uniformity across species and display a similar range of defects. Most abnormalities result from defective migration and alignment of the CC relative to the nucleus. The most severe manifestation is that of acephalic sperm, while angled tail attachment, abaxial and multiflagellate sperm reflect additional defective forms. The stump-tail defect is not observed in birds. A comparison of defective sperm formation and centrosomal dysfunction at the molecular level is currently difficult owing to the paucity of relevant information on avian sperm. Copyright © 2016 Elsevier B.V. All rights reserved.

Differential regulation of immature articular cartilage compressive moduli and Poisson's ratios by in vitro stimulation with IGF-1 and TGF-beta1.

PubMed

Williams, Gregory M; Dills, Kristin J; Flores, Christian R; Stender, Michael E; Stewart, Kevin M; Nelson, Lauren M; Chen, Albert C; Masuda, Koichi; Hazelwood, Scott J; Klisch, Stephen M; Sah, Robert L

2010-09-17

Mechanisms of articular cartilage growth and maturation have been elucidated by studying composition-function dynamics during in vivo development and in vitro culture with stimuli such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta 1 (TGF-beta1). This study tested the hypothesis that IGF-1 and TGF-beta1 regulate immature cartilage compressive moduli and Poisson's ratios in a manner consistent with known effects on tensile properties. Bovine calf articular cartilage from superficial-articular (S) and middle-growth (M) regions were analyzed fresh or following culture in medium with IGF-1 or TGF-beta1. Mechanical properties in confined (CC) and unconfined (UCC) compression, cartilage matrix composition, and explant size were assessed. Culture with IGF-1 resulted in softening in CC and UCC, increased Poisson's ratios, substantially increased tissue volume, and accumulation of glycosaminoglycan (GAG) and collagen (COL). Culture with TGF-beta1 promoted maturational changes in the S layer, including stiffening in CC and UCC and increased concentrations of GAG, COL, and pyridinoline crosslinks (PYR), but little growth. Culture of M layer explants with TGF-beta1 was nearly homeostatic. Across treatment groups, compressive moduli in CC and UCC were positively related to GAG, COL, and PYR concentrations, while Poisson's ratios were negatively related to concentrations of these matrix components. Thus, IGF-1 and TGF-beta1 differentially regulate the compressive mechanical properties and size of immature articular cartilage in vitro. Prescribing tissue growth, maturation, or homeostasis by controlling the in vitro biochemical environment with such growth factors may have applications in cartilage repair and tissue engineering.

Molecular basis and drug sensitivity of the delayed rectifier (IKr) in the fish heart.

PubMed

Hassinen, Minna; Haverinen, Jaakko; Vornanen, Matti

2015-01-01

Fishes are increasingly used as models for human cardiac diseases, creating a need for a better understanding of the molecular basis of fish cardiac ion currents. To this end we cloned KCNH6 channel of the crucian carp (Carassius carassius) that produces the rapid component of the delayed rectifier K(+) current (IKr), the main repolarising current of the fish heart. KCNH6 (ccErg2) was the main isoform of the Kv11 potassium channel family with relative transcript levels of 98.9% and 99.6% in crucian carp atrium and ventricle, respectively. KCNH2 (ccErg1), an orthologue to human cardiac Erg (Herg) channel, was only slightly expressed in the crucian carp heart. The native atrial IKr and the cloned ccErg2 were inhibited by similar concentrations of verapamil, terfenadine and KB-R7943 (P>0.05), while the atrial IKr was about an order of magnitude more sensitive to E-4031 than ccErg2 (P<0.05) suggesting that some accessory β-subunits may be involved. Sensitivity of the crucian carp atrial IKr to E-4031, terfenadine and KB-R7943 was similar to what has been reported for the Herg channel. In contrast, the sensitivity of the crucian carp IKr to verapamil was approximately 30 times higher than the previously reported values for the Herg current. In conclusion, the cardiac IKr is produced by non-orthologous gene products in fish (Erg2) and mammalian hearts (Erg1) and some marked differences exist in drug sensitivity between fish and mammalian Erg1/2 which need to be taken into account when using fish heart as a model for human heart. Copyright © 2015 Elsevier Inc. All rights reserved.

First North American 50 cc Total Artificial Heart Experience: Conversion from a 70 cc Total Artificial Heart.

PubMed

Khalpey, Zain; Kazui, Toshinobu; Ferng, Alice S; Connell, Alana; Tran, Phat L; Meyer, Mark; Rawashdeh, Badi; Smith, Richard G; Sweitzer, Nancy K; Friedman, Mark; Lick, Scott; Slepian, Marvin J; Copeland, Jack G

2016-01-01

The 70 cc total artificial heart (TAH) has been utilized as bridge to transplant (BTT) for biventricular failure. However, the utilization of 70 cc TAH has been limited to large patients for the low output from the pulmonary as well as systemic vein compression after chest closure. Therefore, the 50 cc TAH was developed by SynCardia (Tucson, AZ) to accommodate smaller chest cavity. We report the first TAH exchange from a 70 to 50 cc due to a fit difficulty. The patient failed to be closed with a 70 cc TAH, although the patient met the conventional 70 cc TAH fit criteria. We successfully closed the chest with a 50 cc TAH.

Petrography, fluid inclusion and isotope studies in Ordovician carbonate reservoirs in the Shunnan area, Tarim basin, NW China: Implications for the nature and timing of silicification

NASA Astrophysics Data System (ADS)

Lu, Ziye; Chen, Honghan; Qing, Hairuo; Chi, Guoxiang; Chen, Qianglu; You, Donghua; Yin, Hang; Zhang, Siyang

2017-08-01

The Shunnan (SN) area, located in the center of the Tarim basin, NW China, is a gas field discovered in 2013, where the gas is hosted from deeply buried Ordovician carbonate reservoirs with burial depth > 6000 m and temperature > 190 °C. The most important reservoir rocks in the SN area are silicified limestones, which are characterized by multiple generations/types of authigenic quartz (Qz1-Qz2) and coarse calcite cement (CC1-CC3), in addition to other diagenetic phases. Qz1 is a replacement quartz postdating burial stylolites in both limestone and strongly silicified limestone, and Qz2 are equant and bladed quartz cements developed in fractures or vugs in strongly silicified limestone, also postdating burial stylolite. CC1 is a coarse calcite cement found in the vugs, which postdates medium crystalline dolomite and predates saddle dolomite. CC2 (including CC2a, CC2b and CC2c) is the calcite postdating Qz1 and burial stylolites. CC2a is found in fractures in limestone or slightly silicified limestone. CC2b, CC2c and CC3 are only identified in strongly silicified limestone. CC2b fills intercrystalline pores of Qz1, and CC2c fills fractures, predating Qz2. CC3 is precipitated in remaining space left by Qz2c in fractures or vugs. Sr isotopes were analyzed in CC2a and CC2c. CC2a has 87Sr/86Sr ratios of 0.70890-0.70917. CC2c is characterized with 87Sr/86Sr ratios of 0.70949-0.70972. Fluid inclusions were studied in all the quartz and coarse calcite cements. Fluid inclusions in CC2a are characterized by Th values of 118-131 °C and salinities of 22.9-25.2 wt% NaCl + CaCl2. Fluid inclusions from Qz2a, Qz2b, CC2b and CC2c have Th values of 143-166 °C and salinities of 14.7-23.7 wt% NaCl + CaCl2. Fluid inclusions in Qz2c are characterized by Th values of 125-132 °C and salinities of 24.8-26.8 wt% NaCl + CaCl2, and those in CC3 by Th values of 86-101 °C and salinities of 22.9-25.2 wt% NaCl + CaCl2. The Th drop, from Qz2a, Qz2b and CC2c to Qz2c and CC3, cannot be explained by normal burial diagenesis, suggesting a hydrothermal event associated with the main phase of silicification. The relatively low temperature recorded by CC3 implies that the hydrothermal event possibly took place in the Devonian rather than Permian as previously thought.

Cloning, expression analysis, and antibacterial propertiesof three serum amyloid A in common carp (Cyprinus carpio).

PubMed

Yu, Juhua; Tang, Yongkai; Li, Jianlin; Li, Hongxia; Yu, Fan; Yu, Wenjuan; He, Feng; Fu, Chunjie; Mao, Shuntao

2017-06-01

Three serum amyloid A (SAA) genes were identified from the common carp (Cyprinus carpio) by PCR and RT-PCR. Considering both direction and sequence similarity with mammal's orthologs, they were named CcSAA3a, CcSAA3b and CcSAA1. CcSAA3b and CcSAA1 are adjacent on contig LHQP01017858, suggesting that the prototype of or the simplest SAA multigene family have occurred in common carp. A phylogenetic analysis of the SAAs indicated that the fish SAAs were closer to those of invertebrates and Ornithorhynchus anatinus, a primitive mammal, than to mammalian SAAs. Quantitative real-time RT-PCR results displayed different expression profiles of three CcSAAs. The CcSAA3a was detected in all tested tissues, and was most abundant in the muscle; CcSAA3b was predominately expressed in the intestine and liver, and CcSAA1 in the skin. The expression level of CcSAA3a was higher than that of CcSAA3b and CcSAA1 in most tissues. Stimulation with Aeromonas hydrophila dramatically induced the expression of the three CcSAAs in all examined tissues, especially in the liver. Like Epinephelus coioides SAA, all of three rCcSAA fusion proteins could bind to both Gram-negative bacteria (A. hydrophila and E. coli) and Gram-positive bacterium (S. aureus), playing a role in the identification of bacteria. However, only rCcSAA3a showed significantly anti-A. hydrophila and anti-E. coli in vitro antibacterial activity assays. These results suggested that the three CcSAAs were in functional differentiation and play significant roles in the innate immunity of common carp. Copyright © 2017. Published by Elsevier Ltd.

Modular Battery Charge Controller

NASA Technical Reports Server (NTRS)

Button, Robert; Gonzalez, Marcelo

2009-01-01

A new approach to masterless, distributed, digital-charge control for batteries requiring charge control has been developed and implemented. This approach is required in battery chemistries that need cell-level charge control for safety and is characterized by the use of one controller per cell, resulting in redundant sensors for critical components, such as voltage, temperature, and current. The charge controllers in a given battery interact in a masterless fashion for the purpose of cell balancing, charge control, and state-of-charge estimation. This makes the battery system invariably fault-tolerant. The solution to the single-fault failure, due to the use of a single charge controller (CC), was solved by implementing one CC per cell and linking them via an isolated communication bus [e.g., controller area network (CAN)] in a masterless fashion so that the failure of one or more CCs will not impact the remaining functional CCs. Each micro-controller-based CC digitizes the cell voltage (V(sub cell)), two cell temperatures, and the voltage across the switch (V); the latter variable is used in conjunction with V(sub cell) to estimate the bypass current for a given bypass resistor. Furthermore, CC1 digitizes the battery current (I1) and battery voltage (V(sub batt) and CC5 digitizes a second battery current (I2). As a result, redundant readings are taken for temperature, battery current, and battery voltage through the summation of the individual cell voltages given that each CC knows the voltage of the other cells. For the purpose of cell balancing, each CC periodically and independently transmits its cell voltage and stores the received cell voltage of the other cells in an array. The position in the array depends on the identifier (ID) of the transmitting CC. After eight cell voltage receptions, the array is checked to see if one or more cells did not transmit. If one or more transmissions are missing, the missing cell(s) is (are) eliminated from cell-balancing calculations. The cell-balancing algorithm is based on the error between the cell s voltage and the other cells and is categorized into four zones of operation. The algorithm is executed every second and, if cell balancing is activated, the error variable is set to a negative low value. The largest error between the cell and the other cells is found and the zone of operation determined. If the error is zero or negative, then the cell is at the lowest voltage and no balancing action is needed. If the error is less than a predetermined negative value, a Cell Bad Flag is set. If the error is positive, then cell balancing is needed, but a hysteretic zone is added to prevent the bypass circuit from triggering repeatedly near zero error. This approach keeps the cells within a predetermined voltage range.

Bond Energies and Thermochemical Properties of Ring-Opened Diradicals and Carbenes of exo-Tricyclo[5.2.1.0(2,6)]decane.

PubMed

Hudzik, Jason M; Castillo, Álvaro; Bozzelli, Joseph W

2015-09-24

Exo-tricyclo[5.2.1.0(2,6)]decane (TCD) or exo-tetrahydrodicyclopentadiene is an interesting strained ring compound and the single-component high-energy density hydrocarbon fuel known as JP-10. Important initial reactions of TCD at high temperatures could cleave a strained carbon-carbon (C-C) bond in the ring system creating diradicals also constrained by the remaining ring system. This study determines the thermochemical properties of these diradicals (TCD-H2 mJ-nJ where m and n correspond to the cleaved carbons sites) including the carbon-carbon bond dissociation energy (C-C BDE) corresponding to the cleaved TCD site. Thermochemical properties including enthalpies (ΔH°f298), entropies (S(T)), heat capacities (Cp(T)), and C-H and C-C BDEs for the parent (TCD-H2 m-n), radical (TCD-H2 mJ-n and m-nJ), diradical (TCD-H2 mJ-nJ), and carbene (TCD-H2 mJJ-n and m-nJJ) species are determined. Structures, vibrational frequencies, moments of inertia, and internal rotor potentials are calculated at the B3LYP/6-31G(d,p) level of theory. Standard enthalpies of formation in the gas phase for the TCD-H2 m-n parent and radical species are determined using the B3LYP density functional theory and the higher level G3MP2B3 and CBS-QB3 composite methods. For singlet and triplet TCD diradicals and carbenes, M06-2X, ωB97X-D, and CCSD(T) methods are included in the analysis to determine ΔH°f298 values. The C-C BDEs are further calculated using CASMP2(2,2)/aug-cc-pvtz//CASSCF(2,2)/cc-pvtz and with the CASMP2 energies extrapolated to the complete basis set limit. The bond energies calculated with these methods are shown to be comparable to the other calculation methods. Isodesmic work reactions are used for enthalpy analysis of these compounds for effective cancelation of systematic errors arising from ring strain. C-C BDEs range from 77.4 to 84.6 kcal mol(-1) for TCD diradical singlet species. C-H BDEs for the parent TCD-H2 m-n carbon sites range from 93 to 101 kcal mol(-1) with a similar range seen for loss of the second hydrogen to generate the diradical singlet species. A wider range for C-C BDEs is seen for the carbenes from about 77 to 100 kcal mol(-1) as compared to the diradicals. Results from the DFT methods for the parents, radicals, diradicals, and carbenes are in good agreement with results from the composite methods using our sets of work reactions.

The coordination patterns observed when two hands reach-to-grasp separate objects.

PubMed

Bingham, Geoffrey P; Hughes, Kirstie; Mon-Williams, Mark

2008-01-01

What determines coordination patterns when both hands reach to grasp separate objects at the same time? It is known that synchronous timing is preferred as the most stable mode of bimanual coordination. Nonetheless, normal unimanual prehension behaviour predicts asynchrony when the two hands reach towards unequal targets, with synchrony restricted to targets equal in size and distance. Additionally, sufficiently separated targets require sequential looking. Does synchrony occur in all cases because it is preferred in bimanual coordination or does asynchrony occur because of unimanual task constraints and the need for sequential looking? We investigated coordinative timing when participants (n = 8) moved their right (preferred) hand to the same object at a fixed distance but the left hand to objects of different width (3, 5, and 7 cm) and grip surface size (1, 2, and 3 cm) placed at different distances (20, 30, and 40 cm) over 270 randomised trials. The hand movements consisted of two components: (1) an initial component (IC) during which the hand reached towards the target while forming an appropriate grip aperture, stopping at (but not touching) the object; (2) a completion component (CC) during which the finger and thumb closed on the target. The two limbs started the IC together but did not interact until the deceleration phase when evidence of synchronisation began to appear. Nonetheless, asynchronous timing was present at the end of the IC and preserved through the CC even with equidistant targets. Thus, there was synchrony but requirements for visual information ultimately yielded asynchronous coordinative timing.

SU-E-I-58: Objective Models of Breast Shape Undergoing Mammography and Tomosynthesis Using Principal Component Analysis.

PubMed

Feng, Ssj; Sechopoulos, I

2012-06-01

To develop an objective model of the shape of the compressed breast undergoing mammographic or tomosynthesis acquisition. Automated thresholding and edge detection was performed on 984 anonymized digital mammograms (492 craniocaudal (CC) view mammograms and 492 medial lateral oblique (MLO) view mammograms), to extract the edge of each breast. Principal Component Analysis (PCA) was performed on these edge vectors to identify a limited set of parameters and eigenvectors that. These parameters and eigenvectors comprise a model that can be used to describe the breast shapes present in acquired mammograms and to generate realistic models of breasts undergoing acquisition. Sample breast shapes were then generated from this model and evaluated. The mammograms in the database were previously acquired for a separate study and authorized for use in further research. The PCA successfully identified two principal components and their corresponding eigenvectors, forming the basis for the breast shape model. The simulated breast shapes generated from the model are reasonable approximations of clinically acquired mammograms. Using PCA, we have obtained models of the compressed breast undergoing mammographic or tomosynthesis acquisition based on objective analysis of a large image database. Up to now, the breast in the CC view has been approximated as a semi-circular tube, while there has been no objectively-obtained model for the MLO view breast shape. Such models can be used for various breast imaging research applications, such as x-ray scatter estimation and correction, dosimetry estimates, and computer-aided detection and diagnosis. © 2012 American Association of Physicists in Medicine.

Agent-based modeling of autophagy reveals emergent regulatory behavior of spatio-temporal autophagy dynamics.

PubMed

Börlin, Christoph S; Lang, Verena; Hamacher-Brady, Anne; Brady, Nathan R

2014-09-10

Autophagy is a vesicle-mediated pathway for lysosomal degradation, essential under basal and stressed conditions. Various cellular components, including specific proteins, protein aggregates, organelles and intracellular pathogens, are targets for autophagic degradation. Thereby, autophagy controls numerous vital physiological and pathophysiological functions, including cell signaling, differentiation, turnover of cellular components and pathogen defense. Moreover, autophagy enables the cell to recycle cellular components to metabolic substrates, thereby permitting prolonged survival under low nutrient conditions. Due to the multi-faceted roles for autophagy in maintaining cellular and organismal homeostasis and responding to diverse stresses, malfunction of autophagy contributes to both chronic and acute pathologies. We applied a systems biology approach to improve the understanding of this complex cellular process of autophagy. All autophagy pathway vesicle activities, i.e. creation, movement, fusion and degradation, are highly dynamic, temporally and spatially, and under various forms of regulation. We therefore developed an agent-based model (ABM) to represent individual components of the autophagy pathway, subcellular vesicle dynamics and metabolic feedback with the cellular environment, thereby providing a framework to investigate spatio-temporal aspects of autophagy regulation and dynamic behavior. The rules defining our ABM were derived from literature and from high-resolution images of autophagy markers under basal and activated conditions. Key model parameters were fit with an iterative method using a genetic algorithm and a predefined fitness function. From this approach, we found that accurate prediction of spatio-temporal behavior required increasing model complexity by implementing functional integration of autophagy with the cellular nutrient state. The resulting model is able to reproduce short-term autophagic flux measurements (up to 3 hours) under basal and activated autophagy conditions, and to measure the degree of cell-to-cell variability. Moreover, we experimentally confirmed two model predictions, namely (i) peri-nuclear concentration of autophagosomes and (ii) inhibitory lysosomal feedback on mTOR signaling. Agent-based modeling represents a novel approach to investigate autophagy dynamics, function and dysfunction with high biological realism. Our model accurately recapitulates short-term behavior and cell-to-cell variability under basal and activated conditions of autophagy. Further, this approach also allows investigation of long-term behaviors emerging from biologically-relevant alterations to vesicle trafficking and metabolic state.

Exploration of cellular reaction systems.

PubMed

Kirkilionis, Markus

2010-01-01

We discuss and review different ways to map cellular components and their temporal interaction with other such components to different non-spatially explicit mathematical models. The essential choices made in the literature are between discrete and continuous state spaces, between rule and event-based state updates and between deterministic and stochastic series of such updates. The temporal modelling of cellular regulatory networks (dynamic network theory) is compared with static network approaches in two first introductory sections on general network modelling. We concentrate next on deterministic rate-based dynamic regulatory networks and their derivation. In the derivation, we include methods from multiscale analysis and also look at structured large particles, here called macromolecular machines. It is clear that mass-action systems and their derivatives, i.e. networks based on enzyme kinetics, play the most dominant role in the literature. The tools to analyse cellular reaction networks are without doubt most complete for mass-action systems. We devote a long section at the end of the review to make a comprehensive review of related tools and mathematical methods. The emphasis is to show how cellular reaction networks can be analysed with the help of different associated graphs and the dissection into modules, i.e. sub-networks.

Partial Agenesis and Hypoplasia of the Corpus Callosum in Idiopathic Autism

PubMed Central

Wegiel, Jarek; Flory, Michael; Kaczmarski, Wojciech; Brown, W. Ted; Chadman, Kathryn; Wisniewski, Thomas; Nowicki, Krzysztof; Kuchna, Izabela; Ma, Shuang Yong; Wegiel, Jerzy

2017-01-01

Abstract To test the hypothesis that developmental anomalies of the corpus callosum (CC), contribute to the pathogenesis of autism, we characterized the type, topography, and severity of CC pathology corresponding to reduced CC areas that are detected by magnetic resonance imaging in the brains of 11 individuals with autism and 11 controls. In the brains of 3 autistic subjects, partial CC agenesis resulted in complete or partial lack of interhemispheric axonal connections in CC segments III–V. In these cases, a combination of focal agenesis and uniform axonal deficit caused reduction of CC areas by 37%, of axon numbers by 62%, and of the numerical density of axons by 39%. In the CC of 8 autistic subjects without agenesis, there was an 18% deficit of the midsagittal CC area, 48.4% deficit of axon numbers, and 37% reduction of the numerical density of axons. The significantly thinner CC, reduced CC area, and uniform axonal deficit in all autistic subjects were classified as CC hypoplasia. Thus, the byproduct of partial CC agenesis and hypoplasia is reduction of axonal connections between cortical areas known to be involved in behavioral alterations observed in people with autism. PMID:28395085

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with low within-herd prevalence of intra-mammary infections in dairy cows: Genotyping of isolates.

PubMed

Luini, M; Cremonesi, P; Magro, G; Bianchini, V; Minozzi, G; Castiglioni, B; Piccinini, R

2015-08-05

Staphylococcus aureus is one of the most common mastitis-causing pathogens worldwide. In the last decade, livestock-associated methicillin-resistant S. aureus (LA-MRSA) infections have been described in several species, included the bovines. Hence, this paper investigates the diffusion of MRSA within Italian dairy herds; the strains were further characterized using a DNA microarray, which detects 330 different sequences, including the methicillin-resistance genes mecA and mecC and SCCmec typing. The analysis of overall patterns allows the assignment to Clonal Complexes (CC). Overall 163 S. aureus isolates, collected from quarter milk samples in 61 herds, were tested. MRSA strains were further processed using spa typing. Fifteen strains (9.2%), isolated in 9 herds (14.75%), carried mecA, but none harboured mecC. MRSA detection was significantly associated (P<0.011) with a within-herd prevalence of S. aureus intra-mammary infections (IMI) ≤5%. Ten MRSA strains were assigned to CC398, the remaining ones to CC97 (n=2), CC1 (n=2) or CC8 (n=1). In 3 herds, MRSA and MSSA co-existed: CC97-MRSA with CC398-MSSA, CC1-MRSA with CC8-MSSA and CC398-MRSA with CC126-MSSA. The results of spa typing showed an overall similar profile of the strains belonging to the same CC: t127-CC1, t1730-CC97, t899 in 8 out of 10 CC398. In the remaining 2 isolates a new spa type, t14644, was identified. The single CC8 was a t3092. The SCCmec cassettes were classified as type IV, type V or type IV/V composite. All or most strains harboured the genes encoding the β-lactamase operon and the tetracycline resistance. Streptogramin resistance gene was related to CC398. Enterotoxin and leukocidin genes were carried only by CC1, CC8 and CC97-MRSA. The persistence of MRSA clones characterized by broader host range, in epidemiologically unrelated areas and in dairy herds with low prevalence of S. aureus IMI, might enhance the risk for adaptation to human species. Copyright © 2015 Elsevier B.V. All rights reserved.

Method of synthesizing a low density material

DOEpatents

Lorensen, L.E.; Monaco, S.B.

1987-02-27

A novel method of synthesizing a polymeric material of low density of the order of 50mg/cc or less. Such a low density material has applications in many areas including laser target fabrication. The method comprises preparing a polymer blend of two incompatible polymers as a major and a minor phase by mixing them and extruding the mixture, and then selectively extracting the major component, to yield a fine, low density structure.

Simulation Based Optimization of Complex Monolithic Composite Structures Using Cellular Core Technology

NASA Astrophysics Data System (ADS)

Hickmott, Curtis W.

Cellular core tooling is a new technology which has the capability to manufacture complex integrated monolithic composite structures. This novel tooling method utilizes thermoplastic cellular cores as inner tooling. The semi-rigid nature of the cellular cores makes them convenient for lay-up, and under autoclave temperature and pressure they soften and expand providing uniform compaction on all surfaces including internal features such as ribs and spar tubes. This process has the capability of developing fully optimized aerospace structures by reducing or eliminating assembly using fasteners or bonded joints. The technology is studied in the context of evaluating its capabilities, advantages, and limitations in developing high quality structures. The complex nature of these parts has led to development of a model using the Finite Element Analysis (FEA) software Abaqus and the plug-in COMPRO Common Component Architecture (CCA) provided by Convergent Manufacturing Technologies. This model utilizes a "virtual autoclave" technique to simulate temperature profiles, resin flow paths, and ultimately deformation from residual stress. A model has been developed simulating the temperature profile during curing of composite parts made with the cellular core technology. While modeling of composites has been performed in the past, this project will look to take this existing knowledge and apply it to this new manufacturing method capable of building more complex parts and develop a model designed specifically for building large, complex components with a high degree of accuracy. The model development has been carried out in conjunction with experimental validation. A double box beam structure was chosen for analysis to determine the effects of the technology on internal ribs and joints. Double box beams were manufactured and sectioned into T-joints for characterization. Mechanical behavior of T-joints was performed using the T-joint pull-off test and compared to traditional tooling methods. Components made with the cellular core tooling method showed an improved strength at the joints. It is expected that this knowledge will help optimize the processing of complex, integrated structures and benefit applications in aerospace where lighter, structurally efficient components would be advantageous.

Appointing silver and bronze standards for noncovalent interactions: A comparison of spin-component-scaled (SCS), explicitly correlated (F12), and specialized wavefunction approaches

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

Burns, Lori A.; Marshall, Michael S.; Sherrill, C. David, E-mail: sherrill@gatech.edu

2014-12-21

A systematic examination of noncovalent interactions as modeled by wavefunction theory is presented in comparison to gold-standard quality benchmarks available for 345 interaction energies of 49 bimolecular complexes. Quantum chemical techniques examined include spin-component-scaling (SCS) variations on second-order perturbation theory (MP2) [SCS, SCS(N), SCS(MI)] and coupled cluster singles and doubles (CCSD) [SCS, SCS(MI)]; also, method combinations designed to improve dispersion contacts [DW-MP2, MP2C, MP2.5, DW-CCSD(T)-F12]; where available, explicitly correlated (F12) counterparts are also considered. Dunning basis sets augmented by diffuse functions are employed for all accessible ζ-levels; truncations of the diffuse space are also considered. After examination of both accuracymore » and performance for 394 model chemistries, SCS(MI)-MP2/cc-pVQZ can be recommended for general use, having good accuracy at low cost and no ill-effects such as imbalance between hydrogen-bonding and dispersion-dominated systems or non-parallelity across dissociation curves. Moreover, when benchmarking accuracy is desirable but gold-standard computations are unaffordable, this work recommends silver-standard [DW-CCSD(T**)-F12/aug-cc-pVDZ] and bronze-standard [MP2C-F12/aug-cc-pVDZ] model chemistries, which support accuracies of 0.05 and 0.16 kcal/mol and efficiencies of 97.3 and 5.5 h for adenine·thymine, respectively. Choice comparisons of wavefunction results with the best symmetry-adapted perturbation theory [T. M. Parker, L. A. Burns, R. M. Parrish, A. G. Ryno, and C. D. Sherrill, J. Chem. Phys. 140, 094106 (2014)] and density functional theory [L. A. Burns, Á. Vázquez-Mayagoitia, B. G. Sumpter, and C. D. Sherrill, J. Chem. Phys. 134, 084107 (2011)] methods previously studied for these databases are provided for readers' guidance.« less

Identification of a cobia (Rachycentron canadum) CC chemokine gene and its involvement in the inflammatory response.

PubMed

Su, Youlu; Guo, Zhixun; Xu, Liwen; Jiang, Jingzhe; Wang, Jiangyong; Feng, Juan

2012-01-01

The chemokines regulate immune cell migration under inflammatory and physiological conditions. We investigated a CC chemokine gene (RcCC1) from cobia (Rachycentron canadum). The full-length RcCC1 cDNA is comprised 673 nucleotides and encodes a four-cysteine arrangement 99-amino-acid protein typical of known CC chemokines. The genomic DNA of RcCC1 consists of three exons and two introns. Phylogenetic analysis showed that RcCC1 was closest to the MIP group of CC chemokines. Quantitative real-time RT-PCR (qRT-PCR) analysis revealed RcCC1 was constitutively expressed in all tissues examined, with relative strong expression in gill, blood, kidney, spleen, and head kidney. The RcCC1 transcripts in the head kidney, spleen, and liver were quickly up-regulated after stimulation with formalin-inactivated Vibrio carchariae (bacterial vaccine) or polyriboinosinic polyribocytidylic acid (poly I:C). These results indicate RcCC1 not only plays a role in homeostasis, but also may be involved in inflammatory responses to bacterial and viral infection. Copyright © 2011 Elsevier Ltd. All rights reserved.

Emerging Biomimetic Applications of DNA Nanotechnology.

PubMed

Shen, Haijing; Wang, Yingqian; Wang, Jie; Li, Zhihao; Yuan, Quan

2018-06-25

Re-engineering cellular components and biological processes has received great interest and promised compelling advantages in applications ranging from basic cell biology to biomedicine. With the advent of DNA nanotechnology, the programmable self-assembly ability makes DNA an appealing candidate for rational design of artificial components with different structures and functions. This Forum Article summarizes recent developments of DNA nanotechnology in mimicking the structures and functions of existing cellular components. We highlight key successes in the achievements of DNA-based biomimetic membrane proteins and discuss the assembly behavior of these artificial proteins. Then, we focus on the construction of higher-order structures by DNA nanotechnology to recreate cell-like structures. Finally, we explore the current challenges and speculate on future directions of DNA nanotechnology in biomimetics.

Polyphenols from Cymbopogon citratus leaves as topical anti-inflammatory agents.

PubMed

Costa, Gustavo; Ferreira, João Pinto; Vitorino, Carla; Pina, Maria Eugénia; Sousa, João José; Figueiredo, Isabel Vitória; Batista, Maria Teresa

2016-02-03

A variety of plant polyphenols have been reported to have anti-inflammatory, frequently associated with erythema, edema, hyperplasia, skin photoaging and photocarcinogenesis. Cymbopogon citratus (DC). Stapf (Poaceae) is a worldwide known medicinal plant, used in traditional medicine in inflammation-related conditions. In this work, the anti-inflammatory potential of C. citratus infusion (CcI) and its polyphenols as topical agents was evaluated in vivo. The plant extract was prepared and its fractioning led two polyphenol-rich fractions: flavonoids fraction (CcF) and tannins fraction (CcT). An oil/water emulsion was developed with each active (CcI, CcF+CcT and diclofenac), pH and texture having been evaluated. Release tests were further performed using static Franz diffusion cells and all collected samples were monitored by HPLC-PDA. In vivo topical anti-inflammatory activity evaluation was performed by the carrageenan-induced rat paw edema model. The texture analysis revealed statistically significant differences for all tested parameters to CcF+CcT, supporting its topical application. Release experiments lead to the detection of the phenolic compounds from each sample in the receptor medium and the six major flavonoids were quantified, by HPLC-PDA: carlinoside, isoorientin, cynaroside, luteolin 7-O-neohesperidoside, kurilesin A and cassiaoccidentalin B. The CcF+CcT formulation prompted to the higher release rate for all these flavonoids. CcI4%, CcI1% and CcF+CcT exhibited an edema reduction of 43.18, 29.55 and 59.09%, respectively. Our findings highlight that CcI, containing luteolin 7-O-neohesperidoside, cassiaoccidentalin B, carlinoside, cynaroside and tannins have a potential anti-inflammatory topical activity, suggesting their promising application in the treatment of skin inflammatory pathologies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Small field out-put factors comparison between ion chambers and diode dedectors for different photon energies

NASA Astrophysics Data System (ADS)

Tas, B.; Durmus, I. F.

2018-02-01

To compare small fields out-put factors of linear accelerator by using different ion chambers and diode dedectors for different photon energies. We measured small fields (1×1 to 5×5 cm2) out-put factors by using IBA® cc003 nano chamber, cc01 Razor, cc01, cc04, cc13, fc65 ion chambers and SFD, Razor diode dedectors for 6MV, 10MV, 15MV, 6MV FFF and 10MV FFF energies. We determined the most compatible out-put factors between ion chamber and diode dedector by using cc003 nano ion chamber for 1×1cm2 field size. We determined less than %2 dose difference between cc003 nano chamber, cc01 Razor, cc01, cc04 and cc13 ion chambers from 2×2 to 5×5 cm2. We determined %12±2 and %13±1 underestimate doses by using cc01 and cc13 ion chambers, also we determined %57±2 underesimate dose by using fc65 ion chamber's than razor diode for 1×1 cm2 field size. These results show that we shouldn't measure out-put factors of 1×1 cm2 field size by using cc01, cc13 and fc65 ion chambers. The dose difference between SFD and Razor diodes were determined less than %1.5. If we would like to use ion chambers for ≤1×1cm2 field size out-put measurement, we should use correction factor while commisionning linear accelerator. Otherwise we could determine underestimate dose by using ion chambers.

Important cellular targets for antimicrobial photodynamic therapy.

PubMed

Awad, Mariam M; Tovmasyan, Artak; Craik, James D; Batinic-Haberle, Ines; Benov, Ludmil T

2016-09-01

The persistent problem of antibiotic resistance has created a strong demand for new methods for therapy and disinfection. Photodynamic inactivation (PDI) of microbes has demonstrated promising results for eradication of antibiotic-resistant strains. PDI is based on the use of a photosensitive compound (photosensitizer, PS), which upon illumination with visible light generates reactive species capable of damaging and killing microorganisms. Since photogenerated reactive species are short lived, damage is limited to close proximity of the PS. It is reasonable to expect that the larger the number of damaged targets is and the greater their variety is, the higher the efficiency of PDI is and the lower the chances for development of resistance are. Exact molecular mechanisms and specific targets whose damage is essential for microbial inactivation have not been unequivocally established. Two main cellular components, DNA and plasma membrane, are regarded as the most important PDI targets. Using Zn porphyrin-based PSs and Escherichia coli as a model Gram-negative microorganism, we demonstrate that efficient photoinactivation of bacteria can be achieved without detectable DNA modification. Among the cellular components which are modified early during illumination and constitute key PDI targets are cytosolic enzymes, membrane-bound protein complexes, and the plasma membrane. As a result, membrane barrier function is lost, and energy and reducing equivalent production is disrupted, which in turn compromises cell defense mechanisms, thus augmenting the photoinduced oxidative injury. In conclusion, high PDI antimicrobial effectiveness does not necessarily require impairment of a specific critical cellular component and can be achieved by inducing damage to multiple cellular targets.

Age-Specific Dynamics of Corpus Callosum Development in Children and its Peculiarities in Infantile Cerebral Palsy.

PubMed

Krasnoshchekova, E I; Zykin, P A; Tkachenko, L A; Aleksandrov, T A; Sereda, V M; Yalfimov, A N

2016-10-01

The age dynamics of corpus callosum development was studied on magnetic resonance images of the brain in children aged 2-11 years without neurological abnormalities and with infantile cerebral palsy. The areas of the total corpus callosum and its segments are compared in the midsagittal images. Analysis is carried out with the use of an original formula: proportion of areas of the anterior (genu, CC2; and anterior part, CC3) and posterior (isthmus, CC6 and splenium, CC7) segments: kCC=(CC2+CC3)×CC6/CC7. The results characterize age-specific dynamics of the corpus callosum development and can be used for differentiation, with high confidence, of the brain of children without neurological abnormalities from the brain patients with infantile cerebral palsy.

Senescence-Associated MCP-1 Secretion Is Dependent on a Decline in BMI1 in Human Mesenchymal Stromal Cells

PubMed Central

Jin, Hye Jin; Lee, Hyang Ju; Heo, Jinbeom; Lim, Jisun; Kim, Miyeon; Kim, Min Kyung; Nam, Hae Yun; Hong, Gyong Hwa; Cho, You Sook; Choi, Soo Jin; Kim, In-Gyu

2016-01-01

Abstract Aims: Cellular senescence and its secretory phenotype (senescence-associated secretory phenotype [SASP]) develop after long-term expansion of mesenchymal stromal cells (MSCs). Further investigation of this phenotype is required to improve the therapeutic efficacy of MSC-based cell therapies. In this study, we show that positive feedback between SASP and inherent senescence processes plays a crucial role in the senescence of umbilical cord blood-derived MSCs (UCB-MSCs). Results: We found that monocyte chemoattractant protein-1 (MCP-1) was secreted as a dominant component of the SASP during expansion of UCB-MSCs and reinforced senescence via its cognate receptor chemokine (c-c motif) receptor 2 (CCR2) by activating the ROS-p38-MAPK-p53/p21 signaling cascade in both an autocrine and paracrine manner. The activated p53 in turn increased MCP-1 secretion, completing a feed-forward loop that triggered the senescence program in UCB-MSCs. Accordingly, knockdown of CCR2 in UCB-MSCs significantly improved their therapeutic ability to alleviate airway inflammation in an experimental allergic asthma model. Moreover, BMI1, a polycomb protein, repressed the expression of MCP-1 by binding to its regulatory elements. The reduction in BMI1 levels during UCB-MSC senescence altered the epigenetic status of MCP-1, including the loss of H2AK119Ub, and resulted in derepression of MCP-1. Innovation: Our results provide the first evidence supporting the existence of the SASP as a causative contributor to UCB-MSC senescence and reveal a so far unappreciated link between epigenetic regulation and SASP for maintaining a stable senescent phenotype. Conclusion: Senescence of UCB-MSCs is orchestrated by MCP-1, which is secreted as a major component of the SASP and is epigenetically regulated by BMI1. Antioxid. Redox Signal. 24, 471–485. PMID:26573462

Development of a pericardial acellular matrix biomaterial: biochemical and mechanical effects of cell extraction.

PubMed

Courtman, D W; Pereira, C A; Kashef, V; McComb, D; Lee, J M; Wilson, G J

1994-06-01

There is evidence to suggest that the cellular components of homografts and bioprosthetic xenografts may contribute to calcification or immunogenic reactions. A four-step detergent and enzymatic extraction process has been developed to remove cellular components from bovine pericardial tissue. The process results in an acellular matrix material consisting primarily of elastin, insoluble collagen, and tightly bound glycosaminoglycans. Light and electron microscopy confirmed that nearly all cellular constituents are removed without ultrastructural evidence of damage to fibrous components. Collagen denaturation temperatures remained unaltered. Biochemical analysis confirmed the retention of collagen and elastin and some differential extraction of glycosaminoglycans. Low strain rate fracture testing and high strain rate viscoelastic characterization showed that, with the exception of slightly increased stress relaxation, the mechanical properties of the fresh tissue were preserved in the pericardial acellular matrix. Crosslinking of the material in glutaraldehyde or poly(glycidyl ether) produced mechanical changes consistent with the same treatments of fresh tissue. The pericardial acellular matrix is a promising approach to the production of biomaterials for heart valve or cardiovascular patching applications.

Quantifying white matter tract diffusion parameters in the presence of increased extra-fiber cellularity and vasogenic edema

PubMed Central

Chiang, Chia-Wen; Wang, Yong; Sun, Peng; Lin, Tsen-Hsuan; Trinkaus, Kathryn; Cross, Anne H.; Song, Sheng-Kwei

2014-01-01

The effect of extra-fiber structural and pathological components confounding diffusion tensor imaging (DTI) computation was quantitatively investigated using data generated by both Monte-Carlo simulations and tissue phantoms. Increased extent of vasogenic edema, by addition of various amount of gel to fixed normal mouse trigeminal nerves or by increasing non-restricted isotropic diffusion tensor components in Monte-Carlo simulations, significantly decreased fractional anisotropy (FA), increased radial diffusivity, while less significantly increased axial diffusivity derived by DTI. Increased cellularity, mimicked by graded increase of the restricted isotropic diffusion tensor component in Monte-Carlo simulations, significantly decreased FA and axial diffusivity with limited impact on radial diffusivity derived by DTI. The MC simulation and tissue phantom data were also analyzed by the recently developed diffusion basis spectrum imaging (DBSI) to simultaneously distinguish and quantify the axon/myelin integrity and extra-fiber diffusion components. Results showed that increased cellularity or vasogenic edema did not affect the DBSI-derived fiber FA, axial or radial diffusivity. Importantly, the extent of extra-fiber cellularity and edema estimated by DBSI correlated with experimentally added gel and Monte-Carlo simulations. We also examined the feasibility of applying 25-direction diffusion encoding scheme for DBSI analysis on coherent white matter tracts. Results from both phantom experiments and simulations suggested that the 25-direction diffusion scheme provided comparable DBSI estimation of both fiber diffusion parameters and extra-fiber cellularity/edema extent as those by 99-direction scheme. An in vivo 25-direction DBSI analysis was performed on experimental autoimmune encephalomyelitis (EAE, an animal model of human multiple sclerosis) optic nerve as an example to examine the validity of derived DBSI parameters with post-imaging immunohistochemistry verification. Results support that in vivo DBSI using 25-direction diffusion scheme correctly reflect the underlying axonal injury, demyelination, and inflammation of optic nerves in EAE mice. PMID:25017446

Body Fluids Monitor

NASA Technical Reports Server (NTRS)

Siconolfi, Steven F. (Inventor)

2000-01-01

Method and apparatus are described for determining volumes of body fluids in a subject using bioelectrical response spectroscopy. The human body is represented using an electrical circuit. Intra-cellular water is represented by a resistor in series with a capacitor; extra-cellular water is represented by a resistor in series with two parallel inductors. The parallel inductors represent the resistance due to vascular fluids. An alternating, low amperage, multifrequency signal is applied to determine a subject's impedance and resistance. From these data, statistical regression is used to determine a 1% impedance where the subject's impedance changes by no more than 1% over a 25 kHz interval. Circuit component, of the human body circuit are determined based on the 1% impedance. Equations for calculating total body water, extra-cellular water, total blood volume, and plasma volume are developed based on the circuit components.

Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues.

PubMed

Cifola, Ingrid; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A

2011-06-13

Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches aimed to study genes or pathways involved in ccRCC etiopathogenesis and to identify novel clinical markers or therapeutic targets. Moreover, SNP array technology proved to be a powerful tool to better define the cell composition and homogeneity of RCC primary cultures. © 2011 Cifola et al; licensee BioMed Central Ltd.

Adipose tissue fibrosis in human cancer cachexia: the role of TGFβ pathway.

PubMed

Alves, Michele Joana; Figuerêdo, Raquel Galvão; Azevedo, Flavia Figueiredo; Cavallaro, Diego Alexandre; Neto, Nelson Inácio Pinto; Lima, Joanna Darck Carola; Matos-Neto, Emidio; Radloff, Katrin; Riccardi, Daniela Mendes; Camargo, Rodolfo Gonzalez; De Alcântara, Paulo Sérgio Martins; Otoch, José Pinhata; Junior, Miguel Luiz Batista; Seelaender, Marília

2017-03-14

Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGFβ) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGFβ in inducing AT remodeling in weight-losing cancer patients are poorly understood. This study examined the modulation of ECM components mediated by TGFβ pathway in fibrotic AT obtained from cachectic gastrointestinal cancer patients. After signing the informed consent form, patients were enrolled into the following groups: cancer cachexia (CC, n = 21), weight-stable cancer (WSC, n = 17), and control (n = 21). The total amount of collagen and elastic fibers in the subcutaneous AT was assessed by histological analysis and by immunohistochemistry. TGFβ isoforms expression was analyzed by Multiplex assay and by immunohistochemistry. Alpha-smooth muscle actin (αSMA), fibroblast-specific protein (FSP1), Smad3 and 4 were quantified by qPCR and/or by immunohistochemistry. Interleukin (IL) 2, IL5, IL8, IL13 and IL17 content, cytokines known to be associated with fibrosis, was measured by Multiplex assay. There was an accumulation of collagen and elastic fibers in the AT of CC, as compared with WSC and controls. Collagens type I, III, VI, and fibronectin expression was enhanced in the tissue of CC, compared with both WSC and control. The pronounced expression of αSMA in the surrounding of adipocytes, and the increased mRNA content for FSP1 (20-fold) indicate the presence of activated myofibroblasts; particularly in CC. TGFβ1 and TGFβ3 levels were up-regulated by cachexia in AT, as well in the isolated adipocytes. Smad3 and Smad4 labeling was found to be more evident in the fibrotic areas of CC adipose tissue. Cancer cachexia promotes the development of AT fibrosis, in association with altered TGFβ signaling, compromising AT organization and function.

Does Core Length Taken per cc of Prostate Volume in Prostate Biopsy Affect the Diagnosis of Prostate Cancer?

PubMed

Deliktas, Hasan; Sahin, Hayrettin; Cetinkaya, Mehmet; Dere, Yelda; Erdogan, Omer; Baldemir, Ercan

2016-08-01

The aim of this study was to determine the minimal core length to be taken per cc of prostate volume for an effective prostate biopsy. A retrospective analysis was performed on the records of 379 patients who underwent a first prostate biopsy with 12 to 16 cores under transrectal ultrasound guidance between September 2012 and April 2015. For each patient, the core length per cc of the prostate and the percentage of sampled prostate volume were calculated, and these values were compared between the patients with and without prostate cancer. A total of 348 patients were included in the study. Cancer was determined in 26.4% of patients. The mean core length taken per cc of prostate and the percentage of sampled prostate volume were determined to be 3.40 ± 0.15 mm/cc (0.26%; range, 0.08-0.63 cc) in patients with cancer and 2.75 ± 0.08 mm/cc (0.20%; range, 0.04-0.66 cc) in patients without cancer (P = .000 and P = .000), respectively. Core length taken per cc of prostate of > 3.31 mm/cc was found to be related to an increase in the rates of prostate cancer diagnosis (odds ratio, 2.84; 95% confidence interval, 1.68-4.78). The rate of cancer determination for core length taken per cc of prostate of < 3.31 mm/cc was 19.9% and of > 3.31 mm/cc, 41.1%. Core length taken per cc of prostate and the percentage of sampled prostate volume are important morphometric parameters in the determination of prostate cancer. The results of study suggest a core length per cc of the prostate of > 3.31 mm/cc as a cutoff value for quality assurance. Copyright © 2016 Elsevier Inc. All rights reserved.

Selective ablation of Ppp1cc gene in testicular germ cells causes oligo-teratozoospermia and infertility in mice.

PubMed

Sinha, Nilam; Puri, Pawan; Nairn, Angus C; Vijayaraghavan, Srinivasan

2013-11-01

The four isoforms of serine/threonine phosphoprotein phosphatase 1 (PP1), derived from three genes, are among the most conserved proteins known. The Ppp1cc gene encodes two alternatively spliced variants, PP1 gamma1 (PPP1CC1) and PP1 gamma2 (PPP1CC2). Global deletion of the Ppp1cc gene, which causes loss of both isoforms, results in male infertility due to impaired spermatogenesis. This phenotype was assumed to be due to the loss of PPP1CC2, which is abundant in testis. While PPP1CC2 is predominant, other PP1 isoforms are also expressed in testis. Given the significant homology between the four PP1 isoforms, the lack of compensation by the other PP1 isoforms for loss of one, only in testis, is surprising. Here we document, for the first time, expression patterns of the PP1 isoforms in postnatal developing and adult mouse testis. The timing and sites of testis expression of PPP1CC1 and PPP1CC2 in testis are nonoverlapping. PPP1CC2 is the only one of the four PP1 isoforms not detected in sertoli cells and spermatogonia. Conversely, PPP1CC2 may be the only PP1 isoform expressed in postmeiotic germ cells. Deletion of the Ppp1cc gene in germ cells at the differentiated spermatogonia stage of development and beyond in Stra8 promoter-driven Cre transgenic mice results in oligo-terato-asthenozoospermia and male infertility, thus phenocopying global Ppp1cc null (-/-) mice. Taken together, these results confirm that spermatogenic defects observed in the global Ppp1cc knockout mice and in mice expressing low levels of PPP1CC2 in testis are due to compromised functions of PPP1CC2 in meiotic and postmeiotic germ cells.

An Overview of CC Coherent Pion Production

NASA Astrophysics Data System (ADS)

Williams, Zachary

2017-01-01

Neutrino cross-sections are a critical component to any neutrino measurement. With the modern neutrino experiments aiming to measure precision parameters, such as those in long-baseline oscillation experiments, the need for a detailed understanding of neutrino interactions has become even more important. Within this landscape remains a number of experimental challenges in the regime of low energy neutrino cross-sections. This talk will give an overview of recent publications on Charged Current-Coherent Pion Production (CC-Coh Pion) results from a number of experimental collaborations. Specifically, the lack of observation from the SciBooNE and T2K collaborations to observe CC-Coh Pion below one GeV in contrast to the observation of this signature at higher energies by other experiments. The work presented here is a part of the beginning steps to a reanalysis of the SciBooNE data using a modern neutrino generator in order to better understand the previous results. There will be included details of a liquid Argon purification system that is being built at UTA, and of plans for a ``Baby Time Projection Chamber (TPC)'' which will also be built at UTA, and the instrumentation and detector methods used in their construction. The closing is a look to the future for a new analysis at low neutrino energies utilizing Liquid Argon Time Projection Chambers (LArTPCs) based at Fermilab.

Assessment of cultural competence in Texas nursing faculty.

PubMed

Marzilli, Collen

2016-10-01

Cultural competence [CC] is an essential component of nursing education and nursing practice yet there is a gap in the research evaluating CC in faculty and how to practically develop this skillset for faculty members. To explore CC in faculty as evaluated with the Nurses' Cultural Competence Scale [NCCS] and apply the findings to the Purnell Model of Cultural Competence [PMCC] to guide professional development opportunities for faculty members. This was a concurrent mixed-methods study. Faculty members teaching in Texas nursing programs were recruited for the study. Quantitative data was collected using an online survey tool and qualitative data was collected over the phone. 89 Texas faculty members completed the quantitative strand and a subset of 10 faculty members completed the qualitative strand. Descriptive statistics were used to examine the quantitative data and Strauss and Corbin's methodology guided the evaluation of the qualitative data. These two strands were used to support the results. Faculty in Texas are moderately culturally competent. The qualitative findings support the application of the PMCC to the areas identified by the NCCS. The PMCC may be applied to the application of culture and values in nursing professional education as supported by the NCCS. Recommendations are to include the PMCC as a structure for the creation of professional development opportunities for faculty. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evidence for Extended Aqueous Alteration in CR Carbonaceous Chondrites

NASA Technical Reports Server (NTRS)

Trigo-Rodriquez, J. M.; Moyano-Cambero, C. E.; Mestres, N.; Fraxedas, J.; Zolensky, M.; Nakamura, T.; Martins, Z.

2013-01-01

We are currently studying the chemical interrelationships between the main rockforming components of carbonaceous chondrites (hereafter CC), e.g. silicate chondrules, refractory inclusions and metal grains, and the surrounding meteorite matrices. It is thought that the fine-grained materials that form CC matrices are representing samples of relatively unprocessed protoplanetary disk materials [1-3]. In fact, modern non-destructive analytical techniques have shown that CC matrices host a large diversity of stellar grains from many distinguishable stellar sources [4]. Aqueous alteration has played a role in homogeneizing the isotopic content that allows the identification of presolar grains [5]. On the other hand, detailed analytical techniques have found that the aqueously-altered CR, CM and CI chondrite groups contain matrices in which the organic matter has experienced significant processing concomitant to the formation of clays and other minerals. In this sense, clays have been found to be directly associated with complex organics [6, 7]. CR chondrites are particularly relevant in this context as this chondrite group contains abundant metal grains in the interstitial matrix, and inside glassy silicate chondrules. It is important because CR are known for exhibiting a large complexity of organic compounds [8-10], and only metallic Fe is considered essential in Fischer-Tropsch catalysis of organics [11-13]. Therefore, CR chondrites can be considered primitive materials capable to provide clues on the role played by aqueous alteration in the chemical evolution of their parent asteroids.

Intratumoral heterogeneity analysis reveals hidden associations between protein expression losses and patient survival in clear cell renal cell carcinoma

PubMed Central

Devarajan, Karthik; Parsons, Theodore; Wang, Qiong; O'Neill, Raymond; Solomides, Charalambos; Peiper, Stephen C.; Testa, Joseph R.; Uzzo, Robert; Yang, Haifeng

2017-01-01

Intratumoral heterogeneity (ITH) is a prominent feature of kidney cancer. It is not known whether it has utility in finding associations between protein expression and clinical parameters. We used ITH that is detected by immunohistochemistry (IHC) to aid the association analysis between the loss of SWI/SNF components and clinical parameters.160 ccRCC tumors (40 per tumor stage) were used to generate tissue microarray (TMA). Four foci from different regions of each tumor were selected. IHC was performed against PBRM1, ARID1A, SETD2, SMARCA4, and SMARCA2. Statistical analyses were performed to correlate biomarker losses with patho-clinical parameters. Categorical variables were compared between groups using Fisher's exact tests. Univariate and multivariable analyses were used to correlate biomarker changes and patient survivals. Multivariable analyses were performed by constructing decision trees using the classification and regression trees (CART) methodology. IHC detected widespread ITH in ccRCC tumors. The statistical analysis of the “Truncal loss” (root loss) found additional correlations between biomarker losses and tumor stages than the traditional “Loss in tumor (total)”. Losses of SMARCA4 or SMARCA2 significantly improved prognosis for overall survival (OS). Losses of PBRM1, ARID1A or SETD2 had the opposite effect. Thus “Truncal Loss” analysis revealed hidden links between protein losses and patient survival in ccRCC. PMID:28445125

Guilt, shame and expressed emotion in carers of people with long-term mental health difficulties: A systematic review.

PubMed

Cherry, Mary Gemma; Taylor, Peter James; Brown, Stephen Lloyd; Rigby, Jake Wilfred; Sellwood, William

2017-03-01

Expressed emotion (EE) is a global index of familial emotional climate, whose primary components are emotional over-involvement (EOI) and critical comments (CC)/hostility. There is a strong theoretical rationale for hypothesising that carers' guilt and shame may be differentially associated with their EOI and CC/hostility respectively. This systematic review investigates the magnitude of these theorised associations in carers of people with long-term mental health difficulties. Electronic searches (conducted in May 2016 across Medline, CINAHL, Embase, PsycINFO and ProQuest) were supplemented with iterative hand searches. Ten papers, reporting data from eight studies, were included. Risk of bias was assessed using a standardised checklist. Relevant data were extracted and synthesised narratively. EOI was positively associated with both guilt and shame, whereas CC/hostility was positively associated with shame. The strength of associations varied depending on whether or not guilt and shame were assessed within the context of the caring relationship. Based on these data, an argument can be made for the refinement, development and evaluation of systemic and individual interventions designed to target carers' guilt and shame. However, more research is needed to clarify the strength of these associations and their direction of effect before firm conclusions can be drawn. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

[Effects of different trophic modes on growth characteristics, metabolism and cellular components of Chlorella vulgaris].

PubMed

Kong, Weibao; Wang, Yang; Yang, Hong; Xi, Yuqin; Han, Rui; Niu, Shiquan

2015-03-04

We studied the effects of trophic modes related to glucose and light (photoautotrophy, mixotrophy and heterotrophy) on growth, cellular components and carbon metabolic pathway of Chlorella vulgaris. The parameters about growth of algal cells were investigated by using spectroscopy and chromatography techniques. When trophic mode changed from photoautotrophy to mixotrophy and to heterotrophy successively, the concentrations of soluble sugar, lipid and saturated C16/C18 fatty acids in C. vulgaris increased, whereas the concentrations of unsaturated C16, C18 fatty acids, proteins, photosynthetic pigments and 18 relative amino acids decreased. Light and glucose affect the growth, metabolism and the biochemical components biosynthesis of C. vulgaris. Addition of glucose can promote algal biomass accumulation, stimulate the synthesis of carbonaceous components, but inhibit nitrogenous components. Under illumination cultivation, concentration and consumption level of glucose decided the main trophic modes of C. vulgaris. Mixotrophic and heterotrophic cultivation could promote the growth of algal cells.

Comprehensive circular RNA expression profile in radiation-treated HeLa cells and analysis of radioresistance-related circRNAs.

PubMed

Yu, Duo; Li, Yunfeng; Ming, Zhihui; Wang, Hongyong; Dong, Zhuo; Qiu, Ling; Wang, Tiejun

2018-01-01

Cervical cancer is one of the most common cancers in women worldwide. Malignant tumors develop resistance mechanisms and are less sensitive to or do not respond to irradiation. With the development of high-throughput sequencing technologies, circular RNA (circRNA) has been identified in an increasing number of diseases, especially cancers. It has been reported that circRNA can compete with microRNAs (miRNAs) to change the stability or translation of target RNAs, thus regulating gene expression at the transcriptional level. However, the role of circRNAs in cervical cancer and the radioresistance mechanisms of HeLa cells are unknown. The objective of this study is to investigate the role of circRNAs in radioresistance in HeLa cells. High-throughput sequencing and bioinformatics analysis of irradiated and sham-irradiated HeLa cells. The reliability of high-throughput RNA sequencing was validated using quantitative real-time polymerase chain reaction. The most significant circRNA functions and pathways were selected by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A circRNA-miRNA-target gene interaction network was used to find circRNAs associated with radioresistance. Moreover, a protein-protein interaction network was constructed to identify radioresistance-related hub proteins. High-throughput sequencing allowed the identification of 16,893 circRNAs involved in the response of HeLa cells to radiation. Compared with the control group, there were 153 differentially expressed circRNAs, of which 76 were up-regulated and 77 were down-regulated. GO covered three domains: biological process (BP), cellular component (CC) and molecular function (MF). The terms assigned to the BP domain were peptidyl-tyrosine dephosphorylation and regulation of cell migration. The identified CC terms were cell-cell adherens junction, nucleoplasm and cytosol, and the identified MF terms were protein binding and protein tyrosine phosphatase activity. The top five KEGG pathways were MAPK signaling pathway, endocytosis, axon guidance, neurotrophin signaling pathway, and SNARE interactions in vesicular transport. The protein-protein interaction analysis indicated that 19 proteins might be hub proteins. CircRNAs may play a major role in the response to radiation. These findings may improve our understanding of the role of circRNAs in radioresistance in HeLa cells and allow the development of novel therapeutic approaches.

Mechanistic considerations on the wavelength-dependent variations of UVR genotoxicity and mutagenesis in skin: the discrimination of UVA-signature from UV-signature mutation.

PubMed

Ikehata, Hironobu

2018-05-31

Ultraviolet radiation (UVR) predominantly induces UV-signature mutations, C → T and CC → TT base substitutions at dipyrimidine sites, in the cellular and skin genome. I observed in our in vivo mutation studies of mouse skin that these UVR-specific mutations show a wavelength-dependent variation in their sequence-context preference. The C → T mutation occurs most frequently in the 5'-TCG-3' sequence regardless of the UVR wavelength, but is recovered more preferentially there as the wavelength increases, resulting in prominent occurrences exclusively in the TCG sequence in the UVA wavelength range, which I will designate as a "UVA signature" in this review. The preference of the UVB-induced C → T mutation for the sequence contexts shows a mixed pattern of UVC- and UVA-induced mutations, and a similar pattern is also observed for natural sunlight, in which UVB is the most genotoxic component. In addition, the CC → TT mutation hardly occurs at UVA1 wavelengths, although it is detected rarely but constantly in the UVC and UVB ranges. This wavelength-dependent variation in the sequence-context preference of the UVR-specific mutations could be explained by two different photochemical mechanisms of cyclobutane pyrimidine dimer (CPD) formation. The UV-signature mutations observed in the UVC and UVB ranges are known to be caused mainly by CPDs produced through the conventional singlet/triplet excitation of pyrimidine bases after the direct absorption of the UVC/UVB photon energy in those bases. On the other hand, a novel photochemical mechanism through the direct absorption of the UVR energy to double-stranded DNA, which is called "collective excitation", has been proposed for the UVA-induced CPD formation. The UVA photons directly absorbed by DNA produce CPDs with a sequence context preference different from that observed for CPDs caused by the UVC/UVB-mediated singlet/triplet excitation, causing CPD formation preferentially at thymine-containing dipyrimidine sites and probably also preferably at methyl CpG-associated dipyrimidine sites, which include the TCG sequence. In this review, I present a mechanistic consideration on the wavelength-dependent variation of the sequence context preference of the UVR-specific mutations and rationalize the proposition of the UVA-signature mutation, in addition to the UV-signature mutation.

78 FR 53189 - Dorel Juvenile Group, Denial of Petition for Decision of Inconsequential Noncompliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

... Omega Elite 22187REM Alpha Omega Elite 22187REMA Alpha Omega Elite 22187SAR Alpha Omega Elite 22187SARA Alpha Omega Elite 22465FSM Alpha Omega Elite 22790CGT Deluxe 3 in 1 CC033BMT Alpha Omega Elite CC043ANK Alpha Omega Elite CC043ANL Alpha Omega Elite CC043AQS Alpha Omega Elite CC046AAI Deluxe 3 in 1 CC046AAU...

Evaluation of the Initiation/Promotion Potential of CTFE Trimer Acid

DTIC Science & Technology

1990-11-01

0 1 0 0 0 0 0 0 0 Atrophic hepatic cords 3 Cc Cc Cc Cc Cc Cc Cc 3 0e Ce Ce 0e Ge 0e Ce Steatosis 3 2 4 4 4 4 4 3 2 1 0 2 2 1 2 1 Kuppfercell pigment...with the formation of hepatic tumors. Therefore, the present study was designed to evaluate CTFE trimer acid for both tumor initiation and promoting...oxidation of palmitoyl coenzyme A (CoA) MOelRaso, unpublished findings). Many compounds cause an increase in the number of hepatic peroxisomes and are

The ROSCOE Manual. Volume I-1. Program Description

DTIC Science & Technology

1980-02-29

CA’ CACcc C-’ c-c--c ~cc CCC) - CD Z I n -. cc - cx ccan,- C.) CC a - ~’, Zn cc-a U - -. a cc Zc- *0 F-U- CD~ cx no Ch cc a a I CACAO U) c--C Ccx c...dataset is de - noted by E8. Every dataset is tied t6 the basic dataset along with some important lists such as the object list, the radar list, and the...used for the track initiation and track functions are shown next. Most of these parameters are well de - fined, with the exception of the range gate

Listeria monocytogenes Source Distribution Analysis Indicates Regional Heterogeneity and Ecological Niche Preference among Serotype 4b Clones.

PubMed

Lee, Sangmi; Chen, Yi; Gorski, Lisa; Ward, Todd J; Osborne, Jason; Kathariou, Sophia

2018-04-17

Biodiversity analysis of the foodborne pathogen Listeria monocytogenes recently revealed four serotype 4b major hypervirulent clonal complexes (CCs), i.e., CC1, CC2, CC4, and CC6. Hypervirulence was indicated by overrepresentation of these clones, and serotype 4b as a whole, among human clinical isolates in comparison to food. However, data on potential source-dependent partitioning among serotype 4b clones in diverse regions are sparse. We analyzed a panel of 347 serotype 4b isolates, primarily from North America, to determine the distribution of clones in humans, other animals, food, and water. CC1, CC2, CC4, and CC6 predominated, but surprisingly, only three clones, i.e., CC2 and the singleton sequence types (STs) ST382 and ST639, exhibited significant source-dependent associations, with higher propensity for food (CC2) or water (ST382 and ST639) than other sources. Pairwise comparisons between human and food isolates identified CC4 as the only serotype 4b clone significantly overrepresented among human isolates. Our analysis also revealed several serotype 4b clones emerging in North America. Two such emerging clones, ST382 (implicated in several outbreaks since 2014) and ST639, were primarily encountered among human and water isolates. Findings suggest that in spite of the ubiquity of CC1, CC2, CC4, and CC6, regional heterogeneity in serotype 4b is substantially larger than previously surmised. Analysis of even large strain panels from one region may not adequately predict clones unique to, and emerging in, other areas. Serotype 4b clonal complexes may differ in ecological niche preference, suggesting the need to further elucidate reservoirs and vehicles, especially for emerging clones. IMPORTANCE In Listeria monocytogenes , serotype 4b strains are leading contributors to human disease, but intraserotype distributions among different sources and regions remain poorly elucidated. Analysis of 347 serotype 4b isolates from four different sources, mostly from North America, confirmed the overall predominance of the major clones CC1, CC2, CC4, and CC6 but found that only CC4 was significantly associated with human disease, while CC2 was significantly associated with food. Remarkably, several emerging clones were identified among human isolates from North America, with some of these also exhibiting a propensity for surface water. The latter included the singleton clones ST382, implicated in several outbreaks in the United States since 2014, and ST639. These clones were noticeably underrepresented among much larger panels from other regions. Though associated with North America for the time being, they may eventually become globally disseminated through the food trade or other venues. Copyright © 2018 Lee et al.

Conceptus development and transcriptome at preimplantation stages in lactating dairy cows of distinct genetic groups and estrous cyclic statuses.

PubMed

Ribeiro, E S; Monteiro, A P A; Bisinotto, R S; Lima, F S; Greco, L F; Ealy, A D; Thatcher, W W; Santos, J E P

2016-06-01

The objectives were to compare development and transcriptome of preimplantation conceptuses 15 d after synchronized ovulation and artificial insemination (AI) according to the genetic background of the cow and estrous cyclicity at the initiation of the synchronization program. On d 39±3 postpartum, Holstein cows that were anovular (HA; n=10), Holstein cows that were estrous cyclic (HC; n=25), and Jersey/Holstein crossbred cows that were estrous cyclic (CC; n=25) were randomly selected in a grazing herd and subjected to the Ovsynch protocol. All cows were inseminated on d 49±3 postpartum, which was considered study d 0. Blood was sampled and analyzed for concentrations of progesterone, estradiol, insulin, and insulin-like growth factor 1 (IGF-1) on study d -10, -3, -1, 7, and 15 relative to AI. On study d 15, uteri were flushed and recovered fluid had IFN-τ concentrations measured and subjected to metabolomic analysis. Morphology of the recovered conceptuses was evaluated, and mRNA was extracted and subjected to transcriptome microarray analysis. Compared with HC, CC presented greater concentrations of progesterone and estradiol in plasma, with corpora lutea and preovulatory follicles of similar size. Conceptuses from CC were larger, tended to secrete greater amounts of IFN-τ, and had greater transcript expression of peroxisome proliferator-activated receptor gamma (PPARγ), an important transcription factor that coordinates lipid metabolism and elongation at preimplantation development. In addition, pregnant CC had greater concentrations of anandamide in the uterine flush, which might be important for elongation of the conceptus and early implantation. Conceptuses from HA were also longer and secreted greater amounts of IFN-τ than conceptuses from HC, likely because of the distinct progesterone profiles before and after AI. Nonetheless, anovular cows had reduced concentrations of IGF-1 in plasma, and their conceptuses presented remarkable transcriptomic differences. Some of the altered transcripts suggest that conceptus cells from anovular cows might be under greater cellular stress and presented markers suggesting increased apoptosis and autophagy, which could lead to increased mortality after d 15 of development. Estrous cyclicity had more impact on transcriptome of bovine conceptus than genetic background, and the developmental changes observed during the preimplantation period might be linked to differences in fertility among groups. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Polymorphic differences in the SOD-2 gene may affect the pathogenesis of nephropathy in patients with diabetes and diabetic complications.

PubMed

Houldsworth, Annwyne; Hodgkinson, Andrea; Shaw, Steve; Millward, Ann; Demaine, Andy G

2015-09-10

The effective treatment of diabetes and the prevention of diabetic complications may be improved by a better understanding of the antioxidant function of intracellular defences against oxidative stress. Polymorphisms in antioxidant genes may determine cellular oxidative stress levels as a primary pathogenic role in diabetes and/or in its complications. SOD-2 was investigated in patients with type 1 diabetes mellitus (T1DM) to ascertain if specific genotypes have any protective influences in the pathogenic mechanisms in diabetes and/or in several different complications, including retinopathy, nephropathy and diabetic controls compared to normal healthy controls. 278 (136M:142F) T1DM patients and 135 (72M:63F) normal, healthy controls were investigated for SOD-2 polymorphism in the mitochondrial targeting sequence with Ala/Val (C-9T) substitution. A significant difference in the C-9-T genotype was observed between patients and normal controls but not between diabetic controls and patients with complications. There were significantly more of the diabetic control (DC, n=62) group (11.3%) than the patients with diabetic nephropathy (DN, n=73) (1.4%) with the CC genotype (p=0.03 and χ(2)=4.27, OR=9.16 (1.08

A Unique Fungal Two-Component System Regulates Stress Responses, Drug Sensitivity, Sexual Development, and Virulence of Cryptococcus neoformans

PubMed Central

Bahn, Yong-Sun; Kojima, Kaihei; Cox, Gary M.

2006-01-01

The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and differentiation. The basidiomycetous human fungal pathogen Cryptococcus neoformans uniquely uses the stress-activated Pbs2-Hog1 MAPK system to govern a plethora of cellular events, including stress responses, drug sensitivity, sexual reproduction, and virulence. Here, we characterized a fungal “two-component” system that controls these fundamental cellular functions via the Pbs2-Hog1 MAPK cascade. A typical response regulator, Ssk1, modulated all Hog1-dependent phenotypes by controlling Hog1 phosphorylation, indicating that Ssk1 is the major upstream signaling component of the Pbs2-Hog1 pathway. A second response regulator, Skn7, governs sensitivity to Na+ ions and the antifungal agent fludioxonil, negatively controls melanin production, and functions independently of Hog1 regulation. To control these response regulators, C. neoformans uses multiple sensor kinases, including two-component–like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. Our findings highlight unique adaptations of this global two-component MAPK signaling cascade in a ubiquitous human fungal pathogen. PMID:16672377

A technical review of cellular radio and analysis of a possible protocol

NASA Astrophysics Data System (ADS)

Reese, William D.

1992-09-01

Radio and television technology made the field of cellular radio possible. This thesis shows the development of radio and television technology from both a historical and technical aspect. A review of the important researchers and their contributions is followed by a technical explanation of the theories behind electromagnetic radiation of radio and television signals and the technology which was developed to implement such transmissions. The evolution of development which the paper outlines begins with some of the first theories about electricity and magnetism and the subsequent mathematical foundation developed to explain them. This is followed by a number of experimental and developmental researchers and their contributions. The bulk of the paper is concentrated on explaining the earliest generations of radio and all generations of television. The major components of both radio and television are described in detail along with an explanation of what they do and how they work. Such components, in many cases, found important uses in fields outside those for which they were developed. A brief overview of the regulatory environment of each technology and the U.S. and international standardization efforts is also included. Finally, the paper illustrates a modern-day application of radio technology--the cellular radio industry. A description of the components and their functions is followed by a possible cellular radio protocol and analysis.

Manifestation of the shape-memory effect in polyetherurethane cellular plastics, fabric composites, and sandwich structures under microgravity

NASA Astrophysics Data System (ADS)

Babaevskii, P. G.; Kozlov, N. A.; Agapov, I. G.; Reznichenko, G. M.; Churilo, N. V.; Churilo, I. V.

2016-09-01

The results of experiments that were performed to test the feasibility of creating sandwich structures (consisting of thin-layer sheaths of polymer composites and a cellular polymer core) with the shapememory effect as models of the transformable components of space structures have been given. The data obtained indicate that samples of sandwich structures under microgravity conditions on board the International Space Station have recovered their shape to almost the same degree as under terrestrial conditions, which makes it possible to recommend them for creating components of transformable space structures on their basis.

Optimal Chest Compression Rate and Compression to Ventilation Ratio in Delivery Room Resuscitation: Evidence from Newborn Piglets and Neonatal Manikins

PubMed Central

Solevåg, Anne Lee; Schmölzer, Georg M.

2017-01-01

Cardiopulmonary resuscitation (CPR) duration until return of spontaneous circulation (ROSC) influences survival and neurologic outcomes after delivery room (DR) CPR. High quality chest compressions (CC) improve cerebral and myocardial perfusion. Improved myocardial perfusion increases the likelihood of a faster ROSC. Thus, optimizing CC quality may improve outcomes both by preserving cerebral blood flow during CPR and by reducing the recovery time. CC quality is determined by rate, CC to ventilation (C:V) ratio, and applied force, which are influenced by the CC provider. Thus, provider performance should be taken into account. Neonatal resuscitation guidelines recommend a 3:1 C:V ratio. CCs should be delivered at a rate of 90/min synchronized with ventilations at a rate of 30/min to achieve a total of 120 events/min. Despite a lack of scientific evidence supporting this, the investigation of alternative CC interventions in human neonates is ethically challenging. Also, the infrequent occurrence of extensive CPR measures in the DR make randomized controlled trials difficult to perform. Thus, many biomechanical aspects of CC have been investigated in animal and manikin models. Despite mathematical and physiological rationales that higher rates and uninterrupted CC improve CPR hemodynamics, studies indicate that provider fatigue is more pronounced when CC are performed continuously compared to when a pause is inserted after every third CC as currently recommended. A higher rate (e.g., 120/min) is also more fatiguing, which affects CC quality. In post-transitional piglets with asphyxia-induced cardiac arrest, there was no benefit of performing continuous CC at a rate of 90/min. Not only rate but duty cycle, i.e., the duration of CC/total cycle time, is a known determinant of CC effectiveness. However, duty cycle cannot be controlled with manual CC. Mechanical/automated CC in neonatal CPR has not been explored, and feedback systems are under-investigated in this population. Evidence indicates that providers perform CC at rates both higher and lower than recommended. Video recording of DR CRP has been increasingly applied and observational studies of what is actually done in relation to outcomes could be useful. Different CC rates and ratios should also be investigated under controlled experimental conditions in animals during perinatal transition. PMID:28168185

Comparison of motor diagnoses by Chicago Classification versions 2.0 and 3.0 on esophageal high-resolution manometry.

PubMed

Patel, A; Cassell, B; Sainani, N; Wang, D; Shahid, B; Bennett, M; Mirza, F A; Munigala, S; Gyawali, C P

2017-07-01

The Chicago Classification (CC) uses high-resolution manometry (HRM) software tools to designate esophageal motor diagnoses. We evaluated changes in diagnostic designations between two CC versions, and determined motor patterns not identified by either version. In this observational cohort study of consecutive patients undergoing esophageal HRM over a 6-year period, proportions meeting CC 2.0 and 3.0 criteria were segregated into esophageal outflow obstruction, hypermotility, and hypomotility disorders. Contraction wave abnormalities (CWA), and 'normal' cohorts were recorded. Symptom burden was characterized using dominant symptom intensity and global symptom severity. Motor diagnoses, presenting symptoms, and symptom burden were compared between CC 2.0 and 3.0, and in cohorts not meeting CC diagnoses. Of 2569 eligible studies, 49.9% met CC 2.0 criteria, but only 40.3% met CC 3.0 criteria (P<.0001). Between CC 2.0 and 3.0, 82.8% of diagnoses were concordant. Discordance resulted from decreasing proportions of hypermotility (4.4%) and hypomotility (9.0%) disorders, and increase in 'normal' designations (13.0%); esophageal outflow obstruction showed the least variation between CC versions. Symptom burden was higher with CC 3.0 diagnoses (P≤.005) but not with CC 2.0 diagnoses (P≥.1). Within 'normal' cohorts for both CC versions, CWA were associated with higher likelihood of esophageal symptoms, especially dysphagia, regurgitation, and heartburn, compared to truly normal studies (P≤.02 for each comparison). Despite lower sensitivity, CC 3.0 identifies esophageal motor disorders with higher symptom burden compared to CC 2.0. CWA, which are associated with both transit and perceptive symptoms, are not well identified by either version. © 2017 John Wiley & Sons Ltd.

Impact of Chronic Condition Status and Severity on Dental Utilization for Iowa Medicaid-Enrolled Children

PubMed Central

Chi, Donald L.; Momany, Elizabeth T.; Neff, John; Jones, Michael P.; Warren, John J.; Slayton, Rebecca L.; Weber-Gasparoni, Karin; Damiano, Peter C.

2011-01-01

Background Although Medicaid-enrolled children with a chronic condition (CC) may be less likely to use dental care because of factors related to their CC, dental utilization for this population is poorly understood. Objective To assess the relationship between CC status and CC severity, respectively, on dental utilization for Iowa Medicaid-enrolled children. Research Design Retrospective cohort study of Iowa Medicaid data (January 1, 2003 to December 31, 2006). Subjects Medicaid-enrolled children aged 3 to 14 (N = 71,115) years. Measures The 3M Corporation Clinical Risk Grouping methods were used to assess CC status (no/yes) and CC severity (episodic/life-long/malignancy/complex). The outcome variable was any dental utilization in 2006. Secondary outcomes included use of diagnostic, preventive, routine restorative, or complex restorative dental care. Results After adjusting for model covariates, Iowa Medicaid-enrolled children with a CC were significantly more likely to use each type of dental care except routine restorative care (P = 0.86) than those without a CC, although the differences in the odds were small (4%–6%). Compared with Medicaid-enrolled children with an episodic CC, children with a life-long CC were less likely to use routine restorative care (P < 0.0001), children with a malignancy were more likely to use complex restorative care (P < 0.03), and children with a complex CC were less likely to use each type of dental care except complex restorative care (P = 0.97). Conclusions There were differences in dental utilization for Iowa Medicaid-enrolled children by CC status and CC severity. Children with complex CCs were the least likely to use dental care. Future research efforts should seek to understand why subgroups of Medicaid-enrolled children with a CC exhibit lower dental utilization. PMID:21150799

Evolutionary tradeoffs in cellular composition across diverse bacteria

PubMed Central

Kempes, Christopher P; Wang, Lawrence; Amend, Jan P; Doyle, John; Hoehler, Tori

2016-01-01

One of the most important classic and contemporary interests in biology is the connection between cellular composition and physiological function. Decades of research have allowed us to understand the detailed relationship between various cellular components and processes for individual species, and have uncovered common functionality across diverse species. However, there still remains the need for frameworks that can mechanistically predict the tradeoffs between cellular functions and elucidate and interpret average trends across species. Here we provide a comprehensive analysis of how cellular composition changes across the diversity of bacteria as connected with physiological function and metabolism, spanning five orders of magnitude in body size. We present an analysis of the trends with cell volume that covers shifts in genomic, protein, cellular envelope, RNA and ribosomal content. We show that trends in protein content are more complex than a simple proportionality with the overall genome size, and that the number of ribosomes is simply explained by cross-species shifts in biosynthesis requirements. Furthermore, we show that the largest and smallest bacteria are limited by physical space requirements. At the lower end of size, cell volume is dominated by DNA and protein content—the requirement for which predicts a lower limit on cell size that is in good agreement with the smallest observed bacteria. At the upper end of bacterial size, we have identified a point at which the number of ribosomes required for biosynthesis exceeds available cell volume. Between these limits we are able to discuss systematic and dramatic shifts in cellular composition. Much of our analysis is connected with the basic energetics of cells where we show that the scaling of metabolic rate is surprisingly superlinear with all cellular components. PMID:27046336

CC-10004 but not thalidomide or lenalidomide inhibits lamina propria mononuclear cell TNF-α and MMP-3 production in patients with inflammatory bowel disease.

PubMed

Gordon, J N; Prothero, J D; Thornton, C A; Pickard, K M; Di Sabatino, A; Goggin, P M; Pender, S L; Macdonald, T T

2009-09-01

Thalidomide, one of whose activities is to inhibit Tumour Necrosis Factor (TNF)-α production, has been reported to be an effective treatment for refractory inflammatory bowel disease (IBD). TNF-α driven production of matrix metalloproteinase (MMP)-3 by gut lamina propria mononuclear cells (LPMCs) is a major pathway of tissue injury in IBD; however the effect of thalidomide and newer more potent immunomodulatory derivatives on this pathway has not been studied. To investigate the effect of thalidomide, CC-4047 (pomalidomide), CC-5013 (lenalidomide), and CC-10004 (apremilast) on gut LPMC TNFα and MMP-3 production in patients with IBD. Gut LPMCs and myofibroblasts were isolated from patients with IBD, and cultured with thalidomide, CC-4047, CC-5013, and CC-10004. MMP-3 and TIMP-1 levels were determined by western blotting and real-time PCR, and TNF-α levels by ELISA. CC-10004 significantly reduced both TNF-α production and MMP-3 production by cultured LPMCs. Thalidomide and CC-4047 and CC-5013 had no significant effect on the production of TNF-α or MMP-3 by LPMCs. These results provides a mechanistic rationale for both the failure of lenalidomide (CC-5013) in a recent randomised controlled trial in Crohn's disease, and for the evaluation of CC-10004 as a novel oral therapy in the treatment of CD and UC.

Cymbopogon citratus industrial waste as a potential source of bioactive compounds.

PubMed

Tavares, Filipa; Costa, Gustavo; Francisco, Vera; Liberal, Joana; Figueirinha, Artur; Lopes, Maria Celeste; Cruz, Maria Teresa; Batista, Maria Teresa

2015-10-01

Cymbopogon citratus (Cc), commonly known as lemongrass, is a very important crop worldwide, being grown in tropical countries. It is widely used in the food, pharmaceutical, cosmetic and perfumery industries for its essential oil. Cc aqueous extracts are also used in traditional medicine. They contain high levels of polyphenols, which are known for their antioxidant and anti-inflammatory properties. Hydrodistillation of lemongrass essential oil produces an aqueous waste (CcHD) which is discarded. Therefore a comparative study between CcHD and Cc infusion (CcI) was performed to characterize its phytochemical profile and to research its antioxidant and anti-inflammatory potential. HPLC-PDA/ESI-MS(n) analysis showed that CcI and CcHD have similar phenolic profiles, with CcHD presenting a higher amount of polyphenols. Additionally, both CcI and CcHD showed antioxidant activity against DPPH (EC50 of 41.72 ± 0.05 and 42.29 ± 0.05 µg mL(-1) respectively) and strong anti-inflammatory properties, by reducing NO production and iNOS expression in macrophages and through their NO-scavenging activity, in a dose-dependent manner. Furthermore, no cytotoxicity was observed. The data of this study encourage considering the aqueous solution from Cc leaf hydrodistillation as a source of bioactive compounds, which may add great industrial value to this crop. © 2014 Society of Chemical Industry.

Low Cost, Net Shape Fabrication of Rhenium and High Temperature Materials for Rocket Engine Components

DTIC Science & Technology

2001-03-01

tungsten thin wall nozzle liner removed from reusable mandrel. b) W and Re rocket, nozzle inserts (2 inserts per mandrel) for Air Force. Rhenium PPI...compares the fabrication time for the VPS nozzles with equivalent carbon / carbon composite (C/C) and forged tungsten materials. Table 5: Comparison of...UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADPO1 1181 TITLE: Low Cost, Net Shape Fabrication of Rhenium and High

Aeroelasticity in Turbomachines. Comparison of Theoretical and Experimental Cascade Results.

DTIC Science & Technology

1986-01-01

Y~x)csn1#(x)) It should be noted here that, in computing the blade surface pressure distribution, only components, and not amplitudes or phase angles...oscillation, done on the system is obtained by computing -i ChV+Cc+rhU+c_,Vh (12) Expressed in this way, the aerodynamic work coefficients c., cVh, cva...predictions), so the aerodynamic damping coefficient can easily be computed and plotted. This information is useful to the turbomachine designer for

End-to-end system of license plate localization and recognition

NASA Astrophysics Data System (ADS)

Zhu, Siyu; Dianat, Sohail; Mestha, Lalit K.

2015-03-01

An end-to-end license plate recognition system is proposed. It is composed of preprocessing, detection, segmentation, and character recognition to find and recognize plates from camera-based still images. The system utilizes connected component (CC) properties to quickly extract the license plate region. A two-stage CC filtering is utilized to address both shape and spatial relationship information to produce high precision and to recall values for detection. Floating peak and valleys of projection profiles are used to cut the license plates into individual characters. A turning function-based method is proposed to quickly and accurately recognize each character. It is further accelerated using curvature histogram-based support vector machine. The INFTY dataset is used to train the recognition system, and MediaLab license plate dataset is used for testing. The proposed system achieved 89.45% F-measure for detection and 87.33% accuracy for overall recognition rate which is comparable to current state-of-the-art systems.

Temporal variability and climatology of hydrodynamic, water property and water quality parameters in the West Johor Strait of Singapore.

PubMed

Behera, Manasa Ranjan; Chun, Cui; Palani, Sundarambal; Tkalich, Pavel

2013-12-15

The study presents a baseline variability and climatology study of measured hydrodynamic, water properties and some water quality parameters of West Johor Strait, Singapore at hourly-to-seasonal scales to uncover their dependency and correlation to one or more drivers. The considered parameters include, but not limited by sea surface elevation, current magnitude and direction, solar radiation and air temperature, water temperature, salinity, chlorophyll-a and turbidity. FFT (Fast Fourier Transform) analysis is carried out for the parameters to delineate relative effect of tidal and weather drivers. The group and individual correlations between the parameters are obtained by principal component analysis (PCA) and cross-correlation (CC) technique, respectively. The CC technique also identifies the dependency and time lag between driving natural forces and dependent water property and water quality parameters. The temporal variability and climatology of the driving forces and the dependent parameters are established at the hourly, daily, fortnightly and seasonal scales. Copyright © 2013 Elsevier Ltd. All rights reserved.

Research on Ratio of Dosage of Drugs in Traditional Chinese Prescriptions by Data Mining.

PubMed

Yu, Xing-Wen; Gong, Qing-Yue; Hu, Kong-Fa; Mao, Wen-Jing; Zhang, Wei-Ming

2017-01-01

Maximizing the effectiveness of prescriptions and minimizing adverse effects of drugs is a key component of the health care of patients. In the practice of traditional Chinese medicine (TCM), it is important to provide clinicians a reference for dosing of prescribed drugs. The traditional Cheng-Church biclustering algorithm (CC) is optimized and the data of TCM prescription dose is analyzed by using the optimization algorithm. Based on an analysis of 212 prescriptions related to TCM treatment of kidney diseases, the study generated 87 prescription dose quantum matrices and each sub-matrix represents the referential value of the doses of drugs in different recipes. The optimized CC algorithm can effectively eliminate the interference of zero in the original dose matrix of TCM prescriptions and avoid zero appearing in output sub-matrix. This results in the ability to effectively analyze the reference value of drugs in different prescriptions related to kidney diseases, so as to provide valuable reference for clinicians to use drugs rationally.

Methodological framework for heart rate variability analysis during exercise: application to running and cycling stress testing.

PubMed

Hernando, David; Hernando, Alberto; Casajús, Jose A; Laguna, Pablo; Garatachea, Nuria; Bailón, Raquel

2018-05-01

Standard methodologies of heart rate variability analysis and physiological interpretation as a marker of autonomic nervous system condition have been largely published at rest, but not so much during exercise. A methodological framework for heart rate variability (HRV) analysis during exercise is proposed, which deals with the non-stationary nature of HRV during exercise, includes respiratory information, and identifies and corrects spectral components related to cardiolocomotor coupling (CC). This is applied to 23 male subjects who underwent different tests: maximal and submaximal, running and cycling; where the ECG, respiratory frequency and oxygen consumption were simultaneously recorded. High-frequency (HF) power results largely modified from estimations with the standard fixed band to those obtained with the proposed methodology. For medium and high levels of exercise and recovery, HF power results in a 20 to 40% increase. When cycling, HF power increases around 40% with respect to running, while CC power is around 20% stronger in running.

A molecule with small rotational constants containing an atom with a large nuclear quadrupole moment: The microwave spectrum of trans-1-iodoperfluoropropane

NASA Astrophysics Data System (ADS)

Dewberry, C. T.; Grubbs, G. S.; Cooke, S. A.

2009-09-01

Using pulsed jet chirped-pulse, and cavity-based Fourier transform microwave spectroscopies over 900 transitions have been recorded for the title molecule in the 1-4 GHz and 8-18 GHz regions. The C,C and C carbon-13 species have been observed in natural abundance allowing a substitution structure for the CCC backbone to be determined. Nearly all the transitions observed were either a-type R branches or b-type Q branches. No c-type transitions were observed consistent with only the trans conformer being present under our experimental conditions. The χaa,χbb,χcc and χab components of the iodine nuclear quadrupole coupling tensor have been determined. Of note, several forbidden, ΔJ±2 transitions, and one ΔJ±3 transition were observed with quite reasonable intensity. These observations have been rationalized through considerations of near degeneracies between energy levels connected via a large χab value (≈1 GHz).

Chemical Blistering: Cellular and Macromolecular Components

DTIC Science & Technology

1984-11-15

accumulation of fluid appears to Sbe secondary to fundamental damage to cellular structures (1). As noted by Warthin and Weller (2) and by Sinclair (3...Medicine. fT. P. Fitzpatrick, A. Z. Eisen, K. Wolff, I. M. Freedberg and K. F. Austen, Eds.) McGraw-Hill, New York, pp. 287-294). 2.’ Warthin , A. S., and

Citrullus colocynthis NAC transcription factors CcNAC1 and CcNAC2 are involved in light and auxin signaling.

PubMed

Wang, Zhuoyu; Rashotte, Aaron M; Dane, Fenny

2014-10-01

Two novel NAC transcription factors from C itrullus colocynthis implicated in light and auxin signaling pathway. NAC transcription factors (NAM, ATAF1, 2, CUC2) have multiple functions in plant growth and development. Two NACs, CcNAC1 and CcNAC2, were recently identified in the highly drought-tolerant cucurbit species, Citrullus colocynthis. This study examines the functional role of these genes under different qualities of light based on the in silico analysis of the CcNAC1 and CcNAC2 promoters that revealed the presence of several light-associated motifs. The impact of both light and auxin on CcNAC1 and CcNAC2 expression was examined in C. colocynthis leaves, and using reporter (pCcNAC1, 2::GUS) lines in Arabidopsis. Furthermore, the effects of constitutive overexpression (OE-CcNAC1, 2) in Arabidopsis were also examined under a range of conditions to confirm reporter line linkages. White, blue, red, and far-red light treatments resulted in similar patterns of quantitative changes in CcNAC1and CcNAC2 expression in both species, with the highest transcript increases following red light. Photomorphogenic changes in Arabidopsis hypocotyls were correlated with gene transcript levels. In the absence of light, hypocotyls of OE-CcNAC1/CcNAC2 lines were significantly longer as compared to WT. The addition of exogenous auxin (+IAA) to growth medium also resulted in changes to the hypocotyl lengths of overexpression lines and spatiotemporal reporter line changes in seedlings. Our data suggest that CcNAC1, 2 might be functionally important in the light signaling pathway, and appear connected to the hormone auxin. This is the first study to indicate that NAC genes might play a role in both light and auxin signaling pathways.

Chest compression during sustained inflation versus 3:1 chest compression:ventilation ratio during neonatal cardiopulmonary resuscitation: a randomised feasibility trial.

PubMed

Schmölzer, Georg M; O Reilly, Megan; Fray, Caroline; van Os, Sylvia; Cheung, Po-Yin

2017-10-07

Current neonatal resuscitation guidelines recommend 3:1 compression:ventilation (C:V) ratio. Recently, animal studies reported that continuous chest compressions (CC) during a sustained inflation (SI) significantly improved return of spontaneous circulation (ROSC). The approach of CC during SI (CC+SI) has not been examined in the delivery room during neonatal resuscitation. It is a feasibility study to compare CC+SI versus 3:1 C:V ratio during neonatal resuscitation in the delivery room. We hypothesised that during neonatal resuscitation, CC+SI will reduce the time to ROSC. Our aim was to examine if CC+SI reduces ROSC compared with 3:1 C:V CPR in preterm infants <33 weeks of gestation. Randomised feasibility trial. Once CC was indicated all eligible infants were immediately and randomly allocated to either CC+SI group or 3:1 C:V group. A sequentially numbered, brown, sealed envelope contained a folded card box with the treatment allocation was opened by the clinical team at the start of CC. Infants in the CC+SI group received CC at a rate of 90/min during an SI with a duration of 20 s (CC+SI). After 20 s, the SI was interrupted for 1 s and the next SI was started for another 20 s until ROSC. Infants in the '3:1 group' received CC using 3:1 C:V ratio until ROSC. Overall the mean (SD) time to ROSC was significantly shorter in the CC+SI group with 31 (9) s compared with 138 (72) s in the 3:1 C:V group (p=0.011). CC+SI is feasible in the delivery room. Clinicaltrials.gov NCT02083705, pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The chemokines CCR1 and CCRL2 have a role in colorectal cancer liver metastasis.

PubMed

Akram, Israa G; Georges, Rania; Hielscher, Thomas; Adwan, Hassan; Berger, Martin R

2016-02-01

C-C chemokine receptor type 1 (CCR1) and chemokine C-C motif receptor-like 2 (CCRL2) have not yet been sufficiently investigated for their role in colorectal cancer (CRC). Here, we investigated their expression in rat and human CRC samples, their modulation of expression in a rat liver metastasis model, as well as the effects on cellular properties resulting from their knockdown. One rat and five human colorectal cancer cell lines were used. CC531 rat colorectal cells were injected via the portal vein into rats and re-isolated from rat livers after defined periods. Following mRNA isolation, the gene expression was investigated by microarray. In addition, all cell lines were screened for mRNA expression of CCR1 and CCRL2 by reverse transcription polymerase chain reaction (RT-PCR). Cell lines with detectable expression were used for knockdown experiments; and the respective influence was determined on the cells' proliferation, scratch closure, and colony formation. Finally, specimens from the primaries of 50 patients with CRC were monitored by quantitative RT-PCR for CCR1 and CCRL2 expression levels. The microarray studies showed peak increases of CCR1 and CCRL2 in the early phase of liver colonization. Knockdown was sufficient at mRNA but only moderate at protein levels and resulted in modest but significant inhibition of proliferation (p < 0.05), scratch closure, and colony formation (p < 0.05). All human CRC samples were positive for CCR1 and CCRL2 and showed a significant pairwise correlation (p < 0.0004), but there was no correlation with tumor stage or age of patients. In summary, the data point to an important role of CCR1 and CCRL2 under conditions of organ colonization and both chemokine receptors qualify as targets of treatment during early colorectal cancer liver metastasis.

Capacity on wireless quantum cellular communication system

NASA Astrophysics Data System (ADS)

Zhou, Xiang-Zhen; Yu, Xu-Tao; Zhang, Zai-Chen

2018-03-01

Quantum technology is making excellent prospects in future communication networks. Entanglement generation and purification are two major components in quantum networks. Combining these two techniques with classical cellular mobile communication, we proposed a novel wireless quantum cellular(WQC) communication system which is possible to realize commercial mobile quantum communication. In this paper, the architecture and network topology of WQC communication system are discussed, the mathematical model of WQC system is extracted and the serving capacity, indicating the ability to serve customers, is defined and calculated under certain circumstances.

Renal cell carcinoma with rhabdoid-like features lack intracytoplasmic inclusion bodies and show aggressive behavior.

PubMed

Sugimoto, Masaaki; Kohashi, Kenichi; Kuroiwa, Kentaro; Abe, Tatsuro; Yamada, Yuichi; Shiota, Masaki; Imada, Kenjiro; Naito, Seiji; Oda, Yoshinao

2016-03-01

In renal cell carcinoma (RCC), tumor cells with rhabdoid features are characterized by eccentric nuclei, prominent nucleoli, and eosinophilic cytoplasm with intracytoplasmic inclusion bodies. In RCC, tumor cells have also been observed resembling rhabdomyoblasts or rhabdoid but without intracytoplasmic inclusion bodies, and here, we defined these rhabdoid-like features of these cells. To this end, we studied a series of clear cell RCC (ccRCC) with rhabdoid features and compared them with a series of ccRCC with rhabdoid-like features to clarify the differences in the immunohistochemical profile and biological behavior. From 695 cases of ccRCC (80.8 % of all RCCs), 18 cases with rhabdoid features (2.1 % of all RCCs) and 25 cases with rhabdoid-like features (2.9 % of all RCCs) were investigated. The 5-year survival rate for ccRCC with rhabdoid features was 44.7 % and for ccRCC with rhabdoid-like features 30.3 %. Although ccRCC with rhabdoid features showed immunohistochemical co-expression of epithelial markers and vimentin as seen in malignant rhabdoid tumors, ccRCC with rhabdoid-like features showed no such co-expression. Multivariate analyses of cancer-specific survival revealed that perinephric tissues invasion was an independent prognostic factor in ccRCC with rhabdoid features (p = 0.0253) but not in ccRCC with rhabdoid-like features. In summary, although their prognosis is similar, the marker profile and pattern of extension of ccRCC with rhabdoid-like is different from that of ccRCC with rhabdoid features. Therefore, ccRCC with rhabdoid-like features should be distinguished from ccRCC with rhabdoid features.

Discrete Analog Processing for Tracking and Guidance Control

DTIC Science & Technology

1980-11-01

be called the multi- sample algorithm, satisfies -4 67 tD (Da - d) 0 (4.2.2.3) Thus, this descent algorithm will determine a coefficient vector a... flJ -TI:-* IS; 7" rR(VI Dr TH~I ("vFP)ALLCj TT$ C_ F 2C OH Til TPACK I! NC SYS TE ! f- 1I3 cc cc *’I cc. CC snUpcF FIL1j: C~T 01C 0 (1 cc CC OEJCT F I LF

The diverse and expanding role of mass spectrometry in structural and molecular biology.

PubMed

Lössl, Philip; van de Waterbeemd, Michiel; Heck, Albert Jr

2016-12-15

The emergence of proteomics has led to major technological advances in mass spectrometry (MS). These advancements not only benefitted MS-based high-throughput proteomics but also increased the impact of mass spectrometry on the field of structural and molecular biology. Here, we review how state-of-the-art MS methods, including native MS, top-down protein sequencing, cross-linking-MS, and hydrogen-deuterium exchange-MS, nowadays enable the characterization of biomolecular structures, functions, and interactions. In particular, we focus on the role of mass spectrometry in integrated structural and molecular biology investigations of biological macromolecular complexes and cellular machineries, highlighting work on CRISPR-Cas systems and eukaryotic transcription complexes. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Pericentrin in cellular function and disease

PubMed Central

Delaval, Benedicte

2010-01-01

Pericentrin is an integral component of the centrosome that serves as a multifunctional scaffold for anchoring numerous proteins and protein complexes. Through these interactions, pericentrin contributes to a diversity of fundamental cellular processes. Recent studies link pericentrin to a growing list of human disorders. Studies on pericentrin at the cellular, molecular, and, more recently, organismal level, provide a platform for generating models to elucidate the etiology of these disorders. Although the complexity of phenotypes associated with pericentrin-mediated disorders is somewhat daunting, insights into the cellular basis of disease are beginning to come into focus. In this review, we focus on human conditions associated with loss or elevation of pericentrin and propose cellular and molecular models that might explain them. PMID:19951897

Enhanced mechanical properties of hydrothermal carbamated cellulose nanocomposite film reinforced with graphene oxide.

PubMed

Gan, Sinyee; Zakaria, Sarani; Syed Jaafar, Sharifah Nabihah

2017-09-15

Cellulose carbamate (CC) was synthesized via hydrothermal process and mixed with graphene oxide (GO) to form a homogeneous cellulose matrix nanocomposite films. The properties of CC/GO nanocomposite films fabricated using simple solution-mixing method with different GO loadings were studied. Transmission electron microscope analysis showed the exfoliation of self-synthesized GO nanosheets within the CC matrix. X-ray diffraction results confirmed the crystalline structure of CC/GO films as the CC/GO mass ratio increased from 100/0 to 100/4. The mechanical properties of CC/GO film were significantly improved as compared to neat CC film. From thermogravimetric analysis result, the introduction of GO enhanced the thermal stability and carbon yields. The 3D homogeneous porous structures of the CC/GO films were observed under Field emission scanning electron microscope. These improvements in nanocomposite film properties could be confirmed by Fourier transform infrared spectroscopy due to the strong and good interactions between CC and GO. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism.

PubMed

Ardestani, Amin; Lupse, Blaz; Maedler, Kathrin

2018-05-05

The evolutionarily conserved Hippo pathway is a key regulator of organ size and tissue homeostasis. Its dysregulation is linked to multiple pathological disorders. In addition to regulating development and growth, recent studies show that Hippo pathway components such as MST1/2 and LATS1/2 kinases, as well as YAP/TAZ transcriptional coactivators, are regulated by metabolic pathways and that the Hippo pathway controls metabolic processes at the cellular and organismal levels in physiological and metabolic disease states such as obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), cardiovascular disorders, and cancer. In this review we summarize the connection between key Hippo components and metabolism, and how this interplay regulates cellular metabolism and metabolic pathways. The emerging function of Hippo in the regulation of metabolic homeostasis under physiological and pathological conditions is highlighted. Copyright © 2018 Elsevier Ltd. All rights reserved.

Determining the source and genetic fingerprint of natural gases using noble gas geochemistry: a northern Appalachian Basin case study

USGS Publications Warehouse

Hunt, Andrew G.; Darrah, Thomas H.; Poreda, Robert J.

2012-01-01

Silurian and Devonian natural gas reservoirs present within New York state represent an example of unconventional gas accumulations within the northern Appalachian Basin. These unconventional energy resources, previously thought to be noneconomically viable, have come into play following advances in drilling (i.e., horizontal drilling) and extraction (i.e., hydraulic fracturing) capabilities. Therefore, efforts to understand these and other domestic and global natural gas reserves have recently increased. The suspicion of fugitive mass migration issues within current Appalachian production fields has catalyzed the need to develop a greater understanding of the genetic grouping (source) and migrational history of natural gases in this area. We introduce new noble gas data in the context of published hydrocarbon carbon (C1,C2+) (13C) data to explore the genesis of thermogenic gases in the Appalachian Basin. This study includes natural gases from two distinct genetic groups: group 1, Upper Devonian (Marcellus shale and Canadaway Group) gases generated in situ, characterized by early mature (13C[C1  C2][13C113C2]: –9), isotopically light methane, with low (4He) (average, 1  103 cc/cc) elevated 4He/40Ar and 21Ne/40Ar (where the asterisk denotes excess radiogenic or nucleogenic production beyond the atmospheric ratio), and a variable, atmospherically (air-saturated–water) derived noble gas component; and group 2, a migratory natural gas that emanated from Lower Ordovician source rocks (i.e., most likely, Middle Ordovician Trenton or Black River group) that is currently hosted primarily in Lower Silurian sands (i.e., Medina or Clinton group) characterized by isotopically heavy, mature methane (13C[C1 – C2] [13C113C2]: 3), with high (4He) (average, 1.85  103 cc/cc) 4He/40Ar and 21Ne/40Ar near crustal production levels and elevated crustal noble gas content (enriched 4He,21Ne, 40Ar). Because the release of each crustal noble gas (i.e., He, Ne, Ar) from mineral grains in the shale matrix is regulated by temperature, natural gases obtain and retain a record of the thermal conditions of the source rock. Therefore, noble gases constitute a valuable technique for distinguishing the genetic source and post-genetic processes of natural gases.

Utilization of Molecular, Phenotypic, and Geographical Diversity to Develop Compact Composite Core Collection in the Oilseed Crop, Safflower (Carthamus tinctorius L.) through Maximization Strategy

PubMed Central

Kumar, Shivendra; Ambreen, Heena; Variath, Murali T.; Rao, Atmakuri R.; Agarwal, Manu; Kumar, Amar; Goel, Shailendra; Jagannath, Arun

2016-01-01

Safflower (Carthamus tinctorius L.) is a dryland oilseed crop yielding high quality edible oil. Previous studies have described significant phenotypic variability in the crop and used geographical distribution and phenotypic trait values to develop core collections. However, the molecular diversity component was lacking in the earlier collections thereby limiting their utility in breeding programs. The present study evaluated the phenotypic variability for 12 agronomically important traits during two growing seasons (2011–12 and 2012–13) in a global reference collection of 531 safflower accessions, assessed earlier by our group for genetic diversity and population structure using AFLP markers. Significant phenotypic variation was observed for all the agronomic traits in the representative collection. Cluster analysis of phenotypic data grouped the accessions into five major clusters. Accessions from the Indian Subcontinent and America harbored maximal phenotypic variability with unique characters for a few traits. MANOVA analysis indicated significant interaction between genotypes and environment for both the seasons. Initially, six independent core collections (CC1–CC6) were developed using molecular marker and phenotypic data for two seasons through POWERCORE and MSTRAT. These collections captured the entire range of trait variability but failed to include complete genetic diversity represented in 19 clusters reported earlier through Bayesian analysis of population structure (BAPS). Therefore, we merged the three POWERCORE core collections (CC1–CC3) to generate a composite core collection, CartC1 and three MSTRAT core collections (CC4–CC6) to generate another composite core collection, CartC2. The mean difference percentage, variance difference percentage, variable rate of coefficient of variance percentage, coincidence rate of range percentage, Shannon's diversity index, and Nei's gene diversity for CartC1 were 11.2, 43.7, 132.4, 93.4, 0.47, and 0.306, respectively while the corresponding values for CartC2 were 9.3, 58.8, 124.6, 95.8, 0.46, and 0.301. Each composite core collection represented the complete range of phenotypic and genetic variability of the crop including 19 BAPS clusters. This is the first report describing development of core collections in safflower using molecular marker data with phenotypic values and geographical distribution. These core collections will facilitate identification of genetic determinants of trait variability and effective utilization of the prevalent diversity in crop improvement programs. PMID:27807441

Feline leukemia virus infection requires a post-receptor binding envelope-dependent cellular component.

PubMed

Hussain, Naveen; Thickett, Kelly R; Na, Hong; Leung, Cherry; Tailor, Chetankumar S

2011-12-01

Gammaretrovirus receptors have been suggested to contain the necessary determinants to mediate virus binding and entry. Here, we show that murine NIH 3T3 and baby hamster kidney (BHK) cells overexpressing receptors for subgroup A, B, and C feline leukemia viruses (FeLVs) are weakly susceptible (10(1) to 10(2) CFU/ml) to FeLV pseudotype viruses containing murine leukemia virus (MLV) core (Gag-Pol) proteins, whereas FeLV receptor-expressing murine Mus dunni tail fibroblast (MDTF) cells are highly susceptible (10(4) to 10(6) CFU/ml). However, NIH 3T3 cells expressing the FeLV subgroup B receptor PiT1 are highly susceptible to gibbon ape leukemia virus pseudotype virus, which differs from the FeLV pseudotype viruses only in the envelope protein. FeLV resistance is not caused by a defect in envelope binding, low receptor expression levels, or N-linked glycosylation. Resistance is not alleviated by substitution of the MLV core in the FeLV pseudotype virus with FeLV core proteins. Interestingly, FeLV resistance is alleviated by fusion of receptor-expressing NIH 3T3 and BHK cells with MDTF or human TE671 cells, suggesting the absence of an additional cellular component in NIH 3T3 and BHK cells that is required for FeLV infection. The putative FeLV-specific cellular component is not a secreted factor, as MDTF conditioned medium does not alleviate the block to FeLV infection. Together, our findings suggest that FeLV infection requires an additional envelope-dependent cellular component that is absent in NIH 3T3 and BHK cells but that is present in MDTF and TE671 cells.

Cellular Precipitates Of Iron Oxide in Olivine in a Stratospheric Interplanetary Dust Particle

NASA Technical Reports Server (NTRS)

Rietmeijer, Frans J. M.

1996-01-01

The petrology of a massive olivine-sulphide interplanetary dust particle shows melting of Fe,Ni-sulphide plus complete loss of sulphur and subsequent quenching to a mixture of iron-oxides and Fe,Ni-metal. Oxidation of the fayalite component in olivine produced maghemite discs and cellular intergrowths with olivine and rare andradite-rich garnet. Cellular reactions require no long-range solid-state diffusion and are kinetically favourable during pyrometamorphic oxidation. Local melting of the cellular intergrowths resulted in three dimensional symplectic textures. Dynamic pyrometamorphism of this asteroidal particle occurred at approx. 1100 C during atmospheric entry flash (5-15 s) heating.

Cotton growth modeling and assessment using unmanned aircraft system visual-band imagery

NASA Astrophysics Data System (ADS)

Chu, Tianxing; Chen, Ruizhi; Landivar, Juan A.; Maeda, Murilo M.; Yang, Chenghai; Starek, Michael J.

2016-07-01

This paper explores the potential of using unmanned aircraft system (UAS)-based visible-band images to assess cotton growth. By applying the structure-from-motion algorithm, the cotton plant height (ph) and canopy cover (cc) information were retrieved from the point cloud-based digital surface models (DSMs) and orthomosaic images. Both UAS-based ph and cc follow a sigmoid growth pattern as confirmed by ground-based studies. By applying an empirical model that converts the cotton ph to cc, the estimated cc shows strong correlation (R2=0.990) with the observed cc. An attempt for modeling cotton yield was carried out using the ph and cc information obtained on June 26, 2015, the date when sigmoid growth curves for both ph and cc tended to decline in slope. In a cross-validation test, the correlation between the ground-measured yield and the estimated equivalent derived from the ph and/or cc was compared. Generally, combining ph and cc, the performance of the yield estimation is most comparable against the observed yield. On the other hand, the observed yield and cc-based estimation produce the second strongest correlation, regardless of the complexity of the models.

Effects of viscosity and volume on the patterns of esophageal motility in healthy adults using high-resolution manometry.

PubMed

Park, J H; Lee, H; Rhee, P-L; Park, J H

2015-01-01

The purpose of this study was to determine the effects of age, sex, body mass index (BMI), viscosity, and volume on esophageal motility using high-resolution manometry (HRM). Manometric studies were performed on 60 asymptomatic volunteers (27 men and 33 women, age: 19-56 years) while in a supine position. Manometric protocol included 10 water swallows (5 cc), 10 jelly swallows (5 cc), and 1 water swallow (20 cc). Evaluation of HRM parameters including length of proximal pressure trough (PPT length), distal latency (DL), contractile front velocity (CFV), distal contractile integral (DCI), and 4-second integrated relaxation pressure (IRP) was performed using MATLAB. Significant differences were noted in median IRP between water 5 cc (median 7.2 mmHg [range 5.5-9.6]), jelly 5 cc (median 6.0 mmHg [range 3.8-8.0]), and water 20 cc {(Median 4.8 mmHg [range 3.3-7.4]), P < 0.01}. DL were significantly different between water 5 cc, jelly 5 cc, and water 20 cc (P < 0.01), and in terms of PPT, proportions of small (2 cm ≤ < 5 cm) and large (5 cm≤) break for jelly 5 cc were significantly higher than those for the water 5 cc swallow (P < 0.05). Furthermore, DCI increased with age for water 5 cc, and a significant negative correlation was noticed between proportions of small break and BMI for water 5 cc. Manometric measurements vary depending on age, BMI, viscosity, and volume. These findings need to be taken into account in the interpretation of manometry results. © 2014 International Society for Diseases of the Esophagus.

Chronic ethanol consumption induces erectile dysfunction: Role of oxidative stress.

PubMed

Muniz, Jaqueline J; Leite, Letícia N; De Martinis, Bruno S; Carneiro, Fernando S; Tirapelli, Carlos R

2015-11-15

Investigate the effects of chronic ethanol consumption on erectile function and on the corpus cavernosum (CC) reactivity to endothelin-1 (ET-1). Male Wistar rats were treated with ethanol (20% v/v) for six weeks. Ethanol-treated rats showed impaired erectile function represented by decreased intracavernosal pressure/mean arterial pressure (ICP/MAP) responses. Ethanol consumption increased the contractile response induced by ET-1 in the isolated CC. Tiron increased ET-1-induced contraction in CC from control and ethanol-treated rats. No differences in the maximal contraction to ET-1 were observed after incubation of CC with PEG-catalase. SC560 and SC236 increased ET-1-induced contraction in CC from ethanol-treated rats. Y27632 reduced the contraction induced by ET-1 in CC from control and ethanol-treated rats. Ethanol increased plasma TBARS, superoxide anion (O2(-)) levels and intracellular reactive oxygen species (ROS) generation in the rat CC. Reduced hydrogen peroxide (H2O2) levels in CC and increased catalase (CAT) activity in plasma and CC were detected after treatment with ethanol. Ethanol decreased superoxide dismutase (SOD) activity in the rat CC. Increased expression of COX-1 was observed in CC from ethanol-treated rats. Treatment with ethanol decreased COX-2 expression but did not alter the expression of Nox1, RhoA and p-RhoA (ser(188)) in the rat CC. The major new findings of our study are that ethanol consumption induces erectile dysfunction (ED) and increases the contraction induced by ET-1 in the rat CC by a mechanism that involves decreased generation of H2O2 and vasodilator prostanoids as well as increased activation of the RhoA/Rho-kinase pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Molecular epidemiology of Staphylococcus aureus bacteremia in a single large Minnesota medical center in 2015 as assessed using MLST, core genome MLST and spa typing.

PubMed

Park, Kyung-Hwa; Greenwood-Quaintance, Kerryl E; Uhl, James R; Cunningham, Scott A; Chia, Nicholas; Jeraldo, Patricio R; Sampathkumar, Priya; Nelson, Heidi; Patel, Robin

2017-01-01

Staphylococcus aureus is a leading cause of bacteremia in hospitalized patients. Whether or not S. aureus bacteremia (SAB) is associated with clonality, implicating potential nosocomial transmission, has not, however, been investigated. Herein, we examined the epidemiology of SAB using whole genome sequencing (WGS). 152 SAB isolates collected over the course of 2015 at a single large Minnesota medical center were studied. Staphylococcus protein A (spa) typing was performed by PCR/Sanger sequencing; multilocus sequence typing (MLST) and core genome MLST (cgMLST) were determined by WGS. Forty-eight isolates (32%) were methicillin-resistant S. aureus (MRSA). The isolates encompassed 66 spa types, clustered into 11 spa clonal complexes (CCs) and 10 singleton types. 88% of 48 MRSA isolates belonged to spa CC-002 or -008. Methicillin-susceptible S. aureus (MSSA) isolates were more genotypically diverse, with 61% distributed across four spa CCs (CC-002, CC-012, CC-008 and CC-084). By MLST, there was 31 sequence types (STs), including 18 divided into 6 CCs and 13 singleton STs. Amongst MSSA isolates, the common MLST clones were CC5 (23%), CC30 (19%), CC8 (15%) and CC15 (11%). Common MRSA clones were CC5 (67%) and CC8 (25%); there were no MRSA isolates in CC45 or CC30. By cgMLST analysis, there were 9 allelic differences between two isolates, with the remaining 150 isolates differing from each other by over 40 alleles. The two isolates were retroactively epidemiologically linked by medical record review. Overall, cgMLST analysis resulted in higher resolution epidemiological typing than did multilocus sequence or spa typing.

Comparison of Accessibility, Cost, and Quality of Elective Coronary Revascularization Between Veterans Affairs and Community Care Hospitals

PubMed Central

Hong, Juliette S.; Carey, Evan; Grunwald, Gary K.; Joynt Maddox, Karen; Maddox, Thomas M.

2018-01-01

Importance The Veterans Affairs (VA) Community Care (CC) Program supplements VA care with community-based medical services. However, access gains and value provided by CC have not been well described. Objectives To compare the access, cost, and quality of elective coronary revascularization procedures between VA and CC hospitals and to evaluate if procedural volume or publicly reported quality data can be used to identify high-value care. Design, Setting, and Participants Observational cohort study of veterans younger than 65 years undergoing an elective coronary revascularization, controlling for differences in risk factors using propensity adjustment. The setting was VA and CC hospitals. Participants were veterans undergoing elective percutaneous coronary intervention (PCI) and veterans undergoing coronary artery bypass graft (CABG) procedures between October 1, 2008, and September 30, 2011. The analysis was conducted between July 2014 and July 2017. Exposures Receipt of an elective coronary revascularization at a VA vs CC facility. Main Outcomes and Measures Access to care as measured by travel distance, 30-day mortality, and costs. Results In the 3 years ending on September 30, 2011, a total of 13 237 elective PCIs (79.1% at the VA) and 5818 elective CABG procedures (83.6% at the VA) were performed in VA or CC hospitals among veterans meeting study inclusion criteria. On average, use of CC was associated with reduced net travel by 53.6 miles for PCI and by 73.3 miles for CABG surgery compared with VA-only care. Adjusted 30-day mortality after PCI was higher in CC compared with VA (1.54% for CC vs 0.65% for VA, P < .001) but was similar after CABG surgery (1.33% for CC vs 1.51% for VA, P = .74). There were no differences in adjusted 30-day readmission rates for PCI (7.04% for CC vs 7.73% for VA, P = .66) or CABG surgery (8.13% for CC vs 7.00% for VA, P = .28). The mean adjusted PCI cost was higher in CC ($22 025 for CC vs $15 683 for VA, P < .001). The mean adjusted CABG cost was lower in CC ($55 526 for CC vs $63 144 for VA, P < .01). Neither procedural volume nor publicly reported mortality data identified hospitals that provided higher-value care with the exception that CABG mortality was lower in small-volume CC hospitals. Conclusions and Relevance In this veteran cohort, PCIs performed in CC hospitals were associated with shorter travel distance but with higher mortality, higher costs, and minimal travel savings compared with VA hospitals. The CABG procedures performed in CC hospitals were associated with shorter travel distance, similar mortality, and lower costs. As the VA considers expansion of the CC program, ongoing assessments of value and access gains are essential to optimize veteran outcomes and VA spending. PMID:29299607

Comparison of Accessibility, Cost, and Quality of Elective Coronary Revascularization Between Veterans Affairs and Community Care Hospitals.

PubMed

Barnett, Paul G; Hong, Juliette S; Carey, Evan; Grunwald, Gary K; Joynt Maddox, Karen; Maddox, Thomas M

2018-02-01

The Veterans Affairs (VA) Community Care (CC) Program supplements VA care with community-based medical services. However, access gains and value provided by CC have not been well described. To compare the access, cost, and quality of elective coronary revascularization procedures between VA and CC hospitals and to evaluate if procedural volume or publicly reported quality data can be used to identify high-value care. Observational cohort study of veterans younger than 65 years undergoing an elective coronary revascularization, controlling for differences in risk factors using propensity adjustment. The setting was VA and CC hospitals. Participants were veterans undergoing elective percutaneous coronary intervention (PCI) and veterans undergoing coronary artery bypass graft (CABG) procedures between October 1, 2008, and September 30, 2011. The analysis was conducted between July 2014 and July 2017. Receipt of an elective coronary revascularization at a VA vs CC facility. Access to care as measured by travel distance, 30-day mortality, and costs. In the 3 years ending on September 30, 2011, a total of 13 237 elective PCIs (79.1% at the VA) and 5818 elective CABG procedures (83.6% at the VA) were performed in VA or CC hospitals among veterans meeting study inclusion criteria. On average, use of CC was associated with reduced net travel by 53.6 miles for PCI and by 73.3 miles for CABG surgery compared with VA-only care. Adjusted 30-day mortality after PCI was higher in CC compared with VA (1.54% for CC vs 0.65% for VA, P < .001) but was similar after CABG surgery (1.33% for CC vs 1.51% for VA, P = .74). There were no differences in adjusted 30-day readmission rates for PCI (7.04% for CC vs 7.73% for VA, P = .66) or CABG surgery (8.13% for CC vs 7.00% for VA, P = .28). The mean adjusted PCI cost was higher in CC ($22 025 for CC vs $15 683 for VA, P < .001). The mean adjusted CABG cost was lower in CC ($55 526 for CC vs $63 144 for VA, P < .01). Neither procedural volume nor publicly reported mortality data identified hospitals that provided higher-value care with the exception that CABG mortality was lower in small-volume CC hospitals. In this veteran cohort, PCIs performed in CC hospitals were associated with shorter travel distance but with higher mortality, higher costs, and minimal travel savings compared with VA hospitals. The CABG procedures performed in CC hospitals were associated with shorter travel distance, similar mortality, and lower costs. As the VA considers expansion of the CC program, ongoing assessments of value and access gains are essential to optimize veteran outcomes and VA spending.

Repression of the expression of PPP3CC by ZEB1 confers activation of NF-κB and contributes to invasion and growth in glioma cells.

PubMed

Wang, Hongquan; Zhao, Shuli; Chen, Bo; Fu, Chuhua; Dang, Yanwei; Fang, Peihai; Wang, Jun; Wang, Ning; Liu, Lijun

2018-02-01

Gliomas are highly malignant brain tumors. Aberrant activation of NF-κB plays a crucial role in tumor progression. ELISA assay was used to detect NF-κB activity in glimoas cells with different treatments. PPP3CC expression was evaluated by qRT-PCR and western blot assay. Kaplan-Meier analysis estimated the overall survival rates according to the protein level of PPP3CC. Transwell and MTS assay were performed to determine cell invasion and growth. Chromatin immunoprecipitation combined with luciferase reporter assays illustrated the transcriptional regulation of PPP3CC. We showed that PPP3CC decrease was responsible for constitutive activation of NF-κB in gliomas. Restored PPP3CC expression inhibited activation of NF-κB. PPP3CC was frequently decreased in gliomas and that repression of the expression of PPP3CC correlated glioma progression. The ectopic expression of PPP3CC inhibited the invasive potential of glioma cells, and inhibited glioma cells proliferation in vitro and growth in vivo. Additionally, the expression of Zinc finger E-box-binding homeobox 1(ZEB1) was increased in gliomas and was negatively correlated with clinical outcomes of glioma patients. ZEB1 inversely correlated with the expression of PPP3CC. ZEB1 was also confirmed to physically bind to the PPP3CC promoter. ZEB1 knockdown resulted in an increase in the expression of PPP3CC and elevation of PPP3CC promoter activity in glioma cells. These findings indicated that the down-regulation of PPP3CC by ZEB1 resulted in activation of NF-κB is a critical oncogenic event in gliomas. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost.

PubMed

Taylor, Frederick; Levine, Laurence

2010-01-01

The efficacy of oral clomiphene citrate (CC) in the treatment of male hypogonadism and male infertility (MI) with low serum testosterone and normal gonadotropin levels has been reported. The aim of this article is to evaluate CC and testosterone gel replacement therapy (TGRT) with regard to biochemical and clinical efficacy and cost. The main outcome measures were change in serum testosterone with CC and TGRT therapy, and change in the androgen deficiency in aging male (ADAM) questionnaire scores with CC therapy. Men receiving CC or TGRT with either Androgel 1% or Testim 1% for hypogonadism (defined as testosterone < 300 ng/mL) or MI were included. Serum values were collected 1-2 months after treatment initiation and semi-annually thereafter. Retrospective data collection was performed via chart review. Subjective follow up of patients receiving CC was performed via telephone interview using the ADAM questionnaire. A hundred and four men (65 CC and 39 TGRT) were identified who began CC (50 mg every other day) or TGRT (5 g). Average age (years) was 42(CC) vs. 57 (TGRT). Average follow up was 23 months (CC, range 8-40 months) vs. 46 months (TGRT, range 6-149 months). Average posttreatment testosterone was 573 ng/dL in the CC group and 553 ng/dL in the TGRT group (P value < 0.001). The monthly cost of Testim 1% (5 gm daily) is $270, Androgel 1% (5 gm daily) is $265, and CC (50 mg every other day) is $83. Among CC patients, the average pretreatment ADAM score was 4.9 vs. 2.1 at follow up (P < 0.05). Average pretreatment ADAM sexual function domain score was 0.76 vs. 0.23 at follow up (P < 0.05). There were no adverse events reported. CC represents a treatment option for men with hypogonadism, demonstrating biochemical and clinical efficacy with few side effects and lower cost as compared with TGRT.

'Communicative competence' in the field of augmentative and alternative communication: a review and critique.

PubMed

Teachman, Gail; Gibson, Barbara E

2014-01-01

Understandings of 'communicative competency' (CC) have an important influence on the ways that researchers and practitioners in augmentative and alternative communication (AAC) work toward achieving positive outcomes with AAC users. Yet, very little literature has critically examined conceptualizations of CC in AAC. Following an overview of the emergence of the concept of CC and of the field of AAC, we review seven conceptualizations of CC identified in the literature. To consider the contributions and potential shortcomings of conceptualizations of CC in AAC. We use a critical theoretical approach to review, critique and synthesize conceptualizations of CC in AAC, with a particular focus on uncovering 'taken for granted' assumptions. By historically situating the reviewed literature, we examine the shifting boundaries and tensions among theoretical conceptualizations of CC in AAC and their potential impacts on practice. We suggest ways that revisiting past scholarly work, alongside emergent, innovative conceptualizations of CC might shift ways of thinking about CC in AAC which tend to focus on the individual who communicates differently, toward (re)location of CC as a shared, socially incorporated and performed communication construct. We propose that emerging critical perspectives drawn from AAC and other interdisciplinary literatures offer innovative ways of theorizing communication difference, which might inform evolving conceptualizations of CC in AAC. © 2013 Royal College of Speech and Language Therapists.

Demonstration of immunologic memory using serogroup C meningococcal glycoconjugate vaccine.

PubMed

Snape, Matthew D; Maclennan, Jenny M; Lockhart, Stephen; English, Mike; Yu, Ly-Mee; Moxon, Richard E; Pollard, Andrew J

2009-02-01

Studies of glycoconjugate vaccines have traditionally used an immune challenge with a plain polysaccharide vaccine to demonstrate immunologic memory. Plain polysaccharide vaccines are poorly immunogenic in children and can induce subsequent immunologic hyporesponsiveness. We therefore assessed the use of glycoconjugate vaccines as an alternative method of demonstrating immunologic memory. Children immunized with hepatitis B vaccine or serogroup C meningococcal glycoconjugate vaccine (MenCC) at age 2, 3, 4 months received a plain polysaccharide meningococcal serogroup A/C vaccine (MenACP) or MenCC at age 12 months. A post hoc analysis of serum bactericidal activity responses to MenCC assessed whether this differed in MenCC primed and MenCC naive infants. MenCC primed children displayed higher geometric mean serum bactericidal titers than MenCC naive children following MenACP (1518 compared with 30; P = 0.003). A similar difference was seen after a dose of MenCC to toddlers (MenCC primed: 8663, MenCC naive: 710; P < 0.001). The latter comparison became a borderline significance after adjusting for higher pretoddler immunization serum bactericidal geometric mean titers in the MenCC primed group (P = 0.068). Administration of glycoconjugate vaccines provides an important alternative method of demonstrating immunologic memory, avoiding the use of plain polysaccharide vaccines that are potentially deleterious in children. This has implications for the design of all future clinical trials of glycoconjugate vaccines.

A full scale hydrodynamic simulation of pyrotechnic combustion

NASA Astrophysics Data System (ADS)

Kim, Bohoon; Jang, Seung-Gyo; Yoh, Jack

2017-06-01

A full scale hydrodynamic simulation that requires an accurate reproduction of shock-induced detonation was conducted for design of an energetic component system. A series of small scale gap tests and detailed hydrodynamic simulations were used to validate the reactive flow model for predicting the shock propagation in a train configuration and to quantify the shock sensitivity of the energetic materials. The energetic component system is composed of four main components, namely a donor unit (HNS + HMX), a bulkhead (STS), an acceptor explosive (RDX), and a propellant (BKNO3) for gas generation. The pressurized gases generated from the burning propellant were purged into a 10 cc release chamber for study of the inherent oscillatory flow induced by the interferences between shock and rarefaction waves. The pressure fluctuations measured from experiment and calculation were investigated to further validate the peculiar peak at specific characteristic frequency (ωc = 8.3 kHz). In this paper, a step-by-step numerical description of detonation of high explosive components, deflagration of propellant component, and deformation of metal component is given in order to facilitate the proper implementation of the outlined formulation into a shock physics code for a full scale hydrodynamic simulation of the energetic component system.

Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinoma patients: clinically relevant models for research and personalized medicine.

PubMed

Lobo, Nazleen C; Gedye, Craig; Apostoli, Anthony J; Brown, Kevin R; Paterson, Joshua; Stickle, Natalie; Robinette, Michael; Fleshner, Neil; Hamilton, Robert J; Kulkarni, Girish; Zlotta, Alexandre; Evans, Andrew; Finelli, Antonio; Moffat, Jason; Jewett, Michael A S; Ailles, Laurie

2016-07-16

Patients with clear cell renal cell carcinoma (ccRCC) have few therapeutic options, as ccRCC is unresponsive to chemotherapy and is highly resistant to radiation. Recently targeted therapies have extended progression-free survival, but responses are variable and no significant overall survival benefit has been achieved. Commercial ccRCC cell lines are often used as model systems to develop novel therapeutic approaches, but these do not accurately recapitulate primary ccRCC tumors at the genomic and transcriptional levels. Furthermore, ccRCC exhibits significant intertumor genetic heterogeneity, and the limited cell lines available fail to represent this aspect of ccRCC. Our objective was to generate accurate preclinical in vitro models of ccRCC using tumor tissues from ccRCC patients. ccRCC primary single cell suspensions were cultured in fetal bovine serum (FBS)-containing media or defined serum-free media. Established cultures were characterized by genomic verification of mutations present in the primary tumors, expression of renal epithelial markers, and transcriptional profiling. The apparent efficiency of primary cell culture establishment was high in both culture conditions, but genotyping revealed that the majority of cultures contained normal, not cancer cells. ccRCC characteristically shows biallelic loss of the von Hippel Lindau (VHL) gene, leading to accumulation of hypoxia-inducible factor (HIF) and expression of HIF target genes. Purification of cells based on expression of carbonic anhydrase IX (CA9), a cell surface HIF target, followed by culture in FBS enabled establishment of ccRCC cell cultures with an efficiency of >80 %. Culture in serum-free conditions selected for growth of normal renal proximal tubule epithelial cells. Transcriptional profiling of ccRCC and matched normal cell cultures identified up- and down-regulated networks in ccRCC and comparison to The Cancer Genome Atlas confirmed the clinical validity of our cell cultures. The ability to establish primary cultures of ccRCC cells and matched normal kidney epithelial cells from almost every patient provides a resource for future development of novel therapies and personalized medicine for ccRCC patients.

Chronic Condition and Risk Behaviours in Portuguese Adolescents

PubMed Central

Santos, Teresa; Ferreira, Mafalda; Simões, Maria Celeste; Machado, Maria Céu; de Matos, Margarida Gaspar

2014-01-01

Living with a chronic condition (CC) in adolescence has been historically considered protective for risk behaviours. However, research from the last decade suggest that when compared with healthy peers, adolescents living with a chronic condition can engage in risky behaviours in a similar if not higher rate than their counterparts living with out a CC. This study aims to characterize and evaluate the impact of 1) living with a chronic condition (CC), and 2) how the perception of living with a CC affects school participation, and its association with risk/protective behaviours (drunkenness, physical fight, sadness and self-harm). For this purpose 4 groups were identified: adolescents with mostly healthy behaviours, adolescents with mostly risk behaviours, adolescents with mostly risk-internalizing behaviours and adolescents with mostly risk-externalizing behaviours. A large sample was included in this study, composed by 3494 Portuguese adolescents with an average age of 15 years, who participated in the Portuguese Survey of Health Behaviour in School-aged Children/WHO (HBSC). Main results show that adolescents living with a CC have more risk-internalizing behaviours when compared to adolescents without CC, who present more healthy behaviors. Furthermore, adolescents that report that having a CC affects school participation show more risky behaviours than those not affected by a CC who present more healthy behaviours. Boys with a CC show more healthy behaviours, and those who feel that the CC affects school participation present more risky behaviours. On the other hand, girls with a CC have more risk-internalizing behaviours and less healthy behaviours It is important to point out that dolescents living with a CC represent a vulnerable group, and may engage in experimental/risky behaviours as likely as their non CC peers. Thus, potential benefits can arise from reinforcing interventions within protective contexts (family/peers/school setting). Health/education professionals, more than considering risk behaviours as dangerous in themselves, should offer adolescents with a CC an opportunity to reflect on their own decisions. Educational programs would benefit from looking at risk behaviors more from an experimentation perspective, focusing on constructive ways to help adolescents with CC to proceed into adulthood in a more appropriate developmental way. PMID:24576385

Implementation of Change (IC).

DTIC Science & Technology

1980-06-30

4- co C\\J t ) t r) - 1 )C CC :r E 4-’ c) C- co cn a, ko r- co0 :3 -~ a)~ -D V) 0:3 4-2 CAA-SR-80-5 4-5. SUMMARY. The above discussion suggests that...MTOE documents frequently cost the Army resources; e.g., changes to components of sets, kits and outfits ( SKO ). On the other hand, failure to implement...either retraineo tn recruited to meet the qudlification requiremient. F-13 CAA-SR- KO -5 a. Central Assignment Procedures System (CAP III). Personnel

Ceramic matrix composites - Forerunners of technological breakthrough in space vehicle hot structures and thermal protection system

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

Lacombe, A.; Rouges, J.

1990-01-01

The current status of carbon-carbon and carbon-silicon carbide composites developed for aerospace applications is reviewed. In particular, attention is given to production facilities and technologies for the manufacture of C-C and C-SiC composites, mechanical and thermal characteristics of carbon-carbon and carbon-silicon carbide materials, applications to thermal structures and protection, and technologies developed to build large C-SiC thermostructural components within the Hermes program. 9 refs.

In vitro degradation and cell response of calcium carbonate composite ceramic in comparison with other synthetic bone substitute materials.

PubMed

He, Fupo; Zhang, Jing; Yang, Fanwen; Zhu, Jixiang; Tian, Xiumei; Chen, Xiaoming

2015-05-01

The robust calcium carbonate composite ceramics (CC/PG) can be acquired by fast sintering calcium carbonate at a low temperature (650 °C) using a biocompatible, degradable phosphate-based glass (PG) as sintering agent. In the present study, the in vitro degradation and cell response of CC/PG were assessed and compared with 4 synthetic bone substitute materials, calcium carbonate ceramic (CC), PG, hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) ceramics. The degradation rates in decreasing order were as follows: PG, CC, CC/PG, β-TCP, and HA. The proliferation of rat bone mesenchymal stem cells (rMSCs) cultured on the CC/PG was comparable with that on CC and PG, but inferior to HA and β-TCP. The alkaline phosphatase (ALP) activity of rMSCs on CC/PG was lower than PG, comparable with β-TCP, but higher than HA. The rMSCs on CC/PG and PG had enhanced gene expression in specific osteogenic markers, respectively. Compared to HA and β-TCP, the rMSCs on the CC/PG expressed relatively lower level of collagen I and runt-related transcription factor 2, but showed more considerable expression of osteopontin. Although CC, PG, HA, and β-TCP possessed impressive performances in some specific aspects, they faced extant intrinsic drawbacks in either degradation rate or mechanical strength. Based on considerable compressive strength, moderate degradation rate, good cell response, and being free of obvious shortcoming, the CC/PG is promising as another choice for bone substitute materials. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural changes of the corpus callosum in tinnitus

PubMed Central

Diesch, Eugen; Schummer, Verena; Kramer, Martin; Rupp, Andre

2012-01-01

Objectives: In tinnitus, several brain regions seem to be structurally altered, including the medial partition of Heschl's gyrus (mHG), the site of the primary auditory cortex. The mHG is smaller in tinnitus patients than in healthy controls. The corpus callosum (CC) is the main interhemispheric commissure of the brain connecting the auditory areas of the left and the right hemisphere. Here, we investigate whether tinnitus status is associated with CC volume. Methods: The midsagittal cross-sectional area of the CC was examined in tinnitus patients and healthy controls in which an examination of the mHG had been carried out earlier. The CC was extracted and segmented into subregions which were defined according to the most common CC morphometry schemes introduced by Witelson (1989) and Hofer and Frahm (2006). Results: For both CC segmentation schemes, the CC posterior midbody was smaller in male patients than in male healthy controls and the isthmus, the anterior midbody, and the genou were larger in female patients than in female controls. With CC size normalized relative to mHG volume, the normalized CC splenium was larger in male patients than male controls and the normalized CC splenium, the isthmus and the genou were larger in female patients than female controls. Normalized CC segment size expresses callosal interconnectivity relative to auditory cortex volume. Conclusion: It may be argued that the predominant function of the CC is excitatory. The stronger callosal interconnectivity in tinnitus patients, compared to healthy controls, may facilitate the emergence and maintenance of a positive feedback loop between tinnitus generators located in the two hemispheres. PMID:22470322

The CPP-ACP relieved enamel erosion from a carbonated soft beverage: an in vitro AFM and XRD study.

PubMed

Wang, C P; Huang, S B; Liu, Y; Li, J Y; Yu, H Y

2014-03-01

To investigate the CPP-ACP's effect on enamel against carbonated beverage erosion and explore the potential mechanism. A total of 30 enamel samples were prepared from sound bovine incisors, divided into 3 groups. Samples in the control group were kept in artificial saliva. Specimens' surfaces were smeared with a CPP-ACP agent (Tooth Mousse, TM) for 3 min, rinsed with distilled water for 10s, merged into cola (Coca Cola, CC) for 4 intervals of 2 min, rinsed again for the TM+CC group. In the CC group, specimens were treated solely with cola for 4 intervals (2 min each). The cycles were applied at 0, 12, 24, 36, 48 and 60 h. The surface microhardness (SMH) alterations were measured using a microhardness tester, the surface profiles were analyzed using the atomic force microscope, and the surface crystalline amount (I%) and crystallinity (FWHM) were analyzed using X-ray diffractometer. The SMH were significantly decreased in CC group, showing the largest SMH alteration; the reduction of SMH in TM+CC group was lower than that in CC group, still larger than control. After cycles, the TM+CC group showed rougher surfaces than control, while the CC group had the roughest surfaces. The TM+CC had an I% higher than the CC, and lower than the control. The TM+CC group had a FWHM lower than CC, higher than control. CPP-ACP was able to relieve the erosion on enamel from carbonated beverage. Copyright © 2013 Elsevier Ltd. All rights reserved.

Charmed baryon weak decays with SU(3) flavor symmetry

NASA Astrophysics Data System (ADS)

Geng, C. Q.; Hsiao, Y. K.; Liu, Chia-Wei; Tsai, Tien-Hsueh

2017-11-01

We study the semileptonic and non-leptonic charmed baryon decays with SU(3) flavor symmetry, where the charmed baryons can be B c = (Ξ c 0 , Ξ c + , Λ c + ), B c ' = ( Σ c (++,+,0) , Ξ c ' (+,0) , Ω c 0 ), B cc = (Ξ cc + + , Ξ cc + , Ω c + ) or B cc = Ω ccc + + . With B n (') denoted as the baryon octet (decuplet), we find that the B c → B n ' ℓ + ν ℓ decays are forbidden, while the Ω c 0 → Ω- ℓ + ν ℓ , Ω cc + → Ω c 0 ℓ + ν ℓ , and Ω ccc + + → Ω cc + ℓ + ν ℓ decays are the only existing Cabibbo- allowed modes for B c ' → B n ' ℓ + ν ℓ , B cc → B c ' ℓ + ν ℓ , and B ccc → B cc (') ℓ + ν ℓ , respectively. We predict the rarely studied B c → B n (') M decays, such as B({Ξ}_c^0\\to {Λ}^0{\\overline{K}}^0,{Ξ}_c+\\to {Ξ}^0{π}+)=(8.3± 0.9, 8.0± 4.1)× {10}^{-3} and B({Λ}_c+\\to {Δ}^{++}{π}-,{Ξ}_c^0\\to {Ω}-{K}+)=(5.5± 1.3, 4.8± 0.5)× {10}^{-3} . For the observation, the doubly and triply charmed baryon decays of {Ω}_{cc}+\\to {Ξ}_c+{\\overline{K}}^0,{Ξ}_{cc}^{++}\\to ({Ξ}_c+{π}+,{Σ}_c^{++}{\\overline{K}}^0), and {Ω}_{ccc}^{++}\\to ({Ξ}_{cc}^{++}{\\overline{K}}^0,{Ω}_{cc}+{π}+,{Ξ}_c+{D}+) are the favored Cabibbo-allowed decays, which are accessible to the BESIII and LHCb experiments.

Effect of aerobic exercise and fish oil supplements on plasma levels of inflammatory indexes in mice.

PubMed

Alizadeh, Hamid; Bazgir, Behzad; Daryanoosh, Farhad; Koushki, Maryam; Sobhani, Vahid

2014-01-01

Exercise has positive and negative effects on immune system. Herein, we would like to investigate the effects of incremental aerobic training and fish oil supplementation on the plasma levels of CRP, CPK and IL-17 in trained mice. One of the major roles of immune system is to produce soluble or cellular components that provide the immunity against inflammatory agent. The purpose of this study is to investigate distinct and combine effects of incremental aerobic training and fish oil supplement on plasma levels of IL-17, CPK and CRP in trained male mice. Totally, 54 healthy male mice (2 months old, weight= 34±1 grams) were selected. At first 10 mice were killed to determine base line values, the rest of them were randomly divided into four groups, control group (C, n=11), supplement group (S, n=11), training group (T, n=11) and supplement-training group (ST, n=11).The supplement and supplement-training groups were fed with 0.2cc/day fish oil for 8 weeks. Training and supplement-training groups underwent exercise for 5 sessions per week for a period of 8 weeks on animal treadmill. SPSS 16.0 software and multivariate analysis of variance were used for statistical analysis of data Exercise and fish oil supplement lead to a decrease in CRP levels and subsequently causing a reduction in plasma levels of IL-17 and CK in mice (p<0.05). Combination of exercise and fish oil can reduce regulate inflammatory response caused by incremental exercise.

Protein subcellular location pattern classification in cellular images using latent discriminative models.

PubMed

Li, Jieyue; Xiong, Liang; Schneider, Jeff; Murphy, Robert F

2012-06-15

Knowledge of the subcellular location of a protein is crucial for understanding its functions. The subcellular pattern of a protein is typically represented as the set of cellular components in which it is located, and an important task is to determine this set from microscope images. In this article, we address this classification problem using confocal immunofluorescence images from the Human Protein Atlas (HPA) project. The HPA contains images of cells stained for many proteins; each is also stained for three reference components, but there are many other components that are invisible. Given one such cell, the task is to classify the pattern type of the stained protein. We first randomly select local image regions within the cells, and then extract various carefully designed features from these regions. This region-based approach enables us to explicitly study the relationship between proteins and different cell components, as well as the interactions between these components. To achieve these two goals, we propose two discriminative models that extend logistic regression with structured latent variables. The first model allows the same protein pattern class to be expressed differently according to the underlying components in different regions. The second model further captures the spatial dependencies between the components within the same cell so that we can better infer these components. To learn these models, we propose a fast approximate algorithm for inference, and then use gradient-based methods to maximize the data likelihood. In the experiments, we show that the proposed models help improve the classification accuracies on synthetic data and real cellular images. The best overall accuracy we report in this article for classifying 942 proteins into 13 classes of patterns is about 84.6%, which to our knowledge is the best so far. In addition, the dependencies learned are consistent with prior knowledge of cell organization. http://murphylab.web.cmu.edu/software/.

[Comporison Sduty of Microstructure by Metallographicalk on the Polarized Light and Texture by XRD of CC 5083 and CC 5182 Aluminium Alloy after Cold Rolling and Recrystallization].

PubMed

Chen, Ming-biao; Li, Yong-wei; Tan, Yuan-biao; Ma, Min; Wang, Xue-min; Liu, Wen-chang

2015-03-01

At present the study of relation between microstructure, texture and performance of CC 5083 aluminium alloy after cold tolling and recrystallization processes is still finitude. So that the use of the CC 5083 aluminium alloy be influenced. Be cased into electrical furnace, hot up with unlimited speed followed the furnace hot up to different temperature and annealed 2h respectively, and be cased into salt-beth furnace, hot up quickly to different temperature and annealed 30 min respectively for CC 5083 and CC 5182 aluminum alloy after cold roling with 91.5% reduction. The microstructure be watched use metallographic microscope, the texture be inspected by XRD. The start temperature of recrystallization and grain grow up temperature within annealing in the electric furnace of CC 5083 aluminum alloy board is 343 degrees C, and the shap of grain after grow up with long strip (the innovation point ); The start temperature of recrystallization within annealling in the salt bath furnace of CC 5083 is 343 degrees C. The start temperature and end temperature of recrystallization within annealling of CC 5083 and CC 5182 aluminum alloy is 371 degrees C. The grain grow up outstanding of cold rooled CC 5152 aluminum alloy after annealed with 454 degrees C in the electric furnace and salt bath furnace. The start temperature of grain grow up of CC 5083 alluminurn alloy annealed in the electric furnace and salt bath furnace respectively is higher than the start temperature of grain grow up of CC 5182 alluminum alloy annealed in the electric furnace and salt bath furnace respectively. The strat temperature of recrystallization grain grow up is higher than which annealled with other three manner annealing process. The recrystallization temperature of CC 5182 annealed in the salt bath furnace is higher than which annealed in the electric furnace. The recrystallization temperature of the surface layer of CC 5083 and CC 5182 aluminum alloy is higher than the inner layer (the innovation point). There is a difference each other of the structure and the texture of the four manner annealing aluminum alloy (the innovation point). There is a little difference at the recrystallization processes course reflectived by the observe results of structure transform and by the examination results of texture transmission.

Agent-based models of cellular systems.

PubMed

Cannata, Nicola; Corradini, Flavio; Merelli, Emanuela; Tesei, Luca

2013-01-01

Software agents are particularly suitable for engineering models and simulations of cellular systems. In a very natural and intuitive manner, individual software components are therein delegated to reproduce "in silico" the behavior of individual components of alive systems at a given level of resolution. Individuals' actions and interactions among individuals allow complex collective behavior to emerge. In this chapter we first introduce the readers to software agents and multi-agent systems, reviewing the evolution of agent-based modeling of biomolecular systems in the last decade. We then describe the main tools, platforms, and methodologies available for programming societies of agents, possibly profiting also of toolkits that do not require advanced programming skills.

The long history of hematoxylin.

PubMed

Titford, M

2005-01-01

Hematoxylin is a naturally occurring chemical used as the basis of a dye in laboratories throughout the world to stain nuclei in microscope slide preparations. This chemical is extracted from the logwood tree Hematoxylon campechianum and was discovered by Spanish explorers to the Yucatan in 1502. A vigorous trade soon developed related to growing and preparing hematoxylin for use in dyeing fabrics in Europe. In the mid 1800s, amateur microscopists first used hematoxylin to stain cellular components. Later scientists developed a wide range of techniques to demonstrate different cellular components. Hematoxylin remains the most popular nuclear stain in histology. This paper briefly describes the history of hematoxylin production and use in histology.

Using Movies to Analyse Gene Circuit Dynamics in Single Cells

PubMed Central

Locke, James CW; Elowitz, Michael B

2010-01-01

Preface Many bacterial systems rely on dynamic genetic circuits to control critical processes. A major goal of systems biology is to understand these behaviours in terms of individual genes and their interactions. However, traditional techniques based on population averages wash out critical dynamics that are either unsynchronized between cells or driven by fluctuations, or ‘noise,’ in cellular components. Recently, the combination of time-lapse microscopy, quantitative image analysis, and fluorescent protein reporters has enabled direct observation of multiple cellular components over time in individual cells. In conjunction with mathematical modelling, these techniques are now providing powerful insights into genetic circuit behaviour in diverse microbial systems. PMID:19369953

Chronic stress induced disruption of the peri-infarct neurovascular unit following experimentally induced photothrombotic stroke.

PubMed

Zhao, Zidan; Ong, Lin Kooi; Johnson, Sarah; Nilsson, Michael; Walker, Frederick R

2017-12-01

How stress influences brain repair is an issue of considerable importance, as patients recovering from stroke are known to experience high and often unremitting levels of stress post-event. In the current study, we investigated how chronic stress modified the key cellular components of the neurovascular unit. Using an experimental model of focal cortical ischemia in male C57BL/6 mice, we examined how exposure to a persistently aversive environment, induced by the application of chronic restraint stress, altered the cortical remodeling post-stroke. We focused on systematically investigating changes in the key components of the neurovascular unit (i.e. neurons, microglia, astrocytes, and blood vessels) within the peri-infarct territories using both immunohistochemistry and Western blotting. The results from our study indicated that exposure to chronic stress exerted a significant suppressive effect on each of the key cellular components involved in neurovascular remodeling. Co-incident with these cellular changes, we observed that chronic stress was associated with an exacerbation of motor impairment 42 days post-event. Collectively, these results highlight the vulnerability of the peri-infarct neurovascular unit to the negative effects of chronic stress.

Nanokit for single-cell electrochemical analyses.

PubMed

Pan, Rongrong; Xu, Mingchen; Jiang, Dechen; Burgess, Jame D; Chen, Hong-Yuan

2016-10-11

The development of more intricate devices for the analysis of small molecules and protein activity in single cells would advance our knowledge of cellular heterogeneity and signaling cascades. Therefore, in this study, a nanokit was produced by filling a nanometer-sized capillary with a ring electrode at the tip with components from traditional kits, which could be egressed outside the capillary by electrochemical pumping. At the tip, femtoliter amounts of the kit components were reacted with the analyte to generate hydrogen peroxide for the electrochemical measurement by the ring electrode. Taking advantage of the nanotip and small volume injection, the nanokit was easily inserted into a single cell to determine the intracellular glucose levels and sphingomyelinase (SMase) activity, which had rarely been achieved. High cellular heterogeneities of these two molecules were observed, showing the significance of the nanokit. Compared with the current methods that use a complicated structural design or surface functionalization for the recognition of the analytes, the nanokit has adapted features of the well-established kits and integrated the kit components and detector in one nanometer-sized capillary, which provides a specific device to characterize the reactivity and concentrations of cellular compounds in single cells.

Mutations in the NHEJ Component XRCC4 Cause Primordial Dwarfism

PubMed Central

Murray, Jennie E.; van der Burg, Mirjam; IJspeert, Hanna; Carroll, Paula; Wu, Qian; Ochi, Takashi; Leitch, Andrea; Miller, Edward S.; Kysela, Boris; Jawad, Alireza; Bottani, Armand; Brancati, Francesco; Cappa, Marco; Cormier-Daire, Valerie; Deshpande, Charu; Faqeih, Eissa A.; Graham, Gail E.; Ranza, Emmanuelle; Blundell, Tom L.; Jackson, Andrew P.; Stewart, Grant S.; Bicknell, Louise S.

2015-01-01

Non-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive immune system. In contrast, we have recently found that biallelic mutations in LIG4 are a common cause of microcephalic primordial dwarfism (MPD), a phenotype characterized by prenatal-onset extreme global growth failure. Here we provide definitive molecular genetic evidence supported by biochemical, cellular, and immunological data for mutations in XRCC4, encoding the obligate binding partner of LIG4, causing MPD. We report the identification of biallelic mutations in XRCC4 in five families. Biochemical and cellular studies demonstrate that these alterations substantially decrease XRCC4 protein levels leading to reduced cellular ligase IV activity. Consequently, NHEJ-dependent repair of ionizing-radiation-induced DNA double-strand breaks is compromised in XRCC4 cells. Similarly, immunoglobulin junctional diversification is impaired in cells. However, immunoglobulin levels are normal, and individuals lack overt signs of immunodeficiency. Additionally, in contrast to individuals with LIG4 mutations, pancytopenia leading to bone marrow failure has not been observed. Hence, alterations that alter different NHEJ proteins give rise to a phenotypic spectrum, from SCID to extreme growth failure, with deficiencies in certain key components of this repair pathway predominantly exhibiting growth deficits, reflecting differential developmental requirements for NHEJ proteins to support growth and immune maturation. PMID:25728776

Statistical Analysis of the Effect of Inspection and Maintenance ...

EPA Pesticide Factsheets

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Climate change affecting oil palm agronomy, and oil palm cultivation increasing climate change, require amelioration.

PubMed

Paterson, R Russell M; Lima, Nelson

2018-01-01

Palm oil is used in various valued commodities and is a large global industry worth over US$ 50 billion annually. Oil palms (OP) are grown commercially in Indonesia and Malaysia and other countries within Latin America and Africa. The large-scale land-use change has high ecological, economic, and social impacts. Tropical countries in particular are affected negatively by climate change (CC) which also has a detrimental impact on OP agronomy, whereas the cultivation of OP increases CC. Amelioration of both is required. The reduced ability to grow OP will reduce CC, which may allow more cultivation tending to increase CC, in a decreasing cycle. OP could be increasingly grown in more suitable regions occurring under CC. Enhancing the soil fauna may compensate for the effect of CC on OP agriculture to some extent. The effect of OP cultivation on CC may be reduced by employing reduced emissions from deforestation and forest degradation plans, for example, by avoiding illegal fire land clearing. Other ameliorating methods are reported herein. More research is required involving good management practices that can offset the increases in CC by OP plantations. Overall, OP-growing countries should support the Paris convention on reducing CC as the most feasible scheme for reducing CC.

The cycle characteristics of clomiphene with clomiphene and menotropins in polycystic ovary syndrome and non polycystic ovary syndrome infertile patients.

PubMed

Ghasemi, M; Ashraf, H; Koushyar, H; Mousavifar, N

2013-06-01

This study compares the cycle characteristics of clomiphene (CC) with CC+HMG (Human Menopausal Gonadotropin or Menotropins) in Polycystic Ovary Syndrome (PCOS) and non-PCOS infertile patients. Patients were treated by CC + minimal HMg protocol. The cancellation rate, the mean number of different follicle sizes and endometrial thickness and pattern were compared. The cancelled cycles due to non-responsiveness were significantly higher in CC compared to CC+ minimal HMg protocol. PCOS patients are significantly nonresponsive in CC cycle and hyperresponsive in CC+ minimal HMg cycles. The mean number of different sizes of follicles and the endometrial thickness were significantly higher in CC+ minimal HMg. PCOS patients were significantly different from non-PCOS regarding the number of mature follicle and endometrial thickness. The pregnancy rate was 11% (10.2% in non-PCOS and 12.2% in PCOS). CC+ minimal HMg is a viable alternative to HMg /FSH only protocol in CC failure or resistant patients, and its efficacy can be mostly attributed to improvement of endometrial quality and increase in follicle number. Moreover, due to high cancellation of PCOS patients treated by this protocol, seemingly other alternatives should be found; perhaps sequential letrozole+HMg/FSH that have been shown to improve the ovarian response in this group of patients.

Return of spontaneous Circulation Is Not Affected by Different Chest Compression Rates Superimposed with Sustained Inflations during Cardiopulmonary Resuscitation in Newborn Piglets

PubMed Central

Li, Elliott S.; Cheung, Po-Yin; Lee, Tze-Fun; Lu, Min; O'Reilly, Megan

2016-01-01

Objective Recently, sustained inflations (SI) during chest compression (CC) have been suggested as an alternative to the current approach during neonatal resuscitation. However, the optimal rate of CC during SI has not yet been established. Our aim was to determine whether different CC rates during SI reduce time to return of spontaneous circulation (ROSC) and improve hemodynamic recovery in newborn piglets with asphyxia-induced bradycardia. Intervention and measurements Term newborn piglets were anesthetized, intubated, instrumented and exposed to 45-min normocapnic hypoxia followed by asphyxia. Resuscitation was initiated when heart rate decreased to 25% of baseline. Piglets were randomized into three groups: CC superimposed by SI at a rate of 90 CC per minute (SI+CC 90, n = 8), CC superimposed by SI at a rate of 120 CC per minute (SI+CC 120, n = 8), or a sham group (n = 6). Cardiac function, carotid blood flow, cerebral oxygenation and respiratory parameters were continuously recorded throughout the experiment. Main results Both treatment groups had similar time of ROSC, survival rates, hemodynamic and respiratory parameters during cardiopulmonary resuscitation. The hemodynamic recovery in the subsequent 4h was similar in both groups and was only slightly lower than sham-operated piglets at the end of experiment. Conclusion Newborn piglets resuscitated by SI+CC 120 did not show a significant advantage in ROSC, survival, and hemodynamic recovery as compared to those piglets resuscitated by SI+CC 90. PMID:27304210

Assessment of the Asian Neurogastroenterology and Motility Association Chronic Constipation Criteria: An Asian Multicenter Cross-sectional Study

PubMed Central

Gwee, Kok-Ann; Bergmans, Paul; Kim, JinYong; Coudsy, Bogdana; Sim, Angelia; Chen, Minhu; Lin, Lin; Hou, Xiaohua; Wang, Huahong; Goh, Khean-Lee; Pangilinan, John A; Kim, Nayoung; des Varannes, Stanislas Bruley

2017-01-01

Background/Aims There is a need for a simple and practical tool adapted for the diagnosis of chronic constipation (CC) in the Asian population. This study compared the Asian Neurogastroenterology and Motility Association (ANMA) CC tool and Rome III criteria for the diagnosis of CC in Asian subjects. Methods This multicenter, cross-sectional study included subjects presenting at outpatient gastrointestinal clinics across Asia. Subjects with CC alert symptoms completed a combination Diagnosis Questionnaire to obtain a diagnosis based on 4 different diagnostic methods: self-defined, investigator’s judgment, ANMA CC tool, and Rome III criteria. The primary endpoint was the level of agreement/disagreement between the ANMA CC diagnostic tool and Rome III criteria for the diagnosis of CC. Results The primary analysis comprised of 449 subjects, 414 of whom had a positive diagnosis according to the ANMA CC tool. Rome III positive/ANMA positive and Rome III negative/ANMA negative diagnoses were reported in 76.8% and 7.8% of subjects, respectively, resulting in an overall percentage agreement of 84.6% between the 2 diagnostic methods. The overall percentage disagreement between these 2 diagnostic methods was 15.4%. A higher level of agreement was seen between the ANMA CC tool and self-defined (374 subjects [90.3%]) or investigator’s judgment criteria (388 subjects [93.7%]) compared with the Rome III criteria. Conclusion This study demonstrates that the ANMA CC tool can be a useful for Asian patients with CC. PMID:27764907

First Report of a Thioredoxin Homologue in Jellyfish: Molecular Cloning, Expression and Antioxidant Activity of CcTrx1 from Cyanea capillata

PubMed Central

Zhou, Yonghong; Wang, Qianqian; Chang, Yinlong; Wang, Beilei; Zheng, Jiemin; Zhang, Liming

2014-01-01

Thioredoxins (Trx proteins) are a family of small, highly-conserved and ubiquitous proteins that play significant roles in the resistance of oxidative damage. In this study, a homologue of Trx was identified from the cDNA library of tentacle of the jellyfish Cyanea capillata and named CcTrx1. The full-length cDNA of CcTrx1 was 479 bp with a 312 bp open reading frame encoding 104 amino acids. Bioinformatics analysis revealed that the putative CcTrx1 protein harbored the evolutionarily-conserved Trx active site 31CGPC34 and shared a high similarity with Trx1 proteins from other organisms analyzed, indicating that CcTrx1 is a new member of Trx1 sub-family. CcTrx1 mRNA was found to be constitutively expressed in tentacle, umbrella, oral arm and gonad, indicating a general role of CcTrx1 protein in various physiological processes. The recombinant CcTrx1 (rCcTrx1) protein was expressed in Escherichia coli BL21 (DE3), and then purified by affinity chromatography. The rCcTrx1 protein was demonstrated to possess the expected redox activity in enzymatic analysis and protection against oxidative damage of supercoiled DNA. These results indicate that CcTrx1 may function as an important antioxidant in C. capillata. To our knowledge, this is the first Trx protein characterized from jellyfish species. PMID:24824597

Polyurethane Implants in 2-Stage Breast Reconstruction: 9-Year Clinical Experience.

PubMed

Pompei, Stefano; Arelli, Floriana; Labardi, Lara; Marcasciano, Fabio; Evangelidou, Dora; Ferrante, Gianluigi

2017-02-01

Capsular contracture (CC) is a major complication of breast surgery with smooth and textured implants. Polyurethane (PU) foam-coated breast implants were developed to decrease the incidence of CC. The authors determined the incidence of CC following 2-stage breast reconstruction using PU foam-covered implants, with and without radiation therapy. The records of 92 patients who received 115 PU implants were retrospectively reviewed. The rates of CC over time were compared for irradiated and nonirradiated groups with a Kaplan-Meier analysis and log-rank test. CC rates also were analyzed with respect to age. The median follow-up time for patients was 103.3 months. Nine patients experienced unilateral Baker grade III or IV fibrous CC, including 6 patients from the irradiated group and 3 patients from the nonirradiated group. The overall cumulative incidence of CC at 9 years was 8.1%. In the irradiated and nonirradiated groups, the 9-year cumulative incidence was 10.7% and 5.5%, respectively. CC occurred within 3 years in the irradiated group and within 7 years in the nonirradiated group. The incidence of CC appeared to be higher among younger patients. Radiation therapy increases the risk of high-grade CC with textured or smooth implants. PU implants are associated with a much lower cumulative incidence of CC following 2-stage breast reconstruction, even when radiotherapy is performed. LEVEL OF EVIDENCE 3. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Geometric effects of ICMEs on geomagnetic storms

NASA Astrophysics Data System (ADS)

Cho, KyungSuk; Lee, Jae-Ok

2017-04-01

It has been known that the geomagnetic storm is occurred by the interaction between the Interplanetary Coronal Mass Ejection (ICME) and the Earth's magnetosphere; especially, the southward Bz component of ICME is thought as the main trigger. In this study, we investigate the relationship between Dst index and solar wind conditions; which are the southward Bz, electric field (VBz), and time integral of electric field as well as ICME parameters derived from toroidal fitting model in order to find what is main factor to the geomagnetic storm. We also inspect locations of Earth in ICMEs to understand the geometric effects of the Interplanetary Flux Ropes (IFRs) on the geomagnetic storms. Among 59 CDAW ICME lists, we select 30 IFR events that are available by the toroidal fitting model and classify them into two sub-groups: geomagnetic storms associated with the Magnetic Clouds (MCs) and the compression regions ahead of the MCs (sheath). The main results are as follows: (1) The time integral of electric field has a higher correlation coefficient (cc) with Dst index than the other parameters: cc=0.85 for 25 MC events and cc=0.99 for 5 sheath events. (2) The sheath associated intense storms (Dst ≤-100nT) having usually occur at flank regions of ICMEs while the MC associated intense storms occur regardless of the locations of the Earth in ICMEs. The strength of a geomagnetic storm strongly depends on electric field of IFR and durations of the IFR passages through the Earth.

Nitrogen Limitation Alters Biomass Production but Enhances Steviol Glycoside Concentration in Stevia rebaudiana Bertoni

PubMed Central

Barbet-Massin, Claire; Giuliano, Simon; Alletto, Lionel; Daydé, Jean; Berger, Monique

2015-01-01

The need for medicinal and aromatic plants for industrial uses creates an opportunity for farmers to produce alternative crops. Stevia rebaudiana Bertoni, a perennial shrub originating from Paraguay, is of increasing interest as a source of zero-calorie natural sweeteners: the steviol glycosides (SVglys). The aim of this study was to investigate the relevance of nitrogen (N) supply for leaf yield and for SVgly concentrations in leaves, which are the two major components of S. rebaudiana productivity. In this regard, the relationship between leaf N concentration, CO2 assimilation, leaf production and SVgly accumulation was investigated. The experiments were conducted consecutively in growth-chamber (CC: controlled conditions), in greenhouse (SCC: semi-controlled conditions) and in field conditions (FC) on two genotypes. In CC and SCC, three levels of N fertilization were applied. Plants were grown on four locations in the FC experiment. Both N supply (CC and SCC) and location (FC) had a significant effect on N content in leaves. When light was not limiting (SCC and FC) N content in leaves was positively correlated with CO2 assimilation rate and biomass accumulation. Irrespective of the growth conditions, N content in leaves was negatively correlated with SVgly content. However, increased SVgly content was correlated with a decreased ratio of rebaudioside A over stevioside. The evidence that the increased SVgly accumulation compensates for the negative effect on biomass production suggests that adequate SVgly productivity per plant may be achieved with relatively low fertilization. PMID:26192921

Neutrino Observations from the Sudbury Neutrino Observatory

DOE R&D Accomplishments Database

Q. R. Ahmad, R. C. Allen, T. C. Andersen, J. D. Anglin, G. B?hler, J. C. Barton, E. W. Beier, M. Bercovitch, J. Bigu, S. Biller, R. A. Black, I. Blevis, R. J. Boardman, J. Boger, E. Bonvin, M. G. Boulay, M. G. Bowler, T. J. Bowles, S. J. Brice, M. C. Browne, T. V. Bullard, T. H. Burritt, K. Cameron, J. Cameron, Y. D. Chan, M. Chen, H. H. Chen, X. Chen, M. C. Chon, B. T. Cleveland, E. T. H. Clifford, J. H. M. Cowan, D. F. Cowen, G. A. Cox, Y. Dai, X. Dai, F. Dalnoki-Veress, W. F. Davidson, P. J. Doe, G. Doucas, M. R. Dragowsky, C. A. Duba, F. A. Duncan, J. Dunmore, E. D. Earle, S. R. Elliott, H. C. Evans, G. T. Ewan, J. Farine, H. Fergani, A. P. Ferraris, R. J. Ford, M. M. Fowler, K. Frame, E. D. Frank, W. Frati, J. V. Germani, S. Gil, A. Goldschmidt, D. R. Grant, R. L. Hahn, A. L. Hallin, E. D. Hallman, A. Hamer, A. A. Hamian, R. U. Haq, C. K. Hargrove, P. J. Harvey, R. Hazama, R. Heaton, K. M. Heeger, W. J. Heintzelman, J. Heise, R. L. Helmer, J. D. Hepburn, H. Heron, J. Hewett, A. Hime, M. Howe, J. G. Hykawy, M. C. P. Isaac, P. Jagam, N. A. Jelley, C. Jillings, G. Jonkmans, J. Karn, P. T. Keener, K. Kirch, J. R. Klein, A. B. Knox, R. J. Komar, R. Kouzes, T. Kutter, C. C. M. Kyba, J. Law, I. T. Lawson, M. Lay, H. W. Lee, K. T. Lesko, J. R. Leslie, I. Levine, W. Locke, M. M. Lowry, S. Luoma, J. Lyon, S. Majerus, H. B. Mak, A. D. Marino, N. McCauley, A. B. McDonald, D. S. McDonald, K. McFarlane, G. McGregor, W. McLatchie, R. Meijer Drees, H. Mes, C. Mifflin, G. G. Miller, G. Milton, B. A. Moffat, M. Moorhead, C. W. Nally, M. S. Neubauer, F. M. Newcomer, H. S. Ng, A. J. Noble, E. B. Norman, V. M. Novikov, M. O'Neill, C. E. Okada, R. W. Ollerhead, M. Omori, J. L. Orrell, S. M. Oser, A. W. P. Poon, T. J. Radcliffe, A. Roberge, B. C. Robertson, R. G. H. Robertson, J. K. Rowley, V. L. Rusu, E. Saettler, K. K. Schaffer, A. Schuelke, M. H. Schwendener, H. Seifert, M. Shatkay, J. J. Simpson, D. Sinclair, P. Skensved, A. R. Smith, M. W. E. Smith, N. Starinsky, T. D. Steiger, R. G. Stokstad, R. S. Storey, B. Sur, R. Tafirout, N. Tagg, N. W. Tanner, R. K. Taplin, M. Thorman, P. Thornewell, P. T. Trent, Y. I. Tserkovnyak, R. Van Berg, R. G. Van de Water, C. J. Virtue, C. E. Waltham, J.-X. Wang, D. L. Wark, N. West, J. B. Wilhelmy, J. F. Wilkerson, J. Wilson, P. Wittich, J. M. Wouters, and M. Yeh

2001-09-24

The Sudbury Neutrino Observatory (SNO) is a water imaging Cherenkov detector. Its usage of 1000 metric tons of D{sub 2}O as target allows the SNO detector to make a solar-model independent test of the neutrino oscillation hypothesis by simultaneously measuring the solar {nu}{sub e} flux and the total flux of all active neutrino species. Solar neutrinos from the decay of {sup 8}B have been detected at SNO by the charged-current (CC) interaction on the deuteron and by the elastic scattering (ES) of electrons. While the CC reaction is sensitive exclusively to {nu}{sub e}, the ES reaction also has a small sensitivity to {nu}{sub {mu}} and {nu}{sub {tau}}. In this paper, recent solar neutrino results from the SNO experiment are presented. It is demonstrated that the solar flux from {sup 8}B decay as measured from the ES reaction rate under the no-oscillation assumption is consistent with the high precision ES measurement by the Super-Kamiokande experiment. The {nu}{sub e} flux deduced from the CC reaction rate in SNO differs from the Super-Kamiokande ES results by 3.3{sigma}. This is evidence for an active neutrino component, in additional to {nu}{sub e}, in the solar neutrino flux. These results also allow the first experimental determination of the total active {sup 8}B neutrino flux from the Sun, and is found to be in good agreement with solar model predictions.

Point process models for localization and interdependence of punctate cellular structures.

PubMed

Li, Ying; Majarian, Timothy D; Naik, Armaghan W; Johnson, Gregory R; Murphy, Robert F

2016-07-01

Accurate representations of cellular organization for multiple eukaryotic cell types are required for creating predictive models of dynamic cellular function. To this end, we have previously developed the CellOrganizer platform, an open source system for generative modeling of cellular components from microscopy images. CellOrganizer models capture the inherent heterogeneity in the spatial distribution, size, and quantity of different components among a cell population. Furthermore, CellOrganizer can generate quantitatively realistic synthetic images that reflect the underlying cell population. A current focus of the project is to model the complex, interdependent nature of organelle localization. We built upon previous work on developing multiple non-parametric models of organelles or structures that show punctate patterns. The previous models described the relationships between the subcellular localization of puncta and the positions of cell and nuclear membranes and microtubules. We extend these models to consider the relationship to the endoplasmic reticulum (ER), and to consider the relationship between the positions of different puncta of the same type. Our results do not suggest that the punctate patterns we examined are dependent on ER position or inter- and intra-class proximity. With these results, we built classifiers to update previous assignments of proteins to one of 11 patterns in three distinct cell lines. Our generative models demonstrate the ability to construct statistically accurate representations of puncta localization from simple cellular markers in distinct cell types, capturing the complex phenomena of cellular structure interaction with little human input. This protocol represents a novel approach to vesicular protein annotation, a field that is often neglected in high-throughput microscopy. These results suggest that spatial point process models provide useful insight with respect to the spatial dependence between cellular structures. © 2016 International Society for Advancement of Cytometry. © 2016 International Society for Advancement of Cytometry.

STED Imaging of Golgi Dynamics with Cer-SiR: A Two-Component, Photostable, High-Density Lipid Probe for Live Cells.

PubMed

Erdmann, Roman S; Toomre, Derek; Schepartz, Alanna

2017-01-01

Long time-lapse super-resolution imaging in live cells requires a labeling strategy that combines a bright, photostable fluorophore with a high-density localization probe. Lipids are ideal high-density localization probes, as they are >100 times more abundant than most membrane-bound proteins and simultaneously demark the boundaries of cellular organelles. Here, we describe Cer-SiR, a two-component, high-density lipid probe that is exceptionally photostable. Cer-SiR is generated in cells via a bioorthogonal reaction of two components: a ceramide lipid tagged with trans-cyclooctene (Cer-TCO) and a reactive, photostable Si-rhodamine dye (SiR-Tz). These components assemble within the Golgi apparatus of live cells to form Cer-SiR. Cer-SiR is benign to cellular function, localizes within the Golgi at a high density, and is sufficiently photostable to enable visualization of Golgi structure and dynamics by 3D confocal or long time-lapse STED microscopy.

Sonographic study of the development of fetal corpus callosum in a Chinese population.

PubMed

Zhang, Hai-chun; Yang, Jie; Chen, Zhong-ping; Ma, Xiao-yan

2009-02-01

The observation of fetal corpus callosum (CC) is important for the prenatal sonographic assessment of fetal central nervous system development. The aim of this study was to investigate the development of normal Chinese fetal CC. CC measurements were performed using high-resolution transabdominal sonography on 622 Chinese fetuses between 16 and 39 weeks' gestation. The correlation between CC size and gestational age was investigated. The fetal CC length increased in a linear fashion during pregnancy. The length of the CC as a function of gestational age was expressed by the following regression equation: length (mm) = -9.567 + 1.495 x gestational age (weeks) (r = 0.932, p < 0.001). Knowledge of normal CC appearance may help identify developmental anomalies and enable accurate prenatal counseling. (c) 2008 Wiley Periodicals, Inc.

The complexity of implementing culture change practices in nursing homes.

PubMed

Sterns, Samantha; Miller, Susan C; Allen, Susan

2010-09-01

The culture change (CC) movement aims to transform the traditional nursing home (NH) that is institutional in design with hierarchical management structure into a homelike environment that empowers residents and frontline staff. This study examines differences in adoption of CC practices according to a NH's self-reported extent of CC implementation and its duration of CC adoption. Furthermore, it examines differences in adoption by whether a CC practice is considered less versus more complex, using complexity theory as the theoretical framework for this classification. Using data from a 2007 Commonwealth-funded study, we analyzed a national sample of 291 US nursing homes that identified as being "for the most part" or "completely" CC facilities for "1 to 3 years" or "3+ years." Also, using a complexity theory framework, we ranked 16 practices commonly associated with CC as low, moderately, or highly complex based on level of agreement needed to actuate the process (number of parties involved) and the certainty of intended outcomes. We then examined the prevalence of CC-associated practices in relation to their complexity and the extent and duration of a NH's CC adoption. We found practices ranked as less complex were implemented more frequently in NHs with both shorter and longer durations of CC adoption. However, more complex CC practices were more prevalent among NHs reporting "complete" adoption for 3+ years versus 1 to 3 years. This was not observed in NHs reporting having CC "for the most part." Less complex practices may be more economical and easier to implement. These early successes may result in sufficient momentum so that more complex change can follow. A nursing home that more completely embraces the culture change movement may be more likely to attempt these complex changes. Copyright 2010 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.

Effectiveness and feasibility of assistant push on improvement of chest compression quality: a crossover study.

PubMed

Choi, Sung Soo; Yun, Seong-Woo; Lee, Byung Kook; Jeung, Kyung Woon; Song, Kyoung Hwan; Lee, Chang-Hee; Park, Jung Soo; Jeong, Ji Yeon; Shin, Sang Yeol

2015-03-01

To improve the quality of chest compression (CC), we developed the assistant-push method, whereby the second rescuer pushes the back of the chest compressor during CC. We investigated the effectiveness and feasibility of assistant push in achieving and maintaining the CC quality. This was a randomized crossover trial in which 41 subjects randomly performed both of standard CC (single-rescuer group) and CC with instructor-driven assistant push (assistant-push group) in different order. Each session of CC was performed for 2 minutes using a manikin. Subjects were also assigned to both roles of chest compressor and assistant and together performed CC with subject-driven assistant push. Depth of CC, compression to recoil ratio, duty cycle, and rate of incomplete recoil were quantified. The mean depth of CC (57.0 [56.0-59.0] vs 55.0 [49.5-57.5], P < .001) was significantly deeper, and the compression force (33.8 [29.3-36.4] vs 23.3 [20.4-25.3], P < .001) was stronger in the assistant-push group. The ratio of compression to recoil, duty cycle, and rate of incomplete chest recoil were comparable between the 2 groups. The CC depth in the single-rescuer group decreased significantly every 30 seconds, whereas in the assistant-push group, it was comparable at 60- and 90-second time points (P = .004). The subject assistant-push group performed CCs at a depth comparable with that of the instructor assistant-push group. The assistant-push method improved the depth of CC and attenuated its decline, eventually helping maintain adequate CC depth over time. Subjects were able to feasibly learn assistant push and performed effectively. Copyright © 2014 Elsevier Inc. All rights reserved.

Cost-utility of collaborative care for major depressive disorder in primary care in the Netherlands.

PubMed

Goorden, Maartje; Huijbregts, Klaas M L; van Marwijk, Harm W J; Beekman, Aartjan T F; van der Feltz-Cornelis, Christina M; Hakkaart-van Roijen, Leona

2015-10-01

Major depression is a great burden on society, as it is associated with high disability/costs. The aim of this study was to evaluate the cost-utility of Collaborative Care (CC) for major depressive disorder compared to Care As Usual (CAU) in a primary health care setting from a societal perspective. A cluster randomized controlled trial was conducted, including 93 patients that were identified by screening (45-CC, 48-CAU). Another 57 patients were identified by the GP (56-CC, 1-CAU). The outcome measures were TiC-P, SF-HQL and EQ-5D, respectively measuring health care utilization, production losses and general health related quality of life at baseline three, six, nine and twelve months. A cost-utility analysis was performed for patients included by screening and a sensitivity analysis was done by also including patients identified by the GP. The average annual total costs was €1131 (95% C.I., €-3158 to €750) lower for CC compared to CAU. The average quality of life years (QALYs) gained was 0.02 (95% C.I., -0.004 to 0.04) higher for CC, so CC was dominant from a societal perspective. Taking a health care perspective, CC was less cost-effective due to higher costs, €1173 (95% C.I., €-216 to €2726), of CC compared to CAU which led to an ICER of 53,717 Euro/QALY. The sensitivity analysis showed dominance of CC. The cost-utility analysis from a societal perspective showed that CC was dominant to CAU. CC may be a promising treatment for depression in the primary care setting. Further research should explore the cost-effectiveness of long-term CC. Netherlands Trial Register ISRCTN15266438. Copyright © 2015 Elsevier Inc. All rights reserved.

Transcriptome mining of immune-related genes in the muricid snail Concholepas concholepas.

PubMed

Détrée, Camille; López-Landavery, Edgar; Gallardo-Escárate, Cristian; Lafarga-De la Cruz, Fabiola

2017-12-01

The population of the Chilean endemic marine gastropod Concholepas concholepas locally called "loco" has dramatically decreased in the past 50 years as a result of intense activity of local fisheries and high environmental variability observed along the Chilean coast, including episodes of hypoxia, changes in sea surface temperature, ocean acidification and diseases. In this study, we set out to explore the molecular basis of C. concholepas to cope with biotic stressors such as exposure to the pathogenic bacterium Vibrio anguillarum. Here, 454pyrosequencing was conducted and 61 transcripts related to the immune response in this muricid species were identified. Among these, the expression of six genes (CcNFκβ, CcIκβ, CcLITAF, CcTLR, CcCas8 and CcCath) involved in the regulation of inflammatory, apoptotic and immune processes upon stimuli, were evaluated during the first 33 h post challenge (hpc). The results showed that CcTLR, CcCas8 and CcCath have an initial response at 4 hpc, evidencing an up-regulation from 4 to 24 hpc. Notably, the response of CcNFKB occurred 2 h later with a statistically significant up-regulation at 6 hpc and 10 hpc. Furthermore, the challenge with V. anguillarum induced a statistically significant down-regulation of CcIKB between 2 and 10 hpc as well as a down-regulation of CcLITAF between 2 and 4 hpc followed in both cases by an up-regulation between 24 and 33 hpc. This work describes the first transcriptomic effort to characterize the immune response of C. concholepas and constitutes a valuable transcriptomic resource for future efforts to develop sustainable aquaculture and conservations tools for this endemic marine snail species. Copyright © 2017 Elsevier Ltd. All rights reserved.

[EFFECTS OF VOLUNTARY INTAKE OF FLUIDS (WATER AND SPORTS DRINK) IN AMATEUR MOUNTAIN RUNNERS].

PubMed

Nebot, Vicente; Drehmer, Eraci; Elvira, Laura; Sales, Sonia; Sanchís, Carlos; Esquius, Laura; Pablos, Ana

2015-11-01

21 K and 1 000 m ascent trail-running races can be dangerous if an appropriate liquid replacement isn't maintained. know trail-runners level of dehydration and assess the differences between ad libitum water (CcA) and sport drink (CcB) hydration after a trail running race. 18 subjects, mean age 31.9 (±2.8) and %MG 10.53 (±2.8), completed CcA or CcB. CcA and CcB effects on Weight (P), Fat Mass (MG), Glucose (GL), Lactate (LT), Systolic (TAS) and Diastolic Arterial Tension (TAD), Heart Rate (PPM) and Tympanic Temperature (Tª) were assessed. All measurements were taken at the start (T1) and the finish (T2) of each race. A Friedman ANOVA test was used to calculate the effect of CcA and CcB on each variable. Differences between race time (TC), % bodyweight loss (%PP) and liquid ingestion (LI) were assessed with a Wilcoxon test. All statistical analysis were conducted with SPSS version 20.0 (IBM, Somers, NY, USA). mean %PP was 2.967 (± 0.969) and 2.883 (± 0.730) for CcA and CcB respectively. No significant differences were found between %PP and LI (p > .05) between races. Significant changes were found in P, %MG, GL, L, TAS and PPM between T1 and T2 in CcA condition. While only significant changes in P and PPM were stabilised between T1 and T2 in CcB condition. neither water or sport drink ingestion avoid trail-runners to reach a dehydrated state. However, dehydration effects seems to be more serious when only water is ingested. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Perspectives of health care professionals on cancer cachexia: results from three global surveys

PubMed Central

Muscaritoli, M.; Rossi Fanelli, F.; Molfino, A.

2016-01-01

Background Cachexia has a high prevalence in cancer patients and negatively impacts prognosis, quality of life (QOL), and tolerance/response to treatments. This study reports the results of three surveys designed to gain insights into cancer cachexia (CC) awareness, understanding, and treatment practices among health care professionals (HCPs). Methods Surveys were conducted globally among HCPs involved in CC management. Topics evaluated included definitions and synonyms of CC, diagnosis and treatment practices, and goals and desired improvements of CC treatment. Results In total, 742 HCPs from 14 different countries participated in the surveys. The majority (97%) of participants were medical oncologists or hematologists. CC was most frequently defined as weight loss (86%) and loss of appetite (46%). The terms loss of weight and decreased appetite (51% and 34%, respectively) were often provided as synonyms of CC. Almost half (46%) of the participants reported diagnosing CC and beginning treatment if a patient experienced a weight loss of 10%. However, 48% of the participants would wait until weight loss was ≥15% to diagnose CC and start treatment. HCPs also reported that 61%–77% of cancer patients do not receive any prescription medication for CC before Stage IV of disease is reached. Ability to promote weight gain was rated as the most important factor for selecting CC treatment. Key goals of treatment included ensuring that patients can cope with the cancer and treatment and have a QOL benefit. HCPs expressed desire for treatments with a more CC-specific mode of action and therapies that enhance QOL. Conclusions These surveys underscore the need for increased awareness among HCPs of CC and its management. PMID:28007753

Meta-analysis of Clear Cell Renal Cell Carcinoma Gene Expression Defines a Variant Subgroup and Identifies Gender Influences on Tumor Biology

PubMed Central

Brannon, A. Rose; Haake, Scott M.; Hacker, Kathryn E.; Pruthi, Raj S.; Wallen, Eric M.; Nielsen, Matthew E.; Rathmell, W. Kimryn

2011-01-01

Background Clear cell renal cell carcinoma (ccRCC) displays molecular and histologic heterogeneity. Previously described subsets of this disease, ccA and ccB, were defined based on multigene expression profiles, but it is unclear whether these subgroupings reflect the full spectrum of disease or how these molecular subtypes relate to histologic descriptions or gender. Objective Determine whether additional subtypes of ccRCC exist and whether these subtypes are related to von Hippel-Lindau (VHL) inactivation, hypoxia-inducible factor (HIF) 1 and 2 expression, tumor histology, or gender. Design, setting, and participants Six large, publicly available ccRCC gene expression databases were identified that cumulatively provided data for 480 tumors for meta-analysis via meta-array compilation. Measurements Unsupervised consensus clustering was performed on the meta-arrays. Tumors were examined for the relationship of multigene-defined consensus subtypes and expression signatures of VHL mutation and HIF status, tumor histology, and gender. Results and limitations Two dominant subsets of ccRCC were observed. However, a minor third cluster was revealed that correlated strongly with a wild type (WT) VHL expression profile and indications of variant histologies. When variant histologies were removed, ccA tumors naturally divided by gender. This technique is limited by the potential for persistent batch effect, tumor sampling bias, and restrictions of annotated information. Conclusions The ccA and ccB subsets of ccRCC are robust in meta-analysis among histologically conventional ccRCC tumors. A third group of tumors was identified that may represent a new variant of ccRCC. Within definitively clear cell tumors, gender may delineate tumors in such a way that it could have implications regarding current treatments and future drug development. PMID:22030119

Taming the Sphinx: Mechanisms of Cellular Sphingolipid Homeostasis

PubMed Central

Olson, D. K.; Fröhlich, F.; Farese, R; Walther, T. C.

2016-01-01

Sphingolipids are important structural membrane components of eukaryotic cells, and potent signaling molecules. As such, their levels must be maintained to optimize cellular functions in different cellular membranes. Here, we review the current knowledge of homeostatic sphingolipid regulation. We describe recent studies in Saccharomyces cerevisiae that have provided insights into how cells sense changes in sphingolipid levels in the plasma membrane and acutely regulate sphingolipid biosynthesis by altering signaling pathways. We also discuss how cellular trafficking has emerged as an important determinant of sphingolipid homeostasis. Finally, we highlight areas where work is still needed to elucidate the mechanisms of sphingolipid regulation and the physiological functions of such regulatory networks, especially in mammalian cells. PMID:26747648

Chitosan based hydrogels: characteristics and pharmaceutical applications

PubMed Central

Ahmadi, F.; Oveisi, Z.; Samani, S. Mohammadi; Amoozgar, Z.

2015-01-01

Hydrogel scaffolds serve as semi synthetic or synthetic extra cellular matrix to provide an amenable environment for cellular adherence and cellular remodeling in three dimensional structures mimicking that of natural cellular environment. Additionally, hydrogels have the capacity to carry small molecule drugs and/or proteins, growth factors and other necessary components for cell growth and differentiation. In the context of drug delivery, hydrogels can be utilized to localize drugs, increase drugs concentration at the site of action and consequently reduce off-targeted side effects. The current review aims to describe and classify hydrogels and their methods of production. The main highlight is chitosan-based hydrogels as biocompatible and medically relevant hydrogels for drug delivery. PMID:26430453

Altered Circulating Inflammatory Cytokines Are Associated with Anovulatory Polycystic Ovary Syndrome (PCOS) Women Resistant to Clomiphene Citrate Treatment.

PubMed

Wang, LianLian; Qi, HongBo; Baker, Philip N; Zhen, QianNa; Zeng, Qing; Shi, Rui; Tong, Chao; Ge, Qian

2017-03-01

BACKGROUND Polycystic ovary syndrome (PCOS) is a common gynecological disease characterized by chronic oligoanovulation, clinical/biochemical hyperandrogenism, polycystic ovaries, and insulin resistance. Accumulating evidence has shown that PCOS-related ovarian dysfunction is the main cause of anovulatory infertility. Clomiphene citrate (CC) is the first-line therapy for PCOS patients; however, approximately 15-40% PCOS patients are resistant to CC treatment. It has been demonstrated that PCOS is a chronic pro-inflammatory state, as some pro-inflammatory cytokines were elevated in the peripheral circulation of PCOS patients, but whether altered inflammatory cytokines expression in PCOS patients is associated with blunted response to CC remains unknown. MATERIAL AND METHODS We recruited 44 CC-resistant PCOS patients, along with 55 age and body mass index (BMI)-matched CC-sensitive PCOS patients. Ovulation was induced by administrating 50-100 mg/day CC on days 5 to 9 of each menstrual cycle. The cytokine profiles were detected by cytokine antibody microarrays and further validated by ELISAs. RESULTS CC-resistant patients had higher levels of high-sensitivity C-reactive protein (hsCRP) than the CC-sensitive individuals. A growth factor, angiopoietin-2, was significantly reduced [1.64 (0.93-1.95) vs. 1.08 (0.85-1.34), p<0.05], while a chemokine CXCL-16 was significantly increased (9.10±2.35 vs. 10.41±2.82, p<0.05) in CC-resistant patients compared to the CC-sensitive subjects. CXCL-16 was positively correlated with hsCRP (r=0.33, p<0.01). Logistic regression analysis showed that angiopoietin-2 and CXCL-16 are associated with CC resistance. CONCLUSIONS Circulating cytokines are disturbed in CC-resistant PCOS patients. Altered angiopoietin-2 and CXCL-16 levels might compromise the responsiveness of the ovary to CC through up-regulating angiogenesis and inflammation.

Altered Circulating Inflammatory Cytokines Are Associated with Anovulatory Polycystic Ovary Syndrome (PCOS) Women Resistant to Clomiphene Citrate Treatment

PubMed Central

Wang, LianLian; Qi, HongBo; Baker, Philip N.; Zhen, QianNa; Zeng, Qing; Shi, Rui; Tong, Chao; Ge, Qian

2017-01-01

Background Polycystic ovary syndrome (PCOS) is a common gynecological disease characterized by chronic oligoanovulation, clinical/biochemical hyperandrogenism, polycystic ovaries, and insulin resistance. Accumulating evidence has shown that PCOS-related ovarian dysfunction is the main cause of anovulatory infertility. Clomiphene citrate (CC) is the first-line therapy for PCOS patients; however, approximately 15–40% PCOS patients are resistant to CC treatment. It has been demonstrated that PCOS is a chronic pro-inflammatory state, as some pro-inflammatory cytokines were elevated in the peripheral circulation of PCOS patients, but whether altered inflammatory cytokines expression in PCOS patients is associated with blunted response to CC remains unknown. Material/Methods We recruited 44 CC-resistant PCOS patients, along with 55 age and body mass index (BMI)-matched CC-sensitive PCOS patients. Ovulation was induced by administrating 50–100 mg/day CC on days 5 to 9 of each menstrual cycle. The cytokine profiles were detected by cytokine antibody microarrays and further validated by ELISAs. Results CC-resistant patients had higher levels of high-sensitivity C-reactive protein (hsCRP) than the CC-sensitive individuals. A growth factor, angiopoietin-2, was significantly reduced [1.64 (0.93–1.95) vs. 1.08 (0.85–1.34), p<0.05], while a chemokine CXCL-16 was significantly increased (9.10±2.35 vs. 10.41±2.82, p<0.05) in CC-resistant patients compared to the CC-sensitive subjects. CXCL-16 was positively correlated with hsCRP (r=0.33, p<0.01). Logistic regression analysis showed that angiopoietin-2 and CXCL-16 are associated with CC resistance. Conclusions Circulating cytokines are disturbed in CC-resistant PCOS patients. Altered angiopoietin-2 and CXCL-16 levels might compromise the responsiveness of the ovary to CC through up-regulating angiogenesis and inflammation. PMID:28246376

[Optimal Ovulation Induction in Polycystic Ovary Syndrome Resistant to Clomiphene Citrate or Letrozole.

PubMed

Chen, Ying; Zhang, Dan

2016-11-01

To investigate the optimal ovulation induction with the combination of combining letrozole(LE),clomiphene citrate (CC),and human menopausal gonadotropin (HMG) in polycystic ovary syndrome(PCOS) patients resistant to CC or LE. Two hundreds nine PCOS patients (209 cycles) resistant to CC or LE were randomly divided into three groups: CC+HMG group (59 cycles),LE+HMG group (72 cycles) and LE+CC group (78 cycles).The patients in LE+CC group unable to form the dominant follicle after 54 cycles were enrolled into LE+CC+HMG group.Maximum follicle diameter (MFD),endometrial thickness,number of follicles (diameter>1.4 cm),the level of serum estradiol (E2) were measured on the day of HMG administration.Also these results were observed and compared including the duration of treatment,dosage of HMG,number of ovulated follicles,clinical pregnancy rate,biochemical pregnancy rate,early abortion rate,twinning rate,and ectopic pregnancy rate. The ovulation rate was significantly lower in LE+CC group (30.77%) ( P <0.05),but similar in the other three groups.The number of >1.4 cm follicles and ovulated follicles,ovulation duration and E2 concentration in LE+CC group were also at a lower level ( P <0.05).The patients in LE+CC+HMG group showed higher E2 level and more HMG consumption ( P <0.05).There was no statistical difference in endometrial thickness,MFD,clinical pregnancy rate,biochemical pregnancy rate,early abortion rate and twinning rate among these groups ( P >0.05).No severe ovarian hyperstimulation syndrome (OHSS) or luteinized unruptured follicle (LUF) occurred. Combintion of LE with CC could achieve 1/3 ovulation induction in PCOS resistant to CC or LE alone.When both combined with HMG,the induction of ovulation could be significantly higher than LE+HMG and CC+HMG,while the risk of multiple pregnancy and OHSS was reduced.

Prognostication of patients with clear cell renal cell carcinomas based on quantification of DNA methylation levels of CpG island methylator phenotype marker genes.

PubMed

Tian, Ying; Arai, Eri; Gotoh, Masahiro; Komiyama, Motokiyo; Fujimoto, Hiroyuki; Kanai, Yae

2014-10-20

The CpG island methylator phenotype (CIMP) of clear cell renal cell carcinomas (ccRCCs) is characterized by accumulation of DNA methylation at CpG islands and poorer patient outcome. The aim of this study was to establish criteria for prognostication of patients with ccRCCs using the ccRCC-specific CIMP marker genes. DNA methylation levels at 299 CpG sites in the 14 CIMP marker genes were evaluated quantitatively in tissue specimens of 88 CIMP-negative and 14 CIMP-positive ccRCCs in a learning cohort using the MassARRAY system. An additional 100 ccRCCs were also analyzed as a validation cohort. Receiver operating characteristic curve analysis showed that area under the curve values for the 23 CpG units including the 32 CpG sites in the 7 CIMP-marker genes, i.e. FAM150A, ZNF540, ZNF671, ZNF154, PRAC, TRH and SLC13A5, for discrimination of CIMP-positive from CIMP-negative ccRCCs were larger than 0.95. Criteria combining the 23 CpG units discriminated CIMP-positive from CIMP-negative ccRCCs with 100% sensitivity and specificity in the learning cohort. Cancer-free and overall survival rates of patients with CIMP-positive ccRCCs diagnosed using the criteria combining the 23 CpG units in a validation cohort were significantly lower than those of patients with CIMP-negative ccRCCs (P = 1.41 × 10-5 and 2.43 × 10-13, respectively). Patients with CIMP-positive ccRCCs in the validation cohort had a higher likelihood of disease-related death (hazard ratio, 75.8; 95% confidence interval, 7.81 to 735; P = 1.89 × 10-4) than those with CIMP-negative ccRCCs. The established criteria are able to reproducibly diagnose CIMP-positive ccRCCs and may be useful for personalized medicine for patients with ccRCCs.

A non-invasive tool for detecting cervical cancer odor by trained scent dogs.

PubMed

Guerrero-Flores, Héctor; Apresa-García, Teresa; Garay-Villar, Ónix; Sánchez-Pérez, Alejandro; Flores-Villegas, David; Bandera-Calderón, Artfy; García-Palacios, Raúl; Rojas-Sánchez, Teresita; Romero-Morelos, Pablo; Sánchez-Albor, Verónica; Mata, Osvaldo; Arana-Conejo, Víctor; Badillo-Romero, Jesús; Taniguchi, Keiko; Marrero-Rodríguez, Daniel; Mendoza-Rodríguez, Mónica; Rodríguez-Esquivel, Miriam; Huerta-Padilla, Víctor; Martínez-Castillo, Andrea; Hernández-Gallardo, Irma; López-Romero, Ricardo; Bandala, Cindy; Rosales-Guevara, Juan; Salcedo, Mauricio

2017-01-26

Cervical Cancer (CC) has become a public health concern of alarming proportions in many developing countries such as Mexico, particularly in low income sectors and marginalized regions. As such, an early detection is a key medical factor in improving not only their population's quality of life but also its life expectancy. Interestingly, there has been an increase in the number of reports describing successful attempts at detecting cancer cells in human tissues or fluids using trained (sniffer) dogs. The great odor detection threshold exhibited by dogs is not unheard of. However, this represented a potential opportunity to develop an affordable, accessible, and non-invasive method for detection of CC. Using clicker training, a male beagle was trained to recognize CC odor. During training, fresh CC biopsies were used as a reference point. Other samples used included cervical smears on glass slides and medical surgical bandages used as intimate sanitary pads by CC patients. A double-blind procedure was exercised when testing the beagle's ability to discriminate CC from control samples. The beagle was proven able to detect CC-specific volatile organic compounds (VOC) contained in both fresh cervical smear samples and adsorbent material samples. Beagle's success rate at detecting and discriminating CC and non-CC odors, as indicated by specificity and sensitivity values recorded during the experiment, stood at an overall high (>90%). CC-related VOC in adsorbent materials were detectable after only eight hours of use by CC patients. Present data suggests different applications for VOC from the uterine cervix to be used in the detection and diagnosis of CC. Furthermore, data supports the use of trained dogs as a viable, affordable, non-invasive and, therefore, highly relevant alternative method for detection of CC lesions. Additional benefits of this method include its quick turnaround time and ease of use while remaining highly accurate and robust.

miR-19a correlates with poor prognosis of clear cell renal cell carcinoma patients via promoting cell proliferation and suppressing PTEN/SMAD4 expression.

PubMed

Ma, Qiang; Peng, Zhiqiang; Wang, Lei; Li, Yanming; Wang, Kaizhen; Zheng, Junfang; Liang, Zhiyong; Liu, Tonghua

2016-12-01

MicroRNAs (miRNAs) were reported to be involved in the development of clear cell renal cell carcinoma (ccRCC). However, the study on miRNAs in ccRCC is far from complete. The present study identified miRNAs which could act as potential novel prognostic markers for ccRCC, and analyzed its possible mechanism. We found that miR-19a correlated with poor prognosis of ccRCC patients via promoting cell proliferation and suppressing PTEN/SMAD4 expression. Both the microarray screening result and TCGA KIRC dataset analysis showed that miR-19a was significantly upregulated in ccRCC tissues, and further analysis of TCGA data revealed that the upregulated level of miR-19a was strongly associated with advanced T stage and poor prognosis of ccRCC patients. Consistent with clinical observations, miR-19a overexpression significantly promoted ccRCC cell proliferation in vitro. To further explore the mechanism by which miR-19a correlated with cell proliferation and poor prognosis of ccRCC, we performed gene set enrichment analysis (GSEA) for target genes of miR-19a in ccRCC patients. Result indicated that the key target genes of miR-19a included SMAD4 and PTEN. In ccRCC tissues, expression levels of SMAD4 and PTEN were negatively correlated with expression level of miR-19a, revealing that miR-19a suppressed the expression of SMAD4 and PTEN in ccRCC patients. miR-19a overexpression significantly suppressed the expression of SMAD4 and PTEN in vitro, further verifying that SMAD4 and PTEN were the target genes of miR-19a in ccRCC cells. Our results elucidated the tumor promoting role of miR-19a and established miR-19a as a potential novel prognostic marker for ccRCC.

Effects of water fluoride exposure at crown completion and maturation on caries of permanent first molars.

PubMed

Singh, K A; Spencer, A J; Brennan, D S

2007-01-01

Pre-eruptive fluoride exposure has been shown to be important for caries prevention. This paper aimed to determine the relative effects of water fluoride exposure during crown completion (CC) and maturation on caries experience in first permanent molars. Parental questionnaires covering residential history were linked to oral examinations of 19,885 6- to 15-year-old Australian children conducted in 1992 by the School Dental Services of South Australia and Queensland. The percentage of lifetime exposed to optimally fluoridated water at CC, maturation (MAT) and post-eruption (POST) was calculated. Combined exposure variables describing different levels of CC, maturation and post-eruption were created using a threshold exposure of 50%. Compared to the reference of CC <50%/MAT <50%/POST <50%, the categories CC > or =50%/MAT <50%/POST > or =50% [rate ratio (RR) 0.52], CC > or =50%/MAT > or =50%/POST <50% (RR 0.61) and CC > or =50%/MAT > or =50%/POST > or =50% (RR 0.67) had the strongest caries-preventive effect, followed by CC > or =50%/MAT <50%/POST <50% (RR = 0.79) and CC <50%/MAT > or =50%/POST > or =50% (RR = 0.81) in negative binomial regression models (p < 0.05). The categories CC <50%/MAT > or =50%/POST <50% (RR = 0.85) and CC <50%/MAT <50%/POST > or =50% (RR = 0.84) had weaker, non-significant caries-preventive effects. In conclusion a high exposure at CC was important for caries prevention irrespective of the effect of exposure at maturation and post-eruption. The strongest caries-preventive effect was produced by a high exposure at CC supplemented by a high exposure at maturation and/or post-eruption, but the latter two phases could not produce a significant caries-preventive effect on their own. Since most of the caries occurred on pit and fissure surfaces, the findings relate to this class of lesion.

Comparison of common components analysis with principal components analysis and independent components analysis: Application to SPME-GC-MS volatolomic signatures.

PubMed

Bouhlel, Jihéne; Jouan-Rimbaud Bouveresse, Delphine; Abouelkaram, Said; Baéza, Elisabeth; Jondreville, Catherine; Travel, Angélique; Ratel, Jérémy; Engel, Erwan; Rutledge, Douglas N

2018-02-01

The aim of this work is to compare a novel exploratory chemometrics method, Common Components Analysis (CCA), with Principal Components Analysis (PCA) and Independent Components Analysis (ICA). CCA consists in adapting the multi-block statistical method known as Common Components and Specific Weights Analysis (CCSWA or ComDim) by applying it to a single data matrix, with one variable per block. As an application, the three methods were applied to SPME-GC-MS volatolomic signatures of livers in an attempt to reveal volatile organic compounds (VOCs) markers of chicken exposure to different types of micropollutants. An application of CCA to the initial SPME-GC-MS data revealed a drift in the sample Scores along CC2, as a function of injection order, probably resulting from time-related evolution in the instrument. This drift was eliminated by orthogonalization of the data set with respect to CC2, and the resulting data are used as the orthogonalized data input into each of the three methods. Since the first step in CCA is to norm-scale all the variables, preliminary data scaling has no effect on the results, so that CCA was applied only to orthogonalized SPME-GC-MS data, while, PCA and ICA were applied to the "orthogonalized", "orthogonalized and Pareto-scaled", and "orthogonalized and autoscaled" data. The comparison showed that PCA results were highly dependent on the scaling of variables, contrary to ICA where the data scaling did not have a strong influence. Nevertheless, for both PCA and ICA the clearest separations of exposed groups were obtained after autoscaling of variables. The main part of this work was to compare the CCA results using the orthogonalized data with those obtained with PCA and ICA applied to orthogonalized and autoscaled variables. The clearest separations of exposed chicken groups were obtained by CCA. CCA Loadings also clearly identified the variables contributing most to the Common Components giving separations. The PCA Loadings did not highlight the most influencing variables for each separation, whereas the ICA Loadings highlighted the same variables as did CCA. This study shows the potential of CCA for the extraction of pertinent information from a data matrix, using a procedure based on an original optimisation criterion, to produce results that are complementary, and in some cases may be superior, to those of PCA and ICA. Copyright © 2017 Elsevier B.V. All rights reserved.

Durability Indicators Comparison for SCC and CC in Tropical Coastal Environments.

PubMed

Calado, Carlos; Camões, Aires; Monteiro, Eliana; Helene, Paulo; Barkokébas, Béda

2015-03-27

Self-compacting concrete (SCC) demands more studies of durability at higher temperatures when subjected to more aggressive environments in comparison to the conventional vibrated concrete (CC). This work aims at presenting results of durability indicators of SCC and CC, having the same water/binder relations and constituents. The applied methodologies were electrical resistivity, diffusion of chloride ions and accelerated carbonation experiments, among others, such as microstructure study, scanning electron microscope and microtomography experiments. The tests were performed in a research laboratory and at a construction site of the Pernambuco Arena. The obtained results shows that the SCC presents an average electrical resistivity 11.4% higher than CC; the average chloride ions diffusion was 63.3% of the CC; the average accelerated carbonation penetration was 45.8% of the CC; and the average open porosity was 55.6% of the CC. As the results demonstrated, the SCC can be more durable than CC, which contributes to elucidate the aspects related to its durability and consequent prolonged life cycle.

Durability Indicators Comparison for SCC and CC in Tropical Coastal Environments

PubMed Central

Calado, Carlos; Camões, Aires; Monteiro, Eliana; Helene, Paulo; Barkokébas, Béda

2015-01-01

Self-compacting concrete (SCC) demands more studies of durability at higher temperatures when subjected to more aggressive environments in comparison to the conventional vibrated concrete (CC). This work aims at presenting results of durability indicators of SCC and CC, having the same water/binder relations and constituents. The applied methodologies were electrical resistivity, diffusion of chloride ions and accelerated carbonation experiments, among others, such as microstructure study, scanning electron microscope and microtomography experiments. The tests were performed in a research laboratory and at a construction site of the Pernambuco Arena. The obtained results shows that the SCC presents an average electrical resistivity 11.4% higher than CC; the average chloride ions diffusion was 63.3% of the CC; the average accelerated carbonation penetration was 45.8% of the CC; and the average open porosity was 55.6% of the CC. As the results demonstrated, the SCC can be more durable than CC, which contributes to elucidate the aspects related to its durability and consequent prolonged life cycle. PMID:28788012

Serum calcium, phosphorus and magnesium responses to massive dosing of cholecalciferol (CC) and 25-OH-CC in young and aged ewes.

PubMed

Thomas, B B; Boling, J A; Muir, W M

1981-01-01

Twenty-four ewes were divided into two age groups (one-year-old and nine-year-old) and used to determine the influence of cholecalciferol (CC) and 25-OH-CC on serum concentrations of Ca, P, and Mg with time post-injection. The ewes were maintained in slatted-floor pens and fed 800 g per head daily of a diet which analyzed 0.38% calcium, 0.31% phosphorus, and 0.14% magnesium. This diet was fed throughout the 21-day trial. The ewes were injected on days 0 and 7 as follows: (control) 5 ml ethanol; (CC) 50 mg CC in 5 ml ethanol; and (25-OH-CC) 25 mg 25-OH-CC in ethanol. Blood samples were pre-injection (day 0) and on days 1, 2, 3, 5, 7, 9, 12, 17 and 21 of the trial. Serum Ca averaged 10.81, 11.06 and 11.25 mg/100 ml for the one-year-old ewes and 10.51, 11.06 and 11.54 mg/100 ml for the nine-year-olds across sampling times in groups A to C, respectively. Serum P across sampling times averaged 6.58, 7.80 and 9.51 mg/100 ml in one-year-old ewes and were different (P less than .05) from each other. Serum P averaged 7.06, 8.56 and 8.59 mg/100 ml for the nine-year-old ewes. Serum Mg values were 2.51, 2.32 and 2.19 mg/100 ml for the one-year-old and 2.38, 2.14 and 2.00 mg/100 ml for the nine-year-old ewes across all sampling times for control, CC and 25-OH-CC groups, respectively. Serum Mg in one-year-old ewes was lower (P less than .05) in both CC and 25-OH-CC injected ewes than controls, and was lowest (P less than .05) for 25-OH-CC when compared with the control in nine-year-old ewes. External symptoms of hypervitaminosis (reduced feed intake and leg abnormalities) were apparent after the second injection with 25-OH-CC, and were most pronounced in the aged ewes.

Impact of dosimetric and clinical parameters on clinical side effects in cervix cancer patients treated with 3D pulse-dose-rate intracavitary brachytherapy.

PubMed

Levitchi, Mihai; Charra-Brunaud, Claire; Quetin, Philippe; Haie-Meder, Christine; Kerr, Christine; Castelain, Bernard; Delannes, Martine; Thomas, Laurence; Desandes, Emmanuel; Peiffert, Didier

2012-06-01

To assess the association between dosimetric/clinical parameters and gastrointestinal/urinary grade 2-4 side effects in cervix cancer patients treated with 3D pulse dose rate brachytherapy. Three hundred and fifty-two patients received brachytherapy associated with external-beam radiotherapy (EBRT) for 266 of them; 236 patients underwent surgery. The doses for the most exposed 2, and 0.1 cm(3) (D(2cc) and D(0.1cc)) volumes of the rectum and bladder as well as bladder ICRU point dose (D(ICRU)) were converted into isoeffective doses in 2-Gy fractions. The clinical parameters analyzed were: age, smoking habits, arteritis, diabetes, previous pelvic surgery, FIGO stage, nodal status, pathology, pelvic surgery, EBRT and chemotherapy. Side effects were prospectively assessed using the CTCAEv3.0. Cutoff dose levels were defined separately for patients treated with EBRT and brachytherapy (Group 1) and with preoperative brachytherapy (Group 2). The median follow-up was 23.4months. In Group 1 a significant predictive value of rectum D(0.1cc) and D(2cc), bladder D(0.1cc) and D(ICRU) for gastrointestinal and urinary toxicity was found using as cutoff 83, 68, 109 and 68Gy(α)(/)(β)(3). In Group 2 a significant predictive value of bladder D(0.1cc), D(2cc) and D(ICRU) for urinary toxicity was found using as cutoff 141, 91 and 67Gy(α)(/)(β)(3), but not for the rectum D(0.1cc) and D(2cc); smoking had a significant predictive value on urinary toxicity. For patients treated with brachytherapy and EBRT, rectum D(0.1cc) and D(2cc) and bladder D(0.1cc) and D(ICRU) had a predictive value for toxicity. For patients treated with preoperative brachytherapy, bladder D(0.1cc), D(2cc) and D(ICRU) and smoking had a predictive value for urinary toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Microfluidic systems and methods of transport and lysis of cells and analysis of cell lysate

DOEpatents

Culbertson, Christopher T.; Jacobson, Stephen C.; McClain, Maxine A.; Ramsey, J. Michael

2004-08-31

Microfluidic systems and methods are disclosed which are adapted to transport and lyse cellular components of a test sample for analysis. The disclosed microfluidic systems and methods, which employ an electric field to rupture the cell membrane, cause unusually rapid lysis, thereby minimizing continued cellular activity and resulting in greater accuracy of analysis of cell processes.

Microfluidic systems and methods for transport and lysis of cells and analysis of cell lysate

DOEpatents

Culbertson, Christopher T [Oak Ridge, TN; Jacobson, Stephen C [Knoxville, TN; McClain, Maxine A [Knoxville, TN; Ramsey, J Michael [Knoxville, TN

2008-09-02

Microfluidic systems and methods are disclosed which are adapted to transport and lyse cellular components of a test sample for analysis. The disclosed microfluidic systems and methods, which employ an electric field to rupture the cell membrane, cause unusually rapid lysis, thereby minimizing continued cellular activity and resulting in greater accuracy of analysis of cell processes.

In search of mitochondrial mechanisms: interfield excursions between cell biology and biochemistry.

PubMed

Bechtel, William; Abrahamsen, Adele

2007-01-01

Developing models of biological mechanisms, such as those involved in respiration in cells, often requires collaborative effort drawing upon techniques developed and information generated in different disciplines. Biochemists in the early decades of the 20th century uncovered all but the most elusive chemical operations involved in cellular respiration, but were unable to align the reaction pathways with particular structures in the cell. During the period 1940-1965 cell biology was emerging as a new discipline and made distinctive contributions to understanding the role of the mitochondrion and its component parts in cellular respiration. In particular, by developing techniques for localizing enzymes or enzyme systems in specific cellular components, cell biologists provided crucial information about the organized structures in which the biochemical reactions occurred. Although the idea that biochemical operations are intimately related to and depend on cell structures was at odds with the then-dominant emphasis on systems of soluble enzymes in biochemistry, a reconceptualization of energetic processes in the 1960s and 1970s made it clear why cell structure was critical to the biochemical account. This paper examines how numerous excursions between biochemistry and cell biology contributed a new understanding of the mechanism of cellular respiration.

Raman microscopy of bladder cancer cells expressing green fluorescent protein

NASA Astrophysics Data System (ADS)

Mandair, Gurjit S.; Han, Amy L.; Keller, Evan T.; Morris, Michael D.

2016-11-01

Gene engineering is a commonly used tool in cellular biology to determine changes in function or expression of downstream targets. However, the impact of genetic modulation on biochemical effects is less frequently evaluated. The aim of this study is to use Raman microscopy to assess the biochemical effects of gene silencing on T24 and UMUC-13 bladder cancer cell lines. Cellular biochemical information related to nucleic acid and lipogenic components was obtained from deconvolved Raman spectra. We show that the green fluorescence protein (GFP), the chromophore that served as a fluorescent reporter for gene silencing, could also be detected by Raman microscopy. Only the gene-silenced UMUC-13 cell lines exhibited low-to-moderate GFP fluorescence as determined by fluorescence imaging and Raman spectroscopic studies. Moreover, we show that gene silencing and cell phenotype had a greater effect on nucleic acid and lipogenic components with minimal interference from GFP expression. Gene silencing was also found to perturb cellular protein secondary structure in which the amount of disorderd protein increased at the expense of more ordered protein. Overall, our study identified the spectral signature for cellular GFP expression and elucidated the effects of gene silencing on cancer cell biochemistry and protein secondary structure.

Cellular Plasticity-Targeted Therapy in Head and Neck Cancers.

PubMed

Shang, W; Zhang, Q; Huang, Y; Shanti, R; Alawi, F; Le, A; Jiang, C

2018-06-01

Head and neck cancer is one of the most frequent human malignancies worldwide, with a high rate of recurrence and metastasis. Head and neck squamous cell carcinoma (HNSCC) is cellularly and molecularly heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like properties, called cancer stem cells (CSCs). Epithelial-mesenchymal transition, gene mutation, and epigenetic modification are associated with the formation of cellular plasticity of tumor cells in HNSCC, contributing to the acquisition of invasive, recurrent, and metastatic properties and therapeutic resistance. Tumor microenvironment (TME) plays a supportive role in the initiation, progression, and metastasis of head and neck cancer. Stromal fibroblasts, vasculature, immune cells, cytokines, and hypoxia constitute the main components of TME in HNSCC, which contributes not only to the acquisition of CSC properties but also to the recurrence and therapeutic resistance of the malignancies. In this review, we discuss the potential mechanisms underlying the development of cellular plasticity, especially the emergence of CSCs, in HNSCC. We also highlight recent studies implicating the complex interplays among TME components, plastic CSCs, tumorigenesis, recurrence, and therapeutic resistance of HNSCC. Finally, we summarize the treatment modalities of HNSCC and reinforce the novel concept of therapeutic targeting CSCs in HNSCC.

Enhancing the cellular uptake of siRNA duplexes following noncovalent packaging with protein transduction domain peptides.

PubMed

Meade, Bryan R; Dowdy, Steven F

2008-03-01

The major limitation in utilizing information rich macromolecules for basic science and therapeutic applications is the inability of these large molecules to readily diffuse across the cellular membrane. While this restriction represents an efficient defense system against cellular penetration of unwanted foreign molecules and thus a crucial component of cell survival, overcoming this cellular characteristic for the intracellular delivery of macromolecules has been the focus of a large number of research groups worldwide. Recently, with the discovery of RNA interference, many of these groups have redirected their attention and have applied previously characterized cell delivery methodologies to synthetic short interfering RNA duplexes (siRNA). Protein transduction domain and cell penetrating peptides have been shown to enhance the delivery of multiple types of macromolecular cargo including peptides, proteins and antisense oligonucleotides and are now being utilized to enhance the cellular uptake of siRNA molecules. The dense cationic charge of these peptides that is critical for interaction with cell membrane components prior to internalization has also been shown to readily package siRNA molecules into stable nanoparticles that are capable of traversing the cell membrane. This review discusses the recent advances in noncovalent packaging of siRNA molecules with cationic peptides and the potential for the resulting complexes to successfully induce RNA interference within both in vitro and in vivo settings.

Targeting Protein Quality Control Mechanisms by Natural Products to Promote Healthy Ageing.

PubMed

Wedel, Sophia; Manola, Maria; Cavinato, Maria; Trougakos, Ioannis P; Jansen-Dürr, Pidder

2018-05-19

Organismal ageing is associated with increased chance of morbidity or mortality and it is driven by diverse molecular pathways that are affected by both environmental and genetic factors. The progression of ageing correlates with the gradual accumulation of stressors and damaged biomolecules due to the time-dependent decline of stress resistance and functional capacity, which eventually compromise cellular homeodynamics. As protein machines carry out the majority of cellular functions, proteome quality control is critical for cellular functionality and is carried out through the curating activity of the proteostasis network (PN). Key components of the PN are the two main degradation machineries, namely the ubiquitin-proteasome and autophagy-lysosome pathways along with several stress-responsive pathways, such as that of nuclear factor erythroid 2-related factor 2 (Nrf2), which mobilises cytoprotective genomic responses against oxidative and/or xenobiotic damage. Reportedly, genetic or dietary interventions that activate components of the PN delay ageing in evolutionarily diverse organisms. Natural products (extracts or pure compounds) represent an extraordinary inventory of highly diverse structural scaffolds that offer promising activities towards meeting the challenge of increasing healthspan and/or delaying ageing (e.g., spermidine, quercetin or sulforaphane). Herein, we review those natural compounds that have been found to activate proteostatic and/or anti-stress cellular responses and hence have the potential to delay cellular senescence and/or in vivo ageing.

Beach Changes at Long Beach Island, New Jersey, 1962-73.

DTIC Science & Technology

1980-10-01

c *Ic-.CcI c I -- 4c -’ Astor ~ ~ tP C c N .c C J . 5 -C. -. 1. -- --- N c[ 0. a . ,;u: I -C ,z , I c c c c c c c c c T c c c I c I c c I -I Or ; t...c ’I C CENcc c00’’N cC ,CCl a.z & .. . a t. 4nN 2 a occq~t ,cacc 1 9 44 ;CC0- c or kedcg a I t reI 21152 t I CC CC CCC CC C C~ CCCf I Lc W 9C C~~ I

Influence of the dialyzer membrane material on sodium transport in hemodialysis.

PubMed

Lopot, F; Kotyk, P; Bláha, J; Válek, A

1995-11-01

Traditionally Gibbs-Donnan coefficients based on the mean charge of plasma proteins are used as the only correction factor in equations describing sodium transport across the dialyzer membrane. This ignores the possible impact of the membrane material. Correction coefficients (CC) of the whole dialyzer were measured during in vivo dialysis as a quotient of dialysate to plasma sodium in an equilibrated state for different membrane materials used in commercially available dialyzers. Their mean value and correlation with total plasma protein content (TPP) were evaluated. CC for the six materials evaluated differed both in the intercept and slope of the regression line CC versus TPP: Cuprophan 1: CC = 1.0253 - 0.00017 x TPP; Hemophan 1: CC = 1.119 - 0.00175 x TPP; Hemophan 2: CC = 1.095 - 0.00111 x TPP; PMMA: CC = 1.0353 - 0.00044 x TPP; SCE:CC = 1.114 - 0.00145 x TPP; and Cuprophan 1:CC = 1.0562 - 0.00065 x TPP. The observed differences are attributed to the different charge densities of the membrane materials and suggest that for a precise description of sodium transport, the role of the membrane material needs to be considered.