HIV-1 virion fusion assay: uncoating not required and no effect of Nef on fusion

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

Cavrois, Marielle; Neidleman, Jason; Yonemoto, Wes

2004-10-15

We recently described a sensitive and specific assay that detects the fusion of HIV-1 virions to a broad range of target cells, including primary CD4 cells. This assay involves the use of virions containing {beta}-lactamase-Vpr (BlaM-Vpr) and the loading of target cells with CCF2, a fluorogenic substrate of {beta}-lactamase. Since Vpr strongly associates with the viral core, uncoating of the viral particle might be required for effective cleavage of CCF2 by BlaM-Vpr. Here, we show that BlaM-Vpr within mature viral cores effectively cleaves CCF2, indicating that this assay measures virion fusion independently of uncoating. We also show that wildtype andmore » Nef-deficient HIV-1 virions fuse with equivalent efficiency to HeLa-CD4 cells, SupT1 T cells, and primary CD4 T cells. Since Nef enhances cytoplasmic delivery of viral cores and increases viral infectivity, these findings indicate that Nef enhances an early post-fusion event in the multistep process of viral entry. Possible sites of Nef action include enlargement of the fusion pore, enhanced uncoating of viral particles, and more efficient passage of viral cores through the dense cortical actin network located immediately beneath the plasma membrane.« less

HIV-1 Nef binds with human GCC185 protein and regulates mannose 6 phosphate receptor recycling

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

Kumar, Manjeet; Kaur, Supinder; Nazir, Aamir

HIV-1 Nef modulates cellular function that enhances viral replication in vivo which culminate into AIDS pathogenesis. With no enzymatic activity, Nef regulates cellular function through host protein interaction. Interestingly, trans-cellular introduction of recombinant Nef protein in Caenorhabditis elegans results in AIDS like pathogenesis which might share common pathophysiology because the gene sequence of C. elegans and humans share considerable homology. Therefore employing C. elegans based initial screen complemented with sequence based homology search we identified GCC185 as novel host protein interacting with HIV-1 Nef. The detailed molecular characterization revealed N-terminal EEEE{sub 65} acidic domain of Nef as key region for interaction. GCC185 ismore » a tethering protein that binds with Rab9 transport vesicles. Our results show that Nef-GCC185 interaction disrupts Rab9 interaction resulting in delocalization of CI-MPR (cation independent Mannose 6 phosphate receptor) resulting in elevated secretion of hexosaminidase. In agreement with this, our studies identified novel host GCC185 protein that interacts with Nef EEEE65 acidic domain interfering GCC185-Rab9 vesicle membrane fusion responsible for retrograde vesicular transport of CI-MPR from late endosomes to TGN. In light of existing report suggesting critical role of Nef-GCC185 interaction reveals valuable mechanistic insights affecting specific protein transport pathway in docking of late endosome derived Rab9 bearing transport vesicle at TGN elucidating role of Nef during viral pathogenesis. -- Highlights: •Nef, an accessory protein of HIV-1 interacts with host factor and culminates into AIDS pathogenesis. •Using Caenorhabditis elegans based screen system, novel Nef interacting cellular protein GCC185 was identified. •Molecular characterization of Nef and human protein GCC185 revealed Nef EEEE{sub 65} key region interacted with full length GCC185. •Nef impeded the GCC185-Rab 9 interaction and perturb the mannose 6 phosphate receptor recycling. •Our study identified novel Nef interacting human GCC185 protein and their role regulation of M6P receptor recycling.« less

Binding of human nucleotide exchange factors to heat shock protein 70 (Hsp70) generates functionally distinct complexes in vitro.

PubMed

Rauch, Jennifer N; Gestwicki, Jason E

2014-01-17

Proteins with Bcl2-associated anthanogene (BAG) domains act as nucleotide exchange factors (NEFs) for the molecular chaperone heat shock protein 70 (Hsp70). There are six BAG family NEFs in humans, and each is thought to link Hsp70 to a distinct cellular pathway. However, little is known about how the NEFs compete for binding to Hsp70 or how they might differentially shape its biochemical activities. Toward these questions, we measured the binding of human Hsp72 (HSPA1A) to BAG1, BAG2, BAG3, and the unrelated NEF Hsp105. These studies revealed a clear hierarchy of affinities: BAG3 > BAG1 > Hsp105 ≫ BAG2. All of the NEFs competed for binding to Hsp70, and their relative affinity values predicted their potency in nucleotide and peptide release assays. Finally, we combined the Hsp70-NEF pairs with cochaperones of the J protein family (DnaJA1, DnaJA2, DnaJB1, and DnaJB4) to generate 16 permutations. The activity of the combinations in ATPase and luciferase refolding assays were dependent on the identity and stoichiometry of both the J protein and NEF so that some combinations were potent chaperones, whereas others were inactive. Given the number and diversity of cochaperones in mammals, it is likely that combinatorial assembly could generate a large number of distinct permutations.

Small heat shock protein 27: An effective adjuvant for enhancement of HIV-1 Nef antigen-specific immunity.

PubMed

Milani, Alireza; Bolhassani, Azam; Shahbazi, Sepideh; Motevalli, Fatemeh; Sadat, Seyed Mehdi; Soleymani, Sepehr

2017-11-01

Novel vaccine modalities have been designed to improve the efficiency of vaccines against HIV infections. In this way, the HIV-1 Nef protein has been known as an attractive antigenic candidate in therapeutic vaccine development. Moreover, the endogenous adjuvants such as heat shock proteins (HSPs) and high mobility group box 1 protein (HMGB1) have been suggested effectively to induce antigen-specific humoral and cellular immune responses. In this study, different Nef DNA and protein constructs were produced in eukaryotic and prokaryotic expression systems, and their immunostimulatory properties were evaluated using small heat shock protein 27 (Hsp27) and the HMGB1-derived peptide (Hp91) in a mouse model. Generally, our results indicated that the Hsp27-Nef fusion DNA or protein could significantly elicit higher humoral and cellular immune responses than Nef DNA or protein, respectively. Analysis of the immune responses demonstrated that the Hsp27-Nef fusion protein, and also the mixture of Nef and Hp91 significantly enhanced the Nef-specific T cell responses. Indeed, these regimens induced high levels of IgG2a and IFN-γ directed toward Th1 responses and also Granzyme B secretion as compared to other immunization strategies. The immunostimulatory properties of Freund's adjuvant were significantly less than Hsp27 and Hp91 peptide in various immunization strategies. These findings showed that the use of Hsp27 and Hp91 in protein strategy could improve HIV-1 Nef-specific B- and T-cell immune responses, and also represent a promising HIV-1 vaccine candidate in future. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

A Role for an Hsp70 Nucleotide Exchange Factor in the Regulation of Synaptic Vesicle Endocytosis

PubMed Central

Morgan, Jennifer R.; Jiang, Jianwen; Oliphint, Paul A.; Jin, Suping; Gimenez, Luis E.; Busch, David J.; Foldes, Andrea E.; Zhuo, Yue; Sousa, Rui; Lafer, Eileen M.

2013-01-01

Neurotransmission requires a continuously available pool of synaptic vesicles (SVs) that can fuse with the plasma membrane and release their neurotransmitter contents upon stimulation. After fusion, SV membranes and membrane proteins are retrieved from the presynaptic plasma membrane by clathrin-mediated endocytosis. Following the internalization of a clathrin coated vesicle (CCV), the vesicle must uncoat to replenish the pool of SVs. CCV uncoating requires ATP and is mediated by the ubiquitous molecular chaperone Hsc70. In vitro, depolymerized clathrin forms a stable complex with Hsc70*ADP. This complex can be dissociated by nucleotide exchange factors (NEFs) that release ADP from Hsc70, allowing ATP to bind and induce disruption of the clathrin:Hsc70 association. Whether NEFs generally play similar roles in vesicle trafficking in vivo, and whether they play such roles in SV endocytosis in particular is unknown. To address this question we used information from recent structural and mechanistic studies of Hsp70:NEF and Hsp70:cochaperone interactions to design a NEF inhibitor. Using acute perturbations at giant reticulospinal synapses of the sea lamprey (Petromyzon marinus), we found that this NEF inhibitor inhibited SV endocytosis. When this inhibitor was mutated so it could no longer bind and inhibit Hsp110--a NEF that we find to be highly abundant in brain cytosol--its ability to inhibit SV endocytosis was eliminated. These observations indicate that the action of a NEF, most likely Hsp110, is normally required during SV trafficking to release clathrin from Hsc70 and make it available for additional rounds of endocytosis. PMID:23637191

HIV-1 Nef limits communication between linker of activated T cells and SLP-76 to reduce formation of SLP-76-signaling microclusters following TCR stimulation.

PubMed

Abraham, Libin; Bankhead, Peter; Pan, Xiaoyu; Engel, Ulrike; Fackler, Oliver T

2012-08-15

Signal initiation by engagement of the TCR triggers actin rearrangements, receptor clustering, and dynamic organization of signaling complexes to elicit and sustain downstream signaling. Nef, a pathogenicity factor of HIV, disrupts early TCR signaling in target T cells. To define the mechanism underlying this Nef-mediated signal disruption, we employed quantitative single-cell microscopy following surface-mediated TCR stimulation that allows for dynamic visualization of distinct signaling complexes as microclusters (MCs). Despite marked inhibition of actin remodeling and cell spreading, the induction of MCs containing TCR-CD3 or ZAP70 was not affected significantly by Nef. However, Nef potently inhibited the subsequent formation of MCs positive for the signaling adaptor Src homology-2 domain-containing leukocyte protein of 76 kDa (SLP-76) to reduce MC density in Nef-expressing and HIV-1-infected T cells. Further analyses suggested that Nef prevents formation of SLP-76 MCs at the level of the upstream adaptor protein, linker of activated T cells (LAT), that couples ZAP70 to SLP-76. Nef did not disrupt pre-existing MCs positive for LAT. However, the presence of the viral protein prevented de novo recruitment of active LAT into MCs due to retargeting of LAT to an intracellular compartment. These modulations in MC formation and composition depended on Nef's ability to simultaneously disrupt both actin remodeling and subcellular localization of TCR-proximal machinery. Nef thus employs a dual mechanism to disturb early TCR signaling by limiting the communication between LAT and SLP-76 and preventing the dynamic formation of SLP-76-signaling MCs.

The HIV Nef protein modulates cellular and exosomal miRNA profiles in human monocytic cells.

PubMed

Aqil, Madeeha; Naqvi, Afsar Raza; Mallik, Saurav; Bandyopadhyay, Sanghamitra; Maulik, Ujjwal; Jameel, Shahid

2014-01-01

The HIV Nef protein is a multifunctional virulence factor that perturbs intracellular membranes and signalling and is secreted into exosomes. While Nef-containing exosomes have a distinct proteomic profile, no comprehensive analysis of their miRNA cargo has been carried out. Since Nef functions as a viral suppressor of RNA interference and disturbs the distribution of RNA-induced silencing complex proteins between cells and exosomes, we hypothesized that it might also affect the export of miRNAs into exosomes. Exosomes were purified from human monocytic U937 cells that stably expressed HIV-1 Nef. The RNA from cells and exosomes was profiled for 667 miRNAs using a Taqman Low Density Array. Selected miRNAs and their mRNA targets were validated by quantitative RT-PCR. Bioinformatics analyses were used to identify targets and predict pathways. Nef expression affected a significant fraction of miRNAs in U937 cells. Our analysis showed 47 miRNAs to be selectively secreted into Nef exosomes and 2 miRNAs to be selectively retained in Nef-expressing cells. The exosomal miRNAs were predicted to target several cellular genes in inflammatory cytokine and other pathways important for HIV pathogenesis, and an overwhelming majority had targets within the HIV genome. This is the first study to report miRnome analysis of HIV Nef expressing monocytes and exosomes. Our results demonstrate that Nef causes large-scale dysregulation of cellular miRNAs, including their secretion through exosomes. We suggest this to be a novel viral strategy to affect pathogenesis and to limit the effects of RNA interference on viral replication and persistence.

Predicting the impact of blocking human immunodeficiency virus type 1 Nef in vivo.

PubMed

Wick, W David; Gilbert, Peter B; Yang, Otto O

2009-03-01

Human immunodeficiency virus type 1 (HIV-1) Nef is a multifunctional protein that confers an ability to evade killing by cytotoxic T lymphocytes (CTLs) as well as other advantages to the virus in vivo. Here we exploited mathematical modeling and related statistical methods to estimate the impact of Nef activity on viral replication in vivo in relation to CTLs. Our results indicate that downregulation of major histocompatibility complex class I (MHC-I) A and B by wild-type Nef confers an advantage to the virus of about 82% in decreased CTL killing efficiency on average, meaning that abolishing the MHC-I downregulation function of Nef would increase killing by more than fivefold. We incorporated this estimate, as well as prior estimates of replicative enhancement by Nef, into a previously published model of HIV-1 and CTLs in vivo (W. D. Wick, O. O. Yang, L. Corey, and S. G. Self, J. Virol. 79:13579-13586, 2005), generalized to permit CTL recognition of multiple epitopes. A sequence database analysis revealed that 92.9% of HIV-1 epitopes are A or B restricted, and a previous study found an average of about 19 epitopes recognized (M. M. Addo et al., J. Virol. 77:2081-2092, 2003). We combined these estimates in the model in order to predict the impact of inhibiting Nef function in the general (chronically infected) population by a drug. The predicted impact on viral load ranged from negligible to 2.4 orders of magnitude, depending on the effects of the drug and the CTL dynamical scenario assumed. We conclude that inhibiting Nef could make a substantial reduction in disease burden, lengthening the time before the necessity of undertaking combination therapy with other antiretroviral drugs.

Conformational transition of membrane-associated terminally-acylated HIV-1 Nef

PubMed Central

Akgun, Bulent; Satija, Sushil; Nanda, Hirsh; Pirrone, Gregory F.; Shi, Xiaomeng; Engen, John R.; Kent, Michael S.

2013-01-01

Many proteins are post-translationally modified by acylation targetting them to lipid membranes. While methods such as X-ray crystallography and NMR are available to determine the structure of folded proteins in solution, the precise position of folded domains relative to a membrane remains largely unknown. We used neutron and X-ray reflection methods to measure the displacement of the core domain of HIV Nef from lipid membranes upon insertion of the N-terminal myristate group. Nef is one of several HIV-1 accessory proteins and an essential factor in AIDS progression. Upon insertion of the myristate and residues from the N-terminal arm, Nef transitions from a closed to open conformation that positions the core domain 70 Å from the lipid headgroups. This work rules out speculation that the Nef core remains closely associated with the membrane to optimize interactions with the cytoplasmic domain of MHC-1. PMID:24035710

Antitumor HPV E7-specific CTL activity elicited by in vivo engineered exosomes produced through DNA inoculation.

PubMed

Di Bonito, Paola; Chiozzini, Chiara; Arenaccio, Claudia; Anticoli, Simona; Manfredi, Francesco; Olivetta, Eleonora; Ferrantelli, Flavia; Falcone, Emiliana; Ruggieri, Anna; Federico, Maurizio

2017-01-01

We recently proved that exosomes engineered in vitro to deliver high amounts of HPV E7 upon fusion with the Nef mut exosome-anchoring protein elicit an efficient anti-E7 cytotoxic T lymphocyte immune response. However, in view of a potential clinic application of this finding, our exosome-based immunization strategy was faced with possible technical difficulties including industrial manufacturing, cost of production, and storage. To overcome these hurdles, we designed an as yet unproven exosome-based immunization strategy relying on delivery by intramuscular inoculation of a DNA vector expressing Nef mut fused with HPV E7. In this way, we predicted that the expression of the Nef mut /E7 vector in muscle cells would result in a continuous source of endogenous (ie, produced by the inoculated host) engineered exosomes able to induce an E7-specific immune response. To assess this hypothesis, we first demonstrated that the injection of a Nef mut /green fluorescent protein-expressing vector led to the release of fluorescent exosomes, as detected in plasma of inoculated mice. Then, we observed that mice inoculated intramuscularly with a vector expressing Nef mut /E7 developed a CD8 + T-cell immune response against both Nef and E7. Conversely, no CD8 + T-cell responses were detected upon injection of vectors expressing either the wild-type Nef isoform of E7 alone, most likely a consequence of their inefficient exosome incorporation. The production of immunogenic exosomes in the DNA-injected mice was formally demonstrated by the E7-specific CD8 + T-cell immune response we detected in mice inoculated with exosomes isolated from plasma of mice inoculated with the Nef mut /E7 vector. Finally, we provide evidence that the injection of Nef mut /E7 DNA led to the generation of effective antigen-specific cytotoxic T lymphocytes whose activity was likely part of the potent, therapeutic antitumor effect we observed in mice implanted with TC-1 tumor cells. In summary, we established a novel method to generate immunogenic exosomes in vivo by the intramuscular inoculation of DNA vectors expressing the exosome-anchoring protein Nef mut and its derivatives.

Human Immunodeficiency Virus nef signature sequences are associated with pulmonary hypertension.

PubMed

Almodovar, Sharilyn; Knight, Rob; Allshouse, Amanda A; Roemer, Sarah; Lozupone, Catherine; McDonald, Daniel; Widmann, Jeremy; Voelkel, Norbert F; Shelton, Robert J; Suarez, Edu B; Hammer, Kenneth W; Goujard, Cecile; Petrosillo, Nicola; Simonneau, Gerald; Hsue, Priscilla Y; Humbert, Marc; Flores, Sonia C

2012-06-01

Severe pulmonary hypertension (PH) associated with vascular remodeling is a long-term complication of HIV infection (HIV-PH) affecting 1/200 infected individuals vs. 1/200,000 frequency in the uninfected population. Factors accounting for increased PH susceptibility in HIV-infected individuals are unknown. Rhesus macaques infected with chimeric SHIVnef virions but not with SIV display PH-like pulmonary vascular remodeling suggesting that HIV-Nef is associated with PH; these monkeys showed changes in nef sequences that correlated with pathogenesis after passage in vivo. We further examined whether HIV-nef alleles in HIV-PH subjects have signature sequences associated with the disease phenotype. We evaluated specimens from participants with and without HIV-PH from European Registries and validated results with samples collected as part of the Lung-HIV Studies in San Francisco. We found that 10 polymorphisms in nef were overrepresented in blood cells or lung tissue specimens from European HIV-PH individuals but significantly less frequent in HIV-infected individuals without PH. These polymorphisms mapped to known functional domains in Nef. In the validation cohort, 7/10 polymorphisms in the HIV-nef gene were confirmed; these polymorphisms arose independently from viral load, CD4(+) T cell counts, length of infection, and antiretroviral therapy status. Two out of 10 polymorphisms were previously reported in macaques with PH-like pulmonary vascular remodeling. Cloned recombinant Nef proteins from clinical samples down-regulated CD4, suggesting that these primary isolates are functional. This study offers new insights into the association between Nef polymorphisms in functional domains and the HIV-PH phenotype. The utility of these polymorphisms as predictors of PH should be examined in a larger population.

Continuing C3 breakdown after bilateral nephrectomy in patients with membrano-proliferative glomerulonephritis.

PubMed

Vallota, E H; Forristal, J; Spitzer, R E; Davis, N C; West, C D

1971-03-01

Serum levels of complement components and of C3 nephritic factor (C3NeF) were measured serially in two patients with membrano-proliferative glomerulonephritis who were subjected to bilateral nephrectomy and maintained by peritoneal dialysis for 2 wk before renal transplantation. In both patients, low levels of C3 and high levels of preformed alpha 2D, a C3 breakdown product, were present before nephrectomy and remained essentially unchanged during the anephric period. With transplantation, C3 levels rose towards normal and alpha 2D disappeared from the serum. The serum of both patients contained detectable amounts of C3NeF, a factor which has been shown to react with a cofactor found in normal serum to form an enzyme, designated C3 lytic nephritic factor (C3LyNeF), which will cleave C3 to form the breakdown products, beta1A and alpha 2D. The level of C3NeF was high in one patient before nephrectomy, increased somewhat during the anephric period, and fell after transplantation. In the other patient, the C3NeF level was initially lower, remained relatively constant during the anephric period, and was not significantly affected by transplantation. In both patients, levels of C4 and C5 were either normal or elevated over the period of the study and bore no relationship to the C3 level. The following conclusions can be drawn from the data. The high levels of alpha 2D during the anephric period and the disappearance of this protein as C3 levels approach normal at the time of transplantation indicate that the low C3 levels were largely the result of C3 breakdown rather than diminished synthesis. The presence of C3NeF in detectable amounts in both patients suggest that C3LyNeF, formed by the reaction of C3NeF and cofactor, was responsible for the low C3 levels. Finally, the lack of effect of nephrectomy on C3, alpha 2D, and C3NeF levels indicate that the site of C3 breakdown was extrarenal and that C3NeF and cofactor are at least in large part of extrarenal origin.

The interaction between HIV-1 Nef and adaptor protein-2 reduces Nef-mediated CD4+ T cell apoptosis.

PubMed

Jacob, Rajesh Abraham; Johnson, Aaron L; Pawlak, Emily N; Dirk, Brennan S; Van Nynatten, Logan R; Haeryfar, S M Mansour; Dikeakos, Jimmy D

2017-09-01

Acquired Immune Deficiency Syndrome is characterized by a decline in CD4 + T cells. Here, we elucidated the mechanism underlying apoptosis in Human Immunodeficiency Virus-1 (HIV-1) infection by examining host apoptotic pathways hijacked by the HIV-1 Nef protein in the CD4 + T-cell line Sup-T1. Using a panel of Nef mutants unable to bind specific host proteins we uncovered that Nef generates pro- and anti-apoptotic signals. Apoptosis increased upon mutating the motifs involved in the interaction of Nef:AP-1 (Nef M20A or Nef EEEE62-65AAAA ) or Nef:AP-2 (Nef LL164/165AA ), implying these interactions limit Nef-mediated apoptosis. In contrast, disrupting the Nef:PAK2 interaction motifs (Nef H89A or Nef F191A ) reduced apoptosis. To validate further, apoptosis was measured after short-hairpin RNA knock-down of AP-1, AP-2 and PAK2. AP-2α depletion enhanced apoptosis, demonstrating that disrupting the Nef:AP-2α interaction limits Nef-mediated apoptosis. Collectively, we describe a mechanism by which HIV-1 regulates cell survival and demonstrate the consequence of interfering with Nef:host protein interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic features of apo and bound HIV-Nef protein reveal the anti-HIV dimerization inhibition mechanism.

PubMed

Moonsamy, Suri; Bhakat, Soumendranath; Soliman, Mahmoud E S

2015-01-01

The first account on the dynamic features of Nef or negative factor, a small myristoylated protein located in the cytoplasm believes to increase HIV-1 viral titer level, is reported herein. Due to its major role in HIV-1 pathogenicity, Nef protein is considered an emerging target in anti-HIV drug design and discovery process. In this study, comparative long-range all-atom molecular dynamics simulations were employed for apo and bound protein to unveil molecular mechanism of HIV-Nef dimerization and inhibition. Results clearly revealed that B9, a newly discovered Nef inhibitor, binds at the dimeric interface of Nef protein and caused significant separation between orthogonally opposed residues, namely Asp108, Leu112 and Gln104. Large differences in magnitudes were observed in the radius of gyration (∼1.5 Å), per-residue fluctuation (∼2 Å), C-alpha deviations (∼2 Å) which confirm a comparatively more flexible nature of apo conformation due to rapid dimeric association. Compared to the bound conformer, a more globally correlated motion in case of apo structure of HIV-Nef confirms the process of dimeric association. This clearly highlights the process of inhibition as a result of ligand binding. The difference in principal component analysis (PCA) scatter plot and per-residue mobility plot across first two normal modes further justifies the same findings. The in-depth dynamic analyses of Nef protein presented in this report would serve crucial in understanding its function and inhibition mechanisms. Information on inhibitor binding mode would also assist in designing of potential inhibitors against this important HIV target.

Human immunodeficiency virus type 1 Nef protein inhibits NF-kappa B induction in human T cells.

PubMed Central

Niederman, T M; Garcia, J V; Hastings, W R; Luria, S; Ratner, L

1992-01-01

Human immunodeficiency virus type 1 (HIV-1) can establish a persistent and latent infection in CD4+ T lymphocytes (W. C. Greene, N. Engl. J. Med. 324:308-317, 1991; S. M. Schnittman, M. C. Psallidopoulos, H. C. Lane, L. Thompson, M. Baseler, F. Massari, C. H. Fox, N. P. Salzman, and A. S. Fauci, Science 245:305-308, 1989). Production of HIV-1 from latently infected cells requires host cell activation by T-cell mitogens (T. Folks, D. M. Powell, M. M. Lightfoote, S. Benn, M. A. Martin, and A. S. Fauci, Science 231:600-602, 1986; D. Zagury, J. Bernard, R. Leonard, R. Cheynier, M. Feldman, P. S. Sarin, and R. C. Gallo, Science 231:850-853, 1986). This activation is mediated by the host transcription factor NF-kappa B [G. Nabel and D. Baltimore, Nature (London) 326:711-717, 1987]. We report here that the HIV-1-encoded Nef protein inhibits the induction of NF-kappa B DNA-binding activity by T-cell mitogens. However, Nef does not affect the DNA-binding activity of other transcription factors implicated in HIV-1 regulation, including SP-1, USF, URS, and NF-AT. Additionally, Nef inhibits the induction of HIV-1- and interleukin 2-directed gene expression, and the effect on HIV-1 transcription depends on an intact NF-kappa B-binding site. These results indicate that defective recruitment of NF-kappa B may underlie Nef's negative transcriptional effects on the HIV-1 and interleukin 2 promoters. Further evidence suggests that Nef inhibits NF-kappa B induction by interfering with a signal derived from the T-cell receptor complex. Images PMID:1527859

Stress- and sequence-dependent release into the culture medium of HIV-1 Nef produced in Saccharomyces cerevisiae.

PubMed

Macreadie, I G; Castelli, L A; Lucantoni, A; Azad, A A

1995-09-11

We have produced human immunodeficiency virus type 1 (HIV-1) Nef (a myristylated 206-amino-acid protein) in Saccharomyces cerevisaie and shown that, while Nef is normally found as a predominantly intracellular protein, amounts up to 40 micrograms/ml of Nef are also released into the extracellular medium during stress. By electrophoretic (SDS-PAGE) analysis the extracellular Nef is indistinguishable from intracellular Nef. Conditions of stress that lead to the release of Nef include elevated levels of copper or magnesium ions or growth at elevated temperatures. This release appears to be dependent upon the N-terminal sequences of Nef, including the presence of a myristylation site. Our observations concerning Nef release in yeast suggest new ways in which the behaviour of Nef should be examined in order to gain further insights into the development of AIDS. If the release of Nef is important in the development of AIDS, our work reveals that Nef-associated symptoms may be reduced or delayed by reducing stresses, such as fevers.

A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities

PubMed Central

Martínez-Bonet, Marta; Palladino, Claudia; Briz, Veronica; Rudolph, Jochen M.; Fackler, Oliver T.; Relloso, Miguel; Muñoz-Fernandez, Maria Angeles; Madrid, Ricardo

2015-01-01

To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121–137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection. PMID:26700863

On the origin of C3 nephritic factor (antibody to the alternative pathway C3 convertase): evidence for the Adam and Eve concept of autoantibody production.

PubMed

Spitzer, R E; Stitzel, A E; Tsokos, G

1992-09-01

The antibody to the alternative pathway C3 convertase, designated C3 nephritic factor or C3NeF, is an autoantibody that is produced in everyone from the time of birth. The elaboration of C3NeF utilizes germline V-region genes which undergo antigen-driven affinity maturation, resulting in an autoantibody that is produced in large amounts with high affinity and narrow specificity. Our data also suggest that under normal conditions, the idiotypic network may play an important part in the control of this autoantibody. Further, a defect in the network with loss of control or inappropriate stimulation may be an underlying mechanism in the unrestricted production of C3NeF in patients with membranoproliferative glomerulonephritis.

Nitrite-embedded packaging film effects on fresh and frozen beef color development and stability as influenced by meat age and muscle type.

PubMed

Claus, James R; Du, Chen

2013-11-01

Muscles (Longissimus lumborum, LL; Psoas major, PM, semitendinosus, ST) were aged (2, 9d postmortem), cut into steaks, anaerobically packaged (nitrite-embedded film, NEF), and displayed (fresh, 19d; frozen, 39d). Fresh NEF increased (P<0.05) in redness (first 48h). Upon opening fresh NEF (d 6) and overwrapping in PVC film, redness declined (P<0.05). NEF cooked LL had more red surface compared to non-NEF. Meat age influenced NEF color. Intact NEF maintained acceptable red color throughout display. Residual nitrite and nitrate associated with fresh NEF and nitrate in NEF cooked LL were found (P<0.05) in the outer layer. Consideration should be given to providing sufficient time for nitric oxide myoglobin development when using NEF which may be influenced by meat age and muscle differences. NEF packaging has potential to extend fresh beef color display life. NEF appears to offer the opportunity to display bright red beef in frozen display by limiting typical effects of photooxidation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Primate lentiviruses use at least three alternative strategies to suppress NF-κB-mediated immune activation

PubMed Central

Gawanbacht, Ali; Van Driessche, Benoît; Van Lint, Carine; Peeters, Martine; Kirchhoff, Frank

2017-01-01

Primate lentiviruses have evolved sophisticated strategies to suppress the immune response of their host species. For example, HIV-2 and most simian immunodeficiency viruses (SIVs) use their accessory protein Nef to prevent T cell activation and antiviral gene expression by downmodulating the T cell receptor CD3. This Nef function was lost in HIV-1 and other vpu-encoding viruses suggesting that the acquisition of Vpu-mediated NF-κB inhibition reduced the selection pressure for inhibition of T cell activation by Nef. To obtain further insights into the modulation of NF-κB activity by primate lentiviral accessory factors, we analyzed 32 Vpr proteins from a large panel of divergent primate lentiviruses. We found that those of SIVcol and SIVolc infecting Colobinae monkeys showed the highest efficacy in suppressing NF-κB activation. Vpr-mediated inhibition of NF-κB resulted in decreased IFNβ promoter activity and suppressed type I IFN induction in virally infected primary cells. Interestingly, SIVcol and SIVolc differ from all other primate lentiviruses investigated by the lack of both, a vpu gene and efficient Nef-mediated downmodulation of CD3. Thus, primate lentiviruses have evolved at least three alternative strategies to inhibit NF-κB-dependent immune activation. Functional analyses showed that the inhibitory activity of SIVolc and SIVcol Vprs is independent of DCAF1 and the induction of cell cycle arrest. While both Vprs target the IKK complex or a factor further downstream in the NF-κB signaling cascade, only SIVolc Vpr stabilizes IκBα and inhibits p65 phosphorylation. Notably, only de-novo synthesized but not virion-associated Vpr suppressed the activation of NF-κB, thus enabling NF-κB-dependent initiation of viral gene transcription during early stages of the replication cycle, while minimizing antiviral gene expression at later stages. Our findings highlight the key role of NF-κB in antiviral immunity and demonstrate that primate lentiviruses follow distinct evolutionary paths to modulate NF-κB-dependent expression of viral and antiviral genes. PMID:28859166

Interaction with the Src homology (SH3-SH2) region of the Src-family kinase Hck structures the HIV-1 Nef dimer for kinase activation and effector recruitment.

PubMed

Alvarado, John Jeff; Tarafdar, Sreya; Yeh, Joanne I; Smithgall, Thomas E

2014-10-10

HIV-1 Nef supports high titer viral replication in vivo and is essential for AIDS progression. Nef function depends on interactions with multiple host cell effectors, including Hck and other Src-family kinases. Here we describe the x-ray crystal structure of Nef in complex with the Hck SH3-SH2 regulatory region to a resolution of 1.86 Å. The complex crystallized as a dimer of complexes, with the conserved Nef PXXPXR motif engaging the Hck SH3 domain. A new intercomplex contact was found between SH3 Glu-93, and Nef Arg-105. Mutagenesis of Hck SH3 Glu-93 interfered with Nef·Hck complex formation and kinase activation in cells. The Hck SH2 domains impinge on the N-terminal region of Nef to stabilize a dimer conformation that exposes Asp-123, a residue critical for Nef function. Our results suggest that in addition to serving as a kinase effector for Nef, Hck binding may reorganize the Nef dimer for functional interaction with other signaling partners. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Interaction with the Src Homology (SH3-SH2) Region of the Src-family Kinase Hck Structures the HIV-1 Nef Dimer for Kinase Activation and Effector Recruitment*

PubMed Central

Alvarado, John Jeff; Tarafdar, Sreya; Yeh, Joanne I.; Smithgall, Thomas E.

2014-01-01

HIV-1 Nef supports high titer viral replication in vivo and is essential for AIDS progression. Nef function depends on interactions with multiple host cell effectors, including Hck and other Src-family kinases. Here we describe the x-ray crystal structure of Nef in complex with the Hck SH3-SH2 regulatory region to a resolution of 1.86 Å. The complex crystallized as a dimer of complexes, with the conserved Nef PXXPXR motif engaging the Hck SH3 domain. A new intercomplex contact was found between SH3 Glu-93, and Nef Arg-105. Mutagenesis of Hck SH3 Glu-93 interfered with Nef·Hck complex formation and kinase activation in cells. The Hck SH2 domains impinge on the N-terminal region of Nef to stabilize a dimer conformation that exposes Asp-123, a residue critical for Nef function. Our results suggest that in addition to serving as a kinase effector for Nef, Hck binding may reorganize the Nef dimer for functional interaction with other signaling partners. PMID:25122770

Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 1 Nef Proteins Show Distinct Patterns and Mechanisms of Src Kinase Activation

PubMed Central

Greenway, Alison L.; Dutartre, Hélène; Allen, Kelly; McPhee, Dale A.; Olive, Daniel; Collette, Yves

1999-01-01

The nef gene from human and simian immunodeficiency viruses (HIV and SIV) regulates cell function and viral replication, possibly through binding of the nef product to cellular proteins, including Src family tyrosine kinases. We show here that the Nef protein encoded by SIVmac239 interacts with and also activates the human Src kinases Lck and Hck. This is in direct contrast to the inhibitory effect of HIV type 1 (HIV-1) Nef on Lck catalytic activity. Unexpectedly, however, the interaction of SIV Nef with human Lck or Hck is not mediated via its consensus proline motif, which is known to mediate HIV-1 Nef binding to Src homology 3 (SH3) domains, and various experimental analyses failed to show significant interaction of SIV Nef with the SH3 domain of either kinase. Instead, SIV Nef can bind Lck and Hck SH2 domains, and its N-terminal 50 amino acid residues are sufficient for Src kinase binding and activation. Our results provide evidence for multiple mechanisms by which Nef binds to and regulates Src kinases. PMID:10364375

Consequences of HLA-B*13-Associated Escape Mutations on HIV-1 Replication and Nef Function

PubMed Central

Shahid, Aniqa; Olvera, Alex; Anmole, Gursev; Kuang, Xiaomei T.; Cotton, Laura A.; Plana, Montserrat; Brander, Christian; Brockman, Mark A.

2015-01-01

ABSTRACT HLA-B*13 is associated with superior in vivo HIV-1 viremia control. Protection is thought to be mediated by sustained targeting of key cytotoxic T lymphocyte (CTL) epitopes and viral fitness costs of CTL escape in Gag although additional factors may contribute. We assessed the impact of 10 published B*13-associated polymorphisms in Gag, Pol, and Nef, in 23 biologically relevant combinations, on HIV-1 replication capacity and Nef-mediated reduction of cell surface CD4 and HLA class I expression. Mutations were engineered into HIV-1NL4.3, and replication capacity was measured using a green fluorescent protein (GFP) reporter T cell line. Nef-mediated CD4 and HLA-A*02 downregulation was assessed by flow cytometry, and T cell recognition of infected target cells was measured via coculture with an HIV-specific luciferase reporter cell line. When tested individually, only Gag-I147L and Gag-I437L incurred replicative costs (5% and 17%, respectively), consistent with prior reports. The Gag-I437L-mediated replication defect was rescued to wild-type levels by the adjacent K436R mutation. A novel B*13 epitope, comprising 8 residues and terminating at Gag147, was identified in p24Gag (GQMVHQAIGag140–147). No other single or combination Gag, Pol, or Nef mutant impaired viral replication. Single Nef mutations did not affect CD4 or HLA downregulation; however, the Nef double mutant E24Q-Q107R showed 40% impairment in HLA downregulation with no evidence of Nef stability defects. Moreover, target cells infected with HIV-1-NefE24Q-Q107R were recognized better by HIV-specific T cells than those infected with HIV-1NL4.3 or single Nef mutants. Our results indicate that CTL escape in Gag and Nef can be functionally costly and suggest that these effects may contribute to long-term HIV-1 control by HLA-B*13. IMPORTANCE Protective effects of HLA-B*13 on HIV-1 disease progression are mediated in part by fitness costs of CTL escape mutations in conserved Gag epitopes, but other mechanisms remain incompletely known. We extend our knowledge of the impact of B*13-driven escape on HIV-1 replication by identifying Gag-K436R as a compensatory mutation for the fitness-costly Gag-I437L. We also identify Gag-I147L, the most rapidly and commonly selected B*13-driven substitution in HIV-1, as a putative C-terminal anchor residue mutation in a novel B*13 epitope. Most notably, we identify a novel escape-driven fitness defect: B*13-driven substitutions E24Q and Q107R in Nef, when present together, substantially impair this protein's ability to downregulate HLA class I. This, in turn, increases the visibility of infected cells to HIV-specific T cells. Our results suggest that B*13-associated escape mutations impair HIV-1 replication by two distinct mechanisms, that is, by reducing Gag fitness and dampening Nef immune evasion function. PMID:26355081

Discovery of a diaminoquinoxaline benzenesulfonamide antagonist of HIV-1 Nef function using a yeast-based phenotypic screen

PubMed Central

2013-01-01

Background HIV-1 Nef is a viral accessory protein critical for AIDS progression. Nef lacks intrinsic catalytic activity and binds multiple host cell signaling proteins, including Hck and other Src-family tyrosine kinases. Nef binding induces constitutive Hck activation that may contribute to HIV pathogenesis by promoting viral infectivity, replication and downregulation of cell-surface MHC-I molecules. In this study, we developed a yeast-based phenotypic screen to identify small molecules that inhibit the Nef-Hck complex. Results Nef-Hck interaction was faithfully reconstituted in yeast cells, resulting in kinase activation and growth arrest. Yeast cells expressing the Nef-Hck complex were used to screen a library of small heterocyclic compounds for their ability to rescue growth inhibition. The screen identified a dihydrobenzo-1,4-dioxin-substituted analog of 2-quinoxalinyl-3-aminobenzene-sulfonamide (DQBS) as a potent inhibitor of Nef-dependent HIV-1 replication and MHC-I downregulation in T-cells. Docking studies predicted direct binding of DQBS to Nef which was confirmed in differential scanning fluorimetry assays with recombinant purified Nef protein. DQBS also potently inhibited the replication of HIV-1 NL4-3 chimeras expressing Nef alleles representative of all M-group HIV-1 clades. Conclusions Our findings demonstrate the utility of a yeast-based growth reversion assay for the identification of small molecule Nef antagonists. Inhibitors of Nef function discovered with this assay, such as DQBS, may complement the activity of current antiretroviral therapies by enabling immune recognition of HIV-infected cells through the rescue of cell surface MHC-I. PMID:24229420

Function of ubiquitin (Ub) specific protease 15 (USP15) in HIV-1 replication and viral protein degradation.

PubMed

Pyeon, Dohun; Timani, Khalid Amine; Gulraiz, Fahad; He, Johnny J; Park, In-Woo

2016-09-02

HIV-1 Nef is necessary and may be sufficient for HIV-1-associated AIDS pathogenicity, in that knockout of Nef alone can protect HIV-infected patients from AIDS. We therefore investigated the feasibility of physical knockout of Nef, using the host ubiquitin proteasome system in HIV-1-infected cells. Our co-immunoprecipitation analysis demonstrated that Nef interacted with ubiquitin specific protease 15 (USP15), and that USP15, which is known to stabilize cellular proteins, degraded Nef. Nef could also cause decay of USP15, although Nef-mediated degradation of USP15 was weaker than USP15-mediated Nef degradation. Direct interaction between Nef and USP15 was essential for the observed reciprocal decay of the proteins. Further, USP15 degraded not only Nef but also HIV-1 structural protein, Gag, thereby substantially inhibiting HIV-1 replication. However, Gag did not degrade USP15, indicating that the Nef and USP15 complex, in distinction to other viral proteins, play an integral role in coordinating viral protein degradation and hence HIV-1 replication. Moreover, Nef and USP15 globally suppressed ubiquitylation of cellular proteins, indicating that these proteins are major determinants for the stability of cellular as well as viral proteins. Taken together, these data indicate that Nef and USP15 are vital in regulating degradation of viral and cellular proteins and thus HIV-1 replication, and specific degradation of viral, not cellular proteins, by USP15 points to USP15 as a candidate therapeutic agent to combat AIDS by eliminating viral proteins from the infected cells via USP15-mediated proteosomal degradation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

The ABCA1 domain responsible for interaction with HIV-1 Nef is conformational and not linear

PubMed Central

Jacob, Daria; Hunegnaw, Ruth; Sabyrzyanova, Tatyana A.; Pushkarsky, Tatiana; Chekhov, Vladimir O.; Adzhubei, Alexei A.; Kalebina, Tatyana S.; Bukrinsky, Michael

2014-01-01

HIV-1 Nef is an accessory protein responsible for inactivation of a number of host cell proteins essential for anti-viral immune responses. In most cases, Nef binds to the target protein and directs it to a degradation pathway. Our previous studies demonstrated that Nef impairs activity of the cellular cholesterol transporter, ABCA1, and that Nef interacts with ABCA1. Mutation of the 2226DDDHLK motif in the C-terminal cytoplasmic tail of ABCA1 disrupted interaction with Nef. Here, we tested Nef interaction with the ABCA1 C-terminal cytoplasmic fragment using yeast 2-hybrid system assay and co-immunoprecipitation analysis in human cells. Surprisingly, analysis in a yeast 2-hybrid system did not reveal any interaction between Nef and the C-terminal cytoplasmic fragment of ABCA1. Using coimmunoprecipitation from HEK 293T cells expressing these polypeptides, only a very weak interaction could be detected. The 2226DDDHLK motif in the C-terminal cytoplasmic tail of ABCA1 found previously to be essential for interaction between ABCA1 and Nef is insufficient to bestow strong binding to Nef. Molecular modeling suggested that interaction with Nef may be mediated by a conformational epitope composed of the sequences within the cytoplasmic loop of ABCA1 and the C-terminal cytoplasmic domain. Studies are now underway to characterize this epitope. PMID:24406162

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

Jia, Xiaofei; Singh, Rajendra; Homann, Stefanie

The HIV-1 protein Nef inhibits antigen presentation by class I major histocompatibility complex (MHC-I). We determined the mechanism of this activity by solving the crystal structure of a protein complex comprising Nef, the MHC-I cytoplasmic domain (MHC-I CD) and the {mu}1 subunit of the clathrin adaptor protein complex 1. A ternary, cooperative interaction clamps the MHC-I CD into a narrow binding groove at the Nef-{mu}1 interface, which encompasses the cargo-recognition site of {mu}1 and the proline-rich strand of Nef. The Nef C terminus induces a previously unobserved conformational change in {mu}1, whereas the N terminus binds the Nef core tomore » position it optimally for complex formation. Positively charged patches on {mu}1 recognize acidic clusters in Nef and MHC-I. The structure shows how Nef functions as a clathrin-associated sorting protein to alter the specificity of host membrane trafficking and enable viral evasion of adaptive immunity.« less

Neutron Reflectometry Study of the Conformation of HIV Nef Bound to Lipid Membranes

PubMed Central

Kent, Michael S.; Murton, Jaclyn K.; Sasaki, Darryl Y.; Satija, Sushil; Akgun, Bulent; Nanda, Hirsh; Curtis, Joseph E.; Majewski, Jaroslaw; Morgan, Christopher R.; Engen, John R.

2010-01-01

Nef is an HIV-1 accessory protein that directly contributes to AIDS progression. Nef is myristoylated on the N-terminus, associates with membranes, and may undergo a transition from a solution conformation to a membrane-associated conformation. It has been hypothesized that conformational rearrangement enables membrane-associated Nef to interact with cellular proteins. Despite its medical relevance, to our knowledge there is no direct information about the conformation of membrane-bound Nef. In this work, we used neutron reflection to reveal what we believe are the first details of the conformation of membrane-bound Nef. The conformation of Nef was probed upon binding to Langmuir monolayers through the interaction of an N-terminal His tag with a synthetic metal-chelating lipid, which models one of the possible limiting cases for myr-Nef. The data indicate that residues are inserted into the lipid headgroups during interaction, and that the core domain lies directly against the lipid headgroups, with a thickness of ∼40 Å. Binding of Nef through the N-terminal His tag apparently facilitates insertion of residues, as no insertion occurred upon binding of Nef through weak electrostatic interactions in the absence of the specific interaction through the His tag. PMID:20858440

HIV Nef-mediated cellular phenotypes are differentially expressed as a function of intracellular Nef concentrations.

PubMed

Liu, X; Schrager, J A; Lange, G D; Marsh, J W

2001-08-31

Nef is a regulatory protein encoded by the genome of both human and simian immunodeficiency virus. Its expression in T cells leads to CD4 and major histocompatibility complex class I modulation and either enhancement or suppression of T cell activation. How this viral protein achieves multiple and at times opposing activities has been unclear. Through direct measurements of Nef and the Nef-GFP fusion protein, we find that these events are mediated by different Nef concentrations. Relative to the intracellular concentration that down-modulates surface CD4, an order of magnitude increase in Nef-GFP expression is required for a comparable modulation of major histocompatibility complex class I, and a further 3-fold increase is necessary to suppress T cell activation.

Fine mapping of HIV-1 Nef-epitopes by monoclonal antibodies.

PubMed

Siakkou, H; Jahn, S; Kienzle, N; Ulrich, R; Grötzinger, C; Schneider, T; Kohleisen, B; Pauli, G; Spohn, R; Jung, G

1993-01-01

A panel of newly isolated murine monoclonal antibodies is described which are specific for the Nef protein of the human immunodeficiency virus type 1 (HIV-1). Epitope mapping using recombinant Nef-related proteins, synthetic peptides and lipopeptides showed 3 independent antigenic determinants located within the regions of amino acids 83-93, 175-190 and 86-166 of the Nef protein. None of the monoclonal antibodies reacted with recombinant Nef proteins of HIV-2.

Internalization and intracellular retention of CD4 are two separate functions of the human immunodeficiency virus type 1 Nef protein.

PubMed

Giolo, Giorgia; Neri, Francesca; Casartelli, Nicoletta; Potestà, Marina; Belleudi, Francesca; Torrisi, Maria Rosaria; Doria, Margherita

2007-11-01

The pathogenic Nef protein of the human immunodeficiency virus type 1 (HIV-1) downregulates CD4 by inducing its endocytosis and by inhibiting the transport of the receptor to the cell membrane. By means of in vivo-selected mutations, we show that L37, P78 and E177 residues of Nef are required for its effect on CD4 internalization and recycling but dispensable for Nef-induced retention and degradation of intracellular CD4. Of note, the function of Nef on the anterograde transport of newly synthesized CD4 molecules is irrelevant in cells with a slow constitutive CD4 turnover such as T cell lines. Moreover, we show that a mutated CD4 that is unresponsive to Nef-mediated endocytosis, CD4LL(144)AA, is retained intracellularly and degraded by Nef like wild-type CD4. Thus, Nef's abilities to enhance endocytosis and induce intracellular retention of CD4 are mediated by separate protein surfaces and occur through distinct mechanisms.

Ability of HIV-1 Nef to downregulate CD4 and HLA class I differs among viral subtypes

PubMed Central

2013-01-01

Background The highly genetically diverse HIV-1 group M subtypes may differ in their biological properties. Nef is an important mediator of viral pathogenicity; however, to date, a comprehensive inter-subtype comparison of Nef in vitro function has not been undertaken. Here, we investigate two of Nef’s most well-characterized activities, CD4 and HLA class I downregulation, for clones obtained from 360 chronic patients infected with HIV-1 subtypes A, B, C or D. Results Single HIV-1 plasma RNA Nef clones were obtained from N=360 antiretroviral-naïve, chronically infected patients from Africa and North America: 96 (subtype A), 93 (B), 85 (C), and 86 (D). Nef clones were expressed by transfection in an immortalized CD4+ T-cell line. CD4 and HLA class I surface levels were assessed by flow cytometry. Nef expression was verified by Western blot. Subset analyses and multivariable linear regression were used to adjust for differences in age, sex and clinical parameters between cohorts. Consensus HIV-1 subtype B and C Nef sequences were synthesized and functionally assessed. Exploratory sequence analyses were performed to identify potential genotypic correlates of Nef function. Subtype B Nef clones displayed marginally greater CD4 downregulation activity (p = 0.03) and markedly greater HLA class I downregulation activity (p < 0.0001) than clones from other subtypes. Subtype C Nefs displayed the lowest in vitro functionality. Inter-subtype differences in HLA class I downregulation remained statistically significant after controlling for differences in age, sex, and clinical parameters (p < 0.0001). The synthesized consensus subtype B Nef showed higher activities compared to consensus C Nef, which was most pronounced in cells expressing lower protein levels. Nef clones exhibited substantial inter-subtype diversity: cohort consensus residues differed at 25% of codons, while a similar proportion of codons exhibited substantial inter-subtype differences in major variant frequency. These amino acids, along with others identified in intra-subtype analyses, represent candidates for mediating inter-subtype differences in Nef function. Conclusions Results support a functional hierarchy of subtype B > A/D > C for Nef-mediated CD4 and HLA class I downregulation. The mechanisms underlying these differences and their relevance to HIV-1 pathogenicity merit further investigation. PMID:24041011

Role of gender in heart failure with normal left ventricular ejection fraction.

PubMed

Regitz-Zagrosek, Vera; Brokat, Sebastian; Tschope, Carsten

2007-01-01

Heart failure with normal ejection fraction (HF-NEF) is frequently believed to be more common in women than in men. However, the interaction of gender and age has rarely been analyzed in detail, and knowledge of the distinction between pre- and postmenopausal women is lacking. Some of the studies that have described a higher prevalence of HF-NEF in women relied on clinical diagnoses of HF together with normal systolic function and did not measure diastolic function. This applies to the analysis of patients hospitalized for HF and some epidemiological investigations that agree on the greater prevalence of HF-NEF in women. Population-based studies with echocardiographic determination of diastolic function have suggested equal or greater prevalence of diastolic dysfunction in men. Major risk factors for HF-NEF include hypertension, aging, obesity, diabetes, and ischemia. Hypertension is more frequent in women and can contribute to left ventricular and arterial stiffening in a gender-specific way. Aging, obesity, and diabetes affect myocardial and vascular stiffness differently and lead to different forms of myocardial hypertrophy in women and men. In contrast, ischemia may play a greater role in men. Gender differences in ventricular diastolic distensibility, in vascular stiffness and ventricular/vascular coupling, in skeletal muscle adaptation to HF, and in the perception of symptoms may contribute to a greater rate of HF-NEF in women. The underlying molecular mechanisms include gender differences in calcium handling, in the NO system, and in natriuretic peptides. Estrogen affects collagen synthesis and degradation and inhibits the renin-angiotensin system. Effects of estrogen may provide benefit to premenopausal women, and the loss of its protective mechanisms may render the heart of postmenopausal women more vulnerable. Thus, a number of molecular mechanisms can contribute to the gender differences in HF-NEF.

Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory

PubMed Central

Chompre, Gladys; Cruz, Emmanuel; Maldonado, Lucianette; Rivera-Amill, Vanessa; Porter, James T.; Noel, Richard J.

2012-01-01

Despite the widespread use of antiretroviral therapy that effectively limits viral replication, memory impairment remains a dilemma for HIV infected people. In the CNS, HIV infection of astrocytes leads to the production of the HIV-1 Nef protein without viral replication. Post mortem studies have found Nef expression in hippocampal astrocytes of people with HIV associated dementia suggesting that astrocytic Nef may contribute to HIV associated cognitive impairment even when viral replication is suppressed. To test whether astrocytic expression of Nef is sufficient to induce cognitive deficits, we examined the effect of implanting primary rat astrocytes expressing Nef into the hippocampus on spatial and recognition memory. Rats implanted unilaterally with astrocytes expressing Nef showed impaired novel location and novel object recognition in comparison with controls implanted with astrocytes expressing green fluorescent protein (GFP). This impairment was correlated with an increase in chemokine ligand 2 (CCL2) expression and the infiltration of peripheral macrophages into the hippocampus at the site of injection. Furthermore, the Nef exposed rats exhibited a bilateral loss of CA3 neurons. These results suggest that Nef protein expressed by the implanted astrocytes activates the immune system leading to neuronal damage and spatial and recognition memory deficits. Therefore, the continued expression of Nef by astrocytes in the absence of viral replication has the potential to contribute to HIV associated cognitive impairment. PMID:22926191

Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.

PubMed

Mahiti, Macdonald; Brumme, Zabrina L; Jessen, Heiko; Brockman, Mark A; Ueno, Takamasa

2015-07-31

HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission. Copyright © 2015 Elsevier Inc. All rights reserved.

Activation/proliferation and apoptosis of bystander goat lymphocytes induced by a macrophage-tropic chimeric caprine arthritis encephalitis virus expressing SIV Nef

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

Bouzar, Baya Amel; Rea, Angela; Hoc-Villet, Stephanie

Caprine arthritis encephalitis virus (CAEV) is the natural lentivirus of goats, well known for its tropism for macrophages and its inability to cause infection in lymphocytes. The viral genome lacks nef, tat, vpu and vpx coding sequences. To test the hypothesis that when nef is expressed by the viral genome, the virus became toxic for lymphocytes during replication in macrophages, we inserted the SIVsmm PBj14 nef coding sequences into the genome of CAEV thereby generating CAEV-nef. This recombinant virus is not infectious for lymphocytes but is fully replication competent in goat macrophages in which it constitutively expresses the SIV Nef.more » We found that goat lymphocytes cocultured with CAEV-nef-infected macrophages became activated, showing increased expression of the interleukin-2 receptor (IL-2R). Activation correlated with increased proliferation of the cells. Interestingly, a dual effect in terms of apoptosis regulation was observed in exposed goat lymphocytes. Nef was found first to induce a protection of lymphocytes from apoptosis during the first few days following exposure to infected macrophages, but later it induced increased apoptosis in the activated lymphocytes. This new recombinant virus provides a model to study the functions of Nef in the context of infection of macrophages, but in absence of infection of T lymphocytes and brings new insights into the biological effects of Nef on lymphocytes.« less

HIV-1 Env and Nef Cooperatively Contribute to Plasmacytoid Dendritic Cell Activation via CD4-Dependent Mechanisms.

PubMed

Reszka-Blanco, Natalia J; Sivaraman, Vijay; Zhang, Liguo; Su, Lishan

2015-08-01

Plasmacytoid dendritic cells (pDCs) are the major source of type I IFN (IFN-I) in response to human immunodeficiency virus type 1 (HIV-1) infection. pDCs are rapidly activated during HIV-1 infection and are implicated in reducing the early viral load, as well as contributing to HIV-1-induced pathogenesis. However, most cell-free HIV-1 isolates are inefficient in activating human pDCs, and the mechanisms of HIV-1 recognition by pDCs and pDC activation are not clearly defined. In this study, we report that two genetically similar HIV-1 variants (R3A and R3B) isolated from a rapid progressor differentially activated pDCs to produce alpha interferon (IFN-α). The highly pathogenic R3A efficiently activated pDCs to induce robust IFN-α production, while the less pathogenic R3B did not. The viral determinant for efficient pDC activation was mapped to the V1V2 region of R3A Env, which also correlated with enhanced CD4 binding activity. Furthermore, we showed that the Nef protein was also required for the activation of pDCs by R3A. Analysis of a panel of R3A Nef functional mutants demonstrated that Nef domains involved in CD4 downregulation were necessary for R3A to activate pDCs. Our data indicate that R3A-induced pDC activation depends on (i) the high affinity of R3A Env for binding the CD4 receptor and (ii) Nef activity, which is involved in CD4 downregulation. Our findings provide new insights into the mechanism by which HIV-1 induces IFN-α in pDCs, which contributes to pathogenesis. Plasmacytoid dendritic cells (pDCs) are the major type I interferon (IFN-I)-producing cells, and IFN-I actually contributes to pathogenesis during chronic viral infections. How HIV-1 activates pDCs and the roles of pDCs/IFN-I in HIV-1 pathogenesis remain unclear. We report here that the highly pathogenic HIV R3A efficiently activated pDCs to induce IFN-α production, while most HIV-1 isolates are inefficient in activating pDCs. We have discovered that R3A-induced pDC activation depends on (i) the high affinity of R3A Env for binding the CD4 receptor and (ii) Nef activity, which is involved in CD4 downregulation. Our findings thus provide new insights into the mechanism by which HIV-1 induces IFN-α in pDCs and contributes to HIV-1 pathogenesis. These novel findings will be of great interest to those working on the roles of IFN and pDCs in HIV-1 pathogenesis in general and on the interaction of HIV-1 with pDCs in particular. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Nucleotide Binding by Lhs1p Is Essential for Its Nucleotide Exchange Activity and for Function in Vivo*

PubMed Central

de Keyzer, Jeanine; Steel, Gregor J.; Hale, Sarah J.; Humphries, Daniel; Stirling, Colin J.

2009-01-01

Protein translocation and folding in the endoplasmic reticulum of Saccharomyces cerevisiae involves two distinct Hsp70 chaperones, Lhs1p and Kar2p. Both proteins have the characteristic domain structure of the Hsp70 family consisting of a conserved N-terminal nucleotide binding domain and a C-terminal substrate binding domain. Kar2p is a canonical Hsp70 whose substrate binding activity is regulated by cochaperones that promote either ATP hydrolysis or nucleotide exchange. Lhs1p is a member of the Grp170/Lhs1p subfamily of Hsp70s and was previously shown to function as a nucleotide exchange factor (NEF) for Kar2p. Here we show that in addition to this NEF activity, Lhs1p can function as a holdase that prevents protein aggregation in vitro. Analysis of the nucleotide requirement of these functions demonstrates that nucleotide binding to Lhs1p stimulates the interaction with Kar2p and is essential for NEF activity. In contrast, Lhs1p holdase activity is nucleotide-independent and unaffected by mutations that interfere with ATP binding and NEF activity. In vivo, these mutants show severe protein translocation defects and are unable to support growth despite the presence of a second Kar2p-specific NEF, Sil1p. Thus, Lhs1p-dependent nucleotide exchange activity is vital for ER protein biogenesis in vivo. PMID:19759005

Genetic and Functional Diversity of Human Immunodeficiency Virus Type 1 Subtype B Nef Primary Isolates

PubMed Central

Foster, John L.; Molina, Rene P.; Luo, Tianci; Arora, Vivek K.; Huang, Yaoxing; Ho, David D.; Garcia, J. Victor

2001-01-01

We have characterized the functional integrity of seven primary Nef isolates: five from a long-term nonprogressing human immunodeficiency virus (HIV)-infected individual and one each from two patients with AIDS. One of the seven Nefs was defective for CD4 downregulation, two others were defective for PAK-2 activation, and one Nef was defective for PAK-2 activation and major histocompatibility complex (MHC) class I downregulation. Five of the Nefs were tested and found to be functional for the enhancement of virus particle infectivity. The structural basis for each of the functional defects has been analyzed by constructing a consensus nef, followed by mutational analysis of the variant amino acid residues. Mutations A29V and F193I were deleterious to CD4 downregulation and PAK-2 activation, respectively, while S189R rendered Nef defective for both MHC class I downregulation and PAK-2 activation. A search of the literature identified HIVs from five patients with Nefs predominantly mutated at F193 and from one patient with Nefs predominantly mutated at A29. A29 is highly conserved in all HIV subtypes except for subtype E. F193 is conserved in subtype B (and possibly in the closely related subtype D), but none of the other HIV group M subtypes. Our results suggest that functional distinctions may exist between HIV subtypes. PMID:11160665

Lentiviral Nef suppresses iron uptake in a strain specific manner through inhibition of Transferrin endocytosis

PubMed Central

2014-01-01

Background Increased cellular iron levels are associated with high mortality in HIV-1 infection. Moreover iron is an important cofactor for viral replication, raising the question whether highly divergent lentiviruses actively modulate iron homeostasis. Here, we evaluated the effect on cellular iron uptake upon expression of the accessory protein Nef from different lentiviral strains. Results Surface Transferrin receptor (TfR) levels are unaffected by Nef proteins of HIV-1 and its simian precursors but elevated in cells expressing Nefs from most other primate lentiviruses due to reduced TfR internalization. The SIV Nef-mediated reduction of TfR endocytosis is dependent on an N-terminal AP2 binding motif that is not required for downmodulation of CD4, CD28, CD3 or MHCI. Importantly, SIV Nef-induced inhibition of TfR endocytosis leads to the reduction of Transferrin uptake and intracellular iron concentration and is accompanied by attenuated lentiviral replication in macrophages. Conclusion Inhibition of Transferrin and thereby iron uptake by SIV Nef might limit viral replication in myeloid cells. Furthermore, this new SIV Nef function could represent a virus-host adaptation that evolved in natural SIV-infected monkeys. PMID:24383984

Characterization of Gag and Nef-specific ELISpot-based CTL responses in HIV-1 infected Indian individuals.

PubMed

Mendiratta, Sanjay; Vajpayee, Madhu; Malhotra, Uma; Kaushik, Shweta; Dar, Lalit; Mojumdar, Kamalika; Chauhan, Neeraj Kumar; Sreenivas, Vishnubhatla

2009-02-01

Cytotoxic T lymphocyte (CTL) responses to Gag have been most frequently linked to control of viremia whereas CTL responses to Nef have direct relationship with viral load. IFN-gamma ELISpot assay was used to screen CTL responses at single peptide level directed at HIV-1 subtype C Gag and Nef proteins in 30 antiretroviral therapy naive HIV-1 infected Indian individuals. PBMCs from 73.3% and 90% of the study population showed response to Gag and Nef antigens, respectively. The magnitude of Gag-specific CTL responses was inversely correlated with plasma viral load (r = -0.45, P = 0.001), whereas magnitude of Nef-specific responses was directly correlated (r = 0.115). Thirteen immunodominant regions (6 in Gag, 7 in Nef) were identified in the current study. The identification of Gag and Nef-specific responses across HIV-1 infected Indian population and targeting epitopes from multiple immunodominant regions may provide useful insight into the designing of new immunotherapy and vaccines.

Neuromorphic Hardware Architecture Using the Neural Engineering Framework for Pattern Recognition.

PubMed

Wang, Runchun; Thakur, Chetan Singh; Cohen, Gregory; Hamilton, Tara Julia; Tapson, Jonathan; van Schaik, Andre

2017-06-01

We present a hardware architecture that uses the neural engineering framework (NEF) to implement large-scale neural networks on field programmable gate arrays (FPGAs) for performing massively parallel real-time pattern recognition. NEF is a framework that is capable of synthesising large-scale cognitive systems from subnetworks and we have previously presented an FPGA implementation of the NEF that successfully performs nonlinear mathematical computations. That work was developed based on a compact digital neural core, which consists of 64 neurons that are instantiated by a single physical neuron using a time-multiplexing approach. We have now scaled this approach up to build a pattern recognition system by combining identical neural cores together. As a proof of concept, we have developed a handwritten digit recognition system using the MNIST database and achieved a recognition rate of 96.55%. The system is implemented on a state-of-the-art FPGA and can process 5.12 million digits per second. The architecture and hardware optimisations presented offer high-speed and resource-efficient means for performing high-speed, neuromorphic, and massively parallel pattern recognition and classification tasks.

Pharmacokinetics of coadministration of levothyroxine sodium and alendronate sodium new effervescent formulation.

PubMed

Bone, H G; Walter, M A; Hurley, M E; Epstein, S

2017-05-01

No clinically important pharmacokinetic interference of alendronate occurred between a new effervescent formulation of alendronate and levothyroxine when coadministered. The combination does not materially affect levothyroxine absorption. Concurrent treatment of osteoporosis with alendronate (Aln) and hypothyroidism with levothyroxine (LT4) may be problematic because both drugs are to be taken separately after fasting overnight. The primary objective was to assess pharmacokinetic interactions between a new effervescent formulation of Aln (Aln-NEF) and LT4. A randomized, open-label, 3-way crossover study was conducted in 30 healthy adults (15 women). Subjects were dosed 3 times, separated by 35 days, after overnight fasts, with Aln-NEF alone (70 mg), LT4 alone (600 μg), or Aln-NEF and LT4 concurrently. Samples were analyzed for plasma Aln and serum LT4. Pharmacokinetic drug-drug interaction was assessed using 90% confidence intervals (CIs) for the test/reference ratio of the geometric means for area under the concentration-time curve from time zero to last measureable time point (AUC 0-t ) and maximum concentration (C max ). Results were compared to the default no-effect boundaries of 80 to 125% for the ratio Aln-NEF and LT4 concurrently/Aln-NEF alone and the ratio Aln-NEF and LT4 concurrently/LT4 alone. Geometric mean ratios (Aln-NEF with LT4/Aln-NEF alone) were 0.927 (90% CI 0.795-1.081) for AUC 0-8 and 0.912 (90% CI 0.773-1.077) for C max , demonstrating LT4 does not appreciably affect the pharmacokinetics of Aln. Geometric mean ratios (LT4 with Aln-NEF/LT4 alone) were 1.049 (90% CI 0.983-1.119) for AUC 0-48 and 1.075 (90% CI 1.006-1.148) for C max , demonstrating LT4 is bioequivalent between the 2 treatments. Coadministration of Aln-NEF and LT4 was well tolerated. There was no clinically important pharmacokinetic interference between the Aln-NEF formulation and LT4. Aln-NEF does not materially affect LT4 absorption.

A Low-Voltage Chopper-Stabilized Amplifier for Fetal ECG Monitoring With a 1.41 Power Efficiency Factor.

PubMed

Song, Shuang; Rooijakkers, Michael; Harpe, Pieter; Rabotti, Chiara; Mischi, Massimo; van Roermund, Arthur H M; Cantatore, Eugenio

2015-04-01

This paper presents a low-voltage current-reuse chopper-stabilized frontend amplifier for fetal ECG monitoring. The proposed amplifier allows for individual tuning of the noise in each measurement channel, minimizing the total power consumption while satisfying all application requirements. The low-voltage current reuse topology exploits power optimization in both the current and the voltage domain, exploiting multiple supply voltages (0.3, 0.6 and 1.2 V). The power management circuitry providing the different supplies is optimized for high efficiency (peak charge-pump efficiency = 90%).The low-voltage amplifier together with its power management circuitry is implemented in a standard 0.18 μm CMOS process and characterized experimentally. The amplifier core achieves both good noise efficiency factor (NEF=1.74) and power efficiency factor (PEF=1.05). Experiments show that the amplifier core can provide a noise level of 0.34 μVrms in a 0.7 to 182 Hz band, consuming 1.17 μW power. The amplifier together with its power management circuitry consumes 1.56 μW, achieving a PEF of 1.41. The amplifier is also validated with adult ECG and pre-recorded fetal ECG measurements.

Low-Power Low-Noise Amplifier Using Attenuation-Adaptive Noise Control for Ultrasound Imaging Systems.

PubMed

Jung, Sung-Jin; Hong, Seong-Kwan; Kwon, Oh-Kyong

2017-02-01

This paper presents a low-noise amplifier (LNA) using attenuation-adaptive noise control (AANC) for ultrasound imaging systems. The proposed AANC reduces unnecessary power consumption of the LNA, which arises from useless noise floor, by controlling the noise floor of the LNA with respect to the attenuation of the ultrasound. In addition, a current feedback amplifier with a source-degenerated input stage reduces variations of the bandwidth and the closed loop gain, which are caused by the AANC. The proposed LNA was fabricated using a 0.18-[Formula: see text] CMOS process. The input-referred voltage noise density of the fabricated LNA is 1.01 [Formula: see text] at the frequency of 5 MHz. The second harmonic distortion is -53.5 dB when the input signal frequency is 5 MHz and the output voltage swing is 2 [Formula: see text]. The power consumption of the LNA using the AANC is 16.2 mW at the supply voltage of 1.8 V, which is reduced to 64% of that without using the AANC. The noise efficiency factor (NEF) of the proposed LNA is 3.69, to our knowledge, which is the lowest NEF compared with previous LNAs for ultrasound imaging.

The Sydney Blood Bank Cohort: implications for viral fitness as a cause of elite control.

PubMed

Zaunders, John; Dyer, Wayne B; Churchill, Melissa

2011-05-01

The Sydney Blood Bank Cohort comprised eight individuals who were infected with an attenuated, nef/LTR-deleted strain of HIV-1 from a single donor. All six recipients with sufficient follow-up, as well as the donor, were long-term nonprogressors. Only three recipients have maintained undetectable plasma viral loads, allowing investigation of factors that determined elite control of attenuated HIV-1 infection. Follow-up of recipients showed that infection with this attenuated HIV-1 strain resulted in either low or absent viral replication in vivo for up to 29 years. The three patients without detectable viraemia have been studied for virological, genetic and immunological correlates of elite control. CD4 proliferation in vitro in response to p24 provided the clearest distinction of elite controllers from the slow progressors. Host factors are believed to differentiate the three elite controllers; only one, C135, has identifiable genetic polymorphisms that probably contributed to nonprogression: Δ32 CCR5 heterozygosity, HLA-B57 and HLA-DR13 alleles, in addition to infection with nef-defective HIV-1. Even nef-defective HIV-1 can lead to sufficient replication in vivo to enable viral evolution and eventual progression to immunodeficiency. Host factors modified the outcome of infection with attenuated HIV-1, as exemplified by the unique patient C135.

Structural defects and variations in the HIV-1 nef gene from rapid, slow and non-progressor children.

PubMed

Casartelli, Nicoletta; Di Matteo, Gigliola; Argentini, Claudio; Cancrini, Caterina; Bernardi, Stefania; Castelli, Guido; Scarlatti, Gabriella; Plebani, Anna; Rossi, Paolo; Doria, Margherita

2003-06-13

Evaluation of sequence evolution as well as structural defects and mutations of the human immunodeficiency virus-type 1 (HIV-1) nef gene in relation to disease progression in infected children. We examined a large number of nef alleles sequentially derived from perinatally HIV-1-infected children with different rates of disease progression: six non-progressors (NPs), four rapid progressors (RPs), and three slow progressors (SPs). Nef alleles (182 total) were isolated from patients' peripheral blood mononuclear cells (PBMCs), sequenced and analysed for their evolutionary pattern, frequency of mutations and occurrence of amino acid variations associated with different stages of disease. The evolution rate of the nef gene apparently correlated with CD4+ decline in all progression groups. Evidence for rapid viral turnover and positive selection for changes were found only in two SPs and two RPs respectively. In NPs, a higher proportion of disrupted sequences and mutations at various functional motifs were observed. Furthermore, NP-derived Nef proteins were often changed at residues localized in the folded core domain at cytotoxic T lymphocytes (CTL) epitopes (E(105), K(106), E(110), Y(132), K(164), and R(200)), while other residues outside the core domain are more often changed in RPs (A(43)) and SPs (N(173) and Y(214)). Our results suggest a link between nef gene functions and the progression rate in HIV-1-infected children. Moreover, non-progressor-associated variations in the core domain of Nef, together with the genetic analysis, suggest that nef gene evolution is shaped by an effective immune system in these patients.

Changes in the Plasticity of HIV-1 Nef RNA during the Evolution of the North American Epidemic

PubMed Central

Manzourolajdad, Amirhossein; Gonzalez, Mileidy; Spouge, John L.

2016-01-01

Because of a high mutation rate, HIV exists as a viral swarm of many sequence variants evolving under various selective pressures from the human immune system. Although the Nef gene codes for the most immunogenic of HIV accessory proteins, which alone makes it of great interest to HIV research, it also encodes an RNA structure, whose contribution to HIV virulence has been largely unexplored. Nef RNA helps HIV escape RNA interference (RNAi) through nucleotide changes and alternative folding. This study examines Historic and Modern Datasets of patient HIV-1 Nef sequences during the evolution of the North American epidemic for local changes in RNA plasticity. By definition, RNA plasticity refers to an RNA molecule’s ability to take alternative folds (i.e., alternative conformations). Our most important finding is that an evolutionarily conserved region of the HIV-1 Nef gene, which we denote by R2, recently underwent a statistically significant increase in its RNA plasticity. Thus, our results indicate that Modern Nef R2 typically accommodates an alternative fold more readily than Historic Nef R2. Moreover, the increase in RNA plasticity resides mostly in synonymous nucleotide changes, which cannot be a response to selective pressures on the Nef protein. R2 may therefore be of interest in the development of antiviral RNAi therapies. PMID:27685447

Molecular characterization of HIV-1 Nef and ACOT8 interaction: insights from in silico structural predictions and in vitro functional assays

NASA Astrophysics Data System (ADS)

Serena, Michela; Giorgetti, Alejandro; Busato, Mirko; Gasparini, Francesca; Diani, Erica; Romanelli, Maria Grazia; Zipeto, Donato

2016-03-01

HIV-1 Nef interacts with several cellular proteins, among which the human peroxisomal thioesterase 8 (ACOT8). This interaction may be involved in the endocytosis regulation of membrane proteins and might modulate lipid composition in membrane rafts. Nef regions involved in the interaction have been experimentally characterized, whereas structural details of the ACOT8 protein are unknown. The lack of structural information hampers the comprehension of the functional consequences of the complex formation during HIV-1 infection. We modelled, through in silico predictions, the ACOT8 structure and we observed a high charge complementarity between Nef and ACOT8 surfaces, which allowed the identification of the ACOT8 putative contact points involved in the interaction. The predictions were validated by in vitro assays through the development of ACOT8 deletion mutants. Coimmunoprecipitation and immunofluorescence analyses showed that ACOT8 Arg45-Phe55 and Arg86-Pro93 regions are involved in Nef association. In addition, K91S mutation abrogated the interaction with Nef, indicating that Lys91 plays a key role in the interaction. Finally, when associated with ACOT8, Nef may be preserved from degradation. These findings improve the comprehension of the association between HIV-1 Nef and ACOT8, helping elucidating the biological effect of their interaction.

HIV-1 Nef sequesters MHC-I intracellularly by targeting early stages of endocytosis and recycling

PubMed Central

Dirk, Brennan S.; Pawlak, Emily N.; Johnson, Aaron L.; Van Nynatten, Logan R.; Jacob, Rajesh A.; Heit, Bryan; Dikeakos, Jimmy D.

2016-01-01

A defining characteristic of HIV-1 infection is the ability of the virus to persist within the host. Specifically, MHC-I downregulation by the HIV-1 accessory protein Nef is of critical importance in preventing infected cells from cytotoxic T-cell mediated killing. Nef downregulates MHC-I by modulating the host membrane trafficking machinery, resulting in the endocytosis and eventual sequestration of MHC-I within the cell. In the current report, we utilized the intracellular protein-protein interaction reporter system, bimolecular fluorescence complementation (BiFC), in combination with super-resolution microscopy, to track the Nef/MHC-I interaction and determine its subcellular localization in cells. We demonstrate that this interaction occurs upon Nef binding the MHC-I cytoplasmic tail early during endocytosis in a Rab5-positive endosome. Disruption of early endosome regulation inhibited Nef-dependent MHC-I downregulation, demonstrating that Nef hijacks the early endosome to sequester MHC-I within the cell. Furthermore, super-resolution imaging identified that the Nef:MHC-I BiFC complex transits through both early and late endosomes before ultimately residing at the trans-Golgi network. Together we demonstrate the importance of the early stages of the endocytic network in the removal of MHC-I from the cell surface and its re-localization within the cell, which allows HIV-1 to optimally evade host immune responses. PMID:27841315

Nef exosomes isolated from the plasma of individuals with HIV-associated dementia (HAD) can induce Aβ(1-42) secretion in SH-SY5Y neural cells.

PubMed

Khan, Mahfuz B; Lang, Michelle J; Huang, Ming-Bo; Raymond, Andrea; Bond, Vincent C; Shiramizu, Bruce; Powell, Michael D

2016-04-01

In the era of combined antiretroviral therapy (CART), many of the complications due to HIV-1 infection have diminished. One exception is HIV-associated neurocognitive disorder (HAND). HAND is a spectrum of disorders in cognitive function that ranges from asymptomatic disease to severe dementia (HAD). The milder form of HAND has actually remained the same or slightly increased in prevalence in the CART era. Even in individuals who have maintained undetectable HIV RNA loads, viral proteins such as Nef and Tat can continue to be expressed. In this report, we show that Nef protein and nef messenger RNA (mRNA) are packaged into exosomes that remain in circulation in patients with HAD. Plasma-derived Nef exosomes from patients with HAD have the ability to interact with the neuroblastoma cell line SH-SY5Y and deliver nef mRNA. The mRNA can induce expression of Nef in target cells and subsequently increase expression and secretion of beta-amyloid (Aβ) and Aβ peptides. Increase secretion of amyloid peptide could contribute to cognitive impairment seen in HAND.

Differential signaling mechanism for HIV-1 Nef-mediated production of IL-6 and IL-8 in human astrocytes.

PubMed

Liu, Xun; Kumar, Anil

2015-06-15

Variety of HIV-1 viral proteins including HIV-1 Nef are known to activate astrocytes and microglia in the brain and cause the release of pro-inflammatory cytokines, which is thought to be one of the mechanisms leading to HIV-1- mediated neurotoxicity. IL-6 and IL-8 have been found in the CSF of patients with HIV-1 associated dementia (HAD), suggesting that they might play important roles in HIV-1 neuropathology. In the present study we examined the effects of HIV-1 Nef on IL-6 and IL-8 induction in astrocytes. The results demonstrate that both IL-6 and IL-8 are significantly induced in HIV-1 Nef-transfected SVGA astrocytes and HIV-1 Nef-treated primary fetal astrocytes. We also determined the molecular mechanisms responsible for the HIV-1 Nef-induced increased IL-6 and IL-8 by using chemical inhibitors and siRNAs against PI3K/Akt/PKC, p38 MAPK, NF-κB, CEBP and AP-1. Our results clearly demonstrate that the PI3K/PKC, p38 MAPK, NF-κB and AP-1 pathways are involved in HIV-1 Nef-induced IL-6 production in astrocytes, while PI3K/PKC and NF-κB pathways are involved in HIV-1 Nef-induced IL-8 production. These results offer new potential targets to develop therapeutic strategy for treatment of HIV-1 associated neurological disorders, prevalent in > 40% of individuals infected with HIV-1.

HIV-1 Nef-induced Down-Regulation of MHC Class I Requires AP-1 and Clathrin but Not PACS-1 and Is Impeded by AP-2

PubMed Central

Lubben, Nienke B.; Sahlender, Daniela A.; Motley, Alison M.; Lehner, Paul J.; Benaroch, Philippe

2007-01-01

Major histocompatibility complex class I is down-regulated from the surface of human immunodeficiency virus (HIV)-1-infected cells by Nef, a virally encoded protein that is thought to reroute MHC-I to the trans-Golgi network (TGN) in a phosphofurin acidic cluster sorting protein (PACS) 1, adaptor protein (AP)-1, and clathrin-dependent manner. More recently, an alternative model has been proposed, in which Nef uses AP-1 to direct MHC-I to endosomes and lysosomes. Here, we show that knocking down either AP-1 or clathrin with small interfering RNA inhibits the down-regulation of HLA-A2 (an MHC-I isotype) by Nef in HeLa cells. However, knocking down PACS-1 has no effect, not only on Nef-induced down-regulation of HLA-A2 but also on the localization of other proteins containing acidic cluster motifs. Surprisingly, knocking down AP-2 actually enhances Nef activity. Immuno-electron microscopy labeling of Nef-expressing cells indicates that HLA-A2 is rerouted not to the TGN, but to endosomes. In AP-2–depleted cells, more of the HLA-A2 localizes to the inner vesicles of multivesicular bodies. We propose that depleting AP-2 potentiates Nef activity by altering the membrane composition and dynamics of endosomes and causing increased delivery of HLA-A2 to a prelysosomal compartment. PMID:17581864

Optimized Replicating Renilla Luciferase Reporter HIV-1 Utilizing Novel Internal Ribosome Entry Site Elements for Native Nef Expression and Function.

PubMed

Alberti, Michael O; Jones, Jennifer J; Miglietta, Riccardo; Ding, Haitao; Bakshi, Rakesh K; Edmonds, Tara G; Kappes, John C; Ochsenbauer, Christina

2015-12-01

We previously developed replication-competent reporter HIV-1 (referred to herein as LucR.T2A reporter viruses), utilizing a "ribosome skipping" T2A peptide strategy to link Renilla luciferase (LucR) with Nef expression. The demonstrated utility for HIV-1 vaccine and transmission study applications included measurement of neutralizing antibody (NAb) activity in vaccine sera, improved cell-mediated virus inhibition assays, such as T cell-mediated virus inhibition and antibody-dependent cell-mediated cytotoxicity (ADCC) assays, and humanized mouse models. Herein, we extend our prior work and introduce reporter virus technology for applications that require fully functional Nef. We demonstrate that in CD4(+) T cells productively infected with LucR.T2A reporter viruses, T2A peptide-driven Nef expression and function, such as down-regulation of surface CD4 and MHC-I, were impaired. We overcame this limitation of LucR.T2A reporter viruses and achieved physiological Nef expression and function by engineering novel LucR reporter HIV-1 comprising 11 different internal ribosome entry site (IRES) elements chosen for size and relative activity. A range of Nef expression was observed in 293T cells transfected with the different LucR.IRES reporter virus constructs. Iteratively, we identified IRES reporter genomes that expressed Nef closest to physiological levels and produced virus with infectivity, titers, and replication kinetics similar to nonreporter viruses. Our results demonstrated that LucR reporter activity was stable over multiple replication cycles in peripheral blood mononuclear cells (PBMCs). Furthermore, we analyzed Nef functionality, i.e., down-modulation of MHC-I and CD4, following infection of T cell lines and PBMCs. Unlike LucR.T2A reporter virus, one of the redesigned LucR.IRES reporter viruses [containing the modified encephalomyocarditis virus (EMCV) 6ATR IRES element, "6ATRi"] demonstrated Nef expression and function similar to parental "nonreporter" virus. In a previously validated (nef-independent) T cell-based NAb neutralization assay, LucR.6ATRi reporter virus performed indistinguishably from LucR.T2A reporter virus. In summary, reporter viruses comprising the "6ATRi" element promise to augment HIV-1 vaccine and transmission research approaches requiring a sensitive reporter readout combined with wild-type Nef function.

Optimized Replicating Renilla Luciferase Reporter HIV-1 Utilizing Novel Internal Ribosome Entry Site Elements for Native Nef Expression and Function

PubMed Central

Alberti, Michael O.; Jones, Jennifer J.; Miglietta, Riccardo; Ding, Haitao; Bakshi, Rakesh K.; Edmonds, Tara G.; Kappes, John C.

2015-01-01

Abstract We previously developed replication-competent reporter HIV-1 (referred to herein as LucR.T2A reporter viruses), utilizing a “ribosome skipping” T2A peptide strategy to link Renilla luciferase (LucR) with Nef expression. The demonstrated utility for HIV-1 vaccine and transmission study applications included measurement of neutralizing antibody (NAb) activity in vaccine sera, improved cell-mediated virus inhibition assays, such as T cell-mediated virus inhibition and antibody-dependent cell-mediated cytotoxicity (ADCC) assays, and humanized mouse models. Herein, we extend our prior work and introduce reporter virus technology for applications that require fully functional Nef. We demonstrate that in CD4+ T cells productively infected with LucR.T2A reporter viruses, T2A peptide-driven Nef expression and function, such as down-regulation of surface CD4 and MHC-I, were impaired. We overcame this limitation of LucR.T2A reporter viruses and achieved physiological Nef expression and function by engineering novel LucR reporter HIV-1 comprising 11 different internal ribosome entry site (IRES) elements chosen for size and relative activity. A range of Nef expression was observed in 293T cells transfected with the different LucR.IRES reporter virus constructs. Iteratively, we identified IRES reporter genomes that expressed Nef closest to physiological levels and produced virus with infectivity, titers, and replication kinetics similar to nonreporter viruses. Our results demonstrated that LucR reporter activity was stable over multiple replication cycles in peripheral blood mononuclear cells (PBMCs). Furthermore, we analyzed Nef functionality, i.e., down-modulation of MHC-I and CD4, following infection of T cell lines and PBMCs. Unlike LucR.T2A reporter virus, one of the redesigned LucR.IRES reporter viruses [containing the modified encephalomyocarditis virus (EMCV) 6ATR IRES element, “6ATRi”] demonstrated Nef expression and function similar to parental “nonreporter” virus. In a previously validated (nef-independent) T cell-based NAb neutralization assay, LucR.6ATRi reporter virus performed indistinguishably from LucR.T2A reporter virus. In summary, reporter viruses comprising the “6ATRi” element promise to augment HIV-1 vaccine and transmission research approaches requiring a sensitive reporter readout combined with wild-type Nef function. PMID:26101895

Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence.

PubMed

Sugden, Scott M; Bego, Mariana G; Pham, Tram N Q; Cohen, Éric A

2016-03-03

The plasma membrane protects the cell from its surroundings and regulates cellular communication, homing, and metabolism. Not surprisingly, the composition of this membrane is highly controlled through the vesicular trafficking of proteins to and from the cell surface. As intracellular pathogens, most viruses exploit the host plasma membrane to promote viral replication while avoiding immune detection. This is particularly true for the enveloped human immunodeficiency virus (HIV), which assembles and obtains its lipid shell directly at the plasma membrane. HIV-1 encodes two proteins, negative factor (Nef) and viral protein U (Vpu), which function primarily by altering the quantity and localization of cell surface molecules to increase virus fitness despite host antiviral immune responses. These proteins are expressed at different stages in the HIV-1 life cycle and employ a variety of mechanisms to target both unique and redundant surface proteins, including the viral receptor CD4, host restriction factors, immunoreceptors, homing molecules, tetraspanins and membrane transporters. In this review, we discuss recent progress in the study of the Nef and Vpu targeting of host membrane proteins with an emphasis on how remodeling of the cell membrane allows HIV-1 to avoid host antiviral immune responses leading to the establishment of systemic and persistent infection.

Immune Selection In Vitro Reveals Human Immunodeficiency Virus Type 1 Nef Sequence Motifs Important for Its Immune Evasion Function In Vivo

PubMed Central

Lee, Patricia; Ng, Hwee L.; Yang, Otto O.

2012-01-01

Human immunodeficiency virus type 1 (HIV-1) Nef downregulates major histocompatibility complex class I (MHC-I), impairing the clearance of infected cells by CD8+ cytotoxic T lymphocytes (CTLs). While sequence motifs mediating this function have been determined by in vitro mutagenesis studies of laboratory-adapted HIV-1 molecular clones, it is unclear whether the highly variable Nef sequences of primary isolates in vivo rely on the same sequence motifs. To address this issue, nef quasispecies from nine chronically HIV-1-infected persons were examined for sequence evolution and altered MHC-I downregulatory function under Gag-specific CTL immune pressure in vitro. This selection resulted in decreased nef diversity and strong purifying selection. Site-by-site analysis identified 13 codons undergoing purifying selection and 1 undergoing positive selection. Of the former, only 6 have been reported to have roles in Nef function, including 4 associated with MHC-I downregulation. Functional testing of naturally occurring in vivo polymorphisms at the 7 sites with no previously known functional role revealed 3 mutations (A84D, Y135F, and G140R) that ablated MHC-I downregulation and 3 (N52A, S169I, and V180E) that partially impaired MHC-I downregulation. Globally, the CTL pressure in vitro selected functional Nef from the in vivo quasispecies mixtures that predominately lacked MHC-I downregulatory function at the baseline. Overall, these data demonstrate that CTL pressure exerts a strong purifying selective pressure for MHC-I downregulation and identifies novel functional motifs present in Nef sequences in vivo. PMID:22553319

Effects of the tat and nef gene products of human immunodeficiency virus type 1 (HIV-1) on transcription controlled by the HIV-1 long terminal repeat and on cell growth in macrophages.

PubMed Central

Murphy, K M; Sweet, M J; Ross, I L; Hume, D A

1993-01-01

The RAW264 murine macrophage cell line was used as a model to examine the role of the tat and nef gene products in the transcription regulation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in macrophages. Contrary to claims that the activity of the HIV-1 LTR responds poorly in rodent cells to trans activation by the viral tat gene product, cotransfection of RAW264 cells with a tat expression plasmid in transient transfection assays caused a > 20-fold increase in reporter gene expression that was inhibited by mutations in the TAR region. RAW264 cells stably transfected with the tat plasmid displayed similarly elevated HIV-1 LTR-driven reporter gene activity. By contrast to previous reports indicating a negative role for nef in HIV transcription, cotransfection of RAW264 cells with a nef expression plasmid trans activated the HIV-1 LTR driving either a chloramphenicol acetyltransferase or a luciferase reporter gene. The action of nef was specific to the LTR, as expression of nef had no effect on the activity of the simian virus 40, c-fms, urokinase plasminogen activator, or type 5 acid phosphatase promoter. trans-activating activity was also manifested by a frameshift mutant expressing only the first 35 amino acids of the protein. The effects of nef were multiplicative with those of tat gene product and occurred even in the presence of bacterial lipopolysaccharide, which itself activated LTR-directed transcription. Examination of the effects of selected mutations in the LTR revealed that neither the kappa B sites in the direct repeat enhancer nor the TAR region was required as a cis-acting element in nef action. The action of nef was not species restricted; it was able to trans activate in the human monocyte-like cell line Mono Mac 6. The presence of a nef expression cassette in a neomycin phosphotransferase gene expression plasmid greatly reduced the number of G418-resistant colonies generated in stable transfection of RAW264 cells, and many of the colonies that were formed exhibited very slow growth. The frameshift mutant was also active in reducing colony generation. Given the absence of any effect of the frameshift mutation on nef function, its actions on macrophage growth and HIV transcription are discussed in terms of the role of the N-terminal 30 amino acids and of stable secondary structures in the mRNA. Images PMID:8230418

Fluctuations in diffusion processes in microgravity.

PubMed

Mazzoni, Stefano; Cerbino, Roberto; Vailati, Alberto; Giglio, Marzio

2006-09-01

It has been shown recently that diffusion processes exhibit giant nonequilibrium fluctuations (NEFs). That is, the diffusing fronts display corrugations whose length scale ranges from the molecular to the macroscopic one. The amplitude of the NEF diverges following a power law behavior proportional to q(-4) (where q is the wave vector). However, fluctuations of wave number smaller than a critical "rolloff" wave vector are quenched by the presence of gravity. It is therefore expected that in microgravity conditions, the amplitude of the NEF should be boosted by the absence of the buoyancy-driven restoring force. This may affect any diffusion process performed in microgravity, such as the crystallization of a protein solution induced by the diffusion of a salt buffer. The aim of GRADFLEX (GRAdient-Driven FLuctuation EXperiment), a joint project of ESA and NASA, is to investigate the presence of NEFs arising in a diffusion process under microgravity conditions. The project consists of two experiments. One is carried out by UNIMI (University of Milan) and INFM (Istituto Nazionale per la Fisica della Materia) and is focused on NEF in a concentration diffusion process. The other experiment is performed by UCSB (University of California at Santa Barbara) concerning temperature NEF in a simple fluid. In the UNIMI part of the GRADFLEX experimental setup, NEFs are induced in a binary mixture by means of the Soret effect. The diagnostic method is an all-optical quantitative shadowgraph technique. The power spectrum of the induced NEFs is obtained by the processing of the shadowgraph images. A detailed description of the experimental apparatus as well as the ground-based experimental results is presented here for the UNIMI-INFM experiment. The GRADFLEX payload is scheduled to fly on the FOTON M3 capsule in April 2007.

HIV-1 Nef disrupts MHC-I trafficking by recruiting AP-1 to the MHC-I cytoplasmic tail

PubMed Central

Roeth, Jeremiah F.; Williams, Maya; Kasper, Matthew R.; Filzen, Tracey M.; Collins, Kathleen L.

2004-01-01

To avoid immune recognition by cytotoxic T lymphocytes (CTLs), human immunodeficiency virus (HIV)-1 Nef disrupts the transport of major histocompatibility complex class I molecules (MHC-I) to the cell surface in HIV-infected T cells. However, the mechanism by which Nef does this is unknown. We report that Nef disrupts MHC-I trafficking by rerouting newly synthesized MHC-I from the trans-Golgi network (TGN) to lysosomal compartments for degradation. The ability of Nef to target MHC-I from the TGN to lysosomes is dependent on expression of the μ1 subunit of adaptor protein (AP) AP-1A, a cellular protein complex implicated in TGN to endolysosomal pathways. We demonstrate that in HIV-infected primary T cells, Nef promotes a physical interaction between endogenous AP-1 and MHC-I. Moreover, we present data that this interaction uses a novel AP-1 binding site that requires amino acids in the MHC-I cytoplasmic tail. In sum, our evidence suggests that binding of AP-1 to the Nef–MHC-I complex is an important step required for inhibition of antigen presentation by HIV. PMID:15569716

Migration of As, Hg, Pb, and Zn in arroyo sediments from a semiarid coastal system influenced by the abandoned gold mining district at El Triunfo, Baja California Sur, Mexico.

PubMed

Marmolejo-Rodríguez, Ana Judith; Sánchez-Martínez, Martha Alicia; Romero-Guadarrama, Juan Armando; Sánchez-González, Alberto; Magallanes-Ordóñez, Víctor René

2011-08-01

Extensive waste deposits (tailings) and ash from the ignition oven of the abandoned gold mine of mining district El Triunfo (MD-ET) in Baja California Sur, Mexico have released trace elements into the sediments of the Hondo-Las Gallinas-El Carrizal arroyo, which connects to the Pacific Ocean through an evaporitic basin. Migration of these elements through the arroyo is mainly caused by winds or tropical hurricanes that occur sporadically during the summer and cause the otherwise dry arroyo to overflow. To evaluate the concentration and distribution of the elements As, Hg, Pb, and Zn along the 48 km arroyo, surface sediments were collected from 26 sites, ranging from close to the MD-ET to the mouth of the arroyo at the Pacific Ocean. Concentrations in tailings and ash were for As 8890 and 505 000 mg kg(-1); for Hg 0.336 and 54.9 mg kg(-1); for Pb 92,700 and 19,300 mg kg(-1); and for Zn 49,600 and 1380 mg kg(-1). The average of the Normalized Enrichment Factor (Av-NEF) in surface sediments, calculated using background levels, indicates that the sediments are severely contaminated with As and Zn (Av-NEF = 22), Pb (Av-NEF = 24) and with a moderate contamination of Hg (Av-NEF = 7.5). The anthropogenic influence of those elements is reflected in the arroyo sediments as far as 18 km away from the MD-ET, whereas the samples closest to the discharge into the Pacific Ocean show a natural to moderate enrichment for As and Zn and low or no enrichment for Hg and Pb. A principal components analysis identified four principal components that explained 90% of the total variance. Factor 1 was characterized by a high positive contribution of the anthropogenic source elements, especially As, Pb, and Zn (37%), whereas Factor 2 was strongly correlated with the oxy-hydroxides of Fe and Mn (27%). Factor 3 was correlated with Li (16%) and Factor 4 with Al (10%), which indicates more than one source of lithogenic composition, though they played a minor role in the distribution of the elements.

Dependence of Golgi apparatus integrity on nitric oxide in vascular cells: implications in pulmonary arterial hypertension

PubMed Central

Lee, Jason E.; Patel, Kirit; Almodóvar, Sharilyn; Tuder, Rubin M.; Flores, Sonia C.

2011-01-01

Although reduced bioavailability of nitric oxide (NO) has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH), its consequences on organellar structure and function within vascular cells is largely unexplored. We investigated the effect of reduced NO on the structure of the Golgi apparatus as assayed by giantin or GM130 immunofluorescence in human pulmonary arterial endothelial (HPAECs) and smooth muscle (HPASMCs) cells, bovine PAECs, and human EA.hy926 endothelial cells. Golgi structure was also investigated in cells in tissue sections of pulmonary vascular lesions in idiopathic PAH (IPAH) and in macaques infected with a chimeric simian immunodeficiency virus containing the human immunodeficiency virus (HIV)-nef gene (SHIV-nef) with subcellular three-dimensional (3D) immunoimaging. Compounds with NO scavenging activity including 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO), methylene blue, N-acetylcysteine, and hemoglobin markedly fragmented the Golgi in all cell types evaluated as did monocrotaline pyrrole, while LY-83583, sildenafil, fasudil, Y-27632, Tiron, Tempol, or H2O2 did not. Golgi fragmentation by NO scavengers was inhibited by diethylamine NONOate, was evident in HPAECs after selective knockdown of endothelial nitric oxide synthase using small interfering RNA (siRNA), was independent of microtubule organization, required the GTPase dynamin 2, and was accompanied by depletion of α-soluble N-ethylmaleimide-sensitive factor (NSF) acceptor protein (α-SNAP) from Golgi membranes and codispersal of the SNAP receptor (SNARE) Vti1a with giantin. Golgi fragmentation was confirmed in endothelial and smooth muscle cells in pulmonary arterial lesions in IPAH and the SHIV-nef-infected macaque with subcellular 3D immunoimaging. In SHIV-nef-infected macaques Golgi fragmentation was observed in cells containing HIV-nef-bearing endosomes. The observed Golgi fragmentation suggests that NO plays a significant role in modulating global protein trafficking patterns that contribute to changes in the cell surface landscape and functional signaling in vascular cells. PMID:21217069

High-level HIV-1 Nef transient expression in Nicotiana benthamiana using the P19 gene silencing suppressor protein of Artichoke Mottled Crinckle Virus

PubMed Central

2009-01-01

Background In recent years, different HIV antigens have been successfully expressed in plants by either stable transformation or transient expression systems. Among HIV proteins, Nef is considered a promising target for the formulation of a multi-component vaccine due to its implication in the first steps of viral infection. Attempts to express Nef as a single protein product (not fused to a stabilizing protein) in transgenic plants resulted in disappointingly low yields (about 0.5% of total soluble protein). In this work we describe a transient expression system based on co-agroinfiltration of plant virus gene silencing suppressor proteins in Nicotiana benthamiana, followed by a two-step affinity purification protocol of plant-derived Nef. Results The effect of three gene silencing viral suppressor proteins (P25 of Potato Virus X, P19 of either Artichoke Mottled Crinckle virus and Tomato Bushy Stunt virus) on Nef transient expression yield was evaluated. The P19 protein of Artichoke Mottled Crinckle virus (AMCV-P19) gave the highest expression yield in vacuum co-agroinfiltration experiments reaching 1.3% of total soluble protein, a level almost three times higher than that previously reported in stable transgenic plants. The high yield observed in the co-agroinfiltrated plants was correlated to a remarkable decrease of Nef-specific small interfering RNAs (siRNAs) indicating an effective modulation of RNA silencing mechanisms by AMCV-P19. Interestingly, we also showed that expression levels in top leaves of vacuum co-agroinfiltrated plants were noticeably reduced compared to bottom leaves. Moreover, purification of Nef from agroinfiltrated tissue was achieved by a two-step immobilized metal ion affinity chromatography protocol with yields of 250 ng/g of fresh tissue. Conclusion We demonstrated that expression level of HIV-1 Nef in plant can be improved using a transient expression system enhanced by the AMCV-P19 gene silencing suppressor protein. Moreover, plant-derived Nef was purified, with enhanced yield, exploiting a two-step purification protocol. These results represent a first step towards the development of a plant-derived HIV vaccine. PMID:19930574

High-level HIV-1 Nef transient expression in Nicotiana benthamiana using the P19 gene silencing suppressor protein of Artichoke Mottled Crinckle Virus.

PubMed

Lombardi, Raffaele; Circelli, Patrizia; Villani, Maria Elena; Buriani, Giampaolo; Nardi, Luca; Coppola, Valentina; Bianco, Linda; Benvenuto, Eugenio; Donini, Marcello; Marusic, Carla

2009-11-20

In recent years, different HIV antigens have been successfully expressed in plants by either stable transformation or transient expression systems. Among HIV proteins, Nef is considered a promising target for the formulation of a multi-component vaccine due to its implication in the first steps of viral infection. Attempts to express Nef as a single protein product (not fused to a stabilizing protein) in transgenic plants resulted in disappointingly low yields (about 0.5% of total soluble protein). In this work we describe a transient expression system based on co-agroinfiltration of plant virus gene silencing suppressor proteins in Nicotiana benthamiana, followed by a two-step affinity purification protocol of plant-derived Nef. The effect of three gene silencing viral suppressor proteins (P25 of Potato Virus X, P19 of either Artichoke Mottled Crinckle virus and Tomato Bushy Stunt virus) on Nef transient expression yield was evaluated. The P19 protein of Artichoke Mottled Crinckle virus (AMCV-P19) gave the highest expression yield in vacuum co-agroinfiltration experiments reaching 1.3% of total soluble protein, a level almost three times higher than that previously reported in stable transgenic plants. The high yield observed in the co-agroinfiltrated plants was correlated to a remarkable decrease of Nef-specific small interfering RNAs (siRNAs) indicating an effective modulation of RNA silencing mechanisms by AMCV-P19. Interestingly, we also showed that expression levels in top leaves of vacuum co-agroinfiltrated plants were noticeably reduced compared to bottom leaves. Moreover, purification of Nef from agroinfiltrated tissue was achieved by a two-step immobilized metal ion affinity chromatography protocol with yields of 250 ng/g of fresh tissue. We demonstrated that expression level of HIV-1 Nef in plant can be improved using a transient expression system enhanced by the AMCV-P19 gene silencing suppressor protein. Moreover, plant-derived Nef was purified, with enhanced yield, exploiting a two-step purification protocol. These results represent a first step towards the development of a plant-derived HIV vaccine.

Bioassay, isolation and studies on the mechanism of action of neurite extension factor

NASA Technical Reports Server (NTRS)

Kligman, D.

1984-01-01

The identification and purification of molecules active in promoting neurite outgrowth requires a sensitive reproducible bioassay. A quantitative bioassay was utilized to purify a neurite extension factor (NEF) based on counting the number of phase bright neurons with processes at least equal to one cell body diameter after 20 hrs. in culture is defined, serum free medium. Using a combination of heat treatment DEAE cellulose chromatography and gel filtration, an acidic protein of M sub r = 75,000 was highly purified. Upon reduction, it yields subunits of M sub r = 37,000. Purified fractions are active half maximally at 100 ng/ml in inducing neurite outgrowth in this bioassay. Currently, monoclonal antibodies to NEF are being produced. Female Balb C mice were immunized with the antigen and fusions with mouse myeloma cells will be performed to yield hybridoma cells.

Identification of SIV Nef CD8(+) T cell epitopes restricted by a MHC class I haplotype associated with lower viral loads in a macaque AIDS model.

PubMed

Nomura, Takushi; Yamamoto, Hiroyuki; Takahashi, Naofumi; Naruse, Taeko K; Kimura, Akinori; Matano, Tetsuro

2014-07-25

Virus-specific CD8(+) T-cell responses are crucial for the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication. Multiple studies on HIV-infected individuals and SIV-infected macaques have indicated association of several major histocompatibility complex class I (MHC-I) genotypes with lower viral loads and delayed AIDS progression. Understanding of the viral control mechanism associated with these MHC-I genotypes would contribute to the development of intervention strategy for HIV control. We have previously reported a rhesus MHC-I haplotype, 90-120-Ia, associated with lower viral loads after SIVmac239 infection. Gag206-216 and Gag241-249 epitope-specific CD8(+) T-cell responses have been shown to play a central role in the reduction of viral loads, whereas the effect of Nef-specific CD8(+) T-cell responses induced in all the 90-120-Ia(+) macaques on SIV replication remains unknown. Here, we identified three CD8(+) T-cell epitopes, Nef9-19, Nef89-97, and Nef193-203, associated with 90-120-Ia. Nef9-19 and Nef193-203 epitope-specific CD8(+) T-cell responses frequently selected for mutations resulting in viral escape from recognition by these CD8(+) T cells, indicating that these CD8(+) T cells exert strong suppressive pressure on SIV replication. Results would be useful for elucidation of the viral control mechanism associated with 90-120-Ia. Copyright © 2014 Elsevier Inc. All rights reserved.

One hundred years and still counting: the story of NEF--yesterday, today, and tomorrow.

PubMed

Bowar-Ferres, Susan L; Fitzpatrick, M Louise; McClure, Margaret L

2014-01-01

Nurses Educational Funds, Inc (NEF) is the oldest and largest professionally endorsed source of funds for advanced study in nursing, which celebrated its Centennial in 2012. This philanthropic nonprofit organization is notable for its roots; NEF was organized by nurses specifically for nurses. Its history dates back to 1912, when it began in memory of Isabel Hampton Robb at Teacher's College, where the first graduate nursing education programs began. The initial Robb Memorial Fund was incorporated as a nonprofit organization in 1941 and officially became Nursing Educational Funds, Inc, in 1954. The NEF's sole mission is to raise money and give it for graduate-level scholarships in nursing education, service, practice, and research. Since its origin, more than 1000 doctoral and master's students from a broad array of schools across the nation have been recipients of awards. The NEF Board is a totally volunteer, highly dedicated group of nursing, business, and other professional leaders, who are steadfastly committed to this critical effort. Scholarships for graduate nursing education are imperative to meet the need to grow the pipeline of faculty. As charged by the 2010 Institute of Medicine report, the goal to increase the number of baccalaureate nurses to 80% of the workforce and to double the number of nurses with doctoral degrees both by 2020 speak to the heart of NEF. Funds raised currently are largely from Board members, individual donors, modest foundational support, and a number of bequests. As the nursing population grows older, the potential for bequests or planned giving becomes a realistic goal. Former NEF scholars have not unfortunately been a financial source, although pay back is an expectation. Nurses are the best ones to tell this compelling story to corporations and foundations as NEF continues to persist in the commitment to support graduate nursing education.

HIV-1 Nef hijacks clathrin coats by stabilizing AP-1:Arf1 polygons.

PubMed

Shen, Qing-Tao; Ren, Xuefeng; Zhang, Rui; Lee, Il-Hyung; Hurley, James H

2015-10-23

The lentiviruses HIV and simian immunodeficiency virus (SIV) subvert intracellular membrane traffic as part of their replication cycle. The lentiviral Nef protein helps viruses evade innate and adaptive immune defenses by hijacking the adaptor protein 1 (AP-1) and AP-2 clathrin adaptors. We found that HIV-1 Nef and the guanosine triphosphatase Arf1 induced trimerization and activation of AP-1. Here we report the cryo-electron microscopy structures of the Nef- and Arf1-bound AP-1 trimer in the active and inactive states. A central nucleus of three Arf1 molecules organizes the trimers. We combined the open trimer with a known dimer structure and thus predicted a hexagonal assembly with inner and outer faces that bind the membranes and clathrin, respectively. Hexagons were directly visualized and the model validated by reconstituting clathrin cage assembly. Arf1 and Nef thus play interconnected roles in allosteric activation, cargo recruitment, and coat assembly, revealing an unexpectedly intricate organization of the inner AP-1 layer of the clathrin coat. Copyright © 2015, American Association for the Advancement of Science.

Sequence- and Interactome-Based Prediction of Viral Protein Hotspots Targeting Host Proteins: A Case Study for HIV Nef

PubMed Central

Sarmady, Mahdi; Dampier, William; Tozeren, Aydin

2011-01-01

Virus proteins alter protein pathways of the host toward the synthesis of viral particles by breaking and making edges via binding to host proteins. In this study, we developed a computational approach to predict viral sequence hotspots for binding to host proteins based on sequences of viral and host proteins and literature-curated virus-host protein interactome data. We use a motif discovery algorithm repeatedly on collections of sequences of viral proteins and immediate binding partners of their host targets and choose only those motifs that are conserved on viral sequences and highly statistically enriched among binding partners of virus protein targeted host proteins. Our results match experimental data on binding sites of Nef to host proteins such as MAPK1, VAV1, LCK, HCK, HLA-A, CD4, FYN, and GNB2L1 with high statistical significance but is a poor predictor of Nef binding sites on highly flexible, hoop-like regions. Predicted hotspots recapture CD8 cell epitopes of HIV Nef highlighting their importance in modulating virus-host interactions. Host proteins potentially targeted or outcompeted by Nef appear crowding the T cell receptor, natural killer cell mediated cytotoxicity, and neurotrophin signaling pathways. Scanning of HIV Nef motifs on multiple alignments of hepatitis C protein NS5A produces results consistent with literature, indicating the potential value of the hotspot discovery in advancing our understanding of virus-host crosstalk. PMID:21738584

ADCC Develops Over Time during Persistent Infection with Live-Attenuated SIV and Is Associated with Complete Protection against SIVmac251 Challenge

PubMed Central

Alpert, Michael D.; Harvey, Jackson D.; Lauer, W. Anderson; Reeves, R. Keith; Piatak, Michael; Carville, Angela; Mansfield, Keith G.; Lifson, Jeffrey D.; Li, Wenjun; Desrosiers, Ronald C.; Johnson, R. Paul; Evans, David T.

2012-01-01

Live-attenuated strains of simian immunodeficiency virus (SIV) routinely confer apparent sterilizing immunity against pathogenic SIV challenge in rhesus macaques. Understanding the mechanisms of protection by live-attenuated SIV may provide important insights into the immune responses needed for protection against HIV-1. Here we investigated the development of antibodies that are functional against neutralization-resistant SIV challenge strains, and tested the hypothesis that these antibodies are associated with protection. In the absence of detectable neutralizing antibodies, Env-specific antibody-dependent cell-mediated cytotoxicity (ADCC) emerged by three weeks after inoculation with SIVΔnef, increased progressively over time, and was proportional to SIVΔnef replication. Persistent infection with SIVΔnef elicited significantly higher ADCC titers than immunization with a non-persistent SIV strain that is limited to a single cycle of infection. ADCC titers were higher against viruses matched to the vaccine strain in Env, but were measurable against viruses expressing heterologous Env proteins. In two separate experiments, which took advantage of either the strain-specificity or the time-dependent maturation of immunity to overcome complete protection against SIVmac251 challenge, measures of ADCC activity were higher among the SIVΔnef-inoculated macaques that remained uninfected than among those that became infected. These observations show that features of the antibody response elicited by SIVΔnef are consistent with hallmarks of protection by live-attenuated SIV, and reveal an association between Env-specific antibodies that direct ADCC and apparent sterilizing protection by SIVΔnef. PMID:22927823

Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins

DOEpatents

Korber, Bette T [Los Alamos, NM; Perkins, Simon [Los Alamos, NM; Bhattacharya, Tanmoy [Los Alamos, NM; Fischer, William M [Los Alamos, NM; Theiler, James [Los Alamos, NM; Letvin, Norman [Boston, MA; Haynes, Barton F [Durham, NC; Hahn, Beatrice H [Birmingham, AL; Yusim, Karina [Los Alamos, NM; Kuiken, Carla [Los Alamos, NM

2012-02-21

The present invention relates to mosaic clade M HIV-1 Nef polypeptides and to compositions comprising same. The polypeptides of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection.

PubMed

Adnan, Sama; Reeves, R Keith; Gillis, Jacqueline; Wong, Fay E; Yu, Yi; Camp, Jeremy V; Li, Qingsheng; Connole, Michelle; Li, Yuan; Piatak, Michael; Lifson, Jeffrey D; Li, Wenjun; Keele, Brandon F; Kozlowski, Pamela A; Desrosiers, Ronald C; Haase, Ashley T; Johnson, R Paul

2016-12-01

Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination.

Rocks and Minerals and How We Use Them.

ERIC Educational Resources Information Center

Marcuccio, Phyllis R., Ed.

1991-01-01

Discusses the use of a National Energy Foundation (NEF) poster, "Rocks and Minerals and How to Use Them." The poster is designed to increase student awareness of the part that minerals play in their daily lives. Information about the NEF and poster availability is provided. (MDH)

Structure and function of Hip, an attenuator of the Hsp70 chaperone cycle.

PubMed

Li, Zhuo; Hartl, F Ulrich; Bracher, Andreas

2013-08-01

The Hsp70-interacting protein, Hip, cooperates with the chaperone Hsp70 in protein folding and prevention of aggregation. Hsp70 interacts with non-native protein substrates in an ATP-dependent reaction cycle regulated by J-domain proteins and nucleotide exchange factors (NEFs). Hip is thought to delay substrate release by slowing ADP dissociation from Hsp70. Here we present crystal structures of the dimerization domain and the tetratricopeptide repeat (TPR) domain of rat Hip. As shown in a cocrystal structure, the TPR core of Hip interacts with the Hsp70 ATPase domain through an extensive interface, to form a bracket that locks ADP in the binding cleft. Hip and NEF binding to Hsp70 are mutually exclusive, and thus Hip attenuates active cycling of Hsp70-substrate complexes. This mechanism explains how Hip enhances aggregation prevention by Hsp70 and facilitates transfer of specific proteins to downstream chaperones or the proteasome.

Rituximab fails where eculizumab restores renal function in C3nef-related DDD.

PubMed

Rousset-Rouvière, Caroline; Cailliez, Mathilde; Garaix, Florentine; Bruno, Daniele; Laurent, Daniel; Tsimaratos, Michel

2014-06-01

Dense deposit disease (DDD), a C3 glomerulopathy (C3G), is a rare disease with unfavorable progression towards end-stage kidney disease. The pathogenesis of DDD is due to cytotoxic effects related to acquired or genetic dysregulation of the complement alternative pathway, which is at times accompanied by the production of C3 nephritic factor (C3NeF), an auto-antibody directed against the alternative C3 convertase. Available treatments include plasma exchange, CD20-targeted antibodies, and a terminal complement blockade via the anti-C5 monoclonal antibody eculizumab. We report here the case of an 8-year-old child with C3NeF and refractory DDD who presented with a nephritic syndrome. She tested positive for C3NeF activity; C3 was undetectable. Genetic analyses of the alternative complement pathway were normal. Methylprednisolone pulses and mycophenolate mofetil treatment resulted in complete recovery of renal function and a reduction in proteinuria. Corticosteroids were tapered and then withdrawn. Four months after corticosteroid discontinuation, hematuria and proteinuria recurred, and a renal biopsy confirmed an active DDD with a majority of extracapillary crescents. Despite an increase in immunosuppressive drugs, including methylprednisolone pulses and rituximab therapy, the patient suffered acute renal failure within 3 weeks, requiring dialysis. Eculizumab treatment resulted in a quick and impressive response. Hematuria very quickly resolved, kidney function improved, and no further dialysis was required. The patient received bimonthly eculizumab injections of 600 mg, allowing for normalization of renal function and reduction of proteinuria to <0.5 g per day. Since then, she continues to receive eculizumab. Complement regulation pathway-targeted therapy may be a specific and useful treatment for rapidly progressing DDD prior to the development of glomerulosclerosis. Our data provide evidence supporting the pivotal role of complement alternative pathway abnormalities in C3G with DDD.

32 CFR 256.10 - Air installations compatible use zone noise descriptors.

Code of Federal Regulations, 2010 CFR

2010-07-01

... available in the Office of the Assistant Secretary of Defense (Installations and Logistics)—IO, Washington... NEF, for meters of policy, noise planning and decisionmaking, areas quieter than Ldn 65 shall be considered approximately equivalent to the previously used CNR Zone 1 and to areas quieter than NEF 30. The...

32 CFR 256.10 - Air installations compatible use zone noise descriptors.

Code of Federal Regulations, 2011 CFR

2011-07-01

... available in the Office of the Assistant Secretary of Defense (Installations and Logistics)—IO, Washington... NEF, for meters of policy, noise planning and decisionmaking, areas quieter than Ldn 65 shall be considered approximately equivalent to the previously used CNR Zone 1 and to areas quieter than NEF 30. The...

Comparison of Three Operative Models for Estimating the Surface Water Deficit using ASTER Reflective and Thermal Data

PubMed Central

García, Mónica; Villagarcía, Luis; Contreras, Sergio; Domingo, Francisco; Puigdefábregas, Juan

2007-01-01

Three operative models with minimum input data requirements for estimating the partition of available surface energy into sensible and latent heat flux using ASTER data have been evaluated in a semiarid area in SE Spain. The non-evaporative fraction (NEF) is proposed as an indicator of the surface water deficit. The best results were achieved with NEF estimated using the “Simplified relationship” for unstable conditions (NEFSeguin) and with the S-SEBI (Simplified Surface Energy Balance Index) model corrected for atmospheric conditions (NEFS-SEBIt,) which both produced equivalent results. However, results with a third model, NEFCarlson, that estimates the exchange coefficient for sensible heat transfer from NDVI, were unrealistic for sites with scarce vegetation cover. These results are very promising for an operative monitoring of the surface water deficit, as validation with field data shows reasonable errors, within those reported in the literature (RMSE were 0.18 and 0.11 for the NEF, and 29.12 Wm-2 and 25.97 Wm-2 for sensible heat flux, with the Seguin and S-SEBIt models, respectively).

Reproducing SIVΔnef vaccine correlates of protection: trimeric gp41 antibody concentrated at mucosal front lines

PubMed Central

Voss, James E.; Macauley, Matthew S.; Rogers, Kenneth A.; Villinger, Francois; Duan, Lijie; Shang, Liang; Fink, Elizabeth A.; Andrabi, Raiees; Colantonio, Arnaud D.; Robinson, James E.; Johnson, R. Paul; Burton, Dennis R.; Haase, Ashley T.

2016-01-01

Vaccination with SIVmac239Δnef provides robust protection against subsequent challenge with wild type SIV, but safety issues have precluded designing an HIV-1 vaccine based on a live attenuated virus concept. Safe immunogens and adjuvants that could reproduce identified immune correlates of SIVmac239Δnef protection therefore offer an alternative path for development of an HIV vaccine. Here we describe SIV envelope trimeric gp41 (gp41t) immunogens based on a protective correlate of antibodies to gp41t concentrated on the path of virus entry by the neonatal Fc receptor (FcRn) in cervical vaginal epithelium. We developed a gp41t immunogen-MPLA adjuvant liposomal nanoparticle for intra-muscular immunization and a gp41t-Fc immunogen for intranasal immunization for pilot studies in mice, rabbits, and rhesus macaques. Repeated immunizations to mimic persistent antigen exposure in infection elicited gp41t antibodies in rhesus macaques that were detectable in FcRn+ cervical vaginal epithelium, thus recapitulating one key feature of SIVmac239Δnef vaccinated and protected animals. While this strategy did not reproduce the system of local production of antibody in SIVmac239Δnef-vaccinated animals, passive immunization experiments supported the concept that sufficiently high levels of antibody can be concentrated by the FcRn at mucosal frontlines, thus setting the stage for assessing protection against vaginal challenge by gp41t immunization. PMID:27428745

HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis

PubMed Central

Harrington, Willie; Bond, Vincent; Huang, Ming Bo; Powell, Michael; Lillard, James; Manne, Upender; Bumpers, Harvey

2010-01-01

CXCR4 receptors have been implicated in tumorigenesis and proliferation, making it a potential target for colorectal cancer therapy. Expression of this chemokine receptor on cellular surfaces appears to promote metastasis by directly stimulating tumor cell migration and invasion. The receptor/ligand, CXCR4/SDF-1α, pair are critically important to angiogenesis and vascular remodeling which supports cancer proliferation. Our work has shown that a novel apoptotic peptide of HIV-1, Nef-M1, can act as a CXCR4 antagonist, inducing apoptosis in CXCR4 containing cells. Four colorectal tumor cell lines (HT-29, LS174t, SW480, WiDr), were evaluated for their response to Nef-M1 peptide via in vivo and in vitro. The presence of CXCR4 receptors on tumor cells was determined using immunohistochemical and RT-PCR analyses. Solid xenografts derived from tumor cell lines grown in SCID mice, were evaluated for the persistence of the receptor. Xenografts propagated in SCID mice from each of the four cell lines demonstrated high levels of receptor expression as well. The effects of Nef-M1 in vivo via splenic injected mice and subsequent hepatic metastasis also demonstrated dramatic reduction of primary tumor growth in the spleen and secondary invasion of the liver. We concluded that Nef-M1 peptide, through physical interaction(s) with CXCR4, drives apoptotic reduction in in vivo primary tumor growth and metastasis. PMID:20383296

Clare Soper's Hat: New Education Fellowship Correspondence between Bloomsbury and New Zealand, 1938-1946

ERIC Educational Resources Information Center

Middleton, Sue

2013-01-01

Broadening horizons beyond nations, transnational histories trace global flows connecting people and places. Historians have studied the New Education Fellowship (NEF) as a global network. Focused within the nation, research on New Zealand's involvement with NEF has emphasised how its activities before the Second World War impacted on the Labour…

Impact of freeway weaving segment design on light-duty vehicle exhaust emissions.

PubMed

Li, Qing; Qiao, Fengxiang; Yu, Lei; Chen, Shuyan; Li, Tiezhu

2018-06-01

In the United States, 26% of greenhouse gas emissions is emitted from the transportation sector; these emisssions meanwhile are accompanied by enormous toxic emissions to humans, such as carbon monoxide (CO), nitrogen oxides (NO x ), and hydrocarbon (HC), approximately 2.5% and 2.44% of a total exhaust emissions for a petrol and a diesel engine, respectively. These exhaust emissions are typically subject to vehicles' intermittent operations, such as hard acceleration and hard braking. In practice, drivers are inclined to operate intermittently while driving through a weaving segment, due to complex vehicle maneuvering for weaving. As a result, the exhaust emissions within a weaving segment ought to vary from those on a basic segment. However, existing emission models usually rely on vehicle operation information, and compute a generalized emission result, regardless of road configuration. This research proposes to explore the impacts of weaving segment configuration on vehicle emissions, identify important predictors for emission estimations, and develop a nonlinear normalized emission factor (NEF) model for weaving segments. An on-board emission test was conducted on 12 subjects on State Highway 288 in Houston, Texas. Vehicles' activity information, road conditions, and real-time exhaust emissions were collected by on-board diagnosis (OBD), a smartphone-based roughness app, and a portable emission measurement system (PEMS), respectively. Five feature selection algorithms were used to identify the important predictors for the response of NEF and the modeling algorithm. The predictive power of four algorithm-based emission models was tested by 10-fold cross-validation. Results showed that emissions are also susceptible to the type and length of a weaving segment. Bagged decision tree algorithm was chosen to develop a 50-grown-tree NEF model, which provided a validation error of 0.0051. The estimated NEFs are highly correlated with the observed NEFs in the training data set as well as in the validation data set, with the R values of 0.91 and 0.90, respectively. Existing emission models usually rely on vehicle operation information to compute a generalized emission result, regardless of road configuration. In practice, while driving through a weaving segment, drivers are inclined to perform erratic maneuvers, such as hard braking and hard acceleration due to the complex weaving maneuver required. As a result, the exhaust emissions within a weaving segment vary from those on a basic segment. This research proposes to involve road configuration, in terms of the type and length of a weaving segment, in constructing an emission nonlinear model, which significantly improves emission estimations at a microscopic level.

The inability to disrupt the immunological synapse between infected human T cells and APCs distinguishes HIV-1 from most other primate lentiviruses

PubMed Central

Arhel, Nathalie; Lehmann, Martin; Clauß, Karen; Nienhaus, G. Ulrich; Piguet, Vincent; Kirchhoff, Frank

2009-01-01

Viruses that infect T cells, including those of the lentivirus genus, such as HIV-1, modulate the responsiveness of infected T cells to stimulation by interacting APCs in a manner that renders the T cells more permissive for viral replication. HIV-1 and other primate lentiviruses use their Nef proteins to manipulate the T cell/APC contact zone, the immunological synapse (IS). It is known that primate lentiviral Nef proteins differ substantially in their ability to modulate cell surface expression of the TCR-CD3 and CD28 receptors critical for the formation and function of the IS. However, the impact of these differences in Nef function on the interaction and communication between virally infected T cells and primary APCs has not been investigated. Here we have used primary human cells to show that Nef proteins encoded by HIV-2 and most SIVs, which downmodulate cell surface expression of TCR-CD3, disrupt formation of the IS between infected T cells and Ag-presenting macrophages or DCs. In contrast, nef alleles from HIV-1 and its simian precursor SIVcpz failed to suppress synapse formation and events downstream of TCR signaling. Our data suggest that most primate lentiviruses disrupt communication between virally infected CD4+ Th cells and APCs, whereas HIV-1 and its SIV precursor have largely lost this capability. The resulting differences in the levels of T cell activation and apoptosis may play a role in the pathogenesis of AIDS. PMID:19759518

Palladium-Catalyzed α-Arylation of Aryl Nitromethanes

PubMed Central

2015-01-01

Catalytic conditions for the α-arylation of aryl nitromethanes have been discovered using parallel microscale experimentation, despite two prior reports of the lack of reactivity of these aryl nitromethane precursors. The method efficiently provides a variety of substituted, isolable diaryl nitromethanes. In addition, it is possible to sequentially append two different aryl groups to nitromethane. Mild oxidation conditions were identified to afford the corresponding benzophenones via the Nef reaction, and reduction conditions were optimized to afford several diaryl methylamines. PMID:26584680

HIV-1 Nef and Vpu Interfere with L-Selectin (CD62L) Cell Surface Expression To Inhibit Adhesion and Signaling in Infected CD4+ T Lymphocytes

PubMed Central

Vassena, Lia; Giuliani, Erica; Koppensteiner, Herwig; Bolduan, Sebastian; Schindler, Michael

2015-01-01

ABSTRACT Leukocyte recirculation between blood and lymphoid tissues is required for the generation and maintenance of immune responses against pathogens and is crucially controlled by the L-selectin (CD62L) leukocyte homing receptor. CD62L has adhesion and signaling functions and initiates the capture and rolling on the vascular endothelium of cells entering peripheral lymph nodes. This study reveals that CD62L is strongly downregulated on primary CD4+ T lymphocytes upon infection with human immunodeficiency virus type 1 (HIV-1). Reduced cell surface CD62L expression was attributable to the Nef and Vpu viral proteins and not due to increased shedding via matrix metalloproteases. Both Nef and Vpu associated with and sequestered CD62L in perinuclear compartments, thereby impeding CD62L transport to the plasma membrane. In addition, Nef decreased total CD62L protein levels. Importantly, infection with wild-type, but not Nef- and Vpu-deficient, HIV-1 inhibited the capacity of primary CD4+ T lymphocytes to adhere to immobilized fibronectin in response to CD62L ligation. Moreover, HIV-1 infection impaired the signaling pathways and costimulatory signals triggered in primary CD4+ T cells by CD62L ligation. We propose that HIV-1 dysregulates CD62L expression to interfere with the trafficking and activation of infected T cells. Altogether, this novel HIV-1 function could contribute to virus dissemination and evasion of host immune responses. IMPORTANCE L-selectin (CD62L) is an adhesion molecule that mediates the first steps of leukocyte homing to peripheral lymph nodes, thus crucially controlling the initiation and maintenance of immune responses to pathogens. Here, we report that CD62L is downmodulated on the surfaces of HIV-1-infected T cells through the activities of two viral proteins, Nef and Vpu, that prevent newly synthesized CD62L molecules from reaching the plasma membrane. We provide evidence that CD62L downregulation on HIV-1-infected primary T cells results in impaired adhesion and signaling functions upon CD62L triggering. Removal of cell surface CD62L may predictably keep HIV-1-infected cells away from lymph nodes, the privileged sites of both viral replication and immune response activation, with important consequences, such as systemic viral spread and evasion of host immune surveillance. Altogether, we propose that Nef- and Vpu-mediated subversion of CD62L function could represent a novel determinant of HIV-1 pathogenesis. PMID:25822027

Thymic pathogenicity of an HIV-1 envelope is associated with increased CXCR4 binding efficiency and V5-gp41-dependent activity, but not V1/V2-associated CD4 binding efficiency and viral entry

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

Meissner, Eric G.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599; Coffield, Vernon M.

2005-06-05

We previously described a thymus-tropic HIV-1 envelope (R3A Env) from a rapid progressor obtained at the time of transmission. An HIV-1 molecular recombinant with the R3A Env supported extensive replication and pathogenesis in the thymus and did not require Nef. Another Env from the same patient did not display the same thymus-tropic pathogenesis (R3B Env). Here, we show that relative to R3B Env, R3A Env enhances viral entry of T cells, increases fusion-induced cytopathicity, and shows elevated binding efficiency for both CD4 and CXCR4, but not CCR5, in vitro. We created chimeric envelopes to determine the region(s) responsible for eachmore » in vitro phenotype and for thymic pathogenesis. Surprisingly, while V1/V2 contributed to enhanced viral entry, CD4 binding efficiency, and cytopathicity in vitro, it made no contribution to thymic pathogenesis. Rather, CXCR4 binding efficiency and V5-gp41-associated activity appear to independently contribute to thymic pathogenesis of the R3A Env. These data highlight the contribution of unique HIV pathogenic factors in the thymic microenvironment and suggest that novel mechanisms may be involved in Env pathogenic activity in vivo.« less

Vertical accumulation of potential toxic elements in a semiarid system that is influenced by an abandoned gold mine

NASA Astrophysics Data System (ADS)

Sánchez-Martínez, Martha A.; Marmolejo-Rodríguez, Ana J.; Magallanes-Ordóñez, Víctor R.; Sánchez-González, Alberto

2013-09-01

The mining zone at El Triunfo, Baja California Sur, Mexico, was exploited for gold extraction for 200 years. This area includes more than 100 abandoned mining sites. These sites contain mine tailings that are highly contaminated with potential toxic elements (PTE), such as As, Cd, Pb, Sb, Zn, and other associated elements. Over time, these wastes have contaminated the sediments in the adjacent fluvial systems. Our aim was to assess the vertical PTE variations in the abandoned mining zone and in the discharge of the main arroyo into a small lagoon at the Pacific Ocean. Sediments were collected from the two following locations in the mining zone near the arroyo basin tailings: 1) an old alluvial terrace (Overbank) and a test pit (TP) and 2) two sediment cores locations at the arroyo discharge into a hypersaline small lagoon. Samples were analyzed by ICP-MS, ICP-OES, and INAA and the methods were validated. The overbank was the most contaminated and had As, Cd, Pb, Sb, and Zn concentrations of 8690, 226, 84,700, 17,400, and 42,600 mg kg-1, respectively, which decreased with depth. In addition, the TP contained elevated As, Cd, Pb, Sb, and Zn concentrations of 694, 18.8, 5001, 39.2, and 4170 mg kg-1, respectively. The sediment cores were less contaminated. However, the As, Cd, Pb, Sb, and Zn concentrations were greater than the concentrations that are generally found in the Earth's crust. The normalized enrichment factors (NEFs), which were calculated from the background concentrations of these elements in the system, showed that extremely severe As, Cd, Pb, Sb, and Zn (NEF > 50) enrichment occurred at the overbank. The TP was severe to very severely enriched with As, Cd, Pb, Sb, and Zn (NEF = 10-50). The sediment cores had a severe enrichment of As, Pb, and Zn (NEF = 10-25). Their vertical profiles showed that anthropogenic influences occurred in the historic sediment deposition at the overbank and TP and in the sediment cores. In addition, the As, Pb, and Zn concentrations in the sediment cores were related to the deposition of fine sediments and organic carbon.

Neutralizing and infection-enhancing antibody responses do not correlate with the differential pathogenicity of SIVmac239delta3 in adult and infant rhesus monkeys.

PubMed

Montefiori, D C; Baba, T W; Li, A; Bilska, M; Ruprecht, R M

1996-12-15

Variants of SIV containing a deletion in the nef gene are attenuated in adult macaques, where they provide protection from challenge with pathogenic SIV, but the mechanism of protection remains unknown. One of these attenuated variants carrying deletions in nef, vpr, and NRE (SIVmac239delta3) was recently found to be pathogenic in infant macaques exposed to the virus at birth. We investigated whether inadequate or inappropriate antiviral humoral immune responses could explain why this virus causes disease in infant macaques. Plasma samples from four infants infected with SIVmac251 and five infants and two adults infected with SIVmac239delta3 were evaluated for neutralizing Abs to a laboratory-passaged stock of SIVmac251, an animal challenge stock of SIVmac239/nef-open, and a stock of SIVmac239delta3 to which animals were exposed. Plasma samples were evaluated further for complement-mediated Ab-dependent enhancement (C'-ADE) of SIVmac239/nef-open in vitro. High-titer neutralizing Abs to SIVmac251 were detected in plasma samples from adults and most infants within 3 to 5 wk of infection with either virus. Neutralizing Abs to SIVmac239/nef-open and SIVmac239delta3 developed more slowly, being undetectable before 23 to 63 wk of infection. Timing, magnitude, and breadth of neutralizing Ab responses did not correlate with progression to disease or lack thereof and gave no indication of an impaired humoral immune response in infants. Furthermore, C'-ADE was detected equally in plasma samples from adults and infants. The results indicate that infection with SIVmac239delta3 causes disease in infant macaques despite their mounting of antiviral humoral immune responses comparable to those of adults.

HIV-I Nef inhibitors: a novel class of HIV-specific immune adjuvants in support of a cure.

PubMed

Dekaban, Gregory A; Dikeakos, Jimmy D

2017-09-12

The success of many current vaccines relies on a formulation that incorporates an immune activating adjuvant. This will hold true for the design of a successful therapeutic HIV vaccine targeted at controlling reactivated virus following cessation of combined antiretroviral therapy (cART). The HIV accessory protein Nef functions by interfering with HIV antigen presentation through the major histocompatibility complex I (MHC-I) pathway thereby suppressing CD8 + cytotoxic T cell (CTL)-mediated killing of HIV infected cells. Thus, this important impediment to HIV vaccine success must be circumvented. This review covers our current knowledge of Nef inhibitors that may serve as immune adjuvants that will specifically restore and enhance CTL-mediated killing of reactivated HIV infected cells as part of an overall vaccine strategy to affect a cure for HIV infection.

A New Education for a New Era: The Contribution of the Conferences of the New Education Fellowship to the Disciplinary Field of Education 1921-1938

ERIC Educational Resources Information Center

Brehony, Kevin J.

2004-01-01

This article examines the role played by the conferences of the New Education Fellowship (NEF) in the emerging disciplinary field of the sciences of education between the two world wars. The NEF was a movement connecting lay enthusiasts for educational reform with major figures in the developing disciplines of psychology and education, such as…

Selective Downregulation of Rhesus Macaque and Sooty Mangabey Major Histocompatibility Complex Class I Molecules by Nef Alleles of Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2▿

PubMed Central

DeGottardi, M. Quinn; Specht, Anke; Metcalf, Benjamin; Kaur, Amitinder; Kirchhoff, Frank; Evans, David T.

2008-01-01

Human immunodeficiency virus type 1 (HIV-1) Nef downregulates HLA-A and -B molecules, but not HLA-C or -E molecules, based on amino acid differences in their cytoplasmic domains to simultaneously evade cytotoxic T lymphocyte (CTL) and natural killer cell surveillance. Rhesus macaques and sooty mangabeys express orthologues of HLA-A, -B, and -E, but not HLA-C, and many of these molecules have unique amino acid differences in their cytoplasmic tails. We found that these differences also resulted in differential downregulation by primary simian immunodeficiency virus (SIV) SIVsmm/mac and HIV-2 Nef alleles. Thus, selective major histocompatibility complex class I downregulation is a conserved mechanism of immune evasion for pathogenic SIV infection of rhesus macaques and nonpathogenic SIV infection of sooty mangabeys. PMID:18199657

A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial

PubMed Central

Rolland, M.; Magaret, C.A.; Rademeyer, C.; Fiore-Gartland, A.; Edlefsen, P.T.; DeCamp, A.; Ahmed, H.; Ngandu, N.; Larsen, B.B.; Frahm, N.; Marais, J.; Thebus, R.; Geraghty, D.; Hural, J.; Corey, L.; Kublin, J.; Gray, G.; McElrath, M.J.; Mullins, J.I.; Gilbert, P.B.; Williamson, C.

2016-01-01

Introduction The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. Materials and methods A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert. Results There was significantly greater protein distances from the vaccine immunogen sequence in Gag (p = 0.045) and Nef (p = 0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p < 0.05) in Gag (n = 10), Pol (n = 7) and Nef (n = 10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A*02:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively. Discussion This study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes. PMID:27756485

Narrative Means to Preventative Ends: A Narrative Engagement Framework for Designing Prevention Interventions

PubMed Central

Miller-Day, Michelle; Hecht, Michael L.

2013-01-01

This paper describes a Narrative Engagement Framework (NEF) for guiding communication-based prevention efforts. This framework suggests that personal narratives have distinctive capabilities in prevention. The paper discusses the concept of narrative, links narrative to prevention, and discusses the central role of youth in developing narrative interventions. As illustration, the authors describe how the NEF is applied in the keepin’ it REAL adolescent drug prevention curriculum, pose theoretical directions, and offer suggestions for future work in prevention communication. PMID:23980613

Vibrational Relaxation and Collision-Induced Dissociation of Xenon Fluoride by Neon

DTIC Science & Technology

1989-03-01

potential energy surface, which consists of a Morse function for the XeF interaction and Lennard - Jones functions for the NeXe and NeF interactions. Rate...interaction and a Lennard - Jones function for the NeXe and the NeF interactions. The values of the Morse potential parameters for XeF are taken from...interactions are calculated using the theoretical data provided by Svehla.59 The parameters for the Morse potential and the Lennard - Jones potentials are listed

Structural analysis of the Sil1-Bip complex reveals the mechanism for Sil1 to function as a nucleotide-exchange factor

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

Yan, Ming; Li, Jingzhi; Sha, Bingdong

2013-01-16

Sil1 functions as a NEF (nucleotide-exchange factor) for the ER (endoplasmic reticulum) Hsp70 (heat-shock protein of 70 kDa) Bip in eukaryotic cells. Sil1 may catalyse the ADP release from Bip by interacting directly with the ATPase domain of Bip. In the present study we show the complex crystal structure of the yeast Bip and the NEF Sil1 at the resolution of 2.3 {angstrom} (1 {angstrom} = 0.1 nm). In the Sil1-Bip complex structure, the Sil1 molecule acts as a 'clamp' which binds lobe IIb of the Bip ATPase domain. The binding of Sil1 causes the rotation of lobe IIb {approx}more » 13.5{sup o} away from the ADP-binding pocket. The complex formation also induces lobe Ib to swing in the opposite direction by {approx} 3.7{sup o}. These conformational changes open up the nucleotide-binding pocket in the Bip ATPase domain and disrupt the hydrogen bonds between Bip and bound ADP, which may catalyse ADP release. Mutation of the Sil1 residues involved in binding the Bip ATPase domain compromise the binding affinity of Sil1 to Bip, and these Sil1 mutants also abolish the ability to stimulate the ATPase activity of Bip.« less

Micropower CMOS Integrated Low-Noise Amplification, Filtering, and Digitization of Multimodal Neuropotentials

PubMed Central

Mollazadeh, Mohsen; Murari, Kartikeya; Cauwenberghs, Gert; Thakor, Nitish

2009-01-01

Electrical activity in the brain spans a wide range of spatial and temporal scales, requiring simultaneous recording of multiple modalities of neurophysiological signals in order to capture various aspects of brain state dynamics. Here, we present a 16-channel neural interface integrated circuit fabricated in a 0.5 μm 3M2P CMOS process for selective digital acquisition of biopotentials across the spectrum of neural signal modalities in the brain, ranging from single spike action potentials to local field potentials (LFP), electrocorticograms (ECoG), and electroencephalograms (EEG). Each channel is composed of a tunable bandwidth, fixed gain front-end amplifier and a programmable gain/resolution continuous-time incremental ΔΣ analog-to-digital converter (ADC). A two-stage topology for the front-end voltage amplifier with capacitive feedback offers independent tuning of the amplifier bandpass frequency corners, and attains a noise efficiency factor (NEF) of 2.9 at 8.2 kHz bandwidth for spike recording, and a NEF of 3.2 at 140 Hz bandwidth for EEG recording. The amplifier has a measured midband gain of 39.6 dB, frequency response from 0.2 Hz to 8.2 kHz, and an input-referred noise of 1.94 μVrms while drawing 12.2 μA of current from a 3.3 V supply. The lower and higher cutoff frequencies of the bandpass filter are adjustable from 0.2 to 94 Hz and 140 Hz to 8.2 kHz, respectively. At 10-bit resolution, the ADC has an SNDR of 56 dB while consuming 76 μW power. Time-modulation feedback in the ADC offers programmable digital gain (1–4096) for auto-ranging, further improving the dynamic range and linearity of the ADC. Experimental recordings with the system show spike signals in rat somatosensory cortex as well as alpha EEG activity in a human subject. PMID:20046962

Investigations on the antiretroviral activity of carbon nanotubes using computational molecular approach.

PubMed

Krishnaraj, R Navanietha; Chandran, Saravanan; Pal, Parimal; Berchmans, Sheela

2014-01-01

Carbon nanotubes are the interesting class of materials with wide range of applications. They have excellent physical, chemical and electrical properties. Numerous reports were made on the antiviral activities of carbon nanotubes. However the mechanism of antiviral action is still in infancy. Herein we report, our recent novel findings on the molecular interactions of carbon nanotubes with the three key target proteins of HIV using computational chemistry approach. Armchair, chiral and zigzag CNTs were modeled and used as ligands for the interaction studies. The structure of the key proteins involved in HIV mediated infection namely HIV- Vpr, Nef and Gag proteins were collected from the PDB database. The docking studies were performed to quantify the interaction of the CNT with the three different disease targets. Results showed that the carbon nanotubes had high binding affinity to these proteins which confirms the antagonistic molecular interaction of carbon nanotubes to the disease targets. The modeled armchair carbon nanotubes had the binding affinities of -12.4 Kcal/mole, -20 Kcal/mole and -11.7 Kcal/mole with the Vpr, Nef and Gag proteins of HIV. Chiral CNTs also had the maximum affinity of -16.4 Kcal/mole to Nef. The binding affinity of chiral CNTs to Vpr and Gag was found to be -10.9 Kcal/mole and -10.3 Kcal/mole respectively. The zigzag CNTs had the binding affinity of -11.1 Kcal/mole with Vpr, -18.3 Kcal/mole with Nef and -10.9 with Gag respectively. The strong molecular interactions suggest the efficacy of CNTs for targeting the HIV mediated retroviral infections.

Effect of advanced aircraft noise reduction technology on the 1990 projected noise environment around Patrick Henry Airport. [development of noise exposure forecast contours for projected traffic volume and aircraft types

NASA Technical Reports Server (NTRS)

Cawthorn, J. M.; Brown, C. G.

1974-01-01

A study has been conducted of the future noise environment of Patric Henry Airport and its neighboring communities projected for the year 1990. An assessment was made of the impact of advanced noise reduction technologies which are currently being considered. These advanced technologies include a two-segment landing approach procedure and aircraft hardware modifications or retrofits which would add sound absorbent material in the nacelles of the engines or which would replace the present two- and three-stage fans with a single-stage fan of larger diameter. Noise Exposure Forecast (NEF) contours were computed for the baseline (nonretrofitted) aircraft for the projected traffic volume and fleet mix for the year 1990. These NEF contours are presented along with contours for a variety of retrofit options. Comparisons of the baseline with the noise reduction options are given in terms of total land area exposed to 30 and 40 NEF levels. Results are also presented of the effects on noise exposure area of the total number of daily operations.

A cell-free stock of simian-human immunodeficiency virus that causes AIDS in pig-tailed macaques has a limited number of amino acid substitutions in both SIVmac and HIV-1 regions of the genome and has offered cytotropism.

PubMed

Stephens, E B; Mukherjee, S; Sahni, M; Zhuge, W; Raghavan, R; Singh, D K; Leung, K; Atkinson, B; Li, Z; Joag, S V; Liu, Z Q; Narayan, O

1997-05-12

We have examined both the sequence changes in the LTR, gag, vif, vpr, vpx, tat, rev, vpu, env, and nef genes and the cell tropism of a cell-free stock of chimeric simian-human immunodeficiency virus (SHIV) isolated from the cerebrospinal fluid of a pig-tailed macaque (PNb) that developed AIDS. This virus (SHIVKU-1) is highly pathogenic when inoculated into other macaques. DNA sequence analysis of PCR-amplified products revealed a total of 5 nucleotide changes in the LTR while vif had 2 consensus amino acid changes. The gag, vif, and vpx had no consensus amino acid substitutions, whereas vpr had 1 consensus substitution. The tat and rev genes of the HXB2 region of SHIVKU-1 had 2 and 1 consensus amino acid changes, respectively. The vpu gene of the HXB2 region of SHIV, which originally had an ACG at the beginning of the gene, reverted to an initiation ATG codon and in addition contained a consensus amino acid substitution at position 69 of this protein. As expected, the majority of the nucleotide substitutions were found in the env and nef genes. Thirteen and 5 amino acid changes were predicted for the corresponding Env and Nef proteins, respectively. In addition, one-third of the env gene clones isolated from the SHIVKU-1 stock had a 5-amino-acid deletion in the V4 region. Using three independent assays, we determined that the changes in the SHIVKU-1 were associated with an increase in the efficiency of replication in macrophages. The strikingly few consensus changes in the virus suggest that conversion of this virus to one capable of causing AIDS in pig-tailed macaques was associated with relatively few changes in the viral envelope and/or accessory genes. These results will provide the basis for the development of a pathogenic, molecular clone of SHIV capable of causing AIDS in pig-tailed macaques.

The design of CMOS general-purpose analog front-end circuit with tunable gain and bandwidth for biopotential signal recording systems.

PubMed

Chen, Wei-Ming; Yang, Wen-Chia; Tsai, Tzung-Yun; Chiueh, Herming; Wu, Chung-Yu

2011-01-01

In this paper an 8-channel CMOS general-purpose analog front-end (AFE) circuit with tunable gain and bandwidth for biopotential signal recording systems is presented. The proposed AFE consists of eight chopper stabilized pre-amplifiers, an 8-to-1 analog multiplexer, and a programmable gain amplifier. It can be used to sense and amplify different kinds of biopotential signals, such as electrocorticogram (ECoG), electrocardiogram (ECG) and electromyogram (EMG). The AFE chip is designed and fabricated in 0.18-μm CMOS technology. The measured maximum gain of AFE is 60.8 dB. The low cutoff frequency can achieve as low as 0.8 Hz and high cutoff frequency can be adjusted from 200 Hz to 10 kHz to suit for different kinds of biopotential signals. The measured input-referred noise is 0.9 μV(rms), with the power consumption of 18μW per channel at 1.8-V power supply. And the noise efficiency factor (NEF) is only 1.3 for pre-amplifier.

A 4 μW/Ch analog front-end module with moderate inversion and power-scalable sampling operation for 3-D neural microsystems.

PubMed

Al-Ashmouny, Khaled M; Chang, Sun-Il; Yoon, Euisik

2012-10-01

We report an analog front-end prototype designed in 0.25 μm CMOS process for hybrid integration into 3-D neural recording microsystems. For scaling towards massive parallel neural recording, the prototype has investigated some critical circuit challenges in power, area, interface, and modularity. We achieved extremely low power consumption of 4 μW/channel, optimized energy efficiency using moderate inversion in low-noise amplifiers (K of 5.98 × 10⁸ or NEF of 2.9), and minimized asynchronous interface (only 2 per 16 channels) for command and data capturing. We also implemented adaptable operations including programmable-gain amplification, power-scalable sampling (up to 50 kS/s/channel), wide configuration range (9-bit) for programmable gain and bandwidth, and 5-bit site selection capability (selecting 16 out of 128 sites). The implemented front-end module has achieved a reduction in noise-energy-area product by a factor of 5-25 times as compared to the state-of-the-art analog front-end approaches reported to date.

HIV-1 Nef-associated Factor 1 Enhances Viral Production by Interacting with CRM1 to Promote Nuclear Export of Unspliced HIV-1 gag mRNA.

PubMed

Ren, Xiao-Xin; Wang, Hai-Bo; Li, Chuan; Jiang, Jin-Feng; Xiong, Si-Dong; Jin, Xia; Wu, Li; Wang, Jian-Hua

2016-02-26

HIV-1 depends on host-cell-encoded factors to complete its life cycle. A comprehensive understanding of how HIV-1 manipulates host machineries during viral infection can facilitate the identification of host targets for antiviral drugs or gene therapy. The cellular protein Naf1 (HIV-1 Nef-associated factor 1) is a CRM1-dependent nucleo-cytoplasmic shuttling protein, and has been identified to regulate multiple receptor-mediated signal pathways in inflammation. The cytoplasm-located Naf1 can inhibit NF-κB activation through binding to A20, and the loss of Naf1 controlled NF-κB activation is associated with multiple autoimmune diseases. However, the effect of Naf1 on HIV-1 mRNA expression has not been characterized. In this study we found that the nucleus-located Naf1 could promote nuclear export of unspliced HIV-1 gag mRNA. We demonstrated that the association between Naf1 and CRM1 was required for this function as the inhibition or knockdown of CRM1 expression significantly impaired Naf1-promoted HIV-1 production. The mutation of Naf1 nuclear export signals (NESs) that account for CRM1 recruitment for nuclear export decreased Naf1 function. Additionally, the mutation of the nuclear localization signal (NLS) of Naf1 diminished its ability to promote HIV-1 production, demonstrating that the shuttling property of Naf1 is required for this function. Our results reveal a novel role of Naf1 in enhancing HIV-1 production, and provide a potential therapeutic target for controlling HIV-1 infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

In this issue: Nef, a lingering problem; are there better immunoglobulins for human use; and Takayasu arteritis, still a mystery.

PubMed

Bot, Adrian

2012-12-01

The current issue of the International Reviews of Immunology brings the latest in three different areas of basic and clinical immunology. First, there is the lingering question of residual HIV-related pathology in patients on chronic antiretroviral therapy. The specific role of Nef in the macrophage-mediated disease manifested through lymphoma, metabolic disease and neurological disorder, is extensively discussed. A second topic is a clinical immunology one, a critical perspective on the efficacy and safety profile of various preparations of immunoglobulin products currently prescribed for a range of immunodeficiencies. Surprisingly, the authors showed that while the available preparations are equivalent from efficacy standpoint, they differ from the standpoint of toxicity. The third subject is again, in the arena of clinical immunology and deals with a relatively rare yet extremely puzzling disease -Takayasu arteritis -with a pathogenesis that needs elucidation and a dire need for better treatments. The authors provide a state of the art in terms of genetic association, other factors possibly involved in the onset and progression of this unusual inflammatory disease of large arteries, and provide a perspective on current standard of care and potential usefulness of TNF-α blockade as therapy for Takayasu arteritis.

Mass transport properties of the tetrahydronaphthalene/n-dodecane mixture measured by investigating non-equilibrium fluctuations

NASA Astrophysics Data System (ADS)

Croccolo, Fabrizio; Scheffold, Frank; Bataller, Henri

2013-04-01

We present preliminary near-field light scattering (NFS) data concerning the analysis of the static power spectrum and of the relaxation time constant as a function of the wave vector for non-equilibrium fluctuations (NEFs). The goal of these measurements is to obtain information about the Soret and the mass diffusion coefficients of a binary mixture undergoing thermodiffusion. In particular, we show how the interaction between NEFs and the gravity force gives rise to a critical wavelength that provides additional information about the Soret coefficient. We suggest that a quantitative analysis can be performed by means of this non-invasive optical technique. In our setup, the sample is monitored parallel to the imposed temperature gradient, thus being insensitive to the refractive index profile along the vertical axis, while at the same time we are able to detect the light scattered by the refractive index fluctuations in horizontal planes. We select a shadowgraph layout for the NFS setup due to the extremely small wave vectors we aim to analyze. From a double-frame differential analysis of the acquired images, we obtain both the static power spectrum and the dynamics of NEFs. As a proof-of-principle experiment, we present Soret and diffusion coefficient data on a liquid mixture of tetrahydronaphthalene/n-dodecane.

Cytotoxic T Lymphocyte Epitopes of HIV-1 Nef

PubMed Central

Lucchiari-Hartz, Maria; van Endert, Peter M.; Lauvau, Grégoire; Maier, Reinhard; Meyerhans, Andreas; Mann, Derek; Eichmann, Klaus; Niedermann, Gabriele

2000-01-01

Although a pivotal role of proteasomes in the proteolytic generation of epitopes for major histocompatibility complex (MHC) class I presentation is undisputed, their precise function is currently the subject of an active debate: do proteasomes generate many epitopes in definitive form, or do they merely generate the COOH termini, whereas the definitive NH2 termini are cleaved by aminopeptidases? We determined five naturally processed MHC class I ligands derived from HIV-1 Nef. Unexpectedly, the five ligands correspond to only three cytotoxic T lymphocyte (CTL) epitopes, two of which occur in two COOH-terminal length variants. Parallel analyses of proteasomal digests of a Nef fragment encompassing the epitopes revealed that all five ligands are direct products of proteasomes. Moreover, in four of the five ligands, the NH2 termini correspond to major proteasome cleavage sites, and putative NH2-terminally extended precursor fragments were detected for only one of the five ligands. All ligands are transported by the transporter associated with antigen processing (TAP). The combined results from these five ligands provide strong evidence that many definitive MHC class I ligands are precisely cleaved at both ends by proteasomes. Additional evidence supporting this conclusion is discussed, along with contrasting results of others who propose a strong role for NH2-terminal trimming with direct proteasomal epitope generation being a rare event. PMID:10637269

Polyfunctional analysis of Gag and Nef specific CD8+ T-cell responses in HIV-1 infected Indian individuals.

PubMed

Mendiratta, Sanjay; Vajpayee, Madhu; Mojumdar, Kamalika; Chauhan, Neeraj K; Sreenivas, Vishnubhatla

2011-02-01

Polyfunctional CD8+ T-cells have been described as most competent in controlling viral replication. We studied the impact of antigen persistence on the polyfunctional immune responses of CD8+ T-lymphocytes to HIV Gag and Nef peptides and polyclonal stimuli in 40 ART naïve HIV infected individuals and analyzed the alterations in T-cell functionality in early and late stages of infection. Significantly elevated level of global response and polyfunctional profile of CD8+ T-cells were observed to polyclonal stimulation, than HIV specific antigens in chronically infected individuals. However no key differences were observed in CD8+ T-cell functional profile in any of the 15 unique subsets for Gag and Nef specific antigens. The subjects in early stage of infection (defined as a gap of 6 months or less between seroconversion and enrolment and with no apparent clinical symptoms) had a higher degree of response functionality (4+ or 3+ different functions simultaneously) than in the late stage infection (defined as time duration since seroconversion greater than 6 months). The data suggest that persistence of antigen during chronic infection leads to functional impairment of HIV specific responses. Copyright © 2010 Elsevier Ltd. All rights reserved.

Role of Occult and Post-acute Phase Replication in Protective Immunity Induced with a Novel Live Attenuated SIV Vaccine

PubMed Central

Ham, Claire; Ferguson, Deborah; Tudor, Hannah; Mattiuzzo, Giada; Klaver, Bep; Page, Mark; Stebbings, Richard; Das, Atze T.; Berkhout, Ben; Almond, Neil; Cranage, Martin P.

2016-01-01

In order to evaluate the role of persisting virus replication during occult phase immunisation in the live attenuated SIV vaccine model, a novel SIVmac239Δnef variant (SIVrtTA) genetically engineered to replicate in the presence of doxycycline was evaluated for its ability to protect against wild-type SIVmac239. Indian rhesus macaques were vaccinated either with SIVrtTA or with SIVmac239Δnef. Doxycycline was withdrawn from 4 of 8 SIVrtTA vaccinates before challenge with wild-type virus. Unvaccinated challenge controls exhibited ~107 peak plasma viral RNA copies/ml persisting beyond the acute phase. Six vaccinates, four SIVmac239Δnef and two SIVrtTA vaccinates exhibited complete protection, defined by lack of wild-type viraemia post-challenge and virus-specific PCR analysis of tissues recovered post-mortem, whereas six SIVrtTA vaccinates were protected from high levels of viraemia. Critically, the complete protection in two SIVrtTA vaccinates was associated with enhanced SIVrtTA replication in the immediate post-acute vaccination period but was independent of doxycycline status at the time of challenge. Mutations were identified in the LTR promoter region and rtTA gene that do not affect doxycycline-control but were associated with enhanced post-acute phase replication in protected vaccinates. High frequencies of total circulating CD8+T effector memory cells and a higher total frequency of SIV-specific CD8+ mono and polyfunctional T cells on the day of wild-type challenge were associated with complete protection but these parameters were not predictive of outcome when assessed 130 days after challenge. Moreover, challenge virus-specific Nef CD8+ polyfunctional T cell responses and antigen were detected in tissues post mortem in completely-protected macaques indicating post-challenge control of infection. Within the parameters of the study design, on-going occult-phase replication may not be absolutely required for protective immunity. PMID:28002473

A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of an Adjuvanted HIV-1 Gag-Pol-Nef Fusion Protein and Adenovirus 35 Gag-RT-Int-Nef Vaccine in Healthy HIV-Uninfected African Adults

PubMed Central

Omosa-Manyonyi, Gloria; Mpendo, Juliet; Ruzagira, Eugene; Kilembe, William; Chomba, Elwyn; Roman, François; Bourguignon, Patricia; Koutsoukos, Marguerite; Collard, Alix; Voss, Gerald; Laufer, Dagna; Stevens, Gwynn; Hayes, Peter; Clark, Lorna; Cormier, Emmanuel; Dally, Len; Barin, Burc; Ackland, Jim; Syvertsen, Kristen; Zachariah, Devika; Anas, Kamaal; Sayeed, Eddy; Lombardo, Angela; Gilmour, Jill; Cox, Josephine; Fast, Patricia; Priddy, Frances

2015-01-01

Background Sequential prime-boost or co-administration of HIV vaccine candidates based on an adjuvanted clade B p24, RT, Nef, p17 fusion protein (F4/AS01) plus a non-replicating adenovirus 35 expressing clade A Gag, RT, Int and Nef (Ad35-GRIN) may lead to a unique immune profile, inducing both strong T-cell and antibody responses. Methods In a phase 1, double-blind, placebo-controlled trial, 146 healthy adult volunteers were randomized to one of four regimens: heterologous prime-boost with two doses of F4/AS01E or F4/AS01B followed by Ad35-GRIN; Ad35-GRIN followed by two doses of F4/AS01B; or three co-administrations of Ad35-GRIN and F4/AS01B. T cell and antibody responses were measured. Results The vaccines were generally well-tolerated, and did not cause serious adverse events. The response rate, by IFN-γ ELISPOT, was greater when Ad35-GRIN was the priming vaccine and in the co-administration groups. F4/AS01 induced CD4+ T-cells expressing primarily CD40L and IL2 +/- TNF-α, while Ad35-GRIN induced predominantly CD8+ T-cells expressing IFN-γ +/- IL2 or TNF-α. Viral inhibition was induced after Ad35-GRIN vaccination, regardless of the regimen. Strong F4-specific antibody responses were induced. Immune responses persisted at least a year after the last vaccination. The complementary response profiles, characteristic of each vaccine, were both expressed after co-administration. Conclusion Co-administration of an adjuvanted protein and an adenovirus vector showed an acceptable safety and reactogenicity profile and resulted in strong, multifunctional and complementary HIV-specific immune responses. Trial Registration ClinicalTrials.gov NCT01264445 PMID:25961283

Decoded fMRI neurofeedback can induce bidirectional confidence changes within single participants.

PubMed

Cortese, Aurelio; Amano, Kaoru; Koizumi, Ai; Lau, Hakwan; Kawato, Mitsuo

2017-04-01

Neurofeedback studies using real-time functional magnetic resonance imaging (rt-fMRI) have recently incorporated the multi-voxel pattern decoding approach, allowing for fMRI to serve as a tool to manipulate fine-grained neural activity embedded in voxel patterns. Because of its tremendous potential for clinical applications, certain questions regarding decoded neurofeedback (DecNef) must be addressed. Specifically, can the same participants learn to induce neural patterns in opposite directions in different sessions? If so, how does previous learning affect subsequent induction effectiveness? These questions are critical because neurofeedback effects can last for months, but the short- to mid-term dynamics of such effects are unknown. Here we employed a within-subjects design, where participants underwent two DecNef training sessions to induce behavioural changes of opposing directionality (up or down regulation of perceptual confidence in a visual discrimination task), with the order of training counterbalanced across participants. Behavioral results indicated that the manipulation was strongly influenced by the order and the directionality of neurofeedback training. We applied nonlinear mathematical modeling to parametrize four main consequences of DecNef: main effect of change in confidence, strength of down-regulation of confidence relative to up-regulation, maintenance of learning effects, and anterograde learning interference. Modeling results revealed that DecNef successfully induced bidirectional confidence changes in different sessions within single participants. Furthermore, the effect of up- compared to down-regulation was more prominent, and confidence changes (regardless of the direction) were largely preserved even after a week-long interval. Lastly, the effect of the second session was markedly diminished as compared to the effect of the first session, indicating strong anterograde learning interference. These results are interpreted in the framework of reinforcement learning and provide important implications for its application to basic neuroscience, to occupational and sports training, and to therapy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Decoded fMRI neurofeedback can induce bidirectional confidence changes within single participants

PubMed Central

Cortese, Aurelio; Amano, Kaoru; Koizumi, Ai; Lau, Hakwan; Kawato, Mitsuo

2017-01-01

Neurofeedback studies using real-time functional magnetic resonance imaging (rt-fMRI) have recently incorporated the multi-voxel pattern decoding approach, allowing for fMRI to serve as a tool to manipulate fine-grained neural activity embedded in voxel patterns. Because of its tremendous potential for clinical applications, certain questions regarding decoded neurofeedback (DecNef) must be addressed. Specifically, can the same participants learn to induce neural patterns in opposite directions in different sessions? If so, how does previous learning affect subsequent induction effectiveness? These questions are critical because neurofeedback effects can last for months, but the short- to mid-term dynamics of such effects are unknown. Here we employed a within-subjects design, where participants underwent two DecNef training sessions to induce behavioural changes of opposing directionality (up or down regulation of perceptual confidence in a visual discrimination task), with the order of training counterbalanced across participants. Behavioral results indicated that the manipulation was strongly influenced by the order and the directionality of neurofeedback training. We applied nonlinear mathematical modeling to parametrize four main consequences of DecNef: main effect of change in confidence, strength of down-regulation of confidence relative to up-regulation, maintenance of learning effects, and anterograde learning interference. Modeling results revealed that DecNef successfully induced bidirectional confidence changes in different sessions within single participants. Furthermore, the effect of up- compared to down-regulation was more prominent, and confidence changes (regardless of the direction) were largely preserved even after a week-long interval. Lastly, the effect of the second session was markedly diminished as compared to the effect of the first session, indicating strong anterograde learning interference. These results are interpreted in the framework of reinforcement learning and provide important implications for its application to basic neuroscience, to occupational and sports training, and to therapy. PMID:28163140

An ultra low-power front-end IC for wearable health monitoring system.

PubMed

Yu-Pin Hsu; Zemin Liu; Hella, Mona M

2016-08-01

This paper presents a low-power front-end IC for wearable health monitoring systems. The IC, designed in a standard 0.13μm CMOS technology, fully integrates a low-noise analog front-end (AFE) to process the weak bio-signals, followed by an analog-to-digital converter (ADC) to digitize the extracted signals. An AC-coupled driving buffer, that interfaces between the AFE and the ADC is introduced to scale down the power supply of the ADC. The power consumption decreases by 50% compared to the case without power supply scaling. The AFE passes signals from 0.5Hz to 280Hz and from 0.7Hz to 160Hz with a simulated input referred noise of 1.6μVrms and achieves a maximum gain of 35dB/41dB respectively, with a noise-efficiency factor (NEF) of the AFE is 1. The 8-bit ADC achieves a simulated 7.96-bit resolution at 10KS/s sampling rate under 0.5V supply voltage. The overall system consumes only 0.86μW at dual supply voltages of 1V (AFE) and 0.5 V (ADC).

Oxygen matters: tissue culture oxygen levels affect mitochondrial function and structure as well as responses to HIV viroproteins.

PubMed

Tiede, L M; Cook, E A; Morsey, B; Fox, H S

2011-12-22

Mitochondrial dysfunction is implicated in a majority of neurodegenerative disorders and much study of neurodegenerative disease is done on cultured neurons. In traditional tissue culture, the oxygen level that cells experience is dramatically higher (21%) than in vivo conditions (1-11%). These differences can alter experimental results, especially, pertaining to mitochondria and oxidative metabolism. Our results show that primary neurons cultured at physiological oxygen levels found in the brain showed higher polarization, lower rates of ROS production, larger mitochondrial networks, greater cytoplasmic fractions of mitochondria and larger mitochondrial perimeters than those cultured at higher oxygen levels. Although neurons cultured in either physiological oxygen or atmospheric oxygen exhibit significant increases in mitochondrial reactive oxygen species (ROS) production when treated with the human immunodeficiency virus (HIV) virotoxin trans-activator of transcription, mitochondria of neurons cultured at physiological oxygen underwent depolarization with dramatically increased cell death, whereas those cultured at atmospheric oxygen became hyperpolarized with no increase in cell death. Studies with a second HIV virotoxin, negative regulation factor (Nef), revealed that Nef treatment also increased mitochondrial ROS production for both the oxygen conditions, but resulted in mitochondrial depolarization and increased death only in neurons cultured in physiological oxygen. These results indicate a role for oxidative metabolism in a mechanism of neurotoxicity during HIV infection and demonstrate the importance of choosing the correct, physiological, culture oxygen in mitochondrial studies performed in neurons.

Advances in fMRI Real-Time Neurofeedback.

PubMed

Watanabe, Takeo; Sasaki, Yuka; Shibata, Kazuhisa; Kawato, Mitsuo

2017-12-01

Functional magnetic resonance imaging (fMRI) neurofeedback is a type of biofeedback in which real-time online fMRI signals are used to self-regulate brain function. Since its advent in 2003 significant progress has been made in fMRI neurofeedback techniques. Specifically, the use of implicit protocols, external rewards, multivariate analysis, and connectivity analysis has allowed neuroscientists to explore a possible causal involvement of modified brain activity in modified behavior. These techniques have also been integrated into groundbreaking new neurofeedback technologies, specifically decoded neurofeedback (DecNef) and functional connectivity-based neurofeedback (FCNef). By modulating neural activity and behavior, DecNef and FCNef have substantially advanced both basic and clinical research. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

HIV-1 Nef in Macrophage-Mediated Disease Pathogenesis

PubMed Central

Lamers, Susanna L.; Fogel, Gary B.; Singer, Elyse J.; Salemi, Marco; Nolan, David J.; Huysentruyt, Leanne C.; McGrath, Michael S.

2013-01-01

Combined anti-retroviral therapy (cART) has significantly reduced the number of AIDS-associated illnesses and changed the course of HIV-1 disease in developed countries. Despite the ability of cART to maintain high CD4+ T-cell counts, a number of macrophage-mediated diseases can still occur in HIV-infected subjects. These diseases include lymphoma, metabolic diseases, and HIV-associated neurological disorders. Within macrophages, the HIV-1 regulatory protein “Nef” can modulate surface receptors, interact with signaling pathways, and promote specific environments that contribute to each of these pathologies. Moreover, genetic variation in Nef may also guide the macrophage response. Herein, we review findings relating to the Nef–macrophage interaction and how this relationship contributes to disease pathogenesis. PMID:23215766

Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

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

Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver

Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequentmore » challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.« less

Cross-reactivity of anti-HIV-1 T cell immune responses among the major HIV-1 clades in HIV-1-positive individuals from 4 continents.

PubMed

Coplan, Paul M; Gupta, Swati B; Dubey, Sheri A; Pitisuttithum, Punnee; Nikas, Alex; Mbewe, Bernard; Vardas, Efthyia; Schechter, Mauro; Kallas, Esper G; Freed, Dan C; Fu, Tong-Ming; Mast, Christopher T; Puthavathana, Pilaipan; Kublin, James; Brown Collins, Kelly; Chisi, John; Pendame, Richard; Thaler, Scott J; Gray, Glenda; Mcintyre, James; Straus, Walter L; Condra, Jon H; Mehrotra, Devan V; Guess, Harry A; Emini, Emilio A; Shiver, John W

2005-05-01

The genetic diversity of human immunodeficiency virus type 1 (HIV-1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified the cross-clade reactivity, among unvaccinated individuals, of anti-HIV-1 T cell responses to the infecting HIV-1 clade relative to other major circulating clades. Cellular immune responses to HIV-1 clades A, B, and C were compared by standardized interferon- gamma enzyme-linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV-1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross-clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous (infecting) clades of HIV-1. Cellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross-clade reactivity of cellular immune responses to HIV-1 clade A, B, and C proteins was substantial for Nef proteins (ratio, 0.97 [95% confidence interval, 0.89-1.05]) and lower for Gag proteins (ratio, 0.67 [95% confidence interval, 0.62-0.73]). The difference in cross-clade reactivity to Nef and Gag proteins was significant (P<.0001). Cross-clade reactivity of cellular immune responses can be substantial but varies by viral protein.

Three dimensional canonical singularity and five dimensional N = 1 SCFT

NASA Astrophysics Data System (ADS)

Xie, Dan; Yau, Shing-Tung

2017-06-01

We conjecture that every three dimensional canonical singularity defines a five dimensional N = 1 SCFT. Flavor symmetry can be found from singularity structure: non-abelian flavor symmetry is read from the singularity type over one dimensional singular locus. The dimension of Coulomb branch is given by the number of compact crepant divisors from a crepant resolution of singularity. The detailed structure of Coulomb branch is described as follows: a) a chamber of Coulomb branch is described by a crepant resolution, and this chamber is given by its Nef cone and the prepotential is computed from triple intersection numbers; b) Crepant resolution is not unique and different resolutions are related by flops; Nef cones from crepant resolutions form a fan which is claimed to be the full Coulomb branch.

Configurable analog-digital conversion using the neural engineering framework

PubMed Central

Mayr, Christian G.; Partzsch, Johannes; Noack, Marko; Schüffny, Rene

2014-01-01

Efficient Analog-Digital Converters (ADC) are one of the mainstays of mixed-signal integrated circuit design. Besides the conventional ADCs used in mainstream ICs, there have been various attempts in the past to utilize neuromorphic networks to accomplish an efficient crossing between analog and digital domains, i.e., to build neurally inspired ADCs. Generally, these have suffered from the same problems as conventional ADCs, that is they require high-precision, handcrafted analog circuits and are thus not technology portable. In this paper, we present an ADC based on the Neural Engineering Framework (NEF). It carries out a large fraction of the overall ADC process in the digital domain, i.e., it is easily portable across technologies. The analog-digital conversion takes full advantage of the high degree of parallelism inherent in neuromorphic networks, making for a very scalable ADC. In addition, it has a number of features not commonly found in conventional ADCs, such as a runtime reconfigurability of the ADC sampling rate, resolution and transfer characteristic. PMID:25100933

Development of Residential SOFC Cogeneration System

NASA Astrophysics Data System (ADS)

Ono, Takashi; Miyachi, Itaru; Suzuki, Minoru; Higaki, Katsuki

2011-06-01

Since 2001 Kyocera has been developing 1kW class Solid Oxide Fuel Cell (SOFC) for power generation system. We have developed a cell, stack, module and system. Since 2004, Kyocera and Osaka Gas Co., Ltd. have been developed SOFC residential co-generation system. From 2007, we took part in the "Demonstrative Research on Solid Oxide Fuel Cells" Project conducted by New Energy Foundation (NEF). Total 57 units of 0.7kW class SOFC cogeneration systems had been installed at residential houses. In spite of residential small power demand, the actual electric efficiency was about 40%(netAC,LHV), and high CO2 reduction performance was achieved by these systems. Hereafter, new joint development, Osaka Gas, Toyota Motors, Kyocera and Aisin Seiki, aims early commercialization of residential SOFC CHP system.

Oxygen matters: tissue culture oxygen levels affect mitochondrial function and structure as well as responses to HIV viroproteins

PubMed Central

Tiede, L M; Cook, E A; Morsey, B; Fox, H S

2011-01-01

Mitochondrial dysfunction is implicated in a majority of neurodegenerative disorders and much study of neurodegenerative disease is done on cultured neurons. In traditional tissue culture, the oxygen level that cells experience is dramatically higher (21%) than in vivo conditions (1–11%). These differences can alter experimental results, especially, pertaining to mitochondria and oxidative metabolism. Our results show that primary neurons cultured at physiological oxygen levels found in the brain showed higher polarization, lower rates of ROS production, larger mitochondrial networks, greater cytoplasmic fractions of mitochondria and larger mitochondrial perimeters than those cultured at higher oxygen levels. Although neurons cultured in either physiological oxygen or atmospheric oxygen exhibit significant increases in mitochondrial reactive oxygen species (ROS) production when treated with the human immunodeficiency virus (HIV) virotoxin trans-activator of transcription, mitochondria of neurons cultured at physiological oxygen underwent depolarization with dramatically increased cell death, whereas those cultured at atmospheric oxygen became hyperpolarized with no increase in cell death. Studies with a second HIV virotoxin, negative regulation factor (Nef), revealed that Nef treatment also increased mitochondrial ROS production for both the oxygen conditions, but resulted in mitochondrial depolarization and increased death only in neurons cultured in physiological oxygen. These results indicate a role for oxidative metabolism in a mechanism of neurotoxicity during HIV infection and demonstrate the importance of choosing the correct, physiological, culture oxygen in mitochondrial studies performed in neurons. PMID:22190005

Obtaining Arbitrary Prescribed Mean Field Dynamics for Recurrently Coupled Networks of Type-I Spiking Neurons with Analytically Determined Weights

PubMed Central

Nicola, Wilten; Tripp, Bryan; Scott, Matthew

2016-01-01

A fundamental question in computational neuroscience is how to connect a network of spiking neurons to produce desired macroscopic or mean field dynamics. One possible approach is through the Neural Engineering Framework (NEF). The NEF approach requires quantities called decoders which are solved through an optimization problem requiring large matrix inversion. Here, we show how a decoder can be obtained analytically for type I and certain type II firing rates as a function of the heterogeneity of its associated neuron. These decoders generate approximants for functions that converge to the desired function in mean-squared error like 1/N, where N is the number of neurons in the network. We refer to these decoders as scale-invariant decoders due to their structure. These decoders generate weights for a network of neurons through the NEF formula for weights. These weights force the spiking network to have arbitrary and prescribed mean field dynamics. The weights generated with scale-invariant decoders all lie on low dimensional hypersurfaces asymptotically. We demonstrate the applicability of these scale-invariant decoders and weight surfaces by constructing networks of spiking theta neurons that replicate the dynamics of various well known dynamical systems such as the neural integrator, Van der Pol system and the Lorenz system. As these decoders are analytically determined and non-unique, the weights are also analytically determined and non-unique. We discuss the implications for measured weights of neuronal networks. PMID:26973503

Obtaining Arbitrary Prescribed Mean Field Dynamics for Recurrently Coupled Networks of Type-I Spiking Neurons with Analytically Determined Weights.

PubMed

Nicola, Wilten; Tripp, Bryan; Scott, Matthew

2016-01-01

A fundamental question in computational neuroscience is how to connect a network of spiking neurons to produce desired macroscopic or mean field dynamics. One possible approach is through the Neural Engineering Framework (NEF). The NEF approach requires quantities called decoders which are solved through an optimization problem requiring large matrix inversion. Here, we show how a decoder can be obtained analytically for type I and certain type II firing rates as a function of the heterogeneity of its associated neuron. These decoders generate approximants for functions that converge to the desired function in mean-squared error like 1/N, where N is the number of neurons in the network. We refer to these decoders as scale-invariant decoders due to their structure. These decoders generate weights for a network of neurons through the NEF formula for weights. These weights force the spiking network to have arbitrary and prescribed mean field dynamics. The weights generated with scale-invariant decoders all lie on low dimensional hypersurfaces asymptotically. We demonstrate the applicability of these scale-invariant decoders and weight surfaces by constructing networks of spiking theta neurons that replicate the dynamics of various well known dynamical systems such as the neural integrator, Van der Pol system and the Lorenz system. As these decoders are analytically determined and non-unique, the weights are also analytically determined and non-unique. We discuss the implications for measured weights of neuronal networks.

Pseudo-merohedral twinning and noncrystallographic symmetry in orthorhombic crystals of SIVmac239 Nef core domain bound to different-length TCRζ fragments

PubMed Central

Kim, Walter M.; Sigalov, Alexander B.; Stern, Lawrence J.

2010-01-01

HIV/SIV Nef mediates many cellular processes through interactions with various cytoplasmic and membrane-associated host proteins, including the signalling ζ subunit of the T-­cell receptor (TCRζ). Here, the crystallization strategy, methods and refinement procedures used to solve the structures of the core domain of the SIVmac239 isolate of Nef (Nefcore) in complex with two different TCRζ fragments are described. The structure of SIVmac239 Nefcore bound to the longer TCRζ polypeptide (Leu51–Asp93) was determined to 3.7 Å resolution (R work = 28.7%) in the tetragonal space group P43212. The structure of SIVmac239 Nefcore in complex with the shorter TCRζ polypeptide (Ala63–Arg80) was determined to 2.05 Å resolution (R work = 17.0%), but only after the detection of nearly perfect pseudo-merohedral crystal twinning and proper assignment of the orthorhombic space group P212121. The reduction in crystal space-group symmetry induced by the truncated TCRζ polypeptide appears to be caused by the rearrangement of crystal-contact hydrogen-bonding networks and the substitution of crystallographic symmetry operations by similar noncrystallographic symmetry (NCS) operations. The combination of NCS rotations that were nearly parallel to the twin operation (k, h, −l) and a and b unit-cell parameters that were nearly identical predisposed the P212121 crystal form to pseudo-merohedral twinning. PMID:20124696

Learning to Associate Orientation with Color in Early Visual Areas by Associative Decoded fMRI Neurofeedback.

PubMed

Amano, Kaoru; Shibata, Kazuhisa; Kawato, Mitsuo; Sasaki, Yuka; Watanabe, Takeo

2016-07-25

Associative learning is an essential brain process where the contingency of different items increases after training. Associative learning has been found to occur in many brain regions [1-4]. However, there is no clear evidence that associative learning of visual features occurs in early visual areas, although a number of studies have indicated that learning of a single visual feature (perceptual learning) involves early visual areas [5-8]. Here, via decoded fMRI neurofeedback termed "DecNef" [9], we tested whether associative learning of orientation and color can be created in early visual areas. During 3 days of training, DecNef induced fMRI signal patterns that corresponded to a specific target color (red) mostly in early visual areas while a vertical achromatic grating was physically presented to participants. As a result, participants came to perceive "red" significantly more frequently than "green" in an achromatic vertical grating. This effect was also observed 3-5 months after the training. These results suggest that long-term associative learning of two different visual features such as orientation and color was created, most likely in early visual areas. This newly extended technique that induces associative learning is called "A-DecNef," and it may be used as an important tool for understanding and modifying brain functions because associations are fundamental and ubiquitous functions in the brain. Copyright © 2016 Elsevier Ltd. All rights reserved.

An Exosome-Based Vaccine Platform Imparts Cytotoxic T Lymphocyte Immunity Against Viral Antigens.

PubMed

Anticoli, Simona; Manfredi, Francesco; Chiozzini, Chiara; Arenaccio, Claudia; Olivetta, Eleonora; Ferrantelli, Flavia; Capocefalo, Antonio; Falcone, Emiliana; Ruggieri, Anna; Federico, Maurizio

2018-04-01

Exosomes are 50-150 nm sized nanovesicles released by all eukaryotic cells. The authors very recently described a method to engineer exosomes in vivo with the E7 protein of Human Papilloma Virus (HPV). This technique consists in the intramuscular injection of a DNA vector expressing HPV-E7 fused at the C-terminus of an exosome-anchoring protein, that is, Nef mut , the authors previously characterized for its high levels of incorporation in exosomes. In this configuration, the ≈11 kDa E7 protein elicited a both strong and effective antigen-specific cytotoxic T lymphocyte (CTL) immunity. Attempting to establish whether this method could have general applicability, the authors expanded the immunogenicity studies toward an array of viral products of various origin and size including Ebola Virus VP24, VP40 and NP, Influenza Virus NP, Crimean-Congo Hemorrhagic Fever NP, West Nile Virus NS3, and Hepatitis C Virus NS3. All antigens appeared stable upon fusion with Nef mut , and are uploaded in exosomes at levels comparable to Nef mut . When injected in mice, DNA vectors expressing the diverse fusion products elicited a well detectable antigen-specific CD8 + T cell response associating with a cytotoxic activity potent enough to kill peptide-loaded and/or antigen-expressing syngeneic cells. These data definitely proven both effectiveness and flexibility of this innovative CTL vaccine platform. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High-level expression of human immunodeficiency virus antigens from the tobacco and tomato plastid genomes.

PubMed

Zhou, Fei; Badillo-Corona, Jesus A; Karcher, Daniel; Gonzalez-Rabade, Nuria; Piepenburg, Katrin; Borchers, A-M Inka; Maloney, Alan P; Kavanagh, Tony A; Gray, John C; Bock, Ralph

2008-12-01

Transgene expression from the plant's plastid genome represents a promising strategy in molecular farming because of the plastid's potential to accumulate foreign proteins to high levels and the increased biosafety provided by the maternal mode of organelle inheritance. In this article, we explore the potential of transplastomic plants to produce human immunodeficiency virus (HIV) antigens as potential components of an acquired immunodeficiency syndrome (AIDS) vaccine. It is shown that the HIV antigens p24 (the major target of T-cell-mediated immune responses in HIV-positive individuals) and Nef can be expressed to high levels in plastids of tobacco, a non-food crop, and tomato, a food crop with an edible fruit. Optimized p24-Nef fusion gene cassettes trigger antigen protein accumulation to up to approximately 40% of the plant's total protein, demonstrating the great potential of transgenic plastids to produce AIDS vaccine components at low cost and high yield.

Role of molecular mimicry to HIV-1 peptides in HIV-1–related immunologic thrombocytopenia

PubMed Central

Li, Zongdong; Nardi, Michael A.; Karpatkin, Simon

2005-01-01

Patients with early HIV-1 infection develop an autoimmune thrombocytopenia in which antibody is directed against an immunodominant epitope of the β3 (glycoprotein IIIa [GPIIIa]) integrin, GPIIIa49-66. This antibody induces thrombocytopenia by a novel complement-independent mechanism in which platelets are fragmented by antibody-induced generation of H2O2 derived from the interaction of platelet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and 12-lipoxygenase. To examine whether sharing of epitope between host and parasite may be responsible for this immunodominant epitope, we screened for antibody-reactive peptides capable of inhibiting platelet lysis and oxidation in vitro, using a filamentous phage display 7-mer peptide library. Fourteen of these phage-peptide clones were identified. Five shared close sequence similarity with GPIIIa49-66, as expected. Ten were molecular mimics with close sequence similarity to HIV-1 proteins nef, gag, env, and pol. Seven were synthesized as 10-mers from their known HIV-1 sequence and found to inhibit anti–GPIIIa49-66–induced platelet oxidation/fragmentation in vitro. Three rabbit antibodies raised against these peptides induced platelet oxidation/fragmentation in vitro and thrombocytopenia in vivo when passively transferred into mice. One of the peptides shared a known epitope region with HIV-1 protein nef and was derived from a variant region of the protein. These data provide strong support for molecular mimicry in HIV-1-immunologic thrombocytopenia within polymorphic regions of HIV-1 proteins. A known epitope of nef is particularly incriminated. PMID:15774614

Magnetic phase diagrams of amorphous (Ni100-xFex)-metalloid alloys: The key role of the electronic density of states at the Fermi level for the onset of magnetic order

NASA Astrophysics Data System (ADS)

Kiss, L. F.; Bakonyi, I.

2017-11-01

There have been extended studies on the appearance of ferromagnetism in transition-metal-metalloid (MD) glasses. In particular, the paramagnetic (PM) to ferromagnetic (FM) transition has been investigated on numerous (Ni100-xFex)-MD alloys upon the introduction of Fe where MD can represent a combination of various metalloid elements, while keeping the metal/metalloid ratio constant. It has been reported that adding a sufficient amount of Fe to a Pauli PM Ni-MD alloy matrix first induces a spin-glass (SG) state at low temperatures which goes over to a PM state at higher temperatures. Beyond a certain Fe content, xc, the SG state transforms to a FM state upon increasing the temperature. By plotting the characteristic transition temperatures as a function of the Fe content, a magnetic phase diagram can be constructed for each Ni-Fe-MD system which has a multicritical point (MCP) at xc. By using the reported magnetic phase diagrams of various Ni-Fe-MD alloy systems, it is shown that the critical Fe content, xc scales inversely with the density of states at the Fermi level, N(EF), of the parent Ni-MD matrix. This means that the higher the N(EF), the lower the critical Fe content to induce ferromagnetism in the Ni-MD matrix. This is then discussed in terms of the Stoner enhancement factor, S, which characterizes the tendency of the matrix to become ferromagnetic.

In vitro modeling of HIV proviral activity in microglia.

PubMed

Campbell, Lee A; Richie, Christopher T; Zhang, Yajun; Heathward, Emily J; Coke, Lamarque M; Park, Emily Y; Harvey, Brandon K

2017-12-01

Microglia, the resident macrophages of the brain, play a key role in the pathogenesis of HIV-associated neurocognitive disorders (HAND) due to their productive infection by HIV. This results in the release of neurotoxic viral proteins and pro-inflammatory compounds which negatively affect the functionality of surrounding neurons. Because models of HIV infection within the brain are limited, we aimed to create a novel microglia cell line with an integrated HIV provirus capable of recreating several hallmarks of HIV infection. We utilized clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing technology and integrated a modified HIV provirus into CHME-5 immortalized microglia to create HIV-NanoLuc CHME-5. In the modified provirus, the Gag-Pol region is replaced with the coding region for NanoLuciferase (NanoLuc), which allows for the rapid assay of HIV long terminal repeat activity using a luminescent substrate, while still containing the necessary genetic material to produce established neurotoxic viral proteins (e.g. tat, nef, gp120). We confirmed that HIV-NanoLuc CHME-5 microglia express NanoLuc, along with the HIV viral protein Nef. We subsequently exposed these cells to a battery of experiments to modulate the activity of the provirus. Proviral activity was enhanced by treating the cells with pro-inflammatory factors lipopolysaccharide (LPS) and tumor necrosis factor alpha and by overexpressing the viral regulatory protein Tat. Conversely, genetic modification of the toll-like receptor-4 gene by CRISPR/Cas9 reduced LPS-mediated proviral activation, and pharmacological application of NF-κB inhibitor sulfasalazine similarly diminished proviral activity. Overall, these data suggest that HIV-NanoLuc CHME-5 may be a useful tool in the study of HIV-mediated neuropathology and proviral regulation. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

National Emphysema Foundation

MedlinePlus

... the needs and wishes of our readers. Featured Articles An improved quality of life is the NEF mission. The NEF’s mission is to improve the quality of life of patients with emphysema and their caregivers by providing and ... 2015 American Thoracic Society Annual Meeting Highlights. The ...

The HIV-1 Tat protein modulates CD4 expression in human T cells through the induction of miR-222.

PubMed

Orecchini, Elisa; Doria, Margherita; Michienzi, Alessandro; Giuliani, Erica; Vassena, Lia; Ciafrè, Silvia Anna; Farace, Maria Giulia; Galardi, Silvia

2014-01-01

Several cellular microRNAs show substantial changes in expression during HIV-1 infection and their active role in the viral life cycle is progressively emerging. In the present study, we found that HIV-1 infection of Jurkat T cells significantly induces the expression of miR-222. We show that this induction depends on HIV-1 Tat protein, which is able to increase the transcriptional activity of NFkB on miR-222 promoter. Moreover, we demonstrate that miR-222 directly targets CD4, a key receptor for HIV-1, thus reducing its expression. We propose that Tat, by inducing miR-222 expression, complements the CD4 downregulation activity exerted by other viral proteins (i.e., Nef, Vpu, and Env), and we suggest that this represents a novel mechanism through which HIV-1 efficiently represses CD4 expression in infected cells.

The HIV-1 Tat protein modulates CD4 expression in human T cells through the induction of miR-222

PubMed Central

Orecchini, Elisa; Doria, Margherita; Michienzi, Alessandro; Giuliani, Erica; Vassena, Lia; Ciafrè, Silvia Anna; Farace, Maria Giulia; Galardi, Silvia

2014-01-01

Several cellular microRNAs show substantial changes in expression during HIV-1 infection and their active role in the viral life cycle is progressively emerging. In the present study, we found that HIV-1 infection of Jurkat T cells significantly induces the expression of miR-222. We show that this induction depends on HIV-1 Tat protein, which is able to increase the transcriptional activity of NFkB on miR-222 promoter. Moreover, we demonstrate that miR-222 directly targets CD4, a key receptor for HIV-1, thus reducing its expression. We propose that Tat, by inducing miR-222 expression, complements the CD4 downregulation activity exerted by other viral proteins (i.e., Nef, Vpu, and Env), and we suggest that this represents a novel mechanism through which HIV-1 efficiently represses CD4 expression in infected cells. PMID:24717285

Birationality and Landau-Ginzburg Models

NASA Astrophysics Data System (ADS)

Clarke, Patrick

2017-08-01

We introduce a new technique for approaching birationality questions that arise in the mirror symmetry of complete intersections in toric varieties. As an application we answer affirmatively and conclusively the question of Batyrev-Nill (Integer points in polyhedra—geometry, number theory, representation theory, algebra, optimization, statistics, volume 452 of Contemporary mathematics. American Mathematical Society, Providence, pp 35-66, 2008) about the birationality of Calabi-Yau families associated to multiple mirror nef-partitions. This completes the progress in this direction made by Li's breakthrough (Li in Adv Math 299:71-107, 2016). In the process, we obtain results in the theory of Borisov's nef-partitions (Borisov in Towards the mirror symmetry for Calabi-Yau complete intersections in Gorenstein toric Fano varieties, 1993. arXiv:alg-geom/9310001 ) and provide new insight into the geometric content of the multiple mirror phenomenon.

Metabolic indicators of habitat differences in four Minnesota deer populations

USGS Publications Warehouse

Seal, U.S.; Nelson, M.E.; Mech, L.D.; Hoskinson, R.L.

1978-01-01

Blood samples were collected from 40 white-tailed deer (Odocoileus virginianus) from 4 winter yards in northeastern Minnesota from 17 March 1974 through 23 April 1975. The results of 26 blood assays were examined for the effects of age, sex, capture date, capture method, disease and location. Age-related effects were found for serum chloride, calcium, gamma globulin, creatine phosphokinase (CPK), lactic dehydrogenase (LDH), and alkaline phosphatase. The only sex difference was lower CPK in males. Date of collection effects were found for erythrocyte count, mean corpuscular volume (MCV), serum glucose, and nonesterified fatty acids (NEF A). Capture method affected serum glucose, acid base balance, and serum enzymes. Effects related primarily to capture location or habitat differences were found for erythrocyte count, MCV, mean corpuscular hemoglobin concentration (MCHC), serum urea, cholesterol, LDH, thyroxine, and NEF A. Animals whose assays indicated the poorest nutritional status inhabited wintering areas with the oldest vegetation. Habitat differences can be detected by measuring the physiological status of the local animal populations.

Expression of CD154 by a Simian Immunodeficiency Virus Vector Induces Only Transitory Changes in Rhesus Macaques

PubMed Central

Hodara, Vida L.; Velasquillo, M. Cristina; Parodi, Laura M.; Giavedoni, Luis D.

2005-01-01

Human immunodeficiency virus infection is characterized by dysregulation of antigen-presenting cell function and defects in cell-mediated immunity. Recent evidence suggests that impaired ability of CD4+ T cells to upregulate the costimulatory molecule CD154 is at the core of this dysregulation. To test the hypothesis that increased expression of CD154 on infected CD4+ T cells could modulate immune function, we constructed a replication-competent simian immunodeficiency virus (SIV) vector that expressed CD154. We found that this recombinant vector directed the expression of CD154 on the surface of infected CD4+ T cells and that expression of CD154 resulted in activation of B cells present in the same cultures. Experimental infection of rhesus macaques resulted in very low viral loads for the CD154-expressing virus and the control virus, indicating that expression of CD154 did not result in increased viral replication. Analyses of the anti-SIV immune responses and the phenotype of lymphocytes in blood and lymphoid tissues showed changes that occurred during the acute phase of infection only in animals infected with the CD154-expressing SIV, but that became indistinguishable from those seen in animals infected with the control virus at later time points. We conclude that the level of expression of CD154 in itself is not responsible for affecting the immune response to an attenuated virus. Considering that the CD154-expressing SIV vector and the virus control did not carry an active nef gene, our results suggest that, in CD4+ T cells infected with wild-type virus, Nef is the viral factor that interferes with the immune mechanisms that regulate expression of CD154. PMID:15795254

24 CFR 51.106 - Implementation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... data. HUD field staff shall make maximum use of noise data prepared by others when such data are... day-night average sound level data are not available may be evaluated from NEF or CNEL analyses using... LCdn. (4) Use of areawide acoustical data. HUD encourages the preparation and use of areawide...

24 CFR 51.106 - Implementation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... day-night average sound level data are not available may be evaluated from NEF or CNEL analyses using.... The day-night average sound level may be estimated from the design hour L10 or Leq values by the.... The Department of Defense uses day-night average sound level based on C-weighted sound level...

77 FR 12333 - Special Nuclear Material License Amendment From Louisiana Energy Services, LLC, for the National...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

... moderate annual impact on local employment for four more years. Environmental justice impacts are described... significant impact. FOR FURTHER INFORMATION CONTACT: Mary T. Adams, Office of Nuclear Material Safety and... NRC issued a final environmental impact statement (EIS) for the NEF (NUREG-1790) (ML051730238 and...

NE-F2: Fluids and Propulsion Design: Summer 2014 Pathways Report

NASA Technical Reports Server (NTRS)

Holland, Katherine M.

2014-01-01

Describes major and minor projects I worked on over this summer and all I learned in the process. I go into detail with my main project, designing a new purge system for GODU LO2. I also highlight some significant events that I really enjoyed during my internship here at KSC

The New Education Fellowship and UNESCO's Programme of Fundamental Education

ERIC Educational Resources Information Center

Watras, Joseph

2011-01-01

This paper will examine the attitudes of progressive educators toward poverty in developing countries. The reformers who formed the New Education Fellowship (NEF) in 1921 will be the subjects. They expanded their thinking from concerns about student freedom to efforts to encourage social reform, and by 1946 they participated in the creation of…

Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus

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

Kaur, Amitinder; Sanford, Hannah B.; Garry, Deirdre

2007-01-20

The immunogenicity and protective capacity of replication-defective herpes simplex virus (HSV) vector-based vaccines were examined in rhesus macaques. Three macaques were inoculated with recombinant HSV vectors expressing Gag, Env, and a Tat-Rev-Nef fusion protein of simian immunodeficiency virus (SIV). Three other macaques were primed with recombinant DNA vectors expressing Gag, Env, and a Pol-Tat-Nef-Vif fusion protein prior to boosting with the HSV vectors. Robust anti-Gag and anti-Env cellular responses were detected in all six macaques. Following intravenous challenge with wild-type, cloned SIV239, peak and 12-week plasma viremia levels were significantly lower in vaccinated compared to control macaques. Plasma SIV RNAmore » in vaccinated macaques was inversely correlated with anti-Rev ELISPOT responses on the day of challenge (P value < 0.05), anti-Tat ELISPOT responses at 2 weeks post challenge (P value < 0.05) and peak neutralizing antibody titers pre-challenge (P value 0.06). These findings support continued study of recombinant herpesviruses as a vaccine approach for AIDS.« less

Functional Interplay Between Murine Leukemia Virus Glycogag, Serinc5, and Surface Glycoprotein Governs Virus Entry, with Opposite Effects on Gammaretroviral and Ebolavirus Glycoproteins.

PubMed

Ahi, Yadvinder S; Zhang, Shu; Thappeta, Yashna; Denman, Audrey; Feizpour, Amin; Gummuluru, Suryaram; Reinhard, Bjoern; Muriaux, Delphine; Fivash, Matthew J; Rein, Alan

2016-11-22

Gammaretroviruses, such as murine leukemia viruses (MLVs), encode, in addition to the canonical Gag, Pol, and Env proteins that will form progeny virus particles, a protein called "glycogag" (glycosylated Gag). MLV glycogag contains the entire Gag sequence plus an 88-residue N-terminal extension. It has recently been reported that glycogag, like the Nef protein of HIV-1, counteracts the antiviral effects of the cellular protein Serinc5. We have found, in agreement with prior work, that glycogag strongly enhances the infectivity of MLVs with some Env proteins but not those with others. In contrast, however, glycogag was detrimental to MLVs carrying Ebolavirus glycoprotein. Glycogag could be replaced, with respect to viral infectivity, by the unrelated S2 protein of equine infectious anemia virus. We devised an assay for viral entry in which virus particles deliver the Cre recombinase into cells, leading to the expression of a reporter. Data from this assay showed that both the positive and the negative effects of glycogag and S2 upon MLV infectivity are exerted at the level of virus entry. Moreover, transfection of the virus-producing cells with a Serinc5 expression plasmid reduced the infectivity and entry capability of MLV carrying xenotropic MLV Env, particularly in the absence of glycogag. Conversely, Serinc5 expression abrogated the negative effects of glycogag upon the infectivity and entry capability of MLV carrying Ebolavirus glycoprotein. As Serinc5 may influence cellular phospholipid metabolism, it seems possible that all of these effects on virus entry derive from changes in the lipid composition of viral membranes. Many murine leukemia viruses (MLVs) encode a protein called "glycogag." The function of glycogag is not fully understood, but it can assist HIV-1 replication in the absence of the HIV-1 protein Nef under some circumstances. In turn, Nef counteracts the cellular protein Serinc5. Glycogag enhances the infectivity of MLVs with some but not all MLV Env proteins (which mediate viral entry into the host cell upon binding to cell surface receptors). We now report that glycogag acts by enhancing viral entry and that, like Nef, glycogag antagonizes Serinc5. Surprisingly, the effects of glycogag and Serinc5 upon the entry and infectivity of MLV particles carrying an Ebolavirus glycoprotein are the opposite of those observed with the MLV Env proteins. The unrelated S2 protein of equine infectious anemia virus (EIAV) is functionally analogous to glycogag in our experiments. Thus, three retroviruses (HIV-1, MLV, and EIAV) have independently evolved accessory proteins that counteract Serinc5. Copyright © 2016 Ahi et al.

MAGTF’s for NEF’s: Revolutionary Adaptive Force Packaging or Getting by with Less

DTIC Science & Technology

1994-02-08

13. 14 Ibid., p. 2. 15. Captain Robert 0. Crawshaw , USN, "What is a Maritime Action Group?" U. S. Naval Institute Proceedings, January 1993. p. 28. 1...Amphibious Force Mediterranean" Headquarters, U. S. Marine Corps, Information Paper, November 1993. Crawshaw , Captain Robert 0., USN, "What is a

Beyond Reading Alone: The Relationship Between Aural Literacy And Asthma Management

PubMed Central

Rosenfeld, Lindsay; Rudd, Rima; Emmons, Karen M.; Acevedo-García, Dolores; Martin, Laurie; Buka, Stephen

2010-01-01

Objectives To examine the relationship between literacy and asthma management with a focus on the oral exchange. Methods Study participants, all of whom reported asthma, were drawn from the New England Family Study (NEFS), an examination of links between education and health. NEFS data included reading, oral (speaking), and aural (listening) literacy measures. An additional survey was conducted with this group of study participants related to asthma issues, particularly asthma management. Data analysis focused on bivariate and multivariable logistic regression. Results In bivariate logistic regression models exploring aural literacy, there was a statistically significant association between those participants with lower aural literacy skills and less successful asthma management (OR:4.37, 95%CI:1.11, 17.32). In multivariable logistic regression analyses, controlling for gender, income, and race in separate models (one-at-a-time), there remained a statistically significant association between those participants with lower aural literacy skills and less successful asthma management. Conclusion Lower aural literacy skills seem to complicate asthma management capabilities. Practice Implications Greater attention to the oral exchange, in particular the listening skills highlighted by aural literacy, as well as other related literacy skills may help us develop strategies for clear communication related to asthma management. PMID:20399060

[Associative Learning between Orientation and Color in Early Visual Areas].

PubMed

Amano, Kaoru; Shibata, Kazuhisa; Kawato, Mitsuo; Sasaki, Yuka; Watanabe, Takeo

2017-08-01

Associative learning is an essential neural phenomenon where the contingency of different items increases after training. Although associative learning has been found to occur in many brain regions, there is no clear evidence that associative learning of visual features occurs in early visual areas. Here, we developed an associative decoded functional magnetic resonance imaging (fMRI) neurofeedback (A-DecNef) to determine whether associative learning of color and orientation can be induced in early visual areas. During the three days' training, A-DecNef induced fMRI signal patterns that corresponded to a specific target color (red) mostly in early visual areas while a vertical achromatic grating was simultaneously, physically presented to participants. Consequently, participants' perception of "red" was significantly more frequently than that of "green" in an achromatic vertical grating. This effect was also observed 3 to 5 months after training. These results suggest that long-term associative learning of two different visual features such as color and orientation, was induced most likely in early visual areas. This newly extended technique that induces associative learning may be used as an important tool for understanding and modifying brain function, since associations are fundamental and ubiquitous with respect to brain function.

Inability to induce consistent T-cell responses recognizing conserved regions within HIIV-1 antigens: a potential mechanism for lack of vaccine efficacy in the step study

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

Korber, Bette; Szinger, James

2009-01-01

T cell based vaccines are based upon the induction of CD8+ T cell memory responses that would be effective in inhibiting infection and subsequent replication of an infecting HIV-1 strain, a process that requires a high probability of matching the epitope induced by vaccination with the infecting viral strain. We compared the frequency and specificity of the CTL epitopes elicited by the replication defective AdS gag/pol/nef vaccine used in the STEP trial with the likelihood of encountering those epitopes among recently sequenced Clade B isolates of HIV-1. On average vaccination elicited only one epitope per gene. Importantly, the highly conservedmore » epitopes in gag, pol, and nef (> 80% of strains in the current collection of the Los Alamos database [www.hiv.lanl.gov]) were rarely elicited by vaccination. Moreover there was a statistically significant skewing of the T cell response to relative variable epitopes of each gene; only 20% of persons possessed > 3 T cell responses to epitopes likely to be found in circulating strains in the CladeB populations in which the Step trial was conducted. This inability to elicit T cell responses likely to be found in circulating viral strains is a likely factor in the lack of efficacy of the vaccine utilized in the STEP trial. Modeling of the epitope specific responses elicited by vaccination, we project that a median of 8-10 CD8+ T cell epitopes are required to provide >80% likelihood of eliciting at least 3 CD8+ T cell epitopes that would be found on a circulating population of viruses. Development of vaccine regimens which elicit either a greater breadth of responses or elicit responses to conserved regions of the HIV-1 genome are needed to fully evaluate the concept of whether induction of T cell immunity can alter HIV-1 in vivo.« less

Lack of adaptation to human tetherin in HIV-1 Group O and P

PubMed Central

2011-01-01

Background HIV-1 viruses are categorized into four distinct groups: M, N, O and P. Despite the same genomic organization, only the group M viruses are responsible for the world-wide pandemic of AIDS, suggesting better adaptation to human hosts. Previously, it has been reported that the group M Vpu protein is capable of both down-modulating CD4 and counteracting BST-2/tetherin restriction, while the group O Vpu cannot antagonize tetherin. This led us to investigate if group O, and the related group P viruses, possess functional anti-tetherin activities in Vpu or another viral protein, and to further map the residues required for group M Vpu to counteract human tetherin. Results We found a lack of activity against human tetherin for both the Vpu and Nef proteins from group O and P viruses. Furthermore, we found no evidence of anti-human tetherin activity in a fully infectious group O proviral clone, ruling out the possibility of an alternative anti-tetherin factor in this virus. Interestingly, an activity against primate tetherins was retained in the Nef proteins from both a group O and a group P virus. By making chimeras between a functional group M and non-functional group O Vpu protein, we were able to map the first 18 amino acids of group M Vpu as playing an essential role in the ability of the protein to antagonize human tetherin. We further demonstrated the importance of residue alanine-18 for the group M Vpu activity. This residue lies on a diagonal face of conserved alanines in the TM domain of the protein, and is necessary for specific Vpu-tetherin interactions. Conclusions The absence of human specific anti-tetherin activities in HIV-1 group O and P suggests a failure of these viruses to adapt to human hosts, which may have limited their spread. PMID:21955466

MRKAd5 HIV-1 Gag/Pol/Nef Vaccine-Induced T-Cell Responses Inadequately Predict Distance of Breakthrough HIV-1 Sequences to the Vaccine or Viral Load

PubMed Central

Janes, Holly; Frahm, Nicole; DeCamp, Allan; Rolland, Morgane; Gabriel, Erin; Wolfson, Julian; Hertz, Tomer; Kallas, Esper; Goepfert, Paul; Friedrich, David P.; Corey, Lawrence; Mullins, James I.; McElrath, M. Juliana; Gilbert, Peter

2012-01-01

Background The sieve analysis for the Step trial found evidence that breakthrough HIV-1 sequences for MRKAd5/HIV-1 Gag/Pol/Nef vaccine recipients were more divergent from the vaccine insert than placebo sequences in regions with predicted epitopes. We linked the viral sequence data with immune response and acute viral load data to explore mechanisms for and consequences of the observed sieve effect. Methods Ninety-one male participants (37 placebo and 54 vaccine recipients) were included; viral sequences were obtained at the time of HIV-1 diagnosis. T-cell responses were measured 4 weeks post-second vaccination and at the first or second week post-diagnosis. Acute viral load was obtained at RNA-positive and antibody-negative visits. Findings Vaccine recipients had a greater magnitude of post-infection CD8+ T cell response than placebo recipients (median 1.68% vs 1.18%; p = 0·04) and greater breadth of post-infection response (median 4.5 vs 2; p = 0·06). Viral sequences for vaccine recipients were marginally more divergent from the insert than placebo sequences in regions of Nef targeted by pre-infection immune responses (p = 0·04; Pol p = 0·13; Gag p = 0·89). Magnitude and breadth of pre-infection responses did not correlate with distance of the viral sequence to the insert (p>0·50). Acute log viral load trended lower in vaccine versus placebo recipients (estimated mean 4·7 vs 5·1) but the difference was not significant (p = 0·27). Neither was acute viral load associated with distance of the viral sequence to the insert (p>0·30). Interpretation Despite evidence of anamnestic responses, the sieve effect was not well explained by available measures of T-cell immunogenicity. Sequence divergence from the vaccine was not significantly associated with acute viral load. While point estimates suggested weak vaccine suppression of viral load, the result was not significant and more viral load data would be needed to detect suppression. PMID:22952672

The Use of Nanotrap Particles Technology in Capturing HIV-1 Virions and Viral Proteins from Infected Cells

PubMed Central

Sampey, Gavin; Shafagati, Nazly; Van Duyne, Rachel; Iordanskiy, Sergey; Kehn-Hall, Kylene; Liotta, Lance; Petricoin, Emanuel; Young, Mary; Lepene, Benjamin; Kashanchi, Fatah

2014-01-01

HIV-1 infection results in a chronic but incurable illness since long-term HAART can keep the virus to an undetectable level. However, discontinuation of therapy rapidly increases viral burden. Moreover, patients under HAART frequently develop various metabolic disorders and HIV-associated neuronal disease. Today, the main challenge of HIV-1 research is the elimination of the residual virus in infected individuals. The current HIV-1 diagnostics are largely comprised of serological and nucleic acid based technologies. Our goal is to integrate the nanotrap technology into a standard research tool that will allow sensitive detection of HIV-1 infection. This study demonstrates that majority of HIV-1 virions in culture supernatants and Tat/Nef proteins spiked in culture medium can be captured by nanotrap particles. To determine the binding affinities of different baits, we incubated target molecules with nanotrap particles at room temperature. After short sequestration, materials were either eluted or remained attached to nanotrap particles prior to analysis. The unique affinity baits of nanotrap particles preferentially bound HIV-1 materials while excluded albumin. A high level capture of Tat or Tat peptide by NT082 and NT084 particles was measured by western blot (WB). Intracellular Nef protein was captured by NT080, while membrane-associated Nef was captured by NT086 and also detected by WB. Selective capture of HIV-1 particles by NT073 and NT086 was measured by reverse transcriptase assay, while capture of infectious HIV-1 by these nanoparticles was demonstrated by functional transactivation in TZM-bl cells. We also demonstrated specific capture of HIV-1 particles and exosomes-containing TAR-RNA in patients' serum by NT086 and NT082 particles, respectively, using specific qRT-PCR. Collectively, our data indicate that certain types of nanotrap particles selectively capture specific HIV-1 molecules, and we propose to use this technology as a platform to enhance HIV-1 detection by concentrating viral proteins and infectious virions from infected samples. PMID:24820173

Specific CD8+ T Cell Responses Correlate with Control of Simian Immunodeficiency Virus Replication in Mauritian Cynomolgus Macaques

PubMed Central

Budde, Melisa L.; Greene, Justin M.; Chin, Emily N.; Ericsen, Adam J.; Scarlotta, Matthew; Cain, Brian T.; Pham, Ngoc H.; Becker, Ericka A.; Harris, Max; Weinfurter, Jason T.; O'Connor, Shelby L.; Piatak, Michael; Lifson, Jeffrey D.; Gostick, Emma; Price, David A.; Friedrich, Thomas C.

2012-01-01

Specific major histocompatibility complex (MHC) class I alleles are associated with an increased frequency of spontaneous control of human and simian immunodeficiency viruses (HIV and SIV). The mechanism of control is thought to involve MHC class I-restricted CD8+ T cells, but it is not clear whether particular CD8+ T cell responses or a broad repertoire of epitope-specific CD8+ T cell populations (termed T cell breadth) are principally responsible for mediating immunologic control. To test the hypothesis that heterozygous macaques control SIV replication as a function of superior T cell breadth, we infected MHC-homozygous and MHC-heterozygous cynomolgus macaques with the pathogenic virus SIVmac239. As measured by a gamma interferon enzyme-linked immunosorbent spot assay (IFN-γ ELISPOT) using blood, T cell breadth did not differ significantly between homozygotes and heterozygotes. Surprisingly, macaques that controlled SIV replication, regardless of their MHC zygosity, shared durable T cell responses against similar regions of Nef. While the limited genetic variability in these animals prevents us from making generalizations about the importance of Nef-specific T cell responses in controlling HIV, these results suggest that the T cell-mediated control of virus replication that we observed is more likely the consequence of targeting specificity rather than T cell breadth. PMID:22573864

Australia reports on AIDS: nef deletions, live vaccines, Chinese travelers.

PubMed

Mascolini, M

1996-03-01

Australian research shows that individuals who share HIV nef deletions and adjacent sequences in the long terminal repeat (LTR) segment of the viral genome may indicate a weakening of the virus. A cluster of long-term survivors who share this enfeebled virus has contributed to the attenuated HIV vaccine debate. The debate was discussed at the Seventh Annual Australian Conference for HIV Medicine. The story began when a researcher discovered a relationship between a gay male blood donor and five recipients, all of whom remain healthy today. This discovery has intensified discussions on the need for developing attenuated HIV vaccines. Vaccines have four potential dangers: they may mutate into an infectious strain, they may seem safe for several years but cause recipients to develop the disease later, they may cause cancer, or they may be passed in vitro from an infected pregnant woman to her fetus. Malpractice threats will probably dictate that they initially be held in developing countries, where the governments decree that the trial is worth the risk of potential AIDS infection. Other topics covered at the conference included a presentation linking Mycobacterium avium complex (MAC) with distal neuropathy, and another showed a relationship between HIV viral load and a heightened risk of dementia.

The Potyviral P3 Protein Targets Eukaryotic Elongation Factor 1A to Promote the Unfolded Protein Response and Viral Pathogenesis1[OPEN

PubMed Central

Shine, M.B.; Cui, Xiaoyan; Chen, Xin; Ma, Na; Kachroo, Pradeep; Zhi, Haijan; Kachroo, Aardra

2016-01-01

The biochemical function of the potyviral P3 protein is not known, although it is known to regulate virus replication, movement, and pathogenesis. We show that P3, the putative virulence determinant of soybean mosaic virus (SMV), targets a component of the translation elongation complex in soybean. Eukaryotic elongation factor 1A (eEF1A), a well-known host factor in viral pathogenesis, is essential for SMV virulence and the associated unfolded protein response (UPR). Silencing GmEF1A inhibits accumulation of SMV and another ER-associated virus in soybean. Conversely, endoplasmic reticulum (ER) stress-inducing chemicals promote SMV accumulation in wild-type, but not GmEF1A-knockdown, plants. Knockdown of genes encoding the eEF1B isoform, which is important for eEF1A function in translation elongation, has similar effects on UPR and SMV resistance, suggesting a link to translation elongation. P3 and GmEF1A promote each other’s nuclear localization, similar to the nuclear-cytoplasmic transport of eEF1A by the Human immunodeficiency virus 1 Nef protein. Our results suggest that P3 targets host elongation factors resulting in UPR, which in turn facilitates SMV replication and place eEF1A upstream of BiP in the ER stress response during pathogen infection. PMID:27356973

Identification of a candidate therapeutic autophagy–inducing peptide

PubMed Central

Shoji-Kawata, Sanae; Sumpter, Rhea; Leveno, Matthew; Campbell, Grant R.; Zou, Zhongju; Kinch, Lisa; Wilkins, Angela D.; Sun, Qihua; Pallauf, Kathrin; MacDuff, Donna; Huerta, Carlos; Virgin, Herbert W.; Helms, J. Bernd; Eerland, Ruud; Tooze, Sharon A.; Xavier, Ramnik; Lenschow, Deborah J.; Yamamoto, Ai; King, David; Lichtarge, Olivier; Grishin, Nick V.; Spector, Stephen A.; Kaloyanova, Dora V.; Levine, Beth

2013-01-01

The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat–beclin 1—derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef—is a potent inducer of autophagy, and interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat–beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases. PMID:23364696

[Measurements of vancomycin concentrations in the blood - a method of personalization the antibiotic therapy in patients with chronic kidney disease].

PubMed

Pondel, Joanna; Krajewski, Piotr; Królikowska, Natalia; Tobiasz, Aleksandra; Augustyniak-Bartosik, Hanna; Hurkacz, Magdalena

2017-04-21

Therapeutic Drug Monitoring is a recognized method of personalizing treatment, having particular application in patients with chronic kidney disease who have frequent infections, requiring administration of vancomycin. International guidelines indicate the need to adjust the dose of the drug to the state of renal function. The recommended therapeutic ranges of minimum and maximum levels should be achieved in order to increase the effectiveness and safety of treatment. The aim of this study was to evaluate the usefulness of measuring the concentration of vancomycin in patients with chronic kidney disease due to bacterial infection. The study included 96 adult patients with chronic kidney disease of varying severity treated with vancomycin Patients were divided into 3 groups: treated by haemodialysis (hd), after renal transplantations (ktx), do not require renal replacement therapy (nef). In subjects were examined the minimum and maximum concentrations of vancomycin in steady-state and were compared with recommended therapeutic ranges. Statistically significant decrease of inflammatory markers was observed only in patients treated with dialysis. In the other groups not significant changes in values of inflammatory parameters were confirmed. Trough concentrations of vancomycin marked in patients were consistent with the recommendation of EUCAST, but exceeded the value recommended by the manufacturers of the drug. Considering absolute values of the minimum concentrations, only about 50% of patients achieved the therapeutic range (58% for recommendation EUCAST and 36% for the manufacturer's instructions). Peak concentration values indicated in dialyzed patients were below the prescribed range of 20-50 mg/l and averaged 17.7 mg / l. In the other subgroups they were correct. The rating of the absolute values of the peak concentrations of vancomycin also showed that only 46% (64% in the ktx, 30% - hd and 53% - nef) was within the recommended range, while 50% were classified as concentrations of sub-therapeutic (36% in the ktx, 42% of the nef group and 65% in hd). Vancomycin concentrations measured in patients with chronic kidney disease, both minimum and maximum, were not fully comply with the recommended therapeutic ranges, despite the use of doses determined based on a calculation of glomerular filtration rate. This points to the need for particularly careful monitoring of therapy and analysis of antibiotic concentrations to improve the effectiveness and reduce the incidence of undesirable consequences of treatment.

Python scripting in the nengo simulator.

PubMed

Stewart, Terrence C; Tripp, Bryan; Eliasmith, Chris

2009-01-01

Nengo (http://nengo.ca) is an open-source neural simulator that has been greatly enhanced by the recent addition of a Python script interface. Nengo provides a wide range of features that are useful for physiological simulations, including unique features that facilitate development of population-coding models using the neural engineering framework (NEF). This framework uses information theory, signal processing, and control theory to formalize the development of large-scale neural circuit models. Notably, it can also be used to determine the synaptic weights that underlie observed network dynamics and transformations of represented variables. Nengo provides rich NEF support, and includes customizable models of spike generation, muscle dynamics, synaptic plasticity, and synaptic integration, as well as an intuitive graphical user interface. All aspects of Nengo models are accessible via the Python interface, allowing for programmatic creation of models, inspection and modification of neural parameters, and automation of model evaluation. Since Nengo combines Python and Java, it can also be integrated with any existing Java or 100% Python code libraries. Current work includes connecting neural models in Nengo with existing symbolic cognitive models, creating hybrid systems that combine detailed neural models of specific brain regions with higher-level models of remaining brain areas. Such hybrid models can provide (1) more realistic boundary conditions for the neural components, and (2) more realistic sub-components for the larger cognitive models.

Effects of short-range order on electronic properties of Zr-Ni glasses as seen from low-temperature specific heat

NASA Astrophysics Data System (ADS)

Kroeger, D. M.; Koch, C. C.; Scarbrough, J. O.; McKamey, C. G.

1984-02-01

Measurements of the low-temperature specific heat Cp of liquid-quenched Zr-Ni glasses for a large number of compositions in the range from 55 to 74 at.% Zr revealed an unusual composition dependence of the density of states at the Fermi level, N(EF). Furthermore, for some compositions the variation of Cp near the superconducting transition temperature Tc indicated the presence of two superconducting phases, i.e., two superconducting transitions were detected. Comparison of the individual Tc's in phase-separated samples to the composition dependence of Tc for all of the samples suggests that amorphous phases with compositions near 60 and 66.7 at.% Zr occur. We discuss these results in terms of an "association model" for liquid alloys (due to Sommer), in which associations of unlike atoms with definite stoichiometries are assumed to exist in equilibrium with unassociated atoms. We conclude that in the composition range studied, associate clusters with the compositions Zr3Ni2 and Zr2Ni occur. In only a few cases are the clusters sufficiently large, compared with the superconducting coherence length, for separate superconducting transitions to be observed. The variation of N(EF) with composition is discussed, as well as the effects of this chemical short-range ordering on the crystallization behavior and glass-forming tendency.

Python Scripting in the Nengo Simulator

PubMed Central

Stewart, Terrence C.; Tripp, Bryan; Eliasmith, Chris

2008-01-01

Nengo (http://nengo.ca) is an open-source neural simulator that has been greatly enhanced by the recent addition of a Python script interface. Nengo provides a wide range of features that are useful for physiological simulations, including unique features that facilitate development of population-coding models using the neural engineering framework (NEF). This framework uses information theory, signal processing, and control theory to formalize the development of large-scale neural circuit models. Notably, it can also be used to determine the synaptic weights that underlie observed network dynamics and transformations of represented variables. Nengo provides rich NEF support, and includes customizable models of spike generation, muscle dynamics, synaptic plasticity, and synaptic integration, as well as an intuitive graphical user interface. All aspects of Nengo models are accessible via the Python interface, allowing for programmatic creation of models, inspection and modification of neural parameters, and automation of model evaluation. Since Nengo combines Python and Java, it can also be integrated with any existing Java or 100% Python code libraries. Current work includes connecting neural models in Nengo with existing symbolic cognitive models, creating hybrid systems that combine detailed neural models of specific brain regions with higher-level models of remaining brain areas. Such hybrid models can provide (1) more realistic boundary conditions for the neural components, and (2) more realistic sub-components for the larger cognitive models. PMID:19352442

Identification of dominant optimal HLA-B60- and HLA-B61-restricted cytotoxic T-lymphocyte (CTL) epitopes: rapid characterization of CTL responses by enzyme-linked immunospot assay.

PubMed

Altfeld, M A; Trocha, A; Eldridge, R L; Rosenberg, E S; Phillips, M N; Addo, M M; Sekaly, R P; Kalams, S A; Burchett, S A; McIntosh, K; Walker, B D; Goulder, P J

2000-09-01

Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL) responses play a major role in the antiviral immune response, but the relative contribution of CTL responses restricted by different HLA class I molecules is less well defined. HLA-B60 or the related allele B61 is expressed in 10 to 20% of Caucasoid populations and is even more highly prevalent in Asian populations, but yet no CTL epitopes restricted by these alleles have been defined. Here we report the definition of five novel HLA-B60-restricted HIV-1-specific CTL epitopes, using peripheral blood mononuclear cells in enzyme-linked immunospot (Elispot) assays and using CTL clones and lines in cytolytic assays. The dominant HLA-B60-restricted epitope, Nef peptide KEKGGLEGL, was targeted by all eight subjects with B60 and also by both subjects with B61 studied. This study additionally establishes the utility of the Elispot assay as a more rapid and efficient method of defining novel CTL epitopes. This approach will help to define new CTL epitopes that may play an important role in the immune control of HIV-1.

2-Aryl-2-nitroacetates as Central Precursors to Aryl Nitromethanes, α-Ketoesters, and α-Amino Acids

PubMed Central

Metz, Alison E.

2013-01-01

Nitroarylacetates are useful small molecular building blocks that act as precursors to α-ketoesters and aryl nitromethanes as well as α-amino acids. Methods were developed that produce each of these compound types in good yields. Two different conditions for decarboxylation are discussed for substrates with neutral and electron-poor aryl groups versus electron-rich aryl groups. For formation of the α-ketoesters, new mild conditions for the Nef disproportionation were identified. PMID:23245626

Eddies and Thermohaline Intrusions of the Shelf/Slope Front off the Northeast Spanish Coast

DTIC Science & Technology

1990-02-15

sain- because of limited hydrographic data coverage in that study. ity. >38.0) due to river runoff . The most important freshwa- they were not able to...ccast. nutrient supply from coastal runoff may also contribute to This high-salinity tongue in fact was located right under the the plankton bloom. near...and J. Tintor . Scmnter frontal contribiution to the fertili . tation of oceanic waters off the NEF coast of Spain. Or canoI. Ac to tn press. 1990

The adaptor protein SLP-76 regulates HIV-1 release and cell to cell transmission in T-cells

PubMed Central

Nagaraja, Tirumuru; Anand, Appakkudal R.; Zhao, Helong; Ganju, Ramesh K.

2014-01-01

HIV-1 infection in T-cells is regulated by T-cell receptor (TCR) activation. However, the cellular proteins of the TCR pathway that regulate HIV-1 infection are poorly characterized. Here, we elucidated the role of SLP-76, a key adaptor protein of the TCR signaling complex, in HIV-1 infection. We observed a significant reduction of HIV-1 virus production in SLP-76-deficient Jurkat T-cells compared to wild-type and SLP-76-reconstituted Jurkat T-cells. We further confirmed the role of SLP-76 in HIV-1 infection by siRNA-mediated knockdown in MT4 cells and PBMCs. Structural-functional analysis revealed that the amino-terminal domain of SLP-76 was important for regulating HIV-1 infection. Further mechanistic studies revealed that lack of SLP-76 impaired virus release, but did not affect viral entry, integration and transcription. We also showed that SLP-76 plays a critical role in cell-to-cell transmission of HIV-1. Signaling studies revealed that SLP-76 associated with viral Nef protein and multiple signaling molecules during HIV-1 infection. Furthermore, SLP-76 facilitated the association of Nef and F-actin, suggesting that SLP-76 mediates the formation of a signaling complex that may regulate viral release via cytoskeletal changes. Taken together, our studies demonstrate a novel role for the adaptor molecule, SLP-76 in regulating HIV-1 infection in T-cells with potential to develop innovative strategies against HIV-1. PMID:22323535

Design and validation of a real-time spiking-neural-network decoder for brain-machine interfaces.

PubMed

Dethier, Julie; Nuyujukian, Paul; Ryu, Stephen I; Shenoy, Krishna V; Boahen, Kwabena

2013-06-01

Cortically-controlled motor prostheses aim to restore functions lost to neurological disease and injury. Several proof of concept demonstrations have shown encouraging results, but barriers to clinical translation still remain. In particular, intracortical prostheses must satisfy stringent power dissipation constraints so as not to damage cortex. One possible solution is to use ultra-low power neuromorphic chips to decode neural signals for these intracortical implants. The first step is to explore in simulation the feasibility of translating decoding algorithms for brain-machine interface (BMI) applications into spiking neural networks (SNNs). Here we demonstrate the validity of the approach by implementing an existing Kalman-filter-based decoder in a simulated SNN using the Neural Engineering Framework (NEF), a general method for mapping control algorithms onto SNNs. To measure this system's robustness and generalization, we tested it online in closed-loop BMI experiments with two rhesus monkeys. Across both monkeys, a Kalman filter implemented using a 2000-neuron SNN has comparable performance to that of a Kalman filter implemented using standard floating point techniques. These results demonstrate the tractability of SNN implementations of statistical signal processing algorithms on different monkeys and for several tasks, suggesting that a SNN decoder, implemented on a neuromorphic chip, may be a feasible computational platform for low-power fully-implanted prostheses. The validation of this closed-loop decoder system and the demonstration of its robustness and generalization hold promise for SNN implementations on an ultra-low power neuromorphic chip using the NEF.

Intermediate coupled superconductivity in yttrium intermetallics

NASA Astrophysics Data System (ADS)

Sharma, Ramesh; Ahmed, Gulzar; Sharma, Yamini

2017-09-01

Non-magnetic YIn3, LaIn3 and LuIn3 with a superconducting transition temperature Tc of 0.78, 0.71 and 0.24 K were investigated for superconductivity. Similarly, rare-earth compound LaSn3 has been reported to exhibit superconductivity around 6.25 K, whereas the non-magnetic YSn3 is a superconductor with Tc of 7 K. The substitution of 13th group In-atoms by 14th group Sn-atoms is seen to enhance Tc by nearly one order, although the lattice parameters increase by ∼1.0% in YSn3 compared to YIn3 compound. It is observed from the ground state properties that the slight difference in the energy band structures of YIn3, YIn2Sn and YSn3 gives rise to various complex Fermi surfaces which are multiply connected and exhibit vast differences. The Fermi level lies on a sharp peak in YSn3 which has a higher density of states N(EF), whereas Fermi level lies on the shoulder of a sharp peak in YIn3. The electron localization function (ELF) and difference charge density maps clearly illustrate the difference in the nature of bonding; the Ysbnd Sn bonds are clearly more ionic (due to larger bond length) than Ysbnd In bonds. These results are consistent with the Bader charges which show loss of charges from Y-atoms and a gain of charges by In/Sn atoms. The dynamical properties also clearly illustrate the difference in the nature of bonds in YX3 intermetallics. A softening of the lowermost acoustic modes is observed in YIn3, whereas all the modes in YSn3 are observed to have positive frequencies which imply its greater stability. Since λel-ph < 1, both YIn3 and YSn3 compounds exhibit type I superconductivity according to BCS theory. However, the smaller N(EF) obtained from the density of states (DOS); the electron-phonon coupling constant λel-ph obtained from the temperature dependent specific heat as well as the instability in phonon modes due to stronger Ysbnd In and Insbnd In bonds in YIn3 may be the cause of lower Tc and filamentary nature of superconductivity. Insertion of Sn-atom in the YIn3 lattice further consolidates the superconducting nature due to increase in N(EF) and γ (electronic component of specific heat), along with lowering of the frequency of imaginary modes from 5.6 THz to 1.5-0.6 THz. Thus Tc is directly related to the valence electron concentration and ternary YIn2Sn may exhibit intermediate superconducting transition temperature.

[Modulation of Metacognition with Decoded Neurofeedback].

PubMed

Koizumi, Ai; Cortese, Aurelio; Amano, Kaoru; Kawato, Mitsuo; Lau, Hakwan

2017-12-01

Humans often assess their confidence in their own perception, e.g., feeling "confident" or "certain" of having seen a friend, or feeling "uncertain" about whether the phone rang. The neural mechanism underlying the metacognitive function that reflects subjective perception still remains under debate. We have previously used decoded neurofeedback (DecNef) to demonstrate that manipulating the multivoxel activation patterns in the frontoparietal network modulates perceptual confidence without affecting perceptual performance. The results provided clear evidence for a dissociation between perceptual confidence and performance and suggested a distinct role of the frontoparietal network in metacognition.

Identification of Dominant Optimal HLA-B60- and HLA-B61-Restricted Cytotoxic T-Lymphocyte (CTL) Epitopes: Rapid Characterization of CTL Responses by Enzyme-Linked Immunospot Assay

PubMed Central

Altfeld, Marcus A.; Trocha, Alicja; Eldridge, Robert L.; Rosenberg, Eric S.; Phillips, Mary N.; Addo, Marylyn M.; Sekaly, Rafick P.; Kalams, Spyros A.; Burchett, Sandra A.; McIntosh, Kenneth; Walker, Bruce D.; Goulder, Philip J. R.

2000-01-01

Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL) responses play a major role in the antiviral immune response, but the relative contribution of CTL responses restricted by different HLA class I molecules is less well defined. HLA-B60 or the related allele B61 is expressed in 10 to 20% of Caucasoid populations and is even more highly prevalent in Asian populations, but yet no CTL epitopes restricted by these alleles have been defined. Here we report the definition of five novel HLA-B60-restricted HIV-1-specific CTL epitopes, using peripheral blood mononuclear cells in enzyme-linked immunospot (Elispot) assays and using CTL clones and lines in cytolytic assays. The dominant HLA-B60-restricted epitope, Nef peptide KEKGGLEGL, was targeted by all eight subjects with B60 and also by both subjects with B61 studied. This study additionally establishes the utility of the Elispot assay as a more rapid and efficient method of defining novel CTL epitopes. This approach will help to define new CTL epitopes that may play an important role in the immune control of HIV-1. PMID:10954555

Antibodies to the HIV-1 Tat protein correlated with nonprogression to AIDS: a rationale for the use of Tat toxoid as an HIV-1 vaccine.

PubMed

Zagury, J F; Sill, A; Blattner, W; Lachgar, A; Le Buanec, H; Richardson, M; Rappaport, J; Hendel, H; Bizzini, B; Gringeri, A; Carcagno, M; Criscuolo, M; Burny, A; Gallo, R C; Zagury, D

1998-01-01

To investigate which immune parameters, such as antibodies against HIV-1 specificities, or viral parameters, such as p24 antigenemia, are predictive of disease progression. We performed studies on serum collected from individuals exhibiting two extremes of disease evolution--67 fast progressors (FP) and 182 nonprogressors (NP)--at their enrollment. After a 1- to 2-year clinical follow-up of 104 nonprogressors after their enrollment, we could determine the best serologic predictors for disease progression. We investigated levels of antibodies to tetanus toxoid and to HIV antigens including Env, Gag, Nef, and Tat proteins, as well as p24 antigenemia, viremia, CD4 cell count, and interferon-alpha (IFN-alpha) titers in FPs and NPs, and we correlated these data with clinical and biologic signs of progression. p24 Antigenemia, a marker of viral replication, and anti-Tat antibodies were highly and inversely correlated in both groups (P < .001). Furthermore, anti-p24 antibodies and low serum IFN-alpha levels were correlated to the NP versus the FP cohort. Finally, among NPs, only antibodies to Tat and not to the other HIV specificities (Env, Nef, Gag) were significantly predictive of clinical stability during their follow-up. Antibodies toward HIV-1 Tat, which are inversely correlated to p24 antigenemia, appear as a critical marker for a lack of disease progression. This study strongly suggests that rising anti-Tat antibodies through active immunization may be beneficial in AIDS vaccine development to control viral replication.

Design and validation of a real-time spiking-neural-network decoder for brain-machine interfaces

NASA Astrophysics Data System (ADS)

Dethier, Julie; Nuyujukian, Paul; Ryu, Stephen I.; Shenoy, Krishna V.; Boahen, Kwabena

2013-06-01

Objective. Cortically-controlled motor prostheses aim to restore functions lost to neurological disease and injury. Several proof of concept demonstrations have shown encouraging results, but barriers to clinical translation still remain. In particular, intracortical prostheses must satisfy stringent power dissipation constraints so as not to damage cortex. Approach. One possible solution is to use ultra-low power neuromorphic chips to decode neural signals for these intracortical implants. The first step is to explore in simulation the feasibility of translating decoding algorithms for brain-machine interface (BMI) applications into spiking neural networks (SNNs). Main results. Here we demonstrate the validity of the approach by implementing an existing Kalman-filter-based decoder in a simulated SNN using the Neural Engineering Framework (NEF), a general method for mapping control algorithms onto SNNs. To measure this system’s robustness and generalization, we tested it online in closed-loop BMI experiments with two rhesus monkeys. Across both monkeys, a Kalman filter implemented using a 2000-neuron SNN has comparable performance to that of a Kalman filter implemented using standard floating point techniques. Significance. These results demonstrate the tractability of SNN implementations of statistical signal processing algorithms on different monkeys and for several tasks, suggesting that a SNN decoder, implemented on a neuromorphic chip, may be a feasible computational platform for low-power fully-implanted prostheses. The validation of this closed-loop decoder system and the demonstration of its robustness and generalization hold promise for SNN implementations on an ultra-low power neuromorphic chip using the NEF.

Vaccination with Gag, Vif, and Nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239.

PubMed

Martins, Mauricio A; Wilson, Nancy A; Piaskowski, Shari M; Weisgrau, Kim L; Furlott, Jessica R; Bonaldo, Myrna C; Veloso de Santana, Marlon G; Rudersdorf, Richard A; Rakasz, Eva G; Keating, Karen D; Chiuchiolo, Maria J; Piatak, Michael; Allison, David B; Parks, Christopher L; Galler, Ricardo; Lifson, Jeffrey D; Watkins, David I

2014-07-01

Broadly targeted cellular immune responses are thought to be important for controlling replication of human and simian immunodeficiency viruses (HIV and SIV). However, eliciting such responses by vaccination is complicated by immunodominance, the preferential targeting of only a few of the many possible epitopes of a given antigen. This phenomenon may be due to the coexpression of dominant and subdominant epitopes by the same antigen-presenting cell and may be overcome by distributing these sequences among several different vaccine constructs. Accordingly, we tested whether vaccinating rhesus macaques with "minigenes" encoding fragments of Gag, Vif, and Nef resulted in broadened cellular responses capable of controlling SIV replication. We delivered these minigenes through combinations of recombinant Mycobacterium bovis BCG (rBCG), electroporated recombinant DNA (rDNA) along with an interleukin-12 (IL-12)-expressing plasmid (EP rDNA plus pIL-12), yellow fever vaccine virus 17D (rYF17D), and recombinant adenovirus serotype 5 (rAd5). Although priming with EP rDNA plus pIL-12 increased the breadth of vaccine-induced T-cell responses, this effect was likely due to the improved antigen delivery afforded by electroporation rather than modulation of immunodominance. Indeed, Mamu-A*01(+) vaccinees mounted CD8(+) T cells directed against only one subdominant epitope, regardless of the vaccination regimen. After challenge with SIVmac239, vaccine efficacy was limited to a modest reduction in set point in some of the groups and did not correlate with standard T-cell measurements. These findings suggest that broad T-cell responses elicited by conventional vectors may not be sufficient to substantially contain AIDS virus replication. Immunodominance poses a major obstacle to the generation of broadly targeted, HIV-specific cellular responses by vaccination. Here we attempted to circumvent this phenomenon and thereby broaden the repertoire of SIV-specific cellular responses by vaccinating rhesus macaques with minigenes encoding fragments of Gag, Vif, and Nef. In contrast to previous mouse studies, this strategy appeared to minimally affect monkey CD8(+) T-cell immundominance hierarchies, as seen by the detection of only one subdominant epitope in Mamu-A*01(+) vaccinees. This finding underscores the difficulty of inducing subdominant CD8(+) T cells by vaccination and demonstrates that strategies other than gene fragmentation may be required to significantly alter immunodominance in primates. Although some of the regimens tested here were extremely immunogenic, vaccine efficacy was limited to a modest reduction in set point viremia after challenge with SIVmac239. No correlates of protection were identified. These results reinforce the notion that vaccine immunogenicity does not predict control of AIDS virus replication. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

The Evolutionary Histories of Antiretroviral Proteins SERINC3 and SERINC5 Do Not Support an Evolutionary Arms Race in Primates.

PubMed

Murrell, Ben; Vollbrecht, Thomas; Guatelli, John; Wertheim, Joel O

2016-09-15

Molecular evolutionary arms races between viruses and their hosts are important drivers of adaptation. These Red Queen dynamics have been frequently observed in primate retroviruses and their antagonists, host restriction factor genes, such as APOBEC3F/G, TRIM5-α, SAMHD1, and BST-2. Host restriction factors have experienced some of the most intense and pervasive adaptive evolution documented in primates. Recently, two novel host factors, SERINC3 and SERINC5, were identified as the targets of HIV-1 Nef, a protein crucial for the optimal infectivity of virus particles. Here, we compared the evolutionary fingerprints of SERINC3 and SERINC5 to those of other primate restriction factors and to a set of other genes with diverse functions. SERINC genes evolved in a manner distinct from the canonical arms race dynamics seen in the other restriction factors. Despite their antiviral activity against HIV-1 and other retroviruses, SERINC3 and SERINC5 have a relatively uneventful evolutionary history in primates. Restriction factors are host proteins that block viral infection and replication. Many viruses, like HIV-1 and related retroviruses, evolved accessory proteins to counteract these restriction factors. The importance of these interactions is evidenced by the intense adaptive selection pressures that dominate the evolutionary histories of both the host and viral genes involved in this so-called arms race. The dynamics of these arms races can point to mechanisms by which these viral infections can be prevented. Two human genes, SERINC3 and SERINC5, were recently identified as targets of an HIV-1 accessory protein important for viral infectivity. Unexpectedly, we found that these SERINC genes, unlike other host restriction factor genes, show no evidence of a recent evolutionary arms race with viral pathogens. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Intracytoplasmic Domain of the Env Transmembrane Protein Is a Locus for Attenuation of Simian Immunodeficiency Virus SIVmac in Rhesus Macaques

PubMed Central

Shacklett, Barbara L.; Weber, Claudia Jo; Shaw, Karen E. S.; Keddie, Elise M.; Gardner, Murray B.; Sonigo, Pierre; Luciw, Paul A.

2000-01-01

The human and simian immunodeficiency virus (HIV-1 and SIVmac) transmembrane proteins contain unusually long intracytoplasmic domains (ICD-TM). These domains are suggested to play a role in envelope fusogenicity, interaction with the viral matrix protein during assembly, viral infectivity, binding of intracellular calmodulin, disruption of membranes, and induction of apoptosis. Here we describe a novel mutant virus, SIVmac-M4, containing multiple mutations in the coding region for the ICD-TM of pathogenic molecular clone SIVmac239. Parental SIVmac239-Nef+ produces high-level persistent viremia and simian AIDS in both juvenile and newborn rhesus macaques. The ICD-TM region of SIVmac-M4 contains three stop codons, a +1 frameshift, and mutation of three highly conserved, charged residues in the conserved C-terminal alpha-helix referred to as lentivirus lytic peptide 1 (LLP-1). Overlapping reading frames for tat, rev, and nef are not affected by these changes. In this study, four juvenile macaques received SIVmac-M4 by intravenous injection. Plasma viremia, as measured by branched-DNA (bDNA) assay, reached a peak at 2 weeks postinoculation but dropped to below detectable levels by 12 weeks. At over 1.5 years postinoculation, all four juvenile macaques remain healthy and asymptomatic. In a subsequent experiment, four neonatal rhesus macaques were given SIVmac-M4 intravenously. These animals exhibited high levels of viremia in the acute phase (2 weeks postinoculation) but are showing a relatively low viral load in the chronic phase of infection, with no clinical signs of disease for 1 year. These findings demonstrated that the intracytoplasmic domain of the transmembrane Env (Env-TM) is a locus for attenuation in rhesus macaques. PMID:10846063

Location and Dynamics of the Immunodominant CD8 T Cell Response to SIVΔnef Immunization and SIVmac251 Vaginal Challenge

PubMed Central

Sasikala-Appukuttan, Arun K.; Kim, Hyeon O.; Kinzel, Nikilyn J.; Hong, Jung Joo; Smith, Anthony J.; Wagstaff, Reece; Reilly, Cavan; Piatak, Michael; Lifson, Jeffrey D.; Reeves, R. Keith; Johnson, R. Paul; Haase, Ashley T.; Skinner, Pamela J.

2013-01-01

Live-attenuated SIV vaccines (LAVs) have been the most effective to date in preventing or partially controlling infection by wild-type SIV in non-human primate models of HIV-1 transmission to women acting by mechanisms of protection that are not well understood. To gain insights into mechanisms of protection by LAVs that could aid development of effective vaccines to prevent HIV-1 transmission to women, we used in situ tetramer staining to determine whether increased densities or changes in the local distribution of SIV-specific CD8 T cells correlated with the maturation of SIVΔnef vaccine-induced protection prior to and after intra-vaginal challenge with wild-type SIVmac251. We evaluated the immunodominant Mamu-A1*001:01/Gag (CM9) and Mamu-A1*001:01/Tat (SL8) epitope response in genital and lymphoid tissues, and found that tetramer+ cells were present at all time points examined. In the cervical vaginal tissues, most tetramer+ cells were distributed diffusely throughout the lamina propria or co-localized with other CD8 T cells within lymphoid aggregates. The distribution and densities of the tetramer+ cells at the portal of entry did not correlate with the maturation of protection or change after challenge. Given these findings, we discuss the possibility that changes in other aspects of the immune system, including the quality of the resident population of virus-specific effector CD8 T cells could contribute to maturation of protection, as well as the potential for vaccine strategies that further increase the size and quality of this effector population to prevent HIV-1 transmission. PMID:24349100

Demographic History of Indigenous Populations in Mesoamerica Based on mtDNA Sequence Data

PubMed Central

González-Martín, Antonio; Gorostiza, Amaya; Regalado-Liu, Lucía; Arroyo-Peña, Sergio; Tirado, Sergio; Nuño-Arana, Ismael; Rubi-Castellanos, Rodrigo; Sandoval, Karla; Coble, Michael D.; Rangel-Villalobos, Héctor

2015-01-01

The genetic characterization of Native American groups provides insights into their history and demographic events. We sequenced the mitochondrial D-loop region (control region) of 520 samples from eight Mexican indigenous groups. In addition to an analysis of the genetic diversity, structure and genetic relationship between 28 Native American populations, we applied Bayesian skyline methodology for a deeper insight into the history of Mesoamerica. AMOVA tests applying cultural, linguistic and geographic criteria were performed. MDS plots showed a central cluster of Oaxaca and Maya populations, whereas those from the North and West were located on the periphery. Demographic reconstruction indicates higher values of the effective number of breeding females (Nef) in Central Mesoamerica during the Preclassic period, whereas this pattern moves toward the Classic period for groups in the North and West. Conversely, Nef minimum values are distributed either in the Lithic period (i.e. founder effects) or in recent periods (i.e. population declines). The Mesomerican regions showed differences in population fluctuation as indicated by the maximum Inter-Generational Rate (IGRmax): i) Center-South from the lithic period until the Preclassic; ii) West from the beginning of the Preclassic period until early Classic; iii) North characterized by a wide range of temporal variation from the Lithic to the Preclassic. Our findings are consistent with the genetic variations observed between central, South and Southeast Mesoamerica and the North-West region that are related to differences in genetic drift, structure, and temporal survival strategies (agriculture versus hunter-gathering, respectively). Interestingly, although the European contact had a major negative demographic impact, we detect a previous decline in Mesoamerica that had begun a few hundred years before. PMID:26292226

Killed whole-HIV vaccine; employing a well established strategy for antiviral vaccines.

PubMed

Kang, C Yong; Gao, Yong

2017-09-12

The development of an efficient prophylactic HIV vaccine has been one of the major challenges in infectious disease research during the last three decades. Here, we present a mini review on strategies employed for the development of HIV vaccines with an emphasis on a well-established vaccine technology, the killed whole-virus vaccine approach. Recently, we reported an evaluation of the safety and the immunogenicity of a genetically modified and killed whole-HIV-1 vaccine designated as SAV001 [1]. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence of the Env signal peptide with that of honeybee melittin to produce an avirulent and replication efficient HIV-1. This genetically modified virus (gmHIV-1 NL4-3 ) was propagated in a human T cell line followed by virus purification and inactivation by aldrithiol-2 and γ-irradiation. We found that SAV001 was well tolerated with no serious adverse events. HIV-1 NL4-3 -specific polymerase chain reaction showed no evidence of vaccine virus replication in participants receiving SAV001 and in human T cells infected in vitro. Furthermore, SAV001 with an adjuvant significantly increased the antibody response to HIV-1 structural proteins. Moreover, antibodies in the plasma from these vaccinations neutralized tier I and tier II of HIV-1 B, A, and D subtypes. These results indicated that the killed whole-HIV vaccine is safe and may trigger appropriate immune responses to prevent HIV infection. Utilization of this killed whole-HIV vaccine strategy may pave the way to develop an effective HIV vaccine.

PEGylated poly(ethylene imine) copolymer-delivered siRNA inhibits HIV replication in vitro.

PubMed

Weber, Nick D; Merkel, Olivia M; Kissel, Thomas; Muñoz-Fernández, María Ángeles

2012-01-10

RNA interference is increasingly being utilized for the specific targeting and down-regulation of disease-causing genes, including targeting viral infections such as HIV. T lymphocytes, the primary target for HIV, are very difficult to treat with gene therapy applications such as RNA interference because of issues with drug delivery. To circumvent these problems, we investigated poly(ethylene imine) (PEI) as a method of improving transfection efficiency of siRNA to T lymphocytes. Additionally, polyethylene glycol (PEG) moieties were engrafted to the PEI polymers with the goals of improving stability and reducing cytotoxicity. Initial studies on PEG-PEI/siRNA polyplex formation, size and their interaction with cell membranes demonstrated their feasibility as drug delivery agents. Assays with lymphocytes revealed low cytotoxicity profiles of the polyplexes at pharmacologically relevant concentrations with PEGylated copolymers obtaining the best results. Successful transfection of a T cell line or primary T cells with siRNA was observed via flow cytometry and confocal microscopy. Finally, the biological effect of copolymer-delivered siRNA was measured. Of particular significance, siRNA targeted to the HIV gene nef and delivered by one of the PEG-PEI copolymers in repetitive treatments every 2-3 days was observed to inhibit HIV replication to the same extent as azidothymidine over the course of 15 days. Copyright © 2011 Elsevier B.V. All rights reserved.

SU-E-T-72: Commissioning of a Standardized SRS Cone Set: Determination of the Bolus Gap Factors in a Passively Scattered Proton Beam

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

Simpson, R; Gordon, I; Ghebremedhin, A

2014-06-01

Purpose: To determine the proton output factors for an SRS cone set using standardized apertures and varied range compensators (bolus blanks); specifically, to determine the best method for modeling the bolus gap factor (BGF) and eliminate the need for patient specific calibrations. Methods: A Standard Imaging A-16 chamber was placed in a Plastic Water phantom to measure the change in dose/MU with different treatment combinations for a proton SRS cone, using standardized apertures and range compensators. Measurements were made with all apertures in the SRS cone set, with four different range compensator thicknesses and five different air gaps between themore » end of the SRS cone and the surface of the phantom. The chamber was located at iso-center and maintained at a constant depth at the center of modulation for all measurements. Each aperture was placed in the cone to measure the change in MU needed to maintain constant dose at the chamber, as the air gap was increased with different thicknesses of bolus. Results: The dose/MU varied significantly with decreasing aperture size, increasing bolus thickness, or increasing air gap. The measured data was fitted with the lowest order polynomials that accurately described the data, to create a model for determining the change in output for any potential combination of devices used to treat a patient. For a given standardized aperture, the BGF could be described by its constituent factors: the bolus thickness factor (BTF) and the nozzle extension factor (NEF). Conclusion: The methods used to model the dose at the calibration point could be used to accurately predict the change in output for SRS proton beams due to the BGF, eliminating the need for patient specific calibrations. This method for modeling SRS treatments could also be applied to model other treatments using passively scattered proton beams.« less

Viral Determinants of Integration Site Preferences of Simian Immunodeficiency Virus-Based Vectors

PubMed Central

Monse, Hella; Laufs, Stephanie; Kuate, Seraphin; Zeller, W. Jens; Fruehauf, Stefan; Überla, Klaus

2006-01-01

Preferential integration into transcriptionally active regions of genomes has been observed for retroviral vectors based on gamma-retroviruses and lentiviruses. However, differences in the integration site preferences were detected, which might be explained by differences in viral components of the preintegration complexes. Viral determinants of integration site preferences have not been defined. Therefore, integration sites of simian immunodeficiency virus (SIV)-based vectors produced in the absence of accessory genes or lacking promoter and enhancer elements were compared. Similar integration patterns for the different SIV vectors indicate that vif, vpr, vpx, nef, env, and promoter or enhancer elements are not required for preferential integration of SIV into transcriptionally active regions of genomes. PMID:16873270

Hsp70 Protein Complexes as Drug Targets

PubMed Central

Assimon, Victoria A.; Gillies, Anne T.; Rauch, Jennifer N.; Gestwicki, Jason E.

2013-01-01

Heat shock protein 70 (Hsp70) plays critical roles in proteostasis and is an emerging target for multiple diseases. However, competitive inhibition of the enzymatic activity of Hsp70 has proven challenging and, in some cases, may not be the most productive way to redirect Hsp70 function. Another approach is to inhibit Hsp70’s interactions with important co-chaperones, such as J proteins, nucleotide exchange factors (NEFs) and tetratricopeptide repeat (TPR) domain-containing proteins. These co-chaperones normally bind Hsp70 and guide its many diverse cellular activities. Complexes between Hsp70 and co-chaperones have been shown to have specific functions, such as pro-folding, pro-degradation and pro-trafficking. Thus, a promising strategy may be to block protein-protein interactions between Hsp70 and its co-chaperones or to target allosteric sites that disrupt these contacts. Such an approach might shift the balance of Hsp70 complexes and re-shape the proteome and it has the potential to restore healthy proteostasis. In this review, we discuss specific challenges and opportunities related to those goals. By pursuing Hsp70 complexes as drug targets, we might not only develop new leads for therapeutic development, but also discover new chemical probes for use in understanding Hsp70 biology. PMID:22920901

Human Immunodeficiency Virus-Specific CD8+ T Cells in Human Breast Milk

PubMed Central

Sabbaj, Steffanie; Edwards, Bradley H.; Ghosh, Mrinal K.; Semrau, Katherine; Cheelo, Sanford; Thea, Donald M.; Kuhn, Louise; Ritter, G. Douglas; Mulligan, Mark J.; Goepfert, Paul A.; Aldrovandi, Grace M.

2002-01-01

Breast-feeding infants of human immunodeficiency virus (HIV)-infected women ingest large amounts of HIV, but most escape infection. While the factors affecting transmission risk are poorly understood, HIV-specific cytotoxic T-lymphocyte (CTL) responses play a critical role in controlling HIV levels in blood. We therefore investigated the ability of breast milk cells (BMC) from HIV-infected women from the United States and Zambia to respond to HIV-1 peptides in a gamma interferon enzyme-linked immunospot assay. All (n = 11) HIV-infected women had responses to pools of Gag peptide (range, 105 to 1,400 spot-forming cells/million; mean = 718), 8 of 11 reacted to Pol, 7 reacted to Nef, and 2 of 5 reacted to Env. Conversely, of four HIV-negative women, none responded to any of the tested HIV peptide pools. Depletion and tetramer staining studies demonstrated that CD8+ T cells mediated these responses, and a chromium-release assay showed that these BMC were capable of lysing target cells in an HIV-specific manner. These data demonstrate the presence of HIV-specific major histocompatibility complex class I-restricted CD8+ CTLs in breast milk. Their presence suggests a role in limiting transmission and provides a rationale for vaccine strategies to enhance these responses. PMID:12097549

Fluidity of HIV-1-Specific T-Cell Responses during Acute and Early Subtype C HIV-1 Infection and Associations with Early Disease Progression ▿

PubMed Central

Mlotshwa, Mandla; Riou, Catherine; Chopera, Denis; de Assis Rosa, Debra; Ntale, Roman; Treunicht, Florette; Woodman, Zenda; Werner, Lise; van Loggerenberg, Francois; Mlisana, Koleka; Abdool Karim, Salim; Williamson, Carolyn; Gray, Clive M.

2010-01-01

Deciphering immune events during early stages of human immunodeficiency virus type 1 (HIV-1) infection is critical for understanding the course of disease. We characterized the hierarchy of HIV-1-specific T-cell gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) assay responses during acute subtype C infection in 53 individuals and associated temporal patterns of responses with disease progression in the first 12 months. There was a diverse pattern of T-cell recognition across the proteome, with the recognition of Nef being immunodominant as early as 3 weeks postinfection. Over the first 6 months, we found that there was a 23% chance of an increased response to Nef for every week postinfection (P = 0.0024), followed by a nonsignificant increase to Pol (4.6%) and Gag (3.2%). Responses to Env and regulatory proteins appeared to remain stable. Three temporal patterns of HIV-specific T-cell responses could be distinguished: persistent, lost, or new. The proportion of persistent T-cell responses was significantly lower (P = 0.0037) in individuals defined as rapid progressors than in those progressing slowly and who controlled viremia. Almost 90% of lost T-cell responses were coincidental with autologous viral epitope escape. Regression analysis between the time to fixed viral escape and lost T-cell responses (r = 0.61; P = 0.019) showed a mean delay of 14 weeks after viral escape. Collectively, T-cell epitope recognition is not a static event, and temporal patterns of IFN-γ-based responses exist. This is due partly to viral sequence variation but also to the recognition of invariant viral epitopes that leads to waves of persistent T-cell immunity, which appears to associate with slower disease progression in the first year of infection. PMID:20826686

Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens

PubMed Central

Asbach, Benedikt; Kliche, Alexander; Köstler, Josef; Perdiguero, Beatriz; Esteban, Mariano; Jacobs, Bertram L.; Montefiori, David C.; LaBranche, Celia C.; Yates, Nicole L.; Tomaras, Georgia D.; Ferrari, Guido; Foulds, Kathryn E.; Roederer, Mario; Landucci, Gary; Forthal, Donald N.; Seaman, Michael S.; Hawkins, Natalie; Self, Steven G.; Sato, Alicia; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, James; Barnett, Susan W.; Burke, Brian; Cristillo, Anthony D.; Weiss, Deborah E.; Francis, Jesse; Galmin, Lindsey; Ding, Song; Heeney, Jonathan L.; Pantaleo, Giuseppe

2016-01-01

ABSTRACT In a follow-up to the modest efficacy observed in the RV144 trial, researchers in the HIV vaccine field seek to substantiate and extend the results by evaluating other poxvirus vectors and combinations with DNA and protein vaccines. Earlier clinical trials (EuroVacc trials 01 to 03) evaluated the immunogenicity of HIV-1 clade C GagPolNef and gp120 antigens delivered via the poxviral vector NYVAC. These showed that a vaccination regimen including DNA-C priming prior to a NYVAC-C boost considerably enhanced vaccine-elicited immune responses compared to those with NYVAC-C alone. Moreover, responses were improved by using three as opposed to two DNA-C primes. In the present study, we assessed in nonhuman primates whether such vaccination regimens can be streamlined further by using fewer and accelerated immunizations and employing a novel generation of improved DNA-C and NYVAC-C vaccine candidates designed for higher expression levels and more balanced immune responses. Three different DNA-C prime/NYVAC-C+ protein boost vaccination regimens were tested in rhesus macaques. All regimens elicited vigorous and well-balanced CD8+ and CD4+ T cell responses that were broad and polyfunctional. Very high IgG binding titers, substantial antibody-dependent cellular cytotoxicity (ADCC), and modest antibody-dependent cell-mediated virus inhibition (ADCVI), but very low neutralization activity, were measured after the final immunizations. Overall, immune responses elicited in all three groups were very similar and of greater magnitude, breadth, and quality than those of earlier EuroVacc vaccines. In conclusion, these findings indicate that vaccination schemes can be simplified by using improved antigens and regimens. This may offer a more practical and affordable means to elicit potentially protective immune responses upon vaccination, especially in resource-constrained settings. IMPORTANCE Within the EuroVacc clinical trials, we previously assessed the immunogenicity of HIV clade C antigens delivered in a DNA prime/NYVAC boost regimen. The trials showed that the DNA prime crucially improved the responses, and three DNA primes with a NYVAC boost appeared to be optimal. Nevertheless, T cell responses were primarily directed toward Env, and humoral responses were modest. The aim of this study was to assess improved antigens for the capacity to elicit more potent and balanced responses in rhesus macaques, even with various simpler immunization regimens. Our results showed that the novel antigens in fact elicited larger numbers of T cells with a polyfunctional profile and a good Env-GagPolNef balance, as well as high-titer and Fc-functional antibody responses. Finally, comparison of the different schedules indicates that a simpler regimen of only two DNA primes and one NYVAC boost in combination with protein may be very efficient, thus showing that the novel antigens allow for easier immunization protocols. PMID:26865719

An Ultra-Low Voltage Analog Front End for Strain Gauge Sensory System Application in 0.18µm CMOS

NASA Astrophysics Data System (ADS)

Edward, Alexander; Chan, Pak Kwong

This paper presents analysis and design of a new ultra-low voltage analog front end (AFE) dedicated to strain sensor applications. The AFE, designed in 0.18µm CMOS process, features a chopper-stabilized instrumentation amplifier (IA), a balanced active MOSFET-C 2nd order low pass filter (LPF), a clock generator and a voltage booster which operate at supply voltage (Vdd) of 0.6V. The designed IA achieves 30dB of closed-loop gain, 101dB of common-mode rejection ratio (CMRR) at 50Hz, 80dB of power-supply rejection ratio (PSRR) at 50Hz, thermal noise floor of 53.4 nV/√Hz, current consumption of 14µA, and noise efficiency factor (NEF) of 9.7. The high CMRR and rail-to-rail output swing capability is attributed to a new low voltage realization of the active-bootstrapped technique using a pseudo-differential gain-boosting operational transconductance amplifier (OTA) and proposed current-driven bulk (CDB) biasing technique. An output capacitor-less low-dropout regulator (LDO), with a new fast start-up LPF technique, is used to regulate this 0.6V supply from a 0.8-1.0V energy harvesting power source. It achieves power supply rejection (PSR) of 42dB at frequency of 1MHz. A cascode compensated pseudo differential amplifier is used as the filter's building block for low power design. The filter's single-ended-to-balanced converter is implemented using a new low voltage amplifier with two-stage common-mode cancellation. The overall AFE was simulated to have 65.6dB of signal-to-noise ratio (SNR), total harmonic distortion (THD) of less than 0.9% for a 100Hz sinusoidal maximum input signal, bandwidth of 2kHz, and power consumption of 51.2µW. Spectre RF simulations were performed to validate the design using BSIM3V3 transistor models provided by GLOBALFOUNDRIES 0.18µm CMOS process.

Genetically modified anthrax lethal toxin safely delivers whole HIV protein antigens into the cytosol to induce T cell immunity

NASA Astrophysics Data System (ADS)

Lu, Yichen; Friedman, Rachel; Kushner, Nicholas; Doling, Amy; Thomas, Lawrence; Touzjian, Neal; Starnbach, Michael; Lieberman, Judy

2000-07-01

Bacillus anthrax lethal toxin can be engineered to deliver foreign proteins to the cytosol for antigen presentation to CD8 T cells. Vaccination with modified toxins carrying 8-9 amino acid peptide epitopes induces protective immunity in mice. To evaluate whether large protein antigens can be used with this system, recombinant constructs encoding several HIV antigens up to 500 amino acids were produced. These candidate HIV vaccines are safe in animals and induce CD8 T cells in mice. Constructs encoding gag p24 and nef stimulate gag-specific CD4 proliferation and a secondary cytotoxic T lymphocyte response in HIV-infected donor peripheral blood mononuclear cells in vitro. These results lay the foundation for future clinical vaccine studies.

Immunologic and Virologic Mechanisms for Partial Protection from Intravenous Challenge by an Integration-Defective SIV Vaccine †

PubMed Central

Wang, Chu; Jiang, Chunlai; Gao, Nan; Zhang, Kaikai; Liu, Donglai; Wang, Wei; Cong, Zhe; Qin, Chuan; Ganusov, Vitaly V.; Ferrari, Guido; LaBranche, Celia; Montefiori, David C.; Kong, Wei; Yu, Xianghui; Gao, Feng

2017-01-01

The suppression of viral loads and identification of selection signatures in non-human primates after challenge are indicators for effective human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) vaccines. To mimic the protective immunity elicited by attenuated SIV vaccines, we developed an integration-defective SIV (idSIV) vaccine by inactivating integrase, mutating sequence motifs critical for integration, and inserting the cytomegalovirus (CMV) promoter for more efficient expression in the SIVmac239 genome. Chinese rhesus macaques were immunized with idSIV DNA and idSIV particles, and the cellular and humoral immune responses were measured. After the intravenous SIVmac239 challenge, viral loads were monitored and selection signatures in viral genomes from vaccinated monkeys were identified by single genome sequencing. T cell responses, heterologous neutralization against tier-1 viruses, and antibody-dependent cellular cytotoxicity (ADCC) were detected in idSIV-vaccinated macaques post immunization. After challenge, the median peak viral load in the vaccine group was significantly lower than that in the control group. However, this initial viral control did not last as viral set-points were similar between vaccinated and control animals. Selection signatures were identified in Nef, Gag, and Env proteins in vaccinated and control macaques, but these signatures were different, suggesting selection pressure on viruses from vaccine-induced immunity in the vaccinated animals. Our results showed that the idSIV vaccine exerted some pressure on the virus population early during the infection but future modifications are needed in order to induce more potent immune responses. PMID:28574482

Mobilization of HIV Spread by Diaphanous 2 Dependent Filopodia in Infected Dendritic Cells

PubMed Central

Aggarwal, Anupriya; Iemma, Tina L.; Shih, Ivy; Newsome, Timothy P.; McAllery, Samantha; Cunningham, Anthony L.; Turville, Stuart G.

2012-01-01

Paramount to the success of persistent viral infection is the ability of viruses to navigate hostile environments en route to future targets. In response to such obstacles, many viruses have developed the ability of establishing actin rich-membrane bridges to aid in future infections. Herein through dynamic imaging of HIV infected dendritic cells, we have observed how viral high-jacking of the actin/membrane network facilitates one of the most efficient forms of HIV spread. Within infected DC, viral egress is coupled to viral filopodia formation, with more than 90% of filopodia bearing immature HIV on their tips at extensions of 10 to 20 µm. Live imaging showed HIV filopodia routinely pivoting at their base, and projecting HIV virions at µm.sec−1 along repetitive arc trajectories. HIV filopodial dynamics lead to up to 800 DC to CD4 T cell contacts per hour, with selection of T cells culminating in multiple filopodia tethering and converging to envelope the CD4 T-cell membrane with budding HIV particles. Long viral filopodial formation was dependent on the formin diaphanous 2 (Diaph2), and not a dominant Arp2/3 filopodial pathway often associated with pathogenic actin polymerization. Manipulation of HIV Nef reduced HIV transfer 25-fold by reducing viral filopodia frequency, supporting the potency of DC HIV transfer was dependent on viral filopodia abundance. Thus our observations show HIV corrupts DC to CD4 T cell interactions by physically embedding at the leading edge contacts of long DC filopodial networks. PMID:22685410

PPARγ and NF-κB regulate the gene promoter activity of their shared repressor, TNIP1

PubMed Central

Gurevich, Igor; Zhang, Carmen; Encarnacao, Priscilla C.; Struzynski, Charles P.; Livings, Sarah E.; Aneskievich, Brian J.

2011-01-01

Human TNFAIP3 interacting protein 1 (TNIP1) has diverse functions including support of HIV replication through its interaction with viral Nef and matrix proteins, reduction of TNFα-induced signaling through its interaction with NF-κB pathway proteins, and corepression of agonist-bound retinoic acid receptors and peroxisome proliferator-activated receptors (PPAR). The wide tissue distribution of TNIP1 provides the opportunity to influence numerous cellular responses in these roles and defining control of TNIP1 expression would be central to improved understanding of its impact on cell function. We cloned 6kb of the human TNIP1 promoter and performed predictive and functional analyses to identify regulatory elements. The promoter region proximal to the transcription start site is GC-rich without a recognizable TATA box. In contrast to this proximal ~500bp region, 6kb of the promoter increased reporter construct constitutive activity over five-fold. Throughout the 6kb length, in silico analysis identified several potential binding sites for both constitutive and inducible transcription factors; among the latter were candidate NF-κB binding sequences and peroxisome proliferator response elements (PPREs). We tested NF-κB and PPAR regulation of the endogenous TNIP1 gene and cloned promoter by expression studies, electrophoretic mobility shift assays, and chromatin immunoprecipitations. We validated NF-κB sites in the TNIP1 promoter proximal and distal regions as well as one PPRE in the distal region. The ultimate control of the TNIP1 promoter is likely to be a combination of constitutive transcription factors and those subject to activation such as NF-κB and PPAR. PMID:22001530

Analysis of simian immunodeficiency virus sequence variation in tissues of rhesus macaques with simian AIDS.

PubMed Central

Kodama, T; Mori, K; Kawahara, T; Ringler, D J; Desrosiers, R C

1993-01-01

One rhesus macaque displayed severe encephalomyelitis and another displayed severe enterocolitis following infection with molecularly cloned simian immunodeficiency virus (SIV) strain SIVmac239. Little or no free anti-SIV antibody developed in these two macaques, and they died relatively quickly (4 to 6 months) after infection. Manifestation of the tissue-specific disease in these macaques was associated with the emergence of variants with high replicative capacity for macrophages and primary infection of tissue macrophages. The nature of sequence variation in the central region (vif, vpr, and vpx), the env gene, and the nef long terminal repeat (LTR) region in brain, colon, and other tissues was examined to see whether specific genetic changes were associated with SIV replication in brain or gut. Sequence analysis revealed strong conservation of the intergenic central region, nef, and the LTR. However, analysis of env sequences in these two macaques and one other revealed significant, interesting patterns of sequence variation. (i) Changes in env that were found previously to contribute to the replicative ability of SIVmac for macrophages in culture were present in the tissues of these animals. (ii) The greatest variability was located in the regions between V1 and V2 and from "V3" through C3 in gp120, which are different in location from the variable regions observed previously in animals with strong antibody responses and long-term persistent infection. (iii) The predominant sequence change of D-->N at position 385 in C3 is most surprising, since this change in both SIV and human immunodeficiency virus type 1 has been associated with dramatically diminished affinity for CD4 and replication in vitro. (iv) The nature of sequence changes at some positions (146, 178, 345, 385, and "V3") suggests that viral replication in brain and gut may be facilitated by specific sequence changes in env in addition to those that impart a general ability to replicate well in macrophages. These results demonstrate that complex selective pressures, including immune responses and varying cell and tissue specificity, can influence the nature of sequence changes in env. Images PMID:8411355

Genotypic and Functional Impact of HIV-1 Adaptation to Its Host Population during the North American Epidemic

PubMed Central

Carlson, Jonathan M.; Chan, Benjamin; Chopera, Denis R.; Brumme, Chanson J.; Markle, Tristan J.; Martin, Eric; Shahid, Aniqa; Anmole, Gursev; Mwimanzi, Philip; Nassab, Pauline; Penney, Kali A.; Rahman, Manal A.; Milloy, M.-J.; Schechter, Martin T.; Markowitz, Martin; Carrington, Mary; Walker, Bruce D.; Wagner, Theresa; Buchbinder, Susan; Fuchs, Jonathan; Koblin, Beryl; Mayer, Kenneth H.; Harrigan, P. Richard; Brockman, Mark A.; Poon, Art F. Y.; Brumme, Zabrina L.

2014-01-01

HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979–1989) and 382 modern (2000–2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a “consensus-like” founder virus, the median “background” frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ∼2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were “pre-adapted” to the average host HLA profile was only ∼2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins. PMID:24762668

Identification of HIV-1 determinants for replication in vivo.

PubMed

Su, L; Kaneshima, H; Bonyhadi, M L; Lee, R; Auten, J; Wolf, A; Du, B; Rabin, L; Hahn, B H; Terwilliger, E; Mccune, J M

1997-01-06

Pathogenic organisms are frequently attenuated after long-term culture in vitro. The mechanisms of the attenuation process are not clear, but probably involve mutations of functions required for replication and pathogenicity in vivo. To identify these functions, a direct comparison must be made between attenuated genomes and those that remain pathogenic in vivo. In this study, we used the heterochimeric SCID-hu Thy/Liv mouse as an in vivo model to define human immunodeficiency virus type 1 (HIV-1) determinants which are uniquely required for replication in vivo. The Lai/IIIB isolate and its associated infectious molecular clones (e.g., HXB2) were found to infect T cell lines but failed to replicate in the SCID-hu Thy/Liv model. When a lab worker was accidentally infected by Lai/IIIB, however, HIV-1 was isolated only from infection of primary PBMC, and not from infection of T cell lines. We hypothesized that the lab worker was exposed to a heterogeneous viral stock which had been attenuated by passage in immortalized T cell lines. Either a rare family member from this stock was selected for in vivo replication or, alternatively, an attenuated genotype dominant in vitro may have reverted to become more infectious in vivo. To address this hypothesis, we have used the SCID-hu Thy/Liv model to study the replication of HXB2 and of HXB2 recombinant viruses with HIV-1 fragments isolated from the infected lab worker. HXB2 showed no or very low levels of replication in the Thy/Liv organ. Replacement of its subgenomic fragment encoding the envelope gene with a corresponding fragment from the lab worker isolate generated a recombinant virus (HXB2/LW) which replicated actively in SCID-hu mice. The NEF mutation in the HXB2 genome is still present in HXB2/LW. Thus, the LW sequences encode HIV-1 determinants which enhance HIV replication in vivo in a NEF-independent mechanism. The specific determinants have been mapped to the V1-V3 regions of the HIV-1 genome. Six unique mutations in the V3 loop region of HXB2/LW have been identified which contribute to the increased replication in vivo.

Structural Ensemble of CD4 Cytoplasmic Tail (402-419) Reveals a Nearly Flat Free-Energy Landscape with Local α-Helical Order in Aqueous Solution.

PubMed

Ahalawat, Navjeet; Arora, Simran; Murarka, Rajesh K

2015-08-27

The human cluster determinant 4 (CD4), expressed primarily on the surface of T helper cells, serves as a coreceptor in T-cell receptor recognition of MHC II antigen complexes. Besides its cellular functions, CD4 serves as a primary receptor of human immunodeficiency virus (HIV) type 1. The cytoplasmic tail of CD4 (residues 402-419) is known to be involved in direct interaction with the HIV-1 proteins Vpu and Nef. These two viral accessory proteins (Vpu and Nef) downregulate CD4 in HIV-1 infected cells by multiple strategies and make the body susceptible to all forms of infections. In this work, we carried out extensive replica exchange molecular dynamics simulations in explicit water with three popular protein force fields Amber ff99SB, Amber ff99SB*-ILDN, and CHARMM36 to characterize the equilibrium conformational ensemble of CD4-tail (402-419) and further validated the simulated ensembles with known NMR data. We found that ff99SB*-ILDN gives a better description of the structural ensemble of this peptide compared with ff99SB and CHARMM36. The peptide adopts multiple distinct conformations with varying degree of residual secondary structures. In particular, we observed 28, 7, and 5% average α-helical, β-strand, and 3(10)-helix content, respectively, for ff99SB*-ILDN. The peptide chain shows the tendency of helix formation in a cooperative manner, seeding at residues 407-410, and subsequently extending toward both ends of the chain. Furthermore, we constructed Markov state model (MSM) from large-scale molecular dynamics simulations to study the dynamics of transitions between different metastable states explored by this peptide. The mean first passage times computed from MSM indicate rapid interconversion of these states, and the time scales of transitions range from several nanoseconds to hundreds of microseconds. Our results show good agreement with experimental data and could help to understand the key molecular mechanisms of T-cell activation and HIV-mediated receptor interference.

Recent Ice thickness helicopter borne radar surveys in Patagonia

NASA Astrophysics Data System (ADS)

Rivera, Andres; Zamora, Rodrigo; Andres Uribe, Jose; Oberreuter, Jonathan; Gacitua, Guisella; Rignot, Eric

2014-05-01

The Patagonian icefields are the biggest temperate ice bodies in southern hemisphere, which have experienced important areal shrinkage and thinning in recent decades, significantly contributing to sea level rise. The main driving factor behind this retreating condition is recent decade atmospheric warming explaining higher melting rates and equilibrium line altitude upward migration. Ice dynamic is also playing an important role especially in glaciers calving into deep fjords or lakes, type of glaciers that are predominant in the Patagonian icefields. In order to better understand their ice dynamics, several recent works have measured ice velocities using feature tracking and other techniques, however, ice thickness is still barely known. In spite of several on the ground radar measurements successfully detecting several hundred of m of ice thickness at the higher plateaus, this variable remains the great missing part of the equation especially when the thickness is approximately deeper than 600 m or where the glacier surfaces are very crevassed or nearby the Equilibrium line Altitude, where on the ground measurements are logistically constrained. In order to tackle the lack of thickness data, a helicopter borne radar system was used to survey several Patagonian temperate glaciers calving into fjords (Glaciares San Rafael and Jorge Montt) or lakes (Nef, Colonia and Steffen). The radar system is comprised by a hanging bow-tie dipole antenna working at a central frequency of 20 MHz. The antenna is an aluminum structure of 7 x 5 x 1.2 m weighting near 350 kg that is hanging at 20 m below a helicopter, and is connected to the helicopter cabin by an optical fiber cable. At the antenna are installed a 3,200 Volts peak transmitter, a two channel radar receiver, and an integrated GPS registering each trace. The helicopter flying speed was kept at near 40 knots and the antenna was normally hanging at 40 m above the ice. The surveys took place along predefined tracks including several longitudinal and transversal profiles. The system was capable of measuring ice thickness in many of the surveyed tracks, where a maximum of near 800 m was detected at the higher plateau of the San Rafael glacier. Several transversal profiles showed typical U shape subglacial forms with ice thicknesses of several hundred meters. Longitudinal profiles showed rougher subglacial bottom topographies. In general the best results were obtained at glaciers having less crevassed surfaces, such as Colonia, Nef and Steffen. At tidewater calving glaciers San Rafael and Jorge Montt, where the surface topographies of the lower tongues are much more crevassed, very little bedrock returns were obtained. The scattering produced by heavily crevassed surfaces, together with the presence of meltwater at the surface, precluded radar waves penetration in many places near the calving tongues. The results are promising, but new improvements are needed to increase penetration ranges and reduce surface scattering.

The molecular basis of induction and formation of tunneling nanotubes.

PubMed

Kimura, Shunsuke; Hase, Koji; Ohno, Hiroshi

2013-04-01

Tunneling nanotubes (TNTs) and associated structures are recently recognized structures for intercellular communication. They are F-actin-containing thin protrusions of the plasma membrane of a cell and allow a direct physical connection to the plasma membranes of remote cells. TNTs and associated structures serve as mediators for intercellular transfer of organelles as well as membrane components and cytoplasmic molecules. Moreover, several pathogens have been shown to exploit these structures to spread among cells. Because of their contribution to normal cellular functions and importance in pathological conditions, studies on TNTs and related structures have accelerated over the past few years. These studies have revealed key molecules for their induction and/or formation; HIV Nef and M-Sec can induce the formation of TNTs in coordination with the remodeling of the actin cytoskeleton and vesicle trafficking.

The great escape: viral strategies to counter BST-2/tetherin.

PubMed

Douglas, Janet L; Gustin, Jean K; Viswanathan, Kasinath; Mansouri, Mandana; Moses, Ashlee V; Früh, Klaus

2010-05-13

The interferon-induced BST-2 protein has the unique ability to restrict the egress of HIV-1, Kaposi's sarcoma-associated herpesvirus (KSHV), Ebola virus, and other enveloped viruses. The observation that virions remain attached to the surface of BST-2-expressing cells led to the renaming of BST-2 as "tetherin". However, viral proteins such as HIV-1 Vpu, simian immunodeficiency virus Nef, and KSHV K5 counteract BST-2, thereby allowing mature virions to readily escape from infected cells. Since the anti-viral function of BST-2 was discovered, there has been an explosion of research into several aspects of this intriguing interplay between host and virus. This review focuses on recent work addressing the molecular mechanisms involved in BST-2 restriction of viral egress and the species-specific countermeasures employed by various viruses.

Quasiparticle Scattering off Defects and Possible Bound States in Charge-Ordered YBa_{2}Cu_{3}O_{y}.

PubMed

Zhou, R; Hirata, M; Wu, T; Vinograd, I; Mayaffre, H; Krämer, S; Horvatić, M; Berthier, C; Reyes, A P; Kuhns, P L; Liang, R; Hardy, W N; Bonn, D A; Julien, M-H

2017-01-06

We report the NMR observation of a skewed distribution of ^{17}O Knight shifts when a magnetic field quenches superconductivity and induces long-range charge-density-wave (CDW) order in YBa_{2}Cu_{3}O_{y}. This distribution is explained by an inhomogeneous pattern of the local density of states N(E_{F}) arising from quasiparticle scattering off, yet unidentified, defects in the CDW state. We argue that the effect is most likely related to the formation of quasiparticle bound states, as is known to occur, under specific circumstances, in some metals and superconductors (but not in the CDW state, in general, except for very few cases in 1D materials). These observations should provide insight into the microscopic nature of the CDW, especially regarding the reconstructed band structure and the sensitivity to disorder.

Total and labile metals in surface sediments of the tropical river-estuary system of Marabasco (Pacific coast of Mexico): Influence of an iron mine.

PubMed

Marmolejo-Rodríguez, Ana Judith; Prego, Ricardo; Meyer-Willerer, Alejandro; Shumilin, Evgueni; Cobelo-García, Antonio

2007-01-01

Marabasco is a tropical river-estuary system comprising the Marabasco river and the Barra de Navidad Lagoon. The river is impacted by the Peña Colorada iron mine, which produces 3.5 million tons of pellets per year. Thirteen surface sediment samples were collected in May 2005 (dry season) in order to establish background levels of Al, Cd, Co, Cu, Fe, Ni, Pb, and Zn in the system and to ascertain the potential mobility of metals in the sediments. Analyses were carried out in the fraction finer than 63 microm, and labile metals extracted according the BCR procedure. Certified reference materials were used for validation of methods. Total concentrations of Cd, Co, Cu, Ni, Pb, and Zn were in the range of 0.05-0.34, 6-95, 0.7-31, 9-26, 2-18, and 53-179 mgkg(-1), respectively; Al and Fe ranges of 24-127, and 26-69 mgg(-1) correspondingly. Cadmium was found to be significantly labile in the sediments (20-100%), followed by Co (0-35%), Ni (3-16%) and Zn (0-25%), whereas the labile fraction for Cu, Fe and Pb was almost negligible (<4%). According with the total metal concentrations, background levels and normalised enrichment factors (NEF) of the metals studied, the impact of the Peña Colorada iron mine on the Marabasco system is lower than expected when compared with other similar World systems influenced by mining activities.

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

PubMed Central

Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani; Gupta, Sanjeev; Singhal, Pravin C

2013-01-01

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. PMID:23806280

CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection

PubMed Central

Pérez-Núñez, Daniel; García-Urdiales, Eduardo; Martínez-Bonet, Marta; Nogal, María L.; Barroso, Susana; Revilla, Yolanda; Madrid, Ricardo

2015-01-01

African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity. PMID:25915900

CD2v Interacts with Adaptor Protein AP-1 during African Swine Fever Infection.

PubMed

Pérez-Núñez, Daniel; García-Urdiales, Eduardo; Martínez-Bonet, Marta; Nogal, María L; Barroso, Susana; Revilla, Yolanda; Madrid, Ricardo

2015-01-01

African swine fever virus (ASFV) CD2v protein is believed to be involved in virulence enhancement, viral hemadsorption, and pathogenesis, although the molecular mechanisms of the function of this viral protein are still not fully understood. Here we describe that CD2v localized around viral factories during ASFV infection, suggesting a role in the generation and/or dynamics of these viral structures and hence in disturbing cellular traffic. We show that CD2v targeted the regulatory trans-Golgi network (TGN) protein complex AP-1, a key element in cellular traffic. This interaction was disrupted by brefeldin A even though the location of CD2v around the viral factory remained unchanged. CD2v-AP-1 binding was independent of CD2v glycosylation and occurred on the carboxy-terminal part of CD2v, where a canonical di-Leu motif previously reported to mediate AP-1 binding in eukaryotic cells, was identified. This motif was shown to be functionally interchangeable with the di-Leu motif present in HIV-Nef protein in an AP-1 binding assay. However, we demonstrated that it was not involved either in CD2v cellular distribution or in CD2v-AP-1 binding. Taken together, these findings shed light on CD2v function during ASFV infection by identifying AP-1 as a cellular factor targeted by CD2v and hence elucidate the cellular pathways used by the virus to enhance infectivity.

Uninfected Bystander Cells Impact the Measurement of HIV-Specific Antibody-Dependent Cellular Cytotoxicity Responses

PubMed Central

Richard, Jonathan; Prévost, Jérémie; Baxter, Amy E.; Ding, Shilei; Medjahed, Halima; Delgado, Gloria G.; Brassard, Nathalie; Stürzel, Christina M.; Kirchhoff, Frank; Hahn, Beatrice H.; Parsons, Matthew S.; Kaufmann, Daniel E.; Evans, David T.

2018-01-01

ABSTRACT The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a “closed” conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs). Therefore, we hypothesized that these bystander cells could impact the interpretation of ADCC measurements. To investigate this, we evaluated the ability of antibodies to CD4i epitopes and broadly neutralizing Abs (bNAbs) to mediate ADCC measured by five ADCC assays commonly used in the field. Our results indicate that the uninfected bystander cells coated with gp120 are efficiently recognized by the CD4i ligands but not the bNabs. Consequently, the uninfected bystander cells substantially affect in vitro measurements made with ADCC assays that fail to identify responses against infected versus uninfected cells. Moreover, using an mRNA flow technique that detects productively infected cells, we found that the vast majority of HIV-1-infected cells in in vitro cultures or ex vivo samples from HIV-1-infected individuals are CD4 negative and therefore do not expose significant levels of CD4i epitopes. Altogether, our results indicate that ADCC assays unable to differentiate responses against infected versus uninfected cells overestimate responses mediated by CD4i ligands. PMID:29559570

Dielectric and impedance spectral characteristics of bulk ZnIn2Se4

NASA Astrophysics Data System (ADS)

El-Nahass, M. M.; Attia, A. A.; Salem, G. F.; Ali, H. A. M.; Ismail, M. I.

2014-02-01

The frequency and temperature dependence of ac conductivity, dielectric constant and dielectric loss of ZnIn2Se4 in a pellet form were investigated in the frequency range of 102-106 Hz and temperature range of 293-356 K. The behavior of ac conductivity was interpreted by the correlated barrier hopping (CBH) model. Temperature dependence of ac conductivity indicates that ac conduction is a thermally activated process. The density of localized states N(EF) and ac activation energy were estimated for various frequencies. Dielectric constant and dielectric loss showed a decrease with increasing frequency and an increase with increasing in temperature. The frequency dependence of real and imaginary parts of the complex impedance was investigated. The relaxation time decreases with the increase in temperature. The impedance spectrum exhibits the appearance of the single semicircular arc. The radius of semicircular arcs decreases with increasing temperature which suggests a mechanism of temperature-dependent on relaxation.

Word Frequency Analysis. MOS: 19E. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

eFl !tt71Ly J3 J3 , .s4𔃺 3 4c K &7v C-~ p t* I 4 A Irr E s~ AF ,r T i6 , V...k U 1 ~ rt 𔃾 ~~rr sI " ’ I TU 7 AS TMLFl ) C 5 IR L1 I F- S ASSP!"’LY V As Fl 4 ty1 I’D9 4 t UtI 2 I /rr!~t 6 T rl Z TTI-TO TS * . 611...41 1 7 1 𔃾 1 ’-L N..-r7 II, 7 L i I Cr ! l 1 11! ~ L. 0’ P66 ’ L1 ’iD 𔄁 I L r 2 410J’ 1 I I ’D ?I’Y 0 -41 Nr * I 41to~r q. j 5 141 NEF I Lr. I!,A

The Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy.

PubMed

Nolan, David J; Rose, Rebecca; Rodriguez, Patricia H; Salemi, Marco; Singer, Elyse J; Lamers, Susanna L; McGrath, Michael S

2018-01-01

Combined antiretroviral therapy (cART) does not eradicate HIV, which persists for years and can re-establish replication if treatment is stopped. The current challenge is identifying those tissues harboring virus through cART. Here, we used HIV env-nef single genome sequencing and HIV gag droplet digital PCR (ddPCR) to survey 50 tissues from five subjects on cART with no detectable plasma viral load at death. The spleen most consistently contained multiple proviral and expressed sequences (4/5 participants). Spleen-derived HIV demonstrated two distinct phylogenetic patterns: multiple identical sequences, often from different tissues, as well as diverse viral sequences on long terminal branches. Our results suggested that ddPCR may overestimate the size of the tissue-based viral reservoir. The spleen, a lymphatic organ at the intersection of the immune and circulatory systems, may play a key role in viral persistence.

Multivoxel neurofeedback selectively modulates confidence without changing perceptual performance

PubMed Central

Cortese, Aurelio; Amano, Kaoru; Koizumi, Ai; Kawato, Mitsuo; Lau, Hakwan

2016-01-01

A central controversy in metacognition studies concerns whether subjective confidence directly reflects the reliability of perceptual or cognitive processes, as suggested by normative models based on the assumption that neural computations are generally optimal. This view enjoys popularity in the computational and animal literatures, but it has also been suggested that confidence may depend on a late-stage estimation dissociable from perceptual processes. Yet, at least in humans, experimental tools have lacked the power to resolve these issues convincingly. Here, we overcome this difficulty by using the recently developed method of decoded neurofeedback (DecNef) to systematically manipulate multivoxel correlates of confidence in a frontoparietal network. Here we report that bi-directional changes in confidence do not affect perceptual accuracy. Further psychophysical analyses rule out accounts based on simple shifts in reporting strategy. Our results provide clear neuroscientific evidence for the systematic dissociation between confidence and perceptual performance, and thereby challenge current theoretical thinking. PMID:27976739

Virus-specific T cell responses in macaques acutely infected with SHIV(sf162p3).

PubMed

Pahar, Bapi; Wang, Xiaolei; Dufour, Jason; Lackner, Andrew A; Veazey, Ronald S

2007-06-20

CD4(+) T helper and CD8(+) cytotoxic T lymphocyte responses are believed to play an important role in the control of primary HIV and SIV infection. However, the role of these cells in macaques acutely infected with SHIV(sf162p3) has not been well characterized. In this study, ten adult rhesus macaques were intravaginally infected with SHIV(sf162p3), and antigen-specific cytokine responses to SHIV-Tat, Nef, Gag and Env peptide pools were examined through 70 days post inoculation (p.i.) using ELISPOT and/or cytokine flow cytometry (CFC). Peak plasma viral replication occurred between 14 and 21 days p.i. followed by low to undetectable plasma viremia by 70 days of infection in most macaques. Although some animals had strong virus-specific cellular immune responses, many had weak or minimal responses that did not correlate with the post peak decline in plasma viremia.

Virus-specific T cell responses in macaques acutely infected with SHIVsf162p3

PubMed Central

Pahar, Bapi; Wang, Xiaolei; Dufour, Jason; Lackner, Andrew A.; Veazey, Ronald S.

2007-01-01

CD4+ T helper and CD8+ cytotoxic T lymphocyte responses are believed to play an important role in the control of primary HIV and SIV infection. However, the role of these cells in macaques acutely infected with SHIVsf162p3 has not been well characterized. In this study, ten adult rhesus macaques were intravaginally infected with SHIVsf162p3, and antigen specific cytokine responses to SHIV-Tat, Nef, Gag and Env peptide pools were examined through 70 days post inoculation (p.i.) using ELISPOT and/or cytokine flow cytometry (CFC). Peak plasma viral replication occurred between 14 and 21 days p.i., followed by low to undetectable plasma viremia by 70 days of infection in most macaques. Although some animals had strong virus-specific cellular immune responses, many had weak or minimal responses that did not correlate with the post peak decline in plasma viremia. PMID:17307212

Novel specific heat and magnetoresistance behavior of Tb0.5Ho0.5Mn2Si2

NASA Astrophysics Data System (ADS)

Pandey, Swati; Siruguri, V.; Rawat, R.

2018-04-01

In this report, we study temperature dependent heat capacity and electrical resistance of Tb1-xHoxMn2Si2 (x = 0.5). Two successive low temperature magnetic transitions T1 (˜15 K) and T2 (˜25 K) are observed from both measurements. Anomalous rise in heat capacity at low temperatures is ascribed to the nuclear Schottky effect. Sommerfeld coefficient (γ), Debye temperature (θD) and density of states at Fermi level N(EF) is calculated from the zero field specific heat data. We observe 4f contribution to heat capacity from T1 to 100K, which is attributed to crystal field effect. In the electrical transport study, application of the magnetic field shows a substantial change around the ordering temperature of rare earth moment resulting in large positive magnetoresistance of about 20% with field change of 6T.

High Resolution Land Surface Modeling over the NEF Basin in the Chilean Patagonia

NASA Astrophysics Data System (ADS)

Somos-Valenzuela, M. A.

2017-12-01

Stakeholders and policy makers perceive that water and climate change adaptation are among the most vulnerable issues that need to be addressed. Therefore, there is a need not only from the scientific community but also from the society to use integrated methodologies that link advances in climatology with hydrology to provide data that helps us to provide adaptation strategies. The Andes and the Chilean-Argentinean Patagonia have been steadily warming up to 0.5 Celsius degrees per decades at the same time that precipitation is decreasing by 10 to 12 % per decade. In the future is expected that these trends will continue which will have impacts in the annual water budget. The Chilean Patagonia has brought a lot of attention during last decade because two hydroelectric project seek to build dams in one of the most pristine environments in the world. Also, in the Baker River basin a series of Glacier Lakes Outburst Flood have occurred which is perceived as an undeniable consequence of the effects of climate change in the glacier system. Major attention is mainly situated in the impact of climate change in glaciers contribution to sea level rise, GLOF studies given the numerous supra glacier lakes that are forming, and the study of stream flow point observation. The objectives of this research are: 1) Study the historical trends of precipitation, temperature, land cover changes and streamflow available in the Baker Basin; 2) Use a couple glacier model with a land surface model to predict the evolution of glaciers and their effects in the water availability. To address these objectives, I will analyze trends in hydro meteorology observations and correlation with trends in Land Cover Changes. Use the WRF-hydro framework to generate data in a small watershed that will allow to calibrate a high resolution hydro glaciology model to understand the partition between glaciered and non-glaciered runoff. The parameters estimated in the small domain could have the potential to be transfer to a regional setting and pseudo climate data will be used to study the impacts of climate change in the Baker River Basin system hydrology. The expected results are: 1) Land cover change maps and trends, and their relationship to changes in streamflow, and climate observations. 2) a calibrated hydro glaciology model for a catchment in the NEF river Basin

Interaction between Tat and Drugs of Abuse during HIV-1 Infection and Central Nervous System Disease

PubMed Central

Maubert, Monique E.; Pirrone, Vanessa; Rivera, Nina T.; Wigdahl, Brian; Nonnemacher, Michael R.

2016-01-01

In many individuals, drug abuse is intimately linked with HIV-1 infection. In addition to being associated with one-third of all HIV-1 infections in the United States, drug abuse also plays a role in disease progression and severity in HIV-1-infected patients, including adverse effects on the central nervous system (CNS). Specific systems within the brain are known to be damaged in HIV-1-infected individuals and this damage is similar to that observed in drug abuse. Even in the era of anti-retroviral therapy (ART), CNS pathogenesis occurs with HIV-1 infection, with a broad range of cognitive impairment observed, collectively referred to as HIV-1-associated neurocognitive disorders (HAND). A number of HIV-1 proteins (Tat, gp120, Nef, Vpr) have been implicated in the etiology of pathogenesis and disease as a result of the biologic activity of the extracellular form of each of the proteins in a number of tissues, including the CNS, even in ART-suppressed patients. In this review, we have made Tat the center of attention for a number of reasons. First, it has been shown to be synthesized and secreted by HIV-1-infected cells in the CNS, despite the most effective suppression therapies available to date. Second, Tat has been shown to alter the functions of several host factors, disrupting the molecular and biochemical balance of numerous pathways contributing to cellular toxicity, dysfunction, and death. In addition, the advantages and disadvantages of ART suppression with regard to controlling the genesis and progression of neurocognitive impairment are currently under debate in the field and are yet to be fully determined. In this review, we discuss the individual and concerted contributions of HIV-1 Tat, drug abuse, and ART with respect to damage in the CNS, and how these factors contribute to the development of HAND in HIV-1-infected patients. PMID:26793168

Theoretical simulations of the structural stabilities, elastic, thermodynamic and electronic properties of Pt3Sc and Pt3Y compounds

NASA Astrophysics Data System (ADS)

Boulechfar, R.; Khenioui, Y.; Drablia, S.; Meradji, H.; Abu-Jafar, M.; Omran, S. Bin; Khenata, R.; Ghemid, S.

2018-05-01

Ab-initio calculations based on density functional theory have been performed to study the structural, electronic, thermodynamic and mechanical properties of intermetallic compounds Pt3Sc and Pt3Y using the full-potential linearized augmented plane wave(FP-LAPW) method. The total energy calculations performed for L12, D022 and D024 structures confirm the experimental phase stability. Using the generalized gradient approximation (GGA), the values of enthalpies formation are -1.23 eV/atom and -1.18 eV/atom for Pt3Sc and Pt3Y, respectively. The densities of states (DOS) spectra show the existence of a pseudo-gap at the Fermi level for both compounds which indicate the strong spd hybridization and directing covalent bonding. Furthermore, the density of states at the Fermi level N(EF), the electronic specific heat coefficient (γele) and the number of bonding electrons per atom are predicted in addition to the elastic constants (C11, C12 and C44). The shear modulus (GH), Young's modulus (E), Poisson's ratio (ν), anisotropy factor (A), ratio of B/GH and Cauchy pressure (C12-C44) are also estimated. These parameters show that the Pt3Sc and Pt3Y are ductile compounds. The thermodynamic properties were calculated using the quasi-harmonic Debye model to account for their lattice vibrations. In addition, the influence of the temperature and pressure was analyzed on the heat capacities (Cp and Cv), thermal expansion coefficient (α), Debye temperature (θD) and Grüneisen parameter (γ).

Genetic Diversity in Endangered Guizhou Snub-Nosed Monkeys (Rhinopithecus brelichi): Contrasting Results from Microsatellite and Mitochondrial DNA Data

PubMed Central

Kolleck, Jakob; Yang, Mouyu; Zinner, Dietmar; Roos, Christian

2013-01-01

To evaluate the conservation status of a species or population it is necessary to gain insight into its ecological requirements, reproduction, genetic population structure, and overall genetic diversity. In our study we examined the genetic diversity of Rhinopithecus brelichi by analyzing microsatellite data and compared them with already existing data derived from mitochondrial DNA, which revealed that R. brelichi exhibits the lowest mitochondrial diversity of all so far studied Rhinopithecus species. In contrast, the genetic diversity of nuclear DNA is high and comparable to other Rhinopithecus species, i.e. the examined microsatellite loci are similarly highly polymorphic as in other species of the genus. An explanation for these differences in mitochondrial and nuclear genetic diversity could be a male biased dispersal. Females most likely stay within their natal band and males migrate between bands, thus mitochondrial DNA will not be exchanged between bands but nuclear DNA via males. A Bayesian Skyline Plot based on mitochondrial DNA sequences shows a strong decrease of the female effective population size (Nef) starting about 3,500 to 4,000 years ago, which concurs with the increasing human population in the area and respective expansion of agriculture. Given that we found no indication for a loss of nuclear DNA diversity in R. brelichi it seems that this factor does not represent the most prominent conservation threat for the long-term survival of the species. Conservation efforts should therefore focus more on immediate threats such as development of tourism and habitat destruction. PMID:24009761

A comparison of community response to aircraft noise at Toronto International and Oshawa Municipal airports†

NASA Astrophysics Data System (ADS)

Taylor, S. M.; Hall, F. L.; Birnie, S. E.

1981-07-01

Debate continues over the validity of a single dose-response relationship to describe annoyance due to transportation noise. Doubts about the appropriateness of a single relationship have centred primarily on the issue of differential response to the same noise level for different sources (e.g., aircraft, road traffic and trains). However, recent work suggests that response may vary for different types of the same source, namely aircraft, dependent upon the character, and specifically the number, of operations. Recent data collected around Toronto International and Oshawa Municipal airports permit a test of differences in four aggregate response variables. For the same NEF level, the percent at all annoyed at the two airports is not statistically different. The percent highly annoyed and the percent reporting speech interference are both significantly greater at Toronto but the percent reporting sleep interruption is greater at Oshawa. These differences can be explained in terms of the operational characteristics of the two airports.

A multi-decadal remote sensing study on glacial change in the North Patagonia Ice Field Chile

NASA Astrophysics Data System (ADS)

Tetteh, Lucy Korlekwor

Glaciers in the North Patagonian Ice Fields are temperate glaciers and can be studied to understand the dynamics of climate change. However, the ice field has been neglected in mass balance studies. In this study, multi decadal study of glacial mass balance, glacier retreat and glacial lake expansion in the North Patagonia were studied. Landsat (TM, ETM+ and 8) and ASTER images were used. San Quintin glacier experienced the highest retreat. Demarcation of glacier lakes boundaries indicated an increase in glacial lake area an addition of 4 new glacial lakes. Nef glacier recorded the highest mass gain of 9.91 plus or minus 1.96 m.w.e.a.-1 and HPN-4 glacier recorded the highest mass loss of -8.9 plus or minus 1.96 m.w.e.a. -1. However, there is a high uncertainty in the elevation values in the DEM due to the rugged nature of the terrain and presence of the heavy snow cover.

A Brain-Machine Interface Operating with a Real-Time Spiking Neural Network Control Algorithm.

PubMed

Dethier, Julie; Nuyujukian, Paul; Eliasmith, Chris; Stewart, Terry; Elassaad, Shauki A; Shenoy, Krishna V; Boahen, Kwabena

2011-01-01

Motor prostheses aim to restore function to disabled patients. Despite compelling proof of concept systems, barriers to clinical translation remain. One challenge is to develop a low-power, fully-implantable system that dissipates only minimal power so as not to damage tissue. To this end, we implemented a Kalman-filter based decoder via a spiking neural network (SNN) and tested it in brain-machine interface (BMI) experiments with a rhesus monkey. The Kalman filter was trained to predict the arm's velocity and mapped on to the SNN using the Neural Engineering Framework (NEF). A 2,000-neuron embedded Matlab SNN implementation runs in real-time and its closed-loop performance is quite comparable to that of the standard Kalman filter. The success of this closed-loop decoder holds promise for hardware SNN implementations of statistical signal processing algorithms on neuromorphic chips, which may offer power savings necessary to overcome a major obstacle to the successful clinical translation of neural motor prostheses.

Canonical and Non-Canonical Autophagy in HIV-1 Replication Cycle

PubMed Central

Leymarie, Olivier; Lepont, Leslie; Berlioz-Torrent, Clarisse

2017-01-01

Autophagy is a lysosomal-dependent degradative process essential for maintaining cellular homeostasis, and is a key player in innate and adaptive immune responses to intracellular pathogens such as human immunodeficiency virus type 1 (HIV-1). In HIV-1 target cells, autophagy mechanisms can (i) selectively direct viral proteins and viruses for degradation; (ii) participate in the processing and presentation of viral-derived antigens through major histocompatibility complexes; and (iii) contribute to interferon production in response to HIV-1 infection. As a consequence, HIV-1 has evolved different strategies to finely regulate the autophagy pathway to favor its replication and dissemination. HIV-1 notably encodes accessory genes encoding Tat, Nef and Vpu proteins, which are able to perturb and hijack canonical and non-canonical autophagy mechanisms. This review outlines the current knowledge on the complex interplay between autophagy and HIV-1 replication cycle, providing an overview of the autophagy-mediated molecular processes deployed both by infected cells to combat the virus and by HIV-1 to evade antiviral response. PMID:28946621

A Comparative Phase I Study of Combination, Homologous Subtype-C DNA, MVA, and Env gp140 Protein/Adjuvant HIV Vaccines in Two Immunization Regimes

PubMed Central

Joseph, Sarah; Quinn, Killian; Greenwood, Aldona; Cope, Alethea V.; McKay, Paul F.; Hayes, Peter J.; Kopycinski, Jakub T.; Gilmour, Jill; Miller, Aleisha N.; Geldmacher, Christof; Nadai, Yuka; Ahmed, Mohamed I. M.; Montefiori, David C.; Dally, Len; Bouliotis, George; Lewis, David J. M.; Tatoud, Roger; Wagner, Ralf; Esteban, Mariano; Shattock, Robin J.; McCormack, Sheena; Weber, Jonathan

2017-01-01

There remains an urgent need for a prophylactic HIV vaccine. We compared combined MVA and adjuvanted gp140 to sequential MVA/gp140 after DNA priming. We expected Env-specific CD4+ T-cells after DNA and MVA priming, and Env-binding antibodies in 100% individuals after boosting with gp140 and that combined vaccines would not compromise safety and might augment immunogenicity. Forty volunteers were primed three times with DNA plasmids encoding (CN54) env and (ZM96) gag-pol-nef at 0, 4 and 8 weeks then boosted with MVA-C (CN54 env and gag-pol-nef) and glucopyranosyl lipid adjuvant—aqueous formulation (GLA-AF) adjuvanted CN54gp140. They were randomised to receive them in combination at the same visit at 16 and 20 weeks (accelerated) or sequentially with MVA-C at 16, 20, and GLA-AF/gp140 at 24 and 28 weeks (standard). All vaccinations were intramuscular. Primary outcomes included ≥grade 3 safety events and the titer of CN54gp140-specific binding IgG. Other outcomes included neutralization, binding antibody specificity and T-cell responses. Two participants experienced asymptomatic ≥grade 3 transaminitis leading to discontinuation of vaccinations, and three had grade 3 solicited local or systemic reactions. A total of 100% made anti-CN54gp140 IgG and combining vaccines did not significantly alter the response; geometric mean titer 6424 (accelerated) and 6578 (standard); neutralization of MW965.2 Tier 1 pseudovirus was superior in the standard group (82 versus 45% responders, p = 0.04). T-cell ELISpot responses were CD4+ and Env-dominant; 85 and 82% responding in the accelerated and standard groups, respectively. Vaccine-induced IgG responses targeted multiple regions within gp120 with the V3 region most immunodominant and no differences between groups detected. Combining MVA and gp140 vaccines did not result in increased adverse events and did not significantly impact upon the titer of Env-specific binding antibodies, which were seen in 100% individuals. The approach did however affect other immune responses; neutralizing antibody responses, seen only to Tier 1 pseudoviruses, were poorer when the vaccines were combined and while T-cell responses were seen in >80% individuals in both groups and similarly CD4 and Env dominant, their breadth/polyfunctionality tended to be lower when the vaccines were combined, suggesting attenuation of immunogenicity and cautioning against this accelerated regimen. PMID:28275375

Polymorphisms in nitric oxide synthase and endothelin genes among children with obstructive sleep apnea.

PubMed

Chatsuriyawong, Siriporn; Gozal, David; Kheirandish-Gozal, Leila; Bhattacharjee, Rakesh; Khalyfa, Ahamed A; Wang, Yang; Sukhumsirichart, Wasana; Khalyfa, Abdelnaby

2013-09-06

Obstructive sleep apnea (OSA) is associated with adverse and interdependent cognitive and cardiovascular consequences. Increasing evidence suggests that nitric oxide synthase (NOS) and endothelin family (EDN) genes underlie mechanistic aspects of OSA-associated morbidities. We aimed to identify single nucleotide polymorphisms (SNPs) in the NOS family (3 isoforms), and EDN family (3 isoforms) to identify potential associations of these SNPs in children with OSA. A pediatric community cohort (ages 5-10 years) enriched for snoring underwent overnight polysomnographic (NPSG) and a fasting morning blood draw. The diagnostic criteria for OSA were an obstructive apnea-hypopnea Index (AHI) >2/h total sleep time (TST), snoring during the night, and a nadir oxyhemoglobin saturation <92%. Control children were defined as non-snoring children with AHI <2/h TST (NOSA). Endothelial function was assessed using a modified post-occlusive hyperemic test. The time to peak reperfusion (Tmax) was considered as the indicator for normal endothelial function (NEF; Tmax<45 sec), or ED (Tmax ≥ 45 sec). Genomic DNA from peripheral blood was extracted and allelic frequencies were assessed for, NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), endothelin receptor A, EDNRA, (27 SNPs), and endothelin receptor B, EDNRB (23 SNPs) using a custom SNPs array. The relative frequencies of NOS-1,-2, and -3, and EDN-1,-2,-3,-EDNRA, and-EDNRB genotypes were evaluated in 608 subjects [128 with OSA, and 480 without OSA (NOSA)]. Furthermore, subjects with OSA were divided into 2 subgroups: OSA with normal endothelial function (OSA-NEF), and OSA with endothelial dysfunction (OSA-ED). Linkage disequilibrium was analyzed using Haploview version 4.2 software. For NOSA vs. OSA groups, 15 differentially distributed SNPs for NOS1 gene, and 1 SNP for NOS3 emerged, while 4 SNPs for EDN1 and 1 SNP for both EDN2 and EDN3 were identified. However, in the smaller sub-group for whom endothelial function was available, none of the significant SNPs was retained due to lack of statistical power. Differences in the distribution of polymorphisms among NOS and EDN gene families suggest that these SNPs could play a contributory role in the pathophysiology and risk of OSA-induced cardiovascular morbidity. Thus, analysis of genotype-phenotype interactions in children with OSA may assist in the formulation of categorical risk estimates.

Synergy of the SimSphere land surface process model with ASTER imagery for the retrieval of spatially distributed estimates of surface turbulent heat fluxes and soil moisture content

NASA Astrophysics Data System (ADS)

Petropoulos, George; Wooster, Martin J.; Carlson, Toby N.; Drake, Nick

2010-05-01

Accurate information on spatially explicit distributed estimates of key land-atmosphere fluxes and related land surface parameters is of key importance in a range of disciplines including hydrology, meteorology, agriculture and ecology. Estimation of those parameters from remote sensing frequently employs the integration of such data with mathematical representations of the transfers of energy, mass and radiation between soil, vegetation and atmosphere continuum, known as Soil Vegetation Atmosphere Transfer (SVAT) models. The ability of one such inversion modelling scheme to resolve for key surface energy fluxes and of soil surface moisture content is examined here using data from a multispectral high spatial resolution imaging instrument, the Advanced Spaceborne Thermal Emission and Reflection Scanning Radiometer (ASTER) and SimSphere one-dimensional SVAT model. Accuracy of the investigated methodology, so-called as the "triangle" method, is verified using validated ground observations obtained from selected days collected from nine CARBOEUROPE IP sites representing a variety of climatic, topographic and environmental conditions. Subsequently, a new framework is suggested for the retrieval of two additional parameters by the investigated method, namely the Evaporative (EF) and the Non-Evaporative (NEF) Fractions. Results indicated a close agreement between the inverted surface fluxes and surface moisture availability maps as well as of the EF and NEF parameters with the observations both spatially and temporally with accuracies comparable to those obtained in similar experiments with high spatial resolution data. Inspection of the inverted surface fluxes maps regionally, showed an explainable distribution in the range of the inverted parameters in relation with the surface heterogeneity. Overall performance of the "triangle" inversion methodology was found to be affected predominantly by the SVAT model "correct" initialisation representative of the test site environment, most importantly the atmospheric conditions required in the SVAT model initial conditions. This study represents the first comprehensive evaluation of the performance of this particular methodological implementation at a European setting using the SimSphere SVAT with the ASTER data. The present work is also very timely in that, a variation of this specific inversion methodology has been proposed for the operational retrieval of the soil surface moisture content by National Polar-orbiting Operational Environmental Satellite System (NPOESS), in a series of satellite platforms that are due to be launched in the next 12 years starting from 2012. KEYWORDS: micrometeorology, surface heat fluxes, soil moisture content, ASTER, triangle method, SimSphere, CarboEurope IP

Heterologous prime-boost regimens with a recombinant chimpanzee adenoviral vector and adjuvanted F4 protein elicit polyfunctional HIV-1-specific T-Cell responses in macaques.

PubMed

Lorin, Clarisse; Vanloubbeeck, Yannick; Baudart, Sébastien; Ska, Michaël; Bayat, Babak; Brauers, Geoffroy; Clarinval, Géraldine; Donner, Marie-Noëlle; Marchand, Martine; Koutsoukos, Marguerite; Mettens, Pascal; Cohen, Joe; Voss, Gerald

2015-01-01

HIV-1-specific CD4+ and CD8+ T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4+ T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8+ T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN ('A'), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 ('P'), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4+ and CD8+ T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4+ T cells. Approximately 50% of AdC7-GRN-induced memory CD8+ T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4+ and CD8+ T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4+ and CD8+ T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4+ T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation.

Heterologous Prime-Boost Regimens with a Recombinant Chimpanzee Adenoviral Vector and Adjuvanted F4 Protein Elicit Polyfunctional HIV-1-Specific T-Cell Responses in Macaques

PubMed Central

Lorin, Clarisse; Vanloubbeeck, Yannick; Baudart, Sébastien; Ska, Michaël; Bayat, Babak; Brauers, Geoffroy; Clarinval, Géraldine; Donner, Marie-Noëlle; Marchand, Martine; Koutsoukos, Marguerite; Mettens, Pascal; Cohen, Joe; Voss, Gerald

2015-01-01

HIV-1-specific CD4+ and CD8+ T lymphocytes are important for HIV-1 replication control. F4/AS01 consists of F4 recombinant fusion protein (containing clade B Gag/p24, Pol/RT, Nef and Gag/p17) formulated in AS01 Adjuvant System, and was shown to induce F4-specific polyfunctional CD4+ T-cell responses in humans. While replication-incompetent recombinant HIV-1/SIV antigen-expressing human adenoviral vectors can elicit high-frequency antigen-specific CD8+ T-cell responses, their use is hampered by widespread pre-existing immunity to human serotypes. Non-human adenovirus serotypes associated with lower prevalence may offer an alternative strategy. We evaluated the immunogenicity of AdC7-GRN (‘A’), a recombinant chimpanzee adenovirus type 7 vector expressing clade B Gag, RT and Nef, and F4/AS01 (‘P’), when delivered intramuscularly in homologous (PP or AA) and heterologous (AAPP or PPAA) prime-boost regimens, in macaques and mice. Vaccine-induced HIV-1-antigen-specific T cells in peripheral blood (macaques), liver, spleen, and intestinal and genital mucosa (mice) were characterized by intracellular cytokine staining. Vaccine-specific IgG antibodies (macaques) were detected using ELISA. In macaques, only the heterologous prime-boost regimens induced polyfunctional, persistent and balanced CD4+ and CD8+ T-cell responses specific to each HIV-1 vaccine antigen. AdC7-GRN priming increased the polyfunctionality of F4/AS01-induced CD4+ T cells. Approximately 50% of AdC7-GRN-induced memory CD8+ T cells exhibited an effector-memory phenotype. HIV-1-specific antibodies were detected with each regimen. In mice, antigen-specific CD4+ and CD8+ T-cell responses were detected in the mucosal and systemic anatomical compartments assessed. When administered in heterologous prime-boost regimens, AdC7-GRN and F4/AS01 candidate vaccines acted complementarily in inducing potent and persistent peripheral blood HIV-1-specific CD4+ and CD8+ T-cell responses and antibodies in macaques. Besides, adenoviral vector priming modulated the cytokine-expression profile of the protein-induced CD4+ T cells. Each regimen induced HIV-1-specific T-cell responses in systemic/local tissues in mice. This suggests that prime-boost regimens combining adjuvanted protein and low-seroprevalent chimpanzee adenoviral vectors represent an attractive vaccination strategy for clinical evaluation. PMID:25856308

Accessory genes confer a high replication rate to virulent feline immunodeficiency virus.

PubMed

Troyer, Ryan M; Thompson, Jesse; Elder, John H; VandeWoude, Sue

2013-07-01

Feline immunodeficiency virus (FIV) is a lentivirus that causes AIDS in domestic cats, similar to human immunodeficiency virus (HIV)/AIDS in humans. The FIV accessory protein Vif abrogates the inhibition of infection by cat APOBEC3 restriction factors. FIV also encodes a multifunctional OrfA accessory protein that has characteristics similar to HIV Tat, Vpu, Vpr, and Nef. To examine the role of vif and orfA accessory genes in FIV replication and pathogenicity, we generated chimeras between two FIV molecular clones with divergent disease potentials: a highly pathogenic isolate that replicates rapidly in vitro and is associated with significant immunopathology in vivo, FIV-C36 (referred to here as high-virulence FIV [HV-FIV]), and a less-pathogenic strain, FIV-PPR (referred to here as low-virulence FIV [LV-FIV]). Using PCR-driven overlap extension, we produced viruses in which vif, orfA, or both genes from virulent HV-FIV replaced equivalent genes in LV-FIV. The generation of these chimeras is more straightforward in FIV than in primate lentiviruses, since FIV accessory gene open reading frames have very little overlap with other genes. All three chimeric viruses exhibited increased replication kinetics in vitro compared to the replication kinetics of LV-FIV. Chimeras containing HV-Vif or Vif/OrfA had replication rates equivalent to those of the virulent HV-FIV parental virus. Furthermore, small interfering RNA knockdown of feline APOBEC3 genes resulted in equalization of replication rates between LV-FIV and LV-FIV encoding HV-FIV Vif. These findings demonstrate that Vif-APOBEC interactions play a key role in controlling the replication and pathogenicity of this immunodeficiency-inducing virus in its native host species and that accessory genes act as mediators of lentiviral strain-specific virulence.

The heme oxygenase-1 inducer THI-56 negatively regulates iNOS expression and HMGB1 release in LPS-activated RAW 264.7 cells and CLP-induced septic mice.

PubMed

Park, Eun Jung; Jang, Hwa Jin; Tsoyi, Konstantin; Kim, Young Min; Park, Sang Won; Kim, Hye Jung; Lee, Jae Heun; Chang, Ki Churl

2013-01-01

The nuclear DNA binding protein high mobility group box 1 (HMGB1) has recently been suggested to act as a late mediator of septic shock. The effect of ((S)-6,7-dihydroxy-1-(4-hydroxynaphthylmethyl)-1,2,3,4-tetrahydroisoquinoline alkaloid, also known as THI-56, in an experimental model of sepsis was investigated. THI-56 exhibited potent anti-inflammatory properties in response to LPS in RAW 264.7 cells. In particular, THI-56 significantly inhibited the expression of inducible nitric oxide synthase (iNOS) and the release of HMGB1 in activated macrophages. THI-56 activated NE-F2-regulated factor 2 (Nrf-2)/heme oxygenase 1 (HO-1). The specific knockdown of the HO-1 gene by HO-1 siRNA significantly reversed the inhibitory effects of THI-56 on iNOS expression and HMGB1 release in LPS-stimulated macrophages. Importantly, THI-56 administration protected animals from death induced by either a lethal dose of LPS or cecal ligation and puncture (CLP). Furthermore, the ALT, AST, BUN, creatinine, and HMGB1 levels in the blood were significantly increased in CLP-induced septic mice, and the administration of THI-56 reduced these levels in a concentration-dependent and zinc protoporphyrin IX (ZnPPIX)-sensitive manner. In addition, the administration of THI-56 significantly ameliorated not only lung damage but also macrophage infiltration in the livers of CLP-induced septic mice, and these effects were also abrogated in the presence of ZnPPIX. Thus, we conclude that THI-56 significantly attenuates the proinflammatory response induced by LPS and reduces organ damage in a CLP-induced sepsis model through the upregulation of Nrf-2/HO-1.

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

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

Cheng, Kang; Rai, Partab; Lan, Xiqian

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic micemore » and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.« less

Correlates of Protective Cellular Immunity Revealed by Analysis of Population-Level Immune Escape Pathways in HIV-1

PubMed Central

Brumme, Chanson J.; Martin, Eric; Listgarten, Jennifer; Brockman, Mark A.; Le, Anh Q.; Chui, Celia K. S.; Cotton, Laura A.; Knapp, David J. H. F.; Riddler, Sharon A.; Haubrich, Richard; Nelson, George; Pfeifer, Nico; DeZiel, Charles E.; Heckerman, David; Apps, Richard; Carrington, Mary; Mallal, Simon; Harrigan, P. Richard; John, Mina

2012-01-01

HLA class I-associated polymorphisms identified at the population level mark viral sites under immune pressure by individual HLA alleles. As such, analysis of their distribution, frequency, location, statistical strength, sequence conservation, and other properties offers a unique perspective from which to identify correlates of protective cellular immunity. We analyzed HLA-associated HIV-1 subtype B polymorphisms in 1,888 treatment-naïve, chronically infected individuals using phylogenetically informed methods and identified characteristics of HLA-associated immune pressures that differentiate protective and nonprotective alleles. Over 2,100 HLA-associated HIV-1 polymorphisms were identified, approximately one-third of which occurred inside or within 3 residues of an optimally defined cytotoxic T-lymphocyte (CTL) epitope. Differential CTL escape patterns between closely related HLA alleles were common and increased with greater evolutionary distance between allele group members. Among 9-mer epitopes, mutations at HLA-specific anchor residues represented the most frequently detected escape type: these occurred nearly 2-fold more frequently than expected by chance and were computationally predicted to reduce peptide-HLA binding nearly 10-fold on average. Characteristics associated with protective HLA alleles (defined using hazard ratios for progression to AIDS from natural history cohorts) included the potential to mount broad immune selection pressures across all HIV-1 proteins except Nef, the tendency to drive multisite and/or anchor residue escape mutations within known CTL epitopes, and the ability to strongly select mutations in conserved regions within HIV's structural and functional proteins. Thus, the factors defining protective cellular immune responses may be more complex than simply targeting conserved viral regions. The results provide new information to guide vaccine design and immunogenicity studies. PMID:23055555

Comparison of human and rhesus macaque T-cell responses elicited by boosting with NYVAC encoding human immunodeficiency virus type 1 clade C immunogens.

PubMed

Mooij, Petra; Balla-Jhagjhoorsingh, Sunita S; Beenhakker, Niels; van Haaften, Patricia; Baak, Ilona; Nieuwenhuis, Ivonne G; Heidari, Shirin; Wolf, Hans; Frachette, Marie-Joelle; Bieler, Kurt; Sheppard, Neil; Harari, Alexandre; Bart, Pierre-Alexandre; Liljeström, Peter; Wagner, Ralf; Pantaleo, Giuseppe; Heeney, Jonathan L

2009-06-01

Rhesus macaques (Macaca mulatta) have played a valuable role in the development of human immunodeficiency virus (HIV) vaccine candidates prior to human clinical trials. However, changes and/or improvements in immunogen quality in the good manufacturing practice (GMP) process or changes in adjuvants, schedule, route, dose, or readouts have compromised the direct comparison of T-cell responses between species. Here we report a comparative study in which T-cell responses from humans and macaques to HIV type 1 antigens (Gag, Pol, Nef, and Env) were induced by the same vaccine batches prepared under GMP and administered according to the same schedules in the absence and presence of priming. Priming with DNA (humans and macaques) or alphavirus (macaques) and boosting with NYVAC induced robust and broad antigen-specific responses, with highly similar Env-specific gamma interferon (IFN-gamma) enzyme-linked immunospot assay responses in rhesus monkeys and human volunteers. Persistent cytokine responses of antigen-specific CD4(+) and CD8(+) T cells of the central memory as well as the effector memory phenotype, capable of simultaneously eliciting multiple cytokines (IFN-gamma, interleukin 2, and tumor necrosis factor alpha), were induced. Responses were highly similar in humans and primates, confirming earlier data indicating that priming is essential for inducing robust NYVAC-boosted IFN-gamma T-cell responses. While significant similarities were observed in Env-specific responses in both species, differences were also observed with respect to responses to other HIV antigens. Future studies with other vaccines using identical lots, immunization schedules, and readouts will establish a broader data set of species similarities and differences with which increased confidence in predicting human responses may be achieved.

Comparison of Human and Rhesus Macaque T-Cell Responses Elicited by Boosting with NYVAC Encoding Human Immunodeficiency Virus Type 1 Clade C Immunogens▿

PubMed Central

Mooij, Petra; Balla-Jhagjhoorsingh, Sunita S.; Beenhakker, Niels; van Haaften, Patricia; Baak, Ilona; Nieuwenhuis, Ivonne G.; Heidari, Shirin; Wolf, Hans; Frachette, Marie-Joelle; Bieler, Kurt; Sheppard, Neil; Harari, Alexandre; Bart, Pierre-Alexandre; Liljeström, Peter; Wagner, Ralf; Pantaleo, Giuseppe; Heeney, Jonathan L.

2009-01-01

Rhesus macaques (Macaca mulatta) have played a valuable role in the development of human immunodeficiency virus (HIV) vaccine candidates prior to human clinical trials. However, changes and/or improvements in immunogen quality in the good manufacturing practice (GMP) process or changes in adjuvants, schedule, route, dose, or readouts have compromised the direct comparison of T-cell responses between species. Here we report a comparative study in which T-cell responses from humans and macaques to HIV type 1 antigens (Gag, Pol, Nef, and Env) were induced by the same vaccine batches prepared under GMP and administered according to the same schedules in the absence and presence of priming. Priming with DNA (humans and macaques) or alphavirus (macaques) and boosting with NYVAC induced robust and broad antigen-specific responses, with highly similar Env-specific gamma interferon (IFN-γ) enzyme-linked immunospot assay responses in rhesus monkeys and human volunteers. Persistent cytokine responses of antigen-specific CD4+ and CD8+ T cells of the central memory as well as the effector memory phenotype, capable of simultaneously eliciting multiple cytokines (IFN-γ, interleukin 2, and tumor necrosis factor alpha), were induced. Responses were highly similar in humans and primates, confirming earlier data indicating that priming is essential for inducing robust NYVAC-boosted IFN-γ T-cell responses. While significant similarities were observed in Env-specific responses in both species, differences were also observed with respect to responses to other HIV antigens. Future studies with other vaccines using identical lots, immunization schedules, and readouts will establish a broader data set of species similarities and differences with which increased confidence in predicting human responses may be achieved. PMID:19321612

Spatial econometric analysis of factors influencing regional energy efficiency in China.

PubMed

Song, Malin; Chen, Yu; An, Qingxian

2018-05-01

Increased environmental pollution and energy consumption caused by the country's rapid development has raised considerable public concern, and has become the focus of the government and public. This study employs the super-efficiency slack-based model-data envelopment analysis (SBM-DEA) to measure the total factor energy efficiency of 30 provinces in China. The estimation model for the spatial interaction intensity of regional total factor energy efficiency is based on Wilson's maximum entropy model. The model is used to analyze the factors that affect the potential value of total factor energy efficiency using spatial dynamic panel data for 30 provinces during 2000-2014. The study found that there are differences and spatial correlations of energy efficiency among provinces and regions in China. The energy efficiency in the eastern, central, and western regions fluctuated significantly, and was mainly because of significant energy efficiency impacts on influences of industrial structure, energy intensity, and technological progress. This research is of great significance to China's energy efficiency and regional coordinated development.

Internal quantum efficiency enhancement of GaInN/GaN quantum-well structures using Ag nanoparticles

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

Iida, Daisuke; Department of Photonics Engineering, Technical University of Denmark, 2800 Lyngby; Faculty of Science and Technology, Meijo University, 1-501 Shiogamaguchi Tempaku, 468-8502 Nagoya

2015-09-15

We report internal quantum efficiency enhancement of thin p-GaN green quantum-well structure using self-assembled Ag nanoparticles. Temperature dependent photoluminescence measurements are conducted to determine the internal quantum efficiency. The impact of excitation power density on the enhancement factor is investigated. We obtain an internal quantum efficiency enhancement by a factor of 2.3 at 756 W/cm{sup 2}, and a factor of 8.1 at 1 W/cm{sup 2}. A Purcell enhancement up to a factor of 26 is estimated by fitting the experimental results to a theoretical model for the efficiency enhancement factor.

Effect of Type-I Interferon on Retroviruses

PubMed Central

Gómez-Lucía, Esperanza; Collado, Victorio M.; Miró, Guadalupe; Doménech, Ana

2009-01-01

Type-I interferons (IFN-I) play an important role in the innate immune response to several retroviruses. They seem to be effective in controlling the in vivo infection, though many of the clinical signs of retroviral infection may be due to their continual presence which over-stimulates the immune system and activates apoptosis. IFN-I not only affect the immune system, but also operate directly on virus replication. Most data suggest that the in vitro treatment with IFN-I of retrovirus infected cells inhibits the final stages of virogenesis, avoiding the correct assembly of viral particles and their budding, even though the mechanism is not well understood. However, in some retroviruses IFN-I may also act at a previous stage as some retroviral LTRs posses sequences homologous to the IFN-stimulated response element (ISRE). When stimulated, ISREs control viral transcription. HIV-1 displays several mechanisms for evading IFN-I, such as through Tat and Nef. Besides IFN-α and IFN-β, some other type I IFN, such as IFN-τ and IFN-ω, have potent antiviral activity and are promising treatment drugs. PMID:21994560

A comparison of directed search target detection versus in-scene target detection in Worldview-2 datasets

NASA Astrophysics Data System (ADS)

Grossman, S.

2015-05-01

Since the events of September 11, 2001, the intelligence focus has moved from large order-of-battle targets to small targets of opportunity. Additionally, the business community has discovered the use of remotely sensed data to anticipate demand and derive data on their competition. This requires the finer spectral and spatial fidelity now available to recognize those targets. This work hypothesizes that directed searches using calibrated data perform at least as well as inscene manually intensive target detection searches. It uses calibrated Worldview-2 multispectral images with NEF generated signatures and standard detection algorithms to compare bespoke directed search capabilities against ENVI™ in-scene search capabilities. Multiple execution runs are performed at increasing thresholds to generate detection rates. These rates are plotted and statistically analyzed. While individual head-to-head comparison results vary, 88% of the directed searches performed at least as well as in-scene searches with 50% clearly outperforming in-scene methods. The results strongly support the premise that directed searches perform at least as well as comparable in-scene searches.

Gene transfer to the cerebellum.

PubMed

Louboutin, Jean-Pierre; Reyes, Beverly A S; Van Bockstaele, Elisabeth J; Strayer, David S

2010-12-01

There are several diseases for which gene transfer therapy to the cerebellum might be practicable. In these studies, we used recombinant Tag-deleted SV40-derived vectors (rSV40s) to study gene delivery targeting the cerebellum. These vectors transduce neurons and microglia very effectively in vitro and in vivo, and so we tested them to evaluate gene transfer to the cerebellum in vivo. Using a rSV40 vector carrying human immunodeficiency virus (HIV)-Nef with a C-terminal FLAG epitope, we characterized the distribution, duration, and cell types transduced. Rats received test and control vectors by stereotaxic injection into the cerebellum. Transgene expression was assessed 1, 2, and 4 weeks later by immunostaining of serial brain sections. FLAG epitope-expressing cells were seen, at all times after vector administration, principally detected in the Purkinje cells of the cerebellum, identified as immunopositive for calbindin. Occasional microglial cells were tranduced; transgene expression was not detected in astrocytes or oligodendrocytes. No inflammatory or other reaction was detected at any time. Thus, SV40-derived vectors can deliver effective, safe, and durable transgene expression to the cerebellum.

Composite Overview and Composite Aerocover Overview

NASA Technical Reports Server (NTRS)

Caraccio, Anne; Tate, LaNetra; Dokos, Adam; Taylor, Brian; Brown, Chad

2014-01-01

Materials Science Division within the Engineering Directorate tasked by the Ares Launch Vehicle Division (LX-V) and the Fluids Testing and Technology Development Branch (NE-F6) to design, fabricate and test an aerodynamic composite shield for potential Heavy Lift Launch Vehicle infusion and a composite strut that will serve as a pathfinder in evaluating calorimeter data for the CRYOSTAT (cryogenic on orbit storage and transfer) Project. ATP project is to carry the design and development of the aerodynamic composite cover or "bracket" from cradle to grave including materials research, purchasing, design, fabrication, testing, analysis and presentation of the final product. Effort consisted of support from the Materials Testing & Corrosion Control Branch (NE-L2) for mechanical testing, the Prototype Development Branch (NE-L3) for CAD drawing, design/analysis, and fabrication, Materials & Processes Engineering Branch (NE-L4) for project management and materials selection; the Applied Physics Branch (NE-LS) for NDE/NDI support; and the Chemical Analysis Branch (NE-L6) for developmental systems evaluation. Funded by the Ares Launch Vehicle Division and the Fluids Testing and Technology Development Branch will provide ODC

Impact of Medicare Advantage penetration and hospital competition on technical efficiency of nursing care in US intensive care units.

PubMed

Min, Ari; Scott, Linda D; Park, Chang; Vincent, Catherine; Ryan, Catherine J; Lee, Taewha

2018-04-10

This study aimed to evaluate technical efficiency of US intensive care units and determine the effects of environmental factors on technical efficiency in providing quality of nursing care. Data were obtained from the 2014 National Database of Nursing Quality Indicators and the Centers for Medicare and Medicaid Services. Data envelopment analysis was used to estimate technical efficiency for each intensive care unit. Multilevel modeling was used to determine the effects of environmental factors on technical efficiency. Overall, Medicare Advantage penetration and hospital competition in a market did not create pressure for intensive care units to become more efficient by reducing their inputs. However, these 2 environmental factors showed positive influences on technical efficiency in intensive care units with certain levels of technical efficiency. The implications of the study results for management strategies and health policy may vary according to the levels of technical efficiency in intensive care units. Further studies are needed to examine why and how intensive care units with particular levels of technical efficiency are differently affected by certain environmental factors. Copyright © 2018 John Wiley & Sons, Ltd.

Ongoing calving-frontal dynamics of glaciers in the Northern Patagonia Icefield, Chile

NASA Astrophysics Data System (ADS)

Bown, F.; Rivera, A.; Burger, F.; Carrión, D.; Cisternas, S.; Gacitúa, G.; Pena, M.; Oberreuter, J.; Silva, R.; Uribe, J. A.; Wendt, A.; Zamora, R.

2013-05-01

Patagonian glaciers are increasingly contributing to the global-sea level rise due to negative mass balances in recent decades, in spite of moderated temperature and precipitation changes taking place in the region. The Austral Chilean glaciers retreat and thinning are strongly influenced by local topography and frontal characteristics, both playing a key role in disrupting glacier responses. One of the main ice bodies in this region is the Northern Patagonian Icefield ( NPI, 46S/73W, 3953 km2), a plateau from where tens of outlet glaciers have been inventoried. Many of these glaciers are ending at sea or freshwater lakes where they are calving. This calving feature is typically associated to non-climatic fluctuations characterized by abnormally-high and sudden retreat and other exacerbated behaviors such as ice flow acceleration and dynamical thinning. The main aim of this work is the study of recent calving dynamics of three glaciers of the NPI, in order to analyze similarities versus differences associated to their location, topographical constraints and bathymetry, among other features. With this aim, airborne LIDAR and radar surveys, as well as field trips were conducted to the area in year 2012 where several instruments and sensors were installed. The selected study sites were the NPI eastern side freshwater calving glaciers Colonia (47.19S/73.29W) and Nef (47.03S/73.27W), and the NPI western margin tidewater calving San Rafael glacier (46.70S/73.76W). With all the collected data, calving fluxes of 0.03 km3 a-1 and 0.08 km3 a-1 were detected at Glaciares Colonia and Nef respectively. At San Rafael, the calving flux was much higher (0.94 km3 a-1) mainly due to a deeper bathymetry near the glacier front, and very high velocities (10m d-1) compared to the eastern side glaciers. At Glaciar San Rafael the calving flux is very likely modulated by tidal components and local buoyancy conditions, while at the eastern glaciers, calving is a near marginal feature compared with ongoing thinning rates due to higher ablation. In the long term perspective, San Rafael is a good example of the tidewater calving cycle described for several glaciers in Alaska and Patagonia. At the eastern side glaciers, frontal retreats have been bigger than at San Rafael in recent years, but in the long term (since the Little Ice Age), San Rafael experienced a much stronger frontal recession (more than 12 km). This contrasting calving behavior between eastern and western margin glaciers, is only enhancing ice losses differences, but not changing ongoing receding trends.;

Induction of Heme Oxygenase-1 Deficiency and Associated Glutamate-Mediated Neurotoxicity Is a Highly Conserved HIV Phenotype of Chronic Macrophage Infection That Is Resistant to Antiretroviral Therapy

PubMed Central

Kovacsics, Colleen E.; Vance, Patricia J.; Collman, Ronald G.

2015-01-01

ABSTRACT Expression of the cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly reduced in the brain prefrontal cortex of HIV-positive individuals with HIV-associated neurocognitive disorders (HAND). Furthermore, this HO-1 deficiency correlates with brain viral load, markers of macrophage activation, and type I interferon responses. In vitro, HIV replication in monocyte-derived macrophages (MDM) selectively reduces HO-1 protein and RNA expression and induces production of neurotoxic levels of glutamate; correction of this HO-1 deficiency reduces neurotoxic glutamate production without an effect on HIV replication. We now demonstrate that macrophage HO-1 deficiency, and the associated neurotoxin production, is a conserved feature of infection with macrophage-tropic HIV-1 strains that correlates closely with the extent of replication, and this feature extends to HIV-2 infection. We further demonstrate that this HO-1 deficiency does not depend specifically upon the HIV-1 accessory genes nef, vpr, or vpu but rather on HIV replication, even when markedly limited. Finally, antiretroviral therapy (ART) applied to MDM after HIV infection is established does not prevent HO-1 loss or the associated neurotoxin production. This work defines a predictable relationship between HIV replication, HO-1 loss, and neurotoxin production in MDM that likely reflects processes in place in the HIV-infected brains of individuals receiving ART. It further suggests that correcting this HO-1 deficiency in HIV-infected MDM could provide neuroprotection above that provided by current ART or proposed antiviral therapies directed at limiting Nef, Vpr, or Vpu functions. The ability of HIV-2 to reduce HO-1 expression suggests that this is a conserved phenotype among macrophage-tropic human immunodeficiency viruses that could contribute to neuropathogenesis. IMPORTANCE The continued prevalence of HIV-associated neurocognitive disorders (HAND) underscores the need for adjunctive therapy that targets the neuropathological processes that persist in antiretroviral therapy (ART)-treated HIV-infected individuals. To this end, we previously identified one such possible process, a deficiency of the antioxidative and anti-inflammatory enzyme heme oxygenase-1 (HO-1) in the brains of individuals with HAND. In the present study, our findings suggest that the HO-1 deficiency associated with excess glutamate production and neurotoxicity in HIV-infected macrophages is a highly conserved phenotype of macrophage-tropic HIV strains and that this phenotype can persist in the macrophage compartment in the presence of ART. This suggests a plausible mechanism by which HIV infection of brain macrophages in ART-treated individuals could exacerbate oxidative stress and glutamate-induced neuronal injury, each of which is associated with neurocognitive dysfunction in infected individuals. Thus, therapies that rescue the HO-1 deficiency in HIV-infected individuals could provide additional neuroprotection to ART. PMID:26269184

[Quality level assessment of lowly efficient Tamarix chinensis secondary shrubs in Laizhou Bay of Yellow River Delta].

PubMed

Xia, Jiang-Bao; Liu, Yu-Ting; Zhu, Jin-Fang; Xu, Jing-Wei; Lu, Zhao-Hua; Liu, Jing-Tao; Liu, Qing

2013-06-01

Taking the Tamarix chinensis secondary shrubs in Laizhou Bay of Yellow River Delta as test objects, and by using synthetic factor method, this paper studied the main factors causing the lowly efficiency of T. chinensis secondary shrubs as well as the main parameters for the classification of lowly efficient T. chinensis secondary shrubs. A total of 24 indices including shrubs growth and soil physical and chemical properties were selected to determine the main affecting factors and parameters in evaluating and classifying the lowly efficient shrubs. There were no obvious correlations between the indices reflecting the shrubs growth and soil quality, and thus, only using shrub growth index to reflect the lowly efficiency level of T. chinensis was not enough, and it would be necessary to combine with soil quality factors to make a comprehensive evaluation. The principal factors reflecting the quality level of lowly efficient T. chinensis shrubs included soil salt content and moisture content, stand age, single tree's aboveground stem, leaf biomass, and basal diameter, followed by soil density, porosity, and soil nutrient status. The lowly efficient T. chinensis shrubs in the Bay could be classified into five types, namely, shrub with growth potential, slightly low quality shrub, moderately lowly efficient shrub, moderately low quality and lowly efficient shrub, and seriously low quality and lowly efficient shrub. The main features, low efficiency causes, and management measures of these shrubs were discussed based on the mean cluster value.

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

NASA Technical Reports Server (NTRS)

Mackey, Jon; Sehirlioglu, Alp; Dynys, Fred

2014-01-01

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

[Influencing factors in preparation of brucine liposomes by ammonium sulfate transmembrane gradients].

PubMed

Wang, Wei; Chen, Jun; Cai, Bao-Chang; Fang, Yun

2008-09-01

To study the influencing factors in preparation of brucine liposomes by ammonium sulfate transmembrane gradients. The brucine liposomes were separated by Sephadex G-50, and the influence of various factors on the entrapment efficiencies were investigated. The entrapment efficiency was enhanced by increased ammonium sulfate concentration, ethanol volume and PC concentration. Burcine liposomes prepared by ammonium sulfate transmembrance gradients can get a high entrapment efficiency, the main influencing factors were ammonium sulfate concentration, ethanol volume and PC concentration.

Measuring the operational efficiency of individual theme park attractions.

PubMed

Kim, Changhee; Kim, Soowook

2016-01-01

This study assesses the operation efficiency of theme park attractions using the data envelopment analysis, utilizing actual data on 15 attractions at Samsung Everland located in Yongin-si, Republic of Korea. In particular, this study identifies crowding and waiting time as one of the main causes of visitor's satisfaction, and analyzes the efficiency of individual attractions in terms of waiting time. The installation area, installation cost, and annual repair cost are set as input factors and the number of annual users and customer satisfaction as output factors. The results show that the roller coaster-type attractions were less efficient than other types of attractions while rotating-type attractions were relatively more efficient. However, an importance performance analysis on individual attraction's efficiency and satisfaction showed that operational efficiency should not be the sole consideration in attraction installation. In addition, the projection points for input factors for efficient use of attractions and the appropriate reference set for benchmarking are provided as guideline for attraction efficiency management.

Factors that influence the efficiency of beef and dairy cattle recording system in Kenya: A SWOT-AHP analysis.

PubMed

Wasike, Chrilukovian B; Magothe, Thomas M; Kahi, Alexander K; Peters, Kurt J

2011-01-01

Animal recording in Kenya is characterised by erratic producer participation and high drop-out rates from the national recording scheme. This study evaluates factors influencing efficiency of beef and dairy cattle recording system. Factors influencing efficiency of animal identification and registration, pedigree and performance recording, and genetic evaluation and information utilisation were generated using qualitative and participatory methods. Pairwise comparison of factors was done by strengths, weaknesses, opportunities and threats-analytical hierarchical process analysis and priority scores to determine their relative importance to the system calculated using Eigenvalue method. For identification and registration, and evaluation and information utilisation, external factors had high priority scores. For pedigree and performance recording, threats and weaknesses had the highest priority scores. Strengths factors could not sustain the required efficiency of the system. Weaknesses of the system predisposed it to threats. Available opportunities could be explored as interventions to restore efficiency in the system. Defensive strategies such as reorienting the system to offer utility benefits to recording, forming symbiotic and binding collaboration between recording organisations and NARS, and development of institutions to support recording were feasible.

Frequent associations between CTL and T-Helper epitopes in HIV-1 genomes and implications for multi-epitope vaccine designs

PubMed Central

2010-01-01

Background Epitope vaccines have been suggested as a strategy to counteract viral escape and development of drug resistance. Multiple studies have shown that Cytotoxic T-Lymphocyte (CTL) and T-Helper (Th) epitopes can generate strong immune responses in Human Immunodeficiency Virus (HIV-1). However, not much is known about the relationship among different types of HIV epitopes, particularly those epitopes that can be considered potential candidates for inclusion in the multi-epitope vaccines. Results In this study we used association rule mining to examine relationship between different types of epitopes (CTL, Th and antibody epitopes) from nine protein-coding HIV-1 genes to identify strong associations as potent multi-epitope vaccine candidates. Our results revealed 137 association rules that were consistently present in the majority of reference and non-reference HIV-1 genomes and included epitopes of two different types (CTL and Th) from three different genes (Gag, Pol and Nef). These rules involved 14 non-overlapping epitope regions that frequently co-occurred despite high mutation and recombination rates, including in genomes of circulating recombinant forms. These epitope regions were also highly conserved at both the amino acid and nucleotide levels indicating strong purifying selection driven by functional and/or structural constraints and hence, the diminished likelihood of successful escape mutations. Conclusions Our results provide a comprehensive systematic survey of CTL, Th and Ab epitopes that are both highly conserved and co-occur together among all subtypes of HIV-1, including circulating recombinant forms. Several co-occurring epitope combinations were identified as potent candidates for inclusion in multi-epitope vaccines, including epitopes that are immuno-responsive to different arms of the host immune machinery and can enable stronger and more efficient immune responses, similar to responses achieved with adjuvant therapies. Signature of strong purifying selection acting at the nucleotide level of the associated epitopes indicates that these regions are functionally critical, although the exact reasons behind such sequence conservation remain to be elucidated. PMID:20696039

First Phase I human clinical trial of a killed whole-HIV-1 vaccine: demonstration of its safety and enhancement of anti-HIV antibody responses.

PubMed

Choi, Eunsil; Michalski, Chad J; Choo, Seung Ho; Kim, Gyoung Nyoun; Banasikowska, Elizabeth; Lee, Sangkyun; Wu, Kunyu; An, Hwa-Yong; Mills, Anthony; Schneider, Stefan; Bredeek, U Fritz; Coulston, Daniel R; Ding, Shilei; Finzi, Andrés; Tian, Meijuan; Klein, Katja; Arts, Eric J; Mann, Jamie F S; Gao, Yong; Kang, C Yong

2016-11-28

Vaccination with inactivated (killed) whole-virus particles has been used to prevent a wide range of viral diseases. However, for an HIV vaccine this approach has been largely negated due to inherent safety concerns, despite the ability of killed whole-virus vaccines to generate a strong, predominantly antibody-mediated immune response in vivo. HIV-1 Clade B NL4-3 was genetically modified by deleting the nef and vpu genes and substituting the coding sequence for the Env signal peptide with that of honeybee melittin signal peptide to produce a less virulent and more replication efficient virus. This genetically modified virus (gmHIV-1 NL4-3 ) was inactivated and formulated as a killed whole-HIV vaccine, and then used for a Phase I human clinical trial (Trial Registration: Clinical Trials NCT01546818). The gmHIV-1 NL4-3 was propagated in the A3.01 human T cell line followed by virus purification and inactivation with aldrithiol-2 and γ-irradiation. Thirty-three HIV-1 positive volunteers receiving cART were recruited for this observer-blinded, placebo-controlled Phase I human clinical trial to assess the safety and immunogenicity. Genetically modified and killed whole-HIV-1 vaccine, SAV001, was well tolerated with no serious adverse events. HIV-1 NL4-3 -specific PCR showed neither evidence of vaccine virus replication in the vaccine virus-infected human T lymphocytes in vitro nor in the participating volunteers receiving SAV001 vaccine. Furthermore, SAV001 with adjuvant significantly increased the pre-existing antibody response to HIV-1 proteins. Antibodies in the plasma of vaccinees were also found to recognize HIV-1 envelope protein on the surface of infected cells as well as showing an enhancement of broadly neutralizing antibodies inhibiting tier I and II of HIV-1 B, D, and A subtypes. The killed whole-HIV vaccine, SAV001, is safe and triggers anti-HIV immune responses. It remains to be determined through an appropriate trial whether this immune response prevents HIV infection.

Efficiency and factors influencing efficiency of Community Health Strategy in providing Maternal and Child Health services in Mwingi District, Kenya: an expert opinion perspective

PubMed Central

Nzioki, Japheth Mativo; Onyango, Rosebella Ogutu; Ombaka, James Herbert

2015-01-01

Introduction Community Health Strategy (CHS) is a new Primary Health Care (PHC) model in Kenya, designed to provide PHC services in Kenya. In 2011, CHS was initiated in Mwingi district as one of the components of APHIA plus kamili program. The objectives of this study was to evaluate the efficiency of the CHS in providing MCH services in Mwingi district and to establish the factors influencing efficiency of the CHS in providing MCH services in the district. Methods This was a qualitative study. Fifteen Key informants were sampled from key stakeholders. Sampling was done using purposive and maximum variation sampling methods. Semi-structured in-depth interviews were used for data collection. Data was managed and analyzed using NVIVO. Framework analysis and quasi statistics were used in data analysis. Results Expert opinion data indicated that the CHS was efficient in providing MCH services. Factors influencing efficiency of the CHS in provision of MCH services were: challenges facing Community Health Workers (CHWs), Social cultural and economic factors influencing MCH in the district, and motivation among CHWs. Conclusion Though CHS was found to be efficient in providing MCH services, this was an expert opinion perspective, a quantitative Cost Effectiveness Analysis (CEA) to confirm these findings is recommended. To improve efficiency of the CHS in the district, challenges facing CHWs and Social cultural and economic factors that influence efficiency of the CHS in the district need to be addressed. PMID:26090046

HIV-1 Full-Genome Phylogenetics of Generalized Epidemics in Sub-Saharan Africa: Impact of Missing Nucleotide Characters in Next-Generation Sequences

PubMed Central

Wymant, Chris; Colijn, Caroline; Danaviah, Siva; Essex, Max; Frost, Simon; Gall, Astrid; Gaseitsiwe, Simani; Grabowski, Mary K.; Gray, Ronald; Guindon, Stephane; von Haeseler, Arndt; Kaleebu, Pontiano; Kendall, Michelle; Kozlov, Alexey; Manasa, Justen; Minh, Bui Quang; Moyo, Sikhulile; Novitsky, Vlad; Nsubuga, Rebecca; Pillay, Sureshnee; Quinn, Thomas C.; Serwadda, David; Ssemwanga, Deogratius; Stamatakis, Alexandros; Trifinopoulos, Jana; Wawer, Maria; Brown, Andy Leigh; de Oliveira, Tulio; Kellam, Paul; Pillay, Deenan; Fraser, Christophe

2017-01-01

Abstract To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the “Phylogenetics and Networks for Generalised HIV Epidemics in Africa” consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n = 2,833; MRC/UVRI Uganda, n = 701; Mochudi Prevention Project, n = 359; Africa Health Research Institute Resistance Cohort, n = 92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai. Partial sequencing failure was primarily associated with low viral load, increased for amplicons closer to the 3′ end of the genome, was not associated with subtype diversity except HIV-1 subtype D, and remained significantly associated with sampling location after controlling for other factors. We assessed the impact of the missing data patterns in PANGEA-HIV sequences on phylogeny reconstruction in simulations. We found a threshold in terms of taxon sampling below which the patchy distribution of missing characters in next-generation sequences (NGS) has an excess negative impact on the accuracy of HIV-1 phylogeny reconstruction, which is attributable to tree reconstruction artifacts that accumulate when branches in viral trees are long. The large number of PANGEA-HIV sequences provides unprecedented opportunities for evaluating HIV-1 transmission dynamics across sub-Saharan Africa and identifying prevention opportunities. Molecular epidemiological analyses of these data must proceed cautiously because sequence sampling remains below the identified threshold and a considerable negative impact of missing characters on phylogeny reconstruction is expected. PMID:28540766

Unc-51 like kinase 1 (ULK1) in silico analysis for biomarker identification: a vital component of autophagy.

PubMed

Randhawa, Rohit; Sehgal, Manika; Singh, Tiratha Raj; Duseja, Ajay; Changotra, Harish

2015-05-10

Autophagy is a degradation pathway involving lysosomal machinery for degradation of damaged organelles like the endoplasmic reticulum and mitochondria into their building blocks to maintain homeostasis within the cell. ULK1, a serine/threonine kinase, is conserved across species, from yeasts to mammals, and plays a central role in autophagy pathway. It receives signals from upstream modulators such as TIP60, mTOR and AMPK and relays them to its downstream substrates like Ambra1 and ZIP kinase. The activity of this complex is regulated through protein-protein interactions and post-translational modifications. Applying in silico analysis we identified (i) conserved patterns of ULK1 that showed its evolutionary relationship between the species which were closely related in a family compared to others. (ii) A total of 23 TFBS distributed throughout ULK1 and nuclear factor (erythroid-derived) 2 (NFE2) is of utmost significance because of its high importance rate. NEF2 has already been shown experimentally to play a role in the autophagy pathway. Most of these were of zinc coordinating class and we suggest that this information could be utilized to modulate this pathway by modifying interactions of these TFs with ULK1. (iii) CATTT haplotype was prominently found with frequency 0.774 in the studied population and nsSNPs which could have harmful effect on ULK1 protein and these could further be tested. (iv) A total of 83 phosphorylation sites were identified; 26 are already known and 57 are new that include one at tyrosine residue which could further be studied for its involvement in ULK1 regulation and hence autophagy. Furthermore, 4 palmitoylation sites at positions 426, 927, 1003 and 1049 were also found which could further be studied for protein-protein interactions as well as in trafficking. Copyright © 2015 Elsevier B.V. All rights reserved.

HIV-1 full-genome phylogenetics of generalized epidemics in sub-Saharan Africa: impact of missing nucleotide characters in next-generation sequences.

PubMed

Ratmann, Oliver; Wymant, Chris; Colijn, Caroline; Danaviah, Siva; Essex, M; Frost, Simon D W; Gall, Astrid; Gaiseitsiwe, Simani; Grabowski, Mary; Gray, Ronald; Guindon, Stephane; von Haeseler, Arndt; Kaleebu, Pontiano; Kendall, Michelle; Kozlov, Alexey; Manasa, Justen; Minh, Bui Quang; Moyo, Sikhulile; Novitsky, Vladimir; Nsubuga, Rebecca; Pillay, Sureshnee; Quinn, Thomas C; Serwadda, David; Ssemwanga, Deogratius; Stamatakis, Alexandros; Trifinopoulos, Jana; Wawer, Maria; Leigh Brown, Andrew; de Oliveira, Tulio; Kellam, Paul; Pillay, Deenan; Fraser, Christophe

2017-05-25

To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3,985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2,833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai. Partial sequencing failure was primarily associated with low viral load, increased for amplicons closer to the 3' end of the genome, was not associated with subtype diversity except HIV-1 subtype D, and remained significantly associated with sampling location after controlling for other factors. We assessed the impact of the missing data patterns in PANGEA-HIV sequences on phylogeny reconstruction in simulations. We found a threshold in terms of taxon sampling below which the patchy distribution of missing characters in next-generation sequences has an excess negative impact on the accuracy of HIV-1 phylogeny reconstruction, which is attributable to tree reconstruction artifacts that accumulate when branches in viral trees are long. The large number of PANGEA-HIV sequences provides unprecedented opportunities for evaluating HIV-1 transmission dynamics across sub-Saharan Africa and identifying prevention opportunities. Molecular epidemiological analyses of these data must proceed cautiously because sequence sampling remains below the identified threshold and a considerable negative impact of missing characters on phylogeny reconstruction is expected.

Changes in agricultural carbon emissions and factors that influence agricultural carbon emissions based on different stages in Xinjiang, China.

PubMed

Xiong, Chuanhe; Yang, Degang; Xia, Fuqiang; Huo, Jinwei

2016-11-10

Xinjiang's agricultural carbon emissions showed three stages of change, i.e., continued to rise, declined and continued to rise, during 1991-2014. The agriculture belonged to the "low emissions and high efficiency" agriculture category, with a lower agricultural carbon emission intensity. By using the logarithmic mean divisia index decomposition method, agricultural carbon emissions were decomposed into an efficiency factor, a structure factor, an economy factor, and a labour factor. We divided the study period into five stages based on the changes in efficiency factor and economy factor. Xinjiang showed different agricultural carbon emission characteristics at different stages. The degree of impact on agricultural carbon emissions at these stages depended on the combined effect of planting-animal husbandry carbon intensity and agricultural labour productivity. The economy factor was the critical factor to promote the increase in agricultural carbon emissions, while the main inhibiting factor for agricultural carbon emissions was the efficiency factor. The labour factor became more and more obvious in increasing agricultural carbon emissions. Finally, we discuss policy recommendations in terms of the main factors, including the development of agricultural science and technology (S&T), the establishment of three major mechanisms and transfer of rural labour in ethnic areas.

Compound Synthesis or Growth and Development of Roots/Stomata Regulate Plant Drought Tolerance or Water Use Efficiency/Water Uptake Efficiency.

PubMed

Meng, Lai-Sheng

2018-04-11

Water is crucial to plant growth and development because it serves as a medium for all cellular functions. Thus, the improvement of plant drought tolerance or water use efficiency/water uptake efficiency is important in modern agriculture. In this review, we mainly focus on new genetic factors for ameliorating drought tolerance or water use efficiency/water uptake efficiency of plants and explore the involvement of these genetic factors in the regulation of improving plant drought tolerance or water use efficiency/water uptake efficiency, which is a result of altered stomata density and improving root systems (primary root length, hair root growth, and lateral root number) and enhanced production of osmotic protectants, which is caused by transcription factors, proteinases, and phosphatases and protein kinases. These results will help guide the synthesis of a model for predicting how the signals of genetic and environmental stress are integrated at a few genetic determinants to control the establishment of either water use efficiency or water uptake efficiency. Collectively, these insights into the molecular mechanism underpinning the control of plant drought tolerance or water use efficiency/water uptake efficiency may aid future breeding or design strategies to increase crop yield.

Coupling efficiency of laser beam to multimode fiber

NASA Astrophysics Data System (ADS)

Niu, Jinfu; Xu, Jianqiu

2007-06-01

The coupling efficiency of laser beam to multimode fiber is given by geometrical optics, and the relation between the maximum coupling efficiency and the beam propagation factor M2 is analyzed. An equivalent factor MF2 for the multimode fiber is introduced to characterize the fiber coupling capability. The coupling efficiency of laser beam to multimode fiber is calculated in respect of the ratio M2/MF2 by the overlapping integral theory. The optimal coupling efficiency can be roughly estimated by the ratio of M2 to MF2 but with a large error range. The deviation comes from the lacks of information on the detail of phase and intensity profile in the beam factor M2.

Engineering RENTA, a DNA prime-MVA boost HIV vaccine tailored for Eastern and Central Africa.

PubMed

Nkolola, J P; Wee, E G-T; Im, E-J; Jewell, C P; Chen, N; Xu, X-N; McMichael, A J; Hanke, T

2004-07-01

For the development of human immunodeficiency virus type 1 (HIV-1) vaccines, traditional approaches inducing virus-neutralizing antibodies have so far failed. Thus the effort is now focused on elicitation of cellular immunity. We are currently testing in clinical trials in the United Kingdom and East Africa a T-cell vaccine consisting of HIV-1 clade A Gag-derived immunogen HIVA delivered in a prime-boost regimen by a DNA plasmid and modified vaccinia virus Ankara (MVA). Here, we describe engineering and preclinical development of a second immunogen RENTA, which will be used in combination with the present vaccine in a four-component DNA/HIVA-RENTA prime-MVA/HIVA-RENTA boost formulation. RENTA is a fusion protein derived from consensus HIV clade A sequences of Tat, reverse transcriptase, Nef and gp41. We inactivated the natural biological activities of the HIV components and confirmed immunogenicities of the pTHr.RENTA and MVA.RENTA vaccines in mice. Furthermore, we demonstrated in mice and rhesus monkeys broadening of HIVA-elicited T-cell responses by a parallel induction of HIVA- and RENTA-specific responses recognizing multiple HIV epitopes.

Physical installation of Pelletron and electron cooling system

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

Hurh, P.

1997-09-01

Bremsstrahlung of 5 MeV electrons at a loss current of 50 microamp in the acceleration region is estimated to produce X-ray intensities of 7 Rad/sec. Radiation losses due to a misteer or sudden obstruction will of course be much higher still (estimated at 87,500 Rad/hr for a 0.5 mA beam current). It is estimated that 1.8 meters of concrete will be necessary to adequately shield the surrounding building areas at any possible Pelletron installation site. To satisfy our present electron cooling development plan, two Pelletron installations are required, the first at our development lab in the Lab B/NEF Enclosure areamore » and the second at the operational Main Injector service building, MI-30, in the main Injector ring. The same actual Pelletron and electron beam-line components will be used at both locations. The Lab B installation will allow experimentation with actual high energy electron beam to develop the optics necessary for the cooling straight while Main Injector/Recycler commissioning is taking place. The MI-30 installation is obviously the permanent home for the Pelletron when electron cooling becomes operational. Construction plans for both installations will be discussed here.« less

Solid State Lasers from an Efficiency Perspective

NASA Technical Reports Server (NTRS)

Barnes, Norman P.

2007-01-01

Solid state lasers have remained a vibrant area of research because several major innovations expanded their capability. Major innovations are presented with emphasis focused on the laser efficiency. A product of efficiencies approach is developed and applied to describe laser performance. Efficiency factors are presented in closed form where practical and energy transfer effects are included where needed. In turn, efficiency factors are used to estimate threshold and slope efficiency, allowing a facile estimate of performance. Spectroscopic, thermal, and mechanical data are provided for common solid state laser materials.

Spectral compression algorithms for the analysis of very large multivariate images

DOEpatents

Keenan, Michael R.

2007-10-16

A method for spectrally compressing data sets enables the efficient analysis of very large multivariate images. The spectral compression algorithm uses a factored representation of the data that can be obtained from Principal Components Analysis or other factorization technique. Furthermore, a block algorithm can be used for performing common operations more efficiently. An image analysis can be performed on the factored representation of the data, using only the most significant factors. The spectral compression algorithm can be combined with a spatial compression algorithm to provide further computational efficiencies.

Empirical Study on Total Factor Productive Energy Efficiency in Beijing-Tianjin-Hebei Region-Analysis based on Malmquist Index and Window Model

NASA Astrophysics Data System (ADS)

Xu, Qiang; Ding, Shuai; An, Jingwen

2017-12-01

This paper studies the energy efficiency of Beijing-Tianjin-Hebei region and to finds out the trend of energy efficiency in order to improve the economic development quality of Beijing-Tianjin-Hebei region. Based on Malmquist index and window analysis model, this paper estimates the total factor energy efficiency in Beijing-Tianjin-Hebei region empirically by using panel data in this region from 1991 to 2014, and provides the corresponding political recommendations. The empirical result shows that, the total factor energy efficiency in Beijing-Tianjin-Hebei region increased from 1991 to 2014, mainly relies on advances in energy technology or innovation, and obvious regional differences in energy efficiency to exist. Throughout the window period of 24 years, the regional differences of energy efficiency in Beijing-Tianjin-Hebei region shrank. There has been significant convergent trend in energy efficiency after 2000, mainly depends on the diffusion and spillover of energy technologies.

Feline immunodeficiency virus envelope glycoproteins antagonize tetherin through a distinctive mechanism that requires virion incorporation.

PubMed

Morrison, James H; Guevara, Rebekah B; Marcano, Adriana C; Saenz, Dyana T; Fadel, Hind J; Rogstad, Daniel K; Poeschla, Eric M

2014-03-01

BST2/tetherin inhibits the release of enveloped viruses from cells. Primate lentiviruses have evolved specific antagonists (Vpu, Nef, and Env). Here we characterized tetherin proteins of species representing both branches of the order Carnivora. Comparison of tiger and cat (Feliformia) to dog and ferret (Caniformia) genes demonstrated that the tiger and cat share a start codon mutation that truncated most of the tetherin cytoplasmic tail early in the Feliformia lineage (19 of 27 amino acids, including the dual tyrosine motif). Alpha interferon (IFN-α) induced tetherin and blocked feline immunodeficiency virus (FIV) replication in lymphoid and nonlymphoid feline cells. Budding of bald FIV and HIV particles was blocked by carnivore tetherins. However, infectious FIV particles were resistant, and spreading FIV replication was uninhibited. Antagonism mapped to the envelope glycoprotein (Env), which rescued FIV from carnivore tetherin restriction when expressed in trans but, in contrast to known antagonists, did not rescue noncognate particles. Also unlike the primate lentiviral antagonists, but similar to the Ebola virus glycoprotein, FIV Env did not reduce intracellular or cell surface tetherin levels. Furthermore, FIV-enveloped FIV particles actually required tetherin for optimal release from cells. The results show that FIV Envs mediate a distinctive tetherin evasion. Well adapted to a phylogenetically ancient tetherin tail truncation in the Felidae, it requires functional virion incorporation of Env, and it shields the budding particle without downregulating plasma membrane tetherin. Moreover, FIV has evolved dependence on this protein: particles containing FIV Env need tetherin for optimal release from the cell, while Env(-) particles do not. HIV-1 antagonizes the restriction factor tetherin with the accessory protein Vpu, while HIV-2 and the filovirus Ebola use their envelope (Env) glycoproteins for this purpose. It turns out that the FIV tetherin antagonist is also its Env protein, but the mechanism is distinctive. Unlike other tetherin antagonists, FIV Env cannot act in trans to rescue vpu-deficient HIV-1. It must be incorporated specifically into FIV virions to be active. Also unlike other retroviral antagonists, but similar to Ebola virus Env, it does not act by downregulating or degrading tetherin. FIV Env might exclude tetherin locally or direct assembly to tetherin-negative membrane domains. Other distinctive features are apparent, including evidence that this virus evolved an equilibrium in which tetherin is both restriction factor and cofactor, as FIV requires tetherin for optimal particle release.

Neratinib Plus Paclitaxel vs Trastuzumab Plus Paclitaxel in Previously Untreated Metastatic ERBB2-Positive Breast Cancer: The NEfERT-T Randomized Clinical Trial.

PubMed

Awada, Ahmad; Colomer, Ramon; Inoue, Kenichi; Bondarenko, Igor; Badwe, Rajendra A; Demetriou, Georgia; Lee, Soo-Chin; Mehta, Ajay O; Kim, Sung-Bae; Bachelot, Thomas; Goswami, Chanchal; Deo, Suryanarayan; Bose, Ron; Wong, Alvin; Xu, Feng; Yao, Bin; Bryce, Richard; Carey, Lisa A

2016-12-01

Efficacious ERBB2 (formerly HER2 or HER2/neu)-directed treatments, in addition to trastuzumab and lapatinib, are needed. To determine whether neratinib, an irreversible pan-ERBB tyrosine kinase inhibitor, plus paclitaxel improves progression-free survival compared with trastuzumab plus paclitaxel in the first-line treatment of recurrent and/or metastatic ERBB2-positive breast cancer. In the randomized, controlled, open-label NEfERT-T trial conducted from August 2009 to December 2014 at 188 centers in 34 countries in Europe, Asia, Africa, and North America, 479 women with previously untreated recurrent and/or metastatic ERBB2-positive breast cancer were randomized to 1 of 2 treatment arms (neratinib-paclitaxel [n = 242] or trastuzumab-paclitaxel [n = 237]). Women with asymptomatic central nervous system metastases were eligible, and randomization was stratified by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. Women received neratinib (240 mg/d orally) or trastuzumab (4 mg/kg then 2 mg/kg weekly), each combined with paclitaxel (80 mg/m2 on days 1, 8, and 15 every 28 days). Primary prophylaxis for diarrhea was not mandatory. The primary outcome was progression-free survival. Secondary end points were response rate, clinical benefit rate, duration of response, frequency, and time to symptomatic and/or progressive central nervous system lesions, and safety. The intent-to-treat population comprised 479 women 18 years or older (neratinib-paclitaxel, n = 242; trastuzumab-paclitaxel, n = 237) randomized and stratified in their respective treatment arms by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. Median progression-free survival was 12.9 months (95% CI, 11.1-14.9) with neratinib-paclitaxel and 12.9 months (95% CI, 11.1-14.8) with trastuzumab-paclitaxel (hazard ratio [HR], 1.02; 95% CI, 0.81-1.27; P =.89). With neratinib-paclitaxel, the incidence of central nervous system recurrences was lower (relative risk, 0.48; 95% CI, 0.29-0.79; P = .002) and time to central nervous system metastases delayed (HR, 0.45; 95% CI, 0.26-0.78; P = .004). Common grade 3 to 4 adverse events were diarrhea (73 of 240 patients [30.4%] with neratinib-paclitaxel and 9 of 234 patients [3.8%] with trastuzumab-paclitaxel), neutropenia (31 patients [12.9%] vs 34 patients [14.5%]) and leukopenia (19 patients [7.9%] vs 25 patients [10.7%]); no grade 4 diarrhea was observed. In first-line ERBB2-positive metastatic breast cancer, neratinib-paclitaxel was not superior to trastuzumab-paclitaxel in terms of progression-free survival. In spite of similar overall efficacy, neratinib-paclitaxel may delay the onset and reduce the frequency of central nervous system progression, a finding that requires a larger study to confirm. clinicaltrials.gov Identifier: NCT00915018.

Induction of Heme Oxygenase-1 Deficiency and Associated Glutamate-Mediated Neurotoxicity Is a Highly Conserved HIV Phenotype of Chronic Macrophage Infection That Is Resistant to Antiretroviral Therapy.

PubMed

Gill, Alexander J; Kovacsics, Colleen E; Vance, Patricia J; Collman, Ronald G; Kolson, Dennis L

2015-10-01

Expression of the cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly reduced in the brain prefrontal cortex of HIV-positive individuals with HIV-associated neurocognitive disorders (HAND). Furthermore, this HO-1 deficiency correlates with brain viral load, markers of macrophage activation, and type I interferon responses. In vitro, HIV replication in monocyte-derived macrophages (MDM) selectively reduces HO-1 protein and RNA expression and induces production of neurotoxic levels of glutamate; correction of this HO-1 deficiency reduces neurotoxic glutamate production without an effect on HIV replication. We now demonstrate that macrophage HO-1 deficiency, and the associated neurotoxin production, is a conserved feature of infection with macrophage-tropic HIV-1 strains that correlates closely with the extent of replication, and this feature extends to HIV-2 infection. We further demonstrate that this HO-1 deficiency does not depend specifically upon the HIV-1 accessory genes nef, vpr, or vpu but rather on HIV replication, even when markedly limited. Finally, antiretroviral therapy (ART) applied to MDM after HIV infection is established does not prevent HO-1 loss or the associated neurotoxin production. This work defines a predictable relationship between HIV replication, HO-1 loss, and neurotoxin production in MDM that likely reflects processes in place in the HIV-infected brains of individuals receiving ART. It further suggests that correcting this HO-1 deficiency in HIV-infected MDM could provide neuroprotection above that provided by current ART or proposed antiviral therapies directed at limiting Nef, Vpr, or Vpu functions. The ability of HIV-2 to reduce HO-1 expression suggests that this is a conserved phenotype among macrophage-tropic human immunodeficiency viruses that could contribute to neuropathogenesis. The continued prevalence of HIV-associated neurocognitive disorders (HAND) underscores the need for adjunctive therapy that targets the neuropathological processes that persist in antiretroviral therapy (ART)-treated HIV-infected individuals. To this end, we previously identified one such possible process, a deficiency of the antioxidative and anti-inflammatory enzyme heme oxygenase-1 (HO-1) in the brains of individuals with HAND. In the present study, our findings suggest that the HO-1 deficiency associated with excess glutamate production and neurotoxicity in HIV-infected macrophages is a highly conserved phenotype of macrophage-tropic HIV strains and that this phenotype can persist in the macrophage compartment in the presence of ART. This suggests a plausible mechanism by which HIV infection of brain macrophages in ART-treated individuals could exacerbate oxidative stress and glutamate-induced neuronal injury, each of which is associated with neurocognitive dysfunction in infected individuals. Thus, therapies that rescue the HO-1 deficiency in HIV-infected individuals could provide additional neuroprotection to ART. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2005-06-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abiraterone acetate, acyline, adalimumab, adenosine triphosphate, AEE-788, AIDSVAX gp120 B/B, AK-602, alefacept, alemtuzumab, alendronic acid sodium salt, alicaforsen sodium, alprazolam, amdoxovir, AMG-162, aminolevulinic acid hydrochloride, aminolevulinic acid methyl ester, aminophylline hydrate, anakinra, anecortave acetate, anti-CTLA-4 MAb, APC-8015, aripiprazole, aspirin, atazanavir sulfate, atomoxetine hydrochloride, atorvastatin calcium, atrasentan, AVE-5883, AZD-2171; Betamethasone dipropionate, bevacizumab, bimatoprost, biphasic human insulin (prb), bortezomib, BR-A-657, BRL-55730, budesonide, busulfan; Calcipotriol, calcipotriol/betamethasone dipropionate, calcium folinate, capecitabine, capravirine, carmustine, caspofungin acetate, cefdinir, certolizumab pegol, CG-53135, chlorambucil, ciclesonide, ciclosporin, cisplatin, clofarabine, clopidogrel hydrogensulfate, clozapine, co-trimoxazole, CP-122721, creatine, CY-2301, cyclophosphamide, cypher, cytarabine, cytolin; D0401, darbepoetin alfa, darifenacin hydrobromide, DASB, desipramine hydrochloride, desloratadine, desvenlafaxine succinate, dexamethasone, didanosine, diquafosol tetrasodium, docetaxel, doxorubicin hydrochloride, drotrecogin alfa (activated), duloxetine hydrochloride, dutasteride; Ecallantide, efalizumab, efavirenz, eletriptan, emtricitabine, enfuvirtide, enoxaparin sodium, estramustine phosphate sodium, etanercept, ethinylestradiol, etonogestrel, etonogestrel/ethinylestradiol, etoposide, exenatide; Famciclovir, fampridine, febuxostat, filgrastim, fludarabine phosphate, fluocinolone acetonide, fluorouracil, fluticasone propionate, fluvastatin sodium, fondaparinux sodium; Gaboxadol, gamma-hydroxybutyrate sodium, gefitinib, gelclair, gemcitabine, gemfibrozil, glibenclamide, glyminox; Haloperidol, heparin sodium, HPV 16/HPV 18 vaccine, human insulin, human insulin; Icatibant, imatinib mesylate, indium 111 (111In) ibritumomab tiuxetan, infliximab, INKP-100, iodine (I131) tositumomab, IoGen, ipratropium bromide, ixabepilone; L-870810, lamivudine, lapatinib, laquinimod, latanoprost, levonorgestrel, licochalcone a, liposomal doxorubicin, lopinavir, lopinavir/ritonavir, lorazepam, lovastatin; Maraviroc, maribavir, matuzumab, MDL-100907, melphalan, methotrexate, methylprednisolone, mitomycin, mitoxantrone hydrochloride, MK-0431, MN-001, MRKAd5 HIV-1 gag/pol/nef, MRKAd5gag, MVA.HIVA, MVA-BN Nef, MVA-Muc1-IL-2, mycophenolate mofetil; Nelfinavir mesilate, nesiritide, NSC-330507; Olanzapine, olmesartan medoxomil, omalizumab, oral insulin, osanetant; PA-457, paclitaxel, paroxetine, paroxetine hydrochloride, PCK-3145, PEG-filgrastim, peginterferon alfa-2a, peginterferon alfa-2b, perillyl alcohol, pexelizumab, pimecrolimus, pitavastatin calcium, porfiromycin, prasterone, prasugrel, pravastatin sodium, prednisone, pregabalin, prinomastat, PRO-2000, propofol, prostate cancer vaccine; Rasagiline mesilate, rhBMP-2/ACS, rhBMP-2/BCP, rhC1, ribavirin, rilpivirine, ritonavir, rituximab, Ro-26-9228, rosuvastatin calcium, rosuvastatin sodium, rubitecan; Selodenoson, simvastatin, sirolimus, sitaxsentan sodium, sorafenib, SS(dsFv)-PE38, St. John's Wort extract, stavudine; Tacrolimus, tadalafil, tafenoquine succinate, talaglumetad, tanomastat, taxus, tegaserod maleate, telithromycin, tempol, tenofovir, tenofovir disoproxil fumarate, testosterone enanthate, TH-9507, thalidomide, tigecycline, timolol maleate, tiotropium bromide, tipifarnib, torcetrapib, trabectedin, travoprost, travoprost/timolol, treprostinil sodium; Valdecoxib, vardenafil hydrochloride hydrate, varenicline, VEGF-2 gene therapy, venlafaxine hydrochloride, vildagliptin, vincristine sulfate, voriconazole, VRX-496, VX-385; Warfarin sodium; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Zanolimumab, zidovudine. Copyright (c) 2005 Prous Science. All rights reserved.

Energy Engineering Analysis Program. Lighting Survey of Selected Buildings, Pine Bluff Arsenal, Pine Bluff, Arkansas. Volume 2A: Appendices

DTIC Science & Technology

1995-06-01

Energy efficient, 30 and 40 watt ballasts are Rapid Start, thermally protected, automatic resetting. Class P, high or low power factor as required...BALLASTS Energy efficient, 30 ana 40 watt Rapic Start, thermally protected, automatic resetting. Class P. high power factor, CEM, sound rated A. unless...BALLASTS Energy efficient, 40 Watt Rapid Start, thermally protected, automatic resetting, Class P, high power factor, CBM, sound rated A, unless

Total Factor Productivity Growth, Technical Progress & Efficiency Change in Vietnam Coal Industry - Nonparametric Approach

NASA Astrophysics Data System (ADS)

Phuong, Vu Hung

2018-03-01

This research applies Data Envelopment Analysis (DEA) approach to analyze Total Factor Productivity (TFP) and efficiency changes in Vietnam coal mining industry from 2007 to 2013. The TFP of Vietnam coal mining companies decreased due to slow technological progress and unimproved efficiency. The decadence of technical efficiency in many enterprises proved that the coal mining industry has a large potential to increase productivity through technical efficiency improvement. Enhancing human resource training, technology and research & development investment could help the industry to improve efficiency and productivity in Vietnam coal mining industry.

10 CFR 430.62 - Submission of data.

Code of Federal Regulations, 2010 CFR

2010-01-01

... energy factor expressed in cycles per kilowatt-hour. (vii) Faucets, the maximum water use in gpm (L/min... seasonal energy efficiency ratio and heating seasonal performance factor. For central air conditioning heat pumps whose seasonal energy efficiency ratio and heating seasonal performance factor are based on an...

Attitudes of clinician educators towards interprofessional education and collaboration: Insights from two interprofessional scales.

PubMed

Ong, Sik Yin; Tan, Nigel C K; Knab, Mary S; Farrell, Susan E; Lim, Wee Shiong

2017-09-01

The increasing complexity of healthcare needs underlines the growing importance of interprofessional education and collaborative practice (IPECP) in enhancing quality of patient care. In particular, clinician educators play an influential role in advocating IPECP. The primary goal of our exploratory pilot study is to explore 34 clinician educators' attitudes towards IPECP by using the adapted 14-item Attitudes Toward Health Care Teams Scale (ATHCTS) and 15-item Readiness for Interprofessional Learning Scale (RIPLS). Mean scores of ATHCTS and RIPLS were 3.81 (SD = 0.90) and 4.02 (SD = 0.79), respectively. Using exploratory factor analysis, we identified four factors: team value (ATHCTS), team efficiency (ATHCTS), teamwork and collaboration (RIPLS), and professional socialisation (RIPLS). The "team efficiency" factor on the ATHCTS scored lowest (factor mean = 3.49) compared with other factors (factor means = 3.87-4.08). Correlation analyses revealed that the "team efficiency" factor had small correlations with other factors (r = -0.05-0.37). Our clinician educators valued IPECP in promoting teamwork and professional socialisation but they perceived IPECP to compromise efficiency. The issue of perceived inefficiency by clinician educators merits attention in order to promote wider implementation of IPECP.

Theoretical Bound of CRLB for Energy Efficient Technique of RSS-Based Factor Graph Geolocation

NASA Astrophysics Data System (ADS)

Kahar Aziz, Muhammad Reza; Heriansyah; Saputra, EfaMaydhona; Musa, Ardiansyah

2018-03-01

To support the increase of wireless geolocation development as the key of the technology in the future, this paper proposes theoretical bound derivation, i.e., Cramer Rao lower bound (CRLB) for energy efficient of received signal strength (RSS)-based factor graph wireless geolocation technique. The theoretical bound derivation is crucially important to evaluate whether the energy efficient technique of RSS-based factor graph wireless geolocation is effective as well as to open the opportunity to further innovation of the technique. The CRLB is derived in this paper by using the Fisher information matrix (FIM) of the main formula of the RSS-based factor graph geolocation technique, which is lied on the Jacobian matrix. The simulation result shows that the derived CRLB has the highest accuracy as a bound shown by its lowest root mean squared error (RMSE) curve compared to the RMSE curve of the RSS-based factor graph geolocation technique. Hence, the derived CRLB becomes the lower bound for the efficient technique of RSS-based factor graph wireless geolocation.

How Can Health System Efficiency Be Improved in Canada?

PubMed Central

Allin, Sara; Veillard, Jeremy; Wang, Li; Grignon, Michel

2015-01-01

Improving value for money in the health system is an often-stated policy goal. This study is the first to systematically measure the efficiency of health regions in Canada in producing health gains with their available resources, and to identify the factors that are associated with increased efficiency. Based on the objective elicited from decision-makers that the health system should ensure access to care for Canadians when they need it, we measured the efficiency with which regions reduce causes of death that are amenable to healthcare interventions using a linear programming approach (data envelopment analysis). Variations in efficiency were explained in part by public health factors, such as the prevalence of obesity and smoking in the population; in part by characteristics of the population, such as their average income; and in part by managerial factors, such as hospital readmissions. PMID:26571467

Supernovae Discovery Efficiency

NASA Astrophysics Data System (ADS)

John, Colin

2018-01-01

Abstract:We present supernovae (SN) search efficiency measurements for recent Hubble Space Telescope (HST) surveys. Efficiency is a key component to any search, and is important parameter as a correction factor for SN rates. To achieve an accurate value for efficiency, many supernovae need to be discoverable in surveys. This cannot be achieved from real SN only, due to their scarcity, so fake SN are planted. These fake supernovae—with a goal of realism in mind—yield an understanding of efficiency based on position related to other celestial objects, and brightness. To improve realism, we built a more accurate model of supernovae using a point-spread function. The next improvement to realism is planting these objects close to galaxies and of various parameters of brightness, magnitude, local galactic brightness and redshift. Once these are planted, a very accurate SN is visible and discoverable by the searcher. It is very important to find factors that affect this discovery efficiency. Exploring the factors that effect detection yields a more accurate correction factor. Further inquires into efficiency give us a better understanding of image processing, searching techniques and survey strategies, and result in an overall higher likelihood to find these events in future surveys with Hubble, James Webb, and WFIRST telescopes. After efficiency is discovered and refined with many unique surveys, it factors into measurements of SN rates versus redshift. By comparing SN rates vs redshift against the star formation rate we can test models to determine how long star systems take from the point of inception to explosion (delay time distribution). This delay time distribution is compared to SN progenitors models to get an accurate idea of what these stars were like before their deaths.

Assessment of Labor Behavior Factors and Selecting Line Managers' Lines of Development at Russian Industrial Enterprises

ERIC Educational Resources Information Center

Zavyalova, Elena K.; Kosheleva, Sofia V.

2009-01-01

Purpose: The paper investigates personal and environmental factors providing for the efficiency of line managers' activity and contributing to their professional and career advancement. The paper studies the prognostic value of the assessment of personal and environmental factors providing for the efficiency of line managers' activity according to…

How Can Health System Efficiency Be Improved in Canada?

PubMed

Allin, Sara; Veillard, Jeremy; Wang, Li; Grignon, Michel

2015-08-01

Improving value for money in the health system is an often-stated policy goal. This study is the first to systematically measure the efficiency of health regions in Canada in producing health gains with their available resources, and to identify the factors that are associated with increased efficiency. Based on the objective elicited from decision-makers that the health system should ensure access to care for Canadians when they need it, we measured the efficiency with which regions reduce causes of death that are amenable to healthcare interventions using a linear programming approach (data envelopment analysis). Variations in efficiency were explained in part by public health factors, such as the prevalence of obesity and smoking in the population; in part by characteristics of the population, such as their average income; and in part by managerial factors, such as hospital readmissions. Copyright © 2015 Longwoods Publishing.

Research on the influencing factors of financing efficiency of big data industry based on panel data model--Empirical evidence from Guizhou province

NASA Astrophysics Data System (ADS)

Li, Chenggang; Feng, Yujia

2018-03-01

This paper mainly studies the influence factors of financing efficiency of Guizhou big data industry, and selects the financial and macro data of 20 Guizhou big data enterprises from 2010 to 2016. Using the DEA model to obtain the financing efficiency of Guizhou big data enterprises. A panel data model is constructed to select the six macro and micro influencing factors for panel data analysis. The results show that the external economic environment, the turnover rate of the total assets of the enterprises, the increase of operating income, the increase of the revenue per share of each share of the business income have positive impact on the financing efficiency of of the big data industry in Guizhou. The key to improve the financing efficiency of Guizhou big data enterprises is to improve.

Analysis of regional total factor energy efficiency in China under environmental constraints: based on undesirable-minds and DEA window model

NASA Astrophysics Data System (ADS)

Zhang, Shuying; Li, Deshan; Li, Shuangqiang; Jiang, Hanyu; Shen, Yuqing

2017-06-01

With China’s entrance into the new economy, the improvement of energy efficiency has become an important indicator to measure the quality of ecological civilization construction and economic development. According to the panel data of Chinese regions in 1996-2014, the nearest distance to the efficient frontier of Undesirable-MinDS Xeon model and DEA window model have been used to calculate the total factor energy efficiency of China’s regions. Study found that: Under environmental constraints, China’s total factor energy efficiency has increased after the first drop in the overall 1996-2014, and then increases again. And the difference between the regions is very large, showing a characteristic of “the east is the highest, the west is lower, and lowest is in the central” finally, this paper puts forward relevant policy suggestions.

Factors influencing foraging search efficiency: why do scarce lappet-faced vultures outperform ubiquitous white-backed vultures?

PubMed

Spiegel, Orr; Getz, Wayne M; Nathan, Ran

2013-05-01

The search phase is a critical component of foraging behavior, affecting interspecific competition and community dynamics. Nevertheless, factors determining interspecific variation in search efficiency are still poorly understood. We studied differences in search efficiency between the lappet-faced vulture (Torgos tracheliotus; LFV) and the white-backed vulture (Gyps africanus; WBV) foraging on spatiotemporally unpredictable carcasses in Etosha National Park, Namibia. We used experimental food supply and high-resolution GPS tracking of free-ranging vultures to quantify search efficiency and elucidate the factors underlying the observed interspecific differences using a biased correlated random walk simulation model bootstrapped with the GPS tracking data. We found that LFV's search efficiency was higher than WBV's in both first-to-find, first-to-land, and per-individual-finding rate measures. Modifying species-specific traits in the simulation model allows us to assess the relative role of each factor in LFV's higher efficiency. Interspecific differences in morphology (through the effect on perceptual range and motion ability) and searchers' spatial dispersion (due to different roost arrangements) are in correspondence with the empirically observed advantage of LFV over WBV searchers, whereas differences in other aspects of the movement patterns appear to play a minor role. Our results provide mechanistic explanations for interspecific variation in search efficiency for species using similar resources and foraging modes.

Fundamental x-ray interaction limits in diagnostic imaging detectors: frequency-dependent Swank noise.

PubMed

Hajdok, G; Battista, J J; Cunningham, I A

2008-07-01

A frequency-dependent x-ray Swank factor based on the "x-ray interaction" modulation transfer function and normalized noise power spectrum is determined from a Monte Carlo analysis. This factor was calculated in four converter materials: amorphous silicon (a-Si), amorphous selenium (a-Se), cesium iodide (CsI), and lead iodide (PbI2) for incident photon energies between 10 and 150 keV and various converter thicknesses. When scaled by the quantum efficiency, the x-ray Swank factor describes the best possible detective quantum efficiency (DQE) a detector can have. As such, this x-ray interaction DQE provides a target performance benchmark. It is expressed as a function of (Fourier-based) spatial frequency and takes into consideration signal and noise correlations introduced by reabsorption of Compton scatter and photoelectric characteristic emissions. It is shown that the x-ray Swank factor is largely insensitive to converter thickness for quantum efficiency values greater than 0.5. Thus, while most of the tabulated values correspond to thick converters with a quantum efficiency of 0.99, they are appropriate to use for many detectors in current use. A simple expression for the x-ray interaction DQE of digital detectors (including noise aliasing) is derived in terms of the quantum efficiency, x-ray Swank factor, detector element size, and fill factor. Good agreement is shown with DQE curves published by other investigators for each converter material, and the conditions required to achieve this ideal performance are discussed. For high-resolution imaging applications, the x-ray Swank factor indicates: (i) a-Si should only be used at low-energy (e.g., mammography); (ii) a-Se has the most promise for any application below 100 keV; and (iii) while quantum efficiency may be increased at energies just above the K edge in CsI and PbI2, this benefit is offset by a substantial drop in the x-ray Swank factor, particularly at high spatial frequencies.

For AAPT: Teaching the Wave Mechanics of McLeods' Stringy Electron, Explicit Nucleons, and Through-the-Earth Projections of Constellations' Stick Figures

NASA Astrophysics Data System (ADS)

McLeod, David Matthew

2011-11-01

McLeods' NEF11#22 submission is from their same-title INVITED presentation at Frontiers in Optics 2011, San Jose, CA. It shows how Hooke's law for electron, proton and neutron strings build electromagnetic waves from strings. These are composed of spirally linked, parallel, north-pole oriented, neutrino and antineutrino strings, stable because of magnetic repulsions. Their Dumbo Proton is antineutrino-scissor cut, and compressed in the vicinity of a neutron star, where electrostatic marriage occurs with a neutrino-scissor cut, and compressed, electron, so a Mickey Neutron emerges. Strings then predict electron charge is -- 1/3 e, Dumbo P is 25 % longer than Mickey N, and Hooke says relaxing springs fuel three separate inflations after each Big Bang oscillation. Gravity can be strings longitudinally linked. Einstein says Herman Grid's black diagonals prove human vision reads its information from algebraically-signed electromagnetic field diffraction patterns known by ray-tracing, not difficult Spatial Fourier Transformation. High-schoolers understand its application to Wave Mechanics, and agree that positive-numbered probabilities do not enter to possibly displease God. Stick figure constellations detected, like Phoenix, Leo, Canis Major, and especially Orion, fool some observers into false beliefs in things like UFHumanoids, or Kokopelli, Pele and Pamola!

CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription

PubMed Central

Carlson, Jonathan; Yan, Jiyu; Akinsiku, Olusimidele T.; Schaefer, Malinda; Sabbaj, Steffanie; Bet, Anne; Levy, David N.; Heath, Sonya; Tang, Jianming; Kaslow, Richard A.; Walker, Bruce D.; Ndung’u, Thumbi; Goulder, Philip J.; Heckerman, David; Hunter, Eric; Goepfert, Paul A.

2010-01-01

Retroviruses pack multiple genes into relatively small genomes by encoding several genes in the same genomic region with overlapping reading frames. Both sense and antisense HIV-1 transcripts contain open reading frames for known functional proteins as well as numerous alternative reading frames (ARFs). At least some ARFs have the potential to encode proteins of unknown function, and their antigenic properties can be considered as cryptic epitopes (CEs). To examine the extent of active immune response to virally encoded CEs, we analyzed human leukocyte antigen class I–associated polymorphisms in HIV-1 gag, pol, and nef genes from a large cohort of South Africans with chronic infection. In all, 391 CEs and 168 conventional epitopes were predicted, with the majority (307; 79%) of CEs derived from antisense transcripts. In further evaluation of CD8 T cell responses to a subset of the predicted CEs in patients with primary or chronic infection, both sense- and antisense-encoded CEs were immunogenic at both stages of infection. In addition, CEs often mutated during the first year of infection, which was consistent with immune selection for escape variants. These findings indicate that the HIV-1 genome might encode and deploy a large potential repertoire of unconventional epitopes to enhance vaccine-induced antiviral immunity. PMID:20065064

Role of carrier density and disorder on anisotropic charge transport in polypyrrole

NASA Astrophysics Data System (ADS)

Varade, Vaibhav; Anjaneyulu, P.; Suchand Sangeeth, C. S.; Ramesh, K. P.; Menon, Reghu

2013-01-01

Polypyrrole (PPy) has been synthesized electrochemically on platinum substrate by varying synthesis temperature and dopant concentration. The charge transport in PPy has been investigated as a function of temperature for both in-plane and out-of-plane geometry in a wide temperature range of 5 K-300 K. The charge transport showed strong anisotropy and various mechanisms were used to explain the transport. The conductivity ratio, σr = σ(300 K)/σ(5 K) is calculated for each sample to quantify the relative disorder. At all the temperatures, the conductivity values for in-plane transport are found to be more for PPy synthesized at lower temperature, while the behavior is found to be different for out-of-plane transport. The carrier density is found to play a crucial role in case of in-plane transport. An effort has been made to correlate charge transport to morphology by analyzing temperature and frequency dependence of conductivity. Charge transport in lateral direction is found to be dominated by hopping whereas tunneling mechanisms are dominated in vertical direction. Parameters such as density of states at the Fermi level [N(EF)], average hopping distance (R), and average hopping energy (W) have been estimated for each samples in both geometry.

Epithelium-Innate Immune Cell Axis in Mucosal Responses to SIV

PubMed Central

Shang, L.; Duan, L.; Perkey, K. E.; Wietgrefe, S.; Zupancic, M.; Smith, A. J.; Southern, P. J.; Johnson, R. P.; Haase, A. T.

2016-01-01

In the SIV-rhesus macaque model of HIV-1 transmission to women, one hallmark of the mucosal response to exposure to high doses of SIV is CD4 T cell recruitment that fuels local virus expansion in early infection. In this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede CD4 T cell recruitment. We show that vaginal exposure to the SIV inoculum rapidly induces chemokine expression in cervical epithelium including CCL3, CCL20, and CXCL8. The chemokine expression is associated with early recruitment of macrophages and plasmacytoid dendritic cells that are co-clustered underneath the cervical epithelium. Production of chemokines CCL3 and CXCL8 by these cells in turn generates a chemokine gradient that is spatially correlated with the recruitment of CD4 T cells. We further show that the protection of SIVmac239Δnef vaccination against vaginal challenge is correlated with the absence of this epithelium-innate immune cell-CD4 T cell axis response in the cervical mucosa. Our results reveal a critical role for cervical epithelium in initiating early mucosal responses to vaginal infection, highlight an important role for macrophages in target cell recruitment and provide further evidence of a paradoxical dampening effect of a protective vaccine on these early mucosal responses. PMID:27435105

CD4-gp120 interaction interface - a gateway for HIV-1 infection in human: molecular network, modeling and docking studies.

PubMed

Pandey, Deeksha; Podder, Avijit; Pandit, Mansi; Latha, Narayanan

2017-09-01

The major causative agent for Acquired Immune Deficiency Syndrome (AIDS) is Human Immunodeficiency Virus-1 (HIV-1). HIV-1 is a predominant subtype of HIV which counts on human cellular mechanism virtually in every aspect of its life cycle. Binding of viral envelope glycoprotein-gp120 with human cell surface CD4 receptor triggers the early infection stage of HIV-1. This study focuses on the interaction interface between these two proteins that play a crucial role for viral infectivity. The CD4-gp120 interaction interface has been studied through a comprehensive protein-protein interaction network (PPIN) analysis and highlighted as a useful step towards identifying potential therapeutic drug targets against HIV-1 infection. We prioritized gp41, Nef and Tat proteins of HIV-1 as valuable drug targets at early stage of viral infection. Lack of crystal structure has made it difficult to understand the biological implication of these proteins during disease progression. Here, computational protein modeling techniques and molecular dynamics simulations were performed to generate three-dimensional models of these targets. Besides, molecular docking was initiated to determine the desirability of these target proteins for already available HIV-1 specific drugs which indicates the usefulness of these protein structures to identify an effective drug combination therapy against AIDS.

Human Immunodeficiency Virus Proteins Mimic Human T Cell Receptors Inducing Cross-Reactive Antibodies

PubMed Central

2017-01-01

Human immunodeficiency virus (HIV) hides from the immune system in part by mimicking host antigens, including human leukocyte antigens. It is demonstrated here that HIV also mimics the V-β-D-J-β of approximately seventy percent of about 600 randomly selected human T cell receptors (TCR). This degree of mimicry is greater than any other human pathogen, commensal or symbiotic organism studied. These data suggest that HIV may be evolving into a commensal organism just as simian immunodeficiency virus has done in some types of monkeys. The gp120 envelope protein, Nef protein and Pol protein are particularly similar to host TCR, camouflaging HIV from the immune system and creating serious barriers to the development of safe HIV vaccines. One consequence of HIV mimicry of host TCR is that antibodies against HIV proteins have a significant probability of recognizing the corresponding TCR as antigenic targets, explaining the widespread observation of lymphocytotoxic autoantibodies in acquired immunodeficiency syndrome (AIDS). Quantitative enzyme-linked immunoadsorption assays (ELISA) demonstrated that every HIV antibody tested recognized at least one of twelve TCR, and as many as seven, with a binding constant in the 10−8 to 10−9 m range. HIV immunity also affects microbiome tolerance in ways that correlate with susceptibility to specific opportunistic infections. PMID:28972547

Binding efficiency of recombinant collagen-binding basic fibroblast growth factors (CBD-bFGFs) and their promotion for NIH-3T3 cell proliferation.

PubMed

Wu, Zhenxu; Zhou, Yulai; Chen, Li; Hu, Mingxin; Wang, Yu; Li, Linlong; Wang, Zongliang; Zhang, Peibiao

2018-03-01

The recombinant basic fibroblast growth factor (bFGF) containing collagen-binding domain (CBD) has been found to be a potential therapeutic factor in tissue regeneration. However, its binding efficiency and quantification remain uncertain. In this research, massive recombinant bFGFs with good bioactivity for enhancing the proliferation of NIH-3T3 cells were achieved. An ELISA-based quantitative method was set up to investigate the binding efficiency of CBD-bFGFs on collagen films. It indicated that the CBDs significantly increased the collagen-binding ability of bFGF (P < .05), with the optimum binding condition first determined to be in the pH range of 7.5-9.5 (P < .05). Then, the relevant equations to calculate the binding density of bFGF, C-bFGF, and V-bFGF were acquired. Analysis confirmed that the bioactivity of immobilized bFGFs was well correlated with the density of growth factor on collagen films. Based on this research, the density of growth factor is a logical and applicable dosage unit for quantification of binding efficiency of growth factors, rather than traditional concentration of soluble growth factors in tissue engineering applications. © 2018 Wiley Periodicals, Inc.

Excessive Cellular Proliferation Negatively Impacts Reprogramming Efficiency of Human Fibroblasts

PubMed Central

Gupta, Manoj K.; Teo, Adrian Kee Keong; Rao, Tata Nageswara; Bhatt, Shweta; Kleinridders, Andre; Shirakawa, Jun; Takatani, Tomozumi; Hu, Jiang; De Jesus, Dario F.; Windmueller, Rebecca; Wagers, Amy J.

2015-01-01

The impact of somatic cell proliferation rate on induction of pluripotent stem cells remains controversial. Herein, we report that rapid proliferation of human somatic fibroblasts is detrimental to reprogramming efficiency when reprogrammed using a lentiviral vector expressing OCT4, SOX2, KLF4, and cMYC in insulin-rich defined medium. Human fibroblasts grown in this medium showed higher proliferation, enhanced expression of insulin signaling and cell cycle genes, and a switch from glycolytic to oxidative phosphorylation metabolism, but they displayed poor reprogramming efficiency compared with cells grown in normal medium. Thus, in contrast to previous studies, our work reveals an inverse correlation between the proliferation rate of somatic cells and reprogramming efficiency, and also suggests that upregulation of proteins in the growth factor signaling pathway limits the ability to induce pluripotency in human somatic fibroblasts. Significance The efficiency with which human cells can be reprogrammed is of interest to stem cell biology. In this study, human fibroblasts cultured in media containing different concentrations of growth factors such as insulin and insulin-like growth factor-1 exhibited variable abilities to proliferate, with consequences on pluripotency. This occurred in part because of changes in the expression of proteins involved in the growth factor signaling pathway, glycolysis, and oxidative phosphorylation. These findings have implications for efficient reprogramming of human cells. PMID:26253715

Time-invariant component-based normalization for a simultaneous PET-MR scanner.

PubMed

Belzunce, M A; Reader, A J

2016-05-07

Component-based normalization is a method used to compensate for the sensitivity of each of the lines of response acquired in positron emission tomography. This method consists of modelling the sensitivity of each line of response as a product of multiple factors, which can be classified as time-invariant, time-variant and acquisition-dependent components. Typical time-variant factors are the intrinsic crystal efficiencies, which are needed to be updated by a regular normalization scan. Failure to do so would in principle generate artifacts in the reconstructed images due to the use of out of date time-variant factors. For this reason, an assessment of the variability and the impact of the crystal efficiencies in the reconstructed images is important to determine the frequency needed for the normalization scans, as well as to estimate the error obtained when an inappropriate normalization is used. Furthermore, if the fluctuations of these components are low enough, they could be neglected and nearly artifact-free reconstructions become achievable without performing a regular normalization scan. In this work, we analyse the impact of the time-variant factors in the component-based normalization used in the Biograph mMR scanner, but the work is applicable to other PET scanners. These factors are the intrinsic crystal efficiencies and the axial factors. For the latter, we propose a new method to obtain fixed axial factors that was validated with simulated data. Regarding the crystal efficiencies, we assessed their fluctuations during a period of 230 d and we found that they had good stability and low dispersion. We studied the impact of not including the intrinsic crystal efficiencies in the normalization when reconstructing simulated and real data. Based on this assessment and using the fixed axial factors, we propose the use of a time-invariant normalization that is able to achieve comparable results to the standard, daily updated, normalization factors used in this scanner. Moreover, to extend the analysis to other scanners, we generated distributions of crystal efficiencies with greater fluctuations than those found in the Biograph mMR scanner and evaluated their impact in simulations with a wide variety of noise levels. An important finding of this work is that a regular normalization scan is not needed in scanners with photodetectors with relatively low dispersion in their efficiencies.

Time-invariant component-based normalization for a simultaneous PET-MR scanner

NASA Astrophysics Data System (ADS)

Belzunce, M. A.; Reader, A. J.

2016-05-01

Component-based normalization is a method used to compensate for the sensitivity of each of the lines of response acquired in positron emission tomography. This method consists of modelling the sensitivity of each line of response as a product of multiple factors, which can be classified as time-invariant, time-variant and acquisition-dependent components. Typical time-variant factors are the intrinsic crystal efficiencies, which are needed to be updated by a regular normalization scan. Failure to do so would in principle generate artifacts in the reconstructed images due to the use of out of date time-variant factors. For this reason, an assessment of the variability and the impact of the crystal efficiencies in the reconstructed images is important to determine the frequency needed for the normalization scans, as well as to estimate the error obtained when an inappropriate normalization is used. Furthermore, if the fluctuations of these components are low enough, they could be neglected and nearly artifact-free reconstructions become achievable without performing a regular normalization scan. In this work, we analyse the impact of the time-variant factors in the component-based normalization used in the Biograph mMR scanner, but the work is applicable to other PET scanners. These factors are the intrinsic crystal efficiencies and the axial factors. For the latter, we propose a new method to obtain fixed axial factors that was validated with simulated data. Regarding the crystal efficiencies, we assessed their fluctuations during a period of 230 d and we found that they had good stability and low dispersion. We studied the impact of not including the intrinsic crystal efficiencies in the normalization when reconstructing simulated and real data. Based on this assessment and using the fixed axial factors, we propose the use of a time-invariant normalization that is able to achieve comparable results to the standard, daily updated, normalization factors used in this scanner. Moreover, to extend the analysis to other scanners, we generated distributions of crystal efficiencies with greater fluctuations than those found in the Biograph mMR scanner and evaluated their impact in simulations with a wide variety of noise levels. An important finding of this work is that a regular normalization scan is not needed in scanners with photodetectors with relatively low dispersion in their efficiencies.

Power factor regulation for household usage

NASA Astrophysics Data System (ADS)

Daud, Nik Ghazali Nik; Hashim, Fakroul Ridzuan; Tarmizi, Muhammad Haziq Ahmad

2018-02-01

Power factor regulator technology has recently drawn attention to the consumer and to power generation company in order for consumers to use electricity efficiently. Controlling of power factor for efficient usage can reduce the production of power in fulfilment demands hence reducing the greenhouse effect. This paper presents the design method of power factor controller for household usage. There are several methods to improve the power factor. The power factor controller used by this method is by using capacitors. Total harmonic distortion also has become a major problem for the reliability of the electrical appliances and techniques to control it will be discussed.

Changes in agricultural carbon emissions and factors that influence agricultural carbon emissions based on different stages in Xinjiang, China

NASA Astrophysics Data System (ADS)

Xiong, Chuanhe; Yang, Degang; Xia, Fuqiang; Huo, Jinwei

2016-11-01

Xinjiang’s agricultural carbon emissions showed three stages of change, i.e., continued to rise, declined and continued to rise, during 1991-2014. The agriculture belonged to the “low emissions and high efficiency” agriculture category, with a lower agricultural carbon emission intensity. By using the logarithmic mean divisia index decomposition method, agricultural carbon emissions were decomposed into an efficiency factor, a structure factor, an economy factor, and a labour factor. We divided the study period into five stages based on the changes in efficiency factor and economy factor. Xinjiang showed different agricultural carbon emission characteristics at different stages. The degree of impact on agricultural carbon emissions at these stages depended on the combined effect of planting-animal husbandry carbon intensity and agricultural labour productivity. The economy factor was the critical factor to promote the increase in agricultural carbon emissions, while the main inhibiting factor for agricultural carbon emissions was the efficiency factor. The labour factor became more and more obvious in increasing agricultural carbon emissions. Finally, we discuss policy recommendations in terms of the main factors, including the development of agricultural science and technology (S&T), the establishment of three major mechanisms and transfer of rural labour in ethnic areas.

Changes in agricultural carbon emissions and factors that influence agricultural carbon emissions based on different stages in Xinjiang, China

PubMed Central

Xiong, Chuanhe; Yang, Degang; Xia, Fuqiang; Huo, Jinwei

2016-01-01

Xinjiang’s agricultural carbon emissions showed three stages of change, i.e., continued to rise, declined and continued to rise, during 1991–2014. The agriculture belonged to the “low emissions and high efficiency” agriculture category, with a lower agricultural carbon emission intensity. By using the logarithmic mean divisia index decomposition method, agricultural carbon emissions were decomposed into an efficiency factor, a structure factor, an economy factor, and a labour factor. We divided the study period into five stages based on the changes in efficiency factor and economy factor. Xinjiang showed different agricultural carbon emission characteristics at different stages. The degree of impact on agricultural carbon emissions at these stages depended on the combined effect of planting-animal husbandry carbon intensity and agricultural labour productivity. The economy factor was the critical factor to promote the increase in agricultural carbon emissions, while the main inhibiting factor for agricultural carbon emissions was the efficiency factor. The labour factor became more and more obvious in increasing agricultural carbon emissions. Finally, we discuss policy recommendations in terms of the main factors, including the development of agricultural science and technology (S&T), the establishment of three major mechanisms and transfer of rural labour in ethnic areas. PMID:27830739

Analysis of recovery efficiency in high-temperature aquifer thermal energy storage: a Rayleigh-based method

NASA Astrophysics Data System (ADS)

Schout, Gilian; Drijver, Benno; Gutierrez-Neri, Mariene; Schotting, Ruud

2014-01-01

High-temperature aquifer thermal energy storage (HT-ATES) is an important technique for energy conservation. A controlling factor for the economic feasibility of HT-ATES is the recovery efficiency. Due to the effects of density-driven flow (free convection), HT-ATES systems applied in permeable aquifers typically have lower recovery efficiencies than conventional (low-temperature) ATES systems. For a reliable estimation of the recovery efficiency it is, therefore, important to take the effect of density-driven flow into account. A numerical evaluation of the prime factors influencing the recovery efficiency of HT-ATES systems is presented. Sensitivity runs evaluating the effects of aquifer properties, as well as operational variables, were performed to deduce the most important factors that control the recovery efficiency. A correlation was found between the dimensionless Rayleigh number (a measure of the relative strength of free convection) and the calculated recovery efficiencies. Based on a modified Rayleigh number, two simple analytical solutions are proposed to calculate the recovery efficiency, each one covering a different range of aquifer thicknesses. The analytical solutions accurately reproduce all numerically modeled scenarios with an average error of less than 3 %. The proposed method can be of practical use when considering or designing an HT-ATES system.

Set of Criteria for Efficiency of the Process Forming the Answers to Multiple-Choice Test Items

ERIC Educational Resources Information Center

Rybanov, Alexander Aleksandrovich

2013-01-01

Is offered the set of criteria for assessing efficiency of the process forming the answers to multiple-choice test items. To increase accuracy of computer-assisted testing results, it is suggested to assess dynamics of the process of forming the final answer using the following factors: loss of time factor and correct choice factor. The model…

Preparation and the influencing factors of timozolomide liposomes.

PubMed

Kong, Bin; Sun, Yong; Li, Yongjian; Hu, Dejian

2009-01-01

To prepare timozolomide liposomes for administration through nasal mucous membrane, we studied the factors of the preparation of the liposomes. The timozolomide liposomes were prepared by the ammonium sulphate gradient method; electroscopy and laser particle analyzer were utilized to determine the conformation, size and distribution of timozolomide liposomes; high performance liquid chromatography (HPLC) was applied to determine the entrapping efficiency of timozolomide liposomes; then we studied the influences of the concentration of ammonium sulphate solution, temperature, and the drug-to-lipid ratio on the entrapping efficiency. The average size of timozolomide liposomes was 185 nm; the entrapping efficiency was 90.3%. The entrapping efficiency was enhanced with the increasing of the concentration of ammonium sulphate solution and the rising of temperature, and decreased with the increasing of the drug-to-lipid ratio. The timozolomide liposomes with high entrapping efficiency, small and even particle sizes could be prepared by the simple and convenient ammonium sulphate gradient method. The primary influencing factors on the entrapping efficiency of timozolomide liposomes were the concentration of ammonium sulphate solution, the temperature, and the drug-to-lipid ratio.

INTEGRATION OF HEAT PUMPS IN PERVAPORATION SYSTEMS FOR IMPROVED ENERGY EFFICIENCY

EPA Science Inventory

The removal of organic compounds from water by pervaporation is highly energy efficient when the separation factor offered by the pervaporation process is high. In cases where the separation factor is relatively small, consequential amounts of water permeate the membrane per uni...

Latent human error analysis and efficient improvement strategies by fuzzy TOPSIS in aviation maintenance tasks.

PubMed

Chiu, Ming-Chuan; Hsieh, Min-Chih

2016-05-01

The purposes of this study were to develop a latent human error analysis process, to explore the factors of latent human error in aviation maintenance tasks, and to provide an efficient improvement strategy for addressing those errors. First, we used HFACS and RCA to define the error factors related to aviation maintenance tasks. Fuzzy TOPSIS with four criteria was applied to evaluate the error factors. Results show that 1) adverse physiological states, 2) physical/mental limitations, and 3) coordination, communication, and planning are the factors related to airline maintenance tasks that could be addressed easily and efficiently. This research establishes a new analytic process for investigating latent human error and provides a strategy for analyzing human error using fuzzy TOPSIS. Our analysis process complements shortages in existing methodologies by incorporating improvement efficiency, and it enhances the depth and broadness of human error analysis methodology. Copyright © 2015 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Industry Efficiency and Total Factor Productivity Growth under Resources and Environmental Constraint in China

PubMed Central

Tao, Feng; Li, Ling; Xia, X. H.

2012-01-01

The growth of China's industry has been seriously depending on energy and environment. This paper attempts to apply the directional distance function and the Luenberger productivity index to measure the environmental efficiency, environmental total factor productivity, and its components at the level of subindustry in China over the period from 1999 to 2009 while considering energy consumption and emission of pollutants. This paper also empirically examines the determinants of efficiency and productivity change. The major findings are as follows. Firstly, the main sources of environmental inefficiency of China's industry are the inefficiency of gross industrial output value, the excessive energy consumption, and pollutant emissions. Secondly, the highest growth rate of environmental total factor productivity among the three industrial categories is manufacturing, followed by mining, and production and supply of electricity, gas, and water. Thirdly, foreign direct investment, capital-labor ratio, ownership structure, energy consumption structure, and environmental regulation have varying degrees of effects on the environmental efficiency and environmental total factor productivity. PMID:23365517

Industry efficiency and total factor productivity growth under resources and environmental constraint in China.

PubMed

Tao, Feng; Li, Ling; Xia, X H

2012-01-01

The growth of China's industry has been seriously depending on energy and environment. This paper attempts to apply the directional distance function and the Luenberger productivity index to measure the environmental efficiency, environmental total factor productivity, and its components at the level of subindustry in China over the period from 1999 to 2009 while considering energy consumption and emission of pollutants. This paper also empirically examines the determinants of efficiency and productivity change. The major findings are as follows. Firstly, the main sources of environmental inefficiency of China's industry are the inefficiency of gross industrial output value, the excessive energy consumption, and pollutant emissions. Secondly, the highest growth rate of environmental total factor productivity among the three industrial categories is manufacturing, followed by mining, and production and supply of electricity, gas, and water. Thirdly, foreign direct investment, capital-labor ratio, ownership structure, energy consumption structure, and environmental regulation have varying degrees of effects on the environmental efficiency and environmental total factor productivity.

[Spectrum simulation based on data derived from red tide].

PubMed

Liu, Zhen-Yu; Cui, Ting-Wei; Yue, Jie; Jiang, Tao; Cao, Wen-Xi; Ma, Yi

2011-11-01

The present paper utilizes the absorption data of red tide water measured during the growing and dying course to retrieve imaginary part of the index of refraction based on Mie theory, carries out the simulation and analysis of average absorption efficiency factors, average backscattering efficiency factors and scattering phase function. The analysis of the simulation shows that Mie theory can be used to reproduce the absorption property of Chaetoceros socialis with an average error of 11%; the average backscattering efficiency factors depend on the value of absorption whose maximum value corresponds to the wavelength range from 400 to 700 nanometer; the average backscattering efficiency factors showed a maximum value on 17th with a low value during the outbreak of red tide and the minimum on 21th; the total scattering, weakly depending on the absorption, is proportional to the size parameters which represent the relative size of cell diameter with respect to the wavelength, while the angle scattering intensity is inversely proportional to wavelength.

Finding an emotional face in a crowd: emotional and perceptual stimulus factors influence visual search efficiency.

PubMed

Lundqvist, Daniel; Bruce, Neil; Öhman, Arne

2015-01-01

In this article, we examine how emotional and perceptual stimulus factors influence visual search efficiency. In an initial task, we run a visual search task, using a large number of target/distractor emotion combinations. In two subsequent tasks, we then assess measures of perceptual (rated and computational distances) and emotional (rated valence, arousal and potency) stimulus properties. In a series of regression analyses, we then explore the degree to which target salience (the size of target/distractor dissimilarities) on these emotional and perceptual measures predict the outcome on search efficiency measures (response times and accuracy) from the visual search task. The results show that both emotional and perceptual stimulus salience contribute to visual search efficiency. The results show that among the emotional measures, salience on arousal measures was more influential than valence salience. The importance of the arousal factor may be a contributing factor to contradictory history of results within this field.

HIV/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates

PubMed Central

García-Arriaza, Juan; Perdiguero, Beatriz; Heeney, Jonathan L.; Seaman, Michael S.; Montefiori, David C.; Yates, Nicole L.; Tomaras, Georgia D.; Ferrari, Guido; Foulds, Kathryn E.; Roederer, Mario; Self, Steven G.; Borate, Bhavesh; Gottardo, Raphael; Phogat, Sanjay; Tartaglia, Jim; Barnett, Susan W.; Burke, Brian; Cristillo, Anthony D.; Weiss, Deborah E.; Lee, Carter; Kibler, Karen V.; Jacobs, Bertram L.; Wagner, Ralf; Ding, Song; Pantaleo, Giuseppe

2017-01-01

ABSTRACT The nonreplicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120) and Gag-Pol-Nef antigens (NYVAC-C) showed limited immunogenicity in phase I clinical trials. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4+ and CD8+ T cells, here we compared the HIV-1-specific immunogenicity elicited in nonhuman primates immunized with two replicating NYVAC vectors that have been modified by the insertion of the K1L and C7L vaccinia virus host range genes and express the clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC). Additionally, one NYVAC-C-KC vector was generated by deleting the viral gene B19R, an inhibitor of the type I interferon response (NYVAC-C-KC-ΔB19R). An immunization protocol mimicking that of the RV144 phase III clinical trial was used. Two groups of macaques received two doses of the corresponding NYVAC-C-KC vectors (weeks 0 and 4) and booster doses with NYVAC-C-KC vectors plus the clade C HIV-1 gp120 protein (weeks 12 and 24). The two replicating NYVAC-C-KC vectors induced enhanced and similar HIV-1-specific CD4+ and CD8+ T cell responses, similar levels of binding IgG antibodies, low levels of IgA antibodies, and high levels of antibody-dependent cellular cytotoxicity responses and HIV-1-neutralizing antibodies. Small differences within the NYVAC-C-KC-ΔB19R group were seen in the magnitude of CD4+ and CD8+ T cells, the induction of some cytokines, and the neutralization of some HIV-1 isolates. Thus, replication-competent NYVAC-C-KC vectors acquired relevant immunological properties as vaccine candidates against HIV/AIDS, and the viral B19 molecule exerts some control of immune functions. IMPORTANCE It is of special importance to find a safe and effective HIV/AIDS vaccine that can induce strong and broad T cell and humoral immune responses correlating with HIV-1 protection. Here we developed novel replicating poxvirus NYVAC-based HIV/AIDS vaccine candidates expressing clade C HIV-1 antigens, with one of them lacking the vaccinia virus B19 protein, an inhibitor of the type I interferon response. Immunization of nonhuman primates with these novel NYVAC-C-KC vectors and the protein component gp120 elicited high levels of T cell and humoral immune responses, with the vector containing a deletion in B19R inducing a trend toward a higher magnitude of CD4+ and CD8+ T cell responses and neutralization of some HIV-1 strains. These poxvirus vectors could be considered HIV/AIDS vaccine candidates based on their activation of potential immune correlates of protection. PMID:28179536

Feed efficiency - how should it be used for the cow herd?

USDA-ARS?s Scientific Manuscript database

In cows, the most critical factor influencing the output component of efficiency is reproductive rate, and not necessarily weight gain. Thus benefits of selecting animals with desirable measures of feed efficiency on cow efficiency remain to be determined. The feed input component of cow efficiency...

Management and genetic factors affecting efficiency of cattle in a grazing environment

USDA-ARS?s Scientific Manuscript database

Much of current efforts to improve efficiency in cattle use measures of individual feed intake in combination with weight gain as an indication of efficiency. This approach provides pertinent information concerning efficiency during the growing phase, but the relationship to cow efficiency remains t...

The determinants of efficiency in the Canadian health care system.

PubMed

Allin, Sara; Grignon, Michel; Wang, Li

2016-01-01

In spite of the vast number of studies measuring economic efficiency in health care, there has been little take-up of this evidence by policy-makers to date. This study provides an illustration of how a system-level study drawing on best practice in empirical measurement of efficiency may be of practical use to health system decision makers and managers. We make use of the rich data available in Canada to undertake a robust two-stage data envelopment analysis to calculate efficiency at the regional (sub-provincial) level. Decisions about what the health system produces (the outcome to measure efficiency against) and what are the resources it has to produce that outcome were based on interviews and consultation with health system decision makers. Overall, we find large inefficiencies in the Canadian health care system, which could improve outcomes (here, measured as a reduction in treatable causes of death) by between 18 and 35% across our analyses. Also, we find that inefficiencies are the result of three main sets of factors that policy makers could pay attention to: management factors, such as hospital re-admissions; public health factors, such as obesity and smoking rates; and environmental factors such as the population's average income.

Prospect of the high efficiency for the VEST (Via-hole Etching for the Separation of Thin films) cell

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

Deguchi, M.; Kawama, Y.; Matsuno, Y.

1994-12-31

The optimum design of the via-holes for the VEST cell was studied. Using a simple model, fill factors of the VEST cell were calculated. As for the via-hole distribution pattern, square grid pattern was found to be most suitable from the view points of the cell performance and the easiness of the electrode designing. It was found that the fill factor large enough (> 0.79) for the high efficiency can be obtained. A fabricated test cell showed the efficiency of 14.4%. Further improvement (efficiency over 18%) is possibly expected.

Airframe technology for aircraft energy efficiency. [economic factors

NASA Technical Reports Server (NTRS)

James, R. L., Jr.; Maddalon, D. V.

1984-01-01

The economic factors that resulted in the implementation of the aircraft energy efficiency program (ACEE) are reviewed and airframe technology elements including content, progress, applications, and future direction are discussed. The program includes the development of laminar flow systems, advanced aerodynamics, active controls, and composite structures.

Performance analysis of hybrid vibrational energy harvesters with experimental verification

NASA Astrophysics Data System (ADS)

Sriramdas, Rammohan; Pratap, Rudra

2018-07-01

In the present work, performance indices for a hybrid energy harvester (HEH) that is composed of piezoelectric and electrodynamic or electromagnetic mechanisms of energy conversion are analyzed. Performance of a HEH is defined in terms of Q-normalized power factor and efficiency of conversion. They are observed to acutely depend on coupling strength or figures of merit in both piezoelectric and electrodynamic domains. The influence of figures of merit on the Q-normalized power factor, and the limits of conversion efficiency are explored. Based on the studies, a suitable range for figures of merit that would maximize both Q-normalized power factor and conversion efficiency in hybrid harvesters is proposed. The proposed idea is verified experimentally for the appropriate values of figures of merit and efficiencies by fabricating and testing four experimental models of the HEHs.

Utilizing an Energy Management System with Distributed Resources to Manage Critical Loads and Reduce Energy Costs

DTIC Science & Technology

2014-09-01

peak shaving, conducting power factor correction, matching critical load to most efficient distributed resource, and islanding a system during...photovoltaic arrays during islanding, and power factor correction, the implementation of the ESS by itself is likely to prove cost prohibitive. The DOD...These functions include peak shaving, conducting power factor correction, matching critical load to most efficient distributed resource, and islanding a

The Role of Interaction Patterns with Hybrid Electric Vehicle Eco-Features for Drivers' Eco-Driving Performance.

PubMed

Arend, Matthias G; Franke, Thomas

2017-03-01

The objective of the present research was to understand drivers' interaction patterns with hybrid electric vehicles' (HEV) eco-features (electric propulsion, regenerative braking, neutral mode) and their relationship to fuel efficiency and driver characteristics (technical system knowledge, eco-driving motivation). Eco-driving (driving behaviors performed to achieve higher fuel efficiency) has the potential to reduce CO 2 emissions caused by road vehicles. Eco-driving in HEVs is particularly challenging due to the systems' dynamic energy flows. As a result, drivers are likely to show diverse eco-driving behaviors, depending on factors like knowledge and motivation. The eco-features represent an interface for the control of the systems' energy flows. A sample of 121 HEV drivers who had constantly logged their fuel consumption prior to the study participated in an online questionnaire. Drivers' interaction patterns with the eco-features were related to fuel efficiency. A common factor was identified in an exploratory factor analysis, characterizing the intensity of actively dealing with electric energy, which was also related to fuel efficiency. Driver characteristics were not related to this factor, yet they were significant predictors of fuel efficiency. From the perspective of user-energy interaction, the relationship of the aggregated factor to fuel efficiency emphasizes the central role of drivers' perception of and interaction with energy conversions in determining HEV eco-driving success. To arrive at an in-depth understanding of drivers' eco-driving behaviors that can guide interface design, authors of future research should be concerned with the psychological processes that underlie drivers' interaction patterns with eco-features.

Factors affecting the labor efficiency of hospital-based blood bank laboratories.

PubMed

Lam, H C; Kominski, G F; Petz, L D; Sofaer, S

1994-09-01

A variety of financing mechanisms and managerial innovations have been developed in the past decade to control hospital costs. Some evidence suggests that those changes have not produced substantial improvements in labor efficiency among employees in the hospital's technical level, such as in the blood bank laboratories. This study measured labor efficiency in 40 hospital-based blood bank laboratories in Southern California during the year from July 1989 to June 1990 and explored the impact of financial, managerial, and operational factors on labor efficiency. With standardized output measures used in all blood bank laboratories, a wide variation of labor efficiency was found. Multivariate analyses indicate that the labor efficiency of blood bank employees was not influenced by organizational financial incentives, but was affected by the managerial styles of blood bank managers. Interpretation of the findings suggests that labor efficiency is affected by operational designs intended to improve responses to variable workloads and reduce slack time.

Gain and Efficiency of a Superconducting Microwave Compressor with a Switching Cavity in an Interference Switch

NASA Astrophysics Data System (ADS)

Artemenko, S. N.; Samoylenko, G. M.

2016-11-01

We study the processes of radiation output from a microwave storage cavity through a superconducting interference switch, which is based on a H-junction with a superconducting switching cavity connected to the side branch of the junction for various ways of controlling the parameters of the switching cavity. It is shown that efficient control over radiation output in such a switch can be achieved by varying the resonance frequency or Q-factor of the switching cavity, as well as by varying these parameters simultaneously. It is found that in the case of controlling the resonance frequency of the switching cavity, there exists an optimal interval of the frequency variation, within which the total efficiency and extraction efficiency are maximum. When the Q-factor of the switching cavity changes, the dependence of the total efficiency and extraction efficiency on the Q-factor has the monotonic character. The mixed regime of radiation output control is also studied. The envelopes of the output compressor pulses are plotted on the basis of recurrent relationships between the amplitudes of the waves in the system for three regimes of switch operation. It is shown that pulses with an almost rectangular shape of the envelope can be formed in the regime of controlling the switching cavity by varying the Q-factor. An example of possible realization of the switching cavity is considered.

High-Efficiency and High-Power Mid-Wave Infrared Cascade Lasers

DTIC Science & Technology

2012-10-01

internal quantum efficiency () and factor (2) is usually called the optical extraction efficiency (). The optical extraction efficiency ... quantum efficiency involves more fundamental parameters corresponding to the microscopic processes of the device operation, nevertheless, it can be...deriving parameters such as the internal quantum efficiency of a QC laser, the entire injector miniband can be treated as a single virtual state

Labor Factor Efficiency in the Agricultural Industry

ERIC Educational Resources Information Center

R?y, Inna U.; Shakulikova, Gulzada T.; Kozhakhmetova, Gulnar A.; Lashkareva, Olga V.; Bondarenko, Elena G.; Bermukhambetova, Botagoz B.; Baimagambetova, Zamzagul A.; Zhetessova, Mariyam T.; Beketova, Kamar N.; Anafiyaeva, Zhibek

2016-01-01

Agricultural problems associated with prospects of the rural population and agriculture in general have recently become an important factor in the modern economic policy development. The urgency of finding ways to improve the labor resource efficiency in agriculture pursuant to the state tasks is determined by the need to restore the agricultural…

Characterization of Staufen1 Ribonucleoproteins by Mass Spectrometry and Biochemical Analyses Reveal the Presence of Diverse Host Proteins Associated with Human Immunodeficiency Virus Type 1

PubMed Central

Milev, Miroslav P.; Ravichandran, Mukunthan; Khan, Morgan F.; Schriemer, David C.; Mouland, Andrew J.

2012-01-01

The human immunodeficiency virus type 1 (HIV-1) unspliced, 9 kb genomic RNA (vRNA) is exported from the nucleus for the synthesis of viral structural proteins and enzymes (Gag and Gag/Pol) and is then transported to sites of virus assembly where it is packaged into progeny virions. vRNA co-exists in the cytoplasm in the context of the HIV-1 ribonucleoprotein (RNP) that is currently defined by the presence of Gag and several host proteins including the double-stranded RNA-binding protein, Staufen1. In this study we isolated Staufen1 RNP complexes derived from HIV-1-expressing cells using tandem affinity purification and have identified multiple host protein components by mass spectrometry. Four viral proteins, including Gag, Gag/Pol, Env and Nef as well as >200 host proteins were identified in these RNPs. Moreover, HIV-1 induces both qualitative and quantitative differences in host protein content in these RNPs. 22% of Staufen1-associated factors are virion-associated suggesting that the RNP could be a vehicle to achieve this. In addition, we provide evidence on how HIV-1 modulates the composition of cytoplasmic Staufen1 RNPs. Biochemical fractionation by density gradient analyses revealed new facets on the assembly of Staufen1 RNPs. The assembly of dense Staufen1 RNPs that contain Gag and several host proteins were found to be entirely RNA-dependent but their assembly appeared to be independent of Gag expression. Gag-containing complexes fractionated into a lighter and another, more dense pool. Lastly, Staufen1 depletion studies demonstrated that the previously characterized Staufen1 HIV-1-dependent RNPs are most likely aggregates of smaller RNPs that accumulate at juxtanuclear domains. The molecular characterization of Staufen1 HIV-1 RNPs will offer important information on virus-host cell interactions and on the elucidation of the function of these RNPs for the transport of Gag and the fate of the unspliced vRNA in HIV-1-producing cells. PMID:23125841

Optimization of Neutral Atom Imagers

NASA Technical Reports Server (NTRS)

Shappirio, M.; Coplan, M.; Balsamo, E.; Chornay, D.; Collier, M.; Hughes, P.; Keller, J.; Ogilvie, K.; Williams, E.

2008-01-01

The interactions between plasma structures and neutral atom populations in interplanetary space can be effectively studied with energetic neutral atom imagers. For neutral atoms with energies less than 1 keV, the most efficient detection method that preserves direction and energy information is conversion to negative ions on surfaces. We have examined a variety of surface materials and conversion geometries in order to identify the factors that determine conversion efficiency. For chemically and physically stable surfaces smoothness is of primary importance while properties such as work function have no obvious correlation to conversion efficiency. For the noble metals, tungsten, silicon, and graphite with comparable smoothness, conversion efficiency varies by a factor of two to three. We have also examined the way in which surface conversion efficiency varies with the angle of incidence of the neutral atom and have found that the highest efficiencies are obtained at angles of incidence greater then 80deg. The conversion efficiency of silicon, tungsten and graphite were examined most closely and the energy dependent variation of conversion efficiency measured over a range of incident angles. We have also developed methods for micromachining silicon in order to reduce the volume to surface area over that of a single flat surface and have been able to reduce volume to surface area ratios by up to a factor of 60. With smooth micro-machined surfaces of the optimum geometry, conversion efficiencies can be increased by an order of magnitude over instruments like LENA on the IMAGE spacecraft without increase the instruments mass or volume.

Multiwell CO2 injectivity: impact of boundary conditions and brine extraction on geologic CO2 storage efficiency and pressure buildup.

PubMed

Heath, Jason E; McKenna, Sean A; Dewers, Thomas A; Roach, Jesse D; Kobos, Peter H

2014-01-21

CO2 storage efficiency is a metric that expresses the portion of the pore space of a subsurface geologic formation that is available to store CO2. Estimates of storage efficiency for large-scale geologic CO2 storage depend on a variety of factors including geologic properties and operational design. These factors govern estimates on CO2 storage resources, the longevity of storage sites, and potential pressure buildup in storage reservoirs. This study employs numerical modeling to quantify CO2 injection well numbers, well spacing, and storage efficiency as a function of geologic formation properties, open-versus-closed boundary conditions, and injection with or without brine extraction. The set of modeling runs is important as it allows the comparison of controlling factors on CO2 storage efficiency. Brine extraction in closed domains can result in storage efficiencies that are similar to those of injection in open-boundary domains. Geomechanical constraints on downhole pressure at both injection and extraction wells lower CO2 storage efficiency as compared to the idealized scenario in which the same volumes of CO2 and brine are injected and extracted, respectively. Geomechanical constraints should be taken into account to avoid potential damage to the storage site.

An Attempt at Quantifying Factors that Affect Efficiency in the Management of Solid Waste Produced by Commercial Businesses in the City of Tshwane, South Africa

PubMed Central

Worku, Yohannes; Muchie, Mammo

2012-01-01

Objective. The objective was to investigate factors that affect the efficient management of solid waste produced by commercial businesses operating in the city of Pretoria, South Africa. Methods. Data was gathered from 1,034 businesses. Efficiency in solid waste management was assessed by using a structural time-based model designed for evaluating efficiency as a function of the length of time required to manage waste. Data analysis was performed using statistical procedures such as frequency tables, Pearson's chi-square tests of association, and binary logistic regression analysis. Odds ratios estimated from logistic regression analysis were used for identifying key factors that affect efficiency in the proper disposal of waste. Results. The study showed that 857 of the 1,034 businesses selected for the study (83%) were found to be efficient enough with regards to the proper collection and disposal of solid waste. Based on odds ratios estimated from binary logistic regression analysis, efficiency in the proper management of solid waste was significantly influenced by 4 predictor variables. These 4 influential predictor variables are lack of adherence to waste management regulations, wrong perception, failure to provide customers with enough trash cans, and operation of businesses by employed managers, in a decreasing order of importance. PMID:23209483

Feline Immunodeficiency Virus Envelope Glycoproteins Antagonize Tetherin through a Distinctive Mechanism That Requires Virion Incorporation

PubMed Central

Guevara, Rebekah B.; Marcano, Adriana C.; Saenz, Dyana T.; Fadel, Hind J.; Rogstad, Daniel K.

2014-01-01

ABSTRACT BST2/tetherin inhibits the release of enveloped viruses from cells. Primate lentiviruses have evolved specific antagonists (Vpu, Nef, and Env). Here we characterized tetherin proteins of species representing both branches of the order Carnivora. Comparison of tiger and cat (Feliformia) to dog and ferret (Caniformia) genes demonstrated that the tiger and cat share a start codon mutation that truncated most of the tetherin cytoplasmic tail early in the Feliformia lineage (19 of 27 amino acids, including the dual tyrosine motif). Alpha interferon (IFN-α) induced tetherin and blocked feline immunodeficiency virus (FIV) replication in lymphoid and nonlymphoid feline cells. Budding of bald FIV and HIV particles was blocked by carnivore tetherins. However, infectious FIV particles were resistant, and spreading FIV replication was uninhibited. Antagonism mapped to the envelope glycoprotein (Env), which rescued FIV from carnivore tetherin restriction when expressed in trans but, in contrast to known antagonists, did not rescue noncognate particles. Also unlike the primate lentiviral antagonists, but similar to the Ebola virus glycoprotein, FIV Env did not reduce intracellular or cell surface tetherin levels. Furthermore, FIV-enveloped FIV particles actually required tetherin for optimal release from cells. The results show that FIV Envs mediate a distinctive tetherin evasion. Well adapted to a phylogenetically ancient tetherin tail truncation in the Felidae, it requires functional virion incorporation of Env, and it shields the budding particle without downregulating plasma membrane tetherin. Moreover, FIV has evolved dependence on this protein: particles containing FIV Env need tetherin for optimal release from the cell, while Env− particles do not. IMPORTANCE HIV-1 antagonizes the restriction factor tetherin with the accessory protein Vpu, while HIV-2 and the filovirus Ebola use their envelope (Env) glycoproteins for this purpose. It turns out that the FIV tetherin antagonist is also its Env protein, but the mechanism is distinctive. Unlike other tetherin antagonists, FIV Env cannot act in trans to rescue vpu-deficient HIV-1. It must be incorporated specifically into FIV virions to be active. Also unlike other retroviral antagonists, but similar to Ebola virus Env, it does not act by downregulating or degrading tetherin. FIV Env might exclude tetherin locally or direct assembly to tetherin-negative membrane domains. Other distinctive features are apparent, including evidence that this virus evolved an equilibrium in which tetherin is both restriction factor and cofactor, as FIV requires tetherin for optimal particle release. PMID:24390322

Longitudinal monitoring of whole body counter NaI(TI) detector efficiency

USDA-ARS?s Scientific Manuscript database

Assessing accuracy of radiation counting systems over time is critical. We examined long-term WBC performance in detail. Efficiency factors for 54 detectors were updated annually over several years. Newer efficiency values were compared with baseline and with annual values. Overall system efficiency...

Study on a New Combination Method and High Efficiency Outer Rotor Type Permanent Magnet Motors

NASA Astrophysics Data System (ADS)

Enomoto, Yuji; Kitamura, Masashi; Motegi, Yasuaki; Andoh, Takashi; Ochiai, Makoto; Abukawa, Toshimi

The segment stator core, high space factor coil, and high efficiency magnet are indispensable technologies in the development of compact and a high efficiency motors. But adoption of the segment stator core and high space factor coil has not progressed in the field of outer rotor type motors, for the reason that the inner components cannot be laser welded together. Therefore, we have examined a segment stator core combination technology for the purposes of getting a large increase in efficiency and realizing miniaturization. We have also developed a characteristic estimation method which provides the most suitable performance for segment stator core motors.

Psychosocial factors and sleep efficiency: discrepancies between subjective and objective evaluations of sleep.

PubMed

Jackowska, Marta; Dockray, Samantha; Hendrickx, Hilde; Steptoe, Andrew

2011-01-01

Self-reported sleep efficiency may not precisely reflect objective sleep patterns. We assessed whether psychosocial factors and affective responses are associated with discrepancies between subjective reports and objective measures of sleep efficiency. Participants were 199 working women aged 20 to 61 years. Standardized questionnaires were used to assess psychosocial characteristics and affect that included work stress, social support, happiness, and depressive symptoms. Objective measures of sleep were assessed on one week and one leisure night with an Actiheart monitor. Self-reported sleep efficiency was derived from the Jenkins Sleep Problems Scale. Discrepancies between self-reported and objective measures of sleep efficiency were computed by contrasting standardized measures of sleep problems with objectively measured sleep efficiency. Participants varied markedly in the discrepancies between self-reported and objective sleep measures. After adjustment for personal income, age, having children, marital status, body mass index, and negative affect, overcommitment (p = .002), low level of social support (p = .049), and poor self-rated heath (p = .02) were associated with overreporting of sleep difficulties and underestimation of sleep efficiency. Self-reported poor sleep efficiency was more prevalent among those more overcommitted at work (p = .009) and less happy (p = .02), as well as among those with lower level of social support (p = .03) and more depressive symptoms (p = .048), independently of covariates. Objective sleep efficiency was unrelated to psychosocial characteristics or affect. The extent to which self-reported evaluations of sleep efficiency reflect objective experience may be influenced by psychosocial characteristics and affect. Unless potential moderators of self-reported sleep efficiency are taken into account, associations between sleep and psychosocial factors relevant to health may be overestimated.

The efficiency and budgeting of public hospitals: case study of iran.

PubMed

Yusefzadeh, Hasan; Ghaderi, Hossein; Bagherzade, Rafat; Barouni, Mohsen

2013-05-01

Hospitals are the most costly and important components of any health care system, so it is important to know their economic values, pay attention to their efficiency and consider factors affecting them. The aim of this study was to assess the technical scale and economic efficiency of hospitals in the West Azerbaijan province of Iran, for which Data Envelopment Analysis (DEA) was used to propose a model for operational budgeting. This study was a descriptive-analysis that was conducted in 2009 and had three inputs and two outputs. Deap2, 1 software was used for data analysis. Slack and radial movements and surplus of inputs were calculated for selected hospitals. Finally, a model was proposed for performance-based budgeting of hospitals and health sectors using the DEA technique. The average scores of technical efficiency, pure technical efficiency (managerial efficiency) and scale efficiency of hospitals were 0.584, 0.782 and 0.771, respectively. In other words the capacity of efficiency promotion in hospitals without any increase in costs and with the same amount of inputs was about 41.5%. Only four hospitals among all hospitals had the maximum level of technical efficiency. Moreover, surplus production factors were evident in these hospitals. Reduction of surplus production factors through comprehensive planning based on the results of the Data Envelopment Analysis can play a major role in cost reduction of hospitals and health sectors. In hospitals with a technical efficiency score of less than one, the original and projected values of inputs were different; resulting in a surplus. Hence, these hospitals should reduce their values of inputs to achieve maximum efficiency and optimal performance. The results of this method was applied to hospitals a benchmark for making decisions about resource allocation; linking budgets to performance results; and controlling and improving hospitals performance.

An Efficient End-Pumped Ho:Tm:YLF Disk Amplifier

NASA Technical Reports Server (NTRS)

Yu, Ji-Rong; Petros, Mulugeta; Singh, Upendra N.; Barnes, Norman P.

2000-01-01

An efficient diode-pumped, room temperature Ho:Tm:YLF disk amplifier was realized by end-pump configuration. Compared to side pump configuration, about a factor three improvement in system efficiency has been demonstrated.

[Eco-efficiency change and its driving factors in Tongling City of Anhui Province].

PubMed

Wang, Yi-Chen; Wang, Yuan; Zhu, Xiao-Dong; Wu, Xiao-Qing; Wang, Ke; Ren, Ke-Xiu; Lu, Gen-Fa

2011-02-01

This paper first applied material flow analysis (MFA) to construct three levels of regional eco-efficiency indicators, i.e., regional direct eco-efficiency (RDE), regional total eco-efficiency (RTE), and holistic eco-efficiency (HE), and adopted the newly developed data envelopment analysis (DEA) to evaluate the eco-efficiency of Tongling City during the period of 1990-2008. We also applied Malmquist productivity index (MPI) to explore the eco-efficiency change between two following years and its driving factors. The main results were summarized as 1) though the RDE of Tongling City in 1990-2008 kept an increasing trend, its mean eco-efficiency was not high (close to 0.8 in 80% of the years), being lower than that of the RTE and HE, and 2) the RDE change was closely relevant to the improvement in resource management and the technical input in environmental protection in recent years. In order to further improve the RDE of the City, it would be necessary to raise its eco-efficiency via expanding raw material input, reducing domestic extraction, promoting resources productivity, and taking more measures on environmental protection facilities construction.

Methane, Black Carbon, and Ethane Emissions from Natural Gas Flares in the Bakken Shale, North Dakota.

PubMed

Gvakharia, Alexander; Kort, Eric A; Brandt, Adam; Peischl, Jeff; Ryerson, Thomas B; Schwarz, Joshua P; Smith, Mackenzie L; Sweeney, Colm

2017-05-02

Incomplete combustion during flaring can lead to production of black carbon (BC) and loss of methane and other pollutants to the atmosphere, impacting climate and air quality. However, few studies have measured flare efficiency in a real-world setting. We use airborne data of plume samples from 37 unique flares in the Bakken region of North Dakota in May 2014 to calculate emission factors for BC, methane, ethane, and combustion efficiency for methane and ethane. We find no clear relationship between emission factors and aircraft-level wind speed or between methane and BC emission factors. Observed median combustion efficiencies for methane and ethane are close to expected values for typical flares according to the US EPA (98%). However, we find that the efficiency distribution is skewed, exhibiting log-normal behavior. This suggests incomplete combustion from flares contributes almost 1/5 of the total field emissions of methane and ethane measured in the Bakken shale, more than double the expected value if 98% efficiency was representative. BC emission factors also have a skewed distribution, but we find lower emission values than previous studies. The direct observation for the first time of a heavy-tail emissions distribution from flares suggests the need to consider skewed distributions when assessing flare impacts globally.

Developing Strategic Leadership for Administrators: Private Vocational College Study

ERIC Educational Resources Information Center

Jumnongya, Areeya; Sirisuthi, Chaiyuth; Chansirisira, Pacharawit

2015-01-01

The purpose of this study is to study and define a number of factors measuring quality and efficiency in administrators of private vocational college, and to test and evaluate the efficiency of the strategic leadership program. Twelve factors and 83 indicators were identified as vital for strategic leadership for private vocational college…

Competition between pre-mRNAs for the splicing machinery drives global regulation of splicing

PubMed Central

Munding, Elizabeth M.; Shiue, Lily; Katzman, Sol; Donohue, John Paul; Ares, Manuel

2013-01-01

Summary During meiosis in yeast, global splicing efficiency increases and then decreases. Here we provide evidence that splicing improves due to reduced competition for the splicing machinery. The timing of this regulation corresponds to repression and reactivation of ribosomal protein genes (RPGs) during meiosis. In vegetative cells RPG repression by rapamycin treatment also increases splicing efficiency. Down-regulation of the RPG-dedicated transcription factor gene IFH1 genetically suppresses two spliceosome mutations prp11-1 and prp4-1, and globally restores splicing efficiency in prp4-1 cells. We conclude that the splicing apparatus is limiting and pre-mRNAs compete. Splicing efficiency of a pre-mRNA therefore depends not just on its own concentration and affinity for limiting splicing factor(s) but also on those of competing pre-mRNAs. Competition between RNAs for limiting RNA processing factors appears to be a general condition in eukaryotic cells important for function of a variety of post-transcriptional control mechanisms including miRNA repression, polyadenylation and splicing. PMID:23891561

The effect of economic factors and energy efficiency programs on residential electricity consumption

NASA Astrophysics Data System (ADS)

Sakai, Mihoko

Many countries have implemented policies to correct market and behavioral failures that lead to inefficient energy use. It is important to know what factors and policies can effectively overcome such failures and improve energy efficiency; however, a comprehensive analysis has been difficult because of data limitations. Using state scores compiled by American organizations recently, and adopting fixed-effects regression models, I analyze the joint impacts of relevant factors and policy programs on residential electricity consumption in each U.S. state. The empirical results reveal that increases in electricity price have small and negative effects, and increases in personal income have positive effects on residential electricity sales per capita (a measure of energy efficiency). The results suggest that it may take time for economic factors to affect electricity sales. The effects of personal income suggest the difficulty of controlling residential electricity consumption; however, they also imply that there is some room in households to reduce electricity use. The study also finds that programs and budgets of several policies seem to be associated with electricity sales. The estimates from a model including interaction terms suggest the importance of including multiple policies when analyzing and designing policies to address electricity efficiency. The results also imply the possibility of rebound effects of some policies, whereby improvements in energy efficiency lead to increases in energy consumption due to the associated lower per unit cost. Future studies should analyze both short-term and long-term effects of economic factors and policies, based on improved and accumulated time series and panel data, in order to design more effective policies for improving residential electricity efficiency.

An Efficiency Analysis of U.S. Business Schools

ERIC Educational Resources Information Center

Sexton, Thomas R.

2010-01-01

In the current economic climate, business schools face crucial decisions. As resources become scarcer, schools must either streamline operations or limit them. An efficiency analysis of U.S. business schools is presented that computes, for each business school, an overall efficiency score and provides separate factor efficiency scores, indicating…

Energy efficiency in U.K. shopping centres

NASA Astrophysics Data System (ADS)

Mangiarotti, Michela

Energy efficiency in shopping centres means providing comfortable internal environment and services to the occupants with minimum energy use in a cost-effective and environmentally sensitive manner. This research considers the interaction of three factors affecting the energy efficiency of shopping centres: i) performance of the building fabric and services ii) management of the building in terms of operation, control, maintenance and replacement of the building fabric and services, and company's energy policy iii) occupants' expectation for comfort and awareness of energy efficiency. The aim of the investigation is to determine the role of the above factors in the energy consumption and carbon emissions of shopping centres and the scope for reducing this energy usage by changing one or all the three factors. The study also attempts to prioritize the changes in the above factors that are more cost-effective at reducing that energy consumption and identify the benefits and main economic and legal drivers for energy efficiency in shopping centres. To achieve these targets, three case studies have been analysed. Using energy data from bills, the performance of the selected case studies has been assessed to establish trends and current energy consumption and carbon emissions of shopping centres and their related causes. A regression analysis has attempted to break down the energy consumption of the landlords' area by end-use to identify the main sources of energy usage and consequently introduce cost-effective measures for saving energy. A monitoring and occupants' survey in both landlords' and tenants' areas have been carried out at the same time to compare the objective data of the environmental conditions with the subjective impressions of shoppers and shopkeepers. In particular, the monitoring aimed at assessing the internal environment to identify possible causes of discomfort and opportunities for introducing energy saving measures. The survey looked at determining the occupants' expectation for comfort and awareness of energy efficiency in shopping centres. The results show the complexity of prioritizing the three factors affecting energy efficiency in shopping centres, highlighting the relationships between those factors, and the role of different actors, involved in the life of shopping centres, in the energy and environmental performance of these buildings.

Benchmarking the efficiency of the Chilean water and sewerage companies: a double-bootstrap approach.

PubMed

Molinos-Senante, María; Donoso, Guillermo; Sala-Garrido, Ramon; Villegas, Andrés

2018-03-01

Benchmarking the efficiency of water companies is essential to set water tariffs and to promote their sustainability. In doing so, most of the previous studies have applied conventional data envelopment analysis (DEA) models. However, it is a deterministic method that does not allow to identify environmental factors influencing efficiency scores. To overcome this limitation, this paper evaluates the efficiency of a sample of Chilean water and sewerage companies applying a double-bootstrap DEA model. Results evidenced that the ranking of water and sewerage companies changes notably whether efficiency scores are computed applying conventional or double-bootstrap DEA models. Moreover, it was found that the percentage of non-revenue water and customer density are factors influencing the efficiency of Chilean water and sewerage companies. This paper illustrates the importance of using a robust and reliable method to increase the relevance of benchmarking tools.

Regional-scale calculation of the LS factor using parallel processing

NASA Astrophysics Data System (ADS)

Liu, Kai; Tang, Guoan; Jiang, Ling; Zhu, A.-Xing; Yang, Jianyi; Song, Xiaodong

2015-05-01

With the increase of data resolution and the increasing application of USLE over large areas, the existing serial implementation of algorithms for computing the LS factor is becoming a bottleneck. In this paper, a parallel processing model based on message passing interface (MPI) is presented for the calculation of the LS factor, so that massive datasets at a regional scale can be processed efficiently. The parallel model contains algorithms for calculating flow direction, flow accumulation, drainage network, slope, slope length and the LS factor. According to the existence of data dependence, the algorithms are divided into local algorithms and global algorithms. Parallel strategy are designed according to the algorithm characters including the decomposition method for maintaining the integrity of the results, optimized workflow for reducing the time taken for exporting the unnecessary intermediate data and a buffer-communication-computation strategy for improving the communication efficiency. Experiments on a multi-node system show that the proposed parallel model allows efficient calculation of the LS factor at a regional scale with a massive dataset.

High performance incandescent lighting using a selective emitter and nanophotonic filters

NASA Astrophysics Data System (ADS)

Leroy, Arny; Bhatia, Bikram; Wilke, Kyle; Ilic, Ognjen; Soljačić, Marin; Wang, Evelyn N.

2017-09-01

Previous approaches for improving the efficiency of incandescent light bulbs (ILBs) have relied on tailoring the emitted spectrum using cold-side interference filters that reflect the infrared energy back to the emitter while transmitting the visible light. While this approach has, in theory, potential to surpass light-emitting diodes (LEDs) in terms of luminous efficiency while conserving the excellent color rendering index (CRI) inherent to ILBs, challenges such as low view factor between the emitter and filter, high emitter (>2800 K) and filter temperatures and emitter evaporation have significantly limited the maximum efficiency. In this work, we first analyze the effect of non-idealities in the cold-side filter, the emitter and the view factor on the luminous efficiency. Second, we theoretically and experimentally demonstrate that the loss in efficiency associated with low view factors can be minimized by using a selective emitter (e.g., high emissivity in the visible and low emissivity in the infrared) with a filter. Finally, we discuss the challenges in achieving a high performance and long-lasting incandescent light source including the emitter and filter thermal stability as well as emitter evaporation.

A "hydrokinematic" method of measuring the glide efficiency of a human swimmer.

PubMed

Naemi, Roozbeh; Sanders, Ross H

2008-12-01

The aim of this study was to develop and test a method of quantifying the glide efficiency, defined as the ability of the body to maintain its velocity over time and to minimize deceleration through a rectilinear glide. The glide efficiency should be determined in a way that accounts for both the inertial and resistive characteristics of the gliding body as well as the instantaneous velocity. A displacement function (parametric curve) was obtained from the equation of motion of the body during a horizontal rectilinear glide. The values of the parameters in the displacement curve that provide the best fit to the displacement-time data of a body during a rectilinear horizontal glide represent the glide factor and the initial velocity of the particular glide interval. The glide factor is a measure of glide efficiency and indicates the ability of the body to minimize deceleration at each corresponding velocity. The glide efficiency depends on the hydrodynamic characteristic of the body, which is influenced by the body's shape as well as by the body's size. To distinguish the effects of size and shape on the glide efficiency, a size-related glide constant and a shape-related glide coefficient were determined as separate entities. The glide factor is the product of these two parameters. The goodness of fit statistics indicated that the representative displacement function found for each glide interval closely represents the real displacement data of a body in a rectilinear horizontal glide. The accuracy of the method was indicated by a relative standard error of calculation of less than 2.5%. Also the method was able to distinguish between subjects in their glide efficiency. It was found that the glide factor increased with decreasing velocity. The glide coefficient also increased with decreasing Reynolds number. The method is sufficiently accurate to distinguish between individual swimmers in terms of their glide efficiency. The separation of glide factor to a size-related glide constant and a shape-related glide coefficient enabled the effect of size and shape to be quantified.

Effects of dietary fracture toughness and dental wear on chewing efficiency in geladas (Theropithecus gelada).

PubMed

Venkataraman, Vivek V; Glowacka, Halszka; Fritz, Julia; Clauss, Marcus; Seyoum, Chalachew; Nguyen, Nga; Fashing, Peter J

2014-09-01

Chewing efficiency has been associated with fitness in mammals, yet little is known about the behavioral, ecological, and morphological factors that influence chewing efficiency in wild animals. Although research has established that dental wear and food material properties independently affect chewing efficiency, few studies have addressed the interaction among these factors. We examined chewing efficiency, measured as mean fecal particle size, as a function of seasonal shifts in diet (and corresponding changes in food fracture toughness) in a single breeding population of a grazing primate, the gelada monkey, at Guassa, Ethiopia. We also measured dental topographic traits (slope, angularity, and relief index) and relative two- and three-dimensional shearing crest lengths in a cross-sectional wear series of gelada molars. Chewing efficiency decreased during the dry season, a pattern corresponding to the consumption of foods with higher fracture toughness. Older individuals experienced the most pronounced decreases in chewing efficiency between seasons, implicating dental wear as a causal factor. This pattern is consistent with our finding that dental topographic metrics and three-dimensional relative shearing crest lengths were lowest at the last stage of wear. Integrating these lines of behavioral, ecological, and morphological evidence provides some of the first empirical support for the hypothesis that food fracture toughness and dental wear together contribute to chewing efficiency. Geladas have the highest chewing efficiencies measured thus far in primates, and may be analogous to equids in their emphasis on dental design as a means of particle size reduction in the absence of highly specialized digestive physiology. Copyright © 2014 Wiley Periodicals, Inc.

Efficiency loss of thin film Cu(InxGa1-x)Se(S) solar panels by lamination process

NASA Astrophysics Data System (ADS)

Xu, Li

2017-04-01

Efficiency loss of thin film Cu(InxGa1-x)Se(S) (CIGS) solar panels by lamination process has been compromising the final output power in commercial products of solar modules, but few reports have been published on such issue, as the majority of the investigation is focused on the efficiency at the circuit level, i.e., before lamination process. In this paper, we studied the effect of lamination process to the efficiency loss of thin film CIGS solar panels. It was observed that the fill factor degradation dominated the efficiency loss with the small change of Voc and Jsc. Experiments showed that neither the temperature nor the pressure, nor the two combined in the lamination process is the root cause of the efficiency loss; instead, the ethylene vinyl acetate (EVA) layer as the encapsulation material which directly contacts the solar cell devices was the major factor responsible for the efficiency loss. It was found that the gel content of the cured EVA film after lamination was highly correlated to the efficiency loss. The higher the gel content, the higher the efficiency loss. The mismatch of coefficient of thermal expansion between the EVA film and the CIGS thin film resulted in compressive stress in the device layer after lamination process. The compressive stress is speculated to affect the lattice defects, but need to be confirmed with the measurement of capacitance voltage (CV) and drive level capacitance profiling (DLCP). Three-day sun soak was then carried out and it was observed that the fill factor recovered significantly and so did the efficiency. Experiments also showed that there was no impact of chemical erosion on the front electrode of transparent conductive oxide (TCO) films by chemicals released from the EVA films during lamination.

Experimental evaluation of a mathematical model for predicting transfer efficiency of a high volume-low pressure air spray gun.

PubMed

Tan, Y M; Flynn, M R

2000-10-01

The transfer efficiency of a spray-painting gun is defined as the amount of coating applied to the workpiece divided by the amount sprayed. Characterizing this transfer process allows for accurate estimation of the overspray generation rate, which is important for determining a spray painter's exposure to airborne contaminants. This study presents an experimental evaluation of a mathematical model for predicting the transfer efficiency of a high volume-low pressure spray gun. The effects of gun-to-surface distance and nozzle pressure on the agreement between the transfer efficiency measurement and prediction were examined. Wind tunnel studies and non-volatile vacuum pump oil in place of commercial paint were used to determine transfer efficiency at nine gun-to-surface distances and four nozzle pressure levels. The mathematical model successfully predicts transfer efficiency within the uncertainty limits. The least squares regression between measured and predicted transfer efficiency has a slope of 0.83 and an intercept of 0.12 (R2 = 0.98). Two correction factors were determined to improve the mathematical model. At higher nozzle pressure settings, 6.5 psig and 5.5 psig, the correction factor is a function of both gun-to-surface distance and nozzle pressure level. At lower nozzle pressures, 4 psig and 2.75 psig, gun-to-surface distance slightly influences the correction factor, while nozzle pressure has no discernible effect.

Modelling the Evolution and Spread of HIV Immune Escape Mutants

PubMed Central

Fryer, Helen R.; Frater, John; Duda, Anna; Roberts, Mick G.; Phillips, Rodney E.; McLean, Angela R.

2010-01-01

During infection with human immunodeficiency virus (HIV), immune pressure from cytotoxic T-lymphocytes (CTLs) selects for viral mutants that confer escape from CTL recognition. These escape variants can be transmitted between individuals where, depending upon their cost to viral fitness and the CTL responses made by the recipient, they may revert. The rates of within-host evolution and their concordant impact upon the rate of spread of escape mutants at the population level are uncertain. Here we present a mathematical model of within-host evolution of escape mutants, transmission of these variants between hosts and subsequent reversion in new hosts. The model is an extension of the well-known SI model of disease transmission and includes three further parameters that describe host immunogenetic heterogeneity and rates of within host viral evolution. We use the model to explain why some escape mutants appear to have stable prevalence whilst others are spreading through the population. Further, we use it to compare diverse datasets on CTL escape, highlighting where different sources agree or disagree on within-host evolutionary rates. The several dozen CTL epitopes we survey from HIV-1 gag, RT and nef reveal a relatively sedate rate of evolution with average rates of escape measured in years and reversion in decades. For many epitopes in HIV, occasional rapid within-host evolution is not reflected in fast evolution at the population level. PMID:21124991

Induction of long-lasting multi-specific CD8+ T cells by a four-component DNA-MVA/HIVA-RENTA candidate HIV-1 vaccine in rhesus macaques.

PubMed

Im, Eung-Jun; Nkolola, Joseph P; di Gleria, Kati; McMichael, Andrew J; Hanke, Tomás

2006-10-01

As a part of a long-term effort to develop vaccine against HIV-1 clade A inducing protective T cell responses in humans, we run mutually complementing studies in humans and non-human primates (NHP) with the aim to maximize vaccine immunogenicity. The candidate vaccine under development has four components, pTHr.HIVA and pTH.RENTA DNA, and modified vaccinia virus Ankara (MVA).HIVA and MVA.RENTA, delivered in a heterologous DNA prime-MVA boost regimen. While the HIVA (Gag/epitopes) components have been tested in NHP and over 300 human subjects, we plan to test in humans the RENTA (reverse transcriptase, gp41, Nef, Tat) vaccines designed to broaden HIVA-induced responses in year 2007. Here, we investigated the four-component vaccine long-term immunogenicity in Mamu-A*01-positive rhesus macaques and demonstrated that the vaccine-induced T cells were multi-specific, multi-functional, readily proliferated to recall peptides and were circulating in the peripheral blood of vaccine recipients over 1 year after vaccine administration. The consensus clade A-elicited T cells recognized 50% of tested epitope variants from other HIV-1 clades. Thus, the DNA-MVA/HIVA-RENTA vaccine induced memory T cells of desirable characteristics and similarities to those induced in humans by HIVA vaccines alone; however, single-clade vaccines may not elicit sufficiently cross-reactive responses.

The role of molecular chaperones in clathrin mediated vesicular trafficking

PubMed Central

Sousa, Rui; Lafer, Eileen M.

2015-01-01

The discovery that the 70 kD “uncoating ATPase,” which removes clathrin coats from vesicles after endocytosis, is the constitutively expressed Hsc70 chaperone was a surprise. Subsequent work, however, revealed that uncoating is an archetypal Hsp70 reaction: the cochaperone auxilin, which contains a clathrin binding domain and an Hsc70 binding J domain, recruits Hsc70*ATP to the coat and, concomitant with ATP hydrolysis, transfers it to a hydrophobic Hsc70-binding element found on a flexible tail at the C-terminus of the clathrin heavy chain. Release of clathrin in association with Hsc70*ADP follows, and the subsequent, persistent association of clathrin with Hsc70 is important to prevent aberrant clathrin polymerization. Thus, the two canonical functions of Hsp70—dissociation of existing protein complexes or aggregates, and binding to a protein to inhibit its inappropriate aggregation—are recapitulated in uncoating. Association of clathrin with Hsc70 in vivo is regulated by Hsp110, an Hsp70 NEF that is itself a member of the Hsp70 family. How Hsp110 activity is itself regulated to make Hsc70-free clathrin available for endocytosis is unclear, though at synapses it's possible that the influx of calcium that accompanies depolarization activates the Ca++/calmodulin dependent calcineurin phosphatase which then dephosphorylates and activates Hsp110 to stimulate ADP/ATP exchange and release clathrin from Hsc70*ADP:clathrin complexes. PMID:26042225

First-principles study of the structural, elastic, vibrational, thermodynamic and electronic properties of the Mo2B intermetallic under pressure

NASA Astrophysics Data System (ADS)

Escamilla, R.; Carvajal, E.; Cruz-Irisson, M.; Romero, M.; Gómez, R.; Marquina, V.; Galván, D. H.; Durán, A.

2016-12-01

The structural, elastic, vibrational, thermodynamic and electronic properties of the Mo2B intermetallic under pressure are assessed using first-principles calculations based on the generalized gradient approximation (GGA) proposed by Perdew-Wang (PW91). Our results show that the calculated structural parameters at a pressure of zero GPa are in good agreement with the available experimental data. The effect of high pressures on the lattice constants shows that the compression along the c-axis and along the a-axis are similar. The elastic constants were calculated using the static finite strain technique, and the bulk shear moduli are derived from the ideal polycrystalline aggregate. We find that the elastic constants, elastic modulus and hardness monotonically increase as a function of pressure; consequently, the structure is dynamically stable and tends from brittle to ductile behavior under pressure. The Debye temperature θD increases and the so-called Gru¨ neisen constant γ decreases due to stiffening of the crystal structure. The phonon dispersion curves were obtained using the direct method. Additionally, the internal energy (ΔE), the Helmholtz free energy (ΔF), the entropy (S) and the lattice contribution to the heat capacity Cv were calculated and analyzed with the help of the phonon dispersion curves. The N(EF) and the electron transfer between the B and Mo atoms increase as a function of pressure.

Comparative studies of the structure, morphology and electrical conductivity of polyaniline weakly doped with chlorocarboxylic acids

NASA Astrophysics Data System (ADS)

Gmati, Fethi; Fattoum, Arbi; Bohli, Nadra; Dhaoui, Wadia; Belhadj Mohamed, Abdellatif

2007-08-01

We report the results of studies on two series of polyaniline (PANI), doped with dichloroacetic (DCA) and trichloroacetic (TCA) acids, respectively, at various doping rates and obtained by the in situ polymerization method. Samples were characterized by x-ray diffraction, scanning electron microscopy and conductivity measurements. The direct current (dc) and alternating current (ac) electrical conductivities of PANI salts have been investigated in the temperature range 100-310 K and frequency range 7-106 Hz. The results of this study indicate better chain ordering and higher conductivity for PANI doped with TCA. The dc conductivity of all samples is suitably fitted to Mott's three-dimensional variable-range hopping (VRH) model. Different Mott parameters such as characteristic temperature T0, density of states at the Fermi level (N(EF)), average hopping energy (W) and the average hopping distance (R) have been evaluated. The dependence of such values on the dopant acid used is discussed. At high frequencies, the ac conductivity follows the power law σac(ω,T) = A(T)ωs(T,ω), which is characteristic for charge transport in disordered materials by hopping or tunnelling processes. The observed increase in the frequency exponent s with temperature suggests that the small-polaron tunnelling model best describes the dominant ac conduction mechanism. A direct correlation between conductivity, structure and morphology was obtained in our systems.

Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection

PubMed Central

Dalod, Marc; Dupuis, Marion; Deschemin, Jean-Christophe; Goujard, Cécile; Deveau, Christiane; Meyer, Laurence; Ngo, Nicole; Rouzioux, Christine; Guillet, Jean-Gérard; Delfraissy, Jean-François; Sinet, Martine; Venet, Alain

1999-01-01

HIV-specific CD8+ T cells play a major role in the control of virus during HIV primary infection (PI) but do not completely prevent viral replication. We used IFN-γ enzyme-linked immunospot assay and intracellular staining to characterize the ex vivo CD8+ T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV-specific responses in 71% of subjects. Gag and Nef peptides were more frequently recognized than Env and Pol peptides. The number of peptides recognized was low (median 2, range 0–6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were responders with a median of 5 peptides recognized (range 1–13). The frequency of HIV-specific CD8+ T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8+CD28– terminally differentiated T cells was much lower in PI than at the chronic stage of infection. The weakness of the immune response during HIV PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establishing the goals for effective vaccination. J. Clin. Invest. 104:1431–1439 (1999). PMID:10562305

Human Immunodeficiency Virus Vaccine Trials

PubMed Central

O’Connell, Robert J.; Kim, Jerome H.; Corey, Lawrence; Michael, Nelson L.

2012-01-01

More than 2 million AIDS-related deaths occurred globally in 2008, and more than 33 million people are living with HIV/AIDS. Despite promising advances in prevention, an estimated 2.7 million new HIV infections occurred in that year, so that for every two patients placed on combination antiretroviral treatment, five people became infected. The pandemic poses a formidable challenge to the development, progress, and stability of global society 30 years after it was recognized. Experimental preventive HIV-1 vaccines have been administered to more than 44,000 human volunteers in more than 187 separate trials since 1987. Only five candidate vaccine strategies have been advanced to efficacy testing. The recombinant glycoprotein (rgp)120 subunit vaccines, AIDSVAX B/B and AIDSVAX B/E, and the Merck Adenovirus serotype (Ad)5 viral-vector expressing HIV-1 Gag, Pol, and Nef failed to show a reduction in infection rate or lowering of postinfection viral set point. Most recently, a phase III trial that tested a heterologous prime-boost vaccine combination of ALVAC-HIV vCP1521 and bivalent rgp120 (AIDSVAX B/E) showed 31% efficacy in protection from infection among community-risk Thai participants. A fifth efficacy trial testing a DNA/recombinant(r) Ad5 prime-boost combination is currently under way. We review the clinical trials of HIV vaccines that have provided insight into human immunogenicity or efficacy in preventing HIV-1 infection. PMID:23209178

Immune defence against HIV-1 infection in HIV-1-exposed seronegative persons.

PubMed

Schmechel, S C; Russell, N; Hladik, F; Lang, J; Wilson, A; Ha, R; Desbien, A; McElrath, M J

2001-11-01

Rare individuals who are repeatedly exposed to HIV-1 through unprotected sexual contact fail to acquire HIV-1 infection. These persons represent a unique study population to evaluate mechanisms by which HIV-1 replication is either prevented or controlled. We followed longitudinally a group of healthy HIV-1 seronegative persons each reporting repeated high-risk sexual activities with their HIV-1-infected partner at enrollment. The volunteers were primarily (90%) male homosexuals, maintaining high risk activities with their known infected partner (45%) or multiple other partners (61%). We evaluated the quantity and specificity of HIV-1-specific T cells in 31 exposed seronegatives (ES) using a IFN-gamma ELISPOT assay to enumerate T cells recognizing epitopes within HIV-1 Env, Gag, Pol and Nef. PBMC from only three of the 31 volunteers demonstrated ex vivo HIV-1-specific IFN-gamma secretion, in contrast to nearly 30% exhibiting cytolytic responses in previous studies. These findings suggest that if T cell responses in ES are induced by HIV-1 exposure, the frequency is at low levels in most of them, and below the level of detection using the ELISPOT assay. Alternative approaches to improve the sensitivity of detection may include use of dendritic cells as antigen-presenting cells in the ex vivo assay and more careful definition of the risk behavior and extent of HIV-1 exposure in conjunction with the evaluation of T cell responses.

Rational design based synthetic polyepitope DNA vaccine for eliciting HIV-specific CD8+ T cell responses.

PubMed

Bazhan, S I; Karpenko, L I; Ilyicheva, T N; Belavin, P A; Seregin, S V; Danilyuk, N K; Antonets, D V; Ilyichev, A A

2010-04-01

Advances in defining HIV-1 CD8+ T cell epitopes and understanding endogenous MHC class I antigen processing enable the rational design of polyepitope vaccines for eliciting broadly targeted CD8+ T cell responses to HIV-1. Here we describe the construction and comparison of experimental DNA vaccines consisting of ten selected HLA-A2 epitopes from the major HIV-1 antigens Env, Gag, Pol, Nef, and Vpr. The immunogenicity of designed gene constructs was assessed after double DNA prime, single vaccinia virus boost immunization of HLA-A2 transgenic mice. We compared a number of parameters including different strategies for fusing ubiquitin to the polyepitope and including spacer sequences between epitopes to optimize proteasome liberation and TAP transport. It was demonstrated that the vaccine construct that induced in vitro the largest number of [peptide-MHC class I] complexes was also the most immunogenic in the animal experiments. This most immunogenic vaccine construct contained the N-terminal ubiquitin for targeting the polyepitope to the proteasome and included both proteasome liberation and TAP transport optimized spacer sequences that flanked the epitopes within the polyepitope construct. The immunogenicity of determinants was strictly related to their affinities for HLA-A2. Our finding supports the concept of rational vaccine design based on detailed knowledge of antigen processing. Copyright 2010 Elsevier Ltd. All rights reserved.

Epithelium-innate immune cell axis in mucosal responses to SIV.

PubMed

Shang, L; Duan, L; Perkey, K E; Wietgrefe, S; Zupancic, M; Smith, A J; Southern, P J; Johnson, R P; Haase, A T

2017-03-01

In the SIV (simian immunodeficiency virus)-rhesus macaque model of HIV-1 (human immunodeficiency virus type I) transmission to women, one hallmark of the mucosal response to exposure to high doses of SIV is CD4 T-cell recruitment that fuels local virus expansion in early infection. In this study, we systematically analyzed the cellular events and chemoattractant profiles in cervical tissues that precede CD4 T-cell recruitment. We show that vaginal exposure to the SIV inoculum rapidly induces chemokine expression in cervical epithelium including CCL3, CCL20, and CXCL8. The chemokine expression is associated with early recruitment of macrophages and plasmacytoid dendritic cells that are co-clustered underneath the cervical epithelium. Production of chemokines CCL3 and CXCL8 by these cells in turn generates a chemokine gradient that is spatially correlated with the recruitment of CD4 T cells. We further show that the protection of SIVmac239Δnef vaccination against vaginal challenge is correlated with the absence of this epithelium-innate immune cell-CD4 T-cell axis response in the cervical mucosa. Our results reveal a critical role for cervical epithelium in initiating early mucosal responses to vaginal infection, highlight an important role for macrophages in target cell recruitment, and provide further evidence of a paradoxical dampening effect of a protective vaccine on these early mucosal responses.

Effectiveness of a caries preventive program in pregnant women and new mothers on their offspring.

PubMed

Gomez, S S; Weber, A A

2001-03-01

The medical centre at Almirante Nef Naval Hospital, Vina del Mar, Chile, operates a mother and child preventive dental program (PDP) which includes women from their fourth month of pregnancy and mothers with their offspring. The aim was to evaluate the effectiveness of this prenatal and postnatal prevention program after the first four years. The prevalence of early childhood caries of 180 1- to 3.5-year-old children enrolled in the PDP was compared with 180 non-participating children. The control group was randomly selected from the rolls of the healthy child system of of the Valparaiso-San Antonio Health Service and was comparable by age, socio-economic status and level of fluoride in the drinking water (1.0 p.p.m. F) with the PDP group. Clinical caries examinations were conducted by two calibrated examiners using the WHO visual criteria. In the PDP group, 97% of the children were caries free compared with the 77% in the control group. The dft (mean +/- SD) of the PDP children was 0.11 +/- 0.78 versus 0.66 +/- 1.55 for the control children, a difference of 83.3%. The differences between the groups in caries-free status and caries prevalence were both statistically significant (P < 0.05). The preventive dental program was effective in inhibiting caries in pre-school children, even in a population already receiving the benefits of community water fluoridation.

A multichannel integrated circuit for electrical recording of neural activity, with independent channel programmability.

PubMed

Mora Lopez, Carolina; Prodanov, Dimiter; Braeken, Dries; Gligorijevic, Ivan; Eberle, Wolfgang; Bartic, Carmen; Puers, Robert; Gielen, Georges

2012-04-01

Since a few decades, micro-fabricated neural probes are being used, together with microelectronic interfaces, to get more insight in the activity of neuronal networks. The need for higher temporal and spatial recording resolutions imposes new challenges on the design of integrated neural interfaces with respect to power consumption, data handling and versatility. In this paper, we present an integrated acquisition system for in vitro and in vivo recording of neural activity. The ASIC consists of 16 low-noise, fully-differential input channels with independent programmability of its amplification (from 100 to 6000 V/V) and filtering (1-6000 Hz range) capabilities. Each channel is AC-coupled and implements a fourth-order band-pass filter in order to steeply attenuate out-of-band noise and DC input offsets. The system achieves an input-referred noise density of 37 nV/√Hz, a NEF of 5.1, a CMRR > 60 dB, a THD < 1% and a sampling rate of 30 kS/s per channel, while consuming a maximum of 70 μA per channel from a single 3.3 V. The ASIC was implemented in a 0.35 μm CMOS technology and has a total area of 5.6 × 4.5 mm². The recording system was successfully validated in in vitro and in vivo experiments, achieving simultaneous multichannel recordings of cell activity with satisfactory signal-to-noise ratios.

Ovulation Statuses of Surrogate Gilts Are Associated with the Efficiency of Excellent Pig Cloning.

PubMed

Huan, Yanjun; Hu, Kui; Xie, Bingteng; Shi, Yongqian; Wang, Feng; Zhou, Yang; Liu, Shichao; Huang, Bo; Zhu, Jiang; Liu, Zhongfeng; He, Yilong; Li, Jingyu; Kong, Qingran; Liu, Zhonghua

2015-01-01

Somatic cell nuclear transfer (SCNT) is an assisted reproductive technique that can produce multiple copies of excellent livestock. However, low cloning efficiency limits the application of SCNT. In this study, we systematically investigated the major influencing factors related to the overall cloning efficiency in pigs. Here, 13620 cloned embryos derived from excellent pigs were transferred into 79 surrogate gilts, and 119 live cloned piglets were eventually generated. During cloning, group of cloned embryos derived from excellent Landrace or Large white pigs presented no significant differences of cleavage and blastocyst rates, blastocyst cell numbers, surrogate pregnancy and delivery rates, average numbers of piglets born and alive and cloning efficiencies, and group of 101-150, 151-200 or 201-250 cloned embryos transferred per surrogate also displayed a similar developmental efficiency. When estrus stage of surrogate gilts was compared, group of embryo transfer on Day 2 of estrus showed significantly higher pregnancy rate, delivery rate, average number of piglets born, average alive piglet number or cloning efficiency than group on Day 1, Day 3, Day 4 or Day 5, respectively (P<0.05). And, in comparison with the preovulation and postovulation groups, group of surrogate gilts during periovulation displayed a significantly higher overall cloning efficiency (P<0.05). Further investigation of surrogate estrus stage and ovulation status displayed that ovulation status was the real factor underlying estrus stage to determine the overall cloning efficiency. And more, follicle puncture for preovulation, not transfer position shallowed for preovulation or deepened for postovulation, significantly improved the average number of piglets alive and cloning efficiency (P<0.05). In conclusion, our results demonstrated that ovulation status of surrogate gilts was the fundamental factor determining the overall cloning efficiency of excellent pigs, and follicle puncture, not transfer position change, improved cloning efficiency. This work would have important implications in preserving and breeding excellent livestock and improving the overall cloning efficiency.

Ovulation Statuses of Surrogate Gilts Are Associated with the Efficiency of Excellent Pig Cloning

PubMed Central

Huan, Yanjun; Hu, Kui; Xie, Bingteng; Shi, Yongqian; Wang, Feng; Zhou, Yang; Liu, Shichao; Huang, Bo; Zhu, Jiang; Liu, Zhongfeng; He, Yilong; Li, Jingyu; Kong, Qingran; Liu, Zhonghua

2015-01-01

Somatic cell nuclear transfer (SCNT) is an assisted reproductive technique that can produce multiple copies of excellent livestock. However, low cloning efficiency limits the application of SCNT. In this study, we systematically investigated the major influencing factors related to the overall cloning efficiency in pigs. Here, 13620 cloned embryos derived from excellent pigs were transferred into 79 surrogate gilts, and 119 live cloned piglets were eventually generated. During cloning, group of cloned embryos derived from excellent Landrace or Large white pigs presented no significant differences of cleavage and blastocyst rates, blastocyst cell numbers, surrogate pregnancy and delivery rates, average numbers of piglets born and alive and cloning efficiencies, and group of 101–150, 151–200 or 201–250 cloned embryos transferred per surrogate also displayed a similar developmental efficiency. When estrus stage of surrogate gilts was compared, group of embryo transfer on Day 2 of estrus showed significantly higher pregnancy rate, delivery rate, average number of piglets born, average alive piglet number or cloning efficiency than group on Day 1, Day 3, Day 4 or Day 5, respectively (P<0.05). And, in comparison with the preovulation and postovulation groups, group of surrogate gilts during periovulation displayed a significantly higher overall cloning efficiency (P<0.05). Further investigation of surrogate estrus stage and ovulation status displayed that ovulation status was the real factor underlying estrus stage to determine the overall cloning efficiency. And more, follicle puncture for preovulation, not transfer position shallowed for preovulation or deepened for postovulation, significantly improved the average number of piglets alive and cloning efficiency (P<0.05). In conclusion, our results demonstrated that ovulation status of surrogate gilts was the fundamental factor determining the overall cloning efficiency of excellent pigs, and follicle puncture, not transfer position change, improved cloning efficiency. This work would have important implications in preserving and breeding excellent livestock and improving the overall cloning efficiency. PMID:26565717

Growth Factor-Activated Stem Cell Circuits and Stromal Signals Cooperatively Accelerate Non-Integrated iPSC Reprogramming of Human Myeloid Progenitors

PubMed Central

Park, Tea Soon; Huo, Jeffrey S.; Peters, Ann; Talbot, C. Conover; Verma, Karan; Zimmerlin, Ludovic; Kaplan, Ian M.; Zambidis, Elias T.

2012-01-01

Nonviral conversion of skin or blood cells into clinically useful human induced pluripotent stem cells (hiPSC) occurs in only rare fractions (∼0.001%–0.5%) of donor cells transfected with non-integrating reprogramming factors. Pluripotency induction of developmentally immature stem-progenitors is generally more efficient than differentiated somatic cell targets. However, the nature of augmented progenitor reprogramming remains obscure, and its potential has not been fully explored for improving the extremely slow pace of non-integrated reprogramming. Here, we report highly optimized four-factor reprogramming of lineage-committed cord blood (CB) myeloid progenitors with bulk efficiencies of ∼50% in purified episome-expressing cells. Lineage-committed CD33+CD45+CD34− myeloid cells and not primitive hematopoietic stem-progenitors were the main targets of a rapid and nearly complete non-integrated reprogramming. The efficient conversion of mature myeloid populations into NANOG+TRA-1-81+ hiPSC was mediated by synergies between hematopoietic growth factor (GF), stromal activation signals, and episomal Yamanaka factor expression. Using a modular bioinformatics approach, we demonstrated that efficient myeloid reprogramming correlated not to increased proliferation or endogenous Core factor expressions, but to poised expression of GF-activated transcriptional circuits that commonly regulate plasticity in both hematopoietic progenitors and embryonic stem cells (ESC). Factor-driven conversion of myeloid progenitors to a high-fidelity pluripotent state was further accelerated by soluble and contact-dependent stromal signals that included an implied and unexpected role for Toll receptor-NFκB signaling. These data provide a paradigm for understanding the augmented reprogramming capacity of somatic progenitors, and reveal that efficient induced pluripotency in other cell types may also require extrinsic activation of a molecular framework that commonly regulates self-renewal and differentiation in both hematopoietic progenitors and ESC. PMID:22905176

A Framework for Batched and GPU-Resident Factorization Algorithms Applied to Block Householder Transformations

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

Dong, Tingzing Tim; Tomov, Stanimire Z; Luszczek, Piotr R

As modern hardware keeps evolving, an increasingly effective approach to developing energy efficient and high-performance solvers is to design them to work on many small size and independent problems. Many applications already need this functionality, especially for GPUs, which are currently known to be about four to five times more energy efficient than multicore CPUs. We describe the development of one-sided factorizations that work for a set of small dense matrices in parallel, and we illustrate our techniques on the QR factorization based on Householder transformations. We refer to this mode of operation as a batched factorization. Our approach ismore » based on representing the algorithms as a sequence of batched BLAS routines for GPU-only execution. This is in contrast to the hybrid CPU-GPU algorithms that rely heavily on using the multicore CPU for specific parts of the workload. But for a system to benefit fully from the GPU's significantly higher energy efficiency, avoiding the use of the multicore CPU must be a primary design goal, so the system can rely more heavily on the more efficient GPU. Additionally, this will result in the removal of the costly CPU-to-GPU communication. Furthermore, we do not use a single symmetric multiprocessor(on the GPU) to factorize a single problem at a time. We illustrate how our performance analysis, and the use of profiling and tracing tools, guided the development and optimization of our batched factorization to achieve up to a 2-fold speedup and a 3-fold energy efficiency improvement compared to our highly optimized batched CPU implementations based on the MKL library(when using two sockets of Intel Sandy Bridge CPUs). Compared to a batched QR factorization featured in the CUBLAS library for GPUs, we achieved up to 5x speedup on the K40 GPU.« less

Technical efficiency in milk production in underdeveloped production environment of India*.

PubMed

Bardhan, Dwaipayan; Sharma, Murari Lal

2013-12-01

The study was undertaken in Kumaon division of Uttarakhand state of India with the objective of estimating technical efficiency in milk production across different herd-size category households and factors influencing it. Total of 60 farm households having representation from different herd-size categories drawn from six randomly selected villages of plain and hilly regions of the division constituted the ultimate sampling units of the study. Stochastic frontier production function analysis was used to estimate the technical efficiency in milk production. Multivariate regression equations were fitted taking technical efficiency index as the regressand to identify the factors significantly influencing technical efficiency in milk production. The study revealed that variation in output across farms in the study area was due to difference in their technical efficiency levels. However, it was interesting to note that smallholder producers were more technically efficient in milk production than their larger counterparts, especially in the plains. Apart from herd size, intensity of market participation had significant and positive impact on technical efficiency in the plains. This provides definite indication that increasing the level of commercialization of dairy farms would have beneficial impact on their production efficiency.

Investigation on the Efficiency of Financial Companies in Malaysia with Data Envelopment Analysis Model

NASA Astrophysics Data System (ADS)

Weng Siew, Lam; Kah Fai, Liew; Weng Hoe, Lam

2018-04-01

Financial ratio and risk are important financial indicators to evaluate the financial performance or efficiency of the companies. Therefore, financial ratio and risk factor are needed to be taken into consideration to evaluate the efficiency of the companies with Data Envelopment Analysis (DEA) model. In DEA model, the efficiency of the company is measured as the ratio of sum-weighted outputs to sum-weighted inputs. The objective of this paper is to propose a DEA model by incorporating the financial ratio and risk factor in evaluating and comparing the efficiency of the financial companies in Malaysia. In this study, the listed financial companies in Malaysia from year 2004 until 2015 are investigated. The results of this study show that AFFIN, ALLIANZ, APEX, BURSA, HLCAP, HLFG, INSAS, LPI, MNRB, OSK, PBBANK, RCECAP and TA are ranked as efficient companies. This implies that these efficient companies have utilized their resources or inputs optimally to generate the maximum outputs. This study is significant because it helps to identify the efficient financial companies as well as determine the optimal input and output weights in maximizing the efficiency of financial companies in Malaysia.

Improvements in cloning efficiencies may be possible by increasing uniformity in recipient oocytes and donor cells.

PubMed

Miyoshi, Kazuchika; Rzucidlo, S Jacek; Pratt, Scott L; Stice, Steven L

2003-04-01

The low efficiency of somatic cell cloning is the major obstacle to widespread use of this technology. Incomplete nuclear reprogramming following the transfer of donor nuclei into recipient oocytes has been implicated as a primary reason for the low efficiency of the cloning procedure. The mechanisms and factors that affect the progression of the nuclear reprogramming process have not been completely elucidated, but the identification of these factors and their subsequent manipulation would increase cloning efficiency. At present, many groups are studying donor nucleus reprogramming. Here, we present an approach in which the efficiency of producing viable offspring is improved by selecting recipient oocytes and donor cells that will produce cloned embryos with functionally reprogrammed nuclei. This approach will produce information useful in future studies aimed at further deciphering the nuclear reprogramming process.

Exergetic analysis of autonomous power complex for drilling rig

NASA Astrophysics Data System (ADS)

Lebedev, V. A.; Karabuta, V. S.

2017-10-01

The article considers the issue of increasing the energy efficiency of power equipment of the drilling rig. At present diverse types of power plants are used in power supply systems. When designing and choosing a power plant, one of the main criteria is its energy efficiency. The main indicator in this case is the effective efficiency factor calculated by the method of thermal balances. In the article, it is suggested to use the exergy method to determine energy efficiency, which allows to perform estimations of the thermodynamic perfection degree of the system by the example of a gas turbine plant: relative estimation (exergetic efficiency factor) and an absolute estimation. An exergetic analysis of the gas turbine plant operating in a simple scheme was carried out using the program WaterSteamPro. Exergy losses in equipment elements are calculated.

The field experiments and model of the natural dust deposition effects on photovoltaic module efficiency.

PubMed

Jaszczur, Marek; Teneta, Janusz; Styszko, Katarzyna; Hassan, Qusay; Burzyńska, Paulina; Marcinek, Ewelina; Łopian, Natalia

2018-04-20

The maximisation of the efficiency of the photovoltaic system is crucial in order to increase the competitiveness of this technology. Unfortunately, several environmental factors in addition to many alterable and unalterable factors can significantly influence the performance of the PV system. Some of the environmental factors that depend on the site have to do with dust, soiling and pollutants. In this study conducted in the city centre of Kraków, Poland, characterised by high pollution and low wind speed, the focus is on the evaluation of the degradation of efficiency of polycrystalline photovoltaic modules due to natural dust deposition. The experimental results that were obtained demonstrated that deposited dust-related efficiency loss gradually increased with the mass and that it follows the exponential. The maximum dust deposition density observed for rainless exposure periods of 1 week exceeds 300 mg/m 2 and the results in efficiency loss were about 2.1%. It was observed that efficiency loss is not only mass-dependent but that it also depends on the dust properties. The small positive effect of the tiny dust layer which slightly increases in surface roughness on the module performance was also observed. The results that were obtained enable the development of a reliable model for the degradation of the efficiency of the PV module caused by dust deposition. The novelty consists in the model, which is easy to apply and which is dependent on the dust mass, for low and moderate naturally deposited dust concentration (up to 1 and 5 g/m 2 and representative for many geographical regions) and which is applicable to the majority of cases met in an urban and non-urban polluted area can be used to evaluate the dust deposition-related derating factor (efficiency loss), which is very much sought after by the system designers, and tools used for computer modelling and system malfunction detection.

Identifying Nonprovider Factors Affecting Pediatric Emergency Medicine Provider Efficiency.

PubMed

Saleh, Fareed; Breslin, Kristen; Mullan, Paul C; Tillett, Zachary; Chamberlain, James M

2017-10-31

The aim of this study was to create a multivariable model of standardized relative value units per hour by adjusting for nonprovider factors that influence efficiency. We obtained productivity data based on billing records measured in emergency relative value units for (1) both evaluation and management of visits and (2) procedures for 16 pediatric emergency medicine providers with more than 750 hours worked per year. Eligible shifts were in an urban, academic pediatric emergency department (ED) with 2 sites: a tertiary care main campus and a satellite community site. We used multivariable linear regression to adjust for the impact of shift and pediatric ED characteristics on individual-provider efficiency and then removed variables from the model with minimal effect on productivity. There were 2998 eligible shifts for the 16 providers during a 3-year period. The resulting model included 4 variables when looking at both ED sites combined. These variables include the following: (1) number of procedures billed by provider, (2) season of the year, (3) shift start time, and (4) day of week. Results were improved when we separately modeled each ED location. A 3-variable model using procedures billed by provider, shift start time, and season explained 23% of the variation in provider efficiency at the academic ED site. A 3-variable model using procedures billed by provider, patient arrivals per hour, and shift start time explained 45% of the variation in provider efficiency at the satellite ED site. Several nonprovider factors affect provider efficiency. These factors should be considered when designing productivity-based incentives.

Improvement of force factor of magnetostrictive vibration power generator for high efficiency

NASA Astrophysics Data System (ADS)

Kita, Shota; Ueno, Toshiyuki; Yamada, Sotoshi

2015-05-01

We develop high power magnetostrictive vibration power generator for battery-free wireless electronics. The generator is based on a cantilever of parallel beam structure consisting of coil-wound Galfenol and stainless plates with permanent magnet for bias. Oscillating force exerted on the tip bends the cantilever in vibration yields stress variation of Galfenol plate, which causes flux variation and generates voltage on coil due to the law of induction. This generator has advantages over conventional, such as piezoelectric or moving magnet types, in the point of high efficiency, highly robust, and low electrical impedance. Our concern is the improvement of energy conversion efficiency dependent on the dimension. Especially, force factor, the conversion ratio of the electromotive force (voltage) on the tip velocity in vibration, has an important role in energy conversion process. First, the theoretical value of the force factor is formulated and then the validity was verified by experiments, where we compare four types of prototype with parameters of the dimension using 7.0 × 1.5 × 50 mm beams of Galfenol with 1606-turn wound coil. In addition, the energy conversion efficiency of the prototypes depending on load resistance was measured. The most efficient prototype exhibits the maximum instantaneous power of 0.73 W and energy of 4.7 mJ at a free vibration of frequency of 202 Hz in the case of applied force is 25 N. Further, it was found that energy conversion efficiency depends not only on the force factor but also on the damping (mechanical loss) of the vibration.

Study of Core Competency Elements and Factors Affecting Performance Efficiency of Government Teachers in Northeastern Thailand

ERIC Educational Resources Information Center

Chansirisira, Pacharawit

2012-01-01

The research aimed to investigate the core competency elements and the factors affecting the performance efficiency of the civil service teachers in the northeastern region, Thailand. The research procedure consisted of two steps. In the first step, the data were collected using a questionnaire with the reliability (Cronbach's Alpha) of 0.90. The…

Tensor Factorization for Low-Rank Tensor Completion.

PubMed

Zhou, Pan; Lu, Canyi; Lin, Zhouchen; Zhang, Chao

2018-03-01

Recently, a tensor nuclear norm (TNN) based method was proposed to solve the tensor completion problem, which has achieved state-of-the-art performance on image and video inpainting tasks. However, it requires computing tensor singular value decomposition (t-SVD), which costs much computation and thus cannot efficiently handle tensor data, due to its natural large scale. Motivated by TNN, we propose a novel low-rank tensor factorization method for efficiently solving the 3-way tensor completion problem. Our method preserves the low-rank structure of a tensor by factorizing it into the product of two tensors of smaller sizes. In the optimization process, our method only needs to update two smaller tensors, which can be more efficiently conducted than computing t-SVD. Furthermore, we prove that the proposed alternating minimization algorithm can converge to a Karush-Kuhn-Tucker point. Experimental results on the synthetic data recovery, image and video inpainting tasks clearly demonstrate the superior performance and efficiency of our developed method over state-of-the-arts including the TNN and matricization methods.

Efficiency of single-particle engines

NASA Astrophysics Data System (ADS)

Proesmans, Karel; Driesen, Cedric; Cleuren, Bart; Van den Broeck, Christian

2015-09-01

We study the efficiency of a single-particle Szilard and Carnot engine. Within a first order correction to the quasistatic limit, the work distribution is found to be Gaussian and the correction factor to average work and efficiency only depends on the piston speed. The stochastic efficiency is studied for both models and the recent findings on efficiency fluctuations are confirmed numerically. Special features are revealed in the zero-temperature limit.

Ecological efficiency in China and its influencing factors-a super-efficient SBM metafrontier-Malmquist-Tobit model study.

PubMed

Ma, Xiaojun; Wang, Changxin; Yu, Yuanbo; Li, Yudong; Dong, Biying; Zhang, Xinyu; Niu, Xueqi; Yang, Qian; Chen, Ruimin; Li, Yifan; Gu, Yihan

2018-05-15

Ecological problem is one of the core issues that restrain China's economic development at present, and it is urgently needed to be solved properly and effectively. Based on panel data from 30 regions, this paper uses a super efficiency slack-based measure (SBM) model that introduces the undesirable output to calculate the ecological efficiency, and then uses traditional and metafrontier-Malmquist index method to study regional change trends and technology gap ratios (TGRs). Finally, the Tobit regression and principal component analysis methods are used to analysis the main factors affecting eco-efficiency and impact degree. The results show that about 60% of China's provinces have effective eco-efficiency, and the overall ecological efficiency of China is at the superior middling level, but there is a serious imbalance among different provinces and regions. Ecological efficiency has an obvious spatial cluster effect. There are differences among regional TGR values. Most regions show a downward trend and the phenomenon of focusing on economic development at the expense of ecological protection still exists. Expansion of opening to the outside, increases in R&D spending, and improvement of population urbanization rate have positive effects on eco-efficiency. Blind economic expansion, increases of industrial structure, and proportion of energy consumption have negative effects on eco-efficiency.

FACTOR FINDER CD-ROM

EPA Science Inventory

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

Human Ocular Epithelial Cells Endogenously Expressing SOX2 and OCT4 Yield High Efficiency of Pluripotency Reprogramming.

PubMed

Poon, Ming-Wai; He, Jia; Fang, Xiaowei; Zhang, Zhao; Wang, Weixin; Wang, Junwen; Qiu, Fangfang; Tse, Hung-Fat; Li, Wei; Liu, Zuguo; Lian, Qizhou

2015-01-01

A variety of pluripotency reprogramming frequencies from different somatic cells has been observed, indicating cell origin is a critical contributor for efficiency of pluripotency reprogramming. Identifying the cell sources for efficient induced pluripotent stem cells (iPSCs) generation, and defining its advantages or disadvantages on reprogramming, is therefore important. Human ocular tissue-derived conjunctival epithelial cells (OECs) exhibited endogenous expression of reprogramming factors OCT4A (the specific OCT 4 isoform on pluripotency reprogramming) and SOX2. We therefore determined whether OECs could be used for high efficiency of iPSCs generation. We compared the endogenous expression levels of four pluripotency factors and the pluripotency reprograming efficiency of human OECs with that of ocular stromal cells (OSCs). Real-time PCR, microarray analysis, Western blotting and immunostaining assays were employed to compare OECiPSCs with OSCiPSCs on molecular bases of reprogramming efficiency and preferred lineage-differentiation potential. Using the traditional KMOS (KLF4, C-MYC, OCT4 and SOX2) reprogramming protocol, we confirmed that OECs, endogenously expressing reprogramming factors OCT4A and SOX2, yield very high efficiency of iPSCs generation (~1.5%). Furthermore, higher efficiency of retinal pigmented epithelial differentiation (RPE cells) was observed in OECiPSCs compared to OSCiPSCs or skin fibroblast iMR90iPSCs. The findings in this study suggest that conjunctival-derived epithelial (OECs) cells can be easier converted to iPSCs than conjunctival-derived stromal cells (OSCs). This cell type may also have advantages in retinal pigmented epithelial differentiation.

High external quantum efficiency and fill-factor InGaN/GaN heterojunction solar cells grown by NH3-based molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Lang, J. R.; Neufeld, C. J.; Hurni, C. A.; Cruz, S. C.; Matioli, E.; Mishra, U. K.; Speck, J. S.

2011-03-01

High external quantum efficiency (EQE) p-i-n heterojunction solar cells grown by NH3-based molecular beam epitaxy are presented. EQE values including optical losses are greater than 50% with fill-factors over 72% when illuminated with a 1 sun AM0 spectrum. Optical absorption measurements in conjunction with EQE measurements indicate an internal quantum efficiency greater than 90% for the InGaN absorbing layer. By adjusting the thickness of the top p-type GaN window contact layer, it is shown that the short-wavelength (<365 nm) quantum efficiency is limited by the minority carrier diffusion length in highly Mg-doped p-GaN.

Technical efficiency and productivity of Chinese county hospitals: an exploratory study in Henan province, China.

PubMed

Cheng, Zhaohui; Tao, Hongbing; Cai, Miao; Lin, Haifeng; Lin, Xiaojun; Shu, Qin; Zhang, Ru-Ning

2015-09-09

Chinese county hospitals have been excessively enlarging their scale during the healthcare reform since 2009. The purpose of this paper is to examine the technical efficiency and productivity of county hospitals during the reform process, and to determine whether, and how, efficiency is affected by various factors. 114 sample county hospitals were selected from Henan province, China, from 2010 to 2012. Data envelopment analysis was employed to estimate the technical and scale efficiency of sample hospitals. The Malmquist index was used to calculate productivity changes over time. Tobit regression was used to regress against 4 environmental factors and 5 institutional factors that affected the technical efficiency. (1) 112 (98.2%), 112 (98.2%) and 104 (91.2%) of the 114 sample hospitals ran inefficiently in 2010, 2011 and 2012, with average technical efficiency of 0.697, 0.748 and 0.790, respectively. (2) On average, during 2010-2012, productivity of sample county hospitals increased by 7.8%, which was produced by the progress in technical efficiency changes and technological changes of 0.9% and 6.8%, respectively. (3) Tobit regression analysis indicated that government subsidy, hospital size with above 618 beds and average length of stay assumed a negative sign with technical efficiency; bed occupancy rate, ratio of beds to nurses and ratio of nurses to physicians assumed a positive sign with technical efficiency. There was considerable space for technical efficiency improvement in Henan county hospitals. During 2010-2012, sample hospitals experienced productivity progress; however, the adverse change in pure technical efficiency should be emphasised. Moreover, according to the Tobit results, policy interventions that strictly supervise hospital bed scale, shorten the average length of stay and coordinate the proportion among physicians, nurses and beds, would benefit hospital efficiency. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Measuring the efficiency of Palestinian public hospitals during 2010-2015: an application of a two-stage DEA method.

PubMed

Sultan, Wasim I M; Crispim, José

2018-05-29

While health needs and expenditure in the Occupied Palestinian Territories (OPT) are growing, the international donations are declining and the economic situation is worsening. The purpose of this paper is twofold, to evaluate the productive efficiency of public hospitals in West Bank and to study contextual factors contributing to efficiency differences. This study examined technical efficiency among 11 public hospitals in West Bank from 2010 through 2015 targeting a total of 66 observations. Nationally representative data were extracted from the official annual health reports. We applied input-oriented Data Envelopment Analysis (DEA) models to estimate efficiency scores. To elaborate further on performance, we used Tobit regression to identify contextual factors whose impact on inefficient performance is statistically significant. Despite the increase in efficiency mean scores by 4% from 2010 to 2015, findings show potential savings of 14.5% of resource consumption without reducing the volume of the provided services. The significant Tobit model showed four predictors explaining the inefficient performance of a hospital (p <  0.01) are: bed occupancy rate (BOR); the outpatient-inpatient ratio (OPIPR); hospital's size (SIZE); and the availability of primary healthcare centers within the hospital's catchment area (PRC). There is a strong effect of OPIPR on efficiency differences between hospitals: A one unit increase in OPIPR will lead a decrease of 19.7% in the predicted inefficiency level holding all other factors constant. To date, no previous studies have examined the efficiency of public hospitals in the OPT. Our work identified their efficiency levels for potential improvements and the determinants of efficient performance. Based on the measurement of efficiency, the generated information may guide hospitals' managers, policymakers, and international donors improving the performance of the main national healthcare provider. The scope of this study is limited to public hospitals in West Bank. For a better understanding of the Palestinian market, further research on private hospitals and hospitals in Gaza Strip will be useful.

Technical efficiency and productivity of Chinese county hospitals: an exploratory study in Henan province, China

PubMed Central

Cheng, Zhaohui; Tao, Hongbing; Cai, Miao; Lin, Haifeng; Lin, Xiaojun; Shu, Qin; Zhang, Ru-ning

2015-01-01

Objectives Chinese county hospitals have been excessively enlarging their scale during the healthcare reform since 2009. The purpose of this paper is to examine the technical efficiency and productivity of county hospitals during the reform process, and to determine whether, and how, efficiency is affected by various factors. Setting and participants 114 sample county hospitals were selected from Henan province, China, from 2010 to 2012. Outcome measures Data envelopment analysis was employed to estimate the technical and scale efficiency of sample hospitals. The Malmquist index was used to calculate productivity changes over time. Tobit regression was used to regress against 4 environmental factors and 5 institutional factors that affected the technical efficiency. Results (1) 112 (98.2%), 112 (98.2%) and 104 (91.2%) of the 114 sample hospitals ran inefficiently in 2010, 2011 and 2012, with average technical efficiency of 0.697, 0.748 and 0.790, respectively. (2) On average, during 2010–2012, productivity of sample county hospitals increased by 7.8%, which was produced by the progress in technical efficiency changes and technological changes of 0.9% and 6.8%, respectively. (3) Tobit regression analysis indicated that government subsidy, hospital size with above 618 beds and average length of stay assumed a negative sign with technical efficiency; bed occupancy rate, ratio of beds to nurses and ratio of nurses to physicians assumed a positive sign with technical efficiency. Conclusions There was considerable space for technical efficiency improvement in Henan county hospitals. During 2010–2012, sample hospitals experienced productivity progress; however, the adverse change in pure technical efficiency should be emphasised. Moreover, according to the Tobit results, policy interventions that strictly supervise hospital bed scale, shorten the average length of stay and coordinate the proportion among physicians, nurses and beds, would benefit hospital efficiency. PMID:26353864

The Efficiency and Budgeting of Public Hospitals: Case Study of Iran

PubMed Central

Yusefzadeh, Hasan; Ghaderi, Hossein; Bagherzade, Rafat; Barouni, Mohsen

2013-01-01

Background Hospitals are the most costly and important components of any health care system, so it is important to know their economic values, pay attention to their efficiency and consider factors affecting them. Objective The aim of this study was to assess the technical scale and economic efficiency of hospitals in the West Azerbaijan province of Iran, for which Data Envelopment Analysis (DEA) was used to propose a model for operational budgeting. Materials and Methods This study was a descriptive-analysis that was conducted in 2009 and had three inputs and two outputs. Deap2, 1 software was used for data analysis. Slack and radial movements and surplus of inputs were calculated for selected hospitals. Finally, a model was proposed for performance-based budgeting of hospitals and health sectors using the DEA technique. Results The average scores of technical efficiency, pure technical efficiency (managerial efficiency) and scale efficiency of hospitals were 0.584, 0.782 and 0.771, respectively. In other words the capacity of efficiency promotion in hospitals without any increase in costs and with the same amount of inputs was about 41.5%. Only four hospitals among all hospitals had the maximum level of technical efficiency. Moreover, surplus production factors were evident in these hospitals. Conclusions Reduction of surplus production factors through comprehensive planning based on the results of the Data Envelopment Analysis can play a major role in cost reduction of hospitals and health sectors. In hospitals with a technical efficiency score of less than one, the original and projected values of inputs were different; resulting in a surplus. Hence, these hospitals should reduce their values of inputs to achieve maximum efficiency and optimal performance. The results of this method was applied to hospitals a benchmark for making decisions about resource allocation; linking budgets to performance results; and controlling and improving hospitals performance. PMID:24349726

Computing rank-revealing QR factorizations of dense matrices.

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

Bischof, C. H.; Quintana-Orti, G.; Mathematics and Computer Science

1998-06-01

We develop algorithms and implementations for computing rank-revealing QR (RRQR) factorizations of dense matrices. First, we develop an efficient block algorithm for approximating an RRQR factorization, employing a windowed version of the commonly used Golub pivoting strategy, aided by incremental condition estimation. Second, we develop efficiently implementable variants of guaranteed reliable RRQR algorithms for triangular matrices originally suggested by Chandrasekaran and Ipsen and by Pan and Tang. We suggest algorithmic improvements with respect to condition estimation, termination criteria, and Givens updating. By combining the block algorithm with one of the triangular postprocessing steps, we arrive at an efficient and reliablemore » algorithm for computing an RRQR factorization of a dense matrix. Experimental results on IBM RS/6000 SGI R8000 platforms show that this approach performs up to three times faster that the less reliable QR factorization with column pivoting as it is currently implemented in LAPACK, and comes within 15% of the performance of the LAPACK block algorithm for computing a QR factorization without any column exchanges. Thus, we expect this routine to be useful in may circumstances where numerical rank deficiency cannot be ruled out, but currently has been ignored because of the computational cost of dealing with it.« less

Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma

PubMed Central

Xie, Yuran; Merkel, Olivia M

2015-01-01

Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues has limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases and costimulatory factors that have been reported as targets of siRNA mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages and dendritic cells, which could potentially be applied in asthma therapy. PMID:26148454

Lamp mapping technique for independent determination of the water vapor mixing ratio calibration factor for a Raman lidar system

NASA Astrophysics Data System (ADS)

Venable, Demetrius D.; Whiteman, David N.; Calhoun, Monique N.; Dirisu, Afusat O.; Connell, Rasheen M.; Landulfo, Eduardo

2011-08-01

We have investigated a technique that allows for the independent determination of the water vapor mixing ratio calibration factor for a Raman lidar system. This technique utilizes a procedure whereby a light source of known spectral characteristics is scanned across the aperture of the lidar system's telescope and the overall optical efficiency of the system is determined. Direct analysis of the temperature-dependent differential scattering cross sections for vibration and vibration-rotation transitions (convolved with narrowband filters) along with the measured efficiency of the system, leads to a theoretical determination of the water vapor mixing ratio calibration factor. A calibration factor was also obtained experimentally from lidar measurements and radiosonde data. A comparison of the theoretical and experimentally determined values agrees within 5%. We report on the sensitivity of the water vapor mixing ratio calibration factor to uncertainties in parameters that characterize the narrowband transmission filters, the temperature-dependent differential scattering cross section, and the variability of the system efficiency ratios as the lamp is scanned across the aperture of the telescope used in the Howard University Raman Lidar system.

Evaluation of species-dependent detection efficiencies in the aerosol mass spectrometer

USDA-ARS?s Scientific Manuscript database

Mass concentrations of chemical species calculated from the aerosol mass spectrometer (AMS) depend on two factors: particle collection efficiency (CE) and relative ionization efficiency (RIE, relative to the primary calibrant ammonium nitrate). While previous studies have characterized CE, RIE is re...

A neuro-data envelopment analysis approach for optimization of uncorrelated multiple response problems with smaller the better type controllable factors

NASA Astrophysics Data System (ADS)

Bashiri, Mahdi; Farshbaf-Geranmayeh, Amir; Mogouie, Hamed

2013-11-01

In this paper, a new method is proposed to optimize a multi-response optimization problem based on the Taguchi method for the processes where controllable factors are the smaller-the-better (STB)-type variables and the analyzer desires to find an optimal solution with smaller amount of controllable factors. In such processes, the overall output quality of the product should be maximized while the usage of the process inputs, the controllable factors, should be minimized. Since all possible combinations of factors' levels, are not considered in the Taguchi method, the response values of the possible unpracticed treatments are estimated using the artificial neural network (ANN). The neural network is tuned by the central composite design (CCD) and the genetic algorithm (GA). Then data envelopment analysis (DEA) is applied for determining the efficiency of each treatment. Although the important issue for implementation of DEA is its philosophy, which is maximization of outputs versus minimization of inputs, this important issue has been neglected in previous similar studies in multi-response problems. Finally, the most efficient treatment is determined using the maximin weight model approach. The performance of the proposed method is verified in a plastic molding process. Moreover a sensitivity analysis has been done by an efficiency estimator neural network. The results show efficiency of the proposed approach.

Experimental investigations of hybrid PV/Spiral flow thermal collector system performance using Al2O3/water nanofluid

NASA Astrophysics Data System (ADS)

Gangadevi, R.; Vinayagam, B. K.; Senthilraja, S.

2017-05-01

In this paper, the PV/T (Photovoltaic thermal unit) system is investigated experimentally to examine the thermal, electrical and overall efficiency by circulating Al2O3/water nanofluid of 1wt% and 2wt% with an optimum flow rate of 40L/H. The overall efficiency of PVT system is largely influenced by various factors such as heat due to photovoltaic action; energy radiated at the infrared wavelength of the solar spectrum, solar irradiance, mounting structure, tilt angle, wind speed direction, Ambient temperature and panel material composition. However, the major factor is considered in this study to extract the heat generated in the PV panel by using nanofluid as a coolant to increase the overall system efficiency. Therefore, the result shows that by using 2 wt% Al2O3/water nanofluid the electrical efficiency, thermal efficiency and overall efficiency of the PVT system enhanced by 13%, 45%, and 58% respectively compared with water.

Technical efficiency of selected hospitals in Eastern Ethiopia.

PubMed

Ali, Murad; Debela, Megersa; Bamud, Tewfik

2017-12-01

This study examines the relative technical efficiency of 12 hospitals in Eastern Ethiopia. Using six-year-round panel data for the period between 2007/08 and 2012/13, this study examines the technical efficiency, total factor productivity, and determinants of the technical inefficiency of hospitals. Data envelopment analysis (DEA) and DEA- based Malmquist productivity index used to estimate relative technical efficiency, scale efficiency, and total factor productivity index of hospitals. Tobit model used to examine the determinants of the technical inefficiency of hospitals. The DEA Variable Returns to Scale (VRS) estimate indicated that 6 (50%), 5 (42%), 3 (25%), 3 (25%), 4 (33%), and 3 (25%) of the hospitals were technically inefficient while 9 (75%), 9 (75%), 7 (58%), 7 (58%), 7 (58%) and 8 (67%) of hospitals were scale inefficient between 2007/08 and 2012/13, respectively. On average, Malmquist Total Factor Productivity (MTFP) of the hospitals decreased by 3.6% over the panel period. The Tobit model shows that teaching hospital is less efficiency than other hospitals. The Tobit regression model further shows that medical doctor to total staff ratio, the proportion of outpatient visit to inpatient days, and the proportion of inpatients treated per medical doctor were negatively related with technical inefficiency of hospitals. Hence, policy interventions that help utilize excess capacity of hospitals, increase doctor to other staff ratio, and standardize number of inpatients treated per doctor would contribute to the improvement of the technical efficiency of hospitals.

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

Paajanen, A.; Lehto, J.; Santapakka, T.

The efficiencies of 15 commercially available activated carbons were tested for the separation of trace cobalt ({sup 60}Co) in buffer solutions at pH 5.0, 6.7, and 9.1. On the basis of the results four carbon products, Diahope-006, Eurocarb TN5, Hydraffin DG47, and Norit ROW Supra, were selected for further study. These carbons represented varying (low, medium and high) cobalt removal efficiencies and were prepared of three typical raw materials: peat, coconut shell, or coal. Study was made of the effects on sorption efficiencies of factors of interest in metal/radionuclide-bearing waste effluents. These factors were pH, sodium ions, borate, and citrate.

An efficient quantum algorithm for spectral estimation

NASA Astrophysics Data System (ADS)

Steffens, Adrian; Rebentrost, Patrick; Marvian, Iman; Eisert, Jens; Lloyd, Seth

2017-03-01

We develop an efficient quantum implementation of an important signal processing algorithm for line spectral estimation: the matrix pencil method, which determines the frequencies and damping factors of signals consisting of finite sums of exponentially damped sinusoids. Our algorithm provides a quantum speedup in a natural regime where the sampling rate is much higher than the number of sinusoid components. Along the way, we develop techniques that are expected to be useful for other quantum algorithms as well—consecutive phase estimations to efficiently make products of asymmetric low rank matrices classically accessible and an alternative method to efficiently exponentiate non-Hermitian matrices. Our algorithm features an efficient quantum-classical division of labor: the time-critical steps are implemented in quantum superposition, while an interjacent step, requiring much fewer parameters, can operate classically. We show that frequencies and damping factors can be obtained in time logarithmic in the number of sampling points, exponentially faster than known classical algorithms.

Does multi-functionality affect technical efficiency? A non-parametric analysis of the Scottish dairy industry.

PubMed

Barnes, A P

2006-09-01

Recent policy changes within the Common Agricultural Policy have led to a shift from a solely production-led agriculture towards the promotion of multi-functionality. Conversely, the removal of production-led supports would indicate that an increased concentration on production efficiencies would seem a critical strategy for a country's future competitiveness. This paper explores the relationship between the 'multi-functional' farming attitude desired by policy makers and its effect on technical efficiency within Scottish dairy farming. Technical efficiency scores are calculated by applying the non-parametric data envelopment analysis technique and then measured against causes of inefficiency. Amongst these explanatory factors is a constructed score of multi-functionality. This research finds that, amongst other factors, a multi-functional attitude has a significant positive effect on technical efficiency. Consequently, this seems to validate the promotion of a multi-functional approach to farming currently being championed by policy-makers.

Derivation of the open-circuit voltage of organic solar cells

NASA Astrophysics Data System (ADS)

Staple, Douglas B.; Oliver, Patricia A. K.; Hill, Ian G.

2014-05-01

Organic photovoltaic cells have improved in efficiency from 1% two decades ago to over 10% today. Continued improvement necessitates a theoretical understanding of the factors determining efficiency. Organic photovoltaic efficiency can be parameterized in terms of open-circuit voltage, short-circuit current, and fill factor. Here we present a theory that explains the dependencies of open-circuit voltage on semiconductor energy levels, light intensity, solar cell and light-source temperatures, charge-carrier recombination, and external fluorescence efficiency. The present theory also explains why recombination at the donor-acceptor heterointerface is a dominant process in heterojunction-based cells. Furthermore, the Carnot efficiency appears, highlighting the connection to basic thermodynamics. The theory presented here is consistent with and builds on the experimental and theoretical observations already in the literature. Crucially, the present theory can be straightforwardly derived in a line-by-line fashion using standard tools from statistical physics.

A Comparison of Visual and Auditory Processing Tests on the Woodcock-Johnson Tests of Cognitive Ability, Revised and the Learning Efficiency Test-II.

ERIC Educational Resources Information Center

Bolen, L. M.; Kimball, D. J.; Hall, C. W.; Webster, R. E.

1997-01-01

Compares the visual and auditory processing factors of the Woodcock Johnson Tests of Cognitive Ability, Revised (WJR COG) and the visual and auditory memory factors of the Learning Efficiency Test, II (LET-II) among 120 college students. Results indicate two significant performance differences between the WJR COG and LET-II. (RJM)

Batched matrix computations on hardware accelerators based on GPUs

DOE PAGES

Haidar, Azzam; Dong, Tingxing; Luszczek, Piotr; ...

2015-02-09

Scientific applications require solvers that work on many small size problems that are independent from each other. At the same time, the high-end hardware evolves rapidly and becomes ever more throughput-oriented and thus there is an increasing need for an effective approach to develop energy-efficient, high-performance codes for these small matrix problems that we call batched factorizations. The many applications that need this functionality could especially benefit from the use of GPUs, which currently are four to five times more energy efficient than multicore CPUs on important scientific workloads. This study, consequently, describes the development of the most common, one-sidedmore » factorizations, Cholesky, LU, and QR, for a set of small dense matrices. The algorithms we present together with their implementations are, by design, inherently parallel. In particular, our approach is based on representing the process as a sequence of batched BLAS routines that are executed entirely on a GPU. Importantly, this is unlike the LAPACK and the hybrid MAGMA factorization algorithms that work under drastically different assumptions of hardware design and efficiency of execution of the various computational kernels involved in the implementation. Thus, our approach is more efficient than what works for a combination of multicore CPUs and GPUs for the problems sizes of interest of the application use cases. The paradigm where upon a single chip (a GPU or a CPU) factorizes a single problem at a time is not at all efficient in our applications’ context. We illustrate all of these claims through a detailed performance analysis. With the help of profiling and tracing tools, we guide our development of batched factorizations to achieve up to two-fold speedup and three-fold better energy efficiency as compared against our highly optimized batched CPU implementations based on MKL library. Finally, the tested system featured two sockets of Intel Sandy Bridge CPUs and we compared with a batched LU factorizations featured in the CUBLAS library for GPUs, we achieve as high as 2.5× speedup on the NVIDIA K40 GPU.« less

Evaluating the Relationship between Productivity and Quality in Emergency Departments

PubMed Central

Bastian, Nathaniel D.; Riordan, John P.

2017-01-01

Background In the United States, emergency departments (EDs) are constantly pressured to improve operational efficiency and quality in order to gain financial benefits and maintain a positive reputation. Objectives The first objective is to evaluate how efficiently EDs transform their input resources into quality outputs. The second objective is to investigate the relationship between the efficiency and quality performance of EDs and the factors affecting this relationship. Methods Using two data sources, we develop a data envelopment analysis (DEA) model to evaluate the relative efficiency of EDs. Based on the DEA result, we performed multinomial logistic regression to investigate the relationship between ED efficiency and quality performance. Results The DEA results indicated that the main source of inefficiencies was working hours of technicians. The multinomial logistic regression result indicated that the number of electrocardiograms and X-ray procedures conducted in the ED and the length of stay were significantly associated with the trade-offs between relative efficiency and quality. Structural ED characteristics did not influence the relationship between efficiency and quality. Conclusions Depending on the structural and operational characteristics of EDs, different factors can affect the relationship between efficiency and quality. PMID:29065673

Feed efficiency and the microbiota of the alimentary tract

USDA-ARS?s Scientific Manuscript database

There is considerable variation in the efficiency that cattle convert feed for maintenance and product (body weight gain, milk, and conceptus). Both intake and gain are polygenic traits and to better understand factors that contribute to variation in feed efficiency more defined phenotypes are need...

A critical review on factors influencing fermentative hydrogen production.

PubMed

Kothari, Richa; Kumar, Virendra; Pathak, Vinayak V; Ahmad, Shamshad; Aoyi, Ochieng; Tyagi, V V

2017-03-01

Biohydrogen production by dark fermentation of different waste materials is a promising approach to produce bio-energy in terms of renewable energy exploration. This communication has reviewed various influencing factors of dark fermentation process with detailed account of determinants in biohydrogen production. It has also focused on different factors such as improved bacterial strain, reactor design, metabolic engineering and two stage processes to enhance the bioenergy productivity from substrate. The study also suggest that complete utilization of substrates for biological hydrogen production requires the concentrated research and development for efficient functioning of microorganism with integrated application for energy production and bioremediation. Various studies have been taken into account here, to show the comparative efficiency of different substrates and operating conditions with inhibitory factors and pretreatment option for biohydrogen production. The study reveals that an extensive research is needed to observe field efficiency of process using low cost substrates and integration of dark and photo fermentation process. Integrated approach of fermentation process will surely compete with conventional hydrogen process and replace it completely in future.

How to assess performance in cycling: the multivariate nature of influencing factors and related indicators

PubMed Central

Castronovo, A. Margherita; Conforto, Silvia; Schmid, Maurizio; Bibbo, Daniele; D'Alessio, Tommaso

2013-01-01

Finding an optimum for the cycling performance is not a trivial matter, since the literature shows the presence of many controversial aspects. In order to quantify different levels of performance, several indexes have been defined and used in many studies, reflecting variations in physiological and biomechanical factors. In particular, indexes such as Gross Efficiency (GE), Net Efficiency (NE) and Delta Efficiency (DE) have been referred to changes in metabolic efficiency (EffMet), while the Indexes of Effectiveness (IE), defined over the complete crank revolution or over part of it, have been referred to variations in mechanical effectiveness (EffMech). All these indicators quantify the variations of different factors [i.e., muscle fibers type distribution, pedaling cadence, setup of the bicycle frame, muscular fatigue (MFat), environmental variables, ergogenic aids, psychological traits (PsychTr)], which, moreover, show high mutual correlation. In the attempt of assessing cycling performance, most studies in the literature keep all these factors separated. This may bring to misleading results, leaving unanswered the question of how to improve cycling performance. This work provides an overview on the studies involving indexes and factors usually related to performance monitoring and assessment in cycling. In particular, in order to clarify all those aspects, the mutual interactions among these factors are highlighted, in view of a global performance assessment. Moreover, a proposal is presented advocating for a model-based approach that considers all factors mentioned in the survey, including the mutual interaction effects, for the definition of an objective function E representing the overall effectiveness of a training program in terms of both EffMet and EffMech. PMID:23734130

Compatibility of segmented thermoelectric generators

NASA Technical Reports Server (NTRS)

Snyder, J.; Ursell, T.

2002-01-01

It is well known that power generation efficiency improves when materials with appropriate properties are combined either in a cascaded or segmented fashion across a temperature gradient. Past methods for determining materials used in segmentation weremainly concerned with materials that have the highest figure of merit in the temperature range. However, the example of SiGe segmented with Bi2Te3 and/or various skutterudites shows a marked decline in device efficiency even though SiGe has the highest figure of merit in the temperature range. The origin of the incompatibility of SiGe with other thermoelectric materials leads to a general definition of compatibility and intrinsic efficiency. The compatibility factor derived as = (Jl+zr - 1) a is a function of only intrinsic material properties and temperature, which is represented by a ratio of current to conduction heat. For maximum efficiency the compatibility factor should not change with temperature both within a single material, and in the segmented leg as a whole. This leads to a measure of compatibility not only between segments, but also within a segment. General temperature trends show that materials are more self compatible at higher temperatures, and segmentation is more difficult across a larger -T. The compatibility factor can be used as a quantitative guide for deciding whether a material is better suited for segmentation orcascading. Analysis of compatibility factors and intrinsic efficiency for optimal segmentation are discussed, with intent to predict optimal material properties, temperature interfaces, and/or currentheat ratios.

Experimental investigation on the hydrodynamic performance of a wave energy converter

NASA Astrophysics Data System (ADS)

Zheng, Xiong-bo; Ma, Yong; Zhang, Liang; Jiang, Jin; Liu, Heng-xu

2017-06-01

Wave energy is an important type of marine renewable energy. A wave energy converter (WEC) moored with two floating bodies was developed in the present study. To analyze the dynamic performance of the WEC, an experimental device was designed and tested in a tank. The experiment focused on the factors which impact the motion and energy conversion performance of the WEC. Dynamic performance was evaluated by the relative displacements and velocities of the oscillator and carrier which served as the floating bodies of WEC. Four factors were tested, i.e. wave height, wave period, power take-off (PTO) damping, and mass ratio ( R M) of the oscillator and carrier. Experimental results show that these factors greatly affect the energy conversion performance, especially when the wave period matches R M and PTO damping. According to the results, we conclude that: (a) the maximization of the relative displacements and velocities leads to the maximization of the energy conversion efficiency; (b) the larger the wave height, the higher the energy conversion efficiency will be; (c) the relationships of energy conversion efficiency with wave period, PTO damping, and R M are nonlinear, but the maximum efficiency is obtained when these three factors are optimally matched. Experimental results demonstrated that the energy conversion efficiency reached the peak at 28.62% when the wave height was 120 mm, wave period was 1.0 s, R M was 0.21, and the PTO damping was corresponding to the resistance of 100 Ω.

Factors affecting the technical efficiency of general hospitals in Iran: data envelopment analysis.

PubMed

Kalhor, Rohollah; Amini, Saeed; Sokhanvar, Mobin; Lotfi, Farhad; Sharifi, Marziye; Kakemam, Edris

2016-03-01

Restrictions on resource accessibility and its optimal application is the main challenge in organizations nowadays. The aim of this research was to study the technical efficiency and its related factors in Tehran general hospitals. This descriptive analytical study was conducted retrospectively in 2014. Fifty-four hospitals with private, university, and social security ownerships from the total 110 general hospitals were randomly selected for inclusion into this study on the basis of the share of ownership. Data were collected using a checklist with three sections, including background variables, inputs, and outputs. Seventeen (31.48%) hospitals had an efficiency score of 1 (highest efficiency score). The highest average efficiency score was in social security hospitals (84.32). Private and university hospitals ranked next with an average of 84.29 and 79.64, respectively. Analytical results showed that there was a significant relationship between hospital ownership, hospital type in terms of duty and specialization, educational field of the chief executive officer, and technical efficiency. There was no significant relationship between education level of hospital manager and technical efficiency. Most of the studied hospitals were operating at low efficiency. Therefore, policymakers should plan to improve the hospital operations and promote hospitals to an optimal level of efficiency.

Preliminary assessment of injection, storage, and recovery of freshwater in the lower Hawthorn aquifer, Cape Coral, Florida

USGS Publications Warehouse

Quinones-Aponte, Vicente; Wexler, Eliezer J.

1995-01-01

A preliminary assessment of subsurface injection, storage and recovery of fresh canal water was made in the naturally brackish lower Hawthorn aquifer in Cape Coral, southwestern Florida. A digital modeling approach was used for this preliminary assessment, incorporating available data on hydrologic conditions, aquifer properties, and water quality to simulate density-dependent ground-water flow and advective-dispersive transport of a conservative ground-water solute (chloride ion). A baseline simulation was used as reference to compare the effects of changing various operational factors on the recovery efficiency. A recovery efficiency of 64 percent was estimated for the baseline simulation. Based on the model, the recovery efficiency increases if the injection rate and recovery rates are increased and if the ratio of recovery rate to injection rate is increased. Recovery efficiency decreases if the amount of water injected is increased; slightly decreases if the storage time is increased; is not changed significantly if the water is injected to a specific flow zone; increases with successive cycles of injection, storage, and recovery; and decreases if the chloride concentrations in either the injection water or native aquifer water are increased. In everal hypothetical tests, the recovery efficiency fluctuated between 22 and about 100 percent. Two successive cycles could bring the recovery efficiency from 60 to about 80 percent. Interlayer solute mass movement across the upper and lower boundaries seems to be the most important factor affecting the recovery efficiency. A sensitivity analysis was performed applying a technique in which the change in the various factors and the corresponding model responses are normalized so that meaningful comparisons among the responses could be made. The general results from the sensitivity analysis indicated that the permeabilities of the upper and lower flow zones were the most important factors that produced the greatest changes in the relative sensitivity of the recovery efficiency. Almost equally significant changes occurred in the relative sensitivity of the recovery efficiency when all porosity values of the upper and lower flow zones and the leaky confining units and the vertical anisotropy ratio were changed. The advective factors are the most important in the Cape Coral area according to the sensitivity analysis. However, the dispersivity values used in the model were extrapolated from studies conducted at the nearby Lee County Water Treatment Plant, and these values might not be representative of the actual dispersive characteristics of the lower Hawthorn aquifer in the Cape Coral area.

Human Factors and Ergonomics for the Dental Profession.

PubMed

Ross, Al

2016-09-01

This paper proposes that the science of Human Factors and Ergonomics (HFE) is suitable for wide application in dental education, training and practice to improve safety, quality and efficiency. Three areas of interest are highlighted. First it is proposed that individual and team Non-Technical Skills (NTS), such as communication, leadership and stress management can improve error rates and efficiency of procedures. Secondly, in a physically and technically challenging environment, staff can benefit from ergonomic principles which examine design in supporting safe work. Finally, examination of organizational human factors can help anticipate stressors and plan for flexible responses to multiple, variable demands, and fluctuating resources. Clinical relevance: HFE is an evidence-based approach to reducing error rates and procedural complications, and avoiding problems associated with stress and fatigue. Improved teamwork and organizational planning and efficiency can impact directly on patient outcomes.

Optical fiber sensor having an active core

NASA Technical Reports Server (NTRS)

Egalon, Claudio Oliveira (Inventor); Rogowski, Robert S. (Inventor)

1993-01-01

An optical fiber is provided. The fiber is comprised of an active fiber core which produces waves of light upon excitation. A factor ka is identified and increased until a desired improvement in power efficiency is obtained. The variable a is the radius of the active fiber core and k is defined as 2 pi/lambda wherein lambda is the wavelength of the light produced by the active fiber core. In one embodiment, the factor ka is increased until the power efficiency stabilizes. In addition to a bare fiber core embodiment, a two-stage fluorescent fiber is provided wherein an active cladding surrounds a portion of the active fiber core having an improved ka factor. The power efficiency of the embodiment is further improved by increasing a difference between the respective indices of refraction of the active cladding and the active fiber core.

[Environmental efficiency evaluation under carbon emission constraint in Western China].

PubMed

Rong, Jian-bo; Yan, Li-jiao; Huang, Shao-rong; Zhang, Ge

2015-06-01

This research used the SBM model based on undesirable outputs to measure the static environmental efficiency of Western China under carbon emission constraint from 2000 to 2012. The researchers also utilized the Malmquist index to further analyze the change tendency of environmental efficiency. Additionally, Tobit regression analysis was used to study the factors relevant to environmental efficiency. Practical solutions to improve environmental quality in Western China were put forward. The study showed that in Western China, environmental efficiency with carbon emission constraint was significantly lower than that without carbon emission constraint, and the difference could be described as an inverse U-shaped curve which increased at first and then decreased. Guang-xi and Inner Mongolia, the two provinces met the effective environmental efficiency levels all the time under carbon emission constraint. However, the five provinces of Guizhou, Gansu, Qinghai, Ningxia and Xinjiang did not. Furthermore, Ningxia had the lowest level of environmental efficiency, with a score between 0.281-0.386. Although the environmental efficiency of most provinces was currently at an ineffective level, the environmental efficiency quality was gradually improving at an average speed of 6.6%. Excessive CO2 emission and a large amount of energy consumption were the primary factors causing environmental inefficiency in Western China, and energy intensity had the most negative impact on the environmental efficiency. The increase of import and export trade reduced the environmental efficiency significantly in Western China, while the increase of foreign direct investment had a positive effect on its environmental efficiency.

40 CFR 63.1431 - Process vent annual epoxides emission factor plan requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., recovery, or recapture device, along with the expected percent efficiency. (iii) Annual emissions after the... section, kg/yr. R = Expected control efficiency of the combustion, recovery, or recapture device, percent....1426(c) to determine the epoxide control efficiency of the combustion, recovery, or recapture device...

40 CFR 63.1431 - Process vent annual epoxides emission factor plan requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., recovery, or recapture device, along with the expected percent efficiency. (iii) Annual emissions after the... section, kg/yr. R = Expected control efficiency of the combustion, recovery, or recapture device, percent....1426(c) to determine the epoxide control efficiency of the combustion, recovery, or recapture device...

Tag-KEM from Set Partial Domain One-Way Permutations

NASA Astrophysics Data System (ADS)

Abe, Masayuki; Cui, Yang; Imai, Hideki; Kurosawa, Kaoru

Recently a framework called Tag-KEM/DEM was introduced to construct efficient hybrid encryption schemes. Although it is known that generic encode-then-encrypt construction of chosen ciphertext secure public-key encryption also applies to secure Tag-KEM construction and some known encoding method like OAEP can be used for this purpose, it is worth pursuing more efficient encoding method dedicated for Tag-KEM construction. This paper proposes an encoding method that yields efficient Tag-KEM schemes when combined with set partial one-way permutations such as RSA and Rabin's encryption scheme. To our knowledge, this leads to the most practical hybrid encryption scheme of this type. We also present an efficient Tag-KEM which is CCA-secure under general factoring assumption rather than Blum factoring assumption.

On the Efficiency of Particle Injection into the Damping Ring of the Budker Institute of Nuclear Physics

NASA Astrophysics Data System (ADS)

Balakin, V. V.; Vorobev, N. S.; Berkaev, D. V.; Glukhov, S. A.; Gornostaev, P. B.; Dorokhov, V. L.; Chao, Ma Xiao; Meshkov, O. I.; Nikiforov, D. A.; Shashkov, E. V.; Emanov, F. A.; Astrelina, K. V.; Blinov, M. F.; Borin, V. M.

2018-03-01

The efficiency of injection from a linear accelerator into the damping ring of the BINP injection complex has been experimentally studied. The estimations of the injection efficiency are in good agreement with the experimental results. Our method of increasing the capture efficiency can enhance the productivity of the injection complex by a factor of 1.5-2.

Research on the industry environmental total factor productivity in Jiangsu Province based on the SBM-SML

NASA Astrophysics Data System (ADS)

Lingfang, Sun; Han, Wang; Jian, Gong

2017-03-01

This paper uses the SBM-SML to measure the industry environmental total factor productivity in Jiangsu province of its 13 cities during 2005-2014 with SO2 emissions as the undesirable output, and discomposes the total factor productivity into the pure technical efficiency, the scale efficiency change, the pure technical change and the scale technical change. The research shows that the overall trend of the industry environmental total factor productivity is increasing in Jiangsu province during 2005-2014, the technical change is a main reason pushing up growth rates of economy, and the pure technical change is the intrinsic motivation of the technical change.Introduction.

Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction

PubMed Central

Mano, Miguel; Ippodrino, Rudy; Zentilin, Lorena; Zacchigna, Serena; Giacca, Mauro

2015-01-01

Viral vectors based on the adeno-associated virus (AAV) hold great promise for in vivo gene transfer; several unknowns, however, still limit the vectors’ broader and more efficient application. Here, we report the results of a high-throughput, whole-genome siRNA screening aimed at identifying cellular factors regulating AAV transduction. We identified 1,483 genes affecting vector efficiency more than 4-fold and up to 50-fold, either negatively or positively. Most of these factors have not previously been associated to AAV infection. The most effective siRNAs were independent from the virus serotype or analyzed cell type and were equally evident for single-stranded and self-complementary AAV vectors. A common characteristic of the most effective siRNAs was the induction of cellular DNA damage and activation of a cell cycle checkpoint. This information can be exploited for the development of more efficient AAV-based gene delivery procedures. Administration of the most effective siRNAs identified by the screening to the liver significantly improved in vivo AAV transduction efficiency. PMID:26305933

A performance study of sparse Cholesky factorization on INTEL iPSC/860

NASA Technical Reports Server (NTRS)

Zubair, M.; Ghose, M.

1992-01-01

The problem of Cholesky factorization of a sparse matrix has been very well investigated on sequential machines. A number of efficient codes exist for factorizing large unstructured sparse matrices. However, there is a lack of such efficient codes on parallel machines in general, and distributed machines in particular. Some of the issues that are critical to the implementation of sparse Cholesky factorization on a distributed memory parallel machine are ordering, partitioning and mapping, load balancing, and ordering of various tasks within a processor. Here, we focus on the effect of various partitioning schemes on the performance of sparse Cholesky factorization on the Intel iPSC/860. Also, a new partitioning heuristic for structured as well as unstructured sparse matrices is proposed, and its performance is compared with other schemes.

Efficiency for unretained solutes in packed column supercritical fluid chromatography. I. Theory for isothermal conditions and correction factors for carbon dioxide.

PubMed

Poe, Donald P

2005-06-17

A general theory for efficiency of nonuniform columns with compressible mobile phase fluids is applied to the elution of an unretained solute in packed-column supercritical fluid chromatography (pSFC). The theoretical apparent plate height under isothermal conditions is given by the Knox equation multiplied by a compressibility correction factor f1, which is equal to the ratio of the temporal-to-spatial average densities of the mobile phase. If isothermal conditions are maintained, large pressure drops in pSFC should not result in excessive efficiency losses for elution of unretained solutes.

A new approach to estimate the geometrical factors, solid angle approximation, geometrical efficiency and their use in basic interaction cross section measurements

NASA Astrophysics Data System (ADS)

Rao, D. V.; Cesareo, R.; Brunetti, A.; Gigante, G. E.; Takeda, T.; Itai, Y.; Akatsuka, T.

2002-10-01

A new approach is developed to estimate the geometrical factors, solid angle approximation and geometrical efficiency for a system with experimental arrangements using X-ray tube and secondary target as an excitation source in order to produce the nearly monoenergetic Kα radiation to excite the sample. The variation of the solid angle is studied by changing the radius and length of the collimators towards and away from the source and sample. From these values the variation of the total solid angle and geometrical efficiency is deduced and the optimum value is used for the experimental work.

Efficient generation of induced pluripotent stem cells from human bone marrow mesenchymal stem cells.

PubMed

Yulin, X; Lizhen, L; Lifei, Z; Shan, F; Ru, L; Kaimin, H; Huang, H

2012-01-01

Ectopic expression of defined sets of genetic factors can reprogramme somatic cells to induced pluripotent stem cells (iPSCs) that closely resemble embryonic stem cells. However, the low reprogramming efficiency is a significant handicap for mechanistic studies and potential clinical application. In this study, we used human bone marrow-derived mesenchymal stem cells (hBMMSCs) as target cells for reprogramming and investigated efficient iPSC generation from hBMMSCs using the compounds of p53 siRNA, valproic acid (VPA) and vitamin C (Vc) with four transcription factors OCT4, SOX2, KLF4, and c-MYC (compound induction system). The synergetic mechanism of the compounds was studied. Our results showed that the compound induction system could efficiently reprogramme hBMMSCs to iPSCs. hBMMSC-derived iPSC populations expressed pluripotent markers and had multi-potential to differentiate into three germ layer-derived cells. p53 siRNA, VPA and Vc had a synergetic effect on cell reprogramming and the combinatorial use of these substances greatly improved the efficiency of iPSC generation by suppressing the expression of p53, decreasing cell apoptosis, up-regulating the expression of the pluripotent gene OCT4 and modifying the cell cycle. Therefore, our study highlights a straightforward method for improving the speed and efficiency of iPSC generation and provides versatile tools for investigating early developmental processes such as haemopoiesis and relevant diseases. In addition, this study provides a paradigm for the combinatorial use of genetic factors and molecules to improve the efficiency of iPSC generation.

Energy-efficient neural information processing in individual neurons and neuronal networks.

PubMed

Yu, Lianchun; Yu, Yuguo

2017-11-01

Brains are composed of networks of an enormous number of neurons interconnected with synapses. Neural information is carried by the electrical signals within neurons and the chemical signals among neurons. Generating these electrical and chemical signals is metabolically expensive. The fundamental issue raised here is whether brains have evolved efficient ways of developing an energy-efficient neural code from the molecular level to the circuit level. Here, we summarize the factors and biophysical mechanisms that could contribute to the energy-efficient neural code for processing input signals. The factors range from ion channel kinetics, body temperature, axonal propagation of action potentials, low-probability release of synaptic neurotransmitters, optimal input and noise, the size of neurons and neuronal clusters, excitation/inhibition balance, coding strategy, cortical wiring, and the organization of functional connectivity. Both experimental and computational evidence suggests that neural systems may use these factors to maximize the efficiency of energy consumption in processing neural signals. Studies indicate that efficient energy utilization may be universal in neuronal systems as an evolutionary consequence of the pressure of limited energy. As a result, neuronal connections may be wired in a highly economical manner to lower energy costs and space. Individual neurons within a network may encode independent stimulus components to allow a minimal number of neurons to represent whole stimulus characteristics efficiently. This basic principle may fundamentally change our view of how billions of neurons organize themselves into complex circuits to operate and generate the most powerful intelligent cognition in nature. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Calibration of 4π NaI(Tl) detectors with coincidence summing correction using new numerical procedure and ANGLE4 software

NASA Astrophysics Data System (ADS)

Badawi, Mohamed S.; Jovanovic, Slobodan I.; Thabet, Abouzeid A.; El-Khatib, Ahmed M.; Dlabac, Aleksandar D.; Salem, Bohaysa A.; Gouda, Mona M.; Mihaljevic, Nikola N.; Almugren, Kholud S.; Abbas, Mahmoud I.

2017-03-01

The 4π NaI(Tl) γ-ray detectors are consisted of the well cavity with cylindrical cross section, and the enclosing geometry of measurements with large detection angle. This leads to exceptionally high efficiency level and a significant coincidence summing effect, much more than a single cylindrical or coaxial detector especially in very low activity measurements. In the present work, the detection effective solid angle in addition to both full-energy peak and total efficiencies of well-type detectors, were mainly calculated by the new numerical simulation method (NSM) and ANGLE4 software. To obtain the coincidence summing correction factors through the previously mentioned methods, the simulation of the coincident emission of photons was modeled mathematically, based on the analytical equations and complex integrations over the radioactive volumetric sources including the self-attenuation factor. The measured full-energy peak efficiencies and correction factors were done by using 152Eu, where an exact adjustment is required for the detector efficiency curve, because neglecting the coincidence summing effect can make the results inconsistent with the whole. These phenomena, in general due to the efficiency calibration process and the coincidence summing corrections, appear jointly. The full-energy peak and the total efficiencies from the two methods typically agree with discrepancy 10%. The discrepancy between the simulation, ANGLE4 and measured full-energy peak after corrections for the coincidence summing effect was on the average, while not exceeding 14%. Therefore, this technique can be easily applied in establishing the efficiency calibration curves of well-type detectors.

Synergistic effect of electrical and chemical factors on endocytosis in micro-discharge plasma gene transfection

NASA Astrophysics Data System (ADS)

Jinno, M.; Ikeda, Y.; Motomura, H.; Isozaki, Y.; Kido, Y.; Satoh, S.

2017-06-01

We have developed a new micro-discharge plasma (MDP)-based gene transfection method, which transfers genes into cells with high efficiency and low cytotoxicity; however, the mechanism underlying the method is still unknown. Studies revealed that the N-acetylcysteine-mediated inhibition of reactive oxygen species (ROS) activity completely abolished gene transfer. In this study, we used laser-produced plasma to demonstrate that gene transfer does not occur in the absence of electrical factors. Our results show that both electrical and chemical factors are necessary for gene transfer inside cells by microplasma irradiation. This indicates that plasma-mediated gene transfection utilizes the synergy between electrical and chemical factors. The electric field threshold required for transfection was approximately 1 kV m-1 in our MDP system. This indicates that MDP irradiation supplies sufficient concentrations of ROS, and the stimulation intensity of the electric field determines the transfection efficiency in our system. Gene transfer by plasma irradiation depends mainly on endocytosis, which accounts for at least 80% of the transfer, and clathrin-mediated endocytosis is a dominant endocytosis. In plasma-mediated gene transfection, alterations in electrical and chemical factors can independently regulate plasmid DNA adhesion and triggering of endocytosis, respectively. This implies that plasma characteristics can be adjusted according to target cell requirements, and the transfection process can be optimized with minimum damage to cells and maximum efficiency. This may explain how MDP simultaneously achieves high transfection efficiency with minimal cell damage.

Commercial mortgages: An underutilized channel for scaling energy efficiency investments?

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

Mathew, Paul; Wallace, Nancy; Alschuler, Elena

2016-02-01

Commercial mortgages currently do not fully account for energy factors in underwriting and valuation, particularly as it relates to the impact of energy costs and volatility on an owner’s net operating income. As a consequence, energy efficiency is not properly valued and energy risks are not properly assessed and mitigated. Commercial mortgages are a large lever and could be a significant channel for scaling energy efficiency investments. A pilot analysis of loans with different mortgage contract structures and locations showed that when energy cost volatility was included in mortgage valuation, a 20% reduction in energy use resulted in a 1.3%more » average increase in mortgage value. This suggests that the explicit inclusion of energy use and volatility in mortgage valuation can send a strong price signal that financially rewards and values energy efficiency in commercial properties. This paper presents findings from a scoping study addressing energy factors in commercial mortgages. First, we present a review of current practices as it relates to incorporating energy factors into commercial mortgage underwriting and valuation. Next, we detail the impacts of energy factors on property values, net operating income and mortgage valuation. Building operational practices alone can result in energy use variations from -17% to 87%. Finally, we present a set of proposed interventions to properly address energy factors in commercial mortgages, based on extensive discussions with stakeholders including mortgage originators, underwriters, building owners and regulators.« less

Flock Foraging Efficiency in Relation to Food Sensing Ability and Distribution: a Simulation Study

NASA Astrophysics Data System (ADS)

Lee, Sang-Hee

2013-08-01

Flocking may be an advantageous strategy for acquiring food resources. The degree of advantage is related to two factors: the ability of flock members to detect food resources and patterns of food distribution in the environment. To understand foraging efficiency as a function of these factors, I constructed a two-dimensional (2D) flocking model incorporating the two factors. At the start of the simulation, food particles were heterogeneously distributed. The heterogeneity, H, was characterized as a value ranging from 0.0 to 1.0. For each flock member, food sensing ability was defined by two variables: sensing distance, R and sensing angle, θ. Foraging efficiency of a flock was defined as the time, τ, required for a flock to consume all the available food resources. Simulation results showed that flock foraging is most efficient when individuals had an intermediate sensing ability (R = 60), but decreased for low (R < 60) and high (R > 60) sensing ability. When R > 60, patterns in foraging efficiency with increasing sensing distance and food resource aggregation were less consistent. This inconsistency was due to instability of the flock and a higher rate of individuals failing to capture target food resources. In addition, I briefly discuss the benefits obtained by foraging in flocks from an evolutionary perspective.

Occupants' Perceptions of Amenity and Efficiency for Verification of Spatial Design Adequacy.

PubMed

Lee, Sangwon; Wohn, Kwangyun

2016-01-14

The best spatial design condition to satisfy the occupancy needs of amenity and efficiency is determined through analyzing the spatial design adequacy (SDA). In this study, the relationship between the space design elements and space on future occupants' perception are analyzed. The thirty-three participants reported their self-evaluated SDA that describes the quality of eight alternative housing living rooms with different spatial factors. The occupants were guided through the perception processing elaboration in order for them to evaluate the actual perception in the real space. The findings demonstrated that the spatial size (e.g., width, depth, and height) is significantly correlated with the overall satisfaction of amenity. It is also found that the spatial shape (e.g., the width-to-depth ratio, the height-to-area ratio, and room shape) may significantly influence the overall satisfaction of efficiency. The findings also demonstrate that the causal relationship between the spatial factors and space is clearly present in the occupants' perception, reflecting the time-sequential characteristics of the actual experience divided into amenity and efficiency. This result indicates that the correlation between the spatial factors and space of SDA under the occupants' perception processing elaboration can be a useful guide to predict the occupancy satisfaction of amenity and efficiency in real spaces.

Occupants’ Perceptions of Amenity and Efficiency for Verification of Spatial Design Adequacy

PubMed Central

Lee, Sangwon; Wohn, Kwangyun

2016-01-01

The best spatial design condition to satisfy the occupancy needs of amenity and efficiency is determined through analyzing the spatial design adequacy (SDA). In this study, the relationship between the space design elements and space on future occupants’ perception are analyzed. The thirty-three participants reported their self-evaluated SDA that describes the quality of eight alternative housing living rooms with different spatial factors. The occupants were guided through the perception processing elaboration in order for them to evaluate the actual perception in the real space. The findings demonstrated that the spatial size (e.g., width, depth, and height) is significantly correlated with the overall satisfaction of amenity. It is also found that the spatial shape (e.g., the width-to-depth ratio, the height-to-area ratio, and room shape) may significantly influence the overall satisfaction of efficiency. The findings also demonstrate that the causal relationship between the spatial factors and space is clearly present in the occupants’ perception, reflecting the time-sequential characteristics of the actual experience divided into amenity and efficiency. This result indicates that the correlation between the spatial factors and space of SDA under the occupants’ perception processing elaboration can be a useful guide to predict the occupancy satisfaction of amenity and efficiency in real spaces. PMID:26784211

Perceptual load corresponds with factors known to influence visual search

PubMed Central

Roper, Zachary J. J.; Cosman, Joshua D.; Vecera, Shaun P.

2014-01-01

One account of the early versus late selection debate in attention proposes that perceptual load determines the locus of selection. Attention selects stimuli at a late processing level under low-load conditions but selects stimuli at an early level under high-load conditions. Despite the successes of perceptual load theory, a non-circular definition of perceptual load remains elusive. We investigated the factors that influence perceptual load by using manipulations that have been studied extensively in visual search, namely target-distractor similarity and distractor-distractor similarity. Consistent with previous work, search was most efficient when targets and distractors were dissimilar and the displays contained homogeneous distractors; search became less efficient when target-distractor similarity increased irrespective of display heterogeneity. Importantly, we used these same stimuli in a typical perceptual load task that measured attentional spill-over to a task-irrelevant flanker. We found a strong correspondence between search efficiency and perceptual load; stimuli that generated efficient searches produced flanker interference effects, suggesting that such displays involved low perceptual load. Flanker interference effects were reduced in displays that produced less efficient searches. Furthermore, our results demonstrate that search difficulty, as measured by search intercept, has little bearing on perceptual load. These results suggest that perceptual load might be defined in part by well-characterized, continuous factors that influence visual search. PMID:23398258

Bioinspired model of mechanical energy harvesting based on flexoelectric membranes.

PubMed

Rey, Alejandro D; Servio, P; Herrera-Valencia, E E

2013-02-01

Membrane flexoelectricity is an electromechanical coupling process that describes membrane electrical polarization due to bending and membrane bending under electric fields. In this paper we propose, formulate, and characterize a mechanical energy harvesting system consisting of a deformable soft flexoelectric thin membrane subjected to harmonic forcing from contacting bulk fluids. The key elements of the energy harvester are formulated and characterized, including (i) the mechanical-to-electrical energy conversion efficiency, (ii) the electromechanical shape equation connecting fluid forces with membrane curvature and electric displacement, and (iii) the electric power generation and efficiency. The energy conversion efficiency is cast as the ratio of flexoelectric coupling to the product of electric and bending elasticity. The device is described by a second-order curvature dynamics coupled to the electric displacement equation and as such results in mechanical power absorption with a resonant peak whose amplitude decreases with bending viscosity. The electric power generation is proportional to the conversion factor and the power efficiency decreases with frequency. Under high bending viscosity, the power efficiency increases with the conversion factor and under low viscosities it decreases with the conversion factor. The theoretical results presented contribute to the ongoing experimental efforts to develop mechanical energy harvesting from fluid flow energy through solid-fluid interactions and electromechanical transduction.

Factors affecting the development of somatic cell nuclear transfer embryos in Cattle.

PubMed

Akagi, Satoshi; Matsukawa, Kazutsugu; Takahashi, Seiya

2014-01-01

Nuclear transfer is a complex multistep procedure that includes oocyte maturation, cell cycle synchronization of donor cells, enucleation, cell fusion, oocyte activation and embryo culture. Therefore, many factors are believed to contribute to the success of embryo development following nuclear transfer. Numerous attempts to improve cloning efficiency have been conducted since the birth of the first sheep by somatic cell nuclear transfer. However, the efficiency of somatic cell cloning has remained low, and applications have been limited. In this review, we discuss some of the factors that affect the developmental ability of somatic cell nuclear transfer embryos in cattle.

Quality factor concept in piezoceramic transformer performance description.

PubMed

Mezheritsky, Alex V

2006-02-01

A new general approach based on the quality factor concept to piezoceramic transformer (PT) performance description is proposed. The system's quality factor, material elastic anisotropy, and coupling factors of the input and output sections of an electrically excited and electrically loaded PT fully characterize its resonance and near-resonance behavior. The PT efficiency, transformation ratio, and input and output power were analytically analyzed and simulated as functions of the load and frequency for the simplest classical Langevin-type and Rosen-type PT designs. A new formulation of the electrical input impedance allows one to separate the power consumed by PT from the power transferred into the load. The system's PT quality factor takes into account losses in each PT "input-output-load" functional components. The loading process is changing PT input electrical impedance on the way that under loading the minimum series impedance is increasing and the maximum parallel impedance is decreasing coincidentally. The quality-factors ratio, between the states of fully loaded and nonloaded PT, is one of the best measures of PTs dynamic performance--practically, the lower the ratio is, the better PT efficiency. A simple and effective method for the loaded PT quality factor determination is proposed. As was found, a piezoceramic with low piezoelectric anisotropy is required to provide maximum PT efficiency and higher corresponding voltage gain. Limitations on the PT output voltage and power, caused by nonlinear effects in piezoceramics, were established.

Pulmonary Delivery of siRNA via Polymeric Vectors as Therapies of Asthma.

PubMed

Xie, Yuran; Merkel, Olivia M

2015-10-01

Asthma is a chronic inflammatory disease. Despite the fact that current therapies, such as the combination of inhaled corticosteroids and β2-agonists, can control the symptoms of asthma in most patients, there is still an urgent need for an alternative anti-inflammatory therapy for patients who suffer from severe asthma but lack acceptable response to conventional therapies. Many molecular factors are involved in the inflammatory process in asthma, and thus blocking the function of these factors could efficiently alleviate airway inflammation. RNA interference (RNAi) is often thought to be the answer in the search for more efficient and biocompatible treatments. However, difficulties of efficient delivery of small interference RNA (siRNA), the key factor in RNAi, to target cells and tissues have limited its clinical application. In this review, we summarize cytokines and chemokines, transcription factors, tyrosine kinases, and costimulatory factors that have been reported as targets of siRNA-mediated treatment in experimental asthma. Additionally, we conclude several targeted delivery systems of siRNA to specific cells such as T cells, macrophages, and dendritic cells, which could potentially be applied in asthma therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Novel Approach to Measuring Efficiency of Scientific Research Projects: Data Envelopment Analysis.

PubMed

Dilts, David M; Zell, Adrienne; Orwoll, Eric

2015-10-01

Measuring the efficiency of resource allocation for the conduct of scientific projects in medical research is difficult due to, among other factors, the heterogeneity of resources supplied (e.g., dollars or FTEs) and outcomes expected (e.g., grants, publications). While this is an issue in medical science, it has been approached successfully in other fields by using data envelopment analysis (DEA). DEA has a number of advantages over other techniques as it simultaneously uses multiple heterogeneous inputs and outputs to determine which projects are performing most efficiently, referred to as being at the efficiency frontier, when compared to others in the data set. This research uses DEA for the evaluation of supported translational science projects by the Oregon Clinical and Translational Research Institute (OCTRI), a NCATS Clinical & Translational Science Award (CTSA) recipient. These results suggest that the primary determinate of overall project efficiency at OCTRI is the amount of funding, with smaller amounts of funding providing more efficiency than larger funding amounts. These results, and the use of DEA, highlight both the success of using this technique in helping determine medical research efficiency and those factors to consider when distributing funds for new projects at CTSAs. © 2015 Wiley Periodicals, Inc.

Factors limiting device efficiency in organic photovoltaics.

PubMed

Janssen, René A J; Nelson, Jenny

2013-04-04

The power conversion efficiency of the most efficient organic photovoltaic (OPV) cells has recently increased to over 10%. To enable further increases, the factors limiting the device efficiency in OPV must be identified. In this review, the operational mechanism of OPV cells is explained and the detailed balance limit to photovoltaic energy conversion, as developed by Shockley and Queisser, is outlined. The various approaches that have been developed to estimate the maximum practically achievable efficiency in OPV are then discussed, based on empirical knowledge of organic semiconductor materials. Subsequently, approaches made to adapt the detailed balance theory to incorporate some of the fundamentally different processes in organic solar cells that originate from using a combination of two complementary, donor and acceptor, organic semiconductors using thermodynamic and kinetic approaches are described. The more empirical formulations to the efficiency limits provide estimates of 10-12%, but the more fundamental descriptions suggest limits of 20-24% to be reachable in single junctions, similar to the highest efficiencies obtained for crystalline silicon p-n junction solar cells. Closing this gap sets the stage for future materials research and development of OPV. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Simulated Annealing Algorithm for the Optimization of Multistage Depressed Collector Efficiency

NASA Technical Reports Server (NTRS)

Vaden, Karl R.; Wilson, Jeffrey D.; Bulson, Brian A.

2002-01-01

The microwave traveling wave tube amplifier (TWTA) is widely used as a high-power transmitting source for space and airborne communications. One critical factor in designing a TWTA is the overall efficiency. However, overall efficiency is highly dependent upon collector efficiency; so collector design is critical to the performance of a TWTA. Therefore, NASA Glenn Research Center has developed an optimization algorithm based on Simulated Annealing to quickly design highly efficient multi-stage depressed collectors (MDC).

Including Both Time and Accuracy in Defining Text Search Efficiency.

ERIC Educational Resources Information Center

Symons, Sonya; Specht, Jacqueline A.

1994-01-01

Examines factors related to efficiency in a textbook search task. Finds that time and accuracy involved distinct processes and that accuracy was related to verbal competence. Finds further that measures of planning and extracting information accounted for 59% of the variance in search efficiency. Suggests that both accuracy and rate need to be…

Predicting Efficiency of Travel in Young, Visually Impaired Children from Their Other Spatial Skills.

ERIC Educational Resources Information Center

Hill, Anita; And Others

1985-01-01

To test ways of predicting how efficiently visually impaired children learn travel skills, a criteria checklist of spatial skills was developed for close-body space, local space, and geographical/travel space. Comparison was made between predictors of efficient learning including subjective ratings of teachers, personal qualities and factors of…

Approaches to the Organization of the Energy Efficient Activity at the Regional Level in the Context of Limited Budget Resources during the Transformation of Energy Market Paradigm

NASA Astrophysics Data System (ADS)

Vakulenko, Ihor; Myroshnychenko, Iuliia

2015-12-01

The research is devoted to the problem of the assessment of the integrated projects investment efficiency, energy saving and energy efficiency measures for social and municipal buildings within the course aimed at the reduction of the natural gas consumption and its replacement by alternative fuel types, that is important for a number of European countries, and Ukraine in particular. The objectives of the research are as follows: comparative assessment of the quality of integrated and element-by-element approaches to energy saving encompassing investment, environmental, social and organizational aspects; the formulation of practical recommendations to improve the efficiency of development and implementation of integrated programs in the field of energy saving and energy efficiency. It is proposed to use the methodology of system analysis with the elements of deduction that is practical and that allows to set key factors that influence the processes of energy replacement and energy efficiency increase, as well as factors that constrain them.

Technical indicators of economic performance in dairy sheep farming.

PubMed

Theodoridis, A; Ragkos, A; Roustemis, D; Arsenos, G; Abas, Z; Sinapis, E

2014-01-01

In this study, the level of technical efficiency of 58 sheep farms rearing the Chios breed in Greece was measured through the application of the stochastic frontier analysis method. A Translog stochastic frontier production function was estimated using farm accounting data of Chios sheep farms and the impact of various socio-demographic and biophysical factors on the estimated efficiency of the farms was evaluated. The farms were classified into efficiency groups on the basis of the estimated level of efficiency and a technical and economic descriptive analysis was applied in order to illustrate an indicative picture of their structure and productivity. The results of the stochastic frontier model indicate that there are substantial production inefficiencies among the Chios sheep farms and that these farms could increase their production through the improvement of technical efficiency, whereas the results of the inefficiency effects model reveal that the farm-specific explanatory factors can partly explain the observed efficiency differentials. The measurement of technical inefficiency and the detection of its determinants can be used to form the basis of policy recommendations that could contribute to the development of the sector.

Measuring efficiency of cotton cultivation in Pakistan: a restricted production frontier study.

PubMed

Watto, Muhammad Arif; Mugera, Amin

2014-11-01

Massive groundwater pumping for irrigation has started lowering water tables rapidly in different regions of Pakistan. Declining water tables have thus prompted research efforts to improve agricultural productivity and efficiency to make efficient use of scarce water resources. This study employs a restricted stochastic production frontier to estimate the level of, and factors affecting, technical efficiency of groundwater-irrigated cotton farms in the Punjab province of Pakistan. The mean technical efficiency estimates indicate substantial technical inefficiencies among cotton growers. On average, tube-well owners and water buyers can potentially increase cotton production by 19% and 28%, respectively, without increasing the existing input level. The most influential factors affecting technical efficiency positively are the use of improved quality seed, consultation with extension field staff and farmers' perceptions concerning the availability of groundwater resources for irrigation in the future. This study proposes that adopting improved seed for new cotton varieties and providing better extension services regarding cotton production technology would help to achieve higher efficiency in cotton farming. Within the context of falling water tables, educating farmers about the actual crop water requirements and guiding them about groundwater resource availability may also help to achieve higher efficiencies. © 2014 Society of Chemical Industry. © 2014 Society of Chemical Industry.

Photovoltaic power system tests on an 8-kilowatt single-phase line-commutated inverter

NASA Technical Reports Server (NTRS)

Stover, J. B.

1978-01-01

Efficiency and power factor were measured as functions of solar array voltage and current. The effects of input shunt capacitance and series inductance were determined. Tests were conducted from 15 to 75 percent of the 8 kW rated inverter input power. Measured efficiencies ranged from 76 percent to 88 percent at about 50 percent of rated inverter input power. Power factor ranged from 36 percent to 72 percent.

Calculation of Coincidence Summing Correction Factors for an HPGe detector using GEANT4.

PubMed

Giubrone, G; Ortiz, J; Gallardo, S; Martorell, S; Bas, M C

2016-07-01

The aim of this paper was to calculate the True Coincidence Summing Correction Factors (TSCFs) for an HPGe coaxial detector in order to correct the summing effect as a result of the presence of (88)Y and (60)Co in a multigamma source used to obtain a calibration efficiency curve. Results were obtained for three volumetric sources using the Monte Carlo toolkit, GEANT4. The first part of this paper deals with modeling the detector in order to obtain a simulated full energy peak efficiency curve. A quantitative comparison between the measured and simulated values was made across the entire energy range under study. The True Summing Correction Factors were calculated for (88)Y and (60)Co using the full peak efficiencies obtained with GEANT4. This methodology was subsequently applied to (134)Cs, and presented a complex decay scheme. Copyright © 2016 Elsevier Ltd. All rights reserved.

Energy Factors in Commercial Mortgages: Gaps and Opportunities

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

Mathew, Paul; Coleman, Philip; Wallace, Nancy

2016-09-01

The commercial real estate mortgage market is enormous, with almost half a trillion dollars in deals originated in 2015. Relative to other energy efficiency financing mechanisms, very little attention has been paid to the potential of commercial mortgages as a channel for promoting energy efficiency investments. The valuation and underwriting elements of the business are largely driven by the “net operating income” (NOI) metric – essentially, rents minus expenses. While NOI ostensibly includes all expenses, energy factors are in several ways given short shrift in the underwriting process. This is particularly interesting when juxtaposed upon a not insignificant body ofmore » research revealing that there are in fact tangible benefits (such as higher valuations and lower vacancy and default rates) for energy-efficient and “green” commercial buildings. This scoping report characterizes the current status and potential interventions to promote greater inclusion of energy factors in the commercial mortgage process.« less

Measuring self-rated productivity: factor structure and variance component analysis of the Health and Work Questionnaire.

PubMed

von Thiele Schwarz, Ulrica; Sjöberg, Anders; Hasson, Henna; Tafvelin, Susanne

2014-12-01

To test the factor structure and variance components of the productivity subscales of the Health and Work Questionnaire (HWQ). A total of 272 individuals from one company answered the HWQ scale, including three dimensions (efficiency, quality, and quantity) that the respondent rated from three perspectives: their own, their supervisor's, and their coworkers'. A confirmatory factor analysis was performed, and common and unique variance components evaluated. A common factor explained 81% of the variance (reliability 0.95). All dimensions and rater perspectives contributed with unique variance. The final model provided a perfect fit to the data. Efficiency, quality, and quantity and three rater perspectives are valid parts of the self-rated productivity measurement model, but with a large common factor. Thus, the HWQ can be analyzed either as one factor or by extracting the unique variance for each subdimension.

Collection efficiency of a single optical fiber in turbid media.

PubMed

Bargo, Paulo R; Prahl, Scott A; Jacques, Steven L

2003-06-01

If a single optical fiber is used for both delivery and collection of light, two major factors affect the measurement of collected light: (1) the light transport in the medium that describes the amount of light that returns to the fiber and (2) the light coupling to the optical fiber that depends on the angular distribution of photons entering the fiber. We focus on the importance of the latter factor and describe how the efficiency of the coupling depends on the optical properties of the medium. For highly scattering tissues, the efficiency is well predicted by the numerical aperture (NA) of the fiber. For lower scattering, such as in soft tissues, photons arrive at the fiber from deeper depths, and the coupling efficiency could increase twofold to threefold above that predicted by the NA.

Efficient Production of Retroviruses Using PLGA/bPEI-DNA Nanoparticles and Application for Reprogramming Somatic Cells

PubMed Central

Do, Eun Kyoung; Cheon, Hyo Cheon; Heo, Soon Chul; Kwon, Yang Woo; Jeong, Geun Ok; Kim, Ba Reun; Kim, Jae Ho

2013-01-01

Reprogramming of somatic cells to pluripotent cells requires the introduction of factors driving fate switches. Viral delivery has been the most efficient method for generation of induced pluripotent stem cells. Transfection, which precedes virus production, is a commonly-used process for delivery of nucleic acids into cells. The aim of this study is to evaluate the efficiency of PLGA/ bPEI nanoparticles in transfection and virus production. Using a modified method of producing PLGA nanoparticles, PLGA/bPEI-DNA nanoparticles were examined for transfection efficiency and virus production yield in comparison with PLGA-DNA, bPEI-DNA nanoparticles or liposome-DNA complexes. After testing various ratios of PLGA, bPEI, and DNA, the ratio of 6:3:1 (PLGA:bPEI:DNA, w/w/w) was determined to be optimal, with acceptable cellular toxicity. PLGA/bPEI-DNA (6:3:1) nanoparticles showed superior transfection efficiency, especially in multiple gene transfection, and viral yield when compared with liposome-DNA complexes. The culture supernatants of HEK293FT cells transfected with PLGA/bPEI-DNA of viral constructs containing reprogramming factors (Oct4, Sox2, Klf4, or c-Myc) successfully and more efficiently generated induced pluripotent stem cell colonies from mouse embryonic fibroblasts. These results strongly suggest that PLGA/bPEI-DNA nanoparticles can provide significant advantages in studying the effect of multiple factor delivery such as in reprogramming or direct conversion of cell fate. PMID:24098810

European regional efficiency and geographical externalities: a spatial nonparametric frontier analysis

NASA Astrophysics Data System (ADS)

Ramajo, Julián; Cordero, José Manuel; Márquez, Miguel Ángel

2017-10-01

This paper analyses region-level technical efficiency in nine European countries over the 1995-2007 period. We propose the application of a nonparametric conditional frontier approach to account for the presence of heterogeneous conditions in the form of geographical externalities. Such environmental factors are beyond the control of regional authorities, but may affect the production function. Therefore, they need to be considered in the frontier estimation. Specifically, a spatial autoregressive term is included as an external conditioning factor in a robust order- m model. Thus we can test the hypothesis of non-separability (the external factor impacts both the input-output space and the distribution of efficiencies), demonstrating the existence of significant global interregional spillovers into the production process. Our findings show that geographical externalities affect both the frontier level and the probability of being more or less efficient. Specifically, the results support the fact that the spatial lag variable has an inverted U-shaped non-linear impact on the performance of regions. This finding can be interpreted as a differential effect of interregional spillovers depending on the size of the neighboring economies: positive externalities for small values, possibly related to agglomeration economies, and negative externalities for high values, indicating the possibility of production congestion. Additionally, evidence of the existence of a strong geographic pattern of European regional efficiency is reported and the levels of technical efficiency are acknowledged to have converged during the period under analysis.

Efficiency and Productivity of County-level Public Hospitals Based on the Data Envelopment Analysis Model and Malmquist Index in Anhui, China

PubMed Central

Li, Nian-Nian; Wang, Cun-Hui; Ni, Hong; Wang, Heng

2017-01-01

Background: China began to implement the national medical and health system and public hospital reforms in 2009 and 2012, respectively. Anhui Province is one of the four pilot provinces, and the medical reform measures received wide attention nationwide. The effectiveness of the above reform needs to get attention. This study aimed to master the efficiency and productivity of county-level public hospitals based on the data envelopment analysis (DEA) model and Malmquist index in Anhui, China, and then provide improvement measures for the future hospital development. Methods: We chose 12 country-level hospitals based on geographical distribution and the economic development level in Anhui Province. Relevant data that were collected in the field and then sorted were provided by the administrative departments of the hospitals. DEA models were used to calculate the dynamic efficiency and Malmquist index factors for the 12 institutions. Results: During 2010–2015, the overall average relative service efficiency of 12 county-level public hospitals was 0.926, and the number of hospitals achieved an effective DEA for each year from 2010 to 2015 was 4, 6, 7, 7, 6, and 8, respectively, as measured using DEA. During this same period, the average overall production efficiency was 0.983, and the total productivity factor had declined. The overall production efficiency of five hospitals was >1, and the rest are <1 between 2010 and 2015. Conclusions: In 2010–2015, the relative service efficiency of 12 county-level public hospitals in Anhui Province showed a decreasing trend, and the service efficiency of each hospital changed. In the past 6 years, although some hospitals have been effective, the efficiency of the county-level public hospitals in Anhui Province has not improved significantly, and the total factor productivity has not been effectively improved. County-level public hospitals need to combine their own reality to find their own deficiencies. PMID:29176142

Efficiency and Productivity of County-level Public Hospitals Based on the Data Envelopment Analysis Model and Malmquist Index in Anhui, China.

PubMed

Li, Nian-Nian; Wang, Cun-Hui; Ni, Hong; Wang, Heng

2017-12-05

China began to implement the national medical and health system and public hospital reforms in 2009 and 2012, respectively. Anhui Province is one of the four pilot provinces, and the medical reform measures received wide attention nationwide. The effectiveness of the above reform needs to get attention. This study aimed to master the efficiency and productivity of county-level public hospitals based on the data envelopment analysis (DEA) model and Malmquist index in Anhui, China, and then provide improvement measures for the future hospital development. We chose 12 country-level hospitals based on geographical distribution and the economic development level in Anhui Province. Relevant data that were collected in the field and then sorted were provided by the administrative departments of the hospitals. DEA models were used to calculate the dynamic efficiency and Malmquist index factors for the 12 institutions. During 2010-2015, the overall average relative service efficiency of 12 county-level public hospitals was 0.926, and the number of hospitals achieved an effective DEA for each year from 2010 to 2015 was 4, 6, 7, 7, 6, and 8, respectively, as measured using DEA. During this same period, the average overall production efficiency was 0.983, and the total productivity factor had declined. The overall production efficiency of five hospitals was >1, and the rest are <1 between 2010 and 2015. In 2010-2015, the relative service efficiency of 12 county-level public hospitals in Anhui Province showed a decreasing trend, and the service efficiency of each hospital changed. In the past 6 years, although some hospitals have been effective, the efficiency of the county-level public hospitals in Anhui Province has not improved significantly, and the total factor productivity has not been effectively improved. County-level public hospitals need to combine their own reality to find their own deficiencies.

How can we maximize the use of our operating lists? An analysis of factors influencing theatre efficiency in oculoplastic day surgery.

PubMed

Nagendran, Sonali T; Siah, We Fong; Litwin, Andre; Barbosa, Christine; Jayatilake, Jan; Malhotra, Raman

2016-12-01

Operating theatre utilization has become the principal measure of NHS operating theatre service performance. We analysed data from oculoplastic theatres in a tertiary centre to identify factors influencing theatre efficiency. We conducted three audits on operating theatre utilization in 2011, 2014 and 2015. Data was collected from real time information entered into the hospital database, including time of arrival, induction, first cut and close of operation. The primary outcome measure was the operating list utilization rate, a combined value of anaesthetic and surgical time as a proportion of the total planned session time. The initial 2011 audit recorded an operating list utilization rate of 81.2%. However, this dropped to 64.5% in 2014 following new management and a move to a new theatre suite. Analysis of the factors contributing to poor theatre efficiency led to changes that streamlined the patient pathway, including standardized case scheduling and reducing staggered patient arrival. A 2015 reaudit analyzing the effects of these changes demonstrated an increase in the operating list utilization rate to 78%. It was significantly higher (p < 0.01) for whole-day lists (85%) compared to half-day lists (75%), suggesting that whole-day lists were more efficient. Operating theatres are a valuable resource and the factors affecting theatre efficiency within our unit are common and will be relevant to units elsewhere. Correcting them can lead to significant improvements in patient care. Data from this study may provide a benchmark for other units in the United Kingdom.

Bending efficiency through property gradients in bamboo, palm, and wood-based composites.

PubMed

Wegst, Ulrike G K

2011-07-01

Nature, to a greater extent than engineering, takes advantage of hierarchical structures. These allow for optimization at each structural level to achieve mechanical efficiency, meaning mechanical performance per unit mass. Palms and bamboos do this exceptionally well; both are fibre-reinforced cellular materials in which the fibres are aligned parallel to the stem or culm, respectively. The distribution of these fibres is, however, not uniform: there is a density and modulus gradient across the section. This property gradient increases the flexural rigidity of the plants per unit mass, mass being a measure of metabolic investment made into an organism's construction. An analytical model is presented with which a 'gradient shape factor' can be calculated that describes by how much a plant's bending efficiency is increased through gradient structures. Combining the 'gradient shape factor' with a 'microstructural shape factor' that captures the efficiency gained through the cellular nature of the fibre composite's matrix, and a 'macroscopical shape factor' with which the tubular shape of bamboo can be described, for example, it is possible to explore how much each of these three structural levels of the hierarchy contributes to the overall bending performance of the stem or culm. In analogy, the bending efficiency of the commonly used wood-based composite medium-density fibreboard can be analysed; its property gradient is due to its manufacture by hot pressing. A few other engineered materials exist that emulate property gradients; new manufacturing routes to prepare them are currently being explored. It appears worthwhile to pursue these further. Copyright © 2011. Published by Elsevier Ltd.

Key factors of eddy current separation for recovering aluminum from crushed e-waste.

PubMed

Ruan, Jujun; Dong, Lipeng; Zheng, Jie; Zhang, Tao; Huang, Mingzhi; Xu, Zhenming

2017-02-01

Recovery of e-waste in China had caused serious pollutions. Eddy current separation is an environment-friendly technology of separating nonferrous metallic particles from crushed e-waste. However, due to complex particle characters, separation efficiency of traditional eddy current separator was low. In production, controllable operation factors of eddy current separation are feeding speed, (ωR-v), and S p . There is little special information about influencing mechanism and critical parameters of these factors in eddy current separation. This paper provided the special information of these key factors in eddy current separation of recovering aluminum particles from crushed waste refrigerator cabinets. Detachment angles increased as the increase of (ωR-v). Separation efficiency increased with the growing of detachment angles. Aluminum particles were completely separated from plastic particles in critical parameters of feeding speed 0.5m/s and detachment angles greater than 6.61deg. S p /S m of aluminum particles in crushed waste refrigerators ranged from 0.08 to 0.51. Separation efficiency increased as the increase of S p /S m . This enlightened us to develop new separator to separate smaller nonferrous metallic particles in e-waste recovery. High feeding speed destroyed separation efficiency. However, greater S p of aluminum particles brought positive impact on separation efficiency. Greater S p could increase critical feeding speed to offer greater throughput of eddy current separation. This paper will guide eddy current separation in production of recovering nonferrous metals from crushed e-waste. Copyright © 2016 Elsevier Ltd. All rights reserved.

Uninfected Bystander Cells Impact the Measurement of HIV-Specific Antibody-Dependent Cellular Cytotoxicity Responses.

PubMed

Richard, Jonathan; Prévost, Jérémie; Baxter, Amy E; von Bredow, Benjamin; Ding, Shilei; Medjahed, Halima; Delgado, Gloria G; Brassard, Nathalie; Stürzel, Christina M; Kirchhoff, Frank; Hahn, Beatrice H; Parsons, Matthew S; Kaufmann, Daniel E; Evans, David T; Finzi, Andrés

2018-03-20

The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a "closed" conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs). Therefore, we hypothesized that these bystander cells could impact the interpretation of ADCC measurements. To investigate this, we evaluated the ability of antibodies to CD4i epitopes and broadly neutralizing Abs (bNAbs) to mediate ADCC measured by five ADCC assays commonly used in the field. Our results indicate that the uninfected bystander cells coated with gp120 are efficiently recognized by the CD4i ligands but not the bNabs. Consequently, the uninfected bystander cells substantially affect in vitro measurements made with ADCC assays that fail to identify responses against infected versus uninfected cells. Moreover, using an mRNA flow technique that detects productively infected cells, we found that the vast majority of HIV-1-infected cells in in vitro cultures or ex vivo samples from HIV-1-infected individuals are CD4 negative and therefore do not expose significant levels of CD4i epitopes. Altogether, our results indicate that ADCC assays unable to differentiate responses against infected versus uninfected cells overestimate responses mediated by CD4i ligands. IMPORTANCE Emerging evidence supports a role for antibody-dependent cellular cytotoxicity (ADCC) in protection against HIV-1 transmission and disease progression. However, there are conflicting reports regarding the ability of nonneutralizing antibodies targeting CD4-inducible (CD4i) Env epitopes to mediate ADCC. Here, we performed a side-by-side comparison of different methods currently being used in the field to measure ADCC responses to HIV-1. We found that assays which are unable to differentiate virus-infected from uninfected cells greatly overestimate ADCC responses mediated by antibodies to CD4i epitopes and underestimate responses mediated by broadly neutralizing antibodies (bNAbs). Our results strongly argue for the use of assays that measure ADCC against HIV-1-infected cells expressing physiologically relevant conformations of Env to evaluate correlates of protection in vaccine trials. Copyright © 2018 Richard et al.

Methods and analysis of factors impact on the efficiency of the photovoltaic generation

NASA Astrophysics Data System (ADS)

Tianze, Li; Xia, Zhang; Chuan, Jiang; Luan, Hou

2011-02-01

First of all, the thesis elaborates two important breakthroughs which happened In the field of the application of solar energy in the 1950s.The 21st century the development of solar photovoltaic power generation will have the following characteristics: the continued high growth of industrial development, the significantly reducing cost of the solar cell, the large-scale high-tech development of photovoltaic industries, the breakthroughs of the film battery technology, the rapid development of solar PV buildings integration and combined to the grids. The paper makes principles of solar cells the theoretical analysis. On the basis, we study the conversion efficiency of solar cells, find the factors impact on the efficiency of the photovoltaic generation, solve solar cell conversion efficiency of technical problems through the development of new technology, and open up new ways to improve the solar cell conversion efficiency. Finally, the paper connecting with the practice establishes policies and legislation to the use of encourage renewable energy, development strategy, basic applied research etc.

Surface-emitting circular DFB, disk- and ring- Bragg resonator lasers with chirped gratings: a unified theory and comparative study.

PubMed

Sun, Xiankai; Yariv, Amnon

2008-06-09

We have developed a theory that unifies the analysis of the modal properties of surface-emitting chirped circular grating lasers. This theory is based on solving the resonance conditions which involve two types of reflectivities of chirped circular gratings. This approach is shown to be in agreement with previous derivations which use the characteristic equations. Utilizing this unified analysis, we obtain the modal properties of circular DFB, disk-, and ring- Bragg resonator lasers. We also compare the threshold gain, single mode range, quality factor, emission efficiency, and modal area of these types of circular grating lasers. It is demonstrated that, under similar conditions, disk Bragg resonator lasers have the highest quality factor, the highest emission efficiency, and the smallest modal area, indicating their suitability in low-threshold, high-efficiency, ultracompact laser design, while ring Bragg resonator lasers have a large single mode range, high emission efficiency, and large modal area, indicating their suitability for high-efficiency, large-area, high-power applications.

Quantitative Analysis of the Efficiency of OLEDs.

PubMed

Sim, Bomi; Moon, Chang-Ki; Kim, Kwon-Hyeon; Kim, Jang-Joo

2016-12-07

We present a comprehensive model for the quantitative analysis of factors influencing the efficiency of organic light-emitting diodes (OLEDs) as a function of the current density. The model takes into account the contribution made by the charge carrier imbalance, quenching processes, and optical design loss of the device arising from various optical effects including the cavity structure, location and profile of the excitons, effective radiative quantum efficiency, and out-coupling efficiency. Quantitative analysis of the efficiency can be performed with an optical simulation using material parameters and experimental measurements of the exciton profile in the emission layer and the lifetime of the exciton as a function of the current density. This method was applied to three phosphorescent OLEDs based on a single host, mixed host, and exciplex-forming cohost. The three factors (charge carrier imbalance, quenching processes, and optical design loss) were influential in different ways, depending on the device. The proposed model can potentially be used to optimize OLED configurations on the basis of an analysis of the underlying physical processes.

Techno-economical efficiency and productivity change of wastewater treatment plants: the role of internal and external factors.

PubMed

Hernández-Sancho, F; Molinos-Senante, M; Sala-Garrido, R

2011-12-01

Efficiency and productivity are important measures for identifying best practice in businesses and optimising resource-use. This study analyses how these two measures change across the period 2003-2008 for 196 wastewater treatment plants (WWTPs) in Spain, by using the benchmarking methods of Data Envelopment Analysis and the Malmquist Productivity Index. To identify which variables contribute to the sustainability of the WWTPs, differences in efficiency scores and productivity indices for external factors are also investigated. Our results indicate that both efficiency and productivity decreased over the five years. We verify that the productivity drop is primarily explained by technical change. Furthermore, certain external variables affected WWTP efficiency, including plant size, treatment technology and energy consumption. However, plants with low energy consumption are the only ones which improve their productivity. Finally, the benchmarking analyses proved to be useful as management tools in the wastewater sector, by providing vital information for improving the sustainability of plants.

Factor structure and diagnostic efficiency of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for avoidant personality disorder in Hispanic men and women with substance use disorders.

PubMed

Becker, Daniel F; Añez, Luis Miguel; Paris, Manuel; Bedregal, Luis; Grilo, Carlos M

2009-01-01

This study examined the internal consistency, factor structure, and diagnostic efficiency of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for avoidant personality disorder (AVPD) and the extent to which these metrics may be affected by sex. Subjects were 130 monolingual Hispanic adults (90 men, 40 women) who had been admitted to a specialty clinic that provides psychiatric and substance abuse services to Spanish-speaking patients. All were reliably assessed with the Spanish-Language Version of the Diagnostic Interview for DSM-IV Personality Disorders. The AVPD diagnosis was determined by the best-estimate method. After evaluating internal consistency of the AVPD criterion set, an exploratory factor analysis was performed using principal components extraction. Afterward, diagnostic efficiency indices were calculated for all AVPD criteria. Subsequent analyses examined men and women separately. For the overall group, internal consistency of AVPD criteria was good. Exploratory factor analysis revealed a 1-factor solution (accounting for 70% of the variance), supporting the unidimensionality of the AVPD criterion set. The best inclusion criterion was "reluctance to take risks," whereas "interpersonally inhibited" was the best exclusion criterion and the best predictor overall. When men and women were examined separately, similar results were obtained for both internal consistency and factor structure, with slight variations noted between sexes in the patterning of diagnostic efficiency indices. These psychometric findings, which were similar for men and women, support the construct validity of the DSM-IV criteria for AVPD and may also have implications for the treatment of this particular clinical population.

The Impact of Redundancy and Teamwork on Resilience Engineering Factors by Fuzzy Mathematical Programming and Analysis of Variance in a Large Petrochemical Plant.

PubMed

Azadeh, Ali; Salehi, Vahid; Mirzayi, Mahsa

2016-12-01

Resilience engineering (RE) is a new paradigm that can control incidents and reduce their consequences. Integrated RE includes four new factors-self-organization, teamwork, redundancy, and fault-tolerance-in addition to conventional RE factors. This study aimed to evaluate the impacts of these four factors on RE and determine the most efficient factor in an uncertain environment. The required data were collected through a questionnaire in a petrochemical plant in June 2013. The questionnaire was completed by 115 respondents including 37 managers and 78 operators. Fuzzy data envelopment analysis was used in different α-cuts in order to calculate the impact of each factor. Analysis of variance was employed to compare the efficiency score means of the four above-mentioned factors. The results showed that as α approached 0 and the system became fuzzier (α = 0.3 and α = 0.1), teamwork played a significant role and had the highest impact on the resilient system. In contrast, as α approached 1 and the fuzzy system went toward a certain mode (α = 0.9 and α = 1), redundancy had a vital role in the selected resilient system. Therefore, redundancy and teamwork were the most efficient factors. The approach developed in this study could be used for identifying the most important factors in such environments. The results of this study may help managers to have better understanding of weak and strong points in such industries.

Structural, magnetic and magnetocaloric properties of Co-doped nanocrystalline La0.7Te0.3Mn0.7Co0.3O3

NASA Astrophysics Data System (ADS)

Meenakshi; Kumar, Amit; Mahato, Rabindra Nath

2018-02-01

Structural, magnetic and magnetocaloric properties of the nanocrystalline La0.7Te0.3Mn0.7Co0.3O3 perovskite manganite were investigated. X-ray diffraction pattern indicated that the nanocrystalline sample crystallized in orthorhombic crystal structure with Pbnm space group. The average particle size was calculated using scanning electron microscope and it was found to be ∼150 nm. Temperature dependence magnetization measurements revealed ferromagnetic-paramagnetic phase transition and the Curie temperature (TC) was found to be ∼201 K. Field dependence magnetization showed the hysteresis at low temperature with a coercive field of ∼0.34 T and linear dependence at high temperature corresponds to paramagnetic region. Based on the magnetic field dependence magnetization data, the maximum entropy change and relative cooling power (RCP) were estimated and the values were 1.002 J kg-1 K-1 and 90 J kg-1 for a field change of 5 T respectively. Temperature dependent resistivity ρ(T) data exhibited semiconducting-like behavior at high temperature and the electrical transport was well explained by Mott's variable-range hopping (VRH) conduction mechanism in the temperature range of 250 K-300 K. Using the VRH fit, the calculated hoping distance (Rh) at 300 K was 54.4 Å and density of states N(EF) at room temperature was 7.04 × 1018 eV-1 cm-3. These values were comparable to other semiconducting oxides.

Learning to associate orientation with color in early visual areas by associative decoded fMRI neurofeedback

PubMed Central

Amano, Kaoru; Shibata, Kazuhisa; Kawato, Mitsuo; Sasaki, Yuka; Watanabe, Takeo

2016-01-01

Summary Associative learning is an essential brain process where the contingency of different items increases after training. Associative learning has been found to occur in many brain regions [1-4]. However, there is no clear evidence that associative learning of visual features occurs in early visual areas, although a number of studies have indicated that learning of a single visual feature (perceptual learning) involves early visual areas [5-8]. Here, via decoded functional magnetic resonance imaging (fMRI) neurofeedback, termed “DecNef” [9], we tested whether associative learning of color and orientation can be created in early visual areas. During three days' training, DecNef induced fMRI signal patterns that corresponded to a specific target color (red) mostly in early visual areas while a vertical achromatic grating was physically presented to participants. As a result, participants came to perceive “red” significantly more frequently than “green” in an achromatic vertical grating. This effect was also observed 3 to 5 months after the training. These results suggest that long-term associative learning of the two different visual features such as color and orientation was created most likely in early visual areas. This newly extended technique that induces associative learning is called “A(ssociative)-DecNef” and may be used as an important tool for understanding and modifying brain functions, since associations are fundamental and ubiquitous functions in the brain. PMID:27374335

Control of HIV-1 by an HLA-B*52:01-C*12:02 Protective Haplotype.

PubMed

Chikata, Takayuki; Murakoshi, Hayato; Koyanagi, Madoka; Honda, Kazutaka; Gatanaga, Hiroyuki; Oka, Shinichi; Takiguchi, Masafumi

2017-12-12

HLA-B*52:01-C*12:02, which is found in approximately 20% of all Japanese persons, is well known to be associated with ulcerative colitis and Takayasu arteritis. This haplotype is also known to be protective in individuals infected with human immunodeficiency virus (HIV) type 1. Recent studies showed that HLA-B*52:01-restricted HIV-1-specific T cells suppress HIV-1 and that HLA-C*12:02 together with KIR2DL2 play an important role in natural killer cell-mediated control of HIV-1. However, the role of HLA-C*12:02-restricted cytotoxic T lymphocytes (CTLs) in suppressing HIV-1 replication remains unknown. In the present study, we demonstrated that HLA-C*12:02-restricted CTLs specific for 2 immunodominant epitopes, Pol IY11 and Nef MY9, contributed to the suppression of HIV-1 replication in HIV-1-infected individuals. Further analysis demonstrated that these 2 HLA-C*12:02-restricted CTLs together with 4 HLA-B*52:01-restricted ones effectively suppressed HIV-1 in individuals with the HLA-B*52:01-C*12:02 haplotype. Thus, both HLA-C*12:02 and HLA-B*52:01 alleles contribute to HIV-1 suppression via both HIV-1-specific CTLs and natural killer cells in individuals with this haplotype. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The human immunodeficiency virus type 1 (HIV-1) CD4 receptor and its central role in promotion of HIV-1 infection.

PubMed Central

Bour, S; Geleziunas, R; Wainberg, M A

1995-01-01

Interactions between the viral envelope glycoprotein gp120 and the cell surface receptor CD4 are responsible for the entry of human immunodeficiency virus type 1 (HIV-1) into host cells in the vast majority of cases. HIV-1 replication is commonly followed by the disappearance or receptor downmodulation of cell surface CD4. This potentially renders cells nonsusceptible to subsequent infection by HIV-1, as well as by other viruses that use CD4 as a portal of entry. Disappearance of CD4 from the cell surface is mediated by several different viral proteins that act at various stages through the course of the viral life cycle, and it occurs in T-cell lines, peripheral blood CD4+ lymphocytes, and monocytes of both primary and cell line origin. At the cell surface, gp120 itself and in the form of antigen-antibody complexes can trigger cellular pathways leading to CD4 internalization. Intracellularly, the mechanisms leading to CD4 downmodulation by HIV-1 are multiple and complex; these include degradation of CD4 by Vpu, formation of intracellular complexes between CD4 and the envelope precursor gp160, and internalization by the Nef protein. Each of the above doubtless contributes to the ultimate depletion of cell surface CD4, although the relative contribution of each mechanism and the manner in which they interact remain to be definitively established. PMID:7708013

Astrophysics on the Edge: New Instrumental Developments at the ING

NASA Astrophysics Data System (ADS)

Santander-García, M.; Rodríguez-Gil, P.; Tulloch, S.; Rutten, R. G. M.

Present and future key instruments at the Isaac Newton Group of Telescopes (ING) are introduced, and their corresponding latest scientific highlights are presented. GLAS (Ground-layer Laser Adaptive optics System): The recently installed 515 nm laser, mounted on the WHT (William Herschel Telescope), produces a bright artificial star at a height of 15 km. This enables almost full-sky access to Adaptive Optics observations. Recent commissioning observations with the NAOMI+GLAS system showed that very significant improvement in image quality can be obtained, e.g. down to 0.16 arcsec in the H band. QUCAM2 and QUCAM3: Two Low Light Level (L3) CCD cameras for fast or faint-object spectroscopy with the twin-armed ISIS spectrograph at the WHT. Their use opens a new window of high time-frequency observations, as well as access to fainter objects. They are powerful instruments for research on compact objects such as white dwarfs, neutron stars or black holes, stellar pulsations, and compact binaries.HARPS-NEF (High-Accuracy Radial-velocity Planet Searcher of the New Earths Facility): An extremely stable, high-resolution (R ˜ 120, 000) spectrograph for the WHT which is being constructed for commissioning in 2009-2010. Its radial velocity stability of < 1 m s- 1 may in the future be even further improved by using a Fabry-Perot laser-comb, a wavelength calibration unit capable of achieving an accuracy of 1 cm s- 1. This instrument will effectively allow to search for earth-like exoplanets.

Different levels of immunogenicity of two strains of Fowlpox virus as recombinant vaccine vectors eliciting T-cell responses in heterologous prime-boost vaccination strategies.

PubMed

Cottingham, Matthew G; van Maurik, Andre; Zago, Manola; Newton, Angela T; Anderson, Richard J; Howard, M Keith; Schneider, Jörg; Skinner, Michael A

2006-07-01

The FP9 strain of F has been described as a more immunogenic recombinant vaccine vector than the Webster FPV-M (FPW) strain (R. J. Anderson et al., J. Immunol. 172:3094-3100, 2004). This study expands the comparison to include two separate recombinant antigens and multiple, rather than single, independent viral clones derived from the two strains. Dual-poxvirus heterologous prime-boost vaccination regimens using individual clones of recombinant FP9 or FPW in combination with recombinant modified V Ankara expressing the same antigen were evaluated for their ability to elicit T-cell responses against recombinant antigens from Plasmodium berghei (circumsporozoite protein) or human immunodeficiency virus type 1 (a Gag-Pol-Nef fusion protein). Gamma interferon enzyme-linked immunospot assay and fluorescence-activated cell sorting assays of the responses to specific epitopes confirmed the approximately twofold-greater cellular immunogenicity of FP9 compared to FPW, when given as the priming or boosting immunization. Equality of transgene expression in mouse cells infected with the two strains in vitro was verified by Western blotting. Directed partial sequence analysis and PCR analysis of FPW and comparison to available whole-genome sequences revealed that many loci that are mutated in the highly attenuated and culture-adapted FP9 strain are wild type in FPW, including the seven multikilobase deletions. These "passage-specific" alterations are hypothesized to be involved in determining the immunogenicity of fowlpox virus as a recombinant vaccine vector.

Characterization of a Novel Simian Immunodeficiency Virus (SIVmonNG1) Genome Sequence from a Mona Monkey (Cercopithecus mona)

PubMed Central

Barlow, Katrina L.; Ajao, Adebowale Oluwafemi; Clewley, Jonathan P.

2003-01-01

A novel simian immunodeficiency virus (SIV) sequence has been recovered from RNA extracted from the serum of a mona monkey (Cercopithecus mona) wild born in Nigeria. The sequence was obtained by using novel generic (degenerate) PCR primers and spans from two-thirds into the gag gene to the 3′ poly(A) tail of the SIVmonNG1 RNA genome. Analysis of the open reading frames revealed that the SIVmonNG1 genome codes for a Vpu protein, in addition to Gag, Pol, Vif, Vpr, Tat, Rev, Env, and Nef proteins. Previously, only lentiviruses infecting humans (human immunodeficiency virus type 1 [HIV-1]) and chimpanzees (SIVcpz) were known to have a vpu gene; more recently, this has also been found in SIVgsn from Cercopithecus nictitans. Overall, SIVmonNG1 most closely resembles SIVgsn: the env gene sequence groups with HIV-1/SIVcpz env sequences, whereas the pol gene sequence clusters closely with the pol sequence of SIVsyk from Cercopithecus albogaris. By bootscanning and similarity plotting, the first half of pol resembles SIVsyk, whereas the latter part is closer to SIVcol from Colobus guereza. The similarities between the complex mosaic genomes of SIVmonNG1 and SIVgsn are consistent with a shared or common lineage. These data further highlight the intricate nature of the relationships between the SIVs from different primate species and will be helpful for unraveling these associations. PMID:12768007

Iron overload down-regulates the expression of the HIV-1 Rev cofactor eIF5A in infected T lymphocytes.

PubMed

Mancone, Carmine; Grimaldi, Alessio; Refolo, Giulia; Abbate, Isabella; Rozera, Gabriella; Benelli, Dario; Fimia, Gian Maria; Barnaba, Vincenzo; Tripodi, Marco; Piacentini, Mauro; Ciccosanti, Fabiola

2017-01-01

Changes in iron metabolism frequently accompany HIV-1 infection. However, while many clinical and in vitro studies report iron overload exacerbates the development of infection, many others have found no correlation. Therefore, the multi-faceted role of iron in HIV-1 infection remains enigmatic. RT-qPCR targeting the LTR region, gag , Tat and Rev were performed to measure the levels of viral RNAs in response to iron overload. Spike-in SILAC proteomics comparing i) iron-treated, ii) HIV-1-infected and iii) HIV-1-infected/iron treated T lymphocytes was performed to define modifications in the host cell proteome. Data from quantitative proteomics were integrated with the HIV-1 Human Interaction Database for assessing any viral cofactors modulated by iron overload in infected T lymphocytes. Here, we demonstrate that the iron overload down-regulates HIV-1 gene expression by decreasing the levels of viral RNAs. In addition, we found that iron overload modulates the expression of many viral cofactors. Among them, the downregulation of the REV cofactor eIF5A may correlate with the iron-induced inhibition of HIV-1 gene expression. Therefore, we demonstrated that eiF5A downregulation by shRNA resulted in a significant decrease of Nef levels, thus hampering HIV-1 replication. Our study indicates that HIV-1 cofactors influenced by iron metabolism represent potential targets for antiretroviral therapy and suggests eIF5A as a selective target for drug development.

FP-LAPW investigation of Al3(Sc1‑xTix) alloys properties in L12 and D022 structures

NASA Astrophysics Data System (ADS)

Khenioui, Youcef; Boulechfar, Rahima; Maazi, Noureddine; Ghemid, Sebti

2018-06-01

The ab-initio calculations based on the density functional theory (DFT) have been performed to study the structural, mechanical, electronic, thermal and thermodynamic properties of Al3Sc and Al3Ti binary compounds and their ternary mixture Al3(Sc1‑xTix) in L12 and D022 structures. The total energy calculations show that the L12 structure is the more stable one. The Al3Sc0.25Ti0.75 undergoes a martensitic transformation and the formation enthalpies and the lattice parameters decrease with increasing concentration x. The elastic constants are determined and the results show that all compounds are mechanically stable and the cubic cells are more easily deformed by shearing than by unidirectional compression. The elastic modulus indicates that the addition of Ti atoms to Al3Sc improves its ductility. The densities of states (DOSs) calculations show the strong spd hybridization which leads to the formation of a pseudo-gap near the Fermi level in ternary alloys. The densities of states at the Fermi level N(EF) confirm the phase stability. The quasi-harmonic Debye model is used to predict the thermal properties such as heat capacity, Debye temperature, Grüneisen parameter and thermal expansion coefficient of the considered alloys. The determination of Gibbs free mixing energy at different concentrations has been used to calculate the T-x diagram.

Upregulation of Glucose Uptake and Hexokinase Activity of Primary Human CD4+ T Cells in Response to Infection with HIV-1

PubMed Central

Kavanagh Williamson, Maia; Coombes, Naomi; Juszczak, Florian; Athanasopoulos, Marios; Khan, Mariam B.; Eykyn, Thomas R.; Srenathan, Ushani; Dias Zeidler, Julianna; Huthoff, Hendrik

2018-01-01

Infection of primary CD4+ T cells with HIV-1 coincides with an increase in glycolysis. We investigated the expression of glucose transporters (GLUT) and glycolytic enzymes in human CD4+ T cells in response to infection with HIV-1. We demonstrate the co-expression of GLUT1, GLUT3, GLUT4, and GLUT6 in human CD4+ T cells after activation, and their concerted overexpression in HIV-1 infected cells. The investigation of glycolytic enzymes demonstrated activation-dependent expression of hexokinases HK1 and HK2 in human CD4+ T cells, and a highly significant increase in cellular hexokinase enzyme activity in response to infection with HIV-1. HIV-1 infected CD4+ T cells showed a marked increase in expression of HK1, as well as the functionally related voltage-dependent anion channel (VDAC) protein, but not HK2. The elevation of GLUT, HK1, and VDAC expression in HIV-1 infected cells mirrored replication kinetics and was dependent on virus replication, as evidenced by the use of reverse transcription inhibitors. Finally, we demonstrated that the upregulation of HK1 in HIV-1 infected CD4+ T cells is independent of the viral accessory proteins Vpu, Vif, Nef, and Vpr. Though these data are consistent with HIV-1 dependency on CD4+ T cell glucose metabolism, a cellular response mechanism to infection cannot be ruled out. PMID:29518929

Factors Affecting Aerosol Radiative Forcing from Both Production-based and Consumption-based View

NASA Astrophysics Data System (ADS)

Wang, J.; Lin, J.; Ni, R.

2017-12-01

Aerosol radiative forcing (RF) is determined by emissions and various chemical-transport-radiative processes in the atmosphere, a multi-factor problem whose individual contributors have not been well quantified. This problem becomes more complicated when taking into account the role of international trade, which means reallocated aerosol RF due to separation of regions producing goods and emissions and regions consuming those goods. Here we analyze major factors affecting RF of secondary inorganic aerosols (SIOAs, including sulfate, nitrate and ammonium), primary organic aerosol (POA) and black carbon (BC), extending the work of Lin et al. (2016, Nature Geoscience). We contrast five factors determining production-based (RFp, due to a region's production of goods) and consumption-based (RFc, due to a region's consumption) forcing by 11 major regions, including population size, per capita output, emission intensity (emission per output), chemical efficiency (mass per unit emission) and radiative efficiency (RF per unit mass). Comparing across the 11 regions, East Asia produces the strongest RFp and RFc of SIOA and BC and the second largest RFp and RFc of POA primarily due to its high emission intensity. Although Middle East and North Africa has low emissions, its RFp is strengthened by its largest chemical efficiency for POA and BC and second largest chemical efficiency for SIOA. However, RFp of South-East Asia and Pacific is greatly weakened by its lowest chemical efficiency. Economic trade means that net importers (Western Europe, North America and Pacific OECD) have higher RFc than RFp by 50-100%. And such forcing difference is mainly due to the high emission intensity of the exporters supplying these regions. For North America, SIOA's RFc is 50% stronger than RFp, for that emission intensity of SIOA is 5.2 times in East Asia and 2.5 times in Latin America and Caribbean compared with that in North America, and the chemical efficiency in the top four exporters are 1.4-2.1 times of North America. For East Asia, the RFc of SIOA is 20% lower than RFp due to the relatively low emission intensity and chemical efficiency of the top two exporters (Pacific OECD and Western Europe). Overall, economic, emission and atmospheric factors all play important roles in differentiating regions' RFp and RFc.

An Efficient Scheme for Updating Sparse Cholesky Factors

NASA Technical Reports Server (NTRS)

Raghavan, Padma

2002-01-01

Raghavan had earlier developed the software package DCSPACK which can be used for solving sparse linear systems where the coefficient matrix is symmetric and positive definite (this project was not funded by NASA but by agencies such as NSF). DSCPACK-S is the serial code and DSCPACK-P is a parallel implementation suitable for multiprocessors or networks-of-workstations with message passing using MCI. The main algorithm used is the Cholesky factorization of a sparse symmetric positive positive definite matrix A = LL(T). The code can also compute the factorization A = LDL(T). The complexity of the software arises from several factors relating to the sparsity of the matrix A. A sparse N x N matrix A has typically less that cN nonzeroes where c is a small constant. If the matrix were dense, it would have O(N2) nonzeroes. The most complicated part of such sparse Cholesky factorization relates to fill-in, i.e., zeroes in the original matrix that become nonzeroes in the factor L. An efficient implementation depends to a large extent on complex data structures and on techniques from graph theory to reduce, identify, and manage fill. DSCPACK is based on an efficient multifrontal implementation with fill-managing algorithms and implementation arising from earlier research by Raghavan and others. Sparse Cholesky factorization is typically a four step process: (1) ordering to compute a fill-reducing numbering, (2) symbolic factorization to determine the nonzero structure of L, (3) numeric factorization to compute L, and, (4) triangular solution to solve L(T)x = y and Ly = b. The first two steps are symbolic and are performed using the graph of the matrix. The numeric factorization step is of dominant cost and there are several schemes for improving performance by exploiting the nested and dense structure of groups of columns in the factor. The latter are aimed at better utilization of the cache-memory hierarchy on modem processors to prevent cache-misses and provide execution rates (operations/second) that are close to the peak rates for dense matrix computations. Currently, EPISCOPACY is being used in an application at NASA directed by J. Newman and M. James. We propose the implementation of efficient schemes for updating the LL(T) or LDL(T) factors computed in DSCPACK-S to meet the computational requirements of their project. A brief description is provided in the next section.

Factorization-based texture segmentation

DOE PAGES

Yuan, Jiangye; Wang, Deliang; Cheriyadat, Anil M.

2015-06-17

This study introduces a factorization-based approach that efficiently segments textured images. We use local spectral histograms as features, and construct an M × N feature matrix using M-dimensional feature vectors in an N-pixel image. Based on the observation that each feature can be approximated by a linear combination of several representative features, we factor the feature matrix into two matrices-one consisting of the representative features and the other containing the weights of representative features at each pixel used for linear combination. The factorization method is based on singular value decomposition and nonnegative matrix factorization. The method uses local spectral histogramsmore » to discriminate region appearances in a computationally efficient way and at the same time accurately localizes region boundaries. Finally, the experiments conducted on public segmentation data sets show the promise of this simple yet powerful approach.« less

Impacts of market and organizational characteristics on hospital efficiency and uncompensated care.

PubMed

Hsieh, Hui-Min; Clement, Dolores G; Bazzoli, Gloria J

2010-01-01

Hospitals have confronted a difficult financial environment given many factors, including expansion of managed care, changes in public policy, growing market competition for certain services, and growth in the number of uninsured. Policy makers have expressed concern that hospitals may forgo providing care to the indigent as a means to reduce costs and become more efficient when faced with financial pressures. This article examined the effects of environmental pressures on two dimensions of hospital performance: hospital efficiency and uncompensated care provision. Longitudinal data for the Commonwealth of Virginia from 1998 to 2004 were analyzed. Data Envelopment Analysis and bivariate probit were used to examine the factors associated with efficiency and uncompensated care. The results indicated that a positive relationship between hospital efficiency and uncompensated care provision exists. That is, hospitals that are categorized as efficient are likely to provide more uncompensated care. We also found that hospitals tended to provide more uncompensated care when increased demand for these services occurred in a market. Increases in Medicare or Medicaid patient share reduced the provision of uncompensated care. In relation to hospital efficiency, the results indicated that HMO penetration and Medicaid patient share reduced hospital efficiency. This study found that efficient hospitals tend to provide more uncompensated care over time. The findings also suggest that hospitals alter their efficiency and provision of uncompensated care in response to a number of environmental pressures, but it may depend on the type of pressures or uncertainties encountered.

Efficiency and hospital effectiveness in improving Hospital Consumer Assessment of Healthcare Providers and Systems ratings.

PubMed

Al-Amin, Mona; Makarem, Suzanne C; Rosko, Michael

2016-01-01

Efficiency has emerged as a central goal to the operations of health care organizations. There are two competing perspectives on the relationship between efficiency and organizational performance. Some argue that organizational slack is a waste and that efficiency contributes to organizational performance, whereas others maintain that slack acts as a buffer, allowing organizations to adapt to environmental demands and contributing to organizational performance. As value-based purchasing becomes more prevalent, health care organizations are incented to become more efficient and, at the same time, improve their patients' experiences and outcomes. Unused slack resources might facilitate the timely implementation of these improvements. Building on previous research on organizational slack and inertia, we test whether efficiency and other organizational factors predict organizational effectiveness in improving Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) ratings. We rely on data from the American Hospital Association and HCAHPS. We estimate hospital cost-efficiency by Stochastic Frontier Analysis and use regression analysis to determine whether efficiency, competition, hospital size, and other organizational factors are significant predictors of hospital effectiveness. Our findings indicate that efficiency and hospital size have a significant negative association with organizational ability to improve HCAHPS ratings. Although achieving organizational efficiency is necessary for health care organizations, given the changes that are currently occurring in the U.S. health care system, it is important for health care managers to maintain a certain level of slack to respond to environmental demands and have the resources needed to improve their performance.

Hierarchical and coupling model of factors influencing vessel traffic flow.

PubMed

Liu, Zhao; Liu, Jingxian; Li, Huanhuan; Li, Zongzhi; Tan, Zhirong; Liu, Ryan Wen; Liu, Yi

2017-01-01

Understanding the characteristics of vessel traffic flow is crucial in maintaining navigation safety, efficiency, and overall waterway transportation management. Factors influencing vessel traffic flow possess diverse features such as hierarchy, uncertainty, nonlinearity, complexity, and interdependency. To reveal the impact mechanism of the factors influencing vessel traffic flow, a hierarchical model and a coupling model are proposed in this study based on the interpretative structural modeling method. The hierarchical model explains the hierarchies and relationships of the factors using a graph. The coupling model provides a quantitative method that explores interaction effects of factors using a coupling coefficient. The coupling coefficient is obtained by determining the quantitative indicators of the factors and their weights. Thereafter, the data obtained from Port of Tianjin is used to verify the proposed coupling model. The results show that the hierarchical model of the factors influencing vessel traffic flow can explain the level, structure, and interaction effect of the factors; the coupling model is efficient in analyzing factors influencing traffic volumes. The proposed method can be used for analyzing increases in vessel traffic flow in waterway transportation system.

Hierarchical and coupling model of factors influencing vessel traffic flow

PubMed Central

Liu, Jingxian; Li, Huanhuan; Li, Zongzhi; Tan, Zhirong; Liu, Ryan Wen; Liu, Yi

2017-01-01

Understanding the characteristics of vessel traffic flow is crucial in maintaining navigation safety, efficiency, and overall waterway transportation management. Factors influencing vessel traffic flow possess diverse features such as hierarchy, uncertainty, nonlinearity, complexity, and interdependency. To reveal the impact mechanism of the factors influencing vessel traffic flow, a hierarchical model and a coupling model are proposed in this study based on the interpretative structural modeling method. The hierarchical model explains the hierarchies and relationships of the factors using a graph. The coupling model provides a quantitative method that explores interaction effects of factors using a coupling coefficient. The coupling coefficient is obtained by determining the quantitative indicators of the factors and their weights. Thereafter, the data obtained from Port of Tianjin is used to verify the proposed coupling model. The results show that the hierarchical model of the factors influencing vessel traffic flow can explain the level, structure, and interaction effect of the factors; the coupling model is efficient in analyzing factors influencing traffic volumes. The proposed method can be used for analyzing increases in vessel traffic flow in waterway transportation system. PMID:28414747

Cold air investigation of 4 1/2-stage turbine with stage loading factor of 4.66 and high specific work output. 1: Overall performance

NASA Technical Reports Server (NTRS)

Whitney, W. J.; Behning, F. P.; Moffitt, T. P.; Hotz, G. M.

1977-01-01

The turbine developed design specific work output at design speed at a total pressure ratio of 6.745 with a corresponding efficiency of 0.855. The efficiency (0.855)was 3.1 points lower than the estimated efficiency quoted by the contractor in the design report and 0.7 of a point lower than that determined by a reference prediction method. The performance of the turbine, which was a forced vortex design, agreed with the performance determined by the prediction method to about the same extent as did the performance of three reference high stage loading factor turbines, which were free vortex designs.

Energy efficiency in U.S. Forest Service facilities: a multiregion review

Treesearch

Rachelle S. Meyer; David L. Nicholls; Trista M. Patterson; Rachel E. White

2013-01-01

We reviewed energy efficiency measures in facilities across the U.S. Department of Agriculture Forest Service, examining opportunities and obstacles, and identifying factors of project success. The adoption of energy efficiency measures at Forest Service sites was seen to be most likely when decision control was local to the site and when budget timing and structures...

Interdigitated Back-Surface-Contact Solar Cell Modeling Using Silvaco Atlas

DTIC Science & Technology

2015-06-01

11 2. Solar Spectrum ...................................................................................13 3. PV Cell Efficiency...Figure 10. Spectrum of solar radiance, from [12]. 14 3. PV Cell Efficiency There are many factors that affect the efficiency of a solar cell. Metal...BACK-SURFACE-CONTACT SOLAR CELL MODELING USING SILVACO ATLAS by Shawn E. Green June 2015 Thesis Advisor: Sherif Michael Second Reader

Improvement of peanut (Arachis hypogaea L.) transformation efficiency and determination of transgene copy number by relative quantitative real-time PCR

USDA-ARS?s Scientific Manuscript database

The biolistic method is reliable for delivering genes of interest into various species. Low transformation efficiency has been a limiting factor for its application. The DNA coating agent protamine was shown to improve transformation efficiency in rice, while a reduction of plasmid DNA in the bomb...

Proneural transcription factor Atoh1 drives highly efficient differentiation of human pluripotent stem cells into dopaminergic neurons.

PubMed

Sagal, Jonathan; Zhan, Xiping; Xu, Jinchong; Tilghman, Jessica; Karuppagounder, Senthilkumar S; Chen, Li; Dawson, Valina L; Dawson, Ted M; Laterra, John; Ying, Mingyao

2014-08-01

Human pluripotent stem cells (PSCs) are a promising cell resource for various applications in regenerative medicine. Highly efficient approaches that differentiate human PSCs into functional lineage-specific neurons are critical for modeling neurological disorders and testing potential therapies. Proneural transcription factors are crucial drivers of neuron development and hold promise for driving highly efficient neuronal conversion in PSCs. Here, we study the functions of proneural transcription factor Atoh1 in the neuronal differentiation of PSCs. We show that Atoh1 is induced during the neuronal conversion of PSCs and that ectopic Atoh1 expression is sufficient to drive PSCs into neurons with high efficiency. Atoh1 induction, in combination with cell extrinsic factors, differentiates PSCs into functional dopaminergic (DA) neurons with >80% purity. Atoh1-induced DA neurons recapitulate key biochemical and electrophysiological features of midbrain DA neurons, the degeneration of which is responsible for clinical symptoms in Parkinson's disease (PD). Atoh1-induced DA neurons provide a reliable disease model for studying PD pathogenesis, such as neurotoxin-induced neurodegeneration in PD. Overall, our results determine the role of Atoh1 in regulating neuronal differentiation and neuron subtype specification of human PSCs. Our Atoh1-mediated differentiation approach will enable large-scale applications of PD patient-derived midbrain DA neurons in mechanistic studies and drug screening for both familial and sporadic PD. ©AlphaMed Press.

The productivity and its barriers in public hospitals: case study of Iran

PubMed Central

Nabilou, Bahram; Yusefzadeh, Hassan; Rezapour, Aziz; Ebadi Fard Azar, Farbod; Salem Safi, Parviz; Sarabi Asiabar, Ali; Ahmadzadeh, Nahal

2016-01-01

Background: Due to the increasing health care costs, the issue of productivity in hospitals must be taken into great consideration in order to provide, preserve and promote public health services. Thus, increasing the level of productivity must become the main aim of any hospital. Objective of this study is to determine the total factor productivity and its components over the period under the study. Methods: In this cross sectional study, total factor productivity changes of hospitals affiliated to Tehran University of Medical Sciences were measured according to Malmquist index over the period 2009-2014. To estimate total productivity changes using Data Envelopment Analysis method, inputoriented and variable return to scale assumptions were applied and Deap2.1 software was used. Results: The mean value of total productivity changes was 1.013. It means that during the study period the productivity experienced a 1.3% decrease. Technological efficiency changes have the greatest influence on productivity decrease than the other factors. Scale efficiency, managerial efficiency and technical efficiency changes were ranked. Conclusion: Lack of knowledge of hospital personnel on proper application of technology in patient treatment is the main factor leading to productivity decrease resulting from technological changes in the studied hospitals. Therefore, holding courses for personnel in order to teach them the proper use of technology in diagnosis and patient care can be helpful. PMID:27390686

Grain sorghum is a viable feedstock for ethanol production.

PubMed

Wang, D; Bean, S; McLaren, J; Seib, P; Madl, R; Tuinstra, M; Shi, Y; Lenz, M; Wu, X; Zhao, R

2008-05-01

Sorghum is a major cereal crop in the USA. However, sorghum has been underutilized as a renewable feedstock for bioenergy. The goal of this research was to improve the bioconversion efficiency for biofuels and biobased products from processed sorghum. The main focus was to understand the relationship among "genetics-structure-function-conversion" and the key factors impacting ethanol production, as well as to develop an energy life cycle analysis model (ELCAM) to quantify and prioritize the saving potential from factors identified in this research. Genetic lines with extremely high and low ethanol fermentation efficiency and some specific attributes that may be manipulated to improve the bioconversion rate of sorghum were identified. In general, ethanol yield increased as starch content increased. However, no linear relationship between starch content and fermentation efficiency was found. Key factors affecting the ethanol fermentation efficiency of sorghum include protein digestibility, level of extractable proteins, protein and starch interaction, mash viscosity, amount of phenolic compounds, ratio of amylose to amylopectin, and formation of amylose-lipid complexes in the mash. A platform ELCAM with a base case showed a positive net energy value (NEV) = 25,500 Btu/gal EtOH. ELCAM cases were used to identify factors that most impact sorghum use. For example, a yield increase of 40 bu/ac resulted in NEV increasing from 7 million to 12 million Btu/ac. An 8% increase in starch provided an incremental 1.2 million Btu/ac.

A Practical and Secure Coercion-Resistant Scheme for Internet Voting

NASA Astrophysics Data System (ADS)

Araújo, Roberto; Foulle, Sébastien; Traoré, Jacques

Juels, Catalano, and Jakobsson (JCJ) proposed at WPES 2005 the first voting scheme that considers real-world threats and that is more realistic for Internet elections. Their scheme, though, has a quadratic work factor and thereby is not efficient for large scale elections. Based on the work of JCJ, Smith proposed an efficient scheme that has a linear work factor. In this paper we first show that Smith's scheme is insecure. Then we present a new coercion-resistant election scheme with a linear work factor that overcomes the flaw of Smith's proposal. Our solution is based on the group signature scheme of Camenisch and Lysyanskaya (Crypto 2004).

Factors Affecting the Development of Somatic Cell Nuclear Transfer Embryos in Cattle

PubMed Central

AKAGI, Satoshi; MATSUKAWA, Kazutsugu; TAKAHASHI, Seiya

2014-01-01

Nuclear transfer is a complex multistep procedure that includes oocyte maturation, cell cycle synchronization of donor cells, enucleation, cell fusion, oocyte activation and embryo culture. Therefore, many factors are believed to contribute to the success of embryo development following nuclear transfer. Numerous attempts to improve cloning efficiency have been conducted since the birth of the first sheep by somatic cell nuclear transfer. However, the efficiency of somatic cell cloning has remained low, and applications have been limited. In this review, we discuss some of the factors that affect the developmental ability of somatic cell nuclear transfer embryos in cattle. PMID:25341701

FACTORS INFLUENCING TOTAL DIETARY EXPOSURE OF YOUNG CHILDREN

EPA Science Inventory

A deterministic model was developed to identify critical input parameters to assess dietary intake of young children. The model was used as a framework for understanding important factors in data collection and analysis. Factors incorporated included transfer efficiencies of pest...

A data envelope analysis to assess factors affecting technical and economic efficiency of individual broiler breeder hens.

PubMed

Romero, L F; Zuidhof, M J; Jeffrey, S R; Naeima, A; Renema, R A; Robinson, F E

2010-08-01

This study evaluated the effect of feed allocation and energetic efficiency on technical and economic efficiency of broiler breeder hens using the data envelope analysis methodology and quantified the effect of variables affecting technical efficiency. A total of 288 Ross 708 pullets were placed in individual cages at 16 wk of age and assigned to 1 of 4 feed allocation groups. Three of them had feed allocated on a group basis with divergent BW targets: standard, high (standard x 1.1), and low (standard x 0.9). The fourth group had feed allocated on an individual bird basis following the standard BW target. Birds were classified in 3 energetic efficiency categories: low, average, and high, based on estimated maintenance requirements. Technical efficiency considered saleable chicks as output and cumulative ME intake and time as inputs. Economic efficiency of feed allocation treatments was analyzed under different cost scenarios. Birds with low feed allocation exhibited a lower technical efficiency (69.4%) than standard (72.1%), which reflected a reduced egg production rate. Feed allocation of the high treatment could have been reduced by 10% with the same chick production as the standard treatment. The low treatment exhibited reduced economic efficiency at greater capital costs, whereas high had reduced economic efficiency at greater feed costs. The average energetic efficiency hens had a lower technical efficiency in the low compared with the standard feed allocation. A 1% increment in estimated maintenance requirement changed technical efficiency by -0.23%, whereas a 1% increment in ME intake had a -0.47% effect. The negative relationship between technical efficiency and ME intake was counterbalanced by a positive correlation of ME intake and egg production. The negative relationship of technical efficiency and maintenance requirements was synergized by a negative correlation of hen maintenance and egg production. Economic efficiency methodologies are effective tools to assess the economic effect of selection and flock management programs because biological, allocative, and economic factors can be independently analyzed.

Sperm and Spermatids Contain Different Proteins and Bind Distinct Egg Factors

PubMed Central

Teperek, Marta; Miyamoto, Kei; Simeone, Angela; Feret, Renata; Deery, Michael J.; Gurdon, John B.; Jullien, Jerome

2014-01-01

Spermatozoa are more efficient at supporting normal embryonic development than spermatids, their immature, immediate precursors. This suggests that the sperm acquires the ability to support embryonic development during spermiogenesis (spermatid to sperm maturation). Here, using Xenopus laevis as a model organism, we performed 2-D Fluorescence Difference Gel Electrophoresis (2D-DIGE) and mass spectrometry analysis of differentially expressed proteins between sperm and spermatids in order to identify factors that could be responsible for the efficiency of the sperm to support embryonic development. Furthermore, benefiting from the availability of egg extracts in Xenopus, we also tested whether the chromatin of sperm could attract different egg factors compared to the chromatin of spermatids. Our analysis identified: (1) several proteins which were present exclusively in sperm; but not in spermatid nuclei and (2) numerous egg proteins binding to the sperm (but not to the spermatid chromatin) after incubation in egg extracts. Amongst these factors we identified many chromatin-associated proteins and transcriptional repressors. Presence of transcriptional repressors binding specifically to sperm chromatin could suggest its preparation for the early embryonic cell cycles, during which no transcription is observed and suggests that sperm chromatin has a unique protein composition, which facilitates the recruitment of egg chromatin remodelling factors. It is therefore likely that the acquisition of these sperm-specific factors during spermiogenesis makes the sperm chromatin suitable to interact with the maternal factors and, as a consequence, to support efficient embryonic development. PMID:25244019

Screening Efficiency Analysis of Vibrosieves with the Circular Vibrations

NASA Astrophysics Data System (ADS)

Djoković, Jelena M.; Tanikić, Dejan I.; Nikolić, Ružica R.; Kalinović, Saša M.

2017-06-01

The analysis of influence of factors that depend on construction characteristics of the vibrosieves with circular vibrations on screening efficiency is presented in this paper. The dependence of the screening efficiency on the aperture size, length and inclination of the screen, as well as on vibration amplitude, is considered. Based on obtained results, one can see that the screening efficiency increases with vibration amplitude and the screen length increase. Further, increases of the screen inclination and aperture size are causing an initial increase of the screening efficiency, which is later decreasing.

High thermoelectric power factor in two-dimensional crystals of Mo S2

NASA Astrophysics Data System (ADS)

Hippalgaonkar, Kedar; Wang, Ying; Ye, Yu; Qiu, Diana Y.; Zhu, Hanyu; Wang, Yuan; Moore, Joel; Louie, Steven G.; Zhang, Xiang

2017-03-01

The quest for high-efficiency heat-to-electricity conversion has been one of the major driving forces toward renewable energy production for the future. Efficient thermoelectric devices require high voltage generation from a temperature gradient and a large electrical conductivity while maintaining a low thermal conductivity. For a given thermal conductivity and temperature, the thermoelectric power factor is determined by the electronic structure of the material. Low dimensionality (1D and 2D) opens new routes to a high power factor due to the unique density of states (DOS) of confined electrons and holes. The 2D transition metal dichalcogenide (TMDC) semiconductors represent a new class of thermoelectric materials not only due to such confinement effects but especially due to their large effective masses and valley degeneracies. Here, we report a power factor of Mo S2 as large as 8.5 mW m-1K-2 at room temperature, which is among the highest measured in traditional, gapped thermoelectric materials. To obtain these high power factors, we perform thermoelectric measurements on few-layer Mo S2 in the metallic regime, which allows us to access the 2D DOS near the conduction band edge and exploit the effect of 2D confinement on electron scattering rates, resulting in a large Seebeck coefficient. The demonstrated high, electronically modulated power factor in 2D TMDCs holds promise for efficient thermoelectric energy conversion.

Efficiency of private and public primary health facilities accredited by the National Health Insurance Authority in Ghana.

PubMed

Alhassan, Robert Kaba; Nketiah-Amponsah, Edward; Akazili, James; Spieker, Nicole; Arhinful, Daniel Kojo; Rinke de Wit, Tobias F

2015-01-01

Despite improvements in a number of health outcome indicators partly due to the National Health Insurance Scheme (NHIS), Ghana is unlikely to attain all its health-related millennium development goals before the end of 2015. Inefficient use of available limited resources has been cited as a contributory factor for this predicament. This study sought to explore efficiency levels of NHIS-accredited private and public health facilities; ascertain factors that account for differences in efficiency and determine the association between quality care and efficiency levels. The study is a cross-sectional survey of NHIS-accredited primary health facilities (n = 64) in two regions in southern Ghana. Data Envelopment Analysis was used to estimate technical efficiency of sampled health facilities while Tobit regression was employed to predict factors associated with efficiency levels. Spearman correlation test was performed to determine the association between quality care and efficiency. Overall, 20 out of the 64 health facilities (31 %) were optimally efficient relative to their peers. Out of the 20 efficient facilities, 10 (50 %) were Public/government owned facilities; 8 (40 %) were Private-for-profit facilities and 2 (10 %) were Private-not-for-profit/Mission facilities. Mission (Coef. = 52.1; p = 0.000) and Public (Coef. = 42.9; p = 0.002) facilities located in the Western region (predominantly rural) had higher odds of attaining the 100 % technical efficiency benchmark than those located in the Greater Accra region (largely urban). No significant association was found between technical efficiency scores of health facilities and many technical quality care proxies, except in overall quality score per the NHIS accreditation data (Coef. = -0.3158; p < 0.05) and SafeCare Essentials quality score on environmental safety for staff and patients (Coef. = -0.2764; p < 0.05) where the association was negative. The findings suggest some level of wastage of health resources in many healthcare facilities, especially those located in urban areas. The Ministry of Health and relevant stakeholders should undertake more effective need analysis to inform resource allocation, distribution and capacity building to promote efficient utilization of limited resources without compromising quality care standards.

Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors.

PubMed

Chen, Yan; Sun, Ji; Lu, Ying; Tao, Chun; Huang, Jingbin; Zhang, He; Yu, Yuan; Zou, Hao; Gao, Jing; Zhong, Yanqiang

2013-01-01

pH-sensitive liposomes represent an effective gene vector in cancer therapy. However, their use is greatly hampered by their relatively low transfection efficiency. To improve the transfection efficiency of pH-sensitive liposomes, we prepared complexes containing 3β-[N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidyl ethanolamine (DOPE) liposomes and pH-sensitive liposomes composed of cholesteryl hemisuccinate (CHEMS) and DOPE, and evaluated the influence of various factors on plasmid DNA (pDNA) transfection efficiency. All DC-Chol/DOPE liposome/pDNA and pH-sensitive liposome complexes showed similarly potent pH sensitivity. In the presence of serum-containing medium, two optimized complexes of DC-Chol/DOPE liposomes/pDNA and pH-sensitive PEGylated liposomes showed high transfection efficiency of 22.94% and 20.07%, respectively. Notably, DC-Chol/DOPE (2:3) liposomes/pH-sensitive PEGylated (1%) liposome complexes with a charge ratio of 1:1 (m/m [+/-]) showed enhanced accumulation in tumors in vivo. Our results show the influence of various factors on pDNA transfection efficiency in complexes of DC-Chol/DOPE liposomes and pH-sensitive PEGylated liposomes. Understanding of such mechanisms will lead to better design of complexes of DC-Chol/DOPE liposomes and pH-sensitive liposomes for gene therapy.

Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors

PubMed Central

Chen, Yan; Sun, Ji; Lu, Ying; Tao, Chun; Huang, Jingbin; Zhang, He; Yu, Yuan; Zou, Hao; Gao, Jing; Zhong, Yanqiang

2013-01-01

pH-sensitive liposomes represent an effective gene vector in cancer therapy. However, their use is greatly hampered by their relatively low transfection efficiency. To improve the transfection efficiency of pH-sensitive liposomes, we prepared complexes containing 3β-[N-(N′,N′-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidyl ethanolamine (DOPE) liposomes and pH-sensitive liposomes composed of cholesteryl hemisuccinate (CHEMS) and DOPE, and evaluated the influence of various factors on plasmid DNA (pDNA) transfection efficiency. All DC-Chol/DOPE liposome/pDNA and pH-sensitive liposome complexes showed similarly potent pH sensitivity. In the presence of serum-containing medium, two optimized complexes of DC-Chol/DOPE liposomes/pDNA and pH-sensitive PEGylated liposomes showed high transfection efficiency of 22.94% and 20.07%, respectively. Notably, DC-Chol/DOPE (2:3) liposomes/pH-sensitive PEGylated (1%) liposome complexes with a charge ratio of 1:1 (m/m [+/−]) showed enhanced accumulation in tumors in vivo. Our results show the influence of various factors on pDNA transfection efficiency in complexes of DC-Chol/DOPE liposomes and pH-sensitive PEGylated liposomes. Understanding of such mechanisms will lead to better design of complexes of DC-Chol/DOPE liposomes and pH-sensitive liposomes for gene therapy. PMID:23637529

Research on the influence factors of the fall efficiency of the hospitalized geriatric patients with cerebrovascular diseases.

PubMed

Li, Weili; Cheng, Ruilian

2016-11-01

To investigate the fall efficiency and its influence factors of the hospitalized geriatric patients with cerebrovascular diseases. The Modified Fall Efficacy Scale (MFES), Morse Fall Risk Assessment Scales (MFS), Berg Balance Scale (BBS) and Tinetti Gait Analysis (TGA) were adopted and the combined ways of questionnaires and observation were utilized to investigate the 113 hospitalized geriatric patients with cerebrovascular diseases. The fall efficiency of the geriatric patients with cerebrovascular diseases were 7.85±2.57 scores. The two projects "walking up and down stairs" and "taking public transport means" have got the lowest scores; The two projects "stretching out the hand to the box or the drawer for taking something" and "sitting up and down to the chair" have got the highest scores. It was found that there were three factors which had significant influences on the fall efficiency, they were myodynamia of the right upper extremity, Berg balance functions and gait. For the sake of helping the geriatric patients with cerebrovascular diseases to establish the self-confidence of preventing the falls, the medical workers need to take further psychological counseling for the patients and befittingly and specifically to improve the fall efficiency of patients so as to effectively prevent the occurring of the fall on the basis of improving the balance ability and gait of patients.

Perceptual load corresponds with factors known to influence visual search.

PubMed

Roper, Zachary J J; Cosman, Joshua D; Vecera, Shaun P

2013-10-01

One account of the early versus late selection debate in attention proposes that perceptual load determines the locus of selection. Attention selects stimuli at a late processing level under low-load conditions but selects stimuli at an early level under high-load conditions. Despite the successes of perceptual load theory, a noncircular definition of perceptual load remains elusive. We investigated the factors that influence perceptual load by using manipulations that have been studied extensively in visual search, namely target-distractor similarity and distractor-distractor similarity. Consistent with previous work, search was most efficient when targets and distractors were dissimilar and the displays contained homogeneous distractors; search became less efficient when target-distractor similarity increased irrespective of display heterogeneity. Importantly, we used these same stimuli in a typical perceptual load task that measured attentional spillover to a task-irrelevant flanker. We found a strong correspondence between search efficiency and perceptual load; stimuli that generated efficient searches produced flanker interference effects, suggesting that such displays involved low perceptual load. Flanker interference effects were reduced in displays that produced less efficient searches. Furthermore, our results demonstrate that search difficulty, as measured by search intercept, has little bearing on perceptual load. We conclude that rather than be arbitrarily defined, perceptual load might be defined by well-characterized, continuous factors that influence visual search. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Efficient high-throughput biological process characterization: Definitive screening design with the ambr250 bioreactor system.

PubMed

Tai, Mitchell; Ly, Amanda; Leung, Inne; Nayar, Gautam

2015-01-01

The burgeoning pipeline for new biologic drugs has increased the need for high-throughput process characterization to efficiently use process development resources. Breakthroughs in highly automated and parallelized upstream process development have led to technologies such as the 250-mL automated mini bioreactor (ambr250™) system. Furthermore, developments in modern design of experiments (DoE) have promoted the use of definitive screening design (DSD) as an efficient method to combine factor screening and characterization. Here we utilize the 24-bioreactor ambr250™ system with 10-factor DSD to demonstrate a systematic experimental workflow to efficiently characterize an Escherichia coli (E. coli) fermentation process for recombinant protein production. The generated process model is further validated by laboratory-scale experiments and shows how the strategy is useful for quality by design (QbD) approaches to control strategies for late-stage characterization. © 2015 American Institute of Chemical Engineers.

Closing oil palm yield gaps among Indonesian smallholders through industry schemes, pruning, weeding and improved seeds

PubMed Central

Soliman, T.; Lim, F. K. S.; Lee, J. S. H.

2016-01-01

Oil palm production has led to large losses of valuable habitats for tropical biodiversity. Sparing of land for nature could in theory be attained if oil palm yields increased. The efficiency of oil palm smallholders is below its potential capacity, but the factors determining efficiency are poorly understood. We employed a two-stage data envelopment analysis approach to assess the influence of agronomic, supply chain and management factors on oil palm production efficiency in 190 smallholders in six villages in Indonesia. The results show that, on average, yield increases of 65% were possible and that fertilizer and herbicide use was excessive and inefficient. Adopting industry-supported scheme management practices, use of high-quality seeds and higher pruning and weeding rates were found to improve efficiency. Smallholder oil palm production intensification in Indonesia has the capacity to increase production by 26%, an equivalent of 1.75 million hectares of land. PMID:27853605

Evaluation of two typical distributed energy systems

NASA Astrophysics Data System (ADS)

Han, Miaomiao; Tan, Xiu

2018-03-01

According to the two-natural gas distributed energy system driven by gas engine driven and gas turbine, in this paper, the first and second laws of thermodynamics are used to measure the distributed energy system from the two parties of “quantity” and “quality”. The calculation results show that the internal combustion engine driven distributed energy station has a higher energy efficiency, but the energy efficiency is low; the gas turbine driven distributed energy station energy efficiency is high, but the primary energy utilization rate is relatively low. When configuring the system, we should determine the applicable natural gas distributed energy system technology plan and unit configuration plan according to the actual load factors of the project and the actual factors such as the location, background and environmental requirements of the project. “quality” measure, the utilization of waste heat energy efficiency index is proposed.

High-Efficiency Nonfullerene Polymer Solar Cell Enabling by Integration of Film-Morphology Optimization, Donor Selection, and Interfacial Engineering.

PubMed

Zhang, Xin; Li, Weiping; Yao, Jiannian; Zhan, Chuanlang

2016-06-22

Carrier mobility is a vital factor determining the electrical performance of organic solar cells. In this paper we report that a high-efficiency nonfullerene organic solar cell (NF-OSC) with a power conversion efficiency of 6.94 ± 0.27% was obtained by optimizing the hole and electron transportations via following judicious selection of polymer donor and engineering of film-morphology and cathode interlayers: (1) a combination of solvent annealing and solvent vapor annealing optimizes the film morphology and hence both hole and electron mobilities, leading to a trade-off of fill factor and short-circuit current density (Jsc); (2) the judicious selection of polymer donor affords a higher hole and electron mobility, giving a higher Jsc; and (3) engineering the cathode interlayer affords a higher electron mobility, which leads to a significant increase in electrical current generation and ultimately the power conversion efficiency (PCE).

A Method of Efficient Inclination Changes for Low-thrust Spacecraft

NASA Technical Reports Server (NTRS)

Falck, Robert; Gefert, Leon

2002-01-01

The evolution of low-thrust propulsion technologies has reached a point where such systems have become an economical option for many space missions. The development of efficient, low trip time control laws has received an increasing amount of attention in recent years, though few studies have examined the subject of inclination changing maneuvers in detail. A method for performing economical inclination changes through the use of an efficiency factor is derived front Lagrange's planetary equations. The efficiency factor can be used to regulate propellant expenditure at the expense of trip time. Such a method can be used for discontinuous-thrust transfers that offer reduced propellant masses and trip-times in comparison to continuous thrust transfers, while utilizing thrusters that operate at a lower specific impulse. Performance comparisons of transfers utilizing this approach with continuous-thrust transfers are generated through trajectory simulation and are presented in this paper.

Closing oil palm yield gaps among Indonesian smallholders through industry schemes, pruning, weeding and improved seeds.

PubMed

Soliman, T; Lim, F K S; Lee, J S H; Carrasco, L R

2016-08-01

Oil palm production has led to large losses of valuable habitats for tropical biodiversity. Sparing of land for nature could in theory be attained if oil palm yields increased. The efficiency of oil palm smallholders is below its potential capacity, but the factors determining efficiency are poorly understood. We employed a two-stage data envelopment analysis approach to assess the influence of agronomic, supply chain and management factors on oil palm production efficiency in 190 smallholders in six villages in Indonesia. The results show that, on average, yield increases of 65% were possible and that fertilizer and herbicide use was excessive and inefficient. Adopting industry-supported scheme management practices, use of high-quality seeds and higher pruning and weeding rates were found to improve efficiency. Smallholder oil palm production intensification in Indonesia has the capacity to increase production by 26%, an equivalent of 1.75 million hectares of land.

Thin and small form factor cells : simulated behavior.

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

Clews, Peggy Jane; Pluym, Tammy; Grubbs, Robert K.

Thin and small form factor cells have been researched lately by several research groups around the world due to possible lower assembly costs and reduced material consumption with higher efficiencies. Given the popularity of these devices, it is important to have detailed information about the behavior of these devices. Simulation of fabrication processes and device performance reveals some of the advantages and behavior of solar cells that are thin and small. Three main effects were studied: the effect of surface recombination on the optimum thickness, efficiency, and current density, the effect of contact distance on the efficiency for thin cells,more » and lastly the effect of surface recombination on the grams per Watt-peak. Results show that high efficiency can be obtained in thin devices if they are well-passivated and the distance between contacts is short. Furthermore, the ratio of grams per Watt-peak is greatly reduced as the device is thinned.« less

Stochastic Frontier Approach and Data Envelopment Analysis to Total Factor Productivity and Efficiency Measurement of Bangladeshi Rice

PubMed Central

Hossain, Md. Kamrul; Kamil, Anton Abdulbasah; Baten, Md. Azizul; Mustafa, Adli

2012-01-01

The objective of this paper is to apply the Translog Stochastic Frontier production model (SFA) and Data Envelopment Analysis (DEA) to estimate efficiencies over time and the Total Factor Productivity (TFP) growth rate for Bangladeshi rice crops (Aus, Aman and Boro) throughout the most recent data available comprising the period 1989–2008. Results indicate that technical efficiency was observed as higher for Boro among the three types of rice, but the overall technical efficiency of rice production was found around 50%. Although positive changes exist in TFP for the sample analyzed, the average growth rate of TFP for rice production was estimated at almost the same levels for both Translog SFA with half normal distribution and DEA. Estimated TFP from SFA is forecasted with ARIMA (2, 0, 0) model. ARIMA (1, 0, 0) model is used to forecast TFP of Aman from DEA estimation. PMID:23077500