Genome-Wide siRNA Screen Identifies Complementary Signaling Pathways Involved in Listeria Infection and Reveals Different Actin Nucleation Mechanisms during Listeria Cell Invasion and Actin Comet Tail Formation

PubMed Central

Kühbacher, Andreas; Emmenlauer, Mario; Rämo, Pauli; Kafai, Natasha; Dehio, Christoph

2015-01-01

ABSTRACT Listeria monocytogenes enters nonphagocytic cells by a receptor-mediated mechanism that is dependent on a clathrin-based molecular machinery and actin rearrangements. Bacterial intra- and intercellular movements are also actin dependent and rely on the actin nucleating Arp2/3 complex, which is activated by host-derived nucleation-promoting factors downstream of the cell receptor Met during entry and by the bacterial nucleation-promoting factor ActA during comet tail formation. By genome-wide small interfering RNA (siRNA) screening for host factors involved in bacterial infection, we identified diverse cellular signaling networks and protein complexes that support or limit these processes. In addition, we could precise previously described molecular pathways involved in Listeria invasion. In particular our results show that the requirements for actin nucleators during Listeria entry and actin comet tail formation are different. Knockdown of several actin nucleators, including SPIRE2, reduced bacterial invasion while not affecting the generation of comet tails. Most interestingly, we observed that in contrast to our expectations, not all of the seven subunits of the Arp2/3 complex are required for Listeria entry into cells or actin tail formation and that the subunit requirements for each of these processes differ, highlighting a previously unsuspected versatility in Arp2/3 complex composition and function. PMID:25991686

A Light-Weight Inflatable Hypersonic Drag Device for Planetary Entry

NASA Technical Reports Server (NTRS)

McRonald, Angus D.

2000-01-01

The author has analyzed the use of a light-weight inflatable hypersonic drag device, called a ballute, for flight in planetary atmospheres, for entry, aerocapture, and aerobraking. Studies to date include Mars, Venus, Earth, Saturn, Titan, Neptune and Pluto, and data on a Pluto lander and a Mars orbiter will be presented to illustrate the concept. The main advantage of using a ballute is that aero, deceleration and heating in atmospheric entry occurs at much smaller atmospheric density with a ballute than without it. For example, if a ballute has a diameter 10 times as large as the spacecraft, for unchanged total mass, entry speed and entry angle,the atmospheric density at peak convective heating is reduced by a factor of 100, reducing the heating by a factor of 10 for the spacecraft and a factor of 30 for the ballute. Consequently the entry payload (lander, orbiter, etc) is subject to much less heating, requires a much reduced thermal. protection system (possibly only an MLI blanket), and the spacecraft design is therefore relatively unchanged from its vacuum counterpart. The heat flux on the ballute is small enough to be radiated at temperatures below 800 K or so. Also, the heating may be reduced further because the ballute enters at a more shallow angle, even allowing for the increased delivery angle error. Added advantages are less mass ratio of entry system to total entry mass, and freedom from the low-density and transonic instability problems that conventional rigid entry bodies suffer, since the vehicle attitude is determined by the ballute, usually released at continuum conditions (hypersonic for an orbiter, and subsonic for a lander). Also, for a lander the range from entry to touchdown is less, offering a smaller footprint. The ballute derives an entry corridor for aerocapture by entering on a path that would lead to landing, and releasing the ballute adaptively, responding to measured deceleration, at a speed computed to achieve the desired orbiter exit conditions. For a lander an accurate landing point could be achieved by providing the lander with a small gliding capacity, using the large potential energy available from being subsonic at high altitude. Alternatively the ballute can be retained to act as a parachute or soft-landing device, or to float the payload as a buoyant aerobot. As expected, the ballute has smaller size for relatively small entry speeds, such as for Mars and Titan, or for the extensive atmosphere of a low-gravity planet such as Pluto. Details of a ballute to place a small Mars orbiter and a small Pluto lander will be given to illustrate the concept. The author will discuss presently available ballute materials and a development program of aerodynamic tests and materials that would be required for ballutes to achieve their full potential.

Function-oriented development of CXCR4 antagonists as selective human immunodeficiency virus (HIV)-1 entry inhibitors.

PubMed

Wu, Chien-Huang; Wang, Chuan-Jen; Chang, Chun-Ping; Cheng, Yung-Chi; Song, Jen-Shin; Jan, Jiing-Jyh; Chou, Ming-Chen; Ke, Yi-Yu; Ma, Jing; Wong, Ying-Chieh; Hsieh, Tsung-Chih; Tien, Yun-Chen; Gullen, Elizabeth A; Lo, Chen-Fu; Cheng, Chia-Yi; Liu, Yu-Wei; Sadani, Amit A; Tsai, Chia-Hua; Hsieh, Hsin-Pang; Tsou, Lun K; Shia, Kak-Shan

2015-02-12

Motivated by the pivotal role of CXCR4 as an HIV entry co-receptor, we herein report a de novo hit-to-lead effort on the identification of subnanomolar purine-based CXCR4 antagonists against HIV-1 infection. Compound 24, with an EC50 of 0.5 nM against HIV-1 entry into host cells and an IC50 of 16.4 nM for inhibition of radioligand stromal-derived factor-1α (SDF-1α) binding to CXCR4, was also found to be highly selective against closely related chemokine receptors. We rationalized that compound 24 complementarily interacted with the critical CXCR4 residues that are essential for binding to HIV-1 gp120 V3 loop and subsequent viral entry. Compound 24 showed a 130-fold increase in anti-HIV activity compared to that of the marketed CXCR4 antagonist, AMD3100 (Plerixafor), whereas both compounds exhibited similar potency in mobilization of CXCR4(+)/CD34(+) stem cells at a high dose. Our study offers insight into the design of anti-HIV therapeutics devoid of major interference with SDF-1α function.

A Polymorphism within the Internal Fusion Loop of the Ebola Virus Glycoprotein Modulates Host Cell Entry.

PubMed

Hoffmann, Markus; Crone, Lisa; Dietzel, Erik; Paijo, Jennifer; González-Hernández, Mariana; Nehlmeier, Inga; Kalinke, Ulrich; Becker, Stephan; Pöhlmann, Stefan

2017-05-01

The large scale of the Ebola virus disease (EVD) outbreak in West Africa in 2013-2016 raised the question whether the host cell interactions of the responsible Ebola virus (EBOV) strain differed from those of other ebolaviruses. We previously reported that the glycoprotein (GP) of the virus circulating in West Africa in 2014 (EBOV2014) exhibited reduced ability to mediate entry into two nonhuman primate (NHP)-derived cell lines relative to the GP of EBOV1976. Here, we investigated the molecular determinants underlying the differential entry efficiency. We found that EBOV2014-GP-driven entry into diverse NHP-derived cell lines, as well as human monocyte-derived macrophages and dendritic cells, was reduced compared to EBOV1976-GP, although entry into most human- and all bat-derived cell lines tested was comparable. Moreover, EBOV2014 replication in NHP but not human cells was diminished relative to EBOV1976, suggesting that reduced cell entry translated into reduced viral spread. Mutagenic analysis of EBOV2014-GP and EBOV1976-GP revealed that an amino acid polymorphism in the receptor-binding domain, A82V, modulated entry efficiency in a cell line-independent manner and did not account for the reduced EBOV2014-GP-driven entry into NHP cells. In contrast, polymorphism T544I, located in the internal fusion loop in the GP2 subunit, was found to be responsible for the entry phenotype. These results suggest that position 544 is an important determinant of EBOV infectivity for both NHP and certain human target cells. IMPORTANCE The Ebola virus disease outbreak in West Africa in 2013 entailed more than 10,000 deaths. The scale of the outbreak and its dramatic impact on human health raised the question whether the responsible virus was particularly adept at infecting human cells. Our study shows that an amino acid exchange, A82V, that was acquired during the epidemic and that was not observed in previously circulating viruses, increases viral entry into diverse target cells. In contrast, the epidemic virus showed a reduced ability to enter cells of nonhuman primates compared to the virus circulating in 1976, and a single amino acid exchange in the internal fusion loop of the viral glycoprotein was found to account for this phenotype. Copyright © 2017 American Society for Microbiology.

Glioblastoma Stem Cells Respond to Differentiation Cues but Fail to Undergo Commitment and Terminal Cell-Cycle Arrest

PubMed Central

Carén, Helena; Stricker, Stefan H.; Bulstrode, Harry; Gagrica, Sladjana; Johnstone, Ewan; Bartlett, Thomas E.; Feber, Andrew; Wilson, Gareth; Teschendorff, Andrew E.; Bertone, Paul; Beck, Stephan; Pollard, Steven M.

2015-01-01

Summary Glioblastoma (GBM) is an aggressive brain tumor whose growth is driven by stem cell-like cells. BMP signaling triggers cell-cycle exit and differentiation of GBM stem cells (GSCs) and, therefore, might have therapeutic value. However, the epigenetic mechanisms that accompany differentiation remain poorly defined. It is also unclear whether cell-cycle arrest is terminal. Here we find only a subset of GSC cultures exhibit astrocyte differentiation in response to BMP. Although overtly differentiated non-cycling astrocytes are generated, they remain vulnerable to cell-cycle re-entry and fail to appropriately reconfigure DNA methylation patterns. Chromatin accessibility mapping identified loci that failed to alter in response to BMP and these were enriched in SOX transcription factor-binding motifs. SOX transcription factors, therefore, may limit differentiation commitment. A similar propensity for cell-cycle re-entry and de-differentiation was observed in GSC-derived oligodendrocyte-like cells. These findings highlight significant obstacles to BMP-induced differentiation as therapy for GBM. PMID:26607953

Synthesis and anti-H5N1 activity of chiral gossypol derivatives and its analogs implicated by a viral entry blocking mechanism.

PubMed

Yang, Jian; Chen, Gang; Li, Long Long; Pan, Wei; Zhang, Fang; Yang, Jingxiang; Wu, Shuwen; Tien, Po

2013-05-01

A series of chiral gossypol derivatives and its analogs were synthesized and tested in vitro for their anti-H5N1 activity. Interestingly, (+)-gossypol derivatives and its analogs were more active against H5N1 than the corresponding (-)-gossypol derivatives and its analogs. Through a simple chemical modification with amino acids, less active chiral gossypol could be converted into more active derivatives, and most of chiral gossypol derivatives were more potent against H5N1 than 1-adamantylamine. With regard to the mechanism of action, chiral gossypol derivatives and its analogs might impair the virus entry step of cell infection, likely targeting to HA2 protein. Copyright © 2013 Elsevier Ltd. All rights reserved.

9 CFR 95.7 - Wool, hair, and bristles; requirements for unrestricted entry.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Wool, hair, and bristles; requirements... ENTRY INTO THE UNITED STATES § 95.7 Wool, hair, and bristles; requirements for unrestricted entry. Wool, hair, or bristles derived from ruminants and/or swine which do not meet the conditions or requirements...

9 CFR 95.7 - Wool, hair, and bristles; requirements for unrestricted entry.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Wool, hair, and bristles; requirements... ENTRY INTO THE UNITED STATES § 95.7 Wool, hair, and bristles; requirements for unrestricted entry. Wool, hair, or bristles derived from ruminants and/or swine which do not meet the conditions or requirements...

9 CFR 95.7 - Wool, hair, and bristles; requirements for unrestricted entry.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Wool, hair, and bristles; requirements... ENTRY INTO THE UNITED STATES § 95.7 Wool, hair, and bristles; requirements for unrestricted entry. Wool, hair, or bristles derived from ruminants and/or swine which do not meet the conditions or requirements...

A non-capacitative pathway activated by arachidonic acid is the major Ca2+ entry mechanism in rat A7r5 smooth muscle cells stimulated with low concentrations of vasopressin

PubMed Central

Broad, Lisa M; Cannon, Toby R; Taylor, Colin W

1999-01-01

Depletion of the Ca2+ stores of A7r5 cells stimulated Ca2+, though not Sr2+, entry. Vasopressin (AVP) or platelet-derived growth factor (PDGF) stimulated Sr2+ entry. The cells therefore express a capacitative pathway activated by empty stores and a non-capacitative pathway stimulated by receptors; only the former is permeable to Mn2+ and only the latter to Sr2+. Neither empty stores nor inositol 1,4,5-trisphosphate (InsP3) binding to its receptors are required for activation of the non-capacitative pathway, because microinjection of cells with heparin prevented PDGF-evoked Ca2+ mobilization but not Sr2+ entry. Low concentrations of Gd3+ irreversibly blocked capacitative Ca2+ entry without affecting AVP-evoked Sr2+ entry. After inhibition of the capacitative pathway with Gd3+, AVP evoked a substantial increase in cytosolic [Ca2+], confirming that the non-capacitative pathway can evoke a significant increase in cytosolic [Ca2+]. Arachidonic acid mimicked the effect of AVP on Sr2+ entry without stimulating Mn2+ entry; the Sr2+ entry was inhibited by 100 μM Gd3+, but not by 1 μM Gd3+ which completely inhibited capacitative Ca2+ entry. The effects of arachidonic acid did not require its metabolism. AVP-evoked Sr2+ entry was unaffected by isotetrandrine, an inhibitor of G protein-coupled phospholipase A2. U73122, an inhibitor of phosphoinositidase C, inhibited AVP-evoked formation of inositol phosphates and Sr2+ entry. The effects of phorbol esters and Ro31-8220 (a protein kinase C inhibitor) established that protein kinase C did not mediate the effects of AVP on the non-capacitative pathway. An inhibitor of diacylglycerol lipase, RHC-80267, inhibited AVP-evoked Sr2+ entry without affecting capacitative Ca2+ entry or release of Ca2+ stores. Selective inhibition of capacitative Ca2+ entry with Gd3+ revealed that the non-capacitative pathway is the major route for the Ca2+ entry evoked by low AVP concentrations. We conclude that in A7r5 cells, the Ca2+ entry evoked by low concentrations of AVP is mediated largely by a non-capacitative pathway directly regulated by arachidonic acid produced by the sequential activities of phosphoinositidase C and diacylglycerol lipase. PMID:10226154

Synthesis of betulinic acid derivatives as entry inhibitors against HIV-1 and bevirimat-resistant HIV-1 variants.

PubMed

Dang, Zhao; Qian, Keduo; Ho, Phong; Zhu, Lei; Lee, Kuo-Hsiung; Huang, Li; Chen, Chin-Ho

2012-08-15

Betulinic acid derivatives modified at the C28 position are HIV-1entry inhibitors such as compound A43D; however, modified at the C3 position instead of C28 give HIV-1 maturation inhibitor such as bevirimat. Bevirimat exhibited promising pharmacokinetic profiles in clinical trials, but its effectiveness was compromised by the high baseline drug resistance of HIV-1 variants with polymorphism in the putative drug binding site. In an effort to determine whether the viruses with bevirimat resistant polymorphism also altered their sensitivities to the betulinic acid derivatives that inhibit HIV-1 entry, a series of new betulinic acid entry inhibitors were synthesized and tested for their activities against HIV-1 NL4-3 and NL4-3 variants resistant to bevirimat. The results show that the bevirimat resistant viruses were approximately 5- to10-fold more sensitive to three new glutamine ester derivatives (13, 15 and 38) and A43D in an HIV-1 multi-cycle replication assay. In contrast, the wild type NL4-3 and the bevirimat resistant variants were equally sensitive to the HIV-1 RT inhibitor AZT. In addition, these three new compounds markedly improved microsomal stability compared to A43D. Copyright © 2012 Elsevier Ltd. All rights reserved.

Foster care re-entry: Exploring the role of foster care characteristics, in-home child welfare services and cross-sector services.

PubMed

Lee, Sangmoo; Jonson-Reid, Melissa; Drake, Brett

2012-09-01

This study seeks to advance our understanding of how modifiable and non-modifiable factors may impact the likelihood of re-entry into foster care. Children who entered foster care for the first time following at least one report of maltreatment and were then reunified were followed from exit to re-entry, age 18 or the end of the study period using longitudinal administrative data. Risk of re-entry was explored according to a range of modifiable and non-modifiable case and service characteristics. Children removed from homes with parents who had multiple risk factors (e.g., no high school diploma, mental health diagnosis, criminal record, or teen parents) or were receiving AFDC prior to entry were more likely to re-enter. The receipt of in-home child welfare services during or after foster care was associated with reduced risk of re-entry. Having the longest placement with a relative was associated with decreased risk of re-entry. In conclusion, both modifiable and non-modifiable factors are associated with re-entry into foster care. Among modifiable factors, services appear to have a particularly strong relationship to re-entry. Our data also suggest that in-home child welfare services provided during and after foster care may be associated with improved long-term permanency after return home. Given the continued import of caregiver risk factors even among reunified families, services provided to support reunification should include attention to caregiver needs outside parenting.

Foster care re-entry: Exploring the role of foster care characteristics, in-home child welfare services and cross-sector services☆

PubMed Central

Lee, Sangmoo; Jonson-Reid, Melissa; Drake, Brett

2013-01-01

This study seeks to advance our understanding of how modifiable and non-modifiable factors may impact the likelihood of re-entry into foster care. Children who entered foster care for the first time following at least one report of maltreatment and were then reunified were followed from exit to re-entry, age 18 or the end of the study period using longitudinal administrative data. Risk of re-entry was explored according to a range of modifiable and non-modifiable case and service characteristics. Children removed from homes with parents who had multiple risk factors (e.g., no high school diploma, mental health diagnosis, criminal record, or teen parents) or were receiving AFDC prior to entry were more likely to re-enter. The receipt of in-home child welfare services during or after foster care was associated with reduced risk of re-entry. Having the longest placement with a relative was associated with decreased risk of re-entry. In conclusion, both modifiable and non-modifiable factors are associated with re-entry into foster care. Among modifiable factors, services appear to have a particularly strong relationship to re-entry. Our data also suggest that in-home child welfare services provided during and after foster care may be associated with improved long-term permanency after return home. Given the continued import of caregiver risk factors even among reunified families, services provided to support reunification should include attention to caregiver needs outside parenting. PMID:23729947

Calculating second derivatives of population growth rates for ecology and evolution

PubMed Central

Shyu, Esther; Caswell, Hal

2014-01-01

1. Second derivatives of the population growth rate measure the curvature of its response to demographic, physiological or environmental parameters. The second derivatives quantify the response of sensitivity results to perturbations, provide a classification of types of selection and provide one way to calculate sensitivities of the stochastic growth rate. 2. Using matrix calculus, we derive the second derivatives of three population growth rate measures: the discrete-time growth rate λ, the continuous-time growth rate r = log λ and the net reproductive rate R0, which measures per-generation growth. 3. We present a suite of formulae for the second derivatives of each growth rate and show how to compute these derivatives with respect to projection matrix entries and to lower-level parameters affecting those matrix entries. 4. We also illustrate several ecological and evolutionary applications for these second derivative calculations with a case study for the tropical herb Calathea ovandensis. PMID:25793101

Nonlinear unbiased minimum-variance filter for Mars entry autonomous navigation under large uncertainties and unknown measurement bias.

PubMed

Xiao, Mengli; Zhang, Yongbo; Fu, Huimin; Wang, Zhihua

2018-05-01

High-precision navigation algorithm is essential for the future Mars pinpoint landing mission. The unknown inputs caused by large uncertainties of atmospheric density and aerodynamic coefficients as well as unknown measurement biases may cause large estimation errors of conventional Kalman filters. This paper proposes a derivative-free version of nonlinear unbiased minimum variance filter for Mars entry navigation. This filter has been designed to solve this problem by estimating the state and unknown measurement biases simultaneously with derivative-free character, leading to a high-precision algorithm for the Mars entry navigation. IMU/radio beacons integrated navigation is introduced in the simulation, and the result shows that with or without radio blackout, our proposed filter could achieve an accurate state estimation, much better than the conventional unscented Kalman filter, showing the ability of high-precision Mars entry navigation algorithm. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

Microscopy-based Assays for High-throughput Screening of Host Factors Involved in Brucella Infection of Hela Cells.

PubMed

Casanova, Alain; Low, Shyan H; Emmenlauer, Mario; Conde-Alvarez, Raquel; Salcedo, Suzana P; Gorvel, Jean-Pierre; Dehio, Christoph

2016-08-05

Brucella species are facultative intracellular pathogens that infect animals as their natural hosts. Transmission to humans is most commonly caused by direct contact with infected animals or by ingestion of contaminated food and can lead to severe chronic infections. Brucella can invade professional and non-professional phagocytic cells and replicates within endoplasmic reticulum (ER)-derived vacuoles. The host factors required for Brucella entry into host cells, avoidance of lysosomal degradation, and replication in the ER-like compartment remain largely unknown. Here we describe two assays to identify host factors involved in Brucella entry and replication in HeLa cells. The protocols describe the use of RNA interference, while alternative screening methods could be applied. The assays are based on the detection of fluorescently labeled bacteria in fluorescently labeled host cells using automated wide-field microscopy. The fluorescent images are analyzed using a standardized image analysis pipeline in CellProfiler which allows single cell-based infection scoring. In the endpoint assay, intracellular replication is measured two days after infection. This allows bacteria to traffic to their replicative niche where proliferation is initiated around 12 hr after bacterial entry. Brucella which have successfully established an intracellular niche will thus have strongly proliferated inside host cells. Since intracellular bacteria will greatly outnumber individual extracellular or intracellular non-replicative bacteria, a strain constitutively expressing GFP can be used. The strong GFP signal is then used to identify infected cells. In contrast, for the entry assay it is essential to differentiate between intracellular and extracellular bacteria. Here, a strain encoding for a tetracycline-inducible GFP is used. Induction of GFP with simultaneous inactivation of extracellular bacteria by gentamicin enables the differentiation between intracellular and extracellular bacteria based on the GFP signal, with only intracellular bacteria being able to express GFP. This allows the robust detection of single intracellular bacteria before intracellular proliferation is initiated.

Cyclosporin derivatives inhibit hepatitis B virus entry without interfering with NTCP transporter activity.

PubMed

Shimura, Satomi; Watashi, Koichi; Fukano, Kento; Peel, Michael; Sluder, Ann; Kawai, Fumihiro; Iwamoto, Masashi; Tsukuda, Senko; Takeuchi, Junko S; Miyake, Takeshi; Sugiyama, Masaya; Ogasawara, Yuki; Park, Sam-Yong; Tanaka, Yasuhito; Kusuhara, Hiroyuki; Mizokami, Masashi; Sureau, Camille; Wakita, Takaji

2017-04-01

The sodium taurocholate co-transporting polypeptide (NTCP) is the main target of most hepatitis B virus (HBV) specific entry inhibitors. Unfortunately, these agents also block NTCP transport of bile acids into hepatocytes, and thus have the potential to cause adverse effects. We aimed to identify small molecules that inhibit HBV entry while maintaining NTCP transporter function. We characterized a series of cyclosporine (CsA) derivatives for their anti-HBV activity and NTCP binding specificity using HepG2 cells overexpressing NTCP and primary human hepatocytes. The four most potent derivatives were tested for their capacity to prevent HBV entry, but maintain NTCP transporter function. Their antiviral activity against different HBV genotypes was analysed. We identified several CsA derivatives that inhibited HBV infection with a sub-micromolar IC 50 . Among them, SCY446 and SCY450 showed low activity against calcineurin (CN) and cyclophilins (CyPs), two major CsA cellular targets. This suggested that instead, these compounds interacted directly with NTCP to inhibit viral attachment to host cells, and have no immunosuppressive function. Importantly, we found that SCY450 and SCY995 did not impair the NTCP-dependent uptake of bile acids, and inhibited multiple HBV genotypes including a clinically relevant nucleoside analog-resistant HBV isolate. This is the first example of small molecule selective inhibition of HBV entry with no decrease in NTCP transporter activity. It suggests that the anti-HBV activity can be functionally separated from bile acid transport. These broadly active anti-HBV molecules are potential candidates for developing new drugs with fewer adverse effects. In this study, we identified new compounds that selectively inhibited hepatitis B virus (HBV) entry, and did not impair bile acid uptake. Our evidence offers a new strategy for developing anti-HBV drugs with fewer side effects. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Effects of several factors on theoretical predictions of airplane spin characteristics. [dynamic models

NASA Technical Reports Server (NTRS)

Bihrle, W., Jr.; Barnhart, B.

1974-01-01

The influence of different mathematical and aerodynamic models on computed spin motion was investigated along with the importance of some of the aerodynamic and nonaerodynamic quantities defined in these models. An analytical technique was used which included the aerodynamic forces and moments acting on a spinning aircraft due to steady rotational flow and the contribution of the rotary derivatives to the oscillatory component of the total angular rates. It was shown that (1) during experimental-analytical correlation studies, the flight-recorded control time histories must be faithfully duplicated since the spinning motion can be sensitive to a small change in the application of the spin entry controls; (2) an error in the assumed inertias, yawing moments at high angle of attack, and initial spin entry bank angle do not influence the developed spin significantly; (3) damping in pitch derivatives and the center of gravity location play a role in the spinning motion; and (4) the experimental spin investigations conducted in a constant atmospheric density environment duplicate the Froude number only at the initial full-scale spin altitude (since the full-scale airplane at high altitudes experiences large density changes during the spin.)

Predictors of re-entry into the child protection system in Singapore: a cumulative ecological-transactional risk model.

PubMed

Li, Dongdong; Chu, Chi Meng; Ng, Wei Chern; Leong, Wai

2014-11-01

This study examines the risk factors of re-entry for 1,750 child protection cases in Singapore using a cumulative ecological-transactional risk model. Using administrative data, the present study found that the overall percentage of Child Protection Service (CPS) re-entry in Singapore is 10.5% based on 1,750 cases, with a range from 3.9% (within 1 year) to 16.5% (within 8 years after case closure). One quarter of the re-entry cases were observed to occur within 9 months from case closure. Seventeen risk factors, as identified from the extant literature, were tested for their utility to predict CPS re-entry in this study using a series of Cox regression analyses. A final list of seven risk factors (i.e., children's age at entry, case type, case closure result, duration of case, household income, family size, and mother's employment status) was used to create a cumulative risk score. The results supported the cumulative risk model in that higher risk score is related to higher risk of CPS re-entry. Understanding the prevalence of CPS re-entry and the risk factors associated with re-entry is the key to informing practice and policy in a culturally relevant way. The results from this study could then be used to facilitate critical case management decisions in order to enhance positive outcomes of families and children in Singapore's care system. Copyright © 2014 Elsevier Ltd. All rights reserved.

The graduate entry generation: a qualitative study exploring the factors influencing the career expectations and aspirations of a graduating cohort of graduate entry dental students in one London institution

PubMed Central

2011-01-01

Background Dentistry in the UK has a number of new graduate-entry programmes. The aim of the study was to explore the motivation, career expectations and experiences of final year students who chose to pursue a dental career through the graduate entry programme route in one institution; and to explore if, and how, their intended career expectations and aspirations were informed by this choice. Method In-depth interviews of 14 graduate entry students in their final year of study. Data were transcribed verbatim and analysed using framework analysis. Results There were three categories of factors influencing students' choice to study dentistry through graduate entry: 'push', 'pull' and 'mediating'. Mediating factors related to students' personal concerns and circumstances, whereas push and pull factors related to features of their previous and future careers and wider social factors. Routes to Graduate Entry study comprised: 'early career changers', 'established career changers' and those pursuing 'routes to specialisation'. These routes also influenced the students' practice of dentistry, as students integrated skills in their dental studies, and encountered new challenges. Factors which students believed would influence their future careers included: vocational training; opportunities for specialisation or developing special interests and policy-related issues, together with wider professional and social concerns. The graduate entry programme was considered 'hard work' but a quick route to a professional career which had much to offer. Students' felt more could have been made of their pre-dental studies and/or experience during the programme. Factors perceived as influencing students' future contribution to dentistry included personal and social influences. Overall there was strong support for the values of the NHS and 'giving back' to the system in their future career. Conclusion Graduate entry students appear to be motivated to enter dentistry by a range of factors which suit their preferences and circumstances. They generally embrace the programme enthusiastically and seek to serve within healthcare, largely in the public sector. These students, who carry wider responsibilities, bring knowledge, skills and experience to dentistry which could be harnessed further during the programme. The findings suggest that graduate entry students, facilitated by varied career options, will contribute to an engaged workforce. PMID:21942994

The graduate entry generation: a qualitative study exploring the factors influencing the career expectations and aspirations of a graduating cohort of graduate entry dental students in one London institution.

PubMed

Newton, Paul; Cabot, Lyndon; Wilson, Nairn H F; Gallagher, Jennifer E

2011-09-24

Dentistry in the UK has a number of new graduate-entry programmes. The aim of the study was to explore the motivation, career expectations and experiences of final year students who chose to pursue a dental career through the graduate entry programme route in one institution; and to explore if, and how, their intended career expectations and aspirations were informed by this choice. In-depth interviews of 14 graduate entry students in their final year of study. Data were transcribed verbatim and analysed using framework analysis. There were three categories of factors influencing students' choice to study dentistry through graduate entry: 'push', 'pull' and 'mediating'. Mediating factors related to students' personal concerns and circumstances, whereas push and pull factors related to features of their previous and future careers and wider social factors. Routes to Graduate Entry study comprised: 'early career changers', 'established career changers' and those pursuing 'routes to specialisation'. These routes also influenced the students' practice of dentistry, as students integrated skills in their dental studies, and encountered new challenges.Factors which students believed would influence their future careers included: vocational training; opportunities for specialisation or developing special interests and policy-related issues, together with wider professional and social concerns.The graduate entry programme was considered 'hard work' but a quick route to a professional career which had much to offer. Students' felt more could have been made of their pre-dental studies and/or experience during the programme. Factors perceived as influencing students' future contribution to dentistry included personal and social influences. Overall there was strong support for the values of the NHS and 'giving back' to the system in their future career. Graduate entry students appear to be motivated to enter dentistry by a range of factors which suit their preferences and circumstances. They generally embrace the programme enthusiastically and seek to serve within healthcare, largely in the public sector. These students, who carry wider responsibilities, bring knowledge, skills and experience to dentistry which could be harnessed further during the programme. The findings suggest that graduate entry students, facilitated by varied career options, will contribute to an engaged workforce. © 2011 Newton et al; licensee BioMed Central Ltd.

Novel functional hepatitis C virus glycoprotein isolates identified using an optimized viral pseudotype entry assay.

PubMed

Urbanowicz, Richard A; McClure, C Patrick; King, Barnabas; Mason, Christopher P; Ball, Jonathan K; Tarr, Alexander W

2016-09-01

Retrovirus pseudotypes are a highly tractable model used to study the entry pathways of enveloped viruses. This model has been extensively applied to the study of the hepatitis C virus (HCV) entry pathway, preclinical screening of antiviral antibodies and for assessing the phenotype of patient-derived viruses using HCV pseudoparticles (HCVpp) possessing the HCV E1 and E2 glycoproteins. However, not all patient-isolated clones produce particles that are infectious in this model. This study investigated factors that might limit phenotyping of patient-isolated HCV glycoproteins. Genetically related HCV glycoproteins from quasispecies in individual patients were discovered to behave very differently in this entry model. Empirical optimization of the ratio of packaging construct and glycoprotein-encoding plasmid was required for successful HCVpp genesis for different clones. The selection of retroviral packaging construct also influenced the function of HCV pseudoparticles. Some glycoprotein constructs tolerated a wide range of assay parameters, while others were much more sensitive to alterations. Furthermore, glycoproteins previously characterized as unable to mediate entry were found to be functional. These findings were validated using chimeric cell-cultured HCV bearing these glycoproteins. Using the same empirical approach we demonstrated that generation of infectious ebolavirus pseudoviruses (EBOVpv) was also sensitive to the amount and ratio of plasmids used, and that protocols for optimal production of these pseudoviruses are dependent on the exact virus glycoprotein construct. These findings demonstrate that it is crucial for studies utilizing pseudoviruses to conduct empirical optimization of pseudotype production for each specific glycoprotein sequence to achieve optimal titres and facilitate accurate phenotyping.

Human cytomegalovirus glycoprotein complex gH/gL/gO uses PDGFR-α as a key for entry

PubMed Central

Boos, Simone; Resch, Moritz; Brizic, Ilija; Mach, Michael; Scrivano, Laura

2017-01-01

Herpesvirus gH/gL envelope glycoprotein complexes are key players in virus entry as ligands for host cell receptors and by promoting fusion of viral envelopes with cellular membranes. Human cytomegalovirus (HCMV) has two alternative gH/gL complexes, gH/gL/gO and gH/gL/UL128,130,131A which both shape the HCMV tropism. By studying binding of HCMV particles to fibroblasts, we could for the first time show that virion gH/gL/gO binds to platelet-derived growth factor-α (PDGFR-α) on the surface of fibroblasts and that gH/gL/gO either directly or indirectly recruits gB to this complex. PDGFR-α functions as an entry receptor for HCMV expressing gH/gL/gO, but not for HCMV mutants lacking the gH/gL/gO complex. PDGFR-α-dependent entry is not dependent on activation of PDGFR-α. We could also show that the gH/gL/gO—PDGFR-α interaction starts the predominant entry pathway for infection of fibroblasts with free virus. Cell-associated virus spread is either driven by gH/gL/gO interacting with PDGFR-α or by the gH/gL/UL128,130,131A complex. PDGFR-α-positive cells may thus be preferred first target cells for infections with free virus which might have implications for the design of future HCMV vaccines or anti-HCMV drugs. PMID:28403202

The importance of contextual, relational and cognitive factors for novice nurses' emotional state and affective commitment to the profession. A multilevel study.

PubMed

Hoeve, Yvonne Ten; Brouwer, Jasperina; Roodbol, Petrie F; Kunnen, Saskia

2018-05-13

This study explored the effects of contextual, relational and cognitive factors derived from novice nurses' work experiences on emotions and affective commitment to the profession. With an increasing demand for well-trained nurses, it is imperative to investigate which work-related factors most affect their commitment to develop effective strategies to improve work conditions, work satisfaction and emotional attachment. A repeated-measures within subjects design. From September 2013 - September 2014 eighteen novice nurses described work-related experiences in unstructured diaries and scored their emotional state and affective commitment on a scale. The themes that emerged from the 18 diaries (with 580 diary entries) were quantified as contextual, relational and cognitive factors. Contextual factors refer to complexity of care and existential events; relational factors to experiences with patients, support from colleagues, supervisors and physicians; cognitive factors to nurses' perceived competence. The first multilevel regression analysis, based on the 18 diaries with 580 entries, showed that complexity of care, lack of support and lack of competence were negatively related to novice nurses' affective commitment, whereas received support was positively related. The next multilevel regression analyses showed that all contextual, relational and cognitive factors were either related to negative or positive emotions. To retain novice nurses in the profession, it is important to provide support and feedback. This enables novice nurses to deal with the complexity of care and feelings of incompetence and to develop a professional commitment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evolved atmospheric entry corridor with safety factor

NASA Astrophysics Data System (ADS)

Liang, Zixuan; Ren, Zhang; Li, Qingdong

2018-02-01

Atmospheric entry corridors are established in previous research based on the equilibrium glide condition which assumes the flight-path angle to be zero. To get a better understanding of the highly constrained entry flight, an evolved entry corridor that considers the exact flight-path angle is developed in this study. Firstly, the conventional corridor in the altitude vs. velocity plane is extended into a three-dimensional one in the space of altitude, velocity, and flight-path angle. The three-dimensional corridor is generated by a series of constraint boxes. Then, based on a simple mapping method, an evolved two-dimensional entry corridor with safety factor is obtained. The safety factor is defined to describe the flexibility of the flight-path angle for a state within the corridor. Finally, the evolved entry corridor is simulated for the Space Shuttle and the Common Aero Vehicle (CAV) to demonstrate the effectiveness of the corridor generation approach. Compared with the conventional corridor, the evolved corridor is much wider and provides additional information. Therefore, the evolved corridor would benefit more to the entry trajectory design and analysis.

Expression of human factors CD81, claudin-1, scavenger receptor, and occludin in mouse hepatocytes does not confer susceptibility to HCV entry.

PubMed

Hikosaka, Keisuke; Noritake, Hidenao; Kimura, Wataru; Sultana, Nishat; Sharkar, Mohammad T K; Tagawa, Yoh-Ichi; Uezato, Tadayoshi; Kobayashi, Yoshimasa; Wakita, Takaji; Miura, Naoyuki

2011-04-01

No suitable mouse model is available for studying chronic liver disease caused by hepatitis C virus (HCV). CD81, claudin-1, scavenger receptor class B type I, and occludin were recently reported to be the important factors in HCV entry into hepatocytes. We made transgenic mice (Alb-CCSO) expressing the four human proteins and examined whether HCV from a patient serum or HCV pseudoparticles (HCVpp) were capable of infecting them. HCV was not detected in the mouse serum after injecting the mice with HCV from a patient serum. We also found no indications of HCVpp entry into primary hepatocytes from Alb-CCSO mice. In addition, HCV-infectible Hep3B cells were fused with HCV-resistant primary mouse hepatocytes and the fused cells showed 35-fold lower infectivity compared to wild-type Hep3B cells, indicating that primary mouse hepatocytes have the inhibitory factor(s) in HCVpp entry. Our results suggest that the expression of the human factors does not confer susceptibility to HCV entry into the liver.

Simian Immunodeficiency Virus SIVagm Efficiently Utilizes Non-CCR5 Entry Pathways in African Green Monkey Lymphocytes: Potential Role for GPR15 and CXCR6 as Viral Coreceptors.

PubMed

Riddick, Nadeene E; Wu, Fan; Matsuda, Kenta; Whitted, Sonya; Ourmanov, Ilnour; Goldstein, Simoy; Goeken, Robert M; Plishka, Ronald J; Buckler-White, Alicia; Brenchley, Jason M; Hirsch, Vanessa M

2015-12-09

African green monkeys (AGM) are natural hosts of simian immunodeficiency virus (SIV), and infection in these animals is generally nonpathogenic, whereas infection of nonnatural hosts, such as rhesus macaques (RM), is commonly pathogenic. CCR5 has been described as the primary entry coreceptor for SIV in vivo, while human-derived CXCR6 and GPR15 also appear to be used in vitro. However, sooty mangabeys that are genetically deficient in CCR5 due to an out-of-frame deletion are infectible with SIVsmm, indicating that SIVsmm can use alternative coreceptors in vivo. In this study, we examined the CCR5 dependence of SIV strains derived from vervet AGM (SIVagmVer) and the ability of AGM-derived GPR15 and CXCR6 to serve as potential entry coreceptors. We found that SIVagmVer replicated efficiently in AGM and RM peripheral blood mononuclear cells (PBMC) in the presence of the CCR5 antagonist maraviroc, despite the fact that maraviroc was capable of blocking the CCR5-tropic strains SIVmac239, SIVsmE543-3, and simian-human immunodeficiency virus SHIV-AD8 in RM PBMC. We also found that AGM CXCR6 and AGM GPR15, to a lesser extent, supported entry of pseudotype viruses bearing SIVagm envelopes, including SIVagm transmitted/founder envelopes. Lastly, we found that CCR5, GPR15, and CXCR6 mRNAs were detected in AGM and RM memory CD4(+) T cells. These results suggest that GPR15 and CXCR6 are expressed on AGM CD4(+) T cells and are potential alternative coreceptors for SIVagm use in vivo. These data suggest that the use of non-CCR5 entry pathways may be a common feature of SIV replication in natural host species, with the potential to contribute to nonpathogenicity in these animals. African green monkeys (AGM) are natural hosts of SIV, and infection in these animals generally does not cause AIDS, whereas SIV-infected rhesus macaques (RM) typically develop AIDS. Although it has been reported that SIV generally uses CD4 and CCR5 to enter target cells in vivo, other molecules, such as GPR15 and CXCR6, also function as SIV coreceptors in vitro. In this study, we investigated whether SIV from vervet AGM can use non-CCR5 entry pathways, as has been observed in sooty mangabeys. We found that SIVagmVer efficiently replicated in AGM and RM peripheral blood mononuclear cells in the presence of the CCR5 antagonist maraviroc, suggesting that non-CCR5 entry pathways can support SIVagm entry. We found that AGM-derived GPR15 and CXCR6 support SIVagmVer entry in vitro and may serve as entry coreceptors for SIVagm in vivo, since their mRNAs were detected in AGM memory CD4(+) T cells, the preferred target cells of SIV. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Simian Immunodeficiency Virus SIVagm Efficiently Utilizes Non-CCR5 Entry Pathways in African Green Monkey Lymphocytes: Potential Role for GPR15 and CXCR6 as Viral Coreceptors

PubMed Central

Riddick, Nadeene E.; Wu, Fan; Matsuda, Kenta; Whitted, Sonya; Ourmanov, Ilnour; Goldstein, Simoy; Goeken, Robert M.; Plishka, Ronald J.; Buckler-White, Alicia; Brenchley, Jason M.

2015-01-01

ABSTRACT African green monkeys (AGM) are natural hosts of simian immunodeficiency virus (SIV), and infection in these animals is generally nonpathogenic, whereas infection of nonnatural hosts, such as rhesus macaques (RM), is commonly pathogenic. CCR5 has been described as the primary entry coreceptor for SIV in vivo, while human-derived CXCR6 and GPR15 also appear to be used in vitro. However, sooty mangabeys that are genetically deficient in CCR5 due to an out-of-frame deletion are infectible with SIVsmm, indicating that SIVsmm can use alternative coreceptors in vivo. In this study, we examined the CCR5 dependence of SIV strains derived from vervet AGM (SIVagmVer) and the ability of AGM-derived GPR15 and CXCR6 to serve as potential entry coreceptors. We found that SIVagmVer replicated efficiently in AGM and RM peripheral blood mononuclear cells (PBMC) in the presence of the CCR5 antagonist maraviroc, despite the fact that maraviroc was capable of blocking the CCR5-tropic strains SIVmac239, SIVsmE543-3, and simian-human immunodeficiency virus SHIV-AD8 in RM PBMC. We also found that AGM CXCR6 and AGM GPR15, to a lesser extent, supported entry of pseudotype viruses bearing SIVagm envelopes, including SIVagm transmitted/founder envelopes. Lastly, we found that CCR5, GPR15, and CXCR6 mRNAs were detected in AGM and RM memory CD4+ T cells. These results suggest that GPR15 and CXCR6 are expressed on AGM CD4+ T cells and are potential alternative coreceptors for SIVagm use in vivo. These data suggest that the use of non-CCR5 entry pathways may be a common feature of SIV replication in natural host species, with the potential to contribute to nonpathogenicity in these animals. IMPORTANCE African green monkeys (AGM) are natural hosts of SIV, and infection in these animals generally does not cause AIDS, whereas SIV-infected rhesus macaques (RM) typically develop AIDS. Although it has been reported that SIV generally uses CD4 and CCR5 to enter target cells in vivo, other molecules, such as GPR15 and CXCR6, also function as SIV coreceptors in vitro. In this study, we investigated whether SIV from vervet AGM can use non-CCR5 entry pathways, as has been observed in sooty mangabeys. We found that SIVagmVer efficiently replicated in AGM and RM peripheral blood mononuclear cells in the presence of the CCR5 antagonist maraviroc, suggesting that non-CCR5 entry pathways can support SIVagm entry. We found that AGM-derived GPR15 and CXCR6 support SIVagmVer entry in vitro and may serve as entry coreceptors for SIVagm in vivo, since their mRNAs were detected in AGM memory CD4+ T cells, the preferred target cells of SIV. PMID:26656714

Analysis of alternative coordination methods at border ports of entry between the United States and Mexico.

DOT National Transportation Integrated Search

2001-12-01

Phase 1: To identify the intersectorial coordination problems between public agencies in Mexico, the problems that originate from the lack of Bi-national Coordination at the Border Ports of Entry, and the costs derived from these problems. Phase 2: T...

50 CFR 679.80 - Allocation and transfer of rockfish QS.

Code of Federal Regulations, 2014 CFR

2014-10-01

... from which that LLP license was derived during the calendar years 2000 and 2001, unless clear and...) Determine the Total Entry Level Trawl Fishery Transition Rockfish QS pool for each rockfish primary species... Rockfish QS pools. (v) Multiply the Percentage of the Total Entry Level Trawl Fishery Transition Rockfish...

50 CFR 679.80 - Allocation and transfer of rockfish QS.

Code of Federal Regulations, 2013 CFR

2013-10-01

... from which that LLP license was derived during the calendar years 2000 and 2001, unless clear and...) Determine the Total Entry Level Trawl Fishery Transition Rockfish QS pool for each rockfish primary species... Rockfish QS pools. (v) Multiply the Percentage of the Total Entry Level Trawl Fishery Transition Rockfish...

50 CFR 679.80 - Allocation and transfer of rockfish QS.

Code of Federal Regulations, 2012 CFR

2012-10-01

... from which that LLP license was derived during the calendar years 2000 and 2001, unless clear and...) Determine the Total Entry Level Trawl Fishery Transition Rockfish QS pool for each rockfish primary species... Rockfish QS pools. (v) Multiply the Percentage of the Total Entry Level Trawl Fishery Transition Rockfish...

Review of chemical-kinetic problems of future NASA missions, II: Mars entries

NASA Technical Reports Server (NTRS)

Park, Chul; Howe, John T.; Jaffe, Richard L.; Candler, Graham V.

1994-01-01

The present work aims to derive a set of thermomechanical relaxation rate parameters and chemical reaction rate coefficients relevant to future interplanetary missions. It also attempts to assess the impact of thermochemical nonequilibrium phenomena on radiative heating rates for the stagnation point of the Martian entry vehicle.

Dose factor entry and display tool for BNCT radiotherapy

DOEpatents

Wessol, Daniel E.; Wheeler, Floyd J.; Cook, Jeremy L.

1999-01-01

A system for use in Boron Neutron Capture Therapy (BNCT) radiotherapy planning where a biological distribution is calculated using a combination of conversion factors and a previously calculated physical distribution. Conversion factors are presented in a graphical spreadsheet so that a planner can easily view and modify the conversion factors. For radiotherapy in multi-component modalities, such as Fast-Neutron and BNCT, it is necessary to combine each conversion factor component to form an effective dose which is used in radiotherapy planning and evaluation. The Dose Factor Entry and Display System is designed to facilitate planner entry of appropriate conversion factors in a straightforward manner for each component. The effective isodose is then immediately computed and displayed over the appropriate background (e.g. digitized image).

Hypersonic and Supersonic Static Aerodynamics of Mars Science Laboratory Entry Vehicle

NASA Technical Reports Server (NTRS)

Dyakonov, Artem A.; Schoenenberger, Mark; Vannorman, John W.

2012-01-01

This paper describes the analysis of continuum static aerodynamics of Mars Science Laboratory (MSL) entry vehicle (EV). The method is derived from earlier work for Mars Exploration Rover (MER) and Mars Path Finder (MPF) and the appropriate additions are made in the areas where physics are different from what the prior entry systems would encounter. These additions include the considerations for the high angle of attack of MSL EV, ablation of the heatshield during entry, turbulent boundary layer, and other aspects relevant to the flight performance of MSL. Details of the work, the supporting data and conclusions of the investigation are presented.

Amotivation and Indecision in the Decision-Making Processes Associated with University Entry

ERIC Educational Resources Information Center

Jung, Jae Yup

2013-01-01

This study developed and tested two models that examined the decision-making processes of adolescents relating to entry into university, in terms of the extent to which they may be amotivated and undecided. The models incorporated variables derived from self-determination theory, expectancy-value theory, and research on occupational indecision. A…

Shuttle derived atmospheric density model. Part 1: Comparisons of the various ambient atmospheric source data with derived parameters from the first twelve STS entry flights, a data package for AOTV atmospheric development

NASA Technical Reports Server (NTRS)

Findlay, J. T.; Kelly, G. M.; Troutman, P. A.

1984-01-01

The ambient atmospheric parameter comparisons versus derived values from the first twelve Space Shuttle Orbiter entry flights are presented. Available flights, flight data products, and data sources utilized are reviewed. Comparisons are presented based on remote meteorological measurements as well as two comprehensive models which incorporate latitudinal and seasonal effects. These are the Air Force 1978 Reference Atmosphere and the Marshall Space Flight Center Global Reference Model (GRAM). Atmospheric structure sensible in the Shuttle flight data is shown and discussed. A model for consideration in Aero-assisted Orbital Transfer Vehicle (AOTV) trajectory analysis, proposed to modify the GRAM data to emulate Shuttle experiments.

Post-Flight EDL Entry Guidance Performance of the 2011 Mars Science Laboratory Mission

NASA Technical Reports Server (NTRS)

Mendeck, Gavin F.; McGrew, Lynn Craig

2013-01-01

The 2011 Mars Science Laboratory was the first Mars guided entry which safely delivered the rover to a landing within a touchdown ellipse of 19.1 km x 6.9 km. The Entry Terminal Point Controller guidance algorithm is derived from the final phase Apollo Command Module guidance and, like Apollo, modulates the bank angle to control the range flown. The guided entry performed as designed without any significant exceptions. The Curiosity rover was delivered about 2.2 km from the expected touchdown. This miss distance is attributed to little time to correct the downrange drift from the final bank reversal and a suspected tailwind during heading alignment. The successful guided entry for the Mars Science Laboratory lays the foundation for future Mars missions to improve upon.

An organizational field approach to resource environments in healthcare: comparing entries of hospitals and home health agencies in the San Francisco Bay region.

PubMed

Ruef, M; Mendel, P; Scott, W R

1998-02-01

To draw together insights from three perspectives (health economics, organizational ecology, and institutional theory) in order to clarify the factors that influence entries of providers into healthcare markets. A model centered on the concept of an organizational field is advanced as the level of analysis best suited to examining the assortment and interdependence of organizational populations and the institutional forces that shape this co-evolution. In particular, the model argues that: (1) different populations of healthcare providers partition fiscal, geographic, and demographic resource environments in order to ameliorate competition and introduce service complementarities; and (2) competitive barriers to entry within populations of providers vary systematically with regulatory regimens. County-level entries of hospitals and home health agencies in the San Francisco Bay Area using data from the American Hospital Association (1945-1991) and California's Office of Statewide Health Planning and Development (1976-1991). Characteristics of the resource environment are derived from the Area Resource File (ARF) and selected government censuses. A comparative design is applied to contrast influences on hospital and home health agency entries during the post-World War II period. Empirical estimates are obtained using Poisson and negative binomial regression models. Hospital and HHA markets are partitioned primarily by the age and education of consumers and, to a lesser extent, by urbanization levels and public funding expenditures. Such resource partitioning allows independent HHAs to exist comfortably in concentrated hospital markets. For both hospitals and HHAs, the barriers to entry once generated by oligopolistic concentration have declined noticeably with the market-oriented reforms of the past 15 years. A field-level perspective demonstrates that characteristics of local resource environments interact with interdependencies of provider populations and broader regulatory regimes to affect significantly the types of provider organizations likely to enter a given healthcare market.

An organizational field approach to resource environments in healthcare: comparing entries of hospitals and home health agencies in the San Francisco Bay region.

PubMed Central

Ruef, M; Mendel, P; Scott, W R

1998-01-01

OBJECTIVE: To draw together insights from three perspectives (health economics, organizational ecology, and institutional theory) in order to clarify the factors that influence entries of providers into healthcare markets. A model centered on the concept of an organizational field is advanced as the level of analysis best suited to examining the assortment and interdependence of organizational populations and the institutional forces that shape this co-evolution. In particular, the model argues that: (1) different populations of healthcare providers partition fiscal, geographic, and demographic resource environments in order to ameliorate competition and introduce service complementarities; and (2) competitive barriers to entry within populations of providers vary systematically with regulatory regimens. DATA SOURCES: County-level entries of hospitals and home health agencies in the San Francisco Bay Area using data from the American Hospital Association (1945-1991) and California's Office of Statewide Health Planning and Development (1976-1991). Characteristics of the resource environment are derived from the Area Resource File (ARF) and selected government censuses. METHODS OF ANALYSIS: A comparative design is applied to contrast influences on hospital and home health agency entries during the post-World War II period. Empirical estimates are obtained using Poisson and negative binomial regression models. RESULTS: Hospital and HHA markets are partitioned primarily by the age and education of consumers and, to a lesser extent, by urbanization levels and public funding expenditures. Such resource partitioning allows independent HHAs to exist comfortably in concentrated hospital markets. For both hospitals and HHAs, the barriers to entry once generated by oligopolistic concentration have declined noticeably with the market-oriented reforms of the past 15 years. CONCLUSION: A field-level perspective demonstrates that characteristics of local resource environments interact with interdependencies of provider populations and broader regulatory regimes to affect significantly the types of provider organizations likely to enter a given healthcare market. PMID:9460486

Evaluation of the thiazole Schiff bases as β-glucuronidase inhibitors and their in silico studies.

PubMed

Khan, Khalid Mohammed; Karim, Aneela; Saied, Sumayya; Ambreen, Nida; Rustamova, Xayale; Naureen, Shagufta; Mansoor, Sajid; Ali, Muhammad; Perveen, Shahnaz; Choudhary, M Iqbal; Morales, Guillermo Antonio

2014-05-01

Twenty eight (28) derivatives 2-29 were synthesized and four analogs were found to exhibit single-digit IC(50) values as β-glucuronidase inhibitors. Molecular modeling indicates that three factors: substituent R, lone pair on the nitrogen of azomethine part, and the interactions made by the main skeleton of the molecule, determined the enzyme inhibitory potential of these compounds. The planar conformation of the molecules allows them to fit deep inside the pocket while blocking the entry of other physiological substrates seems to play an important role in their activity.

Adolescent Decision-Making Processes regarding University Entry: A Model Incorporating Cultural Orientation, Motivation and Occupational Variables

ERIC Educational Resources Information Center

Jung, Jae Yup

2013-01-01

This study tested a newly developed model of the cognitive decision-making processes of senior high school students related to university entry. The model incorporated variables derived from motivation theory (i.e. expectancy-value theory and the theory of reasoned action), literature on cultural orientation and occupational considerations. A…

The Relationship between Entry Motivation and Professional Satisfaction of No-Fee Preservice Students

ERIC Educational Resources Information Center

Li, Ling; Huang, Yuanyuan; Xu, Xingchun; Han, Yumei

2013-01-01

This study used expectancy-value theory to better understand no-fee teacher education and improve the relevant educational methods and policies. It applies a self-developed scale, derived from the theory, to identify entry motivation and professional satisfaction levels among no-fee teacher education students (N = 700) at Southwest University. The…

Oxford dictionary of Physics

NASA Astrophysics Data System (ADS)

Isaacs, Alan

The dictionary is derived from the Concise Science Dictionary, first published by Oxford University Press in 1984 (third edition, 1996). It consists of all the entries relating to physics in that dictionary, together with some of those entries relating to astronomy that are required for an understanding of astrophysics and many entries that relate to physical chemistry. It also contains a selection of the words used in mathematics that are relevant to physics, as well as the key words in metal science, computing, and electronics. For this third edition a number of words from quantum field physics and statistical mechanics have been added. Cosmology and particle physics have been updated and a number of general entries have been expanded.

Saturn Uranus atmospheric entry probe mission spacecraft system definition study

NASA Technical Reports Server (NTRS)

1973-01-01

The modifications required of the Pioneer F/G spacecraft design for it to deliver an atmospheric entry probe to the planets Saturn and Uranus are investigated. It is concluded that it is feasible to conduct such a mission within the constraints and interfaces defined. The spacecraft required to perform the mission is derived from the Pioneer F/G design, and the modifications required are generally routinely conceived and executed. The entry probe is necessarily a new design, although it draws on the technology of past, present, and imminent programs of planetary atmospheric investigations.

Missile Aerodynamics for Ascent and Re-entry

NASA Technical Reports Server (NTRS)

Watts, Gaines L.; McCarter, James W.

2012-01-01

Aerodynamic force and moment equations are developed for 6-DOF missile simulations of both the ascent phase of flight and a tumbling re-entry. The missile coordinate frame (M frame) and a frame parallel to the M frame were used for formulating the aerodynamic equations. The missile configuration chosen as an example is a cylinder with fixed fins and a nose cone. The equations include both the static aerodynamic coefficients and the aerodynamic damping derivatives. The inclusion of aerodynamic damping is essential for simulating a tumbling re-entry. Appended information provides insight into aerodynamic damping.

Factors associated with re-entry to out-of-home care among children in England.

PubMed

Mc Grath-Lone, Louise; Dearden, Lorraine; Harron, Katie; Nasim, Bilal; Gilbert, Ruth

2017-01-01

Exiting and re-entering out-of-home care (OHC) is considered a disruption to permanence which may have long-lasting, negative consequences for children due to a lack of stability and continuity. Each year approximately one-third of children in OHC in England exit, but information is lacking on rates of re-entries and associated factors. Using national administrative data, we calculated rates of re-entry among children exiting OHC from 2007 to 2012, identified key child and care factors associated with re-entry using Cox proportional hazards modelling, and developed a simple probability calculator to estimate which groups of children are most likely to re-enter OHC within three months. Between 2007 and 2012 re-entries to OHC in England decreased (from 23.3% to 14.4% within one year of exit, p<0.001), possibly due to concurrent changes in the way children exited OHC. Overall, more than one-third of children exiting OHC in 2008 re-entered within five years (35.3%, N=4076), but rates of re-entry varied by child and care characteristics including age, ethnicity, mode of exit, and placement stability. Based on these associated factors, we developed a calculator that can estimate the likelihood of rapid re-entry to OHC for a group of children and could be used by social care practitioners or service planners. Our findings provide insight into which groups of children are most likely to re-enter OHC, who may benefit from additional support or ongoing monitoring. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evaluation and identification of hepatitis B virus entry inhibitors using HepG2 cells overexpressing a membrane transporter NTCP.

PubMed

Iwamoto, Masashi; Watashi, Koichi; Tsukuda, Senko; Aly, Hussein Hassan; Fukasawa, Masayoshi; Fujimoto, Akira; Suzuki, Ryosuke; Aizaki, Hideki; Ito, Takayoshi; Koiwai, Osamu; Kusuhara, Hiroyuki; Wakita, Takaji

2014-01-17

Hepatitis B virus (HBV) entry has been analyzed using infection-susceptible cells, including primary human hepatocytes, primary tupaia hepatocytes, and HepaRG cells. Recently, the sodium taurocholate cotransporting polypeptide (NTCP) membrane transporter was reported as an HBV entry receptor. In this study, we established a strain of HepG2 cells engineered to overexpress the human NTCP gene (HepG2-hNTCP-C4 cells). HepG2-hNTCP-C4 cells were shown to be susceptible to infection by blood-borne and cell culture-derived HBV. HBV infection was facilitated by pretreating cells with 3% dimethyl sulfoxide permitting nearly 50% of the cells to be infected with HBV. Knockdown analysis suggested that HBV infection of HepG2-hNTCP-C4 cells was mediated by NTCP. HBV infection was blocked by an anti-HBV surface protein neutralizing antibody, by compounds known to inhibit NTCP transporter activity, and by cyclosporin A and its derivatives. The infection assay suggested that cyclosporin B was a more potent inhibitor of HBV entry than was cyclosporin A. Further chemical screening identified oxysterols, oxidized derivatives of cholesterol, as inhibitors of HBV infection. Thus, the HepG2-hNTCP-C4 cell line established in this study is a useful tool for the identification of inhibitors of HBV infection as well as for the analysis of the molecular mechanisms of HBV infection. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Genome-wide siRNA screen identifies the retromer as a cellular entry factor for human papillomavirus

PubMed Central

Lipovsky, Alex; Popa, Andreea; Pimienta, Genaro; Wyler, Michael; Bhan, Ashima; Kuruvilla, Leena; Guie, Marie-Aude; Poffenberger, Adrian C.; Nelson, Christian D. S.; Atwood, Walter J.; DiMaio, Daniel

2013-01-01

Despite major advances in our understanding of many aspects of human papillomavirus (HPV) biology, HPV entry is poorly understood. To identify cellular genes required for HPV entry, we conducted a genome-wide screen for siRNAs that inhibited infection of HeLa cells by HPV16 pseudovirus. Many retrograde transport factors were required for efficient infection, including multiple subunits of the retromer, which initiates retrograde transport from the endosome to the trans-Golgi network (TGN). The retromer has not been previously implicated in virus entry. Furthermore, HPV16 capsid proteins arrive in the TGN/Golgi in a retromer-dependent fashion during entry, and incoming HPV proteins form a stable complex with retromer subunits. We propose that HPV16 directly engages the retromer at the early or late endosome and traffics to the TGN/Golgi via the retrograde pathway during cell entry. These results provide important insights into HPV entry, identify numerous potential antiviral targets, and suggest that the role of the retromer in infection by other viruses should be assessed. PMID:23569269

Derivation of lung mesenchymal lineages from the fetal mesothelium requires hedgehog signaling for mesothelial cell entry

PubMed Central

Dixit, Radhika; Ai, Xingbin; Fine, Alan

2013-01-01

Recent studies have shown that mesothelial progenitors contribute to mesenchymal lineages of developing organs. To what extent the overlying mesothelium contributes to lung development remains unknown. To rigorously address this question, we employed Wt1CreERT2/+ mice for high-fidelity lineage tracing after confirming that Cre recombinase was mesothelial specific and faithfully recapitulated endogenous Wilms’ tumor 1 (Wt1) gene expression. We visualized WT1+ mesothelial cell entry into the lung by live imaging and identified their progenies in subpopulations of bronchial smooth muscle cells, vascular smooth muscle cells and desmin+ fibroblasts by lineage tagging. Derivation of these lineages was only observed with Cre recombinase activation during early lung development. Using loss-of-function assays in organ cultures, and targeted mesothelial-restricted hedgehog loss-of-function mice, we demonstrated that mesothelial cell movement into the lung requires the direct action of hedgehog signaling. By contrast, hedgehog signaling was not required for fetal mesothelial heart entry. These findings further support a paradigm wherein the mesothelium is a source of progenitors for mesenchymal lineages during organogenesis and indicate that signals controlling mesothelial cell entry are organ specific. PMID:24130328

Derivation of lung mesenchymal lineages from the fetal mesothelium requires hedgehog signaling for mesothelial cell entry.

PubMed

Dixit, Radhika; Ai, Xingbin; Fine, Alan

2013-11-01

Recent studies have shown that mesothelial progenitors contribute to mesenchymal lineages of developing organs. To what extent the overlying mesothelium contributes to lung development remains unknown. To rigorously address this question, we employed Wt1(CreERT2/+) mice for high-fidelity lineage tracing after confirming that Cre recombinase was mesothelial specific and faithfully recapitulated endogenous Wilms' tumor 1 (Wt1) gene expression. We visualized WT1(+) mesothelial cell entry into the lung by live imaging and identified their progenies in subpopulations of bronchial smooth muscle cells, vascular smooth muscle cells and desmin(+) fibroblasts by lineage tagging. Derivation of these lineages was only observed with Cre recombinase activation during early lung development. Using loss-of-function assays in organ cultures, and targeted mesothelial-restricted hedgehog loss-of-function mice, we demonstrated that mesothelial cell movement into the lung requires the direct action of hedgehog signaling. By contrast, hedgehog signaling was not required for fetal mesothelial heart entry. These findings further support a paradigm wherein the mesothelium is a source of progenitors for mesenchymal lineages during organogenesis and indicate that signals controlling mesothelial cell entry are organ specific.

Hepatitis C virus depends on E-cadherin as an entry factor and regulates its expression in epithelial-to-mesenchymal transition.

PubMed

Li, Qisheng; Sodroski, Catherine; Lowey, Brianna; Schweitzer, Cameron J; Cha, Helen; Zhang, Fang; Liang, T Jake

2016-07-05

Hepatitis C virus (HCV) enters the host cell through interactions with a cascade of cellular factors. Although significant progress has been made in understanding HCV entry, the precise mechanisms by which HCV exploits the receptor complex and host machinery to enter the cell remain unclear. This intricate process of viral entry likely depends on additional yet-to-be-defined cellular molecules. Recently, by applying integrative functional genomics approaches, we identified and interrogated distinct sets of host dependencies in the complete HCV life cycle. Viral entry assays using HCV pseudoparticles (HCVpps) of various genotypes uncovered multiple previously unappreciated host factors, including E-cadherin, that mediate HCV entry. E-cadherin silencing significantly inhibited HCV infection in Huh7.5.1 cells, HepG2/miR122/CD81 cells, and primary human hepatocytes at a postbinding entry step. Knockdown of E-cadherin, however, had no effect on HCV RNA replication or internal ribosomal entry site (IRES)-mediated translation. In addition, an E-cadherin monoclonal antibody effectively blocked HCV entry and infection in hepatocytes. Mechanistic studies demonstrated that E-cadherin is closely associated with claudin-1 (CLDN1) and occludin (OCLN) on the cell membrane. Depletion of E-cadherin drastically diminished the cell-surface distribution of these two tight junction proteins in various hepatic cell lines, indicating that E-cadherin plays an important regulatory role in CLDN1/OCLN localization on the cell surface. Furthermore, loss of E-cadherin expression in hepatocytes is associated with HCV-induced epithelial-to-mesenchymal transition (EMT), providing an important link between HCV infection and liver cancer. Our data indicate that a dynamic interplay among E-cadherin, tight junctions, and EMT exists and mediates an important function in HCV entry.

Beyond 'Inop': Logbook Communication Between Airline Mechanics and Pilots

NASA Technical Reports Server (NTRS)

Munro, Pamela A.; Kanki, Barbara G.; Jordan, Kevin

2008-01-01

When mechanical discrepancies occur on aircraft, effective communication between pilots and mechanics can facilitate identification of the problem. A survey of pilots and mechanics was conducted to determine how often they were able to discuss discrepancies directly and to identify factors that influenced the detail they provided about discrepancies in the aircraft logbook. Logistical factors such as short turn times between flights and crew schedules appeared to present barriers to face-to-face meetings between pilots and mechanics. Guidelines for pilot logbook entries. Pilots reported receiving significantly less training on writing logbook entries and spent significantly less time making individual entries than mechanics. Mechanics indicated greater concern about the Federal Aviation Administration reading their entries than pilots. Mechanics indicated they had little opportunity to follow up with pilots to clarify a logbook entry once pilots departed the aircraft.

Prenatal and Early Postnatal Exposure to Cigarette Smoke Decreases BDNF/TrkB Signaling and Increases Abnormal Behaviors Later in Life

PubMed Central

Xiao, Lan; Kish, Vincent L.; Benders, Katherine M.

2016-01-01

Background: Cigarette smoke exposure during prenatal and early postnatal periods increases the incidence of a variety of abnormal behaviors later in life. The purpose of this study was to identify the possible critical period of susceptibility to cigarette smoke exposure and evaluate the possibe effects of cigarette smoke during early life on brain-derived neurotrophic factor/neurotrophic tyrosine kinase receptor B signaling in the brain. Methods: Three different age of imprinting control region mice were exposed to cigarette smoke or filtered air for 10 consecutive days beginning on either gestational day 7 by maternal exposure, or postnatal days 2 or 21 by direct inhalation. A series of behavioral profiles and neurotrophins in brain were measured 24 hours after mice received acute restraint stress for 1 hour on postnatal day 59. Results: Cigarette smoke exposure in gestational day 7 and postnatal day 2 produced depression-like behaviors as evidenced by significantly increased immobility in both tail suspension and forced-swim test. Increased entry latencies, but not ambulation in the open field test, were also observed in the gestational day 7 and postnatal day 2 cigarette smoke exposure groups. Genetic analysis showed that gestational day 7 cigarette smoke exposure significantly altered mRNA level of brain-derived neurotrophic factor/tyrosine kinase receptor B in the hippocampus. However, behavioral profiles and brain-derived neurotrophic factor/tyrosine kinase receptor B signaling were not significantly changed in PND21 cigarette smoke exposure group compared with FA group. Conclusions: These results suggest that a critical period of susceptibility to cigarette smoke exposure exists in the prenatal and early postnatal period, which results a downregulation in brain-derived neurotrophic factor/tyrosine kinase receptor B signaling in the hippocampus and enhances depression-like behaviors later in life. PMID:26503133

Ebola virus host cell entry.

PubMed

Sakurai, Yasuteru

2015-01-01

Ebola virus is an enveloped virus with filamentous structure and causes a severe hemorrhagic fever in human and nonhuman primates. Host cell entry is the first essential step in the viral life cycle, which has been extensively studied as one of the therapeutic targets. A virus factor of cell entry is a surface glycoprotein (GP), which is an only essential viral protein in the step, as well as the unique particle structure. The virus also interacts with a lot of host factors to successfully enter host cells. Ebola virus at first binds to cell surface proteins and internalizes into cells, followed by trafficking through endosomal vesicles to intracellular acidic compartments. There, host proteases process GPs, which can interact with an intracellular receptor. Then, under an appropriate circumstance, viral and endosomal membranes are fused, which is enhanced by major structural changes of GPs, to complete host cell entry. Recently the basic research of Ebola virus infection mechanism has markedly progressed, largely contributed by identification of host factors and detailed structural analyses of GPs. This article highlights the mechanism of Ebola virus host cell entry, including recent findings.

Development and application of an empirical probability distribution for the prediction error of re-entry body maximum dynamic pressure

NASA Technical Reports Server (NTRS)

Lanzi, R. James; Vincent, Brett T.

1993-01-01

The relationship between actual and predicted re-entry maximum dynamic pressure is characterized using a probability density function and a cumulative distribution function derived from sounding rocket flight data. This paper explores the properties of this distribution and demonstrates applications of this data with observed sounding rocket re-entry body damage characteristics to assess probabilities of sustaining various levels of heating damage. The results from this paper effectively bridge the gap existing in sounding rocket reentry analysis between the known damage level/flight environment relationships and the predicted flight environment.

TIM1 (HAVCR1) Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions.

PubMed

Das, Anshuman; Hirai-Yuki, Asuka; González-López, Olga; Rhein, Bethany; Moller-Tank, Sven; Brouillette, Rachel; Hensley, Lucinda; Misumi, Ichiro; Lovell, William; Cullen, John M; Whitmire, Jason K; Maury, Wendy; Lemon, Stanley M

2017-09-05

Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1) is widely accepted to be the receptor for hepatitis A virus (HAV), an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV) virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-engineered TIM1 knockout. Cell culture-derived, gradient-purified eHAV bound Huh-7.5 human hepatoma cells less efficiently than naked HAV at 4°C, but eliminating TIM1 expression caused no difference in adherence of either form of HAV, nor any impact on infection and replication in these cells. In contrast, TIM1-deficient Vero cells showed a modest reduction in quasi-enveloped eHAV (but not naked HAV) attachment and replication. Thus, TIM1 facilitates quasi-enveloped eHAV entry in Vero cells, most likely by binding phosphatidylserine (PtdSer) residues on the eHAV membrane. Both Tim1 -/- Ifnar1 -/- and Tim4 -/- Ifnar1 -/- double-knockout mice were susceptible to infection upon intravenous challenge with infected liver homogenate, with fecal HAV shedding and serum alanine aminotransferase (ALT) elevations similar to those in Ifnar1 -/- mice. However, intrahepatic HAV RNA and ALT elevations were modestly reduced in Tim1 -/- Ifnar1 -/- mice compared to Ifnar1 -/- mice challenged with a lower titer of gradient-purified HAV or eHAV. We conclude that TIM1 is not an essential hepatovirus entry factor, although its PtdSer-binding activity may contribute to the spread of quasi-enveloped virus and liver injury in mice. IMPORTANCE T cell immunoglobulin and mucin-containing domain protein 1 (TIM1) was reported more than 2 decades ago to be an essential cellular receptor for hepatitis A virus (HAV), a picornavirus in the Hepatovirus genus, resulting in its designation as "hepatitis A virus cellular receptor 1" (HAVCR1) by the Human Genome Organization Gene Nomenclature Committee. However, recent studies have shown that HAV exists in nature as both naked, nonenveloped (HAV) virions and membrane-cloaked, quasi-enveloped infectious virus (eHAV), prompting us to revisit the role of TIM1 in viral entry. We show here that TIM1 (HAVCR1) is not an essential cellular receptor for HAV entry into cultured cells or required for viral replication and pathogenesis in permissive strains of mice, although it may facilitate early stages of infection by binding phosphatidylserine on the eHAV surface. This work thus corrects the published record and sets the stage for future efforts to identify specific hepatovirus entry factors. Copyright © 2017 Das et al.

Market entry, power, pharmacokinetics: what makes a successful drug innovation?

PubMed

Alt, Susanne; Helmstädter, Axel

2018-02-01

Depending on the timing of market entry, radical innovations can be distinguished from incremental innovations. Whereas a radical innovation typically is the first available derivative of a drug class, incremental innovations are launched later and show a certain benefit compared with the radical innovation. Here, we use historical market data relating to pharmacokinetic (PK), pharmacodynamic (PD), and other drug-related properties to investigate which derivatives within certain drug classes have been most successful on the market. Based on our investigations, we suggest naming the most successful drugs 'overtaking innovation', because they often exceed the market share of all the other derivatives. Seven drug classes showed that the overtaking innovation is never a radical innovation, but rather an early incremental innovation, with advantages in manageability and/or tolerance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Racial/Ethnic Disparities in ADHD Diagnosis by Kindergarten Entry

ERIC Educational Resources Information Center

Morgan, Paul L.; Hillemeier, Marianne M.; Farkas, George; Maczuga, Steve

2014-01-01

Background: Whether and to what extent racial/ethnic disparities in attention-deficit/hyperactivity disorder (ADHD) diagnosis occur by kindergarten entry is currently unknown. We investigated risk factors associated with an ADHD diagnosis by kindergarten entry generally, and specifically whether racial/ethnic disparities in ADHD diagnosis occur by…

Near-Optimal Re-Entry Trajectories for Reusable Launch Vehicles

NASA Technical Reports Server (NTRS)

Chou, H.-C.; Ardema, M. D.; Bowles, J. V.

1997-01-01

A near-optimal guidance law for the descent trajectory for earth orbit re-entry of a fully reusable single-stage-to-orbit pure rocket launch vehicle is derived. A methodology is developed to investigate using both bank angle and altitude as control variables and selecting parameters that maximize various performance functions. The method is based on the energy-state model of the aircraft equations of motion. The major task of this paper is to obtain optimal re-entry trajectories under a variety of performance goals: minimum time, minimum surface temperature, minimum heating, and maximum heading change; four classes of trajectories were investigated: no banking, optimal left turn banking, optimal right turn banking, and optimal bank chattering. The cost function is in general a weighted sum of all performance goals. In particular, the trade-off between minimizing heat load into the vehicle and maximizing cross range distance is investigated. The results show that the optimization methodology can be used to derive a wide variety of near-optimal trajectories.

Glycoprotein D of herpes simplex virus (HSV) binds directly to HVEM, a member of the tumor necrosis factor receptor superfamily and a mediator of HSV entry.

PubMed Central

Whitbeck, J C; Peng, C; Lou, H; Xu, R; Willis, S H; Ponce de Leon, M; Peng, T; Nicola, A V; Montgomery, R I; Warner, M S; Soulika, A M; Spruce, L A; Moore, W T; Lambris, J D; Spear, P G; Cohen, G H; Eisenberg, R J

1997-01-01

Glycoprotein D (gD) is a structural component of the herpes simplex virus (HSV) envelope which is essential for virus entry into host cells. Chinese hamster ovary (CHO-K1) cells are one of the few cell types which are nonpermissive for the entry of many HSV strains. However, when these cells are transformed with the gene for the herpesvirus entry mediator (HVEM), the resulting cells, CHO-HVEM12, are permissive for many HSV strains, such as HSV-1(KOS). By virtue of its four cysteine-rich pseudorepeats, HVEM is a member of the tumor necrosis factor receptor superfamily of proteins. Recombinant forms of gD and HVEM, gD-1(306t) and HVEM(200t), respectively, were used to demonstrate a specific physical interaction between these two proteins. This interaction was dependent on native gD conformation but independent of its N-linked oligosaccharides, as expected from previous structure-function studies. Recombinant forms of gD derived from HSV-1(KOS)rid1 and HSV-1(ANG) did not bind to HVEM(200t), explaining the inability of these viruses to infect CHO-HVEM12 cells. A variant gD protein, gD-1(delta290-299t), showed enhanced binding to HVEM(200t) relative to the binding of gD-1(306t). Competition studies showed that gD-1(delta290-299t) and gD-1(306t) bound to the same region of HVEM(200t), suggesting that the differences in binding to HVEM are due to differences in affinity. These differences were also reflected in the ability of gD-1(delta290-299t) but not gD-1(306t) to block HSV type 1 infection of CHO-HVEM12 cells. By gel filtration chromatography, the complex between gD-1(delta290-299t) and HVEM(200t) had a molecular mass of 113 kDa and a molar ratio of 1:2. We conclude that HVEM interacts directly with gD, suggesting that HVEM is a receptor for virion gD and that the interaction between these proteins is a step in HSV entry into HVEM-expressing cells. PMID:9223502

Ground-state transcriptional requirements for skin-derived precursors.

PubMed

Suflita, Michael T; Pfaltzgraff, Elise R; Mundell, Nathan A; Pevny, Larysa H; Labosky, Patricia A

2013-06-15

Skin-derived precursors (SKPs) are an attractive stem cell model for cell-based therapies. SKPs can be readily generated from embryonic and adult mice and adult humans, exhibit a high degree of multipotency, and have the potential to serve as a patient autologous stem cell. The advancement of these cells toward therapeutic use depends on the ability to control precisely the self-renewal and differentiation of SKPs. Here we show that two well-known stem cell factors, Foxd3 and Sox2, are critical regulators of the stem cell properties of SKPs. Deletion of Foxd3 completely abolishes the sphere-forming potential of these cells. In the absence of Sox2, SKP spheres can be formed, but with reduced size and frequency. Our results provide entry points into the gene regulatory networks dictating SKP behavior, and pave the way for future studies on a therapeutically relevant stem cell.

Ground-State Transcriptional Requirements for Skin-Derived Precursors

PubMed Central

Suflita, Michael T.; Pfaltzgraff, Elise R.; Mundell, Nathan A.; Pevny, Larysa H.

2013-01-01

Skin-derived precursors (SKPs) are an attractive stem cell model for cell-based therapies. SKPs can be readily generated from embryonic and adult mice and adult humans, exhibit a high degree of multipotency, and have the potential to serve as a patient autologous stem cell. The advancement of these cells toward therapeutic use depends on the ability to control precisely the self-renewal and differentiation of SKPs. Here we show that two well-known stem cell factors, Foxd3 and Sox2, are critical regulators of the stem cell properties of SKPs. Deletion of Foxd3 completely abolishes the sphere-forming potential of these cells. In the absence of Sox2, SKP spheres can be formed, but with reduced size and frequency. Our results provide entry points into the gene regulatory networks dictating SKP behavior, and pave the way for future studies on a therapeutically relevant stem cell. PMID:23316968

Barriers to Taking Massive Open Online Courses (MOOCs)

ERIC Educational Resources Information Center

Semenova, Tatiana Vadimovna; Rudakova, Lyudmila Mikhailovna

2016-01-01

Researchers of the traditional higher education system identify a number of factors affecting admission to a university (barriers to entry) and factors of its successful completion (barriers to exit). Massive open online courses (MOOCs), available to any Internet user, remove barriers to entry because anyone can study there. But do all students…

Cellular Aspects of Prion Replication In Vitro

PubMed Central

Grassmann, Andrea; Wolf, Hanna; Hofmann, Julia; Graham, James; Vorberg, Ina

2013-01-01

Prion diseases or transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders in mammals that are caused by unconventional agents predominantly composed of aggregated misfolded prion protein (PrP). Prions self-propagate by recruitment of host-encoded PrP into highly ordered β-sheet rich aggregates. Prion strains differ in their clinical, pathological and biochemical characteristics and are likely to be the consequence of distinct abnormal prion protein conformers that stably replicate their alternate states in the host cell. Understanding prion cell biology is fundamental for identifying potential drug targets for disease intervention. The development of permissive cell culture models has greatly enhanced our knowledge on entry, propagation and dissemination of TSE agents. However, despite extensive research, the precise mechanism of prion infection and potential strain effects remain enigmatic. This review summarizes our current knowledge of the cell biology and propagation of prions derived from cell culture experiments. We discuss recent findings on the trafficking of cellular and pathologic PrP, the potential sites of abnormal prion protein synthesis and potential co-factors involved in prion entry and propagation. PMID:23340381

A case study of multi-seam coal mine entry stability analysis with strength reduction method

PubMed Central

Tulu, Ihsan Berk; Esterhuizen, Gabriel S; Klemetti, Ted; Murphy, Michael M.; Sumner, James; Sloan, Michael

2017-01-01

In this paper, the advantage of using numerical models with the strength reduction method (SRM) to evaluate entry stability in complex multiple-seam conditions is demonstrated. A coal mine under variable topography from the Central Appalachian region is used as a case study. At this mine, unexpected roof conditions were encountered during development below previously mined panels. Stress mapping and observation of ground conditions were used to quantify the success of entry support systems in three room-and-pillar panels. Numerical model analyses were initially conducted to estimate the stresses induced by the multiple-seam mining at the locations of the affected entries. The SRM was used to quantify the stability factor of the supported roof of the entries at selected locations. The SRM-calculated stability factors were compared with observations made during the site visits, and the results demonstrate that the SRM adequately identifies the unexpected roof conditions in this complex case. It is concluded that the SRM can be used to effectively evaluate the likely success of roof supports and the stability condition of entries in coal mines. PMID:28239503

A case study of multi-seam coal mine entry stability analysis with strength reduction method.

PubMed

Tulu, Ihsan Berk; Esterhuizen, Gabriel S; Klemetti, Ted; Murphy, Michael M; Sumner, James; Sloan, Michael

2016-03-01

In this paper, the advantage of using numerical models with the strength reduction method (SRM) to evaluate entry stability in complex multiple-seam conditions is demonstrated. A coal mine under variable topography from the Central Appalachian region is used as a case study. At this mine, unexpected roof conditions were encountered during development below previously mined panels. Stress mapping and observation of ground conditions were used to quantify the success of entry support systems in three room-and-pillar panels. Numerical model analyses were initially conducted to estimate the stresses induced by the multiple-seam mining at the locations of the affected entries. The SRM was used to quantify the stability factor of the supported roof of the entries at selected locations. The SRM-calculated stability factors were compared with observations made during the site visits, and the results demonstrate that the SRM adequately identifies the unexpected roof conditions in this complex case. It is concluded that the SRM can be used to effectively evaluate the likely success of roof supports and the stability condition of entries in coal mines.

A combination HIV reporter virus system for measuring post-entry event efficiency and viral outcome in primary CD4+ T cell subsets.

PubMed

Tilton, Carisa A; Tabler, Caroline O; Lucera, Mark B; Marek, Samantha L; Haqqani, Aiman A; Tilton, John C

2014-01-01

Fusion between the viral membrane of human immunodeficiency virus (HIV) and the host cell marks the end of the HIV entry process and the beginning of a series of post-entry events including uncoating, reverse transcription, integration, and viral gene expression. The efficiency of post-entry events can be modulated by cellular factors including viral restriction factors and can lead to several distinct outcomes: productive, latent, or abortive infection. Understanding host and viral proteins impacting post-entry event efficiency and viral outcome is critical for strategies to reduce HIV infectivity and to optimize transduction of HIV-based gene therapy vectors. Here, we report a combination reporter virus system measuring both membrane fusion and viral promoter-driven gene expression. This system enables precise determination of unstimulated primary CD4+ T cell subsets targeted by HIV, the efficiency of post-entry viral events, and viral outcome and is compatible with high-throughput screening and cell-sorting methods. Copyright © 2013 Elsevier B.V. All rights reserved.

Acute Lung Injury: Making the Injured Lung Perform Better and Rebuilding Healthy Lungs

DTIC Science & Technology

2014-04-01

A. Derivation Lung Mesenchymal Lineages from the Fetal Mesothelium Requires Hedgehog Signaling for Mesothelial Cell Entry. Development 140:4398-4405...mesothelial cell entry into the developing lung are largely unknown. The importance of the hedgehog (Hh) signaling pathway in mesenchymal...et al., 1997; Weaver et al., 2003; Polizio et al., 2011; Yoo et al., 2011). Mammals express three Hh ligands: Indian hedgehog (IHH), desert hedgehog

Determination of Barometric Altimeter Errors for the Orion Exploration Flight Test-1 Entry

NASA Technical Reports Server (NTRS)

Brown, Denise L.; Bunoz, Jean-Philippe; Gay, Robert

2012-01-01

The Exploration Flight Test 1 (EFT-1) mission is the unmanned flight test for the upcoming Multi-Purpose Crew Vehicle (MPCV). During entry, the EFT-1 vehicle will trigger several Landing and Recovery System (LRS) events, such as parachute deployment, based on on-board altitude information. The primary altitude source is the filtered navigation solution updated with GPS measurement data. The vehicle also has three barometric altimeters that will be used to measure atmospheric pressure during entry. In the event that GPS data is not available during entry, the altitude derived from the barometric altimeter pressure will be used to trigger chute deployment for the drogues and main parachutes. Therefore it is important to understand the impact of error sources on the pressure measured by the barometric altimeters and on the altitude derived from that pressure. The error sources for the barometric altimeters are not independent, and many error sources result in bias in a specific direction. Therefore conventional error budget methods could not be applied. Instead, high fidelity Monte-Carlo simulation was performed and error bounds were determined based on the results of this analysis. Aerodynamic errors were the largest single contributor to the error budget for the barometric altimeters. The large errors drove a change to the altitude trigger setpoint for FBC jettison deploy.

MSL EDL Entry Guidance using the Entry Terminal Point Controller

NASA Technical Reports Server (NTRS)

2006-01-01

The Mars Science Laboratory will be the first Mars mission to attempt a guided entry with the objective of safely delivering the entry vehicle to a survivable parachute deploy state within 10 km of the pre-designated landing site. The Entry Terminal Point Controller guidance algorithm is derived from the final phase Apollo Command Module guidance and, like Apollo, modulates the bank angle to control range based on deviations in range, altitude rate, and drag acceleration from a reference trajectory. For application to Mars landers which must make use of the tenuous Martian atmosphere, it is critical to balance the lift of the vehicle to minimize the range while still ensuring a safe deploy altitude. An overview of the process to generate optimized guidance settings is presented, discussing improvements made over the last four years. Performance tradeoffs between ellipse size and deploy altitude will be presented, along with imposed constraints of entry acceleration and heating. Performance sensitivities to the bank reversal deadbands, heading alignment, attitude initialization error, and atmospheric delivery errors are presented. Guidance settings for contingency operations, such as those appropriate for severe dust storm scenarios, are evaluated.

Evaluation and Influence of Brachiocephalic Branch Re-entry in Patients With Type A Acute Aortic Dissection.

PubMed

Yasuda, Shota; Imoto, Kiyotaka; Uchida, Keiji; Karube, Norihisa; Minami, Tomoyuki; Goda, Motohiko; Suzuki, Shinichi; Masuda, Munetaka

2016-12-22

Stanford type A acute aortic dissection (A-AAD) extends to the brachiocephalic branches in some patients. After ascending aortic replacement, a remaining re-entry tear in the distal brachiocephalic branches may act as an entry and result in a patent false lumen in the aortic arch. However, the effect of brachiocephalic branch re-entry concomitant with A-AAD remains unknown.Methods and Results:Eighty-five patients with A-AAD who underwent ascending aortic replacement in which both preoperative and postoperative multiple-detector computed tomography (MDCT) scans could be evaluated were retrospectively studied. The presence of a patent false lumen in at least one of the brachiocephalic branches on preoperative MDCT was defined as brachiocephalic branch re-entry, and 41 patients (48%) had this. Postoperatively, 47 of 85 (55%) patients had a patent false lumen in the aortic arch. False lumen remained patent after operation in 34 out of the 41 (83%) patients with brachiocephalic branch re-entry, as compared to that in 13 of the 44 (30%) patients without such re-entry (P<0.001). Brachiocephalic branch re-entry was a significant risk factor for a late increase in the aortic arch diameter greater than 10 mm (P=0.047). Brachiocephalic branch re-entry in patients with A-AAD is related to a patent false lumen in the aortic arch early after ascending aortic replacement and is a risk factor for late aortic arch enlargement.

Predictors of student success in entry-level science courses

NASA Astrophysics Data System (ADS)

Singh, Mamta K.

Although the educational evaluation process is useful and valuable and is supported by the Higher Education Act, a strong research base for program evaluation of college entry-level science courses is still lacking. Studies in science disciplines such as, biology, chemistry, and physics have addressed various affective and demographic factors and their relationships to student achievement. However, the literature contains little information that specifically addresses student biology content knowledge skills (basics and higher order thinking skills) and identifies factors that affect students' success in entry-level college science courses. These gate-keeping courses require detailed evaluation if the goal of an institution is to increase students' performance and success in these courses. These factors are, in fact, a stepping stone for increasing the number of graduates in Science, Technology, Engineering, and Mathematics (STEM) majors. The present study measured students' biology content knowledge and investigated students' performance and success in college biology, chemistry, and physics entry-level courses. Seven variables---gender, ethnicity, high school Grade Point Average (GPA), high school science, college major, school financial aid support, and work hours were used as independent variables and course final performance as a dichotomous dependent variable. The sample comprised voluntary student participants in entry-level science courses. The study attempted to explore eight research questions. Content knowledge assessments, demographic information analysis, multiple regression analysis, and binary logistic regression analysis were used to address research questions. The results suggested that high school GPA was a consistently good predictor of students' performance and success in entry-level science courses. Additionally, high school chemistry was a significant predictor variable for student success in entry-level biology and chemistry courses. Similarly, students' performance and success in entry-level physics courses were influenced by high school physics. Finally, the study developed student success equation with high school GAP and high school chemistry as good predictors of students' success in entry-level science courses.

Characterisation of re-entrant circuit (or rotational activity) in vitro using the HL1-6 myocyte cell line.

PubMed

Houston, Charles; Tzortzis, Konstantinos N; Roney, Caroline; Saglietto, Andrea; Pitcher, David S; Cantwell, Chris D; Chowdhury, Rasheda A; Ng, Fu Siong; Peters, Nicholas S; Dupont, Emmanuel

2018-06-01

Fibrillation is the most common arrhythmia observed in clinical practice. Understanding of the mechanisms underlying its initiation and maintenance remains incomplete. Functional re-entries are potential drivers of the arrhythmia. Two main concepts are still debated, the "leading circle" and the "spiral wave or rotor" theories. The homogeneous subclone of the HL1 atrial-derived cardiomyocyte cell line, HL1-6, spontaneously exhibits re-entry on a microscopic scale due to its slow conduction velocity and the presence of triggers, making it possible to examine re-entry at the cellular level. We therefore investigated the re-entry cores in cell monolayers through the use of fluorescence optical mapping at high spatiotemporal resolution in order to obtain insights into the mechanisms of re-entry. Re-entries in HL1-6 myocytes required at least two triggers and a minimum colony area to initiate (3.5 to 6.4 mm 2 ). After electrical activity was completely stopped and re-started by varying the extracellular K + concentration, re-entries never returned to the same location while 35% of triggers re-appeared at the same position. A conduction delay algorithm also allows visualisation of the core of the re-entries. This work has revealed that the core of re-entries is conduction blocks constituted by lines and/or groups of cells rather than the round area assumed by the other concepts of functional re-entry. This highlights the importance of experimentation at the microscopic level in the study of re-entry mechanisms. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells.

PubMed

Lodge, Robert; Gilmore, Julian C; Ferreira Barbosa, Jérémy A; Lombard-Vadnais, Félix; Cohen, Éric A

2017-12-30

Human immunodeficiency virus type-1 (HIV-1) infection of monocyte/macrophages is modulated by the levels of entry receptors cluster of differentiation 4 (CD4) and C-C chemokine receptor type 5 (CCR5), as well as by host antiviral restriction factors, which mediate several post-entry blocks. We recently identified two microRNAs, miR-221 and miR-222, which limit HIV-1 entry during infection of monocyte-derived macrophages (MDMs) by down-regulating CD4 expression. Interestingly, CD4 is also down-regulated during the differentiation of monocytes into macrophages. In this study, we compared microRNA expression profiles in primary monocytes and macrophages by RNAseq and found that miR-221/miR-222 are enhanced in macrophages. We took advantage of the monocytic THP-1 cell line that, once differentiated, is poorly susceptible to HIV-1. Accordingly, we found that CD4 levels are very low in THP-1 differentiated cells and that this down-regulation of the virus receptor is the result of miR-221/miR-222 up-regulation during differentiation. We thus established a THP-1 cell line stably expressing a modified CD4 (THP-1-CD4 R ) that is not modulated by miR-221/miR-222. We show that in contrast to parental THP-1, this line is productively infected by HIV-1 following differentiation, sustaining efficient HIV-1 CD4-dependent replication and spread. This new THP-1-CD4 R cell line represents a useful tool for the study of HIV-1-macrophage interactions particularly in contexts where spreading of viral infection is necessary.

Regulation of CD4 Receptor and HIV-1 Entry by MicroRNAs-221 and -222 during Differentiation of THP-1 Cells

PubMed Central

Gilmore, Julian C.; Ferreira Barbosa, Jérémy A.; Lombard-Vadnais, Félix

2017-01-01

Human immunodeficiency virus type-1 (HIV-1) infection of monocyte/macrophages is modulated by the levels of entry receptors cluster of differentiation 4 (CD4) and C-C chemokine receptor type 5 (CCR5), as well as by host antiviral restriction factors, which mediate several post-entry blocks. We recently identified two microRNAs, miR-221 and miR-222, which limit HIV-1 entry during infection of monocyte-derived macrophages (MDMs) by down-regulating CD4 expression. Interestingly, CD4 is also down-regulated during the differentiation of monocytes into macrophages. In this study, we compared microRNA expression profiles in primary monocytes and macrophages by RNAseq and found that miR-221/miR-222 are enhanced in macrophages. We took advantage of the monocytic THP-1 cell line that, once differentiated, is poorly susceptible to HIV-1. Accordingly, we found that CD4 levels are very low in THP-1 differentiated cells and that this down-regulation of the virus receptor is the result of miR-221/miR-222 up-regulation during differentiation. We thus established a THP-1 cell line stably expressing a modified CD4 (THP-1-CD4R) that is not modulated by miR-221/miR-222. We show that in contrast to parental THP-1, this line is productively infected by HIV-1 following differentiation, sustaining efficient HIV-1 CD4-dependent replication and spread. This new THP-1-CD4R cell line represents a useful tool for the study of HIV-1-macrophage interactions particularly in contexts where spreading of viral infection is necessary. PMID:29301198

Report on an Investigation into an Entry Level Clinical Doctorate for the Genetic Counseling Profession and a Survey of the Association of Genetic Counseling Program Directors.

PubMed

Reiser, Catherine; LeRoy, Bonnie; Grubs, Robin; Walton, Carol

2015-10-01

The master's degree is the required entry-level degree for the genetic counseling profession in the US and Canada. In 2012 the Association of Genetic Counseling Program Directors (AGCPD) passed resolutions supporting retention of the master's as the entry-level and terminal degree and opposing introduction of an entry-level clinical doctorate (CD) degree. An AGCPD workgroup surveyed directors of all 34 accredited training programs with the objective of providing the Genetic Counseling Advanced Degrees Task Force (GCADTF) with information regarding potential challenges if master's programs were required to transition to an entry-level CD. Program demographics, projected ability to transition to an entry-level CD, factors influencing ability to transition, and potential effects of transition on programs, students and the genetic counseling workforce were characterized. Two programs would definitely be able to transition, four programs would close, thirteen programs would be at risk to close and fourteen programs would probably be able to transition with varying degrees of difficulty. The most frequently cited limiting factors were economic, stress on clinical sites, and administrative approval of a new degree/program. Student enrollment under an entry-level CD model was projected to decrease by 26.2 %, negatively impacting the workforce pipeline. The results further illuminate and justify AGCPD's position to maintain the master's as the entry-level degree.

Fluorescent protein-tagged Vpr dissociates from HIV-1 core after viral fusion and rapidly enters the cell nucleus.

PubMed

Desai, Tanay M; Marin, Mariana; Sood, Chetan; Shi, Jiong; Nawaz, Fatima; Aiken, Christopher; Melikyan, Gregory B

2015-10-29

HIV-1 Vpr is recruited into virions during assembly and appears to remain associated with the viral core after the reverse transcription and uncoating steps of entry. This feature has prompted the use of fluorescently labeled Vpr to visualize viral particles and to follow trafficking of post-fusion HIV-1 cores in the cytoplasm. Here, we tracked single pseudovirus entry and fusion and observed that fluorescently tagged Vpr gradually dissociates from post-fusion viral cores over the course of several minutes and accumulates in the nucleus. Kinetics measurements showed that fluorescent Vpr released from the cores very rapidly entered the cell nucleus. More than 10,000 Vpr molecules can be delivered into the cell nucleus within 45 min of infection by HIV-1 particles pseudotyped with the avian sarcoma and leukosis virus envelope glycoprotein. The fraction of Vpr from cell-bound viruses that accumulated in the nucleus was proportional to the extent of virus-cell fusion and was fully blocked by viral fusion inhibitors. Entry of virus-derived Vpr into the nucleus occurred independently of envelope glycoproteins or target cells. Fluorescence correlation spectroscopy revealed two forms of nuclear Vpr-monomers and very large complexes, likely involving host factors. The kinetics of viral Vpr entering the nucleus after fusion was not affected by point mutations in the capsid protein that alter the stability of the viral core. The independence of Vpr shedding of capsid stability and its relatively rapid dissociation from post-fusion cores suggest that this process may precede capsid uncoating, which appears to occur on a slower time scale. Our results thus demonstrate that a bulk of fluorescently labeled Vpr incorporated into HIV-1 particles is released shortly after fusion. Future studies will address the question whether the quick and efficient nuclear delivery of Vpr derived from incoming viruses can regulate subsequent steps of HIV-1 infection.

Analysis of Ebola Virus Entry Into Macrophages

PubMed Central

Dahlmann, Franziska; Biedenkopf, Nadine; Babler, Anne; Jahnen-Dechent, Willi; Karsten, Christina B.; Gnirß, Kerstin; Schneider, Heike; Wrensch, Florian; O'Callaghan, Christopher A.; Bertram, Stephanie; Herrler, Georg; Becker, Stephan; Pöhlmann, Stefan; Hofmann-Winkler, Heike

2015-01-01

Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)–driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. PMID:25877552

Market entry and exit by biotech and device companies funded by venture capital.

PubMed

Burns, Lawton R; Housman, Michael G; Robinson, Charles A

2009-01-01

Start-up companies in the biotechnology and medical device sectors are important sources of health care innovation. This paper describes the role of venture capital in supporting these companies and charts the growth in venture capital financial support. The paper then uses longitudinal data to describe market entry and exit by these companies. Similar factors are associated with entry and exit in the two sectors. Entries and exits in one sector also appear to influence entry in the other. These findings have important implications for developing innovative technologies and ensuring competitive markets in the life sciences.

MODELNG RADON ENTRY INTO FLORIDA HOUSES WITH CONCRETE SLABS AND CONCRETE-BLOCK STEM WALLS, FLORIDA RADON RESEARCH PROGRAM

EPA Science Inventory

The report discusses results of modeling radon entry into a typical Florida house whose interior is slightly depressurized. he model predicts that the total radon entry rate is relatively low unless the soil or backfill permeability or radium content is high. ost of the factors c...

Mars Science Laboratory Entry Guidance Improvements for Mars 2018 (DRAFT)

NASA Technical Reports Server (NTRS)

Garcia-Llama, Eduardo; Winski, Richard G.; Shidner, Jeremy D.; Ivanov, Mark C.; Grover, Myron R.; Prakash, Ravi

2011-01-01

In 2011, the Mars Science Laboratory (MSL) will be launched in a mission to deliver the largest and most capable rover to date to the surface of Mars. A follow on MSL-derived mission, referred to as Mars 2018, is planned for 2018. Mars 2018 goals include performance enhancements of the Entry, Descent and Landing over that of its predecessor MSL mission of 2011. This paper will discuss the main elements of the modified 2018 EDL preliminary design that will increase performance on the entry phase of the mission. In particular, these elements will increase the parachute deploy altitude to allow for more time margin during the subsequent descent and landing phases and reduce the delivery ellipse size at parachute deploy through modifications in the entry reference trajectory design, guidance trigger logic design, and the effect of additional navigation hardware.

1969 MLA International Bibliography of Books and Articles on the Modern Languages and Literatures. Volume I: General, English, American, Medieval and Neo-Latin, and Celtic Literatures.

ERIC Educational Resources Information Center

Meserole, Harrison T., Comp.

Volume 1 of the 4-volume, international bibliography contains some 9,000 entries referring to books and articles which focus on general, English, American, medieval and neo-Latin, and Celtic literatures. The master list of the nearly 1,500 periodicals from which entries are derived is furnished at the beginning of the volume with a table of…

Regolith-Derived Heat Shield for Planetary Body Entry and Descent System with In-Situ Fabrication

NASA Technical Reports Server (NTRS)

Hogue, Michael D.; Mueller, Robert P.; Sibille, Laurent; Hintze, Paul E.; Rasky, Daniel J.

2012-01-01

High-mass planetary surface access is one of NASA's Grand Challenges involving entry, descent, and landing (EDL). Heat shields fabricated in-situ can provide a thermal protection system for spacecraft that routinely enter a planetary atmosphere. Fabricating the heat shield from extraterrestrial regolith will avoid the costs of launching the heat shield mass from Earth. This project will investigate three methods to fabricate heat shield using extraterrestrial regolith.

On the entry of an emerging arbovirus into host cells: Mayaro virus takes the highway to the cytoplasm through fusion with early endosomes and caveolae-derived vesicles

PubMed Central

Carvalho, Carlos A.M.; Silva, Jerson L.; Oliveira, Andréa C.

2017-01-01

Mayaro virus (MAYV) is an emergent sylvatic alphavirus in South America, related to sporadic outbreaks of a chikungunya-like human febrile illness accompanied by severe arthralgia. Despite its high potential for urban emergence, MAYV is still an obscure virus with scarce information about its infection cycle, including the corresponding early events. Even for prototypical alphaviruses, the cell entry mechanism still has some rough edges to trim: although clathrin-mediated endocytosis is quoted as the putative route, alternative paths as distinct as direct virus genome injection through the cell plasma membrane seems to be possible. Our aim was to clarify crucial details on the entry route exploited by MAYV to gain access into the host cell. Tracking the virus since its first contact with the surface of Vero cells by fluorescence microscopy, we show that its entry occurs by a fast endocytic process and relies on fusion with acidic endosomal compartments. Moreover, blocking clathrin-mediated endocytosis or depleting cholesterol from the cell membrane leads to a strong inhibition of viral infection, as assessed by plaque assays. Following this clue, we found that early endosomes and caveolae-derived vesicles are both implicated as target membranes for MAYV fusion. Our findings unravel the very first events that culminate in a productive infection by MAYV and shed light on potential targets for a rational antiviral therapy, besides providing a better comprehension of the entry routes exploited by alphaviruses to get into the cell. PMID:28462045

Validation and extraction of molecular-geometry information from small-molecule databases.

PubMed

Long, Fei; Nicholls, Robert A; Emsley, Paul; Graǽulis, Saulius; Merkys, Andrius; Vaitkus, Antanas; Murshudov, Garib N

2017-02-01

A freely available small-molecule structure database, the Crystallography Open Database (COD), is used for the extraction of molecular-geometry information on small-molecule compounds. The results are used for the generation of new ligand descriptions, which are subsequently used by macromolecular model-building and structure-refinement software. To increase the reliability of the derived data, and therefore the new ligand descriptions, the entries from this database were subjected to very strict validation. The selection criteria made sure that the crystal structures used to derive atom types, bond and angle classes are of sufficiently high quality. Any suspicious entries at a crystal or molecular level were removed from further consideration. The selection criteria included (i) the resolution of the data used for refinement (entries solved at 0.84 Å resolution or higher) and (ii) the structure-solution method (structures must be from a single-crystal experiment and all atoms of generated molecules must have full occupancies), as well as basic sanity checks such as (iii) consistency between the valences and the number of connections between atoms, (iv) acceptable bond-length deviations from the expected values and (v) detection of atomic collisions. The derived atom types and bond classes were then validated using high-order moment-based statistical techniques. The results of the statistical analyses were fed back to fine-tune the atom typing. The developed procedure was repeated four times, resulting in fine-grained atom typing, bond and angle classes. The procedure will be repeated in the future as and when new entries are deposited in the COD. The whole procedure can also be applied to any source of small-molecule structures, including the Cambridge Structural Database and the ZINC database.

A Method for Semi-quantitative Assessment of Exposure to Pesticides of Applicators and Re-entry Workers: An Application in Three Farming Systems in Ethiopia.

PubMed

Negatu, Beyene; Vermeulen, Roel; Mekonnen, Yalemtshay; Kromhout, Hans

2016-07-01

To develop an inexpensive and easily adaptable semi-quantitative exposure assessment method to characterize exposure to pesticide in applicators and re-entry farmers and farm workers in Ethiopia. Two specific semi-quantitative exposure algorithms for pesticides applicators and re-entry workers were developed and applied to 601 farm workers employed in 3 distinctly different farming systems [small-scale irrigated, large-scale greenhouses (LSGH), and large-scale open (LSO)] in Ethiopia. The algorithm for applicators was based on exposure-modifying factors including application methods, farm layout (open or closed), pesticide mixing conditions, cleaning of spraying equipment, intensity of pesticide application per day, utilization of personal protective equipment (PPE), personal hygienic behavior, annual frequency of application, and duration of employment at the farm. The algorithm for re-entry work was based on an expert-based re-entry exposure intensity score, utilization of PPE, personal hygienic behavior, annual frequency of re-entry work, and duration of employment at the farm. The algorithms allowed estimation of daily, annual and cumulative lifetime exposure for applicators, and re-entry workers by farming system, by gender, and by age group. For all metrics, highest exposures occurred in LSGH for both applicators and female re-entry workers. For male re-entry workers, highest cumulative exposure occurred in LSO farms. Female re-entry workers appeared to be higher exposed on a daily or annual basis than male re-entry workers, but their cumulative exposures were similar due to the fact that on average males had longer tenure. Factors related to intensity of exposure (like application method and farm layout) were indicated as the main driving factors for estimated potential exposure. Use of personal protection, hygienic behavior, and duration of employment in surveyed farm workers contributed less to the contrast in exposure estimates. This study indicated that farmers' and farm workers' exposure to pesticides can be inexpensively characterized, ranked, and classified. Our method could be extended to assess exposure to specific active ingredients provided that detailed information on pesticides used is available. The resulting exposure estimates will consequently be used in occupational epidemiology studies in Ethiopia and other similar countries with few resources. © The Author 2016. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Structure-activity relationships of 3-O-β-chacotriosyl oleanic acid derivatives as entry inhibitors for highly pathogenic H5N1 influenza virus.

PubMed

Li, Sumei; Jia, Xiuhua; Shen, Xintian; Wei, Zhuwen; Jiang, Zhiyan; Liao, Yixian; Guo, Yiming; Zheng, Xiaojun; Zhong, Guohua; Song, Gaopeng

2017-08-15

Highly pathogenic H5N1 virus (H5N1) entry is a key target for the development of novel anti-influenza agents with new mechanisms of action. In our continuing efforts to identify novel potential anti-H5N1 entry inhibitors, a series of 3-O-β-chacotriosyl oleanolic acid analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on two small molecule inhibitors 1 and 2 previously discovered by us. The anti-H5N1 entry activities were determined based on HA/HIV and VSVG/HIV entry assays. Compound 15 displayed the most promising anti-H5N1 entry activities with average IC 50 values of 4.05μM and good selective index (22.9). Detailed structure-activity relationships (SARs) studies suggested that either the introduction of an additional oxo group to position 11 at OA or alteration of the C-3 configuration of OA from 3β- to 3α-forms can significantly enhance the selective index while maintaining their antiviral activities in vitro. Molecular simulation analysis confirmed that the compounds exert their inhibitory activity through binding tightly to hemagglutinin (HA2) protein near the fusion peptide and prevent virus entry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Factors Affecting Success in the Professional Entry Exam for Accountants in Brazil

ERIC Educational Resources Information Center

Lima Rodrigues, Lúcia; Pinho, Carlos; Bugarim, Maria Clara; Craig, Russell; Machado, Diego

2018-01-01

This paper explores factors that have affected the success of candidates in the professional entry exam conducted by Brazil's Federal Council of Accounting. We analyse results of 18,948 candidates who sat for the exam in 2012, using a logistic regression model and the key indicators used by government to monitor the performance of higher education…

Anti-HCV effect of Lentinula edodes mycelia solid culture extracts and low-molecular-weight lignin.

PubMed

Matsuhisa, Koji; Yamane, Seiji; Okamoto, Toru; Watari, Akihiro; Kondoh, Masuo; Matsuura, Yoshiharu; Yagi, Kiyohito

2015-06-19

Lentinula edodes mycelia solid culture extract (MSCE) contains several bioactive molecules, including some polyphenolic compounds, which exert immunomodulatory, antitumor, and hepatoprotective effects. In this study, we examined the anti-hepatitis C virus (HCV) activity of MSCE and low-molecular-weight lignin (LM-lignin), which is the active component responsible for the hepatoprotective effect of MSCE. Both MSCE and LM-lignin inhibited the entry of two HCV pseudovirus (HCVpv) types into Huh7.5.1 cells. LM-lignin inhibited HCVpv entry at a lower concentration than MSCE and inhibited the entry of HCV particles in cell culture (HCVcc). MSCE also inhibited HCV subgenome replication. LM-lignin had no effect on HCV replication, suggesting that MSCE contains additional active substances. We demonstrate here for the first time the anti-HCV effects of plant-derived LM-lignin and MSCE. The hepatoprotective effect of LM-lignin suggests that lignin derivatives, which can be produced in abundance from existing plant resources, may be effective in the treatment of HCV-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Access to natural resources on private property: factors beyond right of entry

Treesearch

Clare Ginger; Marla R. Emery; Michelle J. Baumflek; David E. Punam

2012-01-01

Discussions of access to natural resources on private lands in the United States often focus on property rights and ownership. In Maine, changing ownership of private forestland has been associated with increased posting against trespass. This raises concerns about the terms of physical entry to land for resource use. While the right of entry is an important component...

Herpesvirus Entry Mediator and Ocular Herpesvirus Infection: More than Meets the Eye

PubMed Central

Edwards, Rebecca G.

2017-01-01

ABSTRACT As its name suggests, the host receptor herpesvirus entry mediator (HVEM) facilitates herpes simplex virus (HSV) entry through interactions with a viral envelope glycoprotein. HVEM also bridges several signaling networks, binding ligands from both tumor necrosis factor (TNF) and immunoglobulin (Ig) superfamilies with diverse, and often opposing, outcomes. While HVEM was first identified as a viral entry receptor for HSV, it is only recently that HVEM has emerged as an important host factor in immunopathogenesis of ocular HSV type 1 (HSV-1) infection. Surprisingly, HVEM exacerbates disease development in the eye independently of entry. HVEM signaling has been shown to play a variety of roles in modulating immune responses to HSV and other pathogens, and there is increasing evidence that these effects are responsible for HVEM-mediated pathogenesis in the eye. Here, we review the dual branches of HVEM function during HSV infection: entry and immunomodulation. HVEM is broadly expressed; intersects two important immunologic signaling networks; and impacts autoimmunity, infection, and inflammation. We hope that by understanding the complex range of effects mediated by this receptor, we can offer insights applicable to a wide variety of disease states. PMID:28404853

Entry and Exit Mechanisms at the cis-Face of the Golgi Complex

PubMed Central

Lorente-Rodríguez, Andrés; Barlowe, Charles

2011-01-01

Vesicular transport of protein and lipid cargo from the endoplasmic reticulum (ER) to cis-Golgi compartments depends on coat protein complexes, Rab GTPases, tethering factors, and membrane fusion catalysts. ER-derived vesicles deliver cargo to an ER-Golgi intermediate compartment (ERGIC) that then fuses with and/or matures into cis-Golgi compartments. The forward transport pathway to cis-Golgi compartments is balanced by a retrograde directed pathway that recycles transport machinery back to the ER. How trafficking through the ERGIC and cis-Golgi is coordinated to maintain organelle structure and function is poorly understood and highlights central questions regarding trafficking routes and organization of the early secretory pathway. PMID:21482742

Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma

PubMed Central

Alayli, Farah; Melis, Marta; Kabat, Juraj; Pomerenke, Anna; Altan-Bonnet, Nihal; Zamboni, Fausto; Emerson, Suzanne U.

2018-01-01

Entry of hepatitis C virus (HCV) into hepatocytes is a complex process that involves numerous cellular factors, including the scavenger receptor class B type 1 (SR-B1), the tetraspanin CD81, and the tight junction (TJ) proteins claudin-1 (CLDN1) and occludin (OCLN). Despite expression of all known HCV-entry factors, in vitro models based on hepatoma cell lines do not fully reproduce the in vivo susceptibility of liver cells to primary HCV isolates, implying the existence of additional host factors which are critical for HCV entry and/or replication. Likewise, HCV replication is severely impaired within hepatocellular carcinoma (HCC) tissue in vivo, but the mechanisms responsible for this restriction are presently unknown. Here, we identify tumor-associated calcium signal transducer 2 (TACSTD2), one of the most downregulated genes in primary HCC tissue, as a host factor that interacts with CLDN1 and OCLN and regulates their cellular localization. TACSTD2 gene silencing disrupts the typical linear distribution of CLDN1 and OCLN along the cellular membrane in both hepatoma cells and primary human hepatocytes, recapitulating the pattern observed in vivo in primary HCC tissue. Mechanistic studies suggest that TACSTD2 is involved in the phosphorylation of CLDN1 and OCLN, which is required for their proper cellular localization. Silencing of TACSTD2 dramatically inhibits HCV infection with a pan-genotype effect that occurs at the level of viral entry. Our study identifies TACSTD2 as a novel regulator of two major HCV-entry factors, CLDN1 and OCLN, which is strongly downregulated in malignant hepatocytes. These results provide new insights into the complex process of HCV entry into hepatocytes and may assist in the development of more efficient cellular systems for HCV propagation in vitro. PMID:29538454

Simultaneous tensor decomposition and completion using factor priors.

PubMed

Chen, Yi-Lei; Hsu, Chiou-Ting; Liao, Hong-Yuan Mark

2014-03-01

The success of research on matrix completion is evident in a variety of real-world applications. Tensor completion, which is a high-order extension of matrix completion, has also generated a great deal of research interest in recent years. Given a tensor with incomplete entries, existing methods use either factorization or completion schemes to recover the missing parts. However, as the number of missing entries increases, factorization schemes may overfit the model because of incorrectly predefined ranks, while completion schemes may fail to interpret the model factors. In this paper, we introduce a novel concept: complete the missing entries and simultaneously capture the underlying model structure. To this end, we propose a method called simultaneous tensor decomposition and completion (STDC) that combines a rank minimization technique with Tucker model decomposition. Moreover, as the model structure is implicitly included in the Tucker model, we use factor priors, which are usually known a priori in real-world tensor objects, to characterize the underlying joint-manifold drawn from the model factors. By exploiting this auxiliary information, our method leverages two classic schemes and accurately estimates the model factors and missing entries. We conducted experiments to empirically verify the convergence of our algorithm on synthetic data and evaluate its effectiveness on various kinds of real-world data. The results demonstrate the efficacy of the proposed method and its potential usage in tensor-based applications. It also outperforms state-of-the-art methods on multilinear model analysis and visual data completion tasks.

Who wants to be a surgeon? Patterns of medical student career choice.

PubMed

Shirley, Otis C; Addison, Ben; Poole, Phillippa

2014-11-07

NZ needs a surgical workforce with the capacity to meet the increasing health demands of an aging population. This study determined longitudinal patterns of medical student interest in a surgical career and factors influencing that choice. We studied medical students entering the Auckland medical programme from 2006-2008 who completed an entry and exit questionnaire on career intentions. Four notional groups were created, depending on the level of interest at entry and at exit. Demographic factors for each category were compared. Analysis of influencing factors was also undertaken. Of 488 students, 310 (64%) completed both an entry and exit questionnaire. Over 50% of students had a strong interest in a surgical career at entry, dropping to 26% at exit. The 'Never Evers' (No interest at entry /No interest at exit) made up 39%,'Divergers' (Strong/No) 35%, 'Die Hards' (Strong/Strong) 18%, and 'Convertibles' (No/Strong) 8%. Less interest in a surgical career was seen among female (P=0.001) and older students (P=0.017). Influencing factors differentiating the 'Die Hards' from the 'Divergers' were work hours and flexibility (less influence among 'Die Hards'), with procedural nature and consultants/mentors (higher). There is a significant reduction in interest in a surgical career over the course of the undergraduate programme, especially among female and older students. Yet the level appears sufficient for available training places. Consultant role models are an important career influence. Lack of flexibility in work and training programmes continue to provide challenges in creating a diverse surgical workforce.

Forebody and base region real gas flow in severe planetary entry by a factored implicit numerical method. II - Equilibrium reactive gas

NASA Technical Reports Server (NTRS)

Davy, W. C.; Green, M. J.; Lombard, C. K.

1981-01-01

The factored-implicit, gas-dynamic algorithm has been adapted to the numerical simulation of equilibrium reactive flows. Changes required in the perfect gas version of the algorithm are developed, and the method of coupling gas-dynamic and chemistry variables is discussed. A flow-field solution that approximates a Jovian entry case was obtained by this method and compared with the same solution obtained by HYVIS, a computer program much used for the study of planetary entry. Comparison of surface pressure distribution and stagnation line shock-layer profiles indicates that the two solutions agree well.

Neuronal apoptotic signaling pathways probed and intervened by synthetically and modularly modified (SMM) chemokines.

PubMed

Choi, Won-Tak; Kaul, Marcus; Kumar, Santosh; Wang, Jun; Kumar, I M Krishna; Dong, Chang-Zhi; An, Jing; Lipton, Stuart A; Huang, Ziwei

2007-03-09

As the main coreceptors for human immunodeficiency virus type 1 (HIV-1) entry, CXCR4 and CCR5 play important roles in HIV-associated dementia (HAD). HIV-1 glycoprotein gp120 contributes to HAD by causing neuronal damage and death, either directly by triggering apoptotic pathways or indirectly by stimulating glial cells to release neurotoxins. Here, to understand the mechanism of CXCR4 or CCR5 signaling in neuronal apoptosis associated with HAD, we have applied synthetically and modularly modified (SMM)-chemokine analogs derived from natural stromal cell-derived factor-1alpha or viral macrophage inflammatory protein-II as chemical probes of the mechanism(s) whereby these SMM-chemokines prevent or promote neuronal apoptosis. We show that inherently neurotoxic natural ligands of CXCR4, such as stromal cell-derived factor-1alpha or viral macrophage inflammatory protein-II, can be modified to protect neurons from apoptosis induced by CXCR4-preferring gp120(IIIB), and that the inhibition of CCR5 by antagonist SMM-chemokines, unlike neuroprotective CCR5 natural ligands, leads to neurotoxicity by activating a p38 mitogen-activated protein kinase (MAPK)-dependent pathway. Furthermore, we discover distinct signaling pathways activated by different chemokine ligands that are either natural agonists or synthetic antagonists, thus demonstrating a chemical biology strategy of using chemically engineered inhibitors of chemokine receptors to study the signaling mechanism of neuronal apoptosis and survival.

The Age of Entry into High-Quality Preschool, Child and Family Factors, and Developmental Outcomes in Early Childhood

ERIC Educational Resources Information Center

Zupancic, Maja; Kavcic, Tina

2006-01-01

Three blocks of factors were considered as predictors of four year old children's (N = 286) personality, non-verbal intelligence and social behaviour in preschool: (a) personality characteristics at time 1 (T1) when the participants were three years old; (b) parental education and parenting practices measured at T1; and (c) age of child's entry to…

Analysis of Ebola Virus Entry Into Macrophages.

PubMed

Dahlmann, Franziska; Biedenkopf, Nadine; Babler, Anne; Jahnen-Dechent, Willi; Karsten, Christina B; Gnirß, Kerstin; Schneider, Heike; Wrensch, Florian; O'Callaghan, Christopher A; Bertram, Stephanie; Herrler, Georg; Becker, Stephan; Pöhlmann, Stefan; Hofmann-Winkler, Heike

2015-10-01

Ebolaviruses constitute a public health threat, particularly in Central and Western Africa. Host cell factors required for spread of ebolaviruses may serve as targets for antiviral intervention. Lectins, TAM receptor tyrosine kinases (Tyro3, Axl, Mer), T cell immunoglobulin and mucin domain (TIM) proteins, integrins, and Niemann-Pick C1 (NPC1) have been reported to promote entry of ebolaviruses into certain cellular systems. However, the factors used by ebolaviruses to invade macrophages, major viral targets, are poorly defined. Here, we show that mannose-specific lectins, TIM-1 and Axl augment entry into certain cell lines but do not contribute to Ebola virus (EBOV)-glycoprotein (GP)-driven transduction of macrophages. In contrast, expression of Mer, integrin αV, and NPC1 was required for efficient GP-mediated transduction and EBOV infection of macrophages. These results define cellular factors hijacked by EBOV for entry into macrophages and, considering that Mer and integrin αV promote phagocytosis of apoptotic cells, support the concept that EBOV relies on apoptotic mimicry to invade target cells. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Price analysis of multiple sclerosis disease-modifying therapies marketed in the United States.

PubMed

Bin Sawad, Aseel; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Turkistani, Fatema

2016-11-01

This study assessed trends in the average wholesale price (AWP) at the market entry of disease-modifying therapies (DMTs) approved by Food and Drug Administration (FDA) in the period 1987-2014. DMT regulatory information was derived from the FDA website. The AWPs per unit at market entry data were derived from the Red Book (Truven Health Analytics Inc.). The AWP history for each DMT was collected from its date of approval to 31 December 2014. The FDA approved label defined daily dose (DDD) for adult patients was obtained from FDA approved labels. The AWP per DDD and the AWP/DDD per year of therapy were computed. Descriptive statistics, Wilcoxon tests, t-test, and multiple linear regression were performed. The statistical significance level was set at 0.05. The FDA approved 12 multiple sclerosis (MS) DMTs, including five new drug applications (NDAs) and seven biologic license applications (BLAs) as of 31 December 2014. The FDA granted orphan designation to five DMTs. There was one DMT approved by the FDA in the 1980s, three in the 1990s, three in 2000s, and five in the period 2010-2014. The market entry inflation-adjusted AWP per DDD was $10.23 for the first DMT (mitoxantrone hydrochloride) that was approved in the 1980s. The median market entry inflation-adjusted AWP per DDD was $12.41 (interquartile range [IQR] = 4.51) for DMTs approved in the 1990s, $71.26 (IQR = 58.35) in the 2000s, and $172.56 (IQR = 84.97) in the period 2010-2014. The median AWP per DDD was statistically significantly different (p = 0.011) for orphan (median = $41.82, IQR = 56.077) compared to non-orphan drugs (median = $171.32, IQR = 199.29). Year of market entry was positively associated with DMT prices at US market entry (p = 0.01). The AWP per DDD for DMTs at market entry increased substantially over time. The increase in DMTs prices exceeded the general consumer price index.

Factors associated with a second deferral among donors eligible for re-entry after a false-positive screening test for syphilis, HCV, HBV and HIV.

PubMed

Grégoire, Y; Germain, M; Delage, G

2018-05-01

Since 25 May 2010, all donors at our blood centre who tested false-positive for HIV, HBV, HCV or syphilis are eligible for re-entry after further testing. Donors who have a second false-positive screening test, either during qualification for or after re-entry, are deferred for life. This study reports on factors associated with the occurrence of such deferrals. Rates of second false-positive results were compared by year of deferral, transmissible disease marker, gender, age, donor status (new or repeat) and testing platform (same or different) both at qualification for re-entry and afterwards. Chi-square tests were used to compare proportions. Cox regression was used for multivariate analyses. Participation rates in the re-entry programme were 42·1%: 25·6% failed to qualify for re-entry [different platform: 2·7%; same platform: 42·9% (P < 0·0001)]. After re-entry, rates of deferral for second false-positive results were 8·4% after 3 years [different platform: 1·8%; same platform: 21·4% (P < 0·0001)]. Deferral rates were higher for HIV and HCV than for HBV at qualification when tested on the same platform. The risk, when analysed by multivariate analyses, of a second deferral for a false-positive result, both at qualification and 3 years after re-entry, was lower for donors deferred on a different platform; this risk was higher for HIV, HCV and syphilis than for HBV and for new donors if tested on the same platform. Re-entry is more often successful when donors are tested on a testing platform different from the one on which they obtained their first false-positive result. © 2018 International Society of Blood Transfusion.

A nontranscriptional role for Oct4 in the regulation of mitotic entry

PubMed Central

Zhao, Rui; Deibler, Richard W.; Lerou, Paul H.; Ballabeni, Andrea; Heffner, Garrett C.; Cahan, Patrick; Unternaehrer, Juli J.; Kirschner, Marc W.; Daley, George Q.

2014-01-01

Rapid progression through the cell cycle and a very short G1 phase are defining characteristics of embryonic stem cells. This distinct cell cycle is driven by a positive feedback loop involving Rb inactivation and reduced oscillations of cyclins and cyclin-dependent kinase (Cdk) activity. In this setting, we inquired how ES cells avoid the potentially deleterious consequences of premature mitotic entry. We found that the pluripotency transcription factor Oct4 (octamer-binding transcription factor 4) plays an unappreciated role in the ES cell cycle by forming a complex with cyclin–Cdk1 and inhibiting Cdk1 activation. Ectopic expression of Oct4 or a mutant lacking transcriptional activity recapitulated delayed mitotic entry in HeLa cells. Reduction of Oct4 levels in ES cells accelerated G2 progression, which led to increased chromosomal missegregation and apoptosis. Our data demonstrate an unexpected nontranscriptional function of Oct4 in the regulation of mitotic entry. PMID:25324523

Construction of high quality Gateway™ entry libraries and their application to yeast two-hybrid for the monocot model plant Brachypodium distachyon.

PubMed

Cao, Shuanghe; Siriwardana, Chamindika L; Kumimoto, Roderick W; Holt, Ben F

2011-05-19

Monocots, especially the temperate grasses, represent some of the most agriculturally important crops for both current food needs and future biofuel development. Because most of the agriculturally important grass species are difficult to study (e.g., they often have large, repetitive genomes and can be difficult to grow in laboratory settings), developing genetically tractable model systems is essential. Brachypodium distachyon (hereafter Brachypodium) is an emerging model system for the temperate grasses. To fully realize the potential of this model system, publicly accessible discovery tools are essential. High quality cDNA libraries that can be readily adapted for multiple downstream purposes are a needed resource. Additionally, yeast two-hybrid (Y2H) libraries are an important discovery tool for protein-protein interactions and are not currently available for Brachypodium. We describe the creation of two high quality, publicly available Gateway™ cDNA entry libraries and their derived Y2H libraries for Brachypodium. The first entry library represents cloned cDNA populations from both short day (SD, 8/16-h light/dark) and long day (LD, 20/4-h light/dark) grown plants, while the second library was generated from hormone treated tissues. Both libraries have extensive genome coverage (~5 × 107 primary clones each) and average clone lengths of ~1.5 Kb. These entry libraries were then used to create two recombination-derived Y2H libraries. Initial proof-of-concept screens demonstrated that a protein with known interaction partners could readily re-isolate those partners, as well as novel interactors. Accessible community resources are a hallmark of successful biological model systems. Brachypodium has the potential to be a broadly useful model system for the grasses, but still requires many of these resources. The Gateway™ compatible entry libraries created here will facilitate studies for multiple user-defined purposes and the derived Y2H libraries can be immediately applied to large scale screening and discovery of novel protein-protein interactions. All libraries are freely available for distribution to the research community.

Retro-2 and its dihydroquinazolinone derivatives inhibit filovirus infection.

PubMed

Shtanko, Olena; Sakurai, Yasuteru; Reyes, Ann N; Noël, Romain; Cintrat, Jean-Christophe; Gillet, Daniel; Barbier, Julien; Davey, Robert A

2018-01-01

Members of the family Filoviridae cause severe, often fatal disease in humans, for which there are no approved vaccines and only a few experimental drugs tested in animal models. Retro-2, a small molecule that inhibits retrograde trafficking of bacterial and plant toxins inside host cells, has been demonstrated to be effective against a range of bacterial and virus pathogens, both in vitro and in animal models. Here, we demonstrated that Retro-2 and its derivatives, Retro-2.1 and compound 25, blocked infection by Ebola virus and Marburg virus in vitro. We show that the derivatives were more potent inhibitors of infection as compared to the parent compound. Pseudotyped virus assays indicated that the compounds affected virus entry into cells while virus particle localization to Niemann-Pick C1-positive compartments showed that they acted at a late step in virus entry. Our work demonstrates a potential for Retro-type drugs to be developed into anti-filoviral therapeutics. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Predicting risk of entry into foster care from early childhood experiences: A survival analysis using LONGSCAN data.

PubMed

English, Diana J; Thompson, Richard; White, Catherine Roller

2015-07-01

This study examined whether a multi-domain model of maltreatment informed by an ecological framework-including factors related to the child, caregiver, family, neighborhood, and dimensions of maltreatment experience-predicted entry into foster care between the ages of 4 and 18 among children with no prior foster care experience. To determine which factors predict entry into foster care, secondary data analyses were conducted utilizing a sub-sample from LONGSCAN (Longitudinal Studies of Child Abuse and Neglect) of 942 children and their primary caregivers. Results demonstrate that there are important predictors for entry into out-of-home placement across multiple ecological domains. Characteristics related to child, caregiver, and family characteristics, and neighborhood context, as well as dimensions of maltreatment (particularly emotional maltreatment), predicted risk of placement in out-of-home care. Implications for child welfare practice are discussed. This examination of the effects of multiple ecological domains adds to our understanding of children's risk of removal and entry into out-of-home placement. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976.

PubMed

Hofmann-Winkler, Heike; Gnirß, Kerstin; Wrensch, Florian; Pöhlmann, Stefan

2015-10-01

The ongoing Ebola virus (EBOV) disease (EVD) epidemic in Western Africa is the largest EVD outbreak recorded to date and requires the rapid development and deployment of antiviral measures. The viral glycoprotein (GP) facilitates host cell entry and, jointly with cellular interaction partners, constitutes a potential target for antiviral intervention. However, it is unknown whether the GPs of the currently and previously circulating EBOVs use the same mechanisms for cellular entry and are thus susceptible to inhibition by the same antivirals and cellular defenses. Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52. Thus, the viruses responsible for the ongoing EVD epidemic should be fully susceptible to established antiviral strategies targeting GP and cellular entry factors. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

9 CFR 95.7 - Wool, hair, and bristles; requirements for unrestricted entry.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Mar. 4, 2014. For the convenience of the user, the added text is set forth as follows: § 95.7 Collagen derived from bovines. (a) The importation of collagen derived from bovines is prohibited because of BSE unless: (1) The collagen meets the requirements of either paragraph (b), (c), or (d), as well as the...

Regolith-Derived Heat Shield for Planetary Body Entry and Descent System with In-Situ Fabrication

NASA Technical Reports Server (NTRS)

Hogue, Michael D.; Mueller, Robert P.; Sibille, Laurent; Hintze, Paul E.; Rasky, Daniel J.

2012-01-01

High-mass planetary surface access is one of NASA's Grand Challenges involving entry, descent, and landing (EDL). Heat shields fabricated in-situ can provide a thermal protection system for spacecraft that routinely enter a planetary atmosphere. Fabricating the heat shield from extraterrestrial regolith will avoid the costs of launching the heat shield mass from Earth. This project investigated three methods to fabricate heat shield using extraterrestrial regolith and performed preliminary work on mission architectures.

Entry Atmospheric Flight Control Authority Impacts on GN and C and Trajectory Performance for Orion Exploration Flight Test 1

NASA Technical Reports Server (NTRS)

McNamara, Luke W.

2012-01-01

One of the key design objectives of NASA's Orion Exploration Flight Test 1 (EFT-1) is to execute a guided entry trajectory demonstrating GN&C capability. The focus of this paper is the ight control authority of the vehicle throughout the atmospheric entry ight to the target landing site and its impacts on GN&C, parachute deployment, and integrated performance. The vehicle's attitude control authority is obtained from thrusting 12 Re- action Control System (RCS) engines, with four engines to control yaw, four engines to control pitch, and four engines to control roll. The static and dynamic stability derivatives of the vehicle are determined to assess the inherent aerodynamic stability. The aerodynamic moments at various locations in the entry trajectory are calculated and compared to the available torque provided by the RCS system. Interaction between the vehicle's RCS engine plumes and the aerodynamic conditions are considered to assess thruster effectiveness. This document presents an assessment of Orion's ight control authority and its effectiveness in controlling the vehicle during critical events in the atmospheric entry trajectory.

Hidden factors that influence success in the optics workforce

NASA Astrophysics Data System (ADS)

Leak, Anne E.; Santos, Zackary; Reiter, Erik; Zwickl, Benjamin M.; Martin, Kelly Norris

2018-06-01

To prepare physics students for future careers, educators need to understand the skills and other factors necessary for entry and success on the job. Often these insights are based on CEOs, HR personnel, and managers, who provide broad perspectives regarding successful attributes of new hires. However, such insights are often more general and disconnected from specific jobs than insights gained from entry-level employees who recently transitioned from school to work. Using in-depth descriptive summaries and thematic analysis from interviews with six recently hired technicians and engineers in the field of optics, we explored factors that influenced their entry and success on the job. Six themes arose: documentation, computational skills, specialized learning, question asking, tinkering skills, and navigating cultural differences. We discuss the implications of these themes in both their value to employees as well as integration into the physics curriculum.

The H-PEPSS: an instrument to measure health professionals' perceptions of patient safety competence at entry into practice.

PubMed

Ginsburg, Liane; Castel, Evan; Tregunno, Deborah; Norton, Peter G

2012-08-01

Enhancing competency in patient safety at entry to practice requires introduction and integration of patient safety into health professional education. As efforts to include patient safety in health professional education increase, it is important to capture new health professionals' perspectives of their own patient safety competence at entry to practice. Existing instruments to measure patient safety knowledge, skills and attitudes have been developed largely to examine the impact of specific patient safety curricular initiatives and the psychometric analyses of the instruments used thus far have been exploratory in nature. Confirmatory factor analytic approaches are used to extensively test the Health Professional Education in Patient Safety Survey (H-PEPSS), a newly designed survey rooted in a patient safety competency framework and designed to measure health professionals' self-reported patient safety competence around the time of entry to practice. The H-PEPSS focuses primarily on the socio-cultural aspects of patient safety including culture, teamwork, communication, managing risk and understanding human factors. Results support a parsimonious six-factor measurement model of health professionals' perceptions of patient safety competency. These results support the validity of a reduced version of the H-PEPSS and suggest it can be appropriately used at or near training completion with a variety of health professional groups. Given increased demands for patient safety competency among health professionals at entry to practice and slow, but emerging changes in health professional education, ongoing research to understand the extent of patient safety competency among health professionals around the time of entry to practice will be important.

The H-PEPSS: an instrument to measure health professionals' perceptions of patient safety competence at entry into practice

PubMed Central

Castel, Evan; Tregunno, Deborah; Norton, Peter G

2012-01-01

Background Enhancing competency in patient safety at entry to practice requires introduction and integration of patient safety into health professional education. As efforts to include patient safety in health professional education increase, it is important to capture new health professionals' perspectives of their own patient safety competence at entry to practice. Existing instruments to measure patient safety knowledge, skills and attitudes have been developed largely to examine the impact of specific patient safety curricular initiatives and the psychometric analyses of the instruments used thus far have been exploratory in nature. Methods Confirmatory factor analytic approaches are used to extensively test the Health Professional Education in Patient Safety Survey (H-PEPSS), a newly designed survey rooted in a patient safety competency framework and designed to measure health professionals' self-reported patient safety competence around the time of entry to practice. The H-PEPSS focuses primarily on the socio-cultural aspects of patient safety including culture, teamwork, communication, managing risk and understanding human factors. Results Results support a parsimonious six-factor measurement model of health professionals' perceptions of patient safety competency. These results support the validity of a reduced version of the H-PEPSS and suggest it can be appropriately used at or near training completion with a variety of health professional groups. Conclusions Given increased demands for patient safety competency among health professionals at entry to practice and slow, but emerging changes in health professional education, ongoing research to understand the extent of patient safety competency among health professionals around the time of entry to practice will be important. PMID:22562876

A Novel Role for the Receptor of the Complement Cleavage Fragment C5a, C5aR1, in CCR5-Mediated Entry of HIV into Macrophages.

PubMed

Moreno-Fernandez, Maria E; Aliberti, Julio; Groeneweg, Sander; Köhl, Jörg; Chougnet, Claire A

2016-04-01

The complement system is an ancient pattern recognition system that becomes activated during all stages of HIV infection. Previous studies have shown that C5a can enhance the infection of monocyte-derived macrophages and T cells indirectly through the production of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and the attraction of dendritic cells. C5a exerts its multiple biologic functions mainly through activation of C5a receptor 1 (C5aR1). Here, we assessed the role of C5aR1 as an enhancer of CCR5-mediated HIV infection. We determined CCR5 and C5aR1 heterodimer formation in myeloid cells and the impact of C5aR1 blockade on HIV entry and genomic integration. C5aR1/CCR5 heterodimer formation was identified by immunoprecipitation and western blotting. THP-1 cells and monocyte-derived macrophages (MDM) were infected by R5 laboratory strains or HIV pseudotyped for the vesicular stomatitis virus (VSV) envelope. Levels of integrated HIV were measured by quantitative PCR after targeting of C5aR1 by a C5aR antagonist, neutralizing C5aR1 monoclonal antibody (mAb) or hC5a. C5aR1 was also silenced by specific siRNA prior to viral entry. We found that C5aR1 forms heterodimers with the HIV coreceptor CCR5 in myeloid cells. Targeting C5aR1 significantly decreased integration by R5 viruses but not by VSV-pseudotyped viruses, suggesting that C5aR1 is critical for viral entry. The level of inhibition achieved with C5aR1-blocking reagents was comparable to that of CCR5 antagonists. Mechanistically, C5aR1 targeting decreased CCR5 expression. MDM from CCR5Δ32 homozygous subjects expressed levels of C5aR1 similar to CCR5 WT individuals, suggesting that mere C5aR1 expression is not sufficient for HIV infection. HIV appeared to preferentially enter THP-1 cells expressing high levels of both C5aR1 and CCR5. Targeted reduction of C5aR1 expression in such cells reduced HIV infection by ~50%. Our data thus suggest that C5aR1 acts as an enhancer of CCR5-mediated HIV entry into macrophages, the targeting of which may prove useful to reduce HIV infection by R5 strains.

Major uncertainties influencing entry probe heat shield design

NASA Technical Reports Server (NTRS)

Congdon, W.

1974-01-01

Factors influencing the design of an outer planet probe heat shield are discussed. Major factors included are: uncertainties in composition and scale height of the planet atmospheres; the augmentation/attenuation of entry heating by ablation products requires more computer study and testing; carbon heat shields, especially carbon phenolic, possessing improved resistance to spallation need developing; and white silica reflecting heat shields with improved resistance to bulk vitrification need further developing.

Hepatitis C virus infection in South Australian prisoners: seroprevalence, seroconversion, and risk factors.

PubMed

Miller, Emma Ruth; Bi, Peng; Ryan, Philip

2009-03-01

To determine entry antibody seroprevalence and seroconversion to hepatitis C virus (HCV) and associated risk factors in newly incarcerated prisoners. Males and females entering South Australian prisons completed risk factor surveys and were offered HCV-antibody testing. Participants completed additional surveys and, if HCV-negative at last test, underwent further antibody tests at 3-monthly intervals for up to 15 months. Data were analyzed using univariate and multivariate techniques. HCV seroprevalence among 662 prison entrants was estimated at 42%. Previous injecting history was highly prevalent at entry (64%) and both community and prison injecting independently predicted entry HCV status. Tattooing was not an important risk factor. While community exposure could not be ruled out, three seroconversions were noted in 148 initially HCV-seronegative individuals occurring in a median 121 days--4.6 per 100 person-years. Prison injecting was infrequently reported, but HCV-seropositive participants were significantly more likely to commence IDU in prison than seronegative participants (p=0.035). Entry HCV seroprevalence in South Australian prisoners is extremely high and may have contributed to a 'ceiling effect', minimizing the observable seroconversion rate. Greater frequency of injecting among those already infected with HCV represents a significant threat to other prisoners and prison staff.

The Apc5 Subunit of the Anaphase-Promoting Complex/Cyclosome Interacts with Poly(A) Binding Protein and Represses Internal Ribosome Entry Site-Mediated Translation

PubMed Central

Koloteva-Levine, Nadejda; Pinchasi, Dalia; Pereman, Idan; Zur, Amit; Brandeis, Michael; Elroy-Stein, Orna

2004-01-01

The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit ubiquitin ligase that mediates the proteolysis of cell cycle proteins in mitosis and G1. We used a yeast three-hybrid screen to identify proteins that interact with the internal ribosome entry site (IRES) of platelet-derived growth factor 2 mRNA. Surprisingly, this screen identified Apc5, although it does not harbor a classical RNA binding domain. We found that Apc5 binds the poly(A) binding protein (PABP), which directly binds the IRES element. PABP was found to enhance IRES-mediated translation, whereas Apc5 overexpression counteracted this effect. In addition to its association with the APC/C complex, Apc5 binds much heavier complexes and cosediments with the ribosomal fraction. In contrast to Apc3, which is associated only with the APC/C and remains intact during differentiation, Apc5 is degraded upon megakaryocytic differentiation in correlation with IRES activation. Expression of Apc5 in differentiated cells abolished IRES activation. This is the first report implying an additional role for an APC/C subunit, apart from its being part of the APC/C complex. PMID:15082755

An understanding of human dynamics in urban subway traffic from the Maximum Entropy Principle

NASA Astrophysics Data System (ADS)

Yong, Nuo; Ni, Shunjiang; Shen, Shifei; Ji, Xuewei

2016-08-01

We studied the distribution of entry time interval in Beijing subway traffic by analyzing the smart card transaction data, and then deduced the probability distribution function of entry time interval based on the Maximum Entropy Principle. Both theoretical derivation and data statistics indicated that the entry time interval obeys power-law distribution with an exponential cutoff. In addition, we pointed out the constraint conditions for the distribution form and discussed how the constraints affect the distribution function. It is speculated that for bursts and heavy tails in human dynamics, when the fitted power exponent is less than 1.0, it cannot be a pure power-law distribution, but with an exponential cutoff, which may be ignored in the previous studies.

Identification of a Broad-Spectrum Antiviral Small Molecule against Severe Acute Respiratory Syndrome Coronavirus and Ebola, Hendra, and Nipah Viruses by Using a Novel High-Throughput Screening Assay

PubMed Central

Elshabrawy, Hatem A.; Fan, Jilao; Haddad, Christine S.; Ratia, Kiira; Broder, Christopher C.; Caffrey, Michael

2014-01-01

ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV) and Ebola, Hendra, and Nipah viruses are members of different viral families and are known causative agents of fatal viral diseases. These viruses depend on cathepsin L for entry into their target cells. The viral glycoproteins need to be primed by protease cleavage, rendering them active for fusion with the host cell membrane. In this study, we developed a novel high-throughput screening assay based on peptides, derived from the glycoproteins of the aforementioned viruses, which contain the cathepsin L cleavage site. We screened a library of 5,000 small molecules and discovered a small molecule that can inhibit the cathepsin L cleavage of all viral peptides with minimal inhibition of cleavage of a host protein-derived peptide (pro-neuropeptide Y). The small molecule inhibited the entry of all pseudotyped viruses in vitro and the cleavage of SARS-CoV spike glycoprotein in an in vitro cleavage assay. In addition, the Hendra and Nipah virus fusion glycoproteins were not cleaved in the presence of the small molecule in a cell-based cleavage assay. Furthermore, we demonstrate that the small molecule is a mixed inhibitor of cathepsin L. Our broad-spectrum antiviral small molecule appears to be an ideal candidate for future optimization and development into a potent antiviral against SARS-CoV and Ebola, Hendra, and Nipah viruses. IMPORTANCE We developed a novel high-throughput screening assay to identify small molecules that can prevent cathepsin L cleavage of viral glycoproteins derived from SARS-CoV and Ebola, Hendra, and Nipah viruses that are required for their entry into the host cell. We identified a novel broad-spectrum small molecule that could block cathepsin L-mediated cleavage and thus inhibit the entry of pseudotypes bearing the glycoprotein derived from SARS-CoV or Ebola, Hendra, or Nipah virus. The small molecule can be further optimized and developed into a potent broad-spectrum antiviral drug. PMID:24501399

Identification of a broad-spectrum antiviral small molecule against severe acute respiratory syndrome coronavirus and Ebola, Hendra, and Nipah viruses by using a novel high-throughput screening assay.

PubMed

Elshabrawy, Hatem A; Fan, Jilao; Haddad, Christine S; Ratia, Kiira; Broder, Christopher C; Caffrey, Michael; Prabhakar, Bellur S

2014-04-01

Severe acute respiratory syndrome coronavirus (SARS-CoV) and Ebola, Hendra, and Nipah viruses are members of different viral families and are known causative agents of fatal viral diseases. These viruses depend on cathepsin L for entry into their target cells. The viral glycoproteins need to be primed by protease cleavage, rendering them active for fusion with the host cell membrane. In this study, we developed a novel high-throughput screening assay based on peptides, derived from the glycoproteins of the aforementioned viruses, which contain the cathepsin L cleavage site. We screened a library of 5,000 small molecules and discovered a small molecule that can inhibit the cathepsin L cleavage of all viral peptides with minimal inhibition of cleavage of a host protein-derived peptide (pro-neuropeptide Y). The small molecule inhibited the entry of all pseudotyped viruses in vitro and the cleavage of SARS-CoV spike glycoprotein in an in vitro cleavage assay. In addition, the Hendra and Nipah virus fusion glycoproteins were not cleaved in the presence of the small molecule in a cell-based cleavage assay. Furthermore, we demonstrate that the small molecule is a mixed inhibitor of cathepsin L. Our broad-spectrum antiviral small molecule appears to be an ideal candidate for future optimization and development into a potent antiviral against SARS-CoV and Ebola, Hendra, and Nipah viruses. We developed a novel high-throughput screening assay to identify small molecules that can prevent cathepsin L cleavage of viral glycoproteins derived from SARS-CoV and Ebola, Hendra, and Nipah viruses that are required for their entry into the host cell. We identified a novel broad-spectrum small molecule that could block cathepsin L-mediated cleavage and thus inhibit the entry of pseudotypes bearing the glycoprotein derived from SARS-CoV or Ebola, Hendra, or Nipah virus. The small molecule can be further optimized and developed into a potent broad-spectrum antiviral drug.

Analysis of the obstacles related to treatment entry, adherence and drop-out among alcoholic patients.

PubMed

Fonsi Elbreder, Márcia; Carvalho De Humerez, Dorisdaia; Laranjeira, Ronaldo

2009-01-01

Alcoholism is a complex syndrome involving social, psychological and individual factors in addition to a series of obstacles regarding treatment entry, adherence, and drop-out. These obstacles contribute negatively to both clinical evolution and prognosis of the patients, affecting their quality of life and raising the social costs. This is a bibliographical study in which we address this theme as well as other experiences observed in our daily practice in the Alcohol and Drug Research Unit (UNIAD) based at the Federal University of São Paulo (UNIFESP). The analysis of the obstacles related to treatment entry, attendance, and drop-out among alcoholic patients shows that systemic, social, cultural, and individual factors are all involved, including the structural ones. Women have more obstacles compared to men, and what is thought to be a barrier to one patient may be a factor motivating another patient to search for help. We conclude that several factors at different levels exist that prevent the patient from overcoming these treatment obstacles.

Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor

PubMed Central

Auerbach, David J.; Lin, Yin; Miao, Huiyi; Cimbro, Raffaello; DiFiore, Michelle J.; Gianolini, Monica E.; Furci, Lucinda; Biswas, Priscilla; Fauci, Anthony S.; Lusso, Paolo

2012-01-01

The natural history of HIV-1 infection is highly variable in different individuals, spanning from a rapidly progressive course to a long-term asymptomatic infection. A major determinant of the pace of disease progression is the in vivo level of HIV-1 replication, which is regulated by a complex network of cytokines and chemokines expressed by immune and inflammatory cells. The chemokine system is critically involved in the control of HIV-1 replication by virtue of the role played by specific chemokine receptors, most notably CCR5 and CXCR4, as cell-surface coreceptors for HIV-1 entry; hence, the chemokines that naturally bind such coreceptors act as endogenous inhibitors of HIV-1. Here, we show that the CXC chemokine CXCL4 (PF-4), the most abundant protein contained within the α-granules of platelets, is a broad-spectrum inhibitor of HIV-1 infection. Unlike other known HIV-suppressive chemokines, CXCL4 inhibits infection by the majority of primary HIV-1 isolates regardless of their coreceptor-usage phenotype or genetic subtype. Consistent with the lack of viral phenotype specificity, blockade of HIV-1 infection occurs at the level of virus attachment and entry via a unique mechanism that involves direct interaction of CXCL4 with the major viral envelope glycoprotein, gp120. The binding site for CXCL4 was mapped to a region of the gp120 outer domain proximal to the CD4-binding site. The identification of a platelet-derived chemokine as an endogenous antiviral factor may have relevance for the pathogenesis and treatment of HIV-1 infection. PMID:22645343

Identification of the platelet-derived chemokine CXCL4/PF-4 as a broad-spectrum HIV-1 inhibitor.

PubMed

Auerbach, David J; Lin, Yin; Miao, Huiyi; Cimbro, Raffaello; Difiore, Michelle J; Gianolini, Monica E; Furci, Lucinda; Biswas, Priscilla; Fauci, Anthony S; Lusso, Paolo

2012-06-12

The natural history of HIV-1 infection is highly variable in different individuals, spanning from a rapidly progressive course to a long-term asymptomatic infection. A major determinant of the pace of disease progression is the in vivo level of HIV-1 replication, which is regulated by a complex network of cytokines and chemokines expressed by immune and inflammatory cells. The chemokine system is critically involved in the control of HIV-1 replication by virtue of the role played by specific chemokine receptors, most notably CCR5 and CXCR4, as cell-surface coreceptors for HIV-1 entry; hence, the chemokines that naturally bind such coreceptors act as endogenous inhibitors of HIV-1. Here, we show that the CXC chemokine CXCL4 (PF-4), the most abundant protein contained within the α-granules of platelets, is a broad-spectrum inhibitor of HIV-1 infection. Unlike other known HIV-suppressive chemokines, CXCL4 inhibits infection by the majority of primary HIV-1 isolates regardless of their coreceptor-usage phenotype or genetic subtype. Consistent with the lack of viral phenotype specificity, blockade of HIV-1 infection occurs at the level of virus attachment and entry via a unique mechanism that involves direct interaction of CXCL4 with the major viral envelope glycoprotein, gp120. The binding site for CXCL4 was mapped to a region of the gp120 outer domain proximal to the CD4-binding site. The identification of a platelet-derived chemokine as an endogenous antiviral factor may have relevance for the pathogenesis and treatment of HIV-1 infection.

TIM1 (HAVCR1) Is Not Essential for Cellular Entry of Either Quasi-enveloped or Naked Hepatitis A Virions

PubMed Central

Das, Anshuman; Hirai-Yuki, Asuka; González-López, Olga; Rhein, Bethany; Moller-Tank, Sven; Brouillette, Rachel; Hensley, Lucinda; Misumi, Ichiro; Lovell, William; Cullen, John M.; Whitmire, Jason K.; Maury, Wendy

2017-01-01

ABSTRACT Receptor molecules play key roles in the cellular entry of picornaviruses, and TIM1 (HAVCR1) is widely accepted to be the receptor for hepatitis A virus (HAV), an unusual, hepatotropic human picornavirus. However, its identification as the hepatovirus receptor predated the discovery that hepatoviruses undergo nonlytic release from infected cells as membrane-cloaked, quasi-enveloped HAV (eHAV) virions that enter cells via a pathway distinct from naked, nonenveloped virions. We thus revisited the role of TIM1 in hepatovirus entry, examining both adherence and infection/replication in cells with clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-engineered TIM1 knockout. Cell culture-derived, gradient-purified eHAV bound Huh-7.5 human hepatoma cells less efficiently than naked HAV at 4°C, but eliminating TIM1 expression caused no difference in adherence of either form of HAV, nor any impact on infection and replication in these cells. In contrast, TIM1-deficient Vero cells showed a modest reduction in quasi-enveloped eHAV (but not naked HAV) attachment and replication. Thus, TIM1 facilitates quasi-enveloped eHAV entry in Vero cells, most likely by binding phosphatidylserine (PtdSer) residues on the eHAV membrane. Both Tim1−/− Ifnar1−/− and Tim4−/− Ifnar1−/− double-knockout mice were susceptible to infection upon intravenous challenge with infected liver homogenate, with fecal HAV shedding and serum alanine aminotransferase (ALT) elevations similar to those in Ifnar1−/− mice. However, intrahepatic HAV RNA and ALT elevations were modestly reduced in Tim1−/−Ifnar1−/− mice compared to Ifnar1−/− mice challenged with a lower titer of gradient-purified HAV or eHAV. We conclude that TIM1 is not an essential hepatovirus entry factor, although its PtdSer-binding activity may contribute to the spread of quasi-enveloped virus and liver injury in mice. PMID:28874468

Determining the Involvement and Therapeutic Implications of Host Cellular Factors in Hepatitis C Virus Cell-to-Cell Spread

PubMed Central

Barretto, Naina; Sainz, Bruno; Hussain, Snawar

2014-01-01

ABSTRACT Hepatitis C virus (HCV) infects 180 million people worldwide and is a leading cause of liver diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma. It has been shown that HCV can spread to naive cells using two distinct entry mechanisms, “cell-free” entry of infectious extracellular virions that have been released by infected cells and direct “cell-to-cell” transmission. Here, we examined host cell requirements for HCV spread and found that the cholesterol uptake receptor NPC1L1, which we recently identified as being an antiviral target involved in HCV cell-free entry/spread, is also required for the cell-to-cell spread. In contrast, the very low density lipoprotein (VLDL) pathway, which is required for the secretion of cell-free infectious virus and thus has been identified as an antiviral target for blocking cell-free virus secretion/spread, is not required for cell-to-cell spread. Noting that HCV cell-free and cell-to-cell spread share some common factors but not others, we tested the therapeutic implications of these observations and demonstrate that inhibitors that target cell factors required for both forms of HCV spread exhibit synergy when used in combination with interferon (a representative inhibitor of intracellular HCV production), while inhibitors that block only cell-free spread do not. This provides insight into the mechanistic basis of synergy between interferon and HCV entry inhibitors and highlights the broader, previously unappreciated impact blocking HCV cell-to-cell spread can have on the efficacy of HCV combination therapies. IMPORTANCE HCV can spread to naive cells using distinct mechanisms: “cell-free” entry of extracellular virus and direct “cell-to-cell” transmission. Herein, we identify the host cell HCV entry factor NPC1L1 as also being required for HCV cell-to-cell spread, while showing that the VLDL pathway, which is required for the secretion of cell-free infectious virus, is not required for cell-to-cell spread. While both these host factors are considered viable antiviral targets, we demonstrate that only inhibitors that block factors required for both forms of HCV entry/spread (i.e., NPC1L1) exhibit synergy when used in combination with interferon, while inhibitors that block factors required only for cell-free spread (i.e., VLDL pathway components) do not. Thus, this study advances our understanding of HCV cell-to-cell spread, provides mechanistic insight into the basis of drug synergy, and highlights inhibition of HCV spread as a previously unappreciated consideration in HCV therapy design. PMID:24554660

Regolith-Derived Heat Shield for Planetary Body Entry and Descent System with In Situ Fabrication

NASA Technical Reports Server (NTRS)

Hogue, Michael D.; Mueller, Robert P.; Rasky, Daniel J.; Hintze, Paul E.; Sibille, Laurent

2011-01-01

In this paper we will discuss a new mass-efficient and innovative way of protecting high-mass spacecraft during planetary Entry, Descent & Landing (EDL). Heat shields fabricated in situ can provide a thermal-protection system (TPS) for spacecraft that routinely enter a planetary atmosphere. By fabricating the heat shield with space resources from regolith materials available on moons and asteroids, it is possible to avoid launching the heat-shield mass from Earth. Three regolith processing and manufacturing methods will be discussed: 1) oxygen & metal extraction ISRU processes produce glassy melts enriched in alumina and titania, processed to obtain variable density, high melting point and heat-resistance; 2) compression and sintering of the regolith yield low density materials; 3) in-situ derived high-temperature polymers are created to bind regolith particles together, with a lower energy budget.

Descriptive Analysis of the Rip Entry in Competitive Diving.

ERIC Educational Resources Information Center

Brown, Janet G.; And Others

1984-01-01

Different types of diving entries were filmed both above water and underwater to help identify factors which enable divers to enter the water without apparent splash. Anthropometric measures of subjects were taken to determine body streamlining. Results are presented. (Author/DF)

Mosquito Cellular Factors and Functions in Mediating the Infectious entry of Chikungunya Virus

PubMed Central

Lee, Regina Ching Hua; Hapuarachchi, Hapuarachchige Chanditha; Chen, Karen Caiyun; Hussain, Khairunnisa' Mohamed; Chen, Huixin; Low, Swee Ling; Ng, Lee Ching; Lin, Raymond; Ng, Mary Mah-Lee; Chu, Justin Jang Hann

2013-01-01

Chikungunya virus (CHIKV) is an arthropod-borne virus responsible for recent epidemics in the Asia Pacific regions. A customized gene expression microarray of 18,760 transcripts known to target Aedes mosquito genome was used to identify host genes that are differentially regulated during the infectious entry process of CHIKV infection on C6/36 mosquito cells. Several genes such as epsin I (EPN1), epidermal growth factor receptor pathway substrate 15 (EPS15) and Huntingtin interacting protein I (HIP1) were identified to be differentially expressed during CHIKV infection and known to be involved in clathrin-mediated endocytosis (CME). Transmission electron microscopy analyses further revealed the presence of CHIKV particles within invaginations of the plasma membrane, resembling clathrin-coated pits. Characterization of vesicles involved in the endocytic trafficking processes of CHIKV revealed the translocation of the virus particles to the early endosomes and subsequently to the late endosomes and lysosomes. Treatment with receptor-mediated endocytosis inhibitor, monodansylcadaverine and clathrin-associated drug inhibitors, chlorpromazine and dynasore inhibited CHIKV entry, whereas no inhibition was observed with caveolin-related drug inhibitors. Inhibition of CHIKV entry upon treatment with low-endosomal pH inhibitors indicated that low pH is essential for viral entry processes. CHIKV entry by clathrin-mediated endocytosis was validated via overexpression of a dominant-negative mutant of Eps15, in which infectious entry was reduced, while siRNA-based knockdown of genes associated with CME, low endosomal pH and RAB trafficking proteins exhibited significant levels of CHIKV inhibition. This study revealed, for the first time, that the infectious entry of CHIKV into mosquito cells is mediated by the clathrin-dependent endocytic pathway. PMID:23409203

Maternal factors influencing late entry into prenatal care: a stratified analysis by race or ethnicity and insurance status.

PubMed

Baer, Rebecca J; Altman, Molly R; Oltman, Scott P; Ryckman, Kelli K; Chambers, Christina D; Rand, Larry; Jelliffe-Pawlowski, Laura L

2018-04-22

Examine factors influencing late (> sixth month of gestation) entry into prenatal care by race/ethnicity and insurance payer. The study population was drawn from singleton live births in California from 2007 to 2012 in the birth cohort file maintained by the California Office of Statewide Health Planning and Development, which includes linked birth certificate and mother and infant hospital discharge records. The sample was restricted to infants delivered between 20 and 44 weeks gestation. Logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI) for factors influencing late entry into prenatal care. Maternal age, education, smoking, drug or alcohol abuse/dependence, mental illness, participation in the Women, Infants and Children's program and rural residence were evaluated for women entering prenatal care > sixth month of gestation compared with women entering < fourth month. Backwards stepwise logistic regression was used to create final multivariable models of risk and protective factors for late prenatal care entry for each race or ethnicity and insurance payer. The sample included 2,963,888 women. The percent of women with late entry into prenatal care was consistently higher among women with public versus private insurance. Less than 1% of white non-Hispanic and Asian women with private insurance entered prenatal care late versus more than 4% of white non-Hispanic and black women with public insurance. After stratifying by race or ethnicity and insurance status, women less than 18 years of age were more likely to enter prenatal care late, with young Asian women with private insurance at the highest risk (15.6%; adjusted RR 7.4, 95%CI 5.3-10.5). Among all women with private insurance, > 12-year education or age >34 years at term reduced the likelihood of late prenatal care entry (adjusted RRs 0.5-0.7). Drugs and alcohol abuse/dependence and residing in a rural county were associated with increased risk of late prenatal care across all subgroups (adjusted RRs 1.3-3.8). Participation in the Women, Infants, and Children's program was associated with decreased risk of late prenatal care for women with public insurance (adjusted RRs 0.6-0.7), but increased risk for women with private insurance (adjusted RRs 1.4-2.1). The percent of women with late entry into prenatal care was consistently higher among women with public insurance. Younger women, women with <12-year education, those who used drugs or alcohol or resided in rural counties were more likely to enter prenatal care late, with Asian women <18 years at especially high risk. Participation in the Women, Infants, and Children's program and maternal age >34 years at delivery increased the likelihood of late prenatal care for some subgroups of women and decreased the likelihood for others. These findings can inform institutional factors influencing late prenatal care, especially among lower income women, and may assist efforts aimed at encouraging earlier entry into prenatal care. Optimal prenatal care includes initiation before the 14th week of gestation. Beginning care in the first trimester provides an opportunity for sonographic pregnancy dating or confirmation with best accuracy, which can later prove critical for management of preterm labor, maternal or fetal complications, or prolonged pregnancy. In order to improve maternal and infant health by increasing the number of women seeking prenatal care in the first trimester, it is important to examine the drivers for late entry. Here, we examine factors influencing late (> sixth month of gestation) entry into prenatal care by race/ethnicity and insurance payer. We found the percent of women with late entry into prenatal care was consistently higher among women with public insurance. Younger women, women with <12-year education, those who used drugs or alcohol or resided in rural counties were more likely to enter prenatal care late, with Asian women <18 years at especially high risk. These findings can inform institutional factors influencing late prenatal care, especially among lower income women, and may assist efforts aimed at encouraging earlier entry into prenatal care.

Inhibition of Herpes Simplex Virus gD and Lymphotoxin-α Binding to HveA by Peptide Antagonists

PubMed Central

Sarrias, Maria Rosa; Whitbeck, J. Charles; Rooney, Isabelle; Spruce, Lynn; Kay, Brian K.; Montgomery, Rebecca I.; Spear, Patricia G.; Ware, Carl F.; Eisenberg, Roselyn J.; Cohen, Gary H.; Lambris, John D.

1999-01-01

The herpesvirus entry mediator A (HveA) is a recently characterized member of the tumor necrosis factor receptor family that mediates the entry of most herpes simplex virus type 1 (HSV-1) strains into mammalian cells. Studies on the interaction of HSV-1 with HveA have shown that of all the viral proteins involved in uptake, only gD has been shown to bind directly to HveA, and this binding mediates viral entry into cells. In addition to gD binding to HveA, the latter has been shown to interact with proteins of tumor necrosis factor receptor-associated factor family, lymphotoxin-α (LT-α), and a membrane-associated protein referred to as LIGHT. To study the relationship between HveA, its natural ligands, and the viral proteins involved in HSV entry into cells, we have screened two phage-displayed combinatorial peptide libraries for peptide ligands of a recombinant form of HveA. Affinity selection experiments yielded two peptide ligands, BP-1 and BP-2, which could block the interaction between gD and HveA. Of the two peptides, only BP-2 inhibited HSV entry into CHO cells transfected with an HveA-expressing plasmid. When we analyzed these peptides for the ability to interfere with HveA binding to its natural ligand LT-α, we found that BP-1 inhibited the interaction of cellular LT-α with HveA. Thus, we have dissected the sites of interaction between the cell receptor, its natural ligand LT-α and gD, the virus-specific protein involved in HSV entry into cells. PMID:10364318

Time Domain and Frequency Domain Deterministic Channel Modeling for Tunnel/Mining Environments.

PubMed

Zhou, Chenming; Jacksha, Ronald; Yan, Lincan; Reyes, Miguel; Kovalchik, Peter

2017-01-01

Understanding wireless channels in complex mining environments is critical for designing optimized wireless systems operated in these environments. In this paper, we propose two physics-based, deterministic ultra-wideband (UWB) channel models for characterizing wireless channels in mining/tunnel environments - one in the time domain and the other in the frequency domain. For the time domain model, a general Channel Impulse Response (CIR) is derived and the result is expressed in the classic UWB tapped delay line model. The derived time domain channel model takes into account major propagation controlling factors including tunnel or entry dimensions, frequency, polarization, electrical properties of the four tunnel walls, and transmitter and receiver locations. For the frequency domain model, a complex channel transfer function is derived analytically. Based on the proposed physics-based deterministic channel models, channel parameters such as delay spread, multipath component number, and angular spread are analyzed. It is found that, despite the presence of heavy multipath, both channel delay spread and angular spread for tunnel environments are relatively smaller compared to that of typical indoor environments. The results and findings in this paper have application in the design and deployment of wireless systems in underground mining environments.

Time Domain and Frequency Domain Deterministic Channel Modeling for Tunnel/Mining Environments

PubMed Central

Zhou, Chenming; Jacksha, Ronald; Yan, Lincan; Reyes, Miguel; Kovalchik, Peter

2018-01-01

Understanding wireless channels in complex mining environments is critical for designing optimized wireless systems operated in these environments. In this paper, we propose two physics-based, deterministic ultra-wideband (UWB) channel models for characterizing wireless channels in mining/tunnel environments — one in the time domain and the other in the frequency domain. For the time domain model, a general Channel Impulse Response (CIR) is derived and the result is expressed in the classic UWB tapped delay line model. The derived time domain channel model takes into account major propagation controlling factors including tunnel or entry dimensions, frequency, polarization, electrical properties of the four tunnel walls, and transmitter and receiver locations. For the frequency domain model, a complex channel transfer function is derived analytically. Based on the proposed physics-based deterministic channel models, channel parameters such as delay spread, multipath component number, and angular spread are analyzed. It is found that, despite the presence of heavy multipath, both channel delay spread and angular spread for tunnel environments are relatively smaller compared to that of typical indoor environments. The results and findings in this paper have application in the design and deployment of wireless systems in underground mining environments.† PMID:29457801

Inflammatory Biomarkers Predict Airflow Obstruction After Exposure to World Trade Center Dust

PubMed Central

Nolan, Anna; Naveed, Bushra; Comfort, Ashley L.; Ferrier, Natalia; Hall, Charles B.; Kwon, Sophia; Kasturiarachchi, Kusali J.; Cohen, Hillel W.; Zeig-Owens, Rachel; Glaser, Michelle S.; Webber, Mayris P.; Aldrich, Thomas K.; Rom, William N.; Kelly, Kerry; Prezant, David J.

2012-01-01

Background: The World Trade Center (WTC) collapse on September 11, 2001, produced airflow obstruction in a majority of firefighters receiving subspecialty pulmonary evaluation (SPE) within 6.5 years post-September 11, 2001. Methods: In a cohort of 801 never smokers with normal pre-September 11, 2001, FEV1, we correlated inflammatory biomarkers and CBC counts at monitoring entry within 6 months of September 11, 2001, with a median FEV1 at SPE (34 months; interquartile range, 25-57). Cases of airflow obstruction had FEV1 less than the lower limit of normal (LLN) (100 of 801; 70 of 100 had serum), whereas control subjects had FEV1 greater than or equal to LLN (153 of 801; 124 of 153 had serum). Results: From monitoring entry to SPE years later, FEV1 declined 12% in cases and increased 3% in control subjects. Case subjects had elevated serum macrophage derived chemokine (MDC), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor, and interferon inducible protein-10 levels. Elevated GM-CSF and MDC increased the risk for subsequent FEV1 less than LLN by 2.5-fold (95% CI, 1.2-5.3) and 3.0-fold (95% CI, 1.4-6.1) in a logistic model adjusted for exposure, BMI, age on September 11, 2001, and polymorphonuclear neutrophils. The model had sensitivity of 38% (95% CI, 27-51) and specificity of 88% (95% CI, 80-93). Conclusions: Inflammatory biomarkers can be risk factors for airflow obstruction following dust and smoke exposure. Elevated serum GM-CSF and MDC levels soon after WTC exposure were associated with increased risk of airflow obstruction in subsequent years. Biomarkers of inflammation may help identify pathways producing obstruction after irritant exposure. PMID:21998260

The basic helix-loop-helix transcription factor, heart and neural crest derivatives expressed transcript 2, marks hepatic stellate cells in zebrafish: analysis of stellate cell entry into the developing liver.

PubMed

Yin, Chunyue; Evason, Kimberley J; Maher, Jacquelyn J; Stainier, Didier Y R

2012-11-01

Hepatic stellate cells (HSCs) are liver-specific mesenchymal cells that play vital roles in liver development and injury. Our knowledge of HSC biology is limited by the paucity of in vivo data. HSCs and sinusoidal endothelial cells (SECs) reside in close proximity, and interactions between these two cell types are potentially critical for their development and function. Here, we introduce a transgenic zebrafish line, Tg(hand2:EGFP), that labels HSCs. We find that zebrafish HSCs share many similarities with their mammalian counterparts, including morphology, location, lipid storage, gene-expression profile, and increased proliferation and matrix production, in response to an acute hepatic insult. Using the Tg(hand2:EGFP) line, we conducted time-course analyses during development to reveal that HSCs invade the liver after SECs do. However, HSCs still enter the liver in mutants that lack most endothelial cells, including SECs, indicating that SECs are not required for HSC differentiation or their entry into the liver. In the absence of SECs, HSCs become abnormally associated with hepatic biliary cells, suggesting that SECs influence HSC localization during liver development. We analyzed factors that regulate HSC development and show that inhibition of vascular endothelial growth factor signaling significantly reduces the number of HSCs that enter the liver. We also performed a pilot chemical screen and identified two compounds that affect HSC numbers during development. Our work provides the first comprehensive description of HSC development in zebrafish and reveals the requirement of SECs in HSC localization. The Tg(hand2:EGFP) line represents a unique tool for in vivo analysis and molecular dissection of HSC behavior. Copyright © 2012 American Association for the Study of Liver Diseases.

Quantifying the determinants of decremental response in critical ventricular tachycardia substrate.

PubMed

Beheshti, Mohammadali; Nayyar, Sachin; Magtibay, Karl; Massé, Stéphane; Porta-Sanchez, Andreu; Haldar, Shouvik; Bhaskaran, Abhishek; Vigmond, Edward; Nanthakumar, Kumaraswamy

2018-05-28

Decremental response evoked with extrastimulation (DEEP) is a useful tool for determining diastolic return path of ventricular tachycardia (VT). Though a targeted VT ablation is feasible with this approach, determinants of DEEP response have not been studied OBJECTIVES: To elucidate the effects of clinically relevant factors, specifically, the proximity of the stimulation site to the arrhythmogenic scar, stimulation wave direction, number of channels open in the scar, size of the scar and number of extra stimuli on decrement and entropy of DEEP potentials. In a 3-dimensional bi-domain simulation of human ventricular tissue (TNNP cell model), an irregular subendocardial myopathic region was generated. An irregular channel of healthy tissue with five potential entry branches was shaped into the myopathic region. A bipolar electrogram was derived from two electrodes positioned in the centre of the myopathic region. Evoked delays between far-field and local Electrogram (EGM) following an extrastimulus (S1-S2, 500-350 ms) were measured as the stimulation site, channel branches, and inexcitable tissue size were altered. Stimulation adjacent to the inexcitable tissue from the side opposite to the point-of-entry produces longest DEEP delay. The DEEP delay shortens when the stimulation point is farther away from the scar, and it decreases maximally when stimulation is done from a site beside a conduction barrier. Entropy increases with S2 when stimulation site is from farther away. An unprotected channel structure with multiple side-branch openings had shorter DEEP delay compared to a protected channel structure with a paucity of additional side-branch openings and a point-of-entry on the side opposite to the pacing source. Addition of a second shorter extrastimulus did not universally lead to higher DEEP delay CONCLUSIONS: Location and direction of the wavefront in relation to scar entry and size of scar determine the degree of evoked response while the number of extrastimuli has a small additional decremental effect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Lateral stability and control derivatives extracted from space shuttle Challenger flight data

NASA Technical Reports Server (NTRS)

Schiess, James R.

1988-01-01

Flight data taken from six flights of the Space Transportation System shuttle Challenger (STS-6, 7, 8, 11, 13 and 17) during atmospheric entry are analyzed to determine the shuttle lateral aerodynamic characteristics. Maximum likelihood estimation is applied to data derived from accelerometer and rate gyro measurements and trajectory, meteorological and control surface data to estimate lateral-directional stability and control derivatives. The vehicle stability and control surface effectiveness are compared across the flights and to preflight predicted values.

Lateral stability and control derivatives extracted from five early flights of the space shuttle Columbia

NASA Technical Reports Server (NTRS)

Schiess, J. R.

1986-01-01

Flight data taken from the first five flights (STS-2, 3, 4, 5 and 9) of the Space Transportation System Shuttle Columbia during entry are analyzed to determine the Shuttle lateral aerodynamic characteristics. Maximum likelihood estimation is applied to data derived from accelerometer and rate gyro measurements and trajectory, meteorological and control surface data to estimate lateral-directional stability and control derivatives. The estimated parameters are compared across the five flights and to preflight predicted values.

Inertial measurement unit pre-processors and post-flight STS-1 comparisons

NASA Technical Reports Server (NTRS)

Findlay, J. T.; Mcconnell, J. G.

1981-01-01

The flight results show that the relative tri-redundant Inertial Measurement Unit IMU performance throughout the entire entry flight was within the expected accuracy. Comparisons are presented which show differences in the accumulated sensed velocity changes as measured by the tri-redundant IMUs (in Mean Equator and Equinox of 1950.0), differences in the equivalent inertial Euler angles as measured with respect to the M50 system, and finally, preliminary instrument calibrations determined relative to the ensemble average measurement set. Also, differences in the derived body axes rates and accelerations are presented. Because of the excellent performance of the IMUs during the STS-1 entry, the selection as to which particular IMU would best serve as the dynamic data source for entry reconstruction is arbitrary.

Summary analysis of the Gemini entry aerodynamics

NASA Technical Reports Server (NTRS)

Whitnah, A. M.; Howes, D. B.

1972-01-01

The aerodynamic data that were derived in 1967 from the analysis of flight-generated data for the Gemini entry module are presented. These data represent the aerodynamic characteristics exhibited by the vehicle during the entry portion of Gemini 2, 3, 5, 8, 10, 11, and 12 missions. For the Gemini, 5, 8, 10, 11, and 12 missions, the flight-generated lift-to-drag ratios and corresponding angles of attack are compared with the wind tunnel data. These comparisons show that the flight generated lift-to-drag ratios are consistently lower than were anticipated from the tunnel data. Numerous data uncertainties are cited that provide an insight into the problems that are related to an analysis of flight data developed from instrumentation systems, the primary functions of which are other than the evaluation of flight aerodynamic performance.

Analytic theory of orbit contraction and ballistic entry into planetary atmospheres

NASA Technical Reports Server (NTRS)

Longuski, J. M.; Vinh, N. X.

1980-01-01

A space object traveling through an atmosphere is governed by two forces: aerodynamic and gravitational. On this premise, equations of motion are derived to provide a set of universal entry equations applicable to all regimes of atmospheric flight from orbital motion under the dissipate force of drag through the dynamic phase of reentry, and finally to the point of contact with the planetary surface. Rigorous mathematical techniques such as averaging, Poincare's method of small parameters, and Lagrange's expansion, applied to obtain a highly accurate, purely analytic theory for orbit contraction and ballistic entry into planetary atmospheres. The theory has a wide range of applications to modern problems including orbit decay of artificial satellites, atmospheric capture of planetary probes, atmospheric grazing, and ballistic reentry of manned and unmanned space vehicles.

Translation Initiation Factor eIF4B Interacts with a Picornavirus Internal Ribosome Entry Site in both 48S and 80S Initiation Complexes Independently of Initiator AUG Location

PubMed Central

Ochs, Kerstin; Rust, René C.; Niepmann, Michael

1999-01-01

Most eukaryotic initiation factors (eIFs) are required for internal translation initiation at the internal ribosome entry site (IRES) of picornaviruses. eIF4B is incorporated into ribosomal 48S initiation complexes with the IRES RNA of foot-and-mouth disease virus (FMDV). In contrast to the weak interaction of eIF4B with capped cellular mRNAs and its release upon entry of the ribosomal 60S subunit, eIF4B remains tightly associated with the FMDV IRES during formation of complete 80S ribosomes. Binding of eIF4B to the IRES is energy dependent, and binding of the small ribosomal subunit to the IRES requires the previous energy-dependent association of initiation factors with the IRES. The interaction of eIF4B with the IRES in 48S and 80S complexes is independent of the location of the initiator AUG and thus independent of the mechanism by which the small ribosomal subunit is placed at the actual start codon, either by direct internal ribosomal entry or by scanning. eIF4B does not greatly rearrange its binding to the IRES upon entry of the ribosomal subunits, and the interaction of eIF4B with the IRES is independent of the polypyrimidine tract-binding protein, which enhances FMDV translation. PMID:10438840

The Plant-Derived Naphthoquinone Droserone Inhibits In Vitro Measles Virus Infection.

PubMed

Lieberherr, Christina; Zhang, Guoliang; Grafen, Anika; Singethan, Katrin; Kendl, Sabine; Vogt, Valentin; Maier, Jonathan; Bringmann, Gerhard; Schneider-Schaulies, Jürgen

2017-02-01

The naphthoquinone droserone ( 1 ) is a natural product occurring in dicotyledonous plants. We have now observed that the addition of 1 during infection of tissue culture cells with measles virus considerably reduced the infection. Interestingly, the infection was inhibited only when droserone ( 1 ) was added during virus entry, but not when added to the cells prior to virus uptake or after virus uptake. These findings suggest that 1 interacts with viral particles to reduce infectivity. The formation of progeny measles virus particles was inhibited to 50 % by droserone ( 1 ) at a concentration (IC 50 ) of approximately 2 µM with a half-maximal cytotoxicity (CC 50 ) of about 60 µM for Vero cells. Other tested naphthoquinone derivatives, among them the likewise natural plumbagin ( 2 ), but also synthetic analogs, were either more cytotoxic or not as effective as 1 . Thus, our data do not support the development of naphthoquinone derivatives into antiviral compounds, but suggest that they may be interesting research tools to study measles virus entry into cells. Georg Thieme Verlag KG Stuttgart · New York.

Energy: A Bibliography of Social Science and Related Literature.

ERIC Educational Resources Information Center

Morrison, Denton E.; And Others

This bibliography contains 2,124 listings pertaining primarily to the social factors involved with energy. Some entries report physical energy information as it relates to social science analysis. Entries are listed by author with a subject index for cross reference. Subject categories include: aesthetic, humanistic, and literary; agriculture;…

Delayed School Entry in Uganda

ERIC Educational Resources Information Center

Moyi, Peter

2011-01-01

Since 1997 Uganda has seen a large increase in school enrolment. Despite this increased enrolment, universal education has remained elusive. Many children enrol in school, but not at the recommended age, and they drop out before completing school. This article focuses on one of these problems--delayed school entry. What household factors are…

Technology and operational considerations for low-heat-rate trajectories. [of future winged earth reentry vehicles

NASA Technical Reports Server (NTRS)

Wurster, K. E.; Eldred, C. H.

1979-01-01

A broad parametric study which examines several critical aspects of low-heat-rate entry trajectories is performed. Low planform loadings associated with future winged earth-entry vehicles coupled with the potential application of metallic thermal protection systems (TPS) suggest that such trajectories are of particular interest. Studied are three heating conditions - reference, stagnation, and windward centerline, for both laminar and turbulent flow; configuration-related factors including planform loading and hypersonic angle of attack; and mission-related factors such as cross-range and orbit inclination. Results indicate benefits in the design of TPS to be gained by utilizing moderate angles of attack as opposed to high-lift coefficient, high angles of attack, during entry. An assessment of design and technology implications is made.

Bayesian CP Factorization of Incomplete Tensors with Automatic Rank Determination.

PubMed

Zhao, Qibin; Zhang, Liqing; Cichocki, Andrzej

2015-09-01

CANDECOMP/PARAFAC (CP) tensor factorization of incomplete data is a powerful technique for tensor completion through explicitly capturing the multilinear latent factors. The existing CP algorithms require the tensor rank to be manually specified, however, the determination of tensor rank remains a challenging problem especially for CP rank . In addition, existing approaches do not take into account uncertainty information of latent factors, as well as missing entries. To address these issues, we formulate CP factorization using a hierarchical probabilistic model and employ a fully Bayesian treatment by incorporating a sparsity-inducing prior over multiple latent factors and the appropriate hyperpriors over all hyperparameters, resulting in automatic rank determination. To learn the model, we develop an efficient deterministic Bayesian inference algorithm, which scales linearly with data size. Our method is characterized as a tuning parameter-free approach, which can effectively infer underlying multilinear factors with a low-rank constraint, while also providing predictive distributions over missing entries. Extensive simulations on synthetic data illustrate the intrinsic capability of our method to recover the ground-truth of CP rank and prevent the overfitting problem, even when a large amount of entries are missing. Moreover, the results from real-world applications, including image inpainting and facial image synthesis, demonstrate that our method outperforms state-of-the-art approaches for both tensor factorization and tensor completion in terms of predictive performance.

HIV-1 Clinical Isolates Resistant to CCR5 Antagonists Exhibit Delayed Entry Kinetics That Are Corrected in the Presence of Drug

PubMed Central

Putcharoen, Opass; Lee, Sun Hee; Henrich, Timothy J.; Hu, Zixin; Vanichanan, Jakapat; Coakley, Eoin; Greaves, Wayne; Gulick, Roy M.; Kuritzkes, Daniel R.

2012-01-01

HIV CCR5 antagonists select for env gene mutations that enable virus entry via drug-bound coreceptor. To investigate the mechanisms responsible for viral adaptation to drug-bound coreceptor-mediated entry, we studied viral isolates from three participants who developed CCR5 antagonist resistance during treatment with vicriviroc (VCV), an investigational small-molecule CCR5 antagonist. VCV-sensitive and -resistant viruses were isolated from one HIV subtype C- and two subtype B-infected participants; VCV-resistant isolates had mutations in the V3 loop of gp120 and were cross-resistant to TAK-779, an investigational antagonist, and maraviroc (MVC). All three resistant isolates contained a 306P mutation but had variable mutations elsewhere in the V3 stem. We used a virus-cell β-lactamase (BlaM) fusion assay to determine the entry kinetics of recombinant viruses that incorporated full-length VCV-sensitive and -resistant envelopes. VCV-resistant isolates exhibited delayed entry rates in the absence of drug, relative to pretherapy VCV-sensitive isolates. The addition of drug corrected these delays. These findings were generalizable across target cell types with a range of CD4 and CCR5 surface densities and were observed when either population-derived or clonal envelopes were used to construct recombinant viruses. V3 loop mutations alone were sufficient to restore virus entry in the presence of drug, and the accumulation of V3 mutations during VCV therapy led to progressively higher rates of viral entry. We propose that the restoration of pre-CCR5 antagonist therapy HIV entry kinetics drives the selection of V3 loop mutations and may represent a common mechanism that underlies the emergence of CCR5 antagonist resistance. PMID:22090117

Vpx complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages.

PubMed

Mlcochova, Petra; Watters, Sarah A; Towers, Greg J; Noursadeghi, Mahdad; Gupta, Ravindra K

2014-03-21

It is now known that clinically derived viruses are most commonly R5 tropic with very low infectivity in macrophages. As these viruses utilize CD4 inefficiently, defective entry has been assumed to be the dominant restriction. The implication is that macrophages are not an important reservoir for the majority of circulating viruses. Macrophage infection by clinical transmitted/founder isolates was 10-100 and 30-450 fold less efficient as compared to YU-2 and BaL respectively. Vpx complementation augmented macrophage infection by non-macrophage tropic viruses to the level of infectivity observed for YU-2 in the absence of Vpx. Augmentation was evident even when Vpx was provided 24 hours post-infection. The entry defect was measured as 2.5-5 fold, with a further 3.5-10 fold block at strong stop and subsequent stages of reverse transcription as compared to YU-2. The overall block to infection was critically dependent on the mechanism of entry as demonstrated by rescue of infection after pseudotyping with VSV-G envelope. Reverse transcription in macrophages could not be enhanced using a panel of cytokines or lipopolysaccharide (LPS). Although the predominant block to clinical transmitted/founder viruses is post-entry, infectivity is determined by Env-CD4 interactions and can be rescued with VSV-G pseudotyping. This suggests a functional link between the optimal entry pathway taken by macrophage tropic viruses and downstream events required for reverse transcription. Consistent with a predominantly post-entry block, replication of R5 using viruses can be greatly enhanced by Vpx. We conclude therefore that entry is not the limiting step and that macrophages represent clinically relevant reservoirs for 'non-macrophage tropic' viruses.

Simultaneous Tensor Decomposition and Completion Using Factor Priors.

PubMed

Chen, Yi-Lei; Hsu, Chiou-Ting Candy; Liao, Hong-Yuan Mark

2013-08-27

Tensor completion, which is a high-order extension of matrix completion, has generated a great deal of research interest in recent years. Given a tensor with incomplete entries, existing methods use either factorization or completion schemes to recover the missing parts. However, as the number of missing entries increases, factorization schemes may overfit the model because of incorrectly predefined ranks, while completion schemes may fail to interpret the model factors. In this paper, we introduce a novel concept: complete the missing entries and simultaneously capture the underlying model structure. To this end, we propose a method called Simultaneous Tensor Decomposition and Completion (STDC) that combines a rank minimization technique with Tucker model decomposition. Moreover, as the model structure is implicitly included in the Tucker model, we use factor priors, which are usually known a priori in real-world tensor objects, to characterize the underlying joint-manifold drawn from the model factors. We conducted experiments to empirically verify the convergence of our algorithm on synthetic data, and evaluate its effectiveness on various kinds of real-world data. The results demonstrate the efficacy of the proposed method and its potential usage in tensor-based applications. It also outperforms state-of-the-art methods on multilinear model analysis and visual data completion tasks.

Construct validity test of evaluation tool for professional behaviors of entry-level occupational therapy students in the United States.

PubMed

Yuen, Hon K; Azuero, Andres; Lackey, Kaitlin W; Brown, Nicole S; Shrestha, Sangita

2016-01-01

This study aimed to test the construct validity of an instrument to measure student professional behaviors in entry-level occupational therapy (OT) students in the academic setting. A total of 718 students from 37 OT programs across the United States answered a self-assessment survey of professional behavior that we developed. The survey consisted of ranking 28 attributes, each on a 5-point Likert scale. A split-sample approach was used for exploratory and then confirmatory factor analysis. A three-factor solution with nine items was extracted using exploratory factor analysis [EFA] (n=430, 60%). The factors were 'Commitment to Learning' (2 items), 'Skills for Learning' (4 items), and 'Cultural Competence' (3 items). Confirmatory factor analysis (CFA) on the validation split (n=288, 40%) indicated fair fit for this three-factor model (fit indices: CFI=0.96, RMSEA=0.06, and SRMR=0.05). Internal consistency reliability estimates of each factor and the instrument ranged from 0.63 to 0.79. Results of the CFA in a separate validation dataset provided robust measures of goodness-of-fit for the three-factor solution developed in the EFA, and indicated that the three-factor model fitted the data well enough. Therefore, we can conclude that this student professional behavior evaluation instrument is a structurally validated tool to measure professional behaviors reported by entry-level OT students. The internal consistency reliability of each individual factor and the whole instrument was considered to be adequate to good.

Measurement of RF propagation around corners in underground mines and tunnels

PubMed Central

Jacksha, R.; Zhou, C.

2017-01-01

This paper reports measurement results for radio frequency (RF) propagation around 90° corners in tunnels and underground mines, for vertically, horizontally and longitudinally polarized signals. Measurements of signal power attenuation from a main entry into a crosscut were performed at four frequencies — 455, 915, 2450 and 5800 MHz — that are common to underground radio communication systems. From the measurement data, signal power loss was determined as a function of signal coupling from the main entry into the crosscut. The resultant power loss data show there are many factors that contribute to power attenuation from a main entry into a crosscut, including frequency, antenna polarization and cross-sectional entry dimensions. PMID:28626351

Measurement of RF propagation around corners in underground mines and tunnels.

PubMed

Jacksha, R; Zhou, C

2016-01-01

This paper reports measurement results for radio frequency (RF) propagation around 90° corners in tunnels and underground mines, for vertically, horizontally and longitudinally polarized signals. Measurements of signal power attenuation from a main entry into a crosscut were performed at four frequencies - 455, 915, 2450 and 5800 MHz - that are common to underground radio communication systems. From the measurement data, signal power loss was determined as a function of signal coupling from the main entry into the crosscut. The resultant power loss data show there are many factors that contribute to power attenuation from a main entry into a crosscut, including frequency, antenna polarization and cross-sectional entry dimensions.

Radiative Heating in MSL Entry: Comparison of Flight Heating Discrepancy to Ground Test and Predictive Models

NASA Technical Reports Server (NTRS)

Cruden, Brett A.; Brandis, Aaron M.; White, Todd R.; Mahzari, Milad; Bose, Deepak

2014-01-01

During the recent entry of the Mars Science Laboratory (MSL), the heat shield was equipped with thermocouple stacks to measure in-depth heating of the thermal protection system (TPS). When only convective heating was considered, the derived heat flux from gauges in the stagnation region was found to be underpredicted by as much as 17 W/sq cm, which is significant compared to the peak heating of 32 W/sq cm. In order to quantify the contribution of radiative heating phenomena to the discrepancy, ground tests and predictive simulations that replicated the MSL entry trajectory were performed. An analysis is carried through to assess the quality of the radiation model and the impact to stagnation line heating. The impact is shown to be significant, but does not fully explain the heating discrepancy.

Low Soluble Fms-Like Tyrosine Kinase-1, Endoglin, and Endothelin-1 Levels in Women With Confirmed or Suspected Preeclampsia Using Proton Pump Inhibitors.

PubMed

Saleh, Langeza; Samantar, Raaho; Garrelds, Ingrid M; van den Meiracker, Anton H; Visser, Willy; Danser, A H Jan

2017-09-01

Patients with preeclampsia display elevated placenta-derived sFlt-1 (soluble Fms-like tyrosine kinase-1) and endoglin levels and decreased placental growth factor levels. Proton pump inhibitors (PPIs) decrease trophoblast sFlt-1 and endoglin secretion in vitro. PPIs are used during pregnancy to combat reflux disease. Here, we investigated whether PPIs affect sFlt-1 in women with confirmed/suspected preeclampsia, making use of a prospective cohort study involving 430 women. Of these women, 40 took PPIs (6 esomeprazole, 32 omeprazole, and 2 pantoprazole) for 8 to 45 (median 29) days before sFlt-1 measurement. Measurements were only made once, at study entry between weeks 20 and 41 (median 33 weeks). PPI use was associated with lower sFlt-1 levels, with no change in placental growth factor levels, both when compared with all non-PPI users and with 80 gestational age-matched controls selected from the non-PPI users. No sFlt-1/placental growth factor alterations were observed in women using ferrous fumarate or macrogol while, as expected, women using antihypertensive medication displayed higher sFlt-1 levels and lower placental growth factor levels. The PPI use-associated decrease in sFlt-1 was independent of the application of antihypertensive drugs and also occurred when restricting our analysis to patients with hypertensive disease of pregnancy at study entry. PPI users displayed more cases with preexisting proteinuria, less gestational hypertension, and a lower number of neonatal sepsis cases. Finally, their plasma endoglin and endothelin-1 levels were lower while sFlt-1 levels correlated positively with both. In conclusion, PPI use associates with low sFlt-1, endoglin, and endothelin-1 levels, warranting prospective trials to investigate the therapeutic potential of PPIs in preeclampsia. © 2017 American Heart Association, Inc.

Chloroquine derivatives block the translocation pores and inhibit cellular entry of Clostridium botulinum C2 toxin and Bacillus anthracis lethal toxin.

PubMed

Kreidler, Anna-Maria; Benz, Roland; Barth, Holger

2017-03-01

The pathogenic bacteria Clostridium botulinum and Bacillus anthracis produce the binary protein toxins C2 and lethal toxin (LT), respectively. These toxins consist of a binding/transport (B 7 ) component that delivers the separate enzyme (A) component into the cytosol of target cells where it modifies its specific substrate and causes cell death. The B 7 components of C2 toxin and LT, C2IIa and PA 63 , respectively, are ring-shaped heptamers that bind to their cellular receptors and form complexes with their A components C2I and lethal factor (LF), respectively. After receptor-mediated endocytosis of the toxin complexes, C2IIa and PA 63 insert into the membranes of acidified endosomes and form trans-membrane pores through which C2I and LF translocate across endosomal membranes into the cytosol. C2IIa and PA 63 also form channels in planar bilayer membranes, and we used this approach earlier to identify chloroquine as a potent blocker of C2IIa and PA 63 pores. Here, a series of chloroquine derivatives was investigated to identify more efficient toxin inhibitors with less toxic side effects. Chloroquine, primaquine, quinacrine, and fluphenazine blocked C2IIa and PA 63 pores in planar lipid bilayers and in membranes of living epithelial cells and macrophages, thereby preventing the pH-dependent membrane transport of the A components into the cytosol and protecting cells from intoxication with C2 toxin and LT. These potent inhibitors of toxin entry underline the central role of the translocation pores for cellular uptake of binary bacterial toxins and as relevant drug targets, and might be lead compounds for novel pharmacological strategies against severe enteric diseases and anthrax.

Mordell integrals and Giveon-Kutasov duality

NASA Astrophysics Data System (ADS)

Giasemidis, Georgios; Tierz, Miguel

2016-01-01

We solve, for finite N, the matrix model of supersymmetric U( N) Chern-Simons theory coupled to N f massive hypermultiplets of R-charge 1/2 , together with a Fayet-Iliopoulos term. We compute the partition function by identifying it with a determinant of a Hankel matrix, whose entries are parametric derivatives (of order N f - 1) of Mordell integrals. We obtain finite Gauss sums expressions for the partition functions. We also apply these results to obtain an exhaustive test of Giveon-Kutasov (GK) duality in the N=3 setting, by systematic computation of the matrix models involved. The phase factor that arises in the duality is then obtained explicitly. We give an expression characterized by modular arithmetic (mod 4) behavior that holds for all tested values of the parameters (checked up to N f = 12 flavours).

The effects of market structure and payment rate on the entry of private health plans into the Medicare market.

PubMed

Frakt, Austin B; Pizer, Steven D; Feldman, Roger

2012-01-01

Private insurance firms participating in Medicare can offer up to three principal plan types: coordinated care plans (CCPs), prescription drug plans (PDPs), and private fee-for-service (PFFS) plans. Firms can make entry and marketing decisions separately across plan types and geographic regions. In this study, we estimate firm-level models of Medicare private plan entry using data from the years 2007 to 2009. Our models include a measure of market structure and separately identify CCP, PDP, and PFFS entry. We find evidence that entry barriers associated with CCP market concentration affect all three product types. We also find evidence of cross-product competition and common cost or demand factors that make entry with certain product combinations more likely. We predict that the market presence of CCPs and PFFS plans will decrease and that of PDPs will increase in response to payment reductions included in the new health reform law.

Children's social and scholastic lives in kindergarten: related spheres of influence?

PubMed

Ladd, G W; Birch, S H; Buhs, E S

1999-01-01

Evidence from two studies conducted with kindergarten samples (N = 200, M age = 5.58 years; N = 199, M age = 5.47 years) supported a series of interrelated hypotheses derived from a child x environment model of early school adjustment. The findings obtained were consistent with the following inferences: (1) Entry factors, such as children's cognitive maturity and family backgrounds, directly as well as indirectly influence children's behavior, participation, and achievement in kindergarten; (2) as children enter school, their initial behavioral orientations influence the types of relationships they form with peers and teachers; (3) stressful aspects of children's peer and teacher relationships in the school environment adversely impact classroom participation and achievement; and (4) classroom participation is an important prerequisite for achievement during kindergarten. Collectively, these findings illustrate the need to revise prevailing theories of school adjustment, and the research agendas that evolve from these perspectives, so as to incorporate interpersonal risk factors that operate within the school environment.

Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

USGS Publications Warehouse

Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

2012-01-01

Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

Effects of intermediate wettability on entry capillary pressure in angular pores.

PubMed

Rabbani, Harris Sajjad; Joekar-Niasar, Vahid; Shokri, Nima

2016-07-01

Entry capillary pressure is one of the most important factors controlling drainage and remobilization of the capillary-trapped phases as it is the limiting factor against the two-phase displacement. It is known that the entry capillary pressure is rate dependent such that the inertia forces would enhance entry of the non-wetting phase into the pores. More importantly the entry capillary pressure is wettability dependent. However, while the movement of a meniscus into a strongly water-wet pore is well-defined, the invasion of a meniscus into a weak or intermediate water-wet pore especially in the case of angular pores is ambiguous. In this study using OpenFOAM software, high-resolution direct two-phase flow simulations of movement of a meniscus in a single capillary channel are performed. Interface dynamics in angular pores under drainage conditions have been simulated under constant flow rate boundary condition at different wettability conditions. Our results shows that the relation between the half corner angle of pores and contact angle controls the temporal evolution of capillary pressure during the invasion of a pore. By deviating from pure water-wet conditions, a dip in the temporal evolution of capillary pressure can be observed which will be pronounced in irregular angular cross sections. That enhances the pore invasion with a smaller differential pressure. The interplay between the contact angle and pore geometry can have significant implications for enhanced remobilization of ganglia in intermediate contact angles in real porous media morphologies, where pores are very heterogeneous with small shape factors. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Hyperforin--a key constituent of St. John's wort specifically activates TRPC6 channels.

PubMed

Leuner, Kristina; Kazanski, Victor; Müller, Margarethe; Essin, Kirill; Henke, Bettina; Gollasch, Maik; Harteneck, Christian; Müller, Walter E

2007-12-01

Hyperforin, a bicyclic polyprenylated acylphloroglucinol derivative, is the main active principle of St. John's wort extract responsible for its antidepressive profile. Hyperforin inhibits the neuronal serotonin and norepinephrine uptake comparable to synthetic antidepressants. In contrast to synthetic antidepressants directly blocking neuronal amine uptake, hyperforin increases synaptic serotonin and norepinephrine concentrations by an indirect and yet unknown mechanism. Our attempts to identify the molecular target of hyperforin resulted in the identification of TRPC6. Hyperforin induced sodium and calcium entry as well as currents in TRPC6-expressing cells. Sodium currents and the subsequent breakdown of the membrane sodium gradients may be the rationale for the inhibition of neuronal amine uptake. The hyperforin-induced cation entry was highly specific and related to TRPC6 and was suppressed in cells expressing a dominant negative mutant of TRPC6, whereas phylogenetically related channels, i.e., TRPC3 remained unaffected. Furthermore, hyperforin induces neuronal axonal sprouting like nerve growth factor in a TRPC6-dependent manner. These findings support the role of TRPC channels in neurite extension and identify hyperforin as the first selective pharmacological tool to study TRPC6 function. Hyperforin integrates inhibition of neurotransmitter uptake and neurotrophic property by specific activation of TRPC6 and represents an interesting lead-structure for a new class of antidepressants.

Levels and determinants of pesticide exposure in re-entry workers in vineyards: results of the PESTEXPO study.

PubMed

Baldi, Isabelle; Lebailly, P; Bouvier, G; Rondeau, V; Kientz-Bouchart, V; Canal-Raffin, M; Garrigou, A

2014-07-01

Physical contact with branches, leaves, fruit or vegetables in previously treated crops is responsible for the transfer of pesticides to the worker's skin in agricultural tasks such as harvesting, pruning, thinning, cutting or sorting. Few studies have documented workers' exposure during re-entry in vineyards. In the PESTEXPO study, we described levels of exposure and analyzed their determinants during re-entry and harvesting in vineyards in the Bordeaux area, France. Between 2002 and 2007, volunteers performing re-entry tasks (N=46 days) or harvesting (N=48 days) after dithiocarbamate or folpet treatment were observed. Detailed information on the tasks was collected and dermal contamination was assessed using patches placed on the skin and hand-washing at the end of each working phase. Daily median contamination was 1 967.7 μl of mixture during re-entry (90(e) percentile: 5 045.3 μl) and 18.7 μl during harvesting (90(e) percentile: 911.4 μl). The type of task was the parameter found to be the most strongly associated with contamination. For re-entry, the highest contaminations were observed during raising of wires and cutting of branches. During the harvest, the contamination was maximal for grape-picking. The delay since the last treatment and the rate of active ingredient per hectare played a role, together with other factors such as meteorological factors, crop and farm characteristics, gloves and clothes. Our results underline the necessity to take into account exposures during re-entry and harvest when considering pesticide exposure, both for epidemiological research and preventive action. Copyright © 2014 Elsevier Inc. All rights reserved.

VizieR Online Data Catalog: CCD Hα and R photometry of 334 galaxies (James+, 2004)

NASA Astrophysics Data System (ADS)

James, P. A.; Shane, N. S.; Beckman, J. E.; Cardwell, A.; Collins, C. A.; Etherton, J.; de Jong, R. S.; Fathi, K.; Knapen, J. H.; Peletier, R. F.; Percival, S. M.; Pollacco, D. L.; Seigar, M. S.; Stedman, S.; Steele, I. A.

2004-01-01

Hα plus [NII] and R-band CCD photometry and derived parameters are presented for the full sample of 334 spiral and irregular galaxies. Galaxy distances are derived using a Virgo-infall corrected model which is described in the paper, and star formation rates are derived from Hα plus [NII] fluxes using the conversion defined by Kennicutt et al. (1994ApJ...435...22K). The entries are arranged within five bins in recession velocity, and in order of increasing Right Ascension within these bins. (1 data file).

Up-regulation of Store-operated Ca2+ Entry and Nuclear Factor of Activated T Cells Promote the Acinar Phenotype of the Primary Human Salivary Gland Cells*

PubMed Central

Jang, Shyh-Ing; Ong, Hwei Ling; Liu, Xibao; Alevizos, Ilias; Ambudkar, Indu S.

2016-01-01

The signaling pathways involved in the generation and maintenance of exocrine gland acinar cells have not yet been established. Primary human salivary gland epithelial cells, derived from salivary gland biopsies, acquired an acinar-like phenotype when the [Ca2+] in the serum-free medium (keratinocyte growth medium, KGM) was increased from 0.05 mm (KGM-L) to 1.2 mm (KGM-H). Here we examined the mechanism underlying this Ca2+-dependent generation of the acinar cell phenotype. Compared with cells in KGM-L, those in KGM-H display enhancement of Orai1, STIM1, STIM2, and nuclear factor of activated T cells 1 (NFAT1) expression together with an increase in store-operated Ca2+ entry (SOCE), SOCE-dependent nuclear translocation of pGFP-NFAT1, and NFAT-dependent but not NFκB-dependent gene expression. Importantly, AQP5, an acinar-specific protein critical for function, is up-regulated in KGM-H via SOCE/NFAT-dependent gene expression. We identified critical NFAT binding motifs in the AQP5 promoter that are involved in Ca2+-dependent up-regulation of AQP5. These important findings reveal that the Ca2+-induced switch of salivary epithelial cells to an acinar-like phenotype involves remodeling of SOCE and NFAT signaling, which together control the expression of proteins critically relevant for acinar cell function. Our data provide a novel strategy for generating and maintaining acinar cells in culture. PMID:26903518

Influences on choice of surgery as a career: a study of consecutive cohorts in a medical school.

PubMed

Sobral, Dejano T

2006-06-01

To examine the differential impact of person-based and programme-related features on graduates' dichotomous choice between surgical or non-surgical field specialties for first-year residency. A 10-year cohort study was conducted, following 578 students (55.4% male) who graduated from a university medical school during 1994-2003. Data were collected as follows: at the beginning of medical studies, on career preference and learning frame; during medical studies, on academic achievement, cross-year peer tutoring and selective clinical traineeship, and at graduation, on the first-year residency selected. Contingency and logistic regression analyses were performed, with graduates grouped by the dichotomous choice of surgery or not. Overall, 23% of graduates selected a first-year residency in surgery. Seven time-steady features related to this choice: male sex, high self-confidence, option of surgery at admission, active learning style, preference for surgery after Year 1, peer tutoring on clinical surgery, and selective training in clinical surgery. Logistic regression analysis, including all features, predicted 87.1% of the graduates' choices. Male sex, updated preference, peer tutoring and selective training were the most significant predictors in the pathway to choice. The relative roles of person-based and programme-related factors in the choice process are discussed. The findings suggest that for most students the choice of surgery derives from a temporal summation of influences that encompass entry and post-entry factors blended in variable patterns. It is likely that sex-unbiased peer tutoring and selective training supported the students' search process for personal compatibility with specialty-related domains of content and process.

Air Force Commanders and Barriers to Entry into a Doctoral Business Program

ERIC Educational Resources Information Center

Williams, Tony; LeMire, Steven D.

2011-01-01

The authors examined professionally qualified Air Force commanders' barriers to entry into a business doctoral degree program related to the factors of time, financial means, academics, and motivation. Of the 116 present commanders, 63% were interested in pursuing a doctorate in business. For the commanders interested in obtaining a doctorate…

Education for Perspective Transformation. Women's Re-entry Programs in Community Colleges.

ERIC Educational Resources Information Center

Mezirow, Jack; Marsick, Victoria

The national field study of women's re-entry programs in community colleges reported here was done to identify factors that impeded or facilitated the progress of these programs. After an introduction, the content is presented in three sections. The first section deals with perspective transformation, the adult development process occurring in the…

Predictors of Student Success in Entry-Level Science Courses

ERIC Educational Resources Information Center

Singh, Mamta K.

2009-01-01

Although the educational evaluation process is useful and valuable and is supported by the Higher Education Act, a strong research base for program evaluation of college entry-level science courses is still lacking. Studies in science disciplines such as, biology, chemistry, and physics have addressed various affective and demographic factors and…

An Annotated Bibliography of Gay and Lesbian Communication Studies.

ERIC Educational Resources Information Center

Park, Jan Carl

1979-01-01

The 22 entries in this annotated bibliography represent articles that have lesbian women or gay men as subjects and that deal with a specific verbal or nonverbal communication factor. Topics covered in the entries include patterns of self-disclosure in homosexual and heterosexual college students, interpersonal conflict in homosexual relations,…

School Entrance Recommendation: A Question of Age or Development?

ERIC Educational Resources Information Center

Horstschräer, Julia; Muehler, Grit

2014-01-01

Fixed cutoff dates regulating school entry create disadvantages for children who are young relative to their classmates. Early and late school enrollment, though, might mitigate these disadvantages. In this paper, we analyze in a first step which factors determine school entry, if entrance screenings allow for early and late enrollment. Second, we…

Limitations of the Outback LTD re-entry device in femoropopliteal chronic total occlusions.

PubMed

Shin, Susanna H; Baril, Donald; Chaer, Rabih; Rhee, Robert; Makaroun, Michel; Marone, Luke

2011-05-01

Subintimal recanalization for the treatment of femoropopliteal chronic total occlusions (CTO) occasionally requires re-entry devices to access the true lumen distally, but limited information is available on factors predicting the success or failure of these devices. We evaluated the Outback LTD re-entry device (LuMend, Redwood City, Calif; acquired by Cordis Corp, Miami Lakes, Fla). A retrospective review of patients with femoropopliteal CTO from August 2006 to August 2009 was performed. Age, gender, occlusion length, site of re-entry, and the angle of the aortic bifurcation were recorded. Procedural angiograms were used to assign a calcification score (none, mild, moderate, severe) at the re-entry site. Univariate and multivariate logistic regression analyses were used to identify factors predicting failure of re-entry into the true lumen. Of 249 CTOs treated, the re-entry device was used 52 times (20.9%): 47 superficial femoral artery (SFA) occlusions and 5 combined SFA and popliteal artery occlusions (33 TransAtlantic InterSociety Consensus II type C and 18 type D lesions). Of 48 procedures with available angiograms for review, the target re-entry site was at the adductor canal in 30 (62.5%), the above-knee popliteal artery in 13 (27.1%), behind the knee joint in 4 (8.3%), and the mid-SFA in 2 (4.2%). Patients (54% men) were a mean age of 73.1 years. Re-entry was successful in 34 attempts (64.5%). Causes of failure included inability to re-enter the true lumen in 11 (61.1%), difficulty tracking the device over a wire in 3 (16.7%), acute angle of aortic bifurcation in 2 (11.1%), mechanical failure of the device in 1 (5.6%), and difficulty tracking the device through the lesion in 1 (5.6%). Moderate or severe calcification at the site of re-entry was the only significant predictor of failure (odds ratio, 6.3; 95% confidence interval, 1.45-24.48; P = .01). An aortic bifurcation angle ≥40° did trend toward predicting success (odds ratio, 0.23; 95% confidence interval, 0.05-1.02; P = .054). Although the Outback re-entry device can be successful in extending the applicability of endovascular management to difficult femoropopliteal occlusions, it is not uniformly successful in current clinical practice. Significant calcification at the proposed re-entry site is a strong predictor of failure. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Influence of nonequilibrium radiation and shape change on aerothermal environment of a Jovian entry body

NASA Technical Reports Server (NTRS)

Tiwari, S. N.; Subramanian, S. V.

1981-01-01

The influence of nonequilibrium radiative energy transfer and the effect of probe configuration changes on the flow phenomena around a Jovian entry body are investigated. The radiating shock layer flow is assumed to be axisymmetric, viscous, laminar and in chemical equilibrium. The radiative transfer equations are derived under nonequilibrium conditions which include multilevel energy transitions. The equilibrium radiative transfer analysis is performed with an existing nongray radiation model which accounts for molecular band, atomic line, and continuum transitions. The nonequilibrium results are obtained with and without ablation injection in the shock layer. The nonequilibrium results are found to be greatly influenced by the temperature distribution in the shock layer. In the absence of ablative products, the convective and radiative heating to the entry body are reduced under nonequilibrium conditions. The influence of nonequilibrium is found to be greater at higher entry altitudes. With coupled ablation and carbon phenolic injection, 16 chemical species are used in the ablation layer for radiation absorption. Equilibrium and nonequilibrium results are compared under peak heating conditions.

Discrete influx events refill depleted Ca2+ stores in a chick retinal neuron

PubMed Central

Borges, Salvador; Lindstrom, Sarah; Walters, Cameron; Warrier, Ajithkumar; Wilson, Martin

2008-01-01

The depletion of ER Ca2+ stores, following the release of Ca2+ during intracellular signalling, triggers the Ca2+ entry across the plasma membrane known as store-operated calcium entry (SOCE). We show here that brief, local [Ca2+]i increases (motes) in the thin dendrites of cultured retinal amacrine cells derived from chick embryos represent the Ca2+ entry events of SOCE and are initiated by sphingosine-1-phosphate (S1P), a sphingolipid with multiple cellular signalling roles. Externally applied S1P elicits motes but not through a G protein-coupled membrane receptor. The endogenous precursor to S1P, sphingosine, also elicits motes but its action is suppressed by dimethylsphingosine (DMS), an inhibitor of sphingosine phosphorylation. DMS also suppresses motes induced by store depletion and retards the refilling of depleted stores. These effects are reversed by exogenously applied S1P. In these neurons formation of S1P is a step in the SOCE pathway that promotes Ca2+ entry in the form of motes. PMID:18033816

Discrete influx events refill depleted Ca2+ stores in a chick retinal neuron.

PubMed

Borges, Salvador; Lindstrom, Sarah; Walters, Cameron; Warrier, Ajithkumar; Wilson, Martin

2008-01-15

The depletion of ER Ca2+ stores, following the release of Ca2+ during intracellular signalling, triggers the Ca2+ entry across the plasma membrane known as store-operated calcium entry (SOCE). We show here that brief, local [Ca2+]i increases (motes) in the thin dendrites of cultured retinal amacrine cells derived from chick embryos represent the Ca2+ entry events of SOCE and are initiated by sphingosine-1-phosphate (S1P), a sphingolipid with multiple cellular signalling roles. Externally applied S1P elicits motes but not through a G protein-coupled membrane receptor. The endogenous precursor to S1P, sphingosine, also elicits motes but its action is suppressed by dimethylsphingosine (DMS), an inhibitor of sphingosine phosphorylation. DMS also suppresses motes induced by store depletion and retards the refilling of depleted stores. These effects are reversed by exogenously applied S1P. In these neurons formation of S1P is a step in the SOCE pathway that promotes Ca2+ entry in the form of motes.

[Quality Management and Quality Specifications of Laboratory Tests in Clinical Studies--Challenges in Pre-Analytical Processes in Clinical Laboratories].

PubMed

Ishibashi, Midori

2015-01-01

The cost, speed, and quality are the three important factors recently indicated by the Ministry of Health, Labour and Welfare (MHLW) for the purpose of accelerating clinical studies. Based on this background, the importance of laboratory tests is increasing, especially in the evaluation of clinical study participants' entry and safety, and drug efficacy. To assure the quality of laboratory tests, providing high-quality laboratory tests is mandatory. For providing adequate quality assurance in laboratory tests, quality control in the three fields of pre-analytical, analytical, and post-analytical processes is extremely important. There are, however, no detailed written requirements concerning specimen collection, handling, preparation, storage, and shipping. Most laboratory tests for clinical studies are performed onsite in a local laboratory; however, a part of laboratory tests is done in offsite central laboratories after specimen shipping. As factors affecting laboratory tests, individual and inter-individual variations are well-known. Besides these factors, standardizing the factors of specimen collection, handling, preparation, storage, and shipping, may improve and maintain the high quality of clinical studies in general. Furthermore, the analytical method, units, and reference interval are also important factors. It is concluded that, to overcome the problems derived from pre-analytical processes, it is necessary to standardize specimen handling in a broad sense.

Low temperature simulation of subliming boundary layer flow in Jupiter atmosphere

NASA Technical Reports Server (NTRS)

Chen, C. J.

1976-01-01

A low-temperature approximate simulation for the sublimation of a graphite heat shield under Jovian entry conditions is studied. A set of algebraic equations is derived to approximate the governing equation and boundary conditions, based on order-of-magnitude analysis. Characteristic quantities such as the wall temperature and the subliming velocity are predicted. Similarity parameters that are needed to simulate the most dominant phenomena of the Jovian entry flow are also given. An approximate simulation of the sublimation of the graphite heat shield is performed with an air-dry-ice model. The simulation with the air-dry-ice model may be carried out experimentally at a lower temperature of 3000 to 6000 K instead of the entry temperature of 14,000 K. The rate of graphite sublimation predicted by the present algebraic approximation agrees to the order of magnitude with extrapolated data. The limitations of the simulation method and its utility are discussed.

Entry Guidance for the 2011 Mars Science Laboratory Mission

NASA Technical Reports Server (NTRS)

Mendeck, Gavin F.; Craig, Lynn E.

2011-01-01

The 2011 Mars Science Laboratory will be the first Mars mission to attempt a guided entry to safely deliver the rover to a touchdown ellipse of 25 km x 20 km. The Entry Terminal Point Controller guidance algorithm is derived from the final phase Apollo Command Module guidance and, like Apollo, modulates the bank angle to control the range flown. For application to Mars landers which must make use of the tenuous Martian atmosphere, it is critical to balance the lift of the vehicle to minimize the range error while still ensuring a safe deploy altitude. An overview of the process to generate optimized guidance settings is presented, discussing improvements made over the last nine years. Key dispersions driving deploy ellipse and altitude performance are identified. Performance sensitivities including attitude initialization error and the velocity of transition from range control to heading alignment are presented.

The Survey of Treatment Entry Pressures (STEP): identifying client's reasons for entering substance abuse treatment.

PubMed

Dugosh, Karen Leggett; Festinger, David S; Lynch, Kevin G; Marlowe, Douglas B

2014-10-01

Systematically identifying reasons that clients enter substance abuse treatment may allow clinicians to immediately focus on issues of greatest relevance to the individual and enhance treatment engagement. We developed the Survey of Treatment Entry Pressures (STEP) to identify the specific factors that precipitated an individual's treatment entry. The instrument contains 121 items from 6 psychosocial domains (i.e., family, financial, social, medical, psychiatric, legal). The current study examined the STEP's psychometric properties. A total of 761 participants from various treatment settings and modalities completed the STEP prior to treatment admission and 4-7 days later. Analyses were performed to examine the instrument's psychometric properties including item response rates, test-retest reliability, internal consistency, and factor structure. The items displayed adequate test-retest reliability and internal consistency within each psychosocial domain. Generally, results from exploratory and confirmatory factor analyses support a 2-factor structure reflecting type of reinforcement schedule. The study provides preliminary support for the psychometric properties of the STEP. The STEP may provide a reliable way for clinicians to characterize and capitalize on a client's treatment motivation early on which may serve to improve treatment retention and therapeutic outcomes. © 2014 Wiley Periodicals, Inc.

Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314

PubMed Central

Puopolo, Michelino; Binshtok, Alexander M.; Yao, Gui-Lan; Oh, Seog Bae; Woolf, Clifford J.

2013-01-01

QX-314 (N-ethyl-lidocaine) is a cationic lidocaine derivative that blocks voltage-dependent sodium channels when applied internally to axons or neuronal cell bodies. Coapplication of external QX-314 with the transient receptor potential vanilloid 1 protein (TRPV1) agonist capsaicin produces long-lasting sodium channel inhibition in TRPV1-expressing neurons, suggestive of QX-314 entry into the neurons. We asked whether QX-314 entry occurs directly through TRPV1 channels or through a different pathway (e.g., pannexin channels) activated downstream of TRPV1 and whether QX-314 entry requires the phenomenon of “pore dilation” previously reported for TRPV1. With external solutions containing 10 or 20 mM QX-314 as the only cation, inward currents were activated by stimulation of both heterologously expressed and native TRPV1 channels in rat dorsal root ganglion neurons. QX-314-mediated inward current did not require pore dilation, as it activated within several seconds and in parallel with Cs-mediated outward current, with a reversal potential consistent with PQX-314/PCs = 0.12. QX-314-mediated current was no different when TRPV1 channels were expressed in C6 glioma cells, which lack expression of pannexin channels. Rapid addition of QX-314 to physiological external solutions produced instant partial inhibition of inward currents carried by sodium ions, suggesting that QX-314 is a permeant blocker. Maintained coapplication of QX-314 with capsaicin produced slowly developing reduction of outward currents carried by internal Cs, consistent with intracellular accumulation of QX-314 to concentrations of 50–100 μM. We conclude that QX-314 is directly permeant in the “standard” pore formed by TRPV1 channels and does not require either pore dilation or activation of additional downstream channels for entry. PMID:23303863

Studies of Ebola Virus Glycoprotein-Mediated Entry and Fusion by Using Pseudotyped Human Immunodeficiency Virus Type 1 Virions: Involvement of Cytoskeletal Proteins and Enhancement by Tumor Necrosis Factor Alpha

PubMed Central

Yonezawa, Akihito; Cavrois, Marielle; Greene, Warner C.

2005-01-01

The Ebola filoviruses are aggressive pathogens that cause severe and often lethal hemorrhagic fever syndromes in humans and nonhuman primates. To date, no effective therapies have been identified. To analyze the entry and fusion properties of Ebola virus, we adapted a human immunodeficiency virus type 1 (HIV-1) virion-based fusion assay by substituting Ebola virus glycoprotein (GP) for the HIV-1 envelope. Fusion was detected by cleavage of the fluorogenic substrate CCF2 by β-lactamase-Vpr incorporated into virions and released as a result of virion fusion. Entry and fusion induced by the Ebola virus GP occurred with much slower kinetics than with vesicular stomatitis virus G protein (VSV-G) and were blocked by depletion of membrane cholesterol and by inhibition of vesicular acidification with bafilomycin A1. These properties confirmed earlier studies and validated the assay for exploring other properties of Ebola virus GP-mediated entry and fusion. Entry and fusion of Ebola virus GP pseudotypes, but not VSV-G or HIV-1 Env pseudotypes, were impaired in the presence of the microtubule-disrupting agent nocodazole but were enhanced in the presence of the microtubule-stabilizing agent paclitaxel (Taxol). Agents that impaired microfilament function, including cytochalasin B, cytochalasin D, latrunculin A, and jasplakinolide, also inhibited Ebola virus GP-mediated entry and fusion. Together, these findings suggest that both microtubules and microfilaments may play a role in the effective trafficking of vesicles containing Ebola virions from the cell surface to the appropriate acidified vesicular compartment where fusion occurs. In terms of Ebola virus GP-mediated entry and fusion to various target cells, primary macrophages proved highly sensitive, while monocytes from the same donors displayed greatly reduced levels of entry and fusion. We further observed that tumor necrosis factor alpha, which is released by Ebola virus-infected monocytes/macrophages, enhanced Ebola virus GP-mediated entry and fusion to human umbilical vein endothelial cells. Thus, Ebola virus infection of one target cell may induce biological changes that facilitate infection of secondary target cells that play a key role in filovirus pathogenesis. Finally, these studies indicate that pseudotyping in the HIV-1 virion-based fusion assay may be a valuable approach to the study of entry and fusion properties mediated through the envelopes of other viral pathogens. PMID:15613320

Risk Factors and Neuropsychological Recovery in Clients with Alcohol Use Disorders Who Were Exposed to Different Treatments

ERIC Educational Resources Information Center

Bates, Marsha E.; Barry, Danielle; Labouvie, Erich W.; Fals-Stewart, William; Voelbel, Gerald; Buckman, Jennifer F.

2004-01-01

Risk covariates of neuropsychological ability (NA) at treatment entry and neuropsychological recovery (NR) across 15 months were examined and replicated in 2 samples (Ns = 952 and 774) from Project MATCH, a multisite study of alcoholism treatments. NA at treatment entry was associated with age, education, and other covariates. Statistically…

The School Entry Gap: Socioeconomic, Family, and Health Factors Associated with Children's School Readiness to Learn

ERIC Educational Resources Information Center

Janus, Magdalena; Duku, Eric

2007-01-01

Notwithstanding the constant debate in the scientific and policy literature on the precise meaning of school readiness, research consistently demonstrates a wide variation between groups of children resulting in a gap at school entry. Recently, the teacher-completed Early Development Instrument (EDI), a new measure of children's school readiness…

20 CFR 645.420 - What factors will be used in measuring State performance?

Code of Federal Regulations, 2010 CFR

2010-04-01

... measure State performance: (1) Job entry rate as measured by the proportion of WtW participants who enter either subsidized employment or unsubsidized employment, (2) Substantive job entry rate as measured by... employment of 30 hours or more per week, (3) Retention as measured by the proportion of WtW participants who...

Retail Merchandising Competencies: A Comparison of Perceptions among Entry-Level Managers, Educators, Recruiters, and Students.

ERIC Educational Resources Information Center

McCuaig, Shauna; And Others

1996-01-01

Responses from 38 of 184 retailing graduates, 24 of 111 recruiters in the apparel field, 58 of 200 retail merchandising educators, and 45 of 47 current students found that differences in their ratings of the importance of 53 competencies for entry workers centered on three factors: merchandising, leadership, and monitoring. (SK)

A Comparison of Factors Related to University Students' Learning: College-Transfer and Direct-Entry from High School Students

ERIC Educational Resources Information Center

Acai, Anita; Newton, Genevieve

2015-01-01

Articulation agreements between colleges and universities, whereby students with two-year college diplomas can receive advancement toward a four-year university degree, are provincially mandated in some Canadian provinces and highly encouraged in others. In this study, we compared learning in college transfer and direct-entry from high school…

GRP78 Is an Important Host Factor for Japanese Encephalitis Virus Entry and Replication in Mammalian Cells.

PubMed

Nain, Minu; Mukherjee, Sriparna; Karmakar, Sonali Porey; Paton, Adrienne W; Paton, James C; Abdin, M Z; Basu, Anirban; Kalia, Manjula; Vrati, Sudhanshu

2017-03-15

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of viral encephalitis in Southeast Asia with potential to become a global pathogen. Here, we identify glucose-regulated protein 78 (GRP78) as an important host protein for virus entry and replication. Using the plasma membrane fractions from mouse neuronal (Neuro2a) cells, mass spectroscopy analysis identified GRP78 as a protein interacting with recombinant JEV envelope protein domain III. GRP78 was found to be expressed on the plasma membranes of Neuro2a cells, mouse primary neurons, and human epithelial Huh-7 cells. Antibodies against GRP78 significantly inhibited JEV entry in all three cell types, suggesting an important role of the protein in virus entry. Depletion of GRP78 by small interfering RNA (siRNA) significantly blocked JEV entry into Neuro2a cells, further supporting its role in virus uptake. Immunofluorescence studies showed extensive colocalization of GRP78 with JEV envelope protein in virus-infected cells. This interaction was also confirmed by immunoprecipitation studies. Additionally, GRP78 was shown to have an important role in JEV replication, as treatment of cells post-virus entry with subtilase cytotoxin that specifically cleaved GRP78 led to a substantial reduction in viral RNA replication and protein synthesis, resulting in significantly reduced extracellular virus titers. Our results indicate that GRP78, an endoplasmic reticulum chaperon of the HSP70 family, is a novel host factor involved at multiple steps of the JEV life cycle and could be a potential therapeutic target. IMPORTANCE Recent years have seen a rapid spread of mosquito-borne diseases caused by flaviviruses. The flavivirus family includes West Nile, dengue, Japanese encephalitis, and Zika viruses, which are major threats to public health with potential to become global pathogens. JEV is the major cause of viral encephalitis in several parts of Southeast Asia, affecting a predominantly pediatric population with a high mortality rate. This study is focused on identification of crucial host factors that could be targeted to cripple virus infection and ultimately lead to development of effective antivirals. We have identified a cellular protein, GRP78, that plays a dual role in virus entry and virus replication, two crucial steps of the virus life cycle, and thus is a novel host factor that could be a potential therapeutic target. Copyright © 2017 American Society for Microbiology.

Factors associated with dropout among patients in opioid maintenance treatment (OMT) and predictors of re-entry. A national registry-based study.

PubMed

Bukten, Anne; Skurtveit, Svetlana; Waal, Helge; Clausen, Thomas

2014-10-01

Retention in treatment is often highlighted as one of the key indicators of success in opioid maintenance treatment (OMT). To identify factors associated with long-term retention in opioid maintenance treatment and to analyse predictors of subsequent treatment episodes. Treatment retention and re-entry were examined for a national cohort of patients admitted to OMT in Norway in the period 1997-2003. Multivariate Cox regression models were used to investigate factors associated with treatment dropout 18months after treatment entry. The 18month retention rate among patients admitted to OMT in Norway (n=2431) was 65.8% (n=1599). Dropout from OMT within 18months was associated with younger age (HR 0.97 [0.96-0.98]), high levels of general pre-treatment criminal offences (HR 1.66 [1.32-2.09]) and having drug-related offences during the 30days prior to dropout (HR 1.80 [1.36-2.38]). Of the patients who dropped out (n=832), 42.7% (n=355) were re-engaged in subsequent treatment episodes. Pre-treatment criminal offences were associated with increased odds for treatment re-entry, whereas being younger and having drug-related offences during the first OMT episode were associated with lower odds for re-engagement in OMT. Gender was not associated with treatment dropout and re-entry. High levels of pre-treatment criminal offences and drug offences during the 30days prior to dropout were associated with treatment dropout. Efforts to increase support services to these patients may contribute to higher rates of retention in OMT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Modeling the Association Between Home Care Service Use and Entry Into Residential Aged Care: A Cohort Study Using Routinely Collected Data.

PubMed

Jorgensen, Mikaela; Siette, Joyce; Georgiou, Andrew; Warland, Andrew; Westbrook, Johanna

2018-02-01

To examine home care service-related and person-based factors associated with time to entry into permanent residential aged care. Longitudinal cohort study using routinely collected client management data. A large aged care service provider in New South Wales and the Australian Capital Territory, Australia. A total of 1116 people aged 60 years and older who commenced home care services for higher-level needs between July 1, 2015 and June 30, 2016. Survival analysis methods were used to examine service-related and person-based factors that were associated with time between first home care service and entry into permanent residential aged care. Predictors included service hours per week, combination of service types, demographics, needs, hospital leave, and change in care level. Cluster analysis was used to determine patterns of types of services used. By December 31, 2016, 21.1% of people using home care services had entered into permanent residential care (n = 235). After adjusting for significant factors such as age and care needs, each hour of service received per week was associated with a 6% lower risk of entry into residential care (hazard ratio = 0.94, 95% confidence interval 0.90-0.98). People who were predominant users of social support services, those with an identified carer, and those born in a non-main English-speaking country also remained in their own homes for longer. Greater volume of home care services was associated with significantly delayed entry into permanent residential care. This study provides much-needed evidence about service outcomes that could be used to inform older adults' care choices. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

X-38 V201 Avionics Architecture

NASA Technical Reports Server (NTRS)

Bedos, Thierry; Anderson, Brian L.

1999-01-01

The X-38 is an experimental NASA project developing a core human capable spacecraft at a fraction of the cost of any previous human rated vehicle. The first operational derivative developed from the X-38 program will be the International Space Station (ISS) Crew Return Vehicle (CRV). Although the current X-38 vehicles are designed as re-entry vehicles only, the option exists to modify the vehicle for uses as an upward vehicle launched from an expendable launch vehicle or from the X-33 operational derivative. The Operational CRV, that will be derived from the X-38 spaceflight vehicle, will provide an emergency return capability from the International Space Station (ISS). The spacecraft can hold a crew of up to seven inside a pressurized cabin. The CRV is passively delivered to ISS, stays up to three year on-orbit attached to ISS in a passive mode with periodic functional checkout, before separation from ISS, de-orbit, entry and landing. The X-38 Vehicle 201 (V201) is being developed at NASA/JSC to demonstrate key technologies associated with the development of the CRV design. The X-38 flight test will validate the low cost development concept by demonstrating the entire station departure, re-entry, guidance and landing portions of the CRV mission. All new technologies and subsystems proposed for CRV will be validated during either the on orbit checkout or flight phases of the X-38 space flight test. The X-38 subsystems are required to be similar to those subsystems required for the CRV to the greatest extent possible. In many cases, the subsystems are identical to those that will be utilized on the Operational CRV.

Factors affecting the entry of for-profit providers into a price regulated market for formal long-term care services: a case study from Japan.

PubMed

Tokunaga, Mutsumi; Hashimoto, Hideki

2013-01-01

While the distinct behaviors of for-profit and non-profit providers in the healthcare market have been compared in the economic literature, their choices regarding market entry and exit have only recently been debated. Since 2000, when public Long-Term Care Insurance was introduced in Japan, for-profit providers have been able to provide formal long-term homecare services. The aim of this study is to determine which factors have affected market entry of for-profit providers under price regulation and in competition with existing non-profit providers. We used nation-wide panel data from 2002 to 2010, aggregated at the level of local public insurers (n = 1557), a basic area unit of service provision. The number of for-profit providers per elderly population in the area unit was regressed against factors related to local demand and service costs using first-difference linear regression, a fixed effects model, and Tobit regression for robustness checking. Results showed that demand (the number of eligible care recipients) and cost factors (population density and minimum wage) significantly influenced for-profit providers' choice of market entry. These findings indicate that for-profit providers will strategically choose a local market for maximizing profit. We believe that price regulation should be redesigned to incorporate quality of care and market conditions, regardless of the profit status of the providers, to ensure equal access to efficient delivery of long-term care across all regions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Romance, recovery & community re-entry for criminal justice involved women: Conceptualizing and measuring intimate relationship factors and power

PubMed Central

Walt, Lisa C.; Hunter, Bronwyn; Salina, Doreen; Jason, Leonard

2015-01-01

Researchers have suggested that interpersonal relationships, particularly romantic relationships, may influence women’s attempts at substance abuse recovery and community re-entry after criminal justice system involvement. The present paper evaluates relational and power theories to conceptualize the influence of romantic partner and romantic relationship qualities on pathways in and out of substance abuse and crime. The paper then combines these conceptualizations with a complementary empirical analysis to describe an ongoing research project that longitudinally investigates these relational and power driven factors on women’s substance abuse recovery and community re-entry success among former substance abusing, recently criminally involved women. This paper is designed to encourage the integration of theory and empirical analysis by detailing how each of these concepts are operationalized and measured. Future research and clinical implications are also discussed. PMID:25750487

Role of mannose-6-phosphate receptors in herpes simplex virus entry into cells and cell-to-cell transmission.

PubMed Central

Brunetti, C R; Burke, R L; Hoflack, B; Ludwig, T; Dingwell, K S; Johnson, D C

1995-01-01

Herpes simplex virus (HSV) glycoprotein D (gD) is essential for virus entry into cells, is modified with mannose-6-phosphate (M-6-P), and binds to both the 275-kDa M-6-P receptor (MPR) and the 46-kDa MPR (C. R. Brunetti, R. L. Burke, S. Kornfeld, W. Gregory, K. S. Dingwell, F. Masiarz, and D. C. Johnson, J. Biol. Chem. 269:17067-17074, 1994). Since MPRs are found on the surfaces of mammalian cells, we tested the hypothesis that MPRs could serve as receptors for HSV during virus entry into cells. A soluble form of the 275-kDa MPR, derived from fetal bovine serum, inhibited HSV plaques on monkey Vero cells, as did polyclonal rabbit anti-MPR antibodies. In addition, the number and size of HSV plaques were reduced when cells were treated with bovine serum albumin conjugated with pentamannose-phosphate (PM-PO4-BSA), a bulky ligand which can serve as a high-affinity ligand for MPRs. These data imply that HSV can use MPRs to enter cells; however, other molecules must also serve as receptors for HSV because a reasonable fraction of virus could enter cells treated with even the highest concentrations of these inhibitors. Consistent with the possibility that there are other receptors, HSV produced the same number of plaques on MPR-deficient mouse fibroblasts as were produced on normal mouse fibroblasts, but there was no inhibition with PM-PO4-BSA with either of these embryonic mouse cells. Together, these results demonstrate that HSV does not rely solely on MPRs to enter cells, although MPRs apparently play some role in virus entry into some cell types and, perhaps, act as one of a number of cell surface molecules that can facilitate entry. We also found that HSV produced small plaques on human fibroblasts derived from patients with pseudo-Hurler's polydystrophy, cells in which glycoproteins are not modified with M-6-P residues and yet production of infectious HSV particles was not altered in the pseudo-Hurler cells. In addition, HSV plaque size was reduced by PM-PO4-BSA; therefore, it appears that M-6-P residues and MPRs are required for efficient transmission of HSV between cells, a process which differs in some respects from entry of exogenous virus particles. PMID:7745699

Entry, Descent, and Landing technological barriers and crewed MARS vehicle performance analysis

NASA Astrophysics Data System (ADS)

Subrahmanyam, Prabhakar; Rasky, Daniel

2017-05-01

Mars has been explored historically only by robotic crafts, but a crewed mission encompasses several new engineering challenges - high ballistic coefficient entry, hypersonic decelerators, guided entry for reaching intended destinations within acceptable margins for error in the landing ellipse, and payload mass are all critical factors for evaluation. A comprehensive EDL parametric analysis has been conducted in support of a high mass landing architecture by evaluating three types of vehicles -70° Sphere Cone, Ellipsled and SpaceX hybrid architecture called Red Dragon as potential candidate options for crewed entry vehicles. Aerocapture at the Martian orbit of about 400 km and subsequent Entry-from-orbit scenarios were investigated at velocities of 6.75 km/s and 4 km/s respectively. A study on aerocapture corridor over a range of entry velocities (6-9 km/s) suggests that a hypersonic L/D of 0.3 is sufficient for a Martian aerocapture. Parametric studies conducted by varying aeroshell diameters from 10 m to 15 m for several entry masses up to 150 mt are summarized and results reveal that vehicles with entry masses in the range of about 40-80 mt are capable of delivering cargo with a mass on the order of 5-20 mt. For vehicles with an entry mass of 20 mt to 80 mt, probabilistic Monte Carlo analysis of 5000 cases for each vehicle were run to determine the final landing ellipse and to quantify the statistical uncertainties associated with the trajectory and attitude conditions during atmospheric entry. Strategies and current technological challenges for a human rated Entry, Descent, and Landing to the Martian surface are presented in this study.

Prevalence, serotype diversity, and antimicrobial resistance of Salmonella in imported shipments of spice offered for entry to the United States, FY2007-FY2009.

PubMed

Van Doren, Jane M; Kleinmeier, Daria; Hammack, Thomas S; Westerman, Ann

2013-06-01

In response to increased concerns about spice safety, the U.S. FDA initiated research to characterize the prevalence of Salmonella in imported spices. Shipments of imported spices offered for entry to the United Sates were sampled during the fiscal years 2007-2009. The mean shipment prevalence for Salmonella was 0.066 (95% CI 0.057-0.076). A wide diversity of Salmonella serotypes was isolated from spices; no single serotype constituted more than 7% of the isolates. A small percentage of spice shipments were contaminated with antimicrobial-resistant Salmonella strains (8.3%). Trends in shipment prevalence for Salmonella associated with spice properties, extent of processing, and export country, were examined. A larger proportion of shipments of spices derived from fruit/seeds or leaves of plants were contaminated than those derived from the bark/flower of spice plants. Salmonella prevalence was larger for shipments of ground/cracked capsicum and coriander than for shipments of their whole spice counterparts. No difference in prevalence was observed between shipments of spice blends and non-blended spices. Some shipments reported to have been subjected to a pathogen reduction treatment prior to being offered for U.S. entry were found contaminated. Statistical differences in Salmonella shipment prevalence were also identified on the basis of export country. Published by Elsevier Ltd.

Using CO2:CO Correlations to Improve Inverse Analyses of Carbon Fluxes

NASA Technical Reports Server (NTRS)

Palmer, Paul I.; Suntharalingam, Parvadha; Jones, Dylan B. A.; Jacob, Daniel J.; Streets, David G.; Fu, Qingyan; Vay, Stephanie A.; Sachse, Glen W.

2006-01-01

Observed correlations between atmospheric concentrations of CO2 and CO represent potentially powerful information for improving CO2 surface flux estimates through coupled CO2-CO inverse analyses. We explore the value of these correlations in improving estimates of regional CO2 fluxes in east Asia by using aircraft observations of CO2 and CO from the TRACE-P campaign over the NW Pacific in March 2001. Our inverse model uses regional CO2 and CO surface fluxes as the state vector, separating biospheric and combustion contributions to CO2. CO2-CO error correlation coefficients are included in the inversion as off-diagonal entries in the a priori and observation error covariance matrices. We derive error correlations in a priori combustion source estimates of CO2 and CO by propagating error estimates of fuel consumption rates and emission factors. However, we find that these correlations are weak because CO source uncertainties are mostly determined by emission factors. Observed correlations between atmospheric CO2 and CO concentrations imply corresponding error correlations in the chemical transport model used as the forward model for the inversion. These error correlations in excess of 0.7, as derived from the TRACE-P data, enable a coupled CO2-CO inversion to achieve significant improvement over a CO2-only inversion for quantifying regional fluxes of CO2.

A generalized preferential attachment model for business firms growth rates. II. Mathematical treatment

NASA Astrophysics Data System (ADS)

Buldyrev, S. V.; Pammolli, F.; Riccaboni, M.; Yamasaki, K.; Fu, D.-F.; Matia, K.; Stanley, H. E.

2007-05-01

We present a preferential attachment growth model to obtain the distribution P(K) of number of units K in the classes which may represent business firms or other socio-economic entities. We found that P(K) is described in its central part by a power law with an exponent ϕ = 2+b/(1-b) which depends on the probability of entry of new classes, b. In a particular problem of city population this distribution is equivalent to the well known Zipf law. In the absence of the new classes entry, the distribution P(K) is exponential. Using analytical form of P(K) and assuming proportional growth for units, we derive P(g), the distribution of business firm growth rates. The model predicts that P(g) has a Laplacian cusp in the central part and asymptotic power-law tails with an exponent ζ = 3. We test the analytical expressions derived using heuristic arguments by simulations. The model might also explain the size-variance relationship of the firm growth rates.

Functional Equivalence Acceptance Testing of FUN3D for Entry Descent and Landing Applications

NASA Technical Reports Server (NTRS)

Gnoffo, Peter A.; Wood, William A.; Kleb, William L.; Alter, Stephen J.; Glass, Christopher E.; Padilla, Jose F.; Hammond, Dana P.; White, Jeffery A.

2013-01-01

The functional equivalence of the unstructured grid code FUN3D to the the structured grid code LAURA (Langley Aerothermodynamic Upwind Relaxation Algorithm) is documented for applications of interest to the Entry, Descent, and Landing (EDL) community. Examples from an existing suite of regression tests are used to demonstrate the functional equivalence, encompassing various thermochemical models and vehicle configurations. Algorithm modifications required for the node-based unstructured grid code (FUN3D) to reproduce functionality of the cell-centered structured code (LAURA) are also documented. Challenges associated with computation on tetrahedral grids versus computation on structured-grid derived hexahedral systems are discussed.

24-Month-Old Children with Larger Oral Vocabularies Display Greater Academic and Behavioral Functioning at Kindergarten Entry

ERIC Educational Resources Information Center

Morgan, Paul L.; Farkas, George; Hillemeier, Marianne M.; Hammer, Carol Scheffner; Maczuga, Steve

2015-01-01

Data were analyzed from a population-based, longitudinal sample of 8,650 U.S. children to (a) identify factors associated with or predictive of oral vocabulary size at 24 months of age and (b) evaluate whether oral vocabulary size is uniquely predictive of academic and behavioral functioning at kindergarten entry. Children from higher…

An Exploration of Factors Reducing Recidivism Rates of Formerly Incarcerated Youth with Disabilities Participating in a Re-Entry Intervention

ERIC Educational Resources Information Center

Unruh, Deanne K.; Gau, Jeff M.; Waintrup, Miriam G.

2009-01-01

Juvenile offenders are costly to our society in terms of the monetary and social expenditures from the legal system, victims' person costs, and incarceration. The re-entry and community reintegration outcomes for formerly incarcerated youth with a disabling condition are bleak compared to peers without disabilities. In this study, we examined the…

Child Temperament and Home-Based Parent Involvement at Kindergarten Entry: Evidence from a Low-Income, Urban Sample

ERIC Educational Resources Information Center

Han, Jinjoo; O'Connor, Erin E.; McCormick, Meghan P.; McClowry, Sandee G.

2017-01-01

Research Findings: Home-based involvement--defined as the actions parents take to promote children's learning outside of school--is often the most efficient way for low-income parents to be involved with their children's education. However, there is limited research examining the factors predicting home-based involvement at kindergarten entry for…

Student Success in Entry Level Modules at the University of Kwazulu-Natal

ERIC Educational Resources Information Center

Zewotir, T.; North, D.; Murray, M.

2011-01-01

The University of KwaZulu-Natal is now six years post merger--time to reflect as the institution is now well settled. Modules are offered on multiple campuses, at various levels, ranging from entry level modules through to Ph.D. studies. This article attempts to identify the factors that lead to the successful progression of students to higher…

Distinct Trajectories of Separation Anxiety in the Preschool Years: Persistence at School Entry and Early-Life Associated Factors

ERIC Educational Resources Information Center

Battaglia, Marco; Touchette, Évelyne; Garon-Carrier, Gabrielle; Dionne, Ginette; Côté, Sylvana M.; Vitaro, Frank; Tremblay, Richard E.; Boivin, Michel

2016-01-01

Background: Little is known about how children differ in the onset and evolution of separation anxiety (SA) symptoms during the preschool years, and how SA develops into separation anxiety disorder. In a large, representative population-based sample, we investigated the developmental trajectories of SA symptoms from infancy to school entry, their…

Peer Relationships of Deaf Children with Cochlear Implants: Predictors of Peer Entry and Peer Interaction Success

ERIC Educational Resources Information Center

Martin, Daniela; Bat-Chava, Yael; Lalwani, Anil; Waltzman, Susan B.

2011-01-01

This study investigated factors that affect the development of positive peer relationships among deaf children with cochlear implants. Ten 5- to 6-year-old deaf children with implants were observed under conditions varying peer context difficulty in a Peer Entry task. Results revealed better outcomes for deaf children interacting in one-on-one…

Study of Enlistment Test Scores and Other Attrition Factors from the Navy’s Delayed Entry Program

DTIC Science & Technology

2009-03-01

fiscal years 1999 through 2008 and were provided by the Defense Manpower Data Center (DMDC). Men and women were analyzed separately because of...years 1999 through 2008 and were provided by the Defense Manpower Data Center (DMDC). Men and women were analyzed separately because of historic...ANALYSIS OF DELAYED ENTRY PROGRAM ATTRITION BY WOMEN

A Longitudinal Study of Child Maltreatment and Mental Health Predictors of Admission to Psychiatric Residential Treatment Facilities

PubMed Central

Rose, Roderick A.; Lanier, Paul

2017-01-01

The child welfare system is an access point for children’s mental health services. Psychiatric residential treatment facilities (PRTFs) are the most restrictive, and most expensive setting for children to receive long-term care. Given the high rates of behavioral health concerns among maltreated children in out-of-home care, research is needed to examine the factors that predict entry in PRTFs among children investigated for maltreatment. This exploratory study used cross-sector administrative records linked across multiple systems, including child welfare records and Medicaid claims, from a single state over a five-year period (n = 105,982). Cox proportional hazards modeling was used to predict entry into a PRTF. After controlling for many factors, PRTF entry was predicted by diagnosis code indicating a trauma-related condition, antipsychotic medication prescriptions, and entry into lower levels of out-of-home care, supporting the view that youth are admitted to PRTFs largely due to clinical need. However, PRTF admission is also associated with characteristics of their experiences with the social service system, primarily foster care placement stability and permanency. Implications for practice and research are discussed. PMID:28956825

Medicare risk contracting: Determinants of market entry

PubMed Central

Porell, Frank W.; Wallack, Stanley S.

1990-01-01

The Tax Equity and Fiscal Responsibility Act (TEFRA) of 1982 made it more attractive for health maintenance organizations (HMOs) and other competitive medical plans to enter into risk contracts with Medicare. Since the start of the TEFRA program in April 1985, more than 160 HMOs have had risk contracts with Medicare under the program. An investigation of factors associated with TEFRA risk-market entry at the end of 1986 revealed that high adjusted average per capita cost payment levels, prior Medicare cost-contract experience, and prior Federal qualification were the most important factors distinguishing market entrants from nonentrants. PMID:10113567

Internal velocity factors

NASA Technical Reports Server (NTRS)

Cathcart, J. R.; Frank, A. J.; Massaglia, J. L.

1968-01-01

Computer program analyzes the entries and planetary trajectories of space vehicles. It obtains the equivalence of altitude and flight path angle, respectively, to acceleration load factor with respect to velocity for a given inertial velocity.

9 CFR 95.5 - Untanned hides and skins and bird trophies; requirements for entry.

Code of Federal Regulations, 2014 CFR

2014-01-01

... negligible risk for BSE in which there has been at least one indigenous case of BSE; or (ii) Derived from ruminants that were in a region of negligible risk for BSE in which there has been at least one indigenous...

The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry.

PubMed

Meertens, Laurent; Carnec, Xavier; Lecoin, Manuel Perera; Ramdasi, Rasika; Guivel-Benhassine, Florence; Lew, Erin; Lemke, Greg; Schwartz, Olivier; Amara, Ali

2012-10-18

Dengue viruses (DVs) are responsible for the most medically relevant arboviral diseases. However, the molecular interactions mediating DV entry are poorly understood. We determined that TIM and TAM proteins, two receptor families that mediate the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, serve as DV entry factors. Cells poorly susceptible to DV are robustly infected after ectopic expression of TIM or TAM receptors. Conversely, DV infection of susceptible cells is inhibited by anti-TIM or anti-TAM antibodies or knockdown of TIM and TAM expression. TIM receptors facilitate DV entry by directly interacting with virion-associated PtdSer. TAM-mediated infection relies on indirect DV recognition, in which the TAM ligand Gas6 acts as a bridging molecule by binding to PtdSer within the virion. This dual mode of virus recognition by TIM and TAM receptors reveals how DVs usurp the apoptotic cell clearance pathway for infectious entry. Copyright © 2012 Elsevier Inc. All rights reserved.

Lipopolysaccharide structure impacts the entry kinetics of bacterial outer membrane vesicles into host cells

PubMed Central

Hadis, Mohammed; Alderwick, Luke

2017-01-01

Outer membrane vesicles are nano-sized microvesicles shed from the outer membrane of Gram-negative bacteria and play important roles in immune priming and disease pathogenesis. However, our current mechanistic understanding of vesicle-host cell interactions is limited by a lack of methods to study the rapid kinetics of vesicle entry and cargo delivery to host cells. Here, we describe a highly sensitive method to study the kinetics of vesicle entry into host cells in real-time using a genetically encoded, vesicle-targeted probe. We found that the route of vesicular uptake, and thus entry kinetics and efficiency, are shaped by bacterial cell wall composition. The presence of lipopolysaccharide O antigen enables vesicles to bypass clathrin-mediated endocytosis, which enhances both their entry rate and efficiency into host cells. Collectively, our findings highlight the composition of the bacterial cell wall as a major determinant of secretion-independent delivery of virulence factors during Gram-negative infections. PMID:29186191

A hypersonic vehicle approach to planetary exploration

NASA Technical Reports Server (NTRS)

Murbach, Marcus S.

1993-01-01

An enhanced Mars network class mission using a lifting hypersonic entry vehicle is proposed. The basic vehicle, derived from a mature hypersonic flight system called SWERVE, offers several advantages over more conventional low L/D or ballistic entry systems. The proposed vehicle has greatly improved lateral and cross range capability (e.g., it is capable of reaching the polar regions during less than optimal mission opportunities), is not limited to surface target areas of low elevation, and is less susceptible to problems caused by Martian dust storms. Further, the integrated vehicle has attractive deployment features and allows for a much improved evolutionary path to larger vehicles with greater science capability. Analysis of the vehicle is aided by the development of a Mars Hypersonic Flight Simulator from which flight trajectories are obtained. Atmospheric entry performance of the baseline vehicle is improved by a deceleration skirt and transpiration cooling system which significantly reduce TPS (Thermal Protection System) and flight battery mass. The use of the vehicle is also attractive in that the maturity of the flight systems make it cost-competitive with the development of a conventional low L/D entry system. Finally, the potential application of similar vehicles to other planetary missions is discussed.

Platelet activation suppresses HIV-1 infection of T cells

PubMed Central

2013-01-01

Background Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. Results We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. Conclusions Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens. PMID:23634812

Platelet activation suppresses HIV-1 infection of T cells.

PubMed

Solomon Tsegaye, Theodros; Gnirß, Kerstin; Rahe-Meyer, Niels; Kiene, Miriam; Krämer-Kühl, Annika; Behrens, Georg; Münch, Jan; Pöhlmann, Stefan

2013-05-01

Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.

Hepatitis C Virus Strain-Dependent Usage of Apolipoprotein E Modulates Assembly Efficiency and Specific Infectivity of Secreted Virions.

PubMed

Weller, Romy; Hueging, Kathrin; Brown, Richard J P; Todt, Daniel; Joecks, Sebastian; Vondran, Florian W R; Pietschmann, Thomas

2017-09-15

Hepatitis C virus (HCV) is extraordinarily diverse and uses entry factors in a strain-specific manner. Virus particles associate with lipoproteins, and apolipoprotein E (ApoE) is critical for HCV assembly and infectivity. However, whether ApoE dependency is common to all HCV genotypes remains unknown. Therefore, we compared the roles of ApoE utilizing 10 virus strains from genotypes 1 through 7. ApoA and ApoC also support HCV assembly, so they may contribute to virus production in a strain-dependent fashion. Transcriptome sequencing (RNA-seq) revealed abundant coexpression of ApoE, ApoB, ApoA1, ApoA2, ApoC1, ApoC2, and ApoC3 in primary hepatocytes and in Huh-7.5 cells. Virus production was examined in Huh-7.5 cells with and without ApoE expression and in 293T cells where individual apolipoproteins (ApoE1, -E2, -E3, -A1, -A2, -C1, and -C3) were provided in trans All strains were strictly ApoE dependent. However, ApoE involvement in virus production was strain and cell type specific, because some HCV strains poorly produced infectious virus in ApoE-expressing 293T cells and because ApoE knockout differentially affected virus production of HCV strains in Huh-7.5 cells. ApoE allelic isoforms (ApoE2, -E3, and -E4) complemented virus production of HCV strains to comparable degrees. All tested strains assembled infectious progeny with ApoE in preference to other exchangeable apolipoproteins (ApoA1, -A2, -C1, and -C3). The specific infectivity of HCV particles was similar for 293T- and Huh-7.5-derived particles for most strains; however, it differed by more than 100-fold in some viruses. Collectively, this study reveals strain-dependent and host cell-dependent use of ApoE during HCV assembly. These differences relate to the efficacy of virus production and also to the properties of released virus particles and therefore govern viral fitness at the level of assembly and cell entry. IMPORTANCE Chronic HCV infections are a major cause of liver disease. HCV is highly variable, and strain-specific determinants modulate the response to antiviral therapy, the natural course of infection, and cell entry factor usage. Here we explored whether host factor dependency of HCV in particle assembly is modulated by strain-dependent viral properties. We showed that all examined HCV strains, which represent all seven known genotypes, rely on ApoE expression for assembly of infectious progeny. However, the degree of ApoE dependence is modulated in a strain-specific and cell type-dependent manner. This indicates that HCV strains differ in their assembly properties and host factor usage during assembly of infectious progeny. Importantly, these differences relate not only to the efficiency of virus production and release but also to the infectiousness of virus particles. Thus, strain-dependent features of HCV modulate ApoE usage, with implications for virus fitness at the level of assembly and cell entry. Copyright © 2017 Weller et al.

Sol-gel derived C-SiC composites and protective coatings for sustained durability in the space environment

NASA Astrophysics Data System (ADS)

Haruvy, Yair; Liedtke, Volker

2003-09-01

Composites and coatings were produced via the fast sol-gel process of a mixture of alkoxysilane precursors. The composites were comprised of carbon fibers, fabrics, or their precursors as reinforcement, and sol-gel-derived silicon carbide as matrix, aiming at high-temperature stable ceramics that can be utilized for re-entry structures. The protective coatings were comprised of fluorine-rich sol-gel derived resins, which exhibit high flexibility and coherence to provide sustained ATOX protection necessary for LEO space-exposed elements. For producing the composites, the sol-gel-derived resin is cast onto the reinforcement fibers/fabrics mat (carbon or its precursors) to produce a 'green' composite that is being cured. The 'green' composite is converted into a C-SiC composite via a gradual heat-pressure process under inert atmosphere, during which the organic substituents on the silicon atoms undergo internal oxidative pyrolysis via the schematic reaction: (SiRO3/2)n -> SiC + CO2 + H2O. The composition of the resultant silicon-oxi-carbide is tailorable via modifying the composition of the sol-gel reactants. The reinforcement, when made of carbon precursors, is converted into carbon during the heat-and-pressure processing as well. The C-SiC composites thus derived exhibit superior thermal stability and comparable thermal conductivity, combined with good mechanical strength features and failure resistance, which render them greatly applicable for re-entry shielding, heat-exchange pipes, and the like. Fluorine rich sol-gel derived coatings were developed as well, via the use of HF rich sol-gel process. These coatings provide oxidation-protection via the silica formation process, together with flexibility that allows 18,000 repetitive folding of the coating without cracking.

Energy Factor Analysis for Gas Heat Pump Water Heaters

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

Gluesenkamp, Kyle R

2016-01-01

Gas heat pump water heaters (HPWHs) can improve water heating efficiency with zero GWP and zero ODP working fluids. The energy factor (EF) of a gas HPWH is sensitive to several factors. In this work, expressions are derived for EF of gas HPWHs, as a function of heat pump cycle COP, tank heat losses, burner efficiency, electrical draw, and effectiveness of supplemental heat exchangers. The expressions are used to investigate the sensitivity of EF to each parameter. EF is evaluated on a site energy basis (as used by the US DOE for rating water heater EF), and a primary energy-basismore » energy factor (PEF) is also defined and included. Typical ranges of values for the six parameters are given. For gas HPWHs, using typical ranges for component performance, EF will be 59 80% of the heat pump cycle thermal COP (for example, a COP of 1.60 may result in an EF of 0.94 1.28). Most of the reduction in COP is due to burner efficiency and tank heat losses. Gas-fired HPWHs are theoretically be capable of an EF of up to 1.7 (PEF of 1.6); while an EF of 1.1 1.3 (PEF of 1.0 1.1) is expected from an early market entry.« less

Kinetics of cellular uptake of viruses and nanoparticles via clathrin-mediated endocytosis

NASA Astrophysics Data System (ADS)

Banerjee, Anand; Berezhkovskii, Alexander; Nossal, Ralph

2016-02-01

Several viruses exploit clathrin-mediated endocytosis to gain entry into host cells. This process is also used extensively in biomedical applications to deliver nanoparticles (NPs) to diseased cells. The internalization of these nano-objects is controlled by the assembly of a clathrin-containing protein coat on the cytoplasmic side of the plasma membrane, which drives the invagination of the membrane and the formation of a cargo-containing endocytic vesicle. Current theoretical models of receptor-mediated endocytosis of viruses and NPs do not explicitly take coat assembly into consideration. In this paper we study cellular uptake of viruses and NPs with a focus on coat assembly. We characterize the internalization process by the mean time between the binding of a particle to the membrane and its entry into the cell. Using a coarse-grained model which maps the stochastic dynamics of coat formation onto a one-dimensional random walk, we derive an analytical formula for this quantity. A study of the dependence of the mean internalization time on NP size shows that there is an upper bound above which this time becomes extremely large, and an optimal size at which it attains a minimum. Our estimates of these sizes compare well with experimental data. We also study the sensitivity of the obtained results on coat parameters to identify factors which significantly affect the internalization kinetics.

A theoretical study of the initiation, maintenance and termination of gastric slow wave re-entry.

PubMed

Du, Peng; Paskaranandavadivel, Niranchan; O'Grady, Greg; Tang, Shou-Jiang; Cheng, Leo K

2015-12-01

Gastric slow wave dysrhythmias are associated with motility disorders. Periods of tachygastria associated with slow wave re-entry were recently recognized as one important dysrhythmia mechanism, but factors promoting and sustaining gastric re-entry are currently unknown. This study reports two experimental forms of gastric re-entry and presents a series of multi-scale models that define criteria for slow wave re-entry initiation, maintenance and termination. High-resolution electrical mapping was conducted in porcine and canine models and two spatiotemporal patterns of re-entrant activities were captured: single-loop rotor and double-loop figure-of-eight. Two separate multi-scale mathematical models were developed to reproduce the velocity and entrainment frequency of these experimental recordings. A single-pulse stimulus was used to invoke a rotor re-entry in the porcine model and a figure-of-eight re-entry in the canine model. In both cases, the simulated re-entrant activities were found to be perpetuated by tachygastria that was accompanied by a reduction in the propagation velocity in the re-entrant pathways. The simulated re-entrant activities were terminated by a single-pulse stimulus targeted at the tip of re-entrant wave, after which normal antegrade propagation was restored by the underlying intrinsic frequency gradient. (i) the stability of re-entry is regulated by stimulus timing, intrinsic frequency gradient and conductivity; (ii) tachygastria due to re-entry increases the frequency gradient while showing decreased propagation velocity; (iii) re-entry may be effectively terminated by a targeted stimulus at the core, allowing the intrinsic slow wave conduction system to re-establish itself. © The authors 2014. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

A theoretical study of the initiation, maintenance and termination of gastric slow wave re-entry

PubMed Central

Du, Peng; Paskaranandavadivel, Niranchan; O’Grady, Greg; Tang, Shou-Jiang; Cheng, Leo K.

2015-01-01

Gastric slow wave dysrhythmias are associated with motility disorders. Periods of tachygastria associated with slow wave re-entry were recently recognized as one important dysrhythmia mechanism, but factors promoting and sustaining gastric re-entry are currently unknown. This study reports two experimental forms of gastric re-entry and presents a series of multi-scale models that define criteria for slow wave re-entry initiation, maintenance and termination. High-resolution electrical mapping was conducted in porcine and canine models and two spatiotemporal patterns of re-entrant activities were captured: single-loop rotor and double-loop figure-of-eight. Two separate multi-scale mathematical models were developed to reproduce the velocity and entrainment frequency of these experimental recordings. A single-pulse stimulus was used to invoke a rotor re-entry in the porcine model and a figure-of-eight re-entry in the canine model. In both cases, the simulated re-entrant activities were found to be perpetuated by tachygastria that was accompanied by a reduction in the propagation velocity in the re-entrant pathways. The simulated re-entrant activities were terminated by a single-pulse stimulus targeted at the tip of re-entrant wave, after which normal antegrade propagation was restored by the underlying intrinsic frequency gradient. Main findings: (i) the stability of re-entry is regulated by stimulus timing, intrinsic frequency gradient and conductivity; (ii) tachygastria due to re-entry increases the frequency gradient while showing decreased propagation velocity; (iii) re-entry may be effectively terminated by a targeted stimulus at the core, allowing the intrinsic slow wave conduction system to re-establish itself. PMID:25552487

An Evaluation of Factors Influencing the Academic Self-concept, Self-esteem and Academic Stress for Direct and Re-entry Students in Higher Education.

ERIC Educational Resources Information Center

Michie, Frances; Glachan, Martin; Bray, Diane

2001-01-01

Examines the differences in the undergraduate student experience of direct and re-entry students focusing on undergraduate students (n=112). Used a questionnaire to gather data to investigate the impact of age, gender, past school experiences, and motivation for participating in higher education based on academic self-esteem, self-concept, and…

The Development of Children at Familial Risk for Dyslexia: Birth to Early School Age

ERIC Educational Resources Information Center

Lyytinen, Heikki; Aro, Mikko; Eklund, Kenneth; Erskine, Jane; Guttorm, Tomi; Laakso, Marja-Leena; Leppanen, Paavo H. T.; Lyytinen, Paula; Poikkeus, Anna-Maija; Richardson, Ulla; Torppa, Minna

2004-01-01

Children at risk for familial dyslexia (n = 107) and their controls (n = 93) have been followed from birth to school entry in the Jyvaskyla Longitudinal study of Dyslexia (JLD) on developmental factors linked to reading and dyslexia. At the point of school entry, the majority of the at-risk children displayed decoding ability that fell at least 1…

The Effect of Free Primary Education Policy on Late School Entry in Urban Primary Schools in Kenya

ERIC Educational Resources Information Center

Ngware, Moses W.; Oketch, Moses; Ezeh, Alex C.; Mutisya, Maurice

2013-01-01

Late school entry is driven by several factors, one of the key ones being the cost barrier to schooling. Policies such as free primary education (FPE) that advocate for universal coverage are therefore partly aimed at removing the cost barrier. The Kenyan Government, like many in sub-Saharan Africa (SSA), introduced FPE in 2003 with the aim of…

Health education and competency scale: Development and testing.

PubMed

Hwang, Huei-Lih; Kuo, Mei-Ling; Tu, Chin-Tang

2018-02-01

To develop a tool for measuring competency in conducting health education and to evaluate its psychometric properties in a population of entry-level nurses. Until now, no generic instrument has been developed specifically for measuring competency in health education, which is an essential competency for nurses. Existing scales are either insufficient for psychometric evaluation or are designed specifically for senior nurses. To evaluate curricula and courses designed for entry-level nurses, educators require an instrument for measuring improvement in core competency from baseline to determine whether the minimum level of ability has been achieved. Item development for the survey instrument used for data collection in this study was based on the results of a literature review. The self-evaluated Health Education Competency Scale developed in this study was used to survey 457 nursing students at two nursing schools and 165 clinical nurses at a medical centre in south Taiwan in 2016. The participants were randomly divided into two equal groups. One group was analysed by exploratory factor analysis with varimax rotation, and one group was analysed by confirmatory factor analysis. Factor analysis yielded a four-factor (assessment, pedagogy, motivation and empowerment) solution (18 items) that accounted for 75.9% of the variance. The total scale and subscales had good reliabilities and construct validity coefficients. For measuring competency in entry-level nurses, the Health Education Competency Scale had a good data fit and sound psychometric properties. The proposed scale can be used to assess health education competency for college nursing students and practising nurses. Furthermore, it can provide educators with valuable insight into the minimum competencies required for entry-level nurses to deliver quality health care to clients and can guide them in the practice of client-based teaching. © 2017 John Wiley & Sons Ltd.

The corneal fibrosis response to epithelial-stromal injury

PubMed Central

Torricelli, Andre A. M.; Santhanam, Abirami; Wu, Jiahui; Singh, Vivek; Wilson, Steven E.

2014-01-01

The corneal wound healing response, including the development of stromal opacity in some eyes, is a process that often leads to scarring that occurs after injury, surgery or infection to the cornea. Immediately after epithelial and stromal injury, a complex sequence of processes contributes to wound repair and regeneration of normal corneal structure and function. In some corneas, however, often depending on the type and extent of injury, the response may also lead to the development of mature vimentin+ α-smooth muscle actin+ desmin+ myofibroblasts. Myofibroblasts are specialized fibroblastic cells generated in the cornea from keratocyte-derived or bone marrow-derived precursor cells. The disorganized extracellular matrix components secreted by myofibroblasts, in addition to decreased expression of corneal crystallins in these cells, are central biological processes that result in corneal stromal fibrosis associated with opacity or “haze”. Several factors are associated with myofibroblast generation and haze development after PRK surgery in rabbits, a reproducible model of scarring, including the amount of tissue ablated, which may relate to the extent of keratocyte apoptosis in the early response to injury, irregularity of stromal surface after surgery, and changes on corneal stromal proteoglycans, but normal regeneration of the epithelial basement membrane (EBM) appears to be a critical factor determining whether a cornea heals with relative transparency or vision-limiting stromal opacity. Structural and functional abnormalities of the regenerated EBM facilitate prolonged entry of epithelium-derived growth factors such as transforming growth factor β (TGF-β) and platelet-derived growth factor (PDGF) into the stroma that both drive development of mature myofibroblasts from precursor cells and lead to persistence of the cells in the anterior stroma. A major discovery that has contributed to our understanding of haze development is that keratocytes and corneal fibroblasts, but not myofibroblasts, produce large amounts of critical EBM components, such as nidogen-1, nidogen-2 and perlecan, that are essential for complete regeneration of a normal EBM once laminin secreted by epithelial cells self-polymerizes into a nascent EBM. Mature myofibroblasts that become established in the anterior stroma are a barrier to keratocyte contributions to the nascent EBM. These myofibroblasts, and the opacity they produce, often persist for months or years after the injury. Transparency is subsequently restored when the EBM is completely regenerated, myofibroblasts are deprived of TGFβ and undergo apoptosis, and the keratocytes re-occupy the anterior stroma and reabsorb disordered extracellular matrix. The aim of this review is to highlight factors involved in the generation of stromal haze and its subsequent removal. PMID:26675407

A Case Study of "Empathetic Teaching Artistry"

ERIC Educational Resources Information Center

Risner, Doug

2014-01-01

This case study is one of twenty cases derived from Anderson and Risner's international study of teaching artists in dance, and theatre, which investigated participants' (n=172) artistic and academic preparation in dance, and theatre, initial entry into the teaching artist field, rewards, challenges, and obstacles in participants' work, artists'…

Simulation and Gaming: The Best of ERIC.

ERIC Educational Resources Information Center

Coombs, Don H., Comp.

Most of the 101 citations included in this annotated bibliography on simulation and gaming were derived from a search of the Educational Resources Information Center (ERIC) indexes. Entries were published between 1972 and 1975. The bibliography is divided into nine sections: theory and research; social studies materials; environment, land use, and…

Significance of independent radon entry rate and air exchange rate assessment for the purpose of radon mitigation effectiveness proper evaluation: case studies.

PubMed

Froňka, A; Jílek, K; Moučka, L; Brabec, M

2011-05-01

Two new single-family houses identified as insufficient with regard to existing radon barrier efficiency, have been selected for further examination. A complex set of radon diagnosis procedures has been applied in order to localise and quantify radon entry pathways into the indoor environment. Independent assessment of radon entry rate and air exchange rate has been carried out using the continuous indoor radon measurement and a specific tracer gas application. Simultaneous assessment of these key determining factors has turned out to be absolutely crucial in the context of major cause identification of elevated indoor radon concentration.

ENTRY IN THE ADHD DRUGS MARKET: WELFARE IMPACT OF GENERICS AND ME-TOO'S*

PubMed Central

Bokhari, Farasat A S; Fournier, Gary M

2013-01-01

Recent decades have seen a growth in treatments for attention deficit hyperactivity disorder (ADHD) including many branded and generic drugs. In the early 2000's, new drug entry dramatically altered market shares. We estimate a demand system for ADHD drugs and assess the welfare impact of new drugs. We find that entry induced large welfare gains by reducing prices of substitute drugs, and by providing alternative delivery mechanisms for existing molecules. Our results suggest that the success of follow-on patented drugs may come from unanticipated innovations like delivery mechanisms, a factor ignored by proposals to retard new follow-on drug approvals. PMID:25821242

A multicenter study of outcome in systemic lupus erythematosus. I. Entry variables as predictors of prognosis.

PubMed

Ginzler, E M; Diamond, H S; Weiner, M; Schlesinger, M; Fries, J F; Wasner, C; Medsger, T A; Ziegler, G; Klippel, J H; Hadler, N M; Albert, D A; Hess, E V; Spencer-Green, G; Grayzel, A; Worth, D; Hahn, B H; Barnett, E V

1982-06-01

A retrospective study of factors influencing survival in 1,103 patients with systemic lupus erythematosus (SLE) was carried out at 9 university centers diverse in geographic, socioeconomic, and racial characteristics. The mortality and disease characteristics of the patients at study entry varied widely among centers. The survival rates from the time patients with a diagnosis of SLE were first evaluated at the participating center was 90% at 1 year, 77% at 5 years, and 71% at 10 years. Patients with a serum creatinine greater than 3 mg/dl at study entry had the lowest survival rates: 48%, 29%, and 12% at 1, 5, and 10 years, respectively. Survival rate also correlated independently with the entry hematocrit, degree of proteinuria, number of preliminary American Rheumatism Association criteria for SLE satisfied, and source of funding of medical care. When data were corrected for socioeconomic status, race/ethnic origin did not significantly influence survival. Survival rates varied widely at different participating institutions, generally due to differences in disease severity. Place of treatment was independently associated with survival only in the second year after study entry. Disease duration before study entry did not account for the differences in disease severity.

Protein Corona Modulates Uptake and Toxicity of Nanoceria via Clathrin-Mediated Endocytosis.

PubMed

Mazzolini, Julie; Weber, Ralf J M; Chen, Hsueh-Shih; Khan, Abdullah; Guggenheim, Emily; Shaw, Robert K; Chipman, James K; Viant, Mark R; Rappoport, Joshua Z

2016-08-01

Particles present in diesel exhaust have been proposed as a significant contributor to the development of acute and chronic lung diseases, including respiratory infection and allergic asthma. Nanoceria (CeO2 nanoparticles) are used to increase fuel efficiency in internal combustion engines, are present in exhaust fumes, and could affect cells of the airway. Components from the environment such as biologically derived proteins, carbohydrates, and lipids can form a dynamic layer, commonly referred to as the "protein corona" which alters cellular nanoparticle interactions and internalization. Using confocal reflectance microscopy, we quantified nanoceria uptake by lung-derived cells in the presence and absence of a serum-derived protein corona. Employing mass spectrometry, we identified components of the protein corona, and demonstrated that the interaction between transferrin in the protein corona and the transferrin receptor is involved in mediating the cellular entry of nanoceria via clathrin-mediated endocytosis. Furthermore, under these conditions nanoceria does not affect cell growth, viability, or metabolism, even at high concentration. Alternatively, despite the antioxidant capacity of nanoceria, in serum-free conditions these nanoparticles induce plasma membrane disruption and cause changes in cellular metabolism. Thus, our results identify a specific receptor-mediated mechanism for nanoceria entry, and provide significant insight into the potential for nanoparticle-dependent toxicity. © 2016 Marine Biological Laboratory.

Effect of aerodynamic and angle-of-attack uncertainties on the May 1979 entry flight control system of the Space Shuttle from Mach 8 to 1.5

NASA Technical Reports Server (NTRS)

Stone, H. W.; Powell, R. W.

1985-01-01

A six degree of freedom simulation analysis was performed for the space shuttle orbiter during entry from Mach 8 to Mach 1.5 with realistic off nominal conditions by using the flight control systems defined by the shuttle contractor. The off nominal conditions included aerodynamic uncertainties in extrapolating from wind tunnel derived characteristics to full scale flight characteristics, uncertainties in the estimates of the reaction control system interaction with the orbiter aerodynamics, an error in deriving the angle of attack from onboard instrumentation, the failure of two of the four reaction control system thrusters on each side, and a lateral center of gravity offset coupled with vehicle and flow asymmetries. With combinations of these off nominal conditions, the flight control system performed satisfactorily. At low hypersonic speeds, a few cases exhibited unacceptable performances when errors in deriving the angle of attack from the onboard instrumentation were modeled. The orbiter was unable to maintain lateral trim for some cases between Mach 5 and Mach 2 and exhibited limit cycle tendencies or residual roll oscillations between Mach 3 and Mach 1. Piloting techniques and changes in some gains and switching times in the flight control system are suggested to help alleviate these problems.

Identification and evaluation of competencies of public health nutritionists.

PubMed Central

Sims, L S

1979-01-01

The Delphi Technique was used to elicit a number of essential competencies expected of the "entry-level" public health nutritionist from members of Graduate Faculties of Programs in Public Health Nutrition. Questionnaires composed of "competency statements" were constructed from these responses and sent to practitioners in public health nutrition. The questionnaire requested evaluation of the "necessity" of each competency. Responses served as the basis for "factor analysis" procedures, employed to obtain clusters of competency functions expected of the nutritionist. From the 109 competency items originally identified, 17 competency scales were derived from the factor analysis. A ranking from both faculties and practitioners revealed that both groups highly rated competencies to communicate, to counsel and deal with clients/patients, and to interpret scientific data in "lay language." Less important in the ranking were competencies which dealt with administrative abilities, program planning, legislative activism, and consumer advocacy. These findings have cimplications for the practitioner in public health nutrition as well as for academic groups who must plan and evaluate curricula in public health nutrition and in other fields of public health. PMID:507240

The Hemagglutinin of Bat-Associated Influenza Viruses Is Activated by TMPRSS2 for pH-Dependent Entry into Bat but Not Human Cells

PubMed Central

Hoffmann, Markus; Krüger, Nadine; Zmora, Pawel; Wrensch, Florian; Herrler, Georg; Pöhlmann, Stefan

2016-01-01

New World bats have recently been discovered to harbor influenza A virus (FLUAV)-related viruses, termed bat-associated influenza A-like viruses (batFLUAV). The internal proteins of batFLUAV are functional in mammalian cells. In contrast, no biological functionality could be demonstrated for the surface proteins, hemagglutinin (HA)-like (HAL) and neuraminidase (NA)-like (NAL), and these proteins need to be replaced by their human counterparts to allow spread of batFLUAV in human cells. Here, we employed rhabdoviral vectors to study the role of HAL and NAL in viral entry. Vectors pseudotyped with batFLUAV-HAL and -NAL were able to enter bat cells but not cells from other mammalian species. Host cell entry was mediated by HAL and was dependent on prior proteolytic activation of HAL and endosomal low pH. In contrast, sialic acids were dispensable for HAL-driven entry. Finally, the type II transmembrane serine protease TMPRSS2 was able to activate HAL for cell entry indicating that batFLUAV can utilize human proteases for HAL activation. Collectively, these results identify viral and cellular factors governing host cell entry driven by batFLUAV surface proteins. They suggest that the absence of a functional receptor precludes entry of batFLUAV into human cells while other prerequisites for entry, HAL activation and protonation, are met in target cells of human origin. PMID:27028521

Rhizobium meliloti lipooligosaccharide nodulation factors: different structural requirements for bacterial entry into target root hair cells and induction of plant symbiotic developmental responses.

PubMed

Ardourel, M; Demont, N; Debellé, F; Maillet, F; de Billy, F; Promé, J C; Dénarié, J; Truchet, G

1994-10-01

Rhizobium meliloti produces lipochitooligosaccharide nodulation NodRm factors that are required for nodulation of legume hosts. NodRm factors are O-acetylated and N-acylated by specific C16-unsaturated fatty acids. nodL mutants produce non-O-acetylated factors, and nodFE mutants produce factors with modified acyl substituents. Both mutants exhibited a significantly reduced capacity to elicit infection thread (IT) formation in alfalfa. However, once initiated, ITs developed and allowed the formation of nitrogen-fixing nodules. In contrast, double nodF/nodL mutants were unable to penetrate into legume hosts and to form ITs. Nevertheless, these mutants induced widespread cell wall tip growth in trichoblasts and other epidermal cells and were also able to elicit cortical cell activation at a distance. NodRm factor structural requirements are thus clearly more stringent for bacterial entry than for the elicitation of developmental plant responses.

Brain-Derived Neurotrophic Factor Promotes Vasculature-Associated Migration of Neuronal Precursors toward the Ischemic Striatum

PubMed Central

Grade, Sofia; Weng, Yuan C.; Snapyan, Marina; Kriz, Jasna; Malva, João O.; Saghatelyan, Armen

2013-01-01

Stroke induces the recruitment of neuronal precursors from the subventricular zone (SVZ) into the ischemic striatum. In injured areas, de-routed neuroblasts use blood vessels as a physical scaffold to their migration, in a process that resembles the constitutive migration seen in the rostral migratory stream (RMS). The molecular mechanism underlying injury-induced vasculature-mediated migration of neuroblasts in the post-stroke striatum remains, however, elusive. Using adult mice we now demonstrate that endothelial cells in the ischemic striatum produce brain-derived neurotrophic factor (BDNF), a neurotrophin that promotes the vasculature-mediated migration of neuronal precursors in the RMS, and that recruited neuroblasts maintain expression of p75NTR, a low-affinity receptor for BDNF. Reactive astrocytes, which are widespread throughout the damaged area, ensheath blood vessels and express TrkB, a high-affinity receptor for BDNF. Despite the absence of BDNF mRNA, we observed strong BDNF immunolabeling in astrocytes, suggesting that these glial cells trap extracellular BDNF. Importantly, this pattern of expression is reminiscent of the adult RMS, where TrkB-expressing astrocytes bind and sequester vasculature-derived BDNF, leading to the entry of migrating cells into the stationary phase. Real-time imaging of cell migration in acute brain slices revealed a direct role for BDNF in promoting the migration of neuroblasts to ischemic areas. We also demonstrated that cells migrating in the ischemic striatum display higher exploratory behavior and longer stationary periods than cells migrating in the RMS. Our findings suggest that the mechanisms involved in the injury-induced vasculature-mediated migration of neuroblasts recapitulate, at least partially, those observed during constitutive migration in the RMS. PMID:23383048

Identification and Characterization of a Novel Broad-Spectrum Virus Entry Inhibitor

PubMed Central

Chou, Yi-ying; Cuevas, Christian; Carocci, Margot; Stubbs, Sarah H.; Ma, Minghe; Cureton, David K.; Evesson, Frances; He, Kangmin; Yang, Priscilla L.; Whelan, Sean P.

2016-01-01

ABSTRACT Virus entry into cells is a multistep process that often requires the subversion of subcellular machineries. A more complete understanding of these steps is necessary to develop new antiviral strategies. While studying the potential role of the actin network and one of its master regulators, the small GTPase Cdc42, during Junin virus (JUNV) entry, we serendipitously uncovered the small molecule ZCL278, reported to inhibit Cdc42 function as an entry inhibitor for JUNV and for vesicular stomatitis virus, lymphocytic choriomeningitis virus, and dengue virus but not for the nonenveloped poliovirus. Although ZCL278 did not interfere with JUNV attachment to the cell surface or virus particle internalization into host cells, it prevented the release of JUNV ribonucleoprotein cores into the cytosol and decreased pH-mediated viral fusion with host membranes. We also identified SVG-A astroglial cell-derived cells to be highly permissive for JUNV infection and generated new cell lines expressing fluorescently tagged Rab5c or Rab7a or lacking Cdc42 using clustered regularly interspaced short palindromic repeat (CRISPR)-caspase 9 (Cas9) gene-editing strategies. Aided by these tools, we uncovered that perturbations in the actin cytoskeleton or Cdc42 activity minimally affect JUNV entry, suggesting that the inhibitory effect of ZCL278 is not mediated by ZCL278 interfering with the activity of Cdc42. Instead, ZCL278 appears to redistribute viral particles from endosomal to lysosomal compartments. ZCL278 also inhibited JUNV replication in a mouse model, and no toxicity was detected. Together, our data suggest the unexpected antiviral activity of ZCL278 and highlight its potential for use in the development of valuable new tools to study the intracellular trafficking of pathogens. IMPORTANCE The Junin virus is responsible for outbreaks of Argentine hemorrhagic fever in South America, where 5 million people are at risk. Limited options are currently available to treat infections by Junin virus or other viruses of the Arenaviridae, making the identification of additional tools, including small-molecule inhibitors, of great importance. How Junin virus enters cells is not yet fully understood. Here we describe new cell culture models in which the cells are susceptible to Junin virus infection and to which we applied CRISPR-Cas9 genome engineering strategies to help characterize early steps during virus entry. We also uncovered ZCL278 to be a new antiviral small molecule that potently inhibits the cellular entry of the Junin virus and other enveloped viruses. Moreover, we show that ZCL278 also functions in vivo, thereby preventing Junin virus replication in a mouse model, opening the possibility for the discovery of ZCL278 derivatives of therapeutic potential. PMID:26912630

Regulated portals of entry into the cell

NASA Astrophysics Data System (ADS)

Conner, Sean D.; Schmid, Sandra L.

2003-03-01

The plasma membrane is the interface between cells and their harsh environment. Uptake of nutrients and all communication among cells and between cells and their environment occurs through this interface. `Endocytosis' encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane. It controls entry into the cell and has a crucial role in development, the immune response, neurotransmission, intercellular communication, signal transduction, and cellular and organismal homeostasis. As the complexity of molecular interactions governing endocytosis are revealed, it has become increasingly clear that it is tightly coordinated and coupled with overall cell physiology and thus, must be viewed in a broader context than simple vesicular trafficking.

Thermodynamic energy balance equations for Space Shuttle Orbiter gas compartment during ascent and re-entry

NASA Technical Reports Server (NTRS)

Ting, P. C.

1982-01-01

Thermodynamic energy balance equations are derived and applied to midsection Orbiter-payload atmospheric thermal math models (TMMs) to predict Orbiter component, element, compartment, internal insolation and structure temperatures in support of NASA/JSC mission planning, postflight thermal analysis and payload thermal integration planning. The equations are extended and applied to the forward section, midsection, and aft section of the TMMs for five Orbiter mission phases: prelaunch on pad with purge, lift-off to ascent, re-entry to touchdown, post landing without purge, and post-landing with purge. Predicted results from the 390 node/DFI atmospheric TMM are in good agreement with STS-1 flight measurement data.

Analysis of social optimum for staggered shifts in a single-entry traffic corridor with no late arrivals

NASA Astrophysics Data System (ADS)

Li, Chuan-Yao; Huang, Hai-Jun; Tang, Tie-Qiao

2017-03-01

This paper investigates the traffic flow dynamics under the social optimum (SO) principle in a single-entry traffic corridor with staggered shifts from the analytical and numerical perspectives. The LWR (Lighthill-Whitham and Richards) model and the Greenshield's velocity-density function are utilized to describe the dynamic properties of traffic flow. The closed-form SO solution is analytically derived and some numerical examples are used to further testify the analytical solution. The optimum proportion of the numbers of commuters with different desired arrival times is further discussed, where the analytical and numerical results both indicate that the cumulative outflow curve under the SO principle is piecewise smooth.

An investigation into the validity of specifying 5 "O' levels in the General Certificate of Education as an entry requirement for the education and training of district nurses.

PubMed

Jarvis, P; Gibson, S J

1981-11-01

District nursing, like many other professionalizing occupations, has stipulated that possession of five ordinary level GCE passes might constitute one criterion of entry. This paper reports a longitudinal study over four intakes of district nurse students in one teaching centre and examines the relationship between selection criteria, in particular educational achievement prior to entry to the course, and the students' achievement during this. The research explored the relationship between educational achievement prior to commencing their course of study and the level of academic and practical performance during it. Additionally other factors, including the results of aptitude and personality tests, were examined to see if they would provide indication of the level of the students; grades during training. No factors were discovered that might provide an adequate basis for selection, which raises questions about trying to specify any pre-requisite for selection other than state registration and appropriate professional experience until further research has been undertaken.

Optogenetic manipulation of anatomical re-entry by light-guided generation of a reversible local conduction block.

PubMed

Watanabe, Masaya; Feola, Iolanda; Majumder, Rupamanjari; Jangsangthong, Wanchana; Teplenin, Alexander S; Ypey, Dirk L; Schalij, Martin J; Zeppenfeld, Katja; de Vries, Antoine A F; Pijnappels, Daniël A

2017-03-01

Anatomical re-entry is an important mechanism of ventricular tachycardia, characterized by circular electrical propagation in a fixed pathway. It's current investigative and therapeutic approaches are non-biological, rather unspecific (drugs), traumatizing (electrical shocks), or irreversible (ablation). Optogenetics is a new biological technique that allows reversible modulation of electrical function with unmatched spatiotemporal precision using light-gated ion channels. We therefore investigated optogenetic manipulation of anatomical re-entry in ventricular cardiac tissue. Transverse, 150-μm-thick ventricular slices, obtained from neonatal rat hearts, were genetically modified with lentiviral vectors encoding Ca2+-translocating channelrhodopsin (CatCh), a light-gated depolarizing ion channel, or enhanced yellow fluorescent protein (eYFP) as control. Stable anatomical re-entry was induced in both experimental groups. Activation of CatCh was precisely controlled by 470-nm patterned illumination, while the effects on anatomical re-entry were studied by optical voltage mapping. Regional illumination in the pathway of anatomical re-entry resulted in termination of arrhythmic activity only in CatCh-expressing slices by establishing a local and reversible, depolarization-induced conduction block in the illuminated area. Systematic adjustment of the size of the light-exposed area in the re-entrant pathway revealed that re-entry could be terminated by either wave collision or extinction, depending on the depth (transmurality) of illumination. In silico studies implicated source-sink mismatches at the site of subtransmural conduction block as an important factor in re-entry termination. Anatomical re-entry in ventricular tissue can be manipulated by optogenetic induction of a local and reversible conduction block in the re-entrant pathway, allowing effective re-entry termination. These results provide distinctively new mechanistic insight into re-entry termination and a novel perspective for cardiac arrhythmia management. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Curved-flow, rolling-flow, and oscillatory pure-yawing wind-tunnel test methods for determination of dynamic stability derivatives

NASA Technical Reports Server (NTRS)

Chambers, J. R.; Grafton, S. B.; Lutze, F. H.

1981-01-01

Dynamic stability derivatives are evaluated on the basis of rolling-flow, curved-flow and snaking tests. Attention is given to the hardware associated with curved-flow, rolling-flow and oscillatory pure-yawing wind-tunnel tests. It is found that the snaking technique, when combined with linear- and forced-oscillation methods, yields an important method for evaluating beta derivatives for current configurations at high angles of attack. Since the rolling flow model is fixed during testing, forced oscillations may be imparted to the model, permitting the measurement of damping and cross-derivatives. These results, when coupled with basic rolling-flow or rotary-balance data, yield a highly accurate mathematical model for studies of incipient spin and spin entry.

Trade-associated pathways of alien forest insect entries in Canada

Treesearch

Denys Yemshanov; Frank H. Koch; Mark Ducey; Klaus Koehler

2012-01-01

Long-distance introductions of new invasive species have often been driven by socioeconomic factors, such that traditional ‘‘biological’’ invasion models may not be capable of estimating spread fully and reliably. In this study we present a new methodology to characterize and predict pathways of human-assisted entries of alien forest insects. We have developed a...

Examining Summer Laboratory Research Apprenticeships for High School Students as a Factor in Entry to MD/PhD Programs at Matriculation

ERIC Educational Resources Information Center

Tai, Robert H.; Kong, Xiaoqing; Mitchell, Claire E.; Dabney, Katherine P.; Read, Daniel M.; Jeffe, Donna B.; Andriole, Dorothy A.; Wathington, Heather D.

2017-01-01

Do summer laboratory research apprenticeships during high school have an impact on entry into MD/PhD programs? Apart from the nearly decade-long span of time between high school and matriculation into an MD/PhD program, young people have many life-shaping experiences that presumably impact their education and career trajectories. This quantitative…

Interaction of Human Tumor Viruses with Host Cell Surface Receptors and Cell Entry

PubMed Central

Schäfer, Georgia; Blumenthal, Melissa J.; Katz, Arieh A.

2015-01-01

Currently, seven viruses, namely Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpes virus (KSHV), high-risk human papillomaviruses (HPVs), Merkel cell polyomavirus (MCPyV), hepatitis B virus (HBV), hepatitis C virus (HCV) and human T cell lymphotropic virus type 1 (HTLV-1), have been described to be consistently associated with different types of human cancer. These oncogenic viruses belong to distinct viral families, display diverse cell tropism and cause different malignancies. A key to their pathogenicity is attachment to the host cell and entry in order to replicate and complete their life cycle. Interaction with the host cell during viral entry is characterized by a sequence of events, involving viral envelope and/or capsid molecules as well as cellular entry factors that are critical in target cell recognition, thereby determining cell tropism. Most oncogenic viruses initially attach to cell surface heparan sulfate proteoglycans, followed by conformational change and transfer of the viral particle to secondary high-affinity cell- and virus-specific receptors. This review summarizes the current knowledge of the host cell surface factors and molecular mechanisms underlying oncogenic virus binding and uptake by their cognate host cell(s) with the aim to provide a concise overview of potential target molecules for prevention and/or treatment of oncogenic virus infection. PMID:26008702

Plasma Distribution in Mercury's Magnetosphere Derived from MESSENGER Magnetometer and Fast Imaging Plasma Spectrometer Observations

NASA Technical Reports Server (NTRS)

Korth, Haje; Anderson, Brian J.; Gershman, Daniel J.; Raines, Jim M.; Slavin, James A.; Zurbuchen, Thomas H.; Solomon, Sean C.; McNutt, Ralph L.

2014-01-01

We assess the statistical spatial distribution of plasma in Mercury's magnetosphere from observations of magnetic pressure deficits and plasma characteristics by the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft. The statistical distributions of proton flux and pressure were derived from 10months of Fast Imaging Plasma Spectrometer (FIPS) observations obtained during the orbital phase of the MESSENGER mission. The Magnetometer-derived pressure distributions compare favorably with those deduced from the FIPS observations at locations where depressions in the magnetic field associated with the presence of enhanced plasma pressures are discernible in the Magnetometer data. The magnitudes of the magnetic pressure deficit and the plasma pressure agree on average, although the two measures of plasma pressure may deviate for individual events by as much as a factor of approximately 3. The FIPS distributions provide better statistics in regions where the plasma is more tenuous and reveal an enhanced plasma population near the magnetopause flanks resulting from direct entry of magnetosheath plasma into the low-latitude boundary layer of the magnetosphere. The plasma observations also exhibit a pronounced north-south asymmetry on the nightside, with markedly lower fluxes at low altitudes in the northern hemisphere than at higher altitudes in the south on the same field line. This asymmetry is consistent with particle loss to the southern hemisphere surface during bounce motion in Mercury's offset dipole magnetic field.

Derivation of an occupational exposure limit for inorganic borates using a weight of evidence approach.

PubMed

Maier, A; Vincent, M; Hack, E; Nance, P; Ball, W

2014-04-01

Inorganic borates are encountered in many settings worldwide, spurring international efforts to develop exposure guidance (US EPA, 2004; WHO, 2009; ATSDR, 2010) and occupational exposure limits (OEL) (ACGIH, 2005; MAK, 2011). We derived an updated OEL to reflect new data and current international risk assessment frameworks. We assessed toxicity and epidemiology data on inorganic borates to identify relevant adverse effects. International risk assessment frameworks (IPCS, 2005, 2007) were used to evaluate endpoint candidates: reproductive toxicity, developmental toxicity, and sensory irritation. For each endpoint, a preliminary OEL was derived and adjusted based on consideration of toxicokinetics, toxicodynamics, and other uncertainties. Selection of the endpoint point of departures (PODs) is supported by dose-response modeling. Developmental toxicity was the most sensitive systemic effect. An OEL of 1.6mgB/m(3) was estimated for this effect based on a POD of 63mgB/m(3) with an uncertainty factor (UF) of 40. Sensory irritation was considered to be the most sensitive effect for the portal of entry. An OEL of 1.4mgB/m(3) was estimated for this effect based on the identified POD and an UF of 1. An OEL of 1.4mgB/m(3) as an 8-h time-weighted average (TWA) is recommended. Copyright © 2014 Elsevier Inc. All rights reserved.

[Study on spray-drier preparation technology of weitai granules using orthogonal experiments].

PubMed

Qu, Cai-Hong; Yang, Li; Chen, Zhi-Liang

2006-04-01

To screen preparation technique in order to raise the end-product and economical efficiency of spray-drier preparation technology of weitai granules. Newly Fluid-bed-spray-drier-granulation technique was adoped and taken extracting technique, temperature of exit and entry and the matching of accessories as inspecting factors, two levels of each factors, end-product and the water content of semi-finished weitai granules as inspecting marker, the best preparation technique of weitai granules was screened by orthogonal desing. Among the 3 factors, the matching of accessories was most notalbe (P < 0.01), next was the temperature of exit and entry (P < 0.05). However, the extracting technique was of little importance (P > 0.05). The optimum spray-drier granulation technique of weitai granules is A3B1C3.

Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling.

PubMed

Singec, Ilyas; Crain, Andrew M; Hou, Junjie; Tobe, Brian T D; Talantova, Maria; Winquist, Alicia A; Doctor, Kutbuddin S; Choy, Jennifer; Huang, Xiayu; La Monaca, Esther; Horn, David M; Wolf, Dieter A; Lipton, Stuart A; Gutierrez, Gustavo J; Brill, Laurence M; Snyder, Evan Y

2016-09-13

Controlled differentiation of human embryonic stem cells (hESCs) can be utilized for precise analysis of cell type identities during early development. We established a highly efficient neural induction strategy and an improved analytical platform, and determined proteomic and phosphoproteomic profiles of hESCs and their specified multipotent neural stem cell derivatives (hNSCs). This quantitative dataset (nearly 13,000 proteins and 60,000 phosphorylation sites) provides unique molecular insights into pluripotency and neural lineage entry. Systems-level comparative analysis of proteins (e.g., transcription factors, epigenetic regulators, kinase families), phosphorylation sites, and numerous biological pathways allowed the identification of distinct signatures in pluripotent and multipotent cells. Furthermore, as predicted by the dataset, we functionally validated an autocrine/paracrine mechanism by demonstrating that the secreted protein midkine is a regulator of neural specification. This resource is freely available to the scientific community, including a searchable website, PluriProt. Published by Elsevier Inc.

New imaging algorithm in diffusion tomography

NASA Astrophysics Data System (ADS)

Klibanov, Michael V.; Lucas, Thomas R.; Frank, Robert M.

1997-08-01

A novel imaging algorithm for diffusion/optical tomography is presented for the case of the time dependent diffusion equation. Numerical tests are conducted for ranges of parameters realistic for applications to an early breast cancer diagnosis using ultrafast laser pulses. This is a perturbation-like method which works for both homogeneous a heterogeneous background media. Its main innovation lies in a new approach for a novel linearized problem (LP). Such an LP is derived and reduced to a boundary value problem for a coupled system of elliptic partial differential equations. As is well known, the solution of such a system amounts to the factorization of well conditioned, sparse matrices with few non-zero entries clustered along the diagonal, which can be done very rapidly. Thus, the main advantages of this technique are that it is fast and accurate. The authors call this approach the elliptic systems method (ESM). The ESM can be extended for other data collection schemes.

On the general theory of the origins of retroviruses

PubMed Central

2010-01-01

Background The order retroviridae comprises viruses based on ribonucleic acids (RNA). Some, such as HIV and HTLV, are human pathogens. Newly emerged human retroviruses have zoonotic origins. As far as has been established, both repeated infections (themselves possibly responsible for the evolution of viral mutations (Vm) and host adaptability (Ha)); along with interplay between inhibitors and promoters of cell tropism, are needed to effect retroviral cross-species transmissions. However, the exact modus operadi of intertwine between these factors at molecular level remains to be established. Knowledge of such intertwine could lead to a better understanding of retrovirology and possibly other infectious processes. This study was conducted to derive the mathematical equation of a general theory of the origins of retroviruses. Methods and results On the basis of an arbitrarily non-Euclidian geometrical "thought experiment" involving the cross-species transmission of simian foamy virus (sfv) from a non-primate species Xy to Homo sapiens (Hs), initially excluding all social factors, the following was derived. At the port of exit from Xy (where the species barrier, SB, is defined by the Index of Origin, IO), sfv shedding is (1) enhanced by two transmitting tensors (Tt), (i) virus-specific immunity (VSI) and (ii) evolutionary defenses such as APOBEC, RNA interference pathways, and (when present) expedited therapeutics (denoted e2D); and (2) opposed by the five accepting scalars (At): (a) genomic integration hot spots, gIHS, (b) nuclear envelope transit (NMt) vectors, (c) virus-specific cellular biochemistry, VSCB, (d) virus-specific cellular receptor repertoire, VSCR, and (e) pH-mediated cell membrane transit, (↓pH CMat). Assuming As and Tt to be independent variables, IO = Tt/As. The same forces acting in an opposing manner determine SB at the port of sfv entry (defined here by the Index of Entry, IE = As/Tt). Overall, If sfv encounters no unforeseen effects on transit between Xy and Hs, then the square root of the combined index of sfv transmissibility (√|RTI|) is proportional to the product IO* IE (or ~Vm* Ha* ∑Tt*∑As*Ω), where Ω is the retrovirological constant and ∑ is a function of the ratio Tt/As or As/Tt for sfv transmission from Xy to Hs. Conclusions I present a mathematical formalism encapsulating the general theory of the origins of retroviruses. It summarizes the choreography for the intertwined interplay of factors influencing the probability of retroviral cross-species transmission: Vm, Ha, Tt, As, and Ω. PMID:20158888

Tannic Acid Inhibits Hepatitis C Virus Entry into Huh7.5 Cells

PubMed Central

Hagedorn, Curt H.

2015-01-01

Chronic infection with the hepatitis C virus (HCV) is a cause of cirrhosis and hepatocellular carcinoma worldwide. Although antiviral therapy has dramatically improved recently, a number of patients remain untreated and some do not clear infection with treatment. Viral entry is an essential step in initiating and maintaining chronic HCV infections. One dramatic example of this is the nearly 100% infection of newly transplanted livers in patients with chronic hepatitis C. HCV entry inhibitors could play a critical role in preventing HCV infection of newly transplanted livers. Tannic acid, a polymer of gallic acid and glucose molecules, is a plant-derived polyphenol that defends some plants from insects and microbial infections. It has been shown to have a variety of biological effects, including antiviral activity, and is used as a flavoring agent in foods and beverages. In this study, we demonstrate that tannic acid is a potent inhibitor of HCV entry into Huh7.5 cells at low concentrations (IC50 5.8 μM). It also blocks cell-to-cell spread in infectious HCV cell cultures, but does not inhibit HCV replication following infection. Moreover, experimental results indicate that tannic acid inhibits an early step of viral entry, such as the docking of HCV at the cell surface. Gallic acid, tannic acid’s structural component, did not show any anti-HCV activity including inhibition of HCV entry or replication at concentrations up to 25 μM. It is possible the tannin structure is related on the effect on HCV inhibition. Tannic acid, which is widely distributed in plants and foods, has HCV antiviral activity in cell culture at low micromolar concentrations, may provide a relative inexpensive adjuvant to direct-acting HCV antivirals and warrants future investigation. PMID:26186636

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

PubMed Central

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

2016-01-01

ABSTRACT 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. PMID:27879338

Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)*

PubMed Central

Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

2016-01-01

Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm. Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. PMID:26953343

Infused chemotherapy use in the elderly after patent expiration.

PubMed

Conti, Rena M; Rosenthal, Meredith B; Polite, Blase N; Bach, Peter B; Shih, Ya-Chen Tina

2012-05-01

The use of anticancer drugs (chemotherapies) is an important determinant of national spending trends. Recent policies have aimed to accelerate generic entry among chemotherapies to generate cost savings. We examined the effects of generic entry on the choice of chemotherapy for the treatment of metastatic colorectal cancer (MCRC) between 2006 and 2009 using autoregressive-moving average modeling with case control. A nationally representative sample of oncologists and patients with cancer (age ≥ 65 years) was employed to estimate the magnitude and significance of the impact of the generic entry of irinotecan in February 2008 on the number of administrations of irinotecan compared with oxaliplatin. The generic entry of irinotecan resulted in a 17% to 19% decrease (P < .001) in use among elderly patients with MCRC compared with oxaliplatin. The results were robust to multiple sensitivity checks. This study provides novel and robust estimates of the decline in use of a chemotherapy to treat a common cancer in the elderly after patent expiration. The results suggest estimates from a previous Office of the Inspector General report of the potential savings derived from the generic entry of irinotecan for public payers are an overestimate, likely confounded by oncologists' response to financial incentives, changes in scientific evidence, and promotional activities. As calls for improving the quality and cost efficiency of oncology increase, future empirical work is needed to examine the responsiveness of oncologists' treatment decision making to incentives among patients of all ages and insurance types.

Infused chemotherapy use in the elderly after patent expiration.

PubMed

Conti, Rena M; Rosenthal, Meredith B; Polite, Blase N; Bach, Peter B; Shih, Ya-Chen Tina

2012-05-01

The use of anticancer drugs (chemotherapies) is an important determinant of national spending trends. Recent policies have aimed to accelerate generic entry among chemotherapies to generate cost savings. We examined the effects of generic entry on the choice of chemotherapy for the treatment of metastatic colorectal cancer (MCRC) between 2006 and 2009 using autoregressivemoving average modeling with case control. A nationally representative sample of oncologists and patients with cancer (aged ≥65 years) was employed to estimate the magnitude and significance of the impact of the generic entry of irinotecan in February 2008 on the number of administrations of irinotecan compared with oxaliplatin. The generic entry of irinotecan resulted in a 17% to 19% decrease (P <.001) in use among elderly patients with MCRC compared with oxaliplatin. The results were robust to multiple sensitivity checks. This study provides novel and robust estimates of the decline in use of a chemotherapy to treat a common cancer in the elderly after patent expiration. The results suggest estimates from a previous Office of the Inspector General report of the potential savings derived from the generic entry of irinotecan for public payers are an overestimate, likely confounded by oncologists' response to financial incentives, changes in scientific evidence, and promotional activities. As calls for improving the quality and cost efficiency of oncology increase, future empirical work is needed to examine the responsiveness of oncologists' treatment decision making to incentives among patients of all ages and insurance types.

Field of first magnetic flux entry and pinning strength of superconductors for rf application measured with muon spin rotation

DOE PAGES

Junginger, Tobias; Abidi, S. H.; Maffett, R. D.; ...

2018-03-16

Here, the performance of superconducting radiofrequency (SRF) cavities used for particle accelerators depends on two characteristic material parameters: field of first flux entry H entry and pinning strength. The former sets the limit for the maximum achievable accelerating gradient, while the latter determines how efficiently flux can be expelled related to the maximum achievable quality factor. In this paper, a method based on muon spin rotation (μSR) is developed to probe these parameters on samples. It combines measurements from two different spectrometers, one being specifically built for these studies and samples of different geometries. It is found that annealing atmore » 1400°C virtually eliminates all pinning. Such an annealed substrate is ideally suited to measure H entry of layered superconductors, which might enable accelerating gradients beyond bulk niobium technology.« less

Cognitive ability at kindergarten entry and socioeconomic status.

PubMed

Larson, Kandyce; Russ, Shirley A; Nelson, Bergen B; Olson, Lynn M; Halfon, Neal

2015-02-01

To examine how gradients in socioeconomic status (SES) impact US children's reading and math ability at kindergarten entry and determine the contributions of family background, health, home learning, parenting, and early education factors to those gradients. Analysis of 6600 children with cognitive assessments at kindergarten entry from the US Early Childhood Longitudinal Birth Cohort Study. A composite SES measure based on parent's occupation, education, and income was divided into quintiles. Wald F tests assessed bivariate associations between SES and child's cognitive ability and candidate explanatory variables. A decomposition methodology examined mediators of early cognitive gradients. Average reading percentile rankings increased from 34 to 67 across SES quintiles and math from 33 to 70. Children in lower SES quintiles had younger mothers, less frequent parent reading, less home computer use (27%-84%), and fewer books at home (26-114). Parent's supportive interactions, expectations for their child to earn a college degree (57%-96%), and child's preschool attendance (64%-89%) increased across quintiles. Candidate explanatory factors explained just over half the gradients, with family background factors explaining 8% to 13%, health factors 4% to 6%, home learning environment 18%, parenting style/beliefs 14% to 15%, and early education 6% to 7% of the gaps between the lowest versus highest quintiles in reading and math. Steep social gradients in cognitive outcomes at kindergarten are due to many factors. Findings suggest policies targeting levels of socioeconomic inequality and a range of early childhood interventions are needed to address these disparities. Copyright © 2015 by the American Academy of Pediatrics.

Epidermal Growth Factor Receptor-PI3K Signaling Controls Cofilin Activity To Facilitate Herpes Simplex Virus 1 Entry into Neuronal Cells

PubMed Central

Zheng, Kai; Xiang, Yangfei; Wang, Xiao; Wang, Qiaoli; Zhong, Meigong; Wang, Shaoxiang; Wang, Xiaoyan; Fan, Jianglin; Kitazato, Kaio; Wang, Yifei

2014-01-01

ABSTRACT Herpes simplex virus type 1 (HSV-1) establishes latency in neurons and can cause severe disseminated infection with neurological impairment and high mortality. This neurodegeneration is thought to be tightly associated with virus-induced cytoskeleton disruption. Currently, the regulation pattern of the actin cytoskeleton and the involved molecular mechanisms during HSV-1 entry into neurons remain unclear. Here, we demonstrate that the entry of HSV-1 into neuronal cells induces biphasic remodeling of the actin cytoskeleton and an initial inactivation followed by the subsequent activation of cofilin, a member of the actin depolymerizing factor family that is critical for actin reorganization. The disruption of F-actin dynamics or the modulation of cofilin activity by mutation, knockdown, or overexpression affects HSV-1 entry efficacy and virus-mediated cell ruffle formation. Binding of the HSV-1 envelope initiates the epidermal growth factor receptor (EGFR)-phosphatidylinositide 3-kinase (PI3K) signaling pathway, which leads to virus-induced early cofilin phosphorylation and F-actin polymerization. Moreover, the extracellular signal-regulated kinase (ERK) kinase and Rho-associated, coiled-coil-containing protein kinase 1 (ROCK) are recruited as downstream mediators of the HSV-1-induced cofilin inactivation pathway. Inhibitors specific for those kinases significantly reduce the virus infectivity without affecting virus binding to the target cells. Additionally, lipid rafts are clustered to promote EGFR-associated signaling cascade transduction. We propose that HSV-1 hijacks cofilin to initiate infection. These results could promote a better understanding of the pathogenesis of HSV-1-induced neurological diseases. PMID:24425731

PLK1 Activation in Late G2 Sets Up Commitment to Mitosis.

PubMed

Gheghiani, Lilia; Loew, Damarys; Lombard, Bérangère; Mansfeld, Jörg; Gavet, Olivier

2017-06-06

Commitment to mitosis must be tightly coordinated with DNA replication to preserve genome integrity. While we have previously established that the timely activation of CyclinB1-Cdk1 in late G2 triggers mitotic entry, the upstream regulatory mechanisms remain unclear. Here, we report that Polo-like kinase 1 (Plk1) is required for entry into mitosis during an unperturbed cell cycle and is rapidly activated shortly before CyclinB1-Cdk1. We determine that Plk1 associates with the Cdc25C1 phosphatase and induces its phosphorylation before mitotic entry. Plk1-dependent Cdc25C1 phosphosites are sufficient to promote mitotic entry, even when Plk1 activity is inhibited. Furthermore, we find that activation of Plk1 during G2 relies on CyclinA2-Cdk activity levels. Our findings thus elucidate a critical role for Plk1 in CyclinB1-Cdk1 activation and mitotic entry and outline how CyclinA2-Cdk, an S-promoting factor, poises cells for commitment to mitosis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Host Serine/Threonine Kinases mTOR and Protein Kinase C-α Promote InlB-Mediated Entry of Listeria monocytogenes

PubMed Central

Bhalla, Manmeet; Law, Daria; Dowd, Georgina C.

2017-01-01

ABSTRACT The bacterial pathogen Listeria monocytogenes causes foodborne illnesses resulting in gastroenteritis, meningitis, or abortion. Listeria induces its internalization into some human cells through interaction of the bacterial surface protein InlB with the host receptor tyrosine kinase Met. InlB-dependent entry requires localized polymerization of the host actin cytoskeleton. The signal transduction pathways that act downstream of Met to regulate actin filament assembly or other processes during Listeria uptake remain incompletely characterized. Here, we demonstrate important roles for the human serine/threonine kinases mTOR and protein kinase C-α (PKC-α) in InlB-dependent entry. Experiments involving RNA interference (RNAi) indicated that two multiprotein complexes containing mTOR, mTORC1 and mTORC2, are each needed for efficient internalization of Listeria into cells of the human cell line HeLa. InlB stimulated Met-dependent phosphorylation of mTORC1 or mTORC2 substrates, demonstrating activation of both mTOR-containing complexes. RNAi studies indicated that the mTORC1 effectors 4E-BP1 and hypoxia-inducible factor 1α (HIF-1α) and the mTORC2 substrate PKC-α each control Listeria uptake. Genetic or pharmacological inhibition of PKC-α reduced the internalization of Listeria and the accumulation of actin filaments that normally accompanies InlB-mediated entry. Collectively, our results identify mTOR and PKC-α to be host factors exploited by Listeria to promote infection. PKC-α controls Listeria entry, at least in part, by regulating the actin cytoskeleton downstream of the Met receptor. PMID:28461391

Workforce re-entry for Japanese unemployed dental hygienists.

PubMed

Usui, Y; Miura, H

2015-02-01

The aim of this study was to define the profile of unemployed dental hygienists who could be enticed to re-enter the workforce and the factors that could facilitate their re-entry into the dental field in Japan. The questionnaire was mailed with a postage-paid return envelope to a sample of 3095 licensed dental hygienists. A 50.4% response rate (S = 1477) was observed. The rate of working dental hygienists was 60.3% (n = 891), and of unemployed dental hygienists was 39.7% (n = 586). Of the latter, 31.9% (n = 187) stated intentions of returning to the workplace. The unemployed dental hygienists seeking employment were more often married and had more children, compared with working dental hygienists currently. This group also had significantly fewer total service years. Moreover, only 11.96% of them belonged to the Japan Dental Hygienists' Association, and 41.3% of those attended training workshops. According to their response, they perceived their top three major barriers to re-entry as 'lack sufficient dental hygiene skill', 'child rearing' and 'poor working atmosphere'. 'Flexibility in the work schedule' and 'location' were the most important factors for re-entry from their perspective. There were not many dental hygienists hoping to return to the dental field. The findings suggested that strategies to encourage non-practicing dental hygienists to re-entry should be emphasized in the areas of a flexible working atmosphere, easy access to information on how to return to practice and guidance on how to maintain professionalism during inactivity. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Agricultural Safety and Health: A Resource Guide. Rural Information Center Publication Series, No. 40. Revised Edition.

ERIC Educational Resources Information Center

Zimmerman, Joy, Comp.

This guide lists resource materials that address agricultural occupational injuries and diseases and their prevention. Many of the entries were derived from the AGRICOLA database produced by the National Agricultural Library and include journal articles, books, government reports, training materials, and audiovisual materials. The first section…

49 CFR Appendix D to Part 222 - Determining Risk Levels

Code of Federal Regulations, 2011 CFR

2011-10-01

... prediction formulas can be used to derive the following for each crossing: 1. the predicted collisions (PC) 2... for errors such as data entry errors. The final output is the predicted number of collisions (PC). (e... collisions (PC). (f) For the prediction and severity index formulas, please see the following DOT...

Perceptions of College Readiness and Social Capital of GED Completers in Entry-Level College Courses

ERIC Educational Resources Information Center

Lott, Donalyn Leufroy

2012-01-01

Examining the efficacy of literacy improvement, general education development (GED) completion, and GED completers' perceptions of college readiness and social capital was the purpose of this study. The participant sample (n = 321), derived from the target population (N = 1050), consisted of former participants of Adult Literacy Education…

Caregiver Descriptions of the Developmental Skills of Infants and Toddlers Entering Early Intervention Services

ERIC Educational Resources Information Center

Scarborough, Anita A.; Hebbeler, Kathleen M.; Simeonsson, Rune J.; Spiker, Donna

2007-01-01

The present study was conducted to describe the developmental skills of a national sample of infants and toddlers at entry into early intervention services. Caregivers were asked about their child's skills during a telephone interview. Summary values were derived from descriptions of motor, communication, independence, and cognitive skills. More…

Improved design of a tangential entry cyclone separator for separation of particles from exhaust gas of diesel engine.

PubMed

Mukhopadhyay, N

2011-01-01

An effective design of cyclone separator with tangential inlet is developed applying an equation derived from the correlation of collection efficiency with maximum pressure drop components of the cyclone, which can efficiently remove the particles around 1microm of the exhaust gas of diesel engine.

78 FR 62959 - Kiwifruit Grown in California; Decreased Assessment Rate

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-23

... necessary expenses of the program. The fiscal period began on August 1 and ends July 31. The assessment rate... are derived from such assessments. It is intended that the assessment rate as issued herein will be... the date of the entry of the ruling. This rule decreases the assessment rate established for the...

Pittsburgh Technical Health Training Institute Demonstration Project; Quarterly Report.

ERIC Educational Resources Information Center

Kishkunas, Louis J.

This fifth quarterly report covers the period June 15, 1967 to December 15, 1967 of a project aimed at demonstrating a faster method of training higly qualified workers for the health field. During this period, nurse aides were trained in a pilot program based upon the educational objectives derived from entry level behavioral specifications…

Review: Modelling chemical kinetics and convective heating in giant planet entries

NASA Astrophysics Data System (ADS)

Reynier, Philippe; D'Ammando, Giuliano; Bruno, Domenico

2018-01-01

A review of the existing chemical kinetics models for H2 / He mixtures and related transport and thermodynamic properties is presented as a pre-requisite towards the development of innovative models based on the state-to-state approach. A survey of the available results obtained during the mission preparation and post-flight analyses of the Galileo mission has been undertaken and a computational matrix has been derived. Different chemical kinetics schemes for hydrogen/helium mixtures have been applied to numerical simulations of the selected points along the entry trajectory. First, a reacting scheme, based on literature data, has been set up for computing the flow-field around the probe at high altitude and comparisons with existing numerical predictions are performed. Then, a macroscopic model derived from a state-to-state model has been constructed and incorporated into a CFD code. Comparisons with existing numerical results from the literature have been performed as well as cross-check comparisons between the predictions provided by the different models in order to evaluate the potential of innovative chemical kinetics models based on the state-to-state approach.

Pilot Evaluation of Angiogenesis Signaling Factor Response after Transcatheter Arterial Embolization for Hepatocellular Carcinoma.

PubMed

Ronald, James; Nixon, Andrew B; Marin, Daniele; Gupta, Rajan T; Janas, Gemini; Chen, Willa; Suhocki, Paul V; Pabon-Ramos, Waleska; Sopko, David R; Starr, Mark D; Brady, John C; Hurwitz, Herbert I; Kim, Charles Y

2017-10-01

Purpose To identify changes in a broad panel of circulating angiogenesis factors after bland transcatheter arterial embolization (TAE), a purely ischemic treatment for hepatocellular carcinoma (HCC). Materials and Methods This prospective HIPAA-compliant study was approved by the institutional review board. Informed written consent was obtained from all participants prior to entry into the study. Twenty-five patients (21 men; mean age, 61 years; range, 30-81 years) with Liver Imaging Reporting and Data System category 5 or biopsy-proven HCC and who were undergoing TAE were enrolled from October 15, 2014, through December 2, 2015. Nineteen plasma angiogenesis factors (angiopoietin 2; hepatocyte growth factor; platelet-derived growth factor AA and BB; placental growth factor; vascular endothelial growth factor A and D; vascular endothelial growth factor receptor 1, 2, and 3; osteopontin; transforming growth factor β1 and β2; thrombospondin 2; intercellular adhesion molecule 1; interleukin 6 [IL-6]; stromal cell-derived factor 1; tissue inhibitor of metalloproteinases 1; and vascular cell adhesion molecule 1 [VCAM-1]) were measured by using enzyme-linked immunosorbent assays at 1 day, 2 weeks, and 5 weeks after TAE and were compared with baseline levels by using paired Wilcoxon tests. Tumor response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Angiogenesis factor levels were compared between responders and nonresponders by mRECIST criteria by using unpaired Wilcoxon tests. Results All procedures were technically successful with no complications. Fourteen angiogenesis factors showed statistically significant changes following TAE, but most changes were transient. IL-6 was upregulated only 1 day after the procedure, but showed the largest increases of any factor. Osteopontin and VCAM-1 demonstrated sustained upregulation at all time points following TAE. At 3-month follow-up imaging, 11 patients had responses to TAE (complete response, n = 6; partial response, n = 5) and 11 patients were nonresponders (stable disease, n = 9; progressive disease, n = 2). In nonresponders, the percent change in IL-6 on the day after TAE (P = .033) and the mean percent change in osteopontin after TAE (P = .024) were significantly greater compared with those of responders. Conclusion Multiple angiogenesis factors demonstrated significant upregulation after TAE. VCAM-1 and osteopontin demonstrated sustained upregulation, whereas the rest were transient. IL-6 and osteopontin correlated significantly with radiologic response after TAE. © RSNA, 2017.

Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex.

PubMed

Chiba, Shuichi; Numakawa, Tadahiro; Ninomiya, Midori; Richards, Misty C; Wakabayashi, Chisato; Kunugi, Hiroshi

2012-10-01

Stress and the resulting increase in glucocorticoid levels have been implicated in the pathophysiology of depressive disorders. We investigated the effects of chronic restraint stress (CRS: 6 hours × 28 days) on anxiety- and depression-like behaviors in rats and on the possible changes in glucocorticoid receptor (GR) expression as well as brain-derived neurotrophic factor (BDNF)-dependent neural function in the prefrontal cortex (PFC). We observed significant reductions in body weight gain, food intake and sucrose preference from 1 week after the onset of CRS. In the 5th week of CRS, we conducted open-field (OFT), elevated plus-maze (EPM) and forced swim tests (FST). We observed a decrease in the number of entries into open arms during the EPM (anxiety-like behavior) and increased immobility during the FST (depression-like behavior). When the PFC was removed after CRS and subject to western blot analysis, the GR expression reduced compared with control, while the levels of BDNF and its receptors remained unchanged. Basal glutamate concentrations in PFC acute slice which were measured by high performance liquid chromatography were not influenced by CRS. However, BDNF-induced glutamate release was attenuated after CRS. These results suggest that reduced GR expression and altered BDNF function may be involved in chronic stress-induced anxiety--and depression-like behaviors. Copyright © 2012 Elsevier Inc. All rights reserved.

Linking medical records to an expert system

NASA Technical Reports Server (NTRS)

Naeymi-Rad, Frank; Trace, David; Desouzaalmeida, Fabio

1991-01-01

This presentation will be done using the IMR-Entry (Intelligent Medical Record Entry) system. IMR-Entry is a software program developed as a front-end to our diagnostic consultant software MEDAS (Medical Emergency Decision Assistance System). MEDAS (the Medical Emergency Diagnostic Assistance System) is a diagnostic consultant system using a multimembership Bayesian design for its inference engine and relational database technology for its knowledge base maintenance. Research on MEDAS began at the University of Southern California and the Institute of Critical Care in the mid 1970's with support from NASA and NSF. The MEDAS project moved to Chicago in 1982; its current progress is due to collaboration between Illinois Institute of Technology, The Chicago Medical School, Lake Forest College and NASA at KSC. Since the purpose of an expert system is to derive a hypothesis, its communication vocabulary is limited to features used by its knowledge base. The development of a comprehensive problem based medical record entry system which could handshake with an expert system while creating an electronic medical record at the same time was studied. IMR-E is a computer based patient record that serves as a front end to the expert system MEDAS. IMR-E is a graphically oriented comprehensive medical record. The programs major components are demonstrated.

Validation of nuclear magnetic resonance structures of proteins and nucleic acids: hydrogen geometry and nomenclature.

PubMed

Doreleijers, J F; Vriend, G; Raves, M L; Kaptein, R

1999-11-15

A statistical analysis is reported of 1,200 of the 1,404 nuclear magnetic resonance (NMR)-derived protein and nucleic acid structures deposited in the Protein Data Bank (PDB) before 1999. Excluded from this analysis were the entries not yet fully validated by the PDB and the more than 100 entries that contained < 95% of the expected hydrogens. The aim was to assess the geometry of the hydrogens in the remaining structures and to provide a check on their nomenclature. Deviations in bond lengths, bond angles, improper dihedral angles, and planarity with respect to estimated values were checked. More than 100 entries showed anomalous protonation states for some of their amino acids. Approximately 250,000 (1.7%) atom names differed from the consensus PDB nomenclature. Most of the inconsistencies are due to swapped prochiral labeling. Large deviations from the expected geometry exist for a considerable number of entries, many of which are average structures. The most common causes for these deviations seem to be poor minimization of average structures and an improper balance between force-field constraints for experimental and holonomic data. Some specific geometric outliers are related to the refinement programs used. A number of recommendations for biomolecular databases, modeling programs, and authors submitting biomolecular structures are given.

SHEFEX II - Aerodynamic Re-Entry Controlled Sharp Edge Flight Experiment

NASA Astrophysics Data System (ADS)

Longo, J. M. A.; Turner, J.; Weihs, H.

2009-01-01

In this paper the basic goals and architecture of the SHEFEX II mission is presented. Also launched by a two staged sounding rocket system SHEFEX II is a consequent next step in technology test and demonstration. Considering all experience and collected flight data obtained during the SHEFEX I Mission, the test vehicle has been re-designed and extended by an active control system, which allows active aerodynamic control during the re-entry phase. Thus, ceramic based aerodynamic control elements like rudders, ailerons and flaps, mechanical actuators and an automatic electronic control unit has been implemented. Special focus is taken on improved GNC Elements. In addition, some other experiments including an actively cooled thermal protection element, advanced sensor equipment, high temperature antenna inserts etc. are part of the SHEFEX II experimental payload. A final 2 stage configuration has been selected considering Brazilian solid rocket boosters derived from the S 40 family. During the experiment phase a maximum entry velocity of Mach around 10 is expected for 50 seconds. Considering these flight conditions, the heat loads are not representative for a RLV re-entry, however, it allows to investigate the principal behaviour of such a facetted ceramic TPS, a sharp leading edge at the canards and fins and all associated gas flow effects and their structural response.

Organic matter on the early surface of Mars: An assessment of the contribution by interplanetary dust

NASA Technical Reports Server (NTRS)

Flynn, G. J.

1993-01-01

Calculations by Anders and Chyba et al. have recently revived interest in the suggestion that organic compounds important to the development of life were delivered to the primitive surface of the Earth by comets, asteroids or the interplanetary dust derived from these two sources. Anders has shown that the major post-accretion contribution of extraterrestrial organic matter to the surface of the Earth is from interplanetary dust. Since Mars is a much more favorable site for the gentle deceleration of interplanetary dust particles than is Earth, model calculations show that biologically important organic compounds are likely to have been delivered to the early surface of Mars by the interplanetary dust in an order-of-magnitude higher surface density than onto the early Earth. Using the method described by Flynn and McKay, the size frequency distribution, and the atmospheric entry velocity distribution of IDP's at Mars were calculated. The entry velocity distribution, coupled with the atmospheric entry heating model developed by Whipple and extended by Fraundorf was used to calculate the fraction of the particles in each mass decade which survives atmospheric entry without melting (i.e., those not heated above 1600K). The incident mass and surviving mass in each mass decade are shown for both Earth and Mars.

Characterizing the Anti-HIV Activity of Papuamide A

PubMed Central

Andjelic, Cynthia D; Planelles, Vicente; Barrows, Louis R

2008-01-01

Papuamide A is representative of a class of marine derived cyclic depsipeptides, reported to have cytoprotective activity against HIV-1 in vitro. We show here that papuamide A acts as an entry inhibitor, preventing human immunodeficiency virus infection of host cells and that this inhibition is not specific to R5 or X4 tropic virus. This inhibition of viral entry was determined to not be due to papuamide A binding to CD4 or HIV gp120, the two proteins involved in the cell-virus recognition and binding. Furthermore, papuamide A was able to inhibit HIV pseudotype viruses expressing envelope glycoproteins from vesicular stomatitis virus or amphotropic murine leukemia virus indicating the mechanism of viral entry inhibition is not HIV-1 envelope glycoprotein specific. Time delayed addition studies with the pseudotyped viruses show that papuamide A inhibits viral infection only at the initial stage of the viral life cycle. Additionally, pretreatment studies revealed that the virus, and not the cell, is the target of papuamide A’s action. Together, these results suggest a direct virucidal mechanism of HIV-1 inhibition by papuamide A. We also demonstrate here that the other papuamides (B-D) are able to inhibit viral entry indicating that the free amino moiety of 2,3-diaminobutanoic acid residue is not required for the virucidal activity. PMID:19172193

Parametric Structural Model for a Mars Entry Concept

NASA Technical Reports Server (NTRS)

Lane, Brittney M.; Ahmed, Samee W.

2017-01-01

This paper outlines the process of developing a parametric model for a vehicle that can withstand Earth launch and Mars entry conditions. This model allows the user to change a variety of parameters ranging from dimensions and meshing to materials and atmospheric entry angles to perform finite element analysis on the model for the specified load cases. While this work focuses on an aeroshell for Earth launch aboard the Space Launch System (SLS) and Mars entry, the model can be applied to different vehicles and destinations. This specific project derived from the need to deliver large payloads to Mars efficiently, safely, and cheaply. Doing so requires minimizing the structural mass of the body as much as possible. The code developed for this project allows for dozens of cases to be run with the single click of a button. The end result of the parametric model gives the user a sense of how the body reacts under different loading cases so that it can be optimized for its purpose. The data are reported in this paper and can provide engineers with a good understanding of the model and valuable information for improving the design of the vehicle. In addition, conclusions show that the frequency analysis drives the design and suggestions are made to reduce the significance of normal modes in the design.

Vulnerability to re-entry in simulated two-dimensional cardiac tissue: effects of electrical restitution and stimulation sequence.

PubMed

Tran, Diana X; Yang, Ming-Jim; Weiss, James N; Garfinkel, Alan; Qu, Zhilin

2007-12-01

Ventricular fibrillation is a lethal arrhythmia characterized by multiple wavelets usually starting from a single or figure-of-eight re-entrant circuit. Understanding the factors regulating vulnerability to the re-entry is essential for developing effective therapeutic strategies to prevent ventricular fibrillation. In this study, we investigated how pre-existing tissue heterogeneities and electrical restitution properties affect the initiation of re-entry by premature extrastimuli in two-dimensional cardiac tissue models. We studied two pacing protocols for inducing re-entry following the "sinus" rhythm (S1) beat: (1) a single premature (S2) extrastimulus in heterogeneous tissue; (2) two premature extrastimuli (S2 and S3) in homogeneous tissue. In the first case, the vulnerable window of re-entry is determined by the spatial dimension and extent of the heterogeneity, and is also affected by electrical restitution properties and the location of the premature stimulus. The vulnerable window first increases as the action potential duration (APD) difference between the inside and outside of the heterogeneous region increases, but then decreases as this difference increases further. Steeper APD restitution reduces the vulnerable window of re-entry. In the second case, electrical restitution plays an essential role. When APD restitution is flat, no re-entry can be induced. When APD restitution is steep, re-entry can be induced by an S3 over a range of S1S2 intervals, which is also affected by conduction velocity restitution. When APD restitution is even steeper, the vulnerable window is reduced due to collision of the spiral tips.

Impact of school-entry and education mandates by states on HPV vaccination coverage: Analysis of the 2009-2013 National Immunization Survey-Teen.

PubMed

Perkins, Rebecca B; Lin, Mengyun; Wallington, Sherrie F; Hanchate, Amresh D

2016-06-02

To determine the effectiveness of existing school entry and education mandates on HPV vaccination coverage, we compared coverage among girls residing in states and jurisdictions with and without education and school-entry mandates. Virginia and the District of Columbia enacted school entry mandates, though both laws included liberal opt-out provisions. Ten additional states had mandates requiring distribution of education to parents or provision of education within school curricula. Using data from the National Immunization Survey-Teen from 2009-2013, we estimated multilevel logistic regression models to compare coverage with HPV vaccines for girls ages 13-17 residing in states and jurisdictions with and without school entry and education mandates, adjusting for demographic factors, healthcare access, and provider recommendation. Girls residing in states and jurisdictions with HPV vaccine school entry mandates (DC and VA) and education mandates (LA, MI, CO, IN, IA, IL, NJ, NC, TX, and WA) did not have higher HPV vaccine series initiation or completion than those living in states without mandates for any year (2009-2013). Similar results were seen when comparing girls ages 13-14 to those ages 15-17, and after adjustment for known covariates of vaccination. States and jurisdictions with school-entry and education mandates do not currently have higher HPV vaccination coverage than states without such legislation. Liberal opt-out language in existing school entry mandates may weaken their impact. Policy-makers contemplating legislation to improve vaccination coverage should be aware of the limitations of existing mandates.

Exploring the associations between intimate partner violence victimization during pregnancy and delayed entry into prenatal care: Evidence from a population-based study in Bangladesh.

PubMed

Islam, Md Jahirul; Broidy, Lisa; Baird, Kathleen; Mazerolle, Paul

2017-04-01

Intimate partner violence (IPV) during pregnancy can have serious health consequences for mothers and newborns. The aim of the study is to explore: 1) the influence of experiencing IPV during pregnancy on delayed entry into prenatal care; and 2) whether women's decision-making autonomy and the support for traditional gender roles act to mediate or moderate the relationship between IPV and delayed entry into prenatal care. cross-sectional survey. Multivariate logistic regression models were estimated that control for various socio-demographic and pregnancy related factors to assess whether women who experienced IPV during pregnancy were more likely to delay entry into prenatal care compared with women who had not experienced IPV. The influence of traditional gender roles acceptance and decision-making autonomy were examined both as independent variables and in interaction with IPV, to assess their role as potential mediators or moderators. Chandpur district, Bangladesh. the sample comprised of 426 Bangladeshi women, aged 15-49 years. Postpartum mothers who visited vaccinations centres to receive their children's vaccinations constitute the sampling frame. almost 70% of the women surveyed reported patterns consistent with delayed entry into prenatal care. Accounting for the influence of other covariates, women who experienced physical IPV during pregnancy were 2.61 times more likely (95% CI [1.33, 5.09]) to have delayed entry into prenatal care than their counterparts who did not report physical IPV. Neither sexual nor psychological IPV victimization during pregnancy was linked with late entry into prenatal care. Both gender role attitudes and levels of autonomy mediate the effect of IPV on prenatal care. the results suggest that the high rates of IPV in Bangladesh have effects that can compromise women's health seeking behaviour during pregnancy, putting them and their developing fetus at risk. Specifically, Bangladeshi women who experience physical IPV during pregnancy are more likely to delay or forgo prenatal care, an effect that is further magnified by cultural ideals that emphasize women's traditional roles and limit their autonomy. this study reinforces the need to detect and assist women suffering IPV, not only to offer them help and support but also to increase entry into prenatal care. Healthcare professionals involved in obstetrics and midwifery need to be aware of the risk factors of IPV during pregnancy and be able to identify women who are at risk for delayed entry into prenatal care. Copyright © 2017 Elsevier Ltd. All rights reserved.

Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus

DTIC Science & Technology

2011-01-06

identified viral restriction factors that inhibit infection mediated by the influenza A virus ( IAV ) hemagglutinin (HA) protein. Here we show that IFITM...observations, interferon-b specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV...We observed distinct patterns of IFITM-mediated restriction: compared with IAV , the entry processes of MARV and EBOV were less restricted by IFITM3

Risk Factors for Mosquito House Entry in the Lao PDR

PubMed Central

Hiscox, Alexandra; Khammanithong, Phasouk; Kaul, Surinder; Sananikhom, Pany; Luthi, Ruedi; Brey, Paul T.; Lindsay, Steve W.

2013-01-01

Background Construction of the Nam Theun 2 hydroelectric project and flooding of a 450 km2 area of mountain plateau in south-central Lao PDR resulted in the resettlement of 6,300 people to newly built homes. We examined whether new houses would have altered risk of house entry by mosquitoes compared with traditional homes built from poorer construction materials. Methodology/Principal Findings Surveys were carried out in the Nam Theun 2 resettlement area and a nearby traditional rice farming area in 2010. Mosquitoes were sampled in bedrooms using CDC light traps in 96 resettlement houses and 96 traditional houses and potential risk factors for mosquito house entry were recorded. Risk of mosquito house entry was more than twice as high in traditional bamboo houses compared with those newly constructed from wood (Putative Japanese Encephalitis (JE) vector incidence rate ratio (IRR) = 2.26, 95% CI 1.38–3.70, P = 0.001; Anopheline IRR = 2.35, 95% CI: 1.30–4.23, P = 0.005). Anophelines were more common in homes with cattle compared against those without (IRR = 2.32, 95% CI: 1.29–4.17, P = 0.005).Wood smoke from cooking fires located under the house or indoors was found to be protective against house entry by both groups of mosquito, compared with cooking in a separate room beside the house (Putative JE vector IRR = 0.43, 95% CI: 0.26–0.73, P = 0.002; Anopheline IRR = 0.22, 95% CI: 0.10–0.51, P<0.001). Conclusions/Significance Construction of modern wooden homes should help reduce human-mosquito contact in the Lao PDR. Reduced mosquito contact rates could lead to reduced transmission of diseases such as JE and malaria. Cattle ownership was associated with increased anopheline house entry, so zooprophylaxis for malaria control is not recommended in this area. Whilst wood smoke was protective against putative JE vector and anopheline house entry we do not recommend indoor cooking since smoke inhalation can enhance respiratory disease. PMID:23700411

Analytic Development of a Reference Profile for the First Entry in a Skip Atmospheric Entry

NASA Technical Reports Server (NTRS)

Garcia-Llama, Eduardo

2010-01-01

This note shows that a feasible reference drag profile for the first entry portion of a skip entry can be generated as a polynomial expression of the velocity. The coefficients of that polynomial are found through the resolution of a system composed of m + 1 equations, where m is the degree of the drag polynomial. It has been shown that a minimum of five equations (m = 4) are required to establish the range and the initial and final conditions on velocity and flight path angle. It has been shown that at least one constraint on the trajectory can be imposed through the addition of one extra equation in the system, which must be accompanied by the increase in the degree of the drag polynomial. In order to simplify the resolution of the system of equations, the drag was considered as being a probability density function of the velocity, with the velocity as a distribution function of the drag. Combining this notion with the introduction of empirically derived constants, it has been shown that the system of equations required to generate the drag profile can be successfully reduced to a system of linear algebraic equations. For completeness, the resulting drag profiles have been flown using the feedback linearization method of differential geometric control as a guidance law with the error dynamics of a second order homogeneous equation in the form of a damped oscillator. Satisfactory results were achieved when the gains in the error dynamics were changed at a certain point along the trajectory that is dependent on the velocity and the curvature of the drag as a function of the velocity. Future work should study the capacity to update the drag profile in flight when dispersions are introduced. Also, future studies should attempt to link the first entry, as presented and controlled in this note, with a more standard control concept for the second entry, such as the Apollo entry guidance, to try to assess the overall skip entry performance. A guidance law that includes an integral feedback term, as is the case in the actual Space Shuttle entry guidance and as is proposed in Ref 29, could be tried in future studies to assess whether its use results in an improvement of the tracking performance, and to evaluate the design needs when determining the control gains.

Complex Virus-Host Interactions Involved in the Regulation of Classical Swine Fever Virus Replication: A Minireview.

PubMed

Li, Su; Wang, Jinghan; Yang, Qian; Naveed Anwar, Muhammad; Yu, Shaoxiong; Qiu, Hua-Ji

2017-07-05

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs in many countries. Viruses are small intracellular parasites and thus rely on the cellular factors for replication. Fundamental aspects of CSFV-host interactions have been well described, such as factors contributing to viral attachment, modulation of genomic replication and translation, antagonism of innate immunity, and inhibition of cell apoptosis. However, those host factors that participate in the viral entry, assembly, and release largely remain to be elucidated. In this review, we summarize recent progress in the virus-host interactions involved in the life cycle of CSFV and analyze the potential mechanisms of viral entry, assembly, and release. We conclude with future perspectives and highlight areas that require further understanding.

Complex Virus–Host Interactions Involved in the Regulation of Classical Swine Fever Virus Replication: A Minireview

PubMed Central

Li, Su; Wang, Jinghan; Yang, Qian; Naveed Anwar, Muhammad; Yu, Shaoxiong; Qiu, Hua-Ji

2017-01-01

Classical swine fever (CSF), caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs in many countries. Viruses are small intracellular parasites and thus rely on the cellular factors for replication. Fundamental aspects of CSFV–host interactions have been well described, such as factors contributing to viral attachment, modulation of genomic replication and translation, antagonism of innate immunity, and inhibition of cell apoptosis. However, those host factors that participate in the viral entry, assembly, and release largely remain to be elucidated. In this review, we summarize recent progress in the virus–host interactions involved in the life cycle of CSFV and analyze the potential mechanisms of viral entry, assembly, and release. We conclude with future perspectives and highlight areas that require further understanding. PMID:28678154

Shuttle entry guidance revisited

NASA Technical Reports Server (NTRS)

Mease, Kenneth D.; Kremer, Jean-Paul

1992-01-01

The Shuttle entry guidance concept is reviewed which is aimed at tracking a reference drag trajectory that leads to the specified range and velocity for the initiation of the terminal energy management phase. An approximate method of constructing the domain of attraction is proposed, and its validity is ascertained by simulation. An alternative guidance law yielding global exponential tracking in the absence of control saturation is derived using a feedback linearization method. It is noted that the alternative guidance law does not improve on the stability and performance of the current guidance law, for the operating domain and control capability of the Shuttle. It is suggested that the new guidance law with a larger operating domain and increased lift-to-drag capability would be superior.

Inhibition of HIV-1 entry by the tricyclic coumarin GUT-70 through the modification of membrane fluidity

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

Matsuda, Kouki; Hattori, Shinichiro; Kariya, Ryusho

Membrane fusion between host cells and HIV-1 is the initial step in HIV-1 infection, and plasma membrane fluidity strongly influences infectivity. In the present study, we demonstrated that GUT-70, a natural product derived from Calophyllum brasiliense, stabilized plasma membrane fluidity, inhibited HIV-1 entry, and down-regulated the expression of CD4, CCR5, and CXCR4. Since GUT-70 also had an inhibitory effect on viral replication through the inhibition of NF-κB, it is expected to be used as a dual functional and viral mutation resistant reagent. Thus, these unique properties of GUT-70 enable the development of novel therapeutic agents against HIV-1 infection.

Preliminary analysis of STS-2 entry flight data

NASA Technical Reports Server (NTRS)

1982-01-01

A preliminary analysis of the data obtained during the entry of the STS-2 flight was completed. The stability and control derivatives from STS-2 were examined. Questions still remain throughout the flight envelope and the area below Mach 3 needs more study. With three controls operating in a high gain feedback system, it is difficult to separate the individual effects of each of the controls. Analysis of the aerothermal data shows that wing structural-temperature measurements are generally repeatable and consistent with the trajectories. The measured wing upper surface temperatures are in reasonable agreement with Dryden predictions but wing lower surface temperatures are higher than Dryden predictions. Heating and heat transfer models will be adjusted to improve the temperature prediction capability for future trajectories.

Analysis of space shuttle orbiter entry dynamics from Mach 10 to Mach 2.5 with the November 1976 flight control system

NASA Technical Reports Server (NTRS)

Powell, R. W.; Stone, H. W.

1980-01-01

A six-degree-of-freedom simulation analysis was performed for the space shuttle orbiter entry from Mach 10 to Mach 2.5 with realistic off-nominal conditions using the flight control system referred to as the November 1976 Integrated Digital Autopilot. The off-nominal conditions included: (1) aerodynamic uncertainties in extrapolating from wind tunnel of flight characteristics, (2) error in deriving angle of attack from onboard instrumentation, (3) failure of two of the four reaction control-system thrusters on each side (design specification), and (4) lateral center-of-gravity offset. Many combinations of these off-nominal conditions resulted in a loss of the orbiter. Control-system modifications were identified to prevent this possibility.

Tissue engineering: Dentin - pulp complex regeneration approaches (A review).

PubMed

Hashemi-Beni, Batool; Khoroushi, Maryam; Foroughi, Mohammad Reza; Karbasi, Saeed; Khademi, Abbas Ali

2017-10-01

Dental pulp is a highly specialized tissue that preserves teeth. It is important to maintain the capabilities of dental pulp before a pulpectomy by creating a local restoration of the dentin-pulp complex from residual dental pulp. The articles identified were selected by two reviewers based on entry and exit criteria. All relevant articles indexed in PubMed, Springer, Science Direct, and Scopus with no limitations from 1961 to 2016 were searched. Factors investigated in the selected articles included the following key words: Dentin-Pulp Complex, Regeneration, Tissue Engineering, Scaffold, Stem Cell, and Growth Factors. Of the 233 abstracts retrieved, the papers which were selected had evaluated the clinical aspects of the application of dentin-pulp regeneration. Generally, this study has introduced a new approach to provoke the regeneration of the dentin-pulp complex after a pulpectomy, so that exogenous growth factors and the scaffold are able to induce cells and blood vessels from the residual dental pulp in the tooth root canal. This study further presents a new strategy for local regeneration therapy of the dentin-pulp complex. This review summarizes the current knowledge of the potential beneficial effects derived from the interaction of dental materials with the dentin-pulp complex as well as potential future developments in this exciting field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Factors associated with mortality of patients with myxoedema coma: prospective study in 11 cases treated in a single institution.

PubMed

Rodríguez, I; Fluiters, E; Pérez-Méndez, L F; Luna, R; Páramo, C; García-Mayor, R V

2004-02-01

This study was carried out to investigate the clinical and biochemical factors which might be of importance in predicting the outcome of patients with myxoedema coma. Eleven patients (ten female) aged 68.1+/-19.5 years attended our institution over a period of 18 years. Glasgow and APACHE II scores and serum free thyroxine and TSH were measured in all the patients on entry. Patients were selected at random to be treated with two different regimens of l-thyroxine. Four patients died with the mortality rate being 36.4%. The patients in coma at entry had significantly higher mortality rates than those with minor degrees of consciousness (75% vs 14.3% respectively, P=0.04). The surviving patients had significantly higher Glasgow scores than those who died (11.85+/-2.3 vs 5.25+/-2.2 respectively, P<0.001). Comparison of the mean values of APACHE II scores between the surviving group and those who died was significantly different (18.0+/-2.08 vs 31.5+/-2.08 respectively, P<0.0001). The degree of consciousness, the Glasgow score and the severity of the illness measured by APACHE II score on entry were the main factors that determined the post-treatment outcome of patients with myxoedema coma.

Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands-Relation to Rheumatoid Arthritis.

PubMed

Trier, Nicole; Izarzugaza, Jose; Chailyan, Anna; Marcatili, Paolo; Houen, Gunnar

2018-01-21

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50-60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles encode a conserved sequence of amino acids, referred to as the shared epitope (SE) structure. By analyzing the structure of a HLA-DR molecule in complex with Epstein-Barr virus (EBV), the SE motif is suggested to play a vital role in the interaction of MHC II with the viral glycoprotein (gp) 42, an essential entry factor for EBV. EBV has been repeatedly linked to RA by several lines of evidence and, based on several findings, we suggest that EBV is able to induce the onset of RA in predisposed SE-positive individuals, by promoting entry of B-cells through direct contact between SE and gp42 in the entry complex.

Human MHC-II with Shared Epitope Motifs Are Optimal Epstein-Barr Virus Glycoprotein 42 Ligands—Relation to Rheumatoid Arthritis

PubMed Central

Trier, Nicole; Izarzugaza, Jose; Chailyan, Anna; Marcatili, Paolo; Houen, Gunnar

2018-01-01

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology, which is characterized by inflammation in the synovium and joint damage. Although the pathogenesis of RA remains to be determined, a combination of environmental (e.g., viral infections) and genetic factors influence disease onset. Especially genetic factors play a vital role in the onset of disease, as the heritability of RA is 50–60%, with the human leukocyte antigen (HLA) alleles accounting for at least 30% of the overall genetic risk. Some HLA-DR alleles encode a conserved sequence of amino acids, referred to as the shared epitope (SE) structure. By analyzing the structure of a HLA-DR molecule in complex with Epstein-Barr virus (EBV), the SE motif is suggested to play a vital role in the interaction of MHC II with the viral glycoprotein (gp) 42, an essential entry factor for EBV. EBV has been repeatedly linked to RA by several lines of evidence and, based on several findings, we suggest that EBV is able to induce the onset of RA in predisposed SE-positive individuals, by promoting entry of B-cells through direct contact between SE and gp42 in the entry complex. PMID:29361739

Fad24, a Positive Regulator of Adipogenesis, Is Required for S Phase Re-entry of C2C12 Myoblasts Arrested in G0 Phase and Involved in p27(Kip1) Expression at the Protein Level.

PubMed

Ochiai, Natsuki; Nishizuka, Makoto; Osada, Shigehiro; Imagawa, Masayoshi

2016-05-01

Factor for adipocyte differentiation 24 (fad24) is a positive regulator of adipogenesis. We previously found that human fad24 is abundantly expressed in skeletal muscle. However, the function of fad24 in skeletal muscle remains largely unknown. Because skeletal muscle is a highly regenerative tissue, we focused on the function of fad24 in skeletal muscle regeneration. In this paper, we investigated the role of fad24 in the cell cycle re-entry of quiescent C2C12 myoblasts-mimicked satellite cells. The expression levels of fad24 and histone acetyltransferase binding to ORC1 (hbo1), a FAD24-interacting factor, were elevated at the early phase of the regeneration process in response to cardiotoxin-induced muscle injury. The knockdown of fad24 inhibited the proliferation of quiescent myoblasts, whereas fad24 knockdown did not affect differentiation. S phase entry following serum activation is abrogated by fad24 knockdown in quiescent cells. Furthermore, fad24 knockdown cells show a marked accumulation of p27(Kip1) protein. These results suggest that fad24 may have an important role in the S phase re-entry of quiescent C2C12 cells through the regulation of p27(Kip1) at the protein level.

[Researches on health and welfare promotion based on an approach of social medicine].

PubMed

Kagamimori, Sadanobu

2004-07-01

This article was derived from my memorial talk given when receiving the prize of the Japanese Society for Hygiene at their academic congress. The reader could review my research on health and welfare promotion made by introducing new conceptual health policy based on the approach of social medicine. Through my experience in different research work, the importance of social factors in the etiology of health during childhood, adulthood and old age was discussed. In addition, it was revealed that social factors not only influence the population's health status but also constitute the context within which organized efforts can be made to promote health. For the elderly, the annual health check, stroke patient registration, and insurance for care and spousal bereavement; for adults, the Karoshi and occupational health; and for children, air pollution-atopy predisposition and lifestyles were highlighted as social medicine-related issues. The research on mostly longitudinal population studies showed that health status, including the life expectancy and the prevalence of disability and chronic disorders, are related to one's marital status, social support, psychosocial working conditions and environmental factors as well as to lifestyles such as physical activity and hours of work and sleep at entry. More attention should be directed to independent factors' effects on health, separate from those of adverse health habits and bio-medical situations, under the health and welfare promotion strategy.

Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors

PubMed Central

Mevers, Emily; Higgins, Kathleen W.; Fomina, Yevgenia; Zhang, Jianming; Mandinova, Anna; Newman, David; Shaw, Stanley Y.; Clardy, Jon; Mootha, Vamsi K.

2016-01-01

Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS). Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as “complex I bypass.” In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology. PMID:27622560

40 CFR 92.215 - Maintenance of records; submittal of information; right of entry.

Code of Federal Regulations, 2010 CFR

2010-07-01

... stage to the production stage, or to locomotive (or engine) manufacture, remanufacture, or assembly is...) In the case where a current production engine is modified for use as a certification engine or in a... not derived from a current production engine, a general description of the buildup of the engine (e.g...

Soluble leaf apoplastic constituents of O3-sensitive and tolerant soybeans and snap beans

USDA-ARS?s Scientific Manuscript database

Upon entry into leaves, ozone (O3) and reactive oxygen species (ROS) derived from O3 must pass through the leaf apoplast and cell wall before reacting with the plasma membrane to initiate plant responses. The leaf apoplast, therefore, represents a first line of defense in detoxifying ROS and prevent...

Adults with Learning Disabilities in the Workforce: Lessons for Secondary Transition Programs

ERIC Educational Resources Information Center

Madaus, Joseph W.; Gerber, Paul J.; Price, Lynda A.

2008-01-01

Now almost 15 years after the implementation of the Americans with Disabilities Act (ADA) data are emerging in the literature related to job entry and employment outcomes of adults with learning disabilities (LD). Although these data are derived from varying methodologies, they converge in three critical areas: Knowledge of the ADA, realities of…

The Extended TANF Application Period and Applicant Outcomes: Evidence from Wisconsin

ERIC Educational Resources Information Center

Cancian, Maria; Noyes, Jennifer L.; Ybarra, Marci

2012-01-01

This article examines the characteristics and income patterns associated with welfare entry and nonentry in the context of an extended application period for a sample of 1,664 women who applied for Temporary Assistance for Needy Families services in Wisconsin in the fall of 2006. The study uses data derived from the systematic review of caseworker…

Integrating forest growth and harvesting cost models to improve forest management planning

Treesearch

J.E. Baumgras; C.B. LeDoux

1991-01-01

Two methods of estimating harvesting revenue--reported stumpage prices - and delivered prices minus estimated harvesting and haul costs were compared by estimating entry cash flows and rotation net present value for three simulated even-aged forest management options that included 1 to 3 thinnings over a 90 year rotation. Revenue estimates derived from stumpage prices...

Antiviral interactions of combinations of highly potent 2,4(1H,3H)-pyrimidinedione congeners and other anti-HIV agents.

PubMed

Hartman, Tracy L; Yang, Lu; Buckheit, Robert W

2011-12-01

Structure-activity relationship evaluation of seventy-four 2,4(1H,3H)-pyrimidinedione derivatives identified seven lead compounds based on anti-HIV-1 potency, extended range of action to include HIV-2, virus entry inhibition, reverse transcriptase inhibition, and lack of cytotoxicity to human cells. The selected pyrimidinedione congeners are highly active inhibitors of HIV-1 with EC(50) values ranging from 0.6 to 2 nM in CEM-SS cells infected with laboratory derived viruses, 11-20 nM in fresh human PBMCs infected with subtype B (HT/92/599) virus, and 2-7 nM in PBMCs infected with the clinical subtype C (ZA/97/003) virus. Combination antiviral assays were performed using the laboratory adapted RF strain of HIV-1 in CEM-SS cells and with a clade B and C low passage clinical isolate in fresh human peripheral mononuclear cells and the compound interactions were analyzed using MacSynergy II. The seven pyrimidinedione compounds resulted in additive to synergistic interactions in combination with entry and fusion inhibitors, nonnucleoside and nucleoside reverse transcriptase inhibitors, and the protease inhibitors. No evidence of antagonistic antiviral activity or synergistic cytotoxicity was detected with the combinations of compounds tested. The dual mechanism of action of the pyrimidinediones resulting in inhibition of both virus entry and reverse transcription suggests excellent potential of these lead pyrimidinediones as candidates for combination therapy with other approved HIV inhibitors of varying mechanism of action. Copyright © 2011. Published by Elsevier B.V.

Transport and pharmacodynamics of albitiazolium, an antimalarial drug candidate

PubMed Central

Wein, S; Maynadier, M; Bordat, Y; Perez, J; Maheshwari, S; Bette-Bobillo, P; Tran Van Ba, C; Penarete-Vargas, D; Fraisse, L; Cerdan, R; Vial, H

2012-01-01

BACKGROUND AND PURPOSE Choline analogues, a new type of antimalarials, exert potent in vitro and in vivo antimalarial activity. This has given rise to albitiazolium, which is currently in phase II clinical trials to cure severe malaria. Here we dissected its mechanism of action step by step from choline entry into the infected erythrocyte to its effect on phosphatidylcholine (PC) biosynthesis. EXPERIMENTAL APPROACH We biochemically unravelled the transport and enzymatic steps that mediate de novo synthesis of PC and elucidated how albitiazolium enters the intracellular parasites and affects the PC biosynthesis. KEY RESULTS Choline entry into Plasmodium falciparum-infected erythrocytes is achieved both by the remnant erythrocyte choline carrier and by parasite-induced new permeability pathways (NPP), while parasite entry involves a poly-specific cation transporter. Albitiazolium specifically prevented choline incorporation into its end-product PC, and its antimalarial activity was strongly antagonized by choline. Albitiazolium entered the infected erythrocyte mainly via a furosemide-sensitive NPP and was transported into the parasite by a poly-specific cation carrier. Albitiazolium competitively inhibited choline entry via the parasite-derived cation transporter and also, at a much higher concentration, affected each of the three enzymes conducting de novo synthesis of PC. CONCLUSIONS AND IMPLICATIONS Inhibition of choline entry into the parasite appears to be the primary mechanism by which albitiazolium exerts its potent antimalarial effect. However, the pharmacological response to albitiazolium involves molecular interactions with different steps of the de novo PC biosynthesis pathway, which would help to delay the development of resistance to this drug. PMID:22471905

OSTEOPOROSIS DRUGS MARKETED IN THE UNITED STATES: GENERIC COMPETITION, PRICING STRUCTURE, AND DISPERSION AMONG PAYERS.

PubMed

Balkhi, Bander; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa

2016-01-01

Despite the cost of pharmaceuticals, studies assessing prices of osteoporosis drugs are lacking. This study examined trends in prices of osteoporosis drugs in the United States in the period 1988-2014, assessed pricing structure of osteoporosis drugs, and evaluated price trends before and after generic drugs market entry. Data were derived from the U.S. Food and Drug Administration, the RedBook, the Centers for Medicare & Medicaid Services, and the Federal Supply Schedule (FSS). Descriptive statistics and segmented linear regression analyses were performed. In the period 1988-2014, osteoporosis drug prices increased faster than the inflation. The average wholesale price (AWP) of generic products at market entry represented 90 percent of the AWP for the corresponding brand. Prices of brand products continued to increase after generic entry. Drug prices showed a significant variation when compared with the brand AWP. The brand wholesale acquisition cost (WAC) was typically set at 83.3 percent of the AWP. Community pharmacies acquired osteoporosis brand drugs at a median of 80.5 percent of the brand AWP. Significant reductions in brand AWP were observed for Medicare Part B (78.5 percent of the brand AWP), generic National Average Drug Acquisition Cost (33.7 percent), and FSS (22.5 percent). There are significant differences in the manufacturer prices, pharmacy acquisition costs and reimbursement rates of osteoporosis drugs. Pharmaceutical companies listed prices are higher than the pharmacy actual estimated acquisitions costs, and the prices used for reimbursement to providers. Generic drugs entry significantly drives down prices; still, prices of branded drugs facing generic competition continued to increase after generic market entry.

Glycopeptide Antibiotics Potently Inhibit Cathepsin L in the Late Endosome/Lysosome and Block the Entry of Ebola Virus, Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV).

PubMed

Zhou, Nan; Pan, Ting; Zhang, Junsong; Li, Qianwen; Zhang, Xue; Bai, Chuan; Huang, Feng; Peng, Tao; Zhang, Jianhua; Liu, Chao; Tao, Liang; Zhang, Hui

2016-04-22

Ebola virus infection can cause severe hemorrhagic fever with a high mortality in humans. The outbreaks of Ebola viruses in 2014 represented the most serious Ebola epidemics in history and greatly threatened public health worldwide. The development of additional effective anti-Ebola therapeutic agents is therefore quite urgent. In this study, via high throughput screening of Food and Drug Administration-approved drugs, we identified that teicoplanin, a glycopeptide antibiotic, potently prevents the entry of Ebola envelope pseudotyped viruses into the cytoplasm. Furthermore, teicoplanin also has an inhibitory effect on transcription- and replication-competent virus-like particles, with an IC50 as low as 330 nm Comparative analysis further demonstrated that teicoplanin is able to block the entry of Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) envelope pseudotyped viruses as well. Teicoplanin derivatives such as dalbavancin, oritavancin, and telavancin can also inhibit the entry of Ebola, MERS, and SARS viruses. Mechanistic studies showed that teicoplanin blocks Ebola virus entry by specifically inhibiting the activity of cathepsin L, opening a novel avenue for the development of additional glycopeptides as potential inhibitors of cathepsin L-dependent viruses. Notably, given that teicoplanin has routinely been used in the clinic with low toxicity, our work provides a promising prospect for the prophylaxis and treatment of Ebola, MERS, and SARS virus infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Anomalistic Disturbance Torques during the Entry Phase of the Mars Exploration Rover Missions: A Telemetry and Mars-Surface Investigation

NASA Technical Reports Server (NTRS)

Tolson, Robert H.; Willcockson, William H.; Desai, Prasun N.; Thomas, Paige

2006-01-01

Shortly after landing on Mars, post-flight analysis of the "Spirit" entry data suggested that the vehicle experienced large, anomalistic oscillations in angle-of-attack starting at about M=6. Similar analysis for "Opportunity " found even larger oscillations starting immediately after maximum dynamic pressure at M=14. Where angles-of-attack of 1-2 degrees were expected from maximum dynamic pressure to drogue deployment, the reconstructions suggested 4 to 9 degrees. The next Mars lander, 2007 Phoenix project, was concerned enough to recommend further exploration of the anomalies. Detailed analysis of "Opportunity" data found significant anomalies in the hypersonic aerodynamic torques. The analysis showed that these torques were essentially fixed in the spinning vehicle. Nearly a year after landing, the "Oportunity" rover took pictures of its aeroshell on the surface, which showed that portions of the aeroshell thermal blanket assembly still remained. This blanket assembly was supposed to burn off very early in the entry. An analysis of the aeroshell photographs led to an estimate of the aerodynamic torques that the remnants could have produced. A comparison of two estimates of the aerodynamic torque perturbations (one extracted from telemetry data and the other from Mars surface photographs) showed exceptional agreement. Trajectory simulations using a simple data derived torque perturbation model provided rigid body motions similar to that observed during the "Opportunity" entry. Therefore, the case of the anomalistic attitude behavior for the "Opportunity" EDL is now considered closed and a suggestion is put forth that a similar event occurred for the "Spirit" entry as well.

Post-Flight EDL Entry Guidance Performance of the 2011 Mars Science Laboratory Mission

NASA Technical Reports Server (NTRS)

Mendeck, Gavin F.; McGrew, Lynn Craig

2012-01-01

The 2011 Mars Science Laboratory was the first successful Mars mission to attempt a guided entry which safely delivered the rover to a final position approximately 2 km from its target within a touchdown ellipse of 19.1 km x 6.9 km. The Entry Terminal Point Controller guidance algorithm is derived from the final phase Apollo Command Module guidance and, like Apollo, modulates the bank angle to control the range flown. For application to Mars landers which must make use of the tenuous Martian atmosphere, it is critical to balance the lift of the vehicle to minimize the range error while still ensuring a safe deploy altitude. An overview of the process to generate optimized guidance settings is presented, discussing improvements made over the last nine years. Key dispersions driving deploy ellipse and altitude performance are identified. Performance sensitivities including attitude initialization error and the velocity of transition from range control to heading alignment are presented. Just prior to the entry and landing of MSL in August 2012, the EDL team examined minute tuning of the reference trajectory for the selected landing site, analyzed whether adjustment of bank reversal deadbands were necessary, the heading alignment velocity trigger was in union with other parameters to balance the EDL risks, and the vertical L/D command limits. This paper details a preliminary postflight assessment of the telemetry and trajectory reconstruction that is being performed, and updates the information presented in the former paper Entry Guidance for the 2011 Mars Science Laboratory Mission (AIAA Atmospheric Flight Mechanics Conference; 8-11 Aug. 2011; Portland, OR; United States)

Validation of Veterans Affairs Electronic Medical Record Smoking Data Among Iraq- and Afghanistan-Era Veterans.

PubMed

Calhoun, Patrick S; Wilson, Sarah M; Hertzberg, Jeffrey S; Kirby, Angela C; McDonald, Scott D; Dennis, Paul A; Bastian, Lori A; Dedert, Eric A; Beckham, Jean C

2017-11-01

Research using the Veterans Health Administration (VA) electronic medical records (EMR) has been limited by a lack of reliable smoking data. To evaluate the validity of using VA EMR "Health Factors" data to determine smoking status among veterans with recent military service. Sensitivity, specificity, area under the receiver-operating curve (AUC), and kappa statistics were used to evaluate concordance between VA EMR smoking status and criterion smoking status. Veterans (N = 2025) with service during the wars in Iraq/Afghanistan who participated in the VA Mid-Atlantic Post-Deployment Mental Health (PDMH) Study. Criterion smoking status was based on self-report during a confidential study visit. VA EMR smoking status was measured by coding health factors data entries (populated during automated clinical reminders) in three ways: based on the most common health factor, the most recent health factor, and the health factor within 12 months of the criterion smoking status data collection date. Concordance with PDMH smoking status (current, former, never) was highest when determined by the most commonly observed VA EMR health factor (κ = 0.69) and was not significantly impacted by psychiatric status. Agreement was higher when smoking status was dichotomized: current vs. not current (κ = 0.73; sensitivity = 0.84; specificity = 0.91; AUC = 0.87); ever vs. never (κ = 0.75; sensitivity = 0.85; specificity = 0.90; AUC = 0.87). There were substantial missing Health Factors data when restricting analyses to a 12-month period from the criterion smoking status date. Current smokers had significantly more Health Factors entries compared to never or former smokers. The use of computerized tobacco screening data to determine smoking status is valid and feasible. Results indicating that smokers have significantly more health factors entries than non-smokers suggest that caution is warranted when using the EMR to select cases for cohort studies as the risk for selection bias appears high.

Impact of Virginia's School-Entry Vaccine Mandate on Human Papillomavirus Vaccination Among 13-17-Year-Old Females.

PubMed

Pierre-Victor, Dudith; Page, Timothy F; Trepka, Mary Jo; Stephens, Dionne P; Li, Tan; Madhivanan, Purnima

2017-03-01

The link between human papillomavirus (HPV) and anogenital cancers is well established in the literature. Many states have passed laws requiring funding for HPV education or vaccination. Mandatory HPV vaccination policies have been considered and passed in several states; yet their effectiveness has not been evaluated. This study sought to assess the impact of Virginia's HPV vaccine mandate for school-entry on HPV vaccine uptake among females aged 13-17 years. Data from the National Immunization Survey-Teen for the 2008-2012 period were used, and 3,203 adolescent females were included in the analysis. We performed difference-in-differences estimation and logistic regression with a policy and period interaction term. Virginia was considered the treatment state, and South Carolina and Tennessee were the comparison states to account for nonpolicy factors that may have affected vaccination rates during the time period considered in the analysis. There was no evidence of an effect of Virginia's HPV vaccine mandate for school-entry on vaccination rates or on physician vaccination recommendation using either the difference-by-differences analysis or the policy and period interaction term in the logistic regression. Physician recommendation was the factor most strongly associated with vaccination in the Virginia-South Carolina analysis (adjusted odds ratio [aOR] = 9.33; 95% confidence interval [CI]: 6.11-14.3) and in the Virginia-Tennessee analysis (aOR = 9.33; 95% CI: 6.11-14.3). Study findings suggest that Virginia's HPV vaccine mandate for school-entry did not lead to a significant increase in HPV vaccination among adolescent females or physician recommendations. However, physician recommendation was the factor most strongly associated with vaccination.

Novel Insights into Cell Entry of Emerging Human Pathogenic Arenaviruses.

PubMed

Fedeli, Chiara; Moreno, Héctor; Kunz, Stefan

2018-06-22

Viral hemorrhagic fevers caused by emerging RNA viruses of the Arenavirus family are among the most devastating human diseases. Climate change, global trade, and increasing urbanization promote the emergence and re-emergence of these human pathogenic viruses. Emerging pathogenic arenaviruses are of zoonotic origin and reservoir-to-human transmission is crucial for spillover into human populations. Host cell attachment and entry are the first and most fundamental steps of every virus infection and represent major barriers for zoonotic transmission. During host cell invasion, viruses critically depend on cellular factors, including receptors, co-receptors, and regulatory proteins of endocytosis. An in-depth understanding of the complex interaction of a virus with cellular factors implicated in host cell entry is therefore crucial to predict the risk of zoonotic transmission, define the tissue tropism, and assess disease potential. Over the past years, investigation of the molecular and cellular mechanisms underlying host cell invasion of human pathogenic arenaviruses uncovered remarkable viral strategies and provided novel insights into viral adaptation and virus-host co-evolution that will be covered in the present review. Copyright © 2018. Published by Elsevier Ltd.

Mechanism of Diphtheria Toxin Catalytic Domain Delivery to the Eukaryotic Cell Cytosol and the Cellular Factors that Directly Participate in the Process

PubMed Central

Murphy, John R.

2011-01-01

Research on diphtheria and anthrax toxins over the past three decades has culminated in a detailed understanding of their structure function relationships (e.g., catalytic (C), transmembrane (T), and receptor binding (R) domains), as well as the identification of their eukaryotic cell surface receptor, an understanding of the molecular events leading to the receptor-mediated internalization of the toxin into an endosomal compartment, and the pH triggered conformational changes required for pore formation in the vesicle membrane. Recently, a major research effort has been focused on the development of a detailed understanding of the molecular interactions between each of these toxins and eukaryotic cell factors that play an essential role in the efficient translocation of their respective catalytic domains through the trans-endosomal vesicle membrane pore and delivery into the cell cytosol. In this review, I shall focus on recent findings that have led to a more detailed understanding of the mechanism by which the diphtheria toxin catalytic domain is delivered to the eukaryotic cell cytosol. While much work remains, it is becoming increasingly clear that the entry process is facilitated by specific interactions with a number of cellular factors in an ordered sequential fashion. In addition, since diphtheria, anthrax lethal factor and anthrax edema factor all carry multiple coatomer I complex binding motifs and COPI complex has been shown to play an essential role in entry process, it is likely that the initial steps in catalytic domain entry of these divergent toxins follow a common mechanism. PMID:22069710

A theoretical analysis of anatomical and functional intestinal slow wave re-entry.

PubMed

Du, Peng; O'Grady, Gregory; Cheng, Leo K

2017-07-21

Intestinal bioelectrical slow waves are a key regulator of intestinal motility. Peripheral pacemakers, ectopic initiations and sustained periods of re-entrant activities have all been experimentally observed to be important factors in setting the frequency of intestinal slow waves, but the tissue-level mechanisms underpinning these activities are unclear. This theoretical analysis aimed to define the initiation, maintenance, and termination criteria of two classes of intestinal re-entrant activities: anatomical re-entry and functional re-entry. Anatomical re-entry was modeled in a three-dimensional (3D) cylindrical model, and functional rotor was modeled in a 2D rectangle model. A single-pulse stimulus was used to invoke an anatomical re-entry and a prolonged refractory block was used to invoke the rotor. In both cases, the simulated re-entrant activities operated at frequencies above the baseline entrainment frequency. The anatomical re-entry simulation results demonstrated that a temporary functional refractory block would be required to initiate the re-entrant activity in a single direction around the cylindrical model. The rotor could be terminated by a single-pulse stimulus delivered around the core of the rotor. In conclusion, the simulation results provide the following new insights into the mechanisms of intestinal re-entry: (i) anatomical re-entry is only maintained within a specific range of velocities, outside of which the re-entrant activities become either an ectopic activity or simultaneous activations of the intestinal wall; (ii) a maintained rotor entrained slow waves faster in the antegrade direction than in the retrograde direction. Simulations are shown to be a valuable tool for achieving novel insights into the mechanisms of intestinal slow wave dysrhythmia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of school-entry and education mandates by states on HPV vaccination coverage: Analysis of the 2009–2013 National Immunization Survey-Teen

PubMed Central

Perkins, Rebecca B.; Lin, Mengyun; Wallington, Sherrie F.; Hanchate, Amresh D.

2016-01-01

ABSTRACT Objective: To determine the effectiveness of existing school entry and education mandates on HPV vaccination coverage, we compared coverage among girls residing in states and jurisdictions with and without education and school-entry mandates. Virginia and the District of Columbia enacted school entry mandates, though both laws included liberal opt-out provisions. Ten additional states had mandates requiring distribution of education to parents or provision of education within school curricula. Methods: Using data from the National Immunization Survey-Teen from 2009–2013, we estimated multilevel logistic regression models to compare coverage with HPV vaccines for girls ages 13–17 residing in states and jurisdictions with and without school entry and education mandates, adjusting for demographic factors, healthcare access, and provider recommendation. Results: Girls residing in states and jurisdictions with HPV vaccine school entry mandates (DC and VA) and education mandates (LA, MI, CO, IN, IA, IL, NJ, NC, TX, and WA) did not have higher HPV vaccine series initiation or completion than those living in states without mandates for any year (2009–2013). Similar results were seen when comparing girls ages 13–14 to those ages 15–17, and after adjustment for known covariates of vaccination. Conclusions: States and jurisdictions with school-entry and education mandates do not currently have higher HPV vaccination coverage than states without such legislation. Liberal opt-out language in existing school entry mandates may weaken their impact. Policy-makers contemplating legislation to improve vaccination coverage should be aware of the limitations of existing mandates. PMID:27152418

Maternal well-being and its association to risk of developmental problems in children at school entry

PubMed Central

2010-01-01

Background Children at highest risk of developmental problems benefit from early identification and intervention. Investigating factors affecting child development at the time of transition to school may reveal opportunities to tailor early intervention programs for the greatest effectiveness, social benefit and economic gain. The primary objective of this study was to identify child and maternal factors associated with children who screened at risk of developmental problems at school entry. Methods An existing cohort of 791 mothers who had been followed since early pregnancy was mailed a questionnaire when the children were aged four to six years. The questionnaire included a screening tool for developmental problems, an assessment of the child's social competence, health care utilization and referrals, and maternal factors, including physical health, mental health, social support, parenting morale and sense of competence, and parenting support/resources. Results Of the 491 mothers (62%) who responded, 15% had children who were screened at high risk of developmental problems. Based on a logistic regression model, independent predictors of screening at high risk for developmental problems at age 5 were male gender (OR: 2.3; 95% CI: 1.3, 4.1), maternal history of abuse at pregnancy (OR: 2.4; 95% CI: 1.3, 4.4), and poor parenting morale when the child was 3 years old (OR: 3.9; 95% CI: 2.1, 7.3). A child with all of these risk factors had a 35% predicted probability of screening at high risk of developmental problems, which was reduced to 13% if maternal factors were favourable. Conclusions Risk factors for developmental problems at school entry are related to maternal well being and history of abuse, which can be identified in the prenatal period or when children are preschool age. PMID:20338052

Influence of nonequilibrium radiation and shape change on aerothermal environment of Jovian entry body

NASA Technical Reports Server (NTRS)

Tiwari, S. N.; Subramanian, S. V.

1980-01-01

Radiative transfer equations are derived under nonequilibrium conditions which include multilevel energy transitions. The nonequalibrium results, obtained with and without ablation injection in the shock layer, are found to be greatly influenced by the temperature distribution in the shock layer. In the absence of ablative products, the convective and radiative heating to the entry body are reduced significantly under nonequilibrium conditions. The influence of nonequilibrium is found to be greater at higher entry altitudes. With coupled ablation and carbon phenolic injection, 16 chemical species are used in the ablation layer for radiation absorption. Equilibrium and nonequilibrium results are compared under peak heating conditions. A 45 degree sphere cone, a 35 degree hyperboloid, and a 45 degree ellipsoid were used to study probe shape change. Results indicate that the shock layer flow field and heat transfer to the body are influenced significantly by the probe shape change. The effect of shape change on radiative heating of the afterbodies is found to be considerably larger for the sphere cone and ellipsoid than for the hyperboloid.

Complement Regulator Factor H Mediates a Two-step Uptake of Streptococcus pneumoniae by Human Cells*

PubMed Central

Agarwal, Vaibhav; Asmat, Tauseef M.; Luo, Shanshan; Jensch, Inga; Zipfel, Peter F.; Hammerschmidt, Sven

2010-01-01

Streptococcus pneumoniae, a human pathogen, recruits complement regulator factor H to its bacterial cell surface. The bacterial PspC protein binds Factor H via short consensus repeats (SCR) 8–11 and SCR19–20. In this study, we define how bacterially bound Factor H promotes pneumococcal adherence to and uptake by epithelial cells or human polymorphonuclear leukocytes (PMNs) via a two-step process. First, pneumococcal adherence to epithelial cells was significantly reduced by heparin and dermatan sulfate. However, none of the glycosaminoglycans affected binding of Factor H to pneumococci. Adherence of pneumococci to human epithelial cells was inhibited by monoclonal antibodies recognizing SCR19–20 of Factor H suggesting that the C-terminal glycosaminoglycan-binding region of Factor H mediates the contact between pneumococci and human cells. Blocking of the integrin CR3 receptor, i.e. CD11b and CD18, of PMNs or CR3-expressing epithelial cells reduced significantly the interaction of pneumococci with both cell types. Similarly, an additional CR3 ligand, Pra1, derived from Candida albicans, blocked the interaction of pneumococci with PMNs. Strikingly, Pra1 inhibited also pneumococcal uptake by lung epithelial cells but not adherence. In addition, invasion of Factor H-coated pneumococci required the dynamics of host-cell actin microfilaments and was affected by inhibitors of protein-tyrosine kinases and phosphatidylinositol 3-kinase. In conclusion, pneumococcal entry into host cells via Factor H is based on a two-step mechanism. The first and initial contact of Factor H-coated pneumococci is mediated by glycosaminoglycans expressed on the surface of human cells, and the second step, pneumococcal uptake, is integrin-mediated and depends on host signaling molecules such as phosphatidylinositol 3-kinase. PMID:20504767

Analysis of the entry mechanism of Crimean-Congo hemorrhagic fever virus, using a vesicular stomatitis virus pseudotyping system.

PubMed

Suda, Yuto; Fukushi, Shuetsu; Tani, Hideki; Murakami, Shin; Saijo, Masayuki; Horimoto, Taisuke; Shimojima, Masayuki

2016-06-01

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease causing severe hemorrhagic symptoms with a nearly 30 % case-fatality rate in humans. The experimental use of CCHF virus (CCHFV), which causes CCHF, requires high-biosafety-level (BSL) containment. In contrast, pseudotyping of various viral glycoproteins (GPs) onto vesicular stomatitis virus (VSV) can be used in facilities with lower BSL containment, and this has facilitated studies on the viral entry mechanism and the measurement of neutralizing activity, especially for highly pathogenic viruses. In the present study, we generated high titers of pseudotyped VSV bearing the CCHFV envelope GP and analyzed the mechanisms involved in CCHFV infection. A partial deletion of the CCHFV GP cytoplasmic domain increased the titer of the pseudotyped VSV, the entry mechanism of which was dependent on the CCHFV envelope GP. Using the pseudotype virus, DC-SIGN (a calcium-dependent [C-type] lectin cell-surface molecule) was revealed to enhance viral infection and act as an entry factor for CCHFV.

Natural resistance-associated macrophage protein is a cellular receptor for sindbis virus in both insect and mammalian hosts.

PubMed

Rose, Patrick P; Hanna, Sheri L; Spiridigliozzi, Anna; Wannissorn, Nattha; Beiting, Daniel P; Ross, Susan R; Hardy, Richard W; Bambina, Shelly A; Heise, Mark T; Cherry, Sara

2011-08-18

Alphaviruses, including several emerging human pathogens, are a large family of mosquito-borne viruses with Sindbis virus being a prototypical member of the genus. The host factor requirements and receptors for entry of this class of viruses remain obscure. Using a Drosophila system, we identified the divalent metal ion transporter natural resistance-associated macrophage protein (NRAMP) as a host cell surface molecule required for Sindbis virus binding and entry into Drosophila cells. Consequently, flies mutant for dNRAMP were protected from virus infection. NRAMP2, the ubiquitously expressed vertebrate homolog, mediated binding and infection of Sindbis virus into mammalian cells, and murine cells deficient for NRAMP2 were nonpermissive to infection. Alphavirus glycoprotein chimeras demonstrated that the requirement for NRAMP2 is at the level of Sindbis virus entry. Given the conserved structure of alphavirus glycoproteins, and the widespread use of transporters for viral entry, other alphaviruses may use conserved multipass membrane proteins for infection. Copyright © 2011 Elsevier Inc. All rights reserved.

Endocytic function is critical for influenza A virus infection via DC-SIGN and L-SIGN

PubMed Central

Gillespie, Leah; Roosendahl, Paula; Ng, Wy Ching; Brooks, Andrew G.; Reading, Patrick C.; Londrigan, Sarah L.

2016-01-01

The ubiquitous presence of cell-surface sialic acid (SIA) has complicated efforts to identify specific transmembrane glycoproteins that function as bone fide entry receptors for influenza A virus (IAV) infection. The C-type lectin receptors (CLRs) DC-SIGN (CD209) and L-SIGN (CD209L) enhance IAV infection however it is not known if they act as attachment factors, passing virions to other unknown receptors for virus entry, or as authentic entry receptors for CLR-mediated virus uptake and infection. Sialic acid-deficient Lec2 Chinese Hamster Ovary (CHO) cell lines were resistant to IAV infection whereas expression of DC-SIGN/L-SIGN restored susceptibility of Lec2 cells to pH- and dynamin-dependent infection. Moreover, Lec2 cells expressing endocytosis-defective DC-SIGN/L-SIGN retained capacity to bind IAV but showed reduced susceptibility to infection. These studies confirm that DC-SIGN and L-SIGN are authentic endocytic receptors for IAV entry and infection. PMID:26763587

When Industries Change: The Future of Higher Education.

ERIC Educational Resources Information Center

Collis, David

2001-01-01

Factors altering the higher education industry include radical change in the type of students, necessity of lifetime education, and new technologies. These factors are increasing the entry of private-sector players. Strategic university responses may be strengthening of accreditation, cost-cutting and efficiency measures, horizontal…

Long noncoding RNA PANDA and scaffold-attachment-factor SAFA control senescence entry and exit.

PubMed

Puvvula, Pavan Kumar; Desetty, Rohini Devi; Pineau, Pascal; Marchio, Agnés; Moon, Anne; Dejean, Anne; Bischof, Oliver

2014-11-19

Cellular senescence is a stable cell cycle arrest that limits the proliferation of pre-cancerous cells. Here we demonstrate that scaffold-attachment-factor A (SAFA) and the long noncoding RNA PANDA differentially interact with polycomb repressive complexes (PRC1 and PRC2) and the transcription factor NF-YA to either promote or suppress senescence. In proliferating cells, SAFA and PANDA recruit PRC complexes to repress the transcription of senescence-promoting genes. Conversely, the loss of SAFA-PANDA-PRC interactions allows expression of the senescence programme. Accordingly, we find that depleting either SAFA or PANDA in proliferating cells induces senescence. However, in senescent cells where PANDA sequesters transcription factor NF-YA and limits the expression of NF-YA-E2F-coregulated proliferation-promoting genes, PANDA depletion leads to an exit from senescence. Together, our results demonstrate that PANDA confines cells to their existing proliferative state and that modulating its level of expression can cause entry or exit from senescence.

Care provider order entry (CPOE): a perspective on factors leading to success or to failure.

PubMed

Ozdas, A; Miller, R A

2007-01-01

Authors provide a perspective on factors leading to successful care provider order entry (CPOE) implementations. Viewpoint of authors supported by background literature review. Authors review both benefits and challenges related to CPOE implementation using three guiding principles: (1) a clinical approach to clinical systems, which claims that CPOE implementation is analogous to a "good" clinician delivering care to a patient; (2) a commitment to quality, which advocates that no compromises should be made in implementing system functionality and clinical system content - the highest objective for CPOE implementation is to provide better quality of care and increased safety for patients; (3) a commitment to fairness, as evidenced by respect for individuals and support of local autonomy, which advocates for minimizing disruptions to clinician-users' workflows, and adequate local control over CPOE system design and evolution, including clinical content management. Past experiences with CPOE implementation can inform future installation attempts. Sociocultural factors dominate in determining the success of implementation, and should govern technical factors.

A resource-dependence model of hospital contract management.

PubMed Central

Alexander, J A; Morrisey, M A

1989-01-01

This study empirically examines the determinants of hospital entry into management contracts with multihospital systems. Using a resource-dependence framework, the study tests whether market conditions, regulatory climate, management effectiveness, and certain enabling factors affect the probability of hospital entry into a contract management arrangement. The study used a pooled sample of 312 contract-managed and 936 traditionally managed hospitals. Results suggest the importance of management effectiveness, regulatory climate, and hospital ownership (investor owned or nonprofit) as predisposing conditions of contract management. PMID:2732059

The Inverse of Banded Matrices

DTIC Science & Technology

2013-01-01

indexed entries all zeros. In this paper, generalizing a method of Mallik (1999) [5], we give the LU factorization and the inverse of the matrix Br,n (if it...r ≤ i ≤ r, 1 ≤ j ≤ r, with the remaining un-indexed entries all zeros. In this paper generalizing a method of Mallik (1999) [5...matrices and applications to piecewise cubic approximation, J. Comput. Appl. Math. 8 (4) (1982) 285–288. [5] R.K. Mallik , The inverse of a lower

[Is the ICU staff satisfied with the computerized physician order entry? A cross-sectional survey study].

PubMed

Fumis, Renata Rego Lins; Costa, Eduardo Leite Vieira; Martins, Paulo Sergio; Pizzo, Vladimir; Souza, Ivens Augusto; Schettino, Guilherme de Paula Pinto

2014-01-01

To evaluate the satisfaction of the intensive care unit staff with a computerized physician order entry and to compare the concept of the computerized physician order entry relevance among intensive care unit healthcare workers. We performed a cross-sectional survey to assess the satisfaction of the intensive care unit staff with the computerized physician order entry in a 30-bed medical/surgical adult intensive care unit using a self-administered questionnaire. The questions used for grading satisfaction levels were answered according to a numerical scale that ranged from 1 point (low satisfaction) to 10 points (high satisfaction). The majority of the respondents (n=250) were female (66%) between the ages of 30 and 35 years of age (69%). The overall satisfaction with the computerized physician order entry scored 5.74±2.14 points. The satisfaction was lower among physicians (n=42) than among nurses, nurse technicians, respiratory therapists, clinical pharmacists and diet specialists (4.62±1.79 versus 5.97±2.14, p<0.001); satisfaction decreased with age (p<0.001). Physicians scored lower concerning the potential of the computerized physician order entry for improving patient safety (5.45±2.20 versus 8.09±2.21, p<0.001) and the ease of using the computerized physician order entry (3.83±1.88 versus 6.44±2.31, p<0.001). The characteristics independently associated with satisfaction were the system's user-friendliness, accuracy, capacity to provide clear information, and fast response time. Six months after its implementation, healthcare workers were satisfied, albeit not entirely, with the computerized physician order entry. The overall users' satisfaction with computerized physician order entry was lower among physicians compared to other healthcare professionals. The factors associated with satisfaction included the belief that digitalization decreased the workload and contributed to the intensive care unit quality with a user-friendly and accurate system and that digitalization provided concise information within a reasonable time frame.

A new strategy to identify hepatitis B virus entry inhibitors by AlphaScreen technology targeting the envelope-receptor interaction.

PubMed

Saso, Wakana; Tsukuda, Senko; Ohashi, Hirofumi; Fukano, Kento; Morishita, Ryo; Matsunaga, Satoko; Ohki, Mio; Ryo, Akihide; Park, Sam-Yong; Suzuki, Ryosuke; Aizaki, Hideki; Muramatsu, Masamichi; Sureau, Camille; Wakita, Takaji; Matano, Tetsuro; Watashi, Koichi

2018-06-22

Current anti-hepatitis B virus (HBV) agents have limited effect in curing HBV infection, and thus novel anti-HBV agents with different modes of action are in demand. In this study, we applied AlphaScreen assay to high-throughput screening of small molecules inhibiting the interaction between HBV large surface antigen (LHBs) and the HBV entry receptor, sodium taurocholate cotransporting polypeptide (NTCP). From the chemical screening, we identified that rapamycin, an immunosuppressant, strongly inhibited the LHBs-NTCP interaction. Rapamycin inhibited hepatocyte infection with HBV without significant cytotoxicity. This activity was due to impaired attachment of the LHBs preS1 domain to cell surface. Pretreatment of target cells with rapamycin remarkably reduced their susceptibility to preS1 attachment, while rapamycin pretreatment to preS1 did not affect its attachment activity, suggesting that rapamycin targets the host side. In support of this, a surface plasmon resonance analysis showed a direct interaction of rapamycin with NTCP. Consistently, rapamycin also prevented hepatitis D virus infection, whose entry into cells is also mediated by NTCP. We also identified two rapamycin derivatives, everolimus and temsirolimus, which possessed higher anti-HBV potencies than rapamycin. Thus, this is the first report for application of AlphaScreen technology that monitors a viral envelope-receptor interaction to identify viral entry inhibitors. Copyright © 2018 Elsevier Inc. All rights reserved.

Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry.

PubMed

Rhein, Bethany A; Brouillette, Rachel B; Schaack, Grace A; Chiorini, John A; Maury, Wendy

2016-07-01

Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain. While the residues within the TIM-1 IgV domain that are important for EBOV entry are characterized, the molecular details of virion-TIM-4 interactions have yet to be investigated. As sequences and structural alignments of the TIM proteins suggest distinct differences in the TIM-1 and TIM-4 IgV domain structures, we sought to characterize TIM-4 IgV domain residues required for EBOV entry. Using vesicular stomatitis virus pseudovirions bearing EBOV glycoprotein (EBOV GP/VSVΔG), we evaluated virus binding and entry into cells expressing TIM-4 molecules mutated within the IgV domain, allowing us to identify residues important for entry. Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4 and hTIM-4) were found to be important for EBOV entry. However, additional TIM-4-specific residues were also found to impact EBOV entry, with a total of 8 mTIM-4 and 14 hTIM-4 IgV domain residues being critical for virion binding and internalization. Together, these findings provide a greater understanding of the interaction of TIM-4 with EBOV virions. With more than 28,000 cases and over 11,000 deaths during the largest and most recent Ebola virus (EBOV) outbreak, there has been increased emphasis on the development of therapeutics against filoviruses. Many therapies under investigation target EBOV cell entry. T-cell immunoglobulin mucin (TIM) domain proteins are cell surface factors important for the entry of many enveloped viruses, including EBOV. TIM family member TIM-4 is expressed on macrophages and dendritic cells, which are early cellular targets during EBOV infection. Here, we performed a mutagenesis screening of the IgV domain of murine and human TIM-4 to identify residues that are critical for EBOV entry. Surprisingly, we identified more human than murine TIM-4 IgV domain residues that are required for EBOV entry. Defining the TIM IgV residues needed for EBOV entry clarifies the virus-receptor interactions and paves the way for the development of novel therapeutics targeting virus binding to this cell surface receptor. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Characterization of Human and Murine T-Cell Immunoglobulin Mucin Domain 4 (TIM-4) IgV Domain Residues Critical for Ebola Virus Entry

PubMed Central

Rhein, Bethany A.; Brouillette, Rachel B.; Schaack, Grace A.; Chiorini, John A.

2016-01-01

ABSTRACT Phosphatidylserine (PtdSer) receptors that are responsible for the clearance of dying cells have recently been found to mediate enveloped virus entry. Ebola virus (EBOV), a member of the Filoviridae family of viruses, utilizes PtdSer receptors for entry into target cells. The PtdSer receptors human and murine T-cell immunoglobulin mucin (TIM) domain proteins TIM-1 and TIM-4 mediate filovirus entry by binding to PtdSer on the virion surface via a conserved PtdSer binding pocket within the amino-terminal IgV domain. While the residues within the TIM-1 IgV domain that are important for EBOV entry are characterized, the molecular details of virion–TIM-4 interactions have yet to be investigated. As sequences and structural alignments of the TIM proteins suggest distinct differences in the TIM-1 and TIM-4 IgV domain structures, we sought to characterize TIM-4 IgV domain residues required for EBOV entry. Using vesicular stomatitis virus pseudovirions bearing EBOV glycoprotein (EBOV GP/VSVΔG), we evaluated virus binding and entry into cells expressing TIM-4 molecules mutated within the IgV domain, allowing us to identify residues important for entry. Similar to TIM-1, residues in the PtdSer binding pocket of murine and human TIM-4 (mTIM-4 and hTIM-4) were found to be important for EBOV entry. However, additional TIM-4-specific residues were also found to impact EBOV entry, with a total of 8 mTIM-4 and 14 hTIM-4 IgV domain residues being critical for virion binding and internalization. Together, these findings provide a greater understanding of the interaction of TIM-4 with EBOV virions. IMPORTANCE With more than 28,000 cases and over 11,000 deaths during the largest and most recent Ebola virus (EBOV) outbreak, there has been increased emphasis on the development of therapeutics against filoviruses. Many therapies under investigation target EBOV cell entry. T-cell immunoglobulin mucin (TIM) domain proteins are cell surface factors important for the entry of many enveloped viruses, including EBOV. TIM family member TIM-4 is expressed on macrophages and dendritic cells, which are early cellular targets during EBOV infection. Here, we performed a mutagenesis screening of the IgV domain of murine and human TIM-4 to identify residues that are critical for EBOV entry. Surprisingly, we identified more human than murine TIM-4 IgV domain residues that are required for EBOV entry. Defining the TIM IgV residues needed for EBOV entry clarifies the virus-receptor interactions and paves the way for the development of novel therapeutics targeting virus binding to this cell surface receptor. PMID:27122575

Onion Peel Ethylacetate Fraction and Its Derived Constituent Quercetin 4'-O-β-D Glucopyranoside Attenuates Quorum Sensing Regulated Virulence and Biofilm Formation.

PubMed

Al-Yousef, Hanan M; Ahmed, Atallah F; Al-Shabib, Nasser A; Laeeq, Sameen; Khan, Rais A; Rehman, Md T; Alsalme, Ali; Al-Ajmi, Mohamed F; Khan, Mohammad S; Husain, Fohad M

2017-01-01

The resistance and pathogenesis of bacteria could be related to their ability to sense and respond to population density, termed quorum sensing (QS). Inhibition of the QS system is considered as a novel strategy for the development of antipathogenic agents, especially for combating drug-resistant bacterial infections. In the present study, the anti-QS activity of Onion peel ethylacetate fraction (ONE) was tested against Chromobacterium violaceum CV12472 and Pseudomonas aeruginosa PAO1. ONE inhibit the QS-mediated virulence factors production such as violacein in C. violaceum and elastase, pyocyanin in P. aeruginosa . Further, the treatment with sub-MICs of ONE significantly inhibited the QS-mediated biofilm formation, EPS (Extracellular polymeric substances) production and swarming motility. Further, quercetin 4'- O -β-D glucopyranoside (QGP) was isolated from ONE and its anti-QS potential was confirmed after observing significant inhibition of QS-controlled virulence factors such as violacein, elastase, pyocyanin and biofilm formation in test pathogens. Molecular docking analysis predicted that QGP should be able to bind at the active sites of Vfr and LasR, and if so blocks the entry of active sites in Vfr and LasR.

Relational Aggression in Children with Preschool Onset (PO) Psychiatric Disorders

PubMed Central

Belden, Andy C.; Gaffrey, Michael S.; Luby, Joan L.

2012-01-01

Objective The role of preschool onset (PO) psychiatric disorders as correlates and/or risk factors for relational aggression during kindergarten or 1st grade was tested in a sample of N = 146 preschool-age children (3 to 5.11). Method Axis-I diagnoses and symptom scores were derived using the Preschool Age Psychiatric Assessment. Children’s roles in relational aggression as aggressor, victim, aggressive-victim, or non-aggressor/non-victim were determined at preschool and again 24 months later at elementary school entry. Results Preschoolers diagnosed with PO-psychiatric disorders were 3 times as likely as the healthy preschoolers to be classified aggressors, victims, or aggressive-victims. Children diagnosed with PO-disruptive, depressive, and/or anxiety disorders were at least 6 times as likely as children without PO-psychiatric disorders to become aggressive-victims during elementary school after covarying for other key risk factors. Conclusions Findings suggested that PO-psychiatric disorders differentiated preschool and school-age children’s roles in relational aggression based on teacher-report. Recommendations for future research and preventative intervention aimed at minimizing the development of relational aggression in early childhood by identifying and targeting PO-psychiatric disorders are made. PMID:22917202

Monument Damage Information System (mondis): AN Ontological Approach to Cultural Heritage Documentation

NASA Astrophysics Data System (ADS)

Cacciotti, R.; Valach, J.; Kuneš, P.; Čerňanský, M.; Blaško, M.; Křemen, P.

2013-07-01

Deriving from the complex nature of cultural heritage conservation it is the need for enhancing a systematic but flexible organization of expert knowledge in the field. Such organization should address comprehensively the interrelations and complementariness among the different factors that come into play in the understanding of diagnostic and intervention problems. The purpose of MONDIS is to endorse this kind of organization. The approach consists in applying an ontological representation to the field of heritage conservation in order to establish an appropriate processing of data. The system allows replicating in a computer readable form the basic dependence among factors influencing the description, diagnosis and intervention of damages to immovable objects. More specifically MONDIS allows to input and search entries concerning object description, structural evolution, location characteristics and risk, component, material properties, surveys and measurements, damage typology, damage triggering events and possible interventions. The system supports searching features typical of standard databases, as it allows for the digitalization of a wide range of information including professional reports, books, articles and scientific papers. It also allows for computer aided retrieval of information tailored to user's requirements. The foreseen outputs will include a web user interface and a mobile application for visual inspection purposes.

Cell-free synthesis of functional human epidermal growth factor receptor: Investigation of ligand-independent dimerization in Sf21 microsomal membranes using non-canonical amino acids

PubMed Central

Quast, Robert B.; Ballion, Biljana; Stech, Marlitt; Sonnabend, Andrei; Varga, Balázs R.; Wüstenhagen, Doreen A.; Kele, Péter; Schiller, Stefan M.; Kubick, Stefan

2016-01-01

Cell-free protein synthesis systems represent versatile tools for the synthesis and modification of human membrane proteins. In particular, eukaryotic cell-free systems provide a promising platform for their structural and functional characterization. Here, we present the cell-free synthesis of functional human epidermal growth factor receptor and its vIII deletion mutant in a microsome-containing system derived from cultured Sf21 cells. We provide evidence for embedment of cell-free synthesized receptors into microsomal membranes and asparagine-linked glycosylation. Using the cricket paralysis virus internal ribosome entry site and a repetitive synthesis approach enrichment of receptors inside the microsomal fractions was facilitated thereby providing analytical amounts of functional protein. Receptor tyrosine kinase activation was demonstrated by monitoring receptor phosphorylation. Furthermore, an orthogonal cell-free translation system that provides the site-directed incorporation of p-azido-L-phenylalanine is characterized and applied to investigate receptor dimerization in the absence of a ligand by photo-affinity cross-linking. Finally, incorporated azides are used to generate stable covalently linked receptor dimers by strain-promoted cycloaddition using a novel linker system. PMID:27670253

2011 Mars Science Laboratory Mission Design Overview

NASA Technical Reports Server (NTRS)

Abilleira, Fernando

2010-01-01

Scheduled to launch in the fall of 2011 with arrival at Mars occurring in the summer of 2012, NASA's Mars Science Laboratory will explore and assess whether Mars ever had conditions capable of supporting microbial life. In order to achieve its science objectives, the Mars Science Laboratory will be equipped with the most advanced suite of instruments ever sent to the surface of the Red Planet. Delivering the next mobile science laboratory safely to the surface of Mars has various key challenges derived from a strict set of requirements which include launch vehicle performance, spacecraft mass, communications coverage during Entry, Descent, and Landing, atmosphere-relative entry speeds, latitude accessibility, and dust storm season avoidance among others. The Mars Science Laboratory launch/arrival strategy selected after careful review satisfies all these mission requirements.

Structural and Trajectory Control of Variable Geometry Planetary Entry Systems

NASA Technical Reports Server (NTRS)

Quadrelli, Marco; Kwok, Kawai; Pellegrino, Sergio

2009-01-01

The results presented in this paper apply to a generic vehicle entering a planetary atmosphere which makes use of a variable geometry change to modulate the heat, drag, and acceleration loads. Two structural concepts for implementing the cone angle variation, namely a segmented shell and a corrugated shell, are presented. A structural analysis of these proposed structural configuration shows that the stress levels are tolerable during entry. The analytic expressions of the longitudinal aerodynamic coefficients are also derived, and guidance laws that track reference heat flux, drag, and aerodynamic acceleration loads are also proposed. These guidance laws have been tested in an integrated simulation environment, and the results indicate that use of variable geometry is feasible to track specific profiles of dynamic load conditions during reentry.

Overview of entry risk predictions

NASA Astrophysics Data System (ADS)

Mrozinski, R.; Mendeck, G.; Cutri-Kohart, R.

Risk to people on the ground from uncontrolled entries of spacecraft is a primary concern when analyzing end-of-life disposal options for satellites. Countries must balance this risk with the need to mitigate an exponentially growing space debris population. Currently the United States does this via guidelines that call for a satellite to be disposed of in a controlled manner if an uncontrolled entry would be too risky to people on the ground. This risk is measured by a quantity called "casualty expectation", or E , where casualty expectation is defined as the expectedc number of people suffering death or injury due to a spacecraft entry event. If Ec exceeds 1 in 10,000, U. S. guidelines state that the entry should be controlled rather than uncontrolled. Since this guideline can have serious impacts on the cost, lifetime, and even the mission and functionality of a satellite, it is critical that this quantity be estimated well, and decision makers understand all assumptions and limitations inherent in the resulting value. This paper discusses several issues regarding estimates of casualty expectation, beginning with an overview of relevant United States policies and guidelines. The equation the space industry typically uses to estimate casualty expectation is presented, along with a look at the sensitivity of the results to the typical assumptions, models, and initial condition uncertainties. Differences in these modeling issues with respect to launch failure Ec estimates are included in the discussion. An alternate quantity to assess risks due to spacecraft entries is introduced. "Probability of casualty", or Pc , is defined as the probability of one or more instances of people suffering death or injury due to a spacecraft entry event. The equation to estimate Pc is derived, where the same assumptions, modeling, and initial condition issues for Ec apply. Several examples are then given of both Ec and Pc estimate calculations. Due to the difficult issues in estimating both Ec and Pc, it is argued that "true" absolute quantities can never be computed. However, E and Pc are ideal for relativec analyses against a standard tool that eliminates these issues. Such a tool is recommended for assessing compliance with requirements of regulating institutions.

SPCA2 regulates Orai1 trafficking and store independent Ca2+ entry in a model of lactation

USDA-ARS?s Scientific Manuscript database

An unconventional interaction between SPCA2, an isoform of the Golgi secretory pathway Ca2+-ATPase, and the Ca2+ influx channel Orai1 has previously been shown to contribute to elevated Ca2+ influx in breast cancer derived cells. In order to investigate the physiological role of this interaction, we...

An Empirical Method for Deriving Grade Equivalence for University Entrance Qualifications: An Application to A Levels and the International Baccalaureate

ERIC Educational Resources Information Center

Green, Francis; Vignoles, Anna

2012-01-01

We present a method to compare different qualifications for entry to higher education by studying students' subsequent performance. Using this method for students holding either the International Baccalaureate (IB) or A-levels gaining their degrees in 2010, we estimate an "empirical" equivalence scale between IB grade points and UCAS…

The sympathetic postganglionic fibre and the block by bretylium; the block prevented by hexamethonium and imitated by mecamylamine

PubMed Central

Burn, J. H.; Gibbons, W. R.

1964-01-01

Acetylcholine, in the presence of atropine, has an action like that of sympathetic stimulation. When injected into the splenic artery it causes contraction of the spleen, but this action is blocked by hexamethonium; stimulation of the splenic nerves, however, is still effective. Thus hexamethonium distinguishes between sympathetic nerve stimulation and the action of acetylcholine. If bretylium is used instead of hexamethonium, there is no such distinction, for bretylium blocks the response to nerve stimulation as well as that to acetylcholine. It appeared that hexamethonium might block the action of acetylcholine by preventing its entry into the sympathetic fibre. Acetylcholine has some structural similarity to bretylium, since acetylcholine is a derivative of trimethylammonium and bretylium is a derivative of dimethylethylammonium. It has been found that hexamethonium, pentolinium and hemicholinium (HC-3), which are all bis-quaternary compounds, block the action of bretylium, presumably by preventing its entry into the fibre. Consistent with the view that ability to enter the fibre is important is the observation that mecamylamine and pempidine, which are ganglion-blocking agents, but not either mono- or bis-quaternary compounds, often abolish the response to stimulation of the sympathetic postganglionic fibre. PMID:14211685

Toxicological database of soil and derived products (BDT).

PubMed

Uricchio, Vito Felice

2008-01-01

The Toxicological database of soil and derived products is a project firstly proposed by the Regional Environmental Authority of Apulia. Such a project aims to provide comprehensive and updated information on the regional environmental characteristics, on the pollution state of the regional soil, on the main pollutants and on the reclaim techniques to be used in case of both non-point (agricultural activities) and point (industrial activities) sources of pollution. The project's focus is on the soil pollution because of the fundamental role played by the soil in supporting the biological cycle. Furthermore, the reasons for the project are related both to the reduction of human health risks due to toxic substances ingestion (these substances are present in some ring of the eating chain), and to the recognition of the importance of the groundwater quality safety (primary source of fresh water in many Mediterranean Regions). The essential requirements of a data entry are the following: speed and simplicity of the data entry; reliability and stability of the database structures; speed, easiness and pliability of the queries. Free consultation of the database represents one of the most remarkable advantages coming from the use of an "open" system.

Marrow-derived mesenchymal stem cells: role in epithelial tumor cell determination.

PubMed

Fierro, Fernando A; Sierralta, Walter D; Epuñan, Maria J; Minguell, José J

2004-01-01

Marrow stroma represents an advantageous environment for development of micrometastatic cells. Within the cellular structure of marrow stroma, mesenchymal stem cells (MSC) have been postulated as an interacting target for disseminated cancer cells. The studies reported here were performed to gain more information on the interaction of the human breast cancer cell line MCF-7 with human bone marrow-derived MSC cells and to investigate whether this interaction affects tumor cell properties. The results showed that after co-culture with MSC, changes were detected in the morphology, proliferative capacity and aggregation pattern of MCF-7 cells, but these parameters were not affected after the co-culture of MSC cells with a non-tumorigenic breast epithelial cell line, MCF-10. Since the indirect culture of MCF-7 with MSC or its products also resulted in functional changes in the tumor cells, we evaluated whether these effects could be attributed to growth factors produced by MSC cells. It was found that VEGF and IL-6 mimic the effects produced by MSC or its products on the proliferation and aggregation properties of MCF-7, cells, respectively. Thus, it seems that after entry of disseminated tumor cells into the marrow space, their proliferative and morphogenetic organization patterns are modified after interaction with distinct stromal cells and/or with specific signals from the marrow microenvironment.

Radio occultation measurements of Pluto's neutral atmosphere with New Horizons

NASA Astrophysics Data System (ADS)

Hinson, D. P.; Linscott, I. R.; Young, L. A.; Tyler, G. L.; Stern, S. A.; Beyer, R. A.; Bird, M. K.; Ennico, K.; Gladstone, G. R.; Olkin, C. B.; Pätzold, M.; Schenk, P. M.; Strobel, D. F.; Summers, M. E.; Weaver, H. A.; Woods, W. W.

2017-07-01

On 14 July 2015 New Horizons performed a radio occultation (RO) that sounded Pluto's atmosphere down to the surface. The sensitivity of the measurements was enhanced by a unique configuration of ground equipment and spacecraft instrumentation. Signals were transmitted simultaneously by four antennas of the NASA Deep Space Network, each radiating 20 kW at a wavelength of 4.2 cm. The polarization was right circular for one pair of signals and left circular for the other pair. New Horizons received the four signals and separated them by polarization for processing by two independent receivers, each referenced to a different ultra-stable oscillator. The two data streams were digitized, filtered, and stored on the spacecraft for later transmission to Earth. The results reported here are the first to utilize the complete set of observations. We calibrated each signal to remove effects not associated with Pluto's atmosphere, including the limb diffraction pattern. We then applied a specialized method of analysis to retrieve profiles of number density, pressure, and temperature from the combined phase measurements. Occultation entry sounded the atmosphere at sunset at 193.5°E, 17.0°S - on the southeast margin of an ice-filled basin known informally as Sputnik Planitia (SP); occultation exit occurred at sunrise at 15.7°E, 15.1°N - near the center of the Charon-facing hemisphere. Above 1215 km radius (∼25 km altitude) there is no discernible difference between the measurements at entry and exit, and the RO profiles are consistent with results derived from ground-based stellar occultation measurements. At lower altitudes the RO measurements reveal horizontal variations in atmospheric structure that had not been observed previously, and they are the first to reach the ground. The entry profile has a strong temperature inversion that ends 3.5 km above the surface, and the temperature in the cold boundary layer beneath the inversion is nearly constant, 38.9 ± 2.1 K, and close to the saturation temperature of N2. The exit profile has a much weaker inversion that extends all the way to the ground, where the air temperature is 51.6 ± 3.8 K. Three factors appear to be responsible for the presence of a cold boundary layer in the entry profile (Forget et al., 2017): a substantial diurnal cycle of sublimation and condensation of N2 ice in SP, the local time of the RO observation, and confinement within SP by the surrounding topography and katabatic winds. We have also determined the surface pressure and the local radius at both entry and exit. The best pressure reference is the mean value: 11.5 ± 0.7 microbar at 1189.9 ± 0.2 km.

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

Junginger, Tobias; Abidi, S. H.; Maffett, R. D.

Here, the performance of superconducting radiofrequency (SRF) cavities used for particle accelerators depends on two characteristic material parameters: field of first flux entry H entry and pinning strength. The former sets the limit for the maximum achievable accelerating gradient, while the latter determines how efficiently flux can be expelled related to the maximum achievable quality factor. In this paper, a method based on muon spin rotation (μSR) is developed to probe these parameters on samples. It combines measurements from two different spectrometers, one being specifically built for these studies and samples of different geometries. It is found that annealing atmore » 1400°C virtually eliminates all pinning. Such an annealed substrate is ideally suited to measure H entry of layered superconductors, which might enable accelerating gradients beyond bulk niobium technology.« less

Entry of uranium, thorium, and radium isotopes into plants from soils and fertilizers

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

Shishkunova, L.V.; Grashchenko, S.M.; Strukov, V.N.

1989-01-01

We studied the effect of phosphorus fertilizers on the entry of /sup 238/U, /sup 234/U, /sup 228/Th, /sup 230/Th, /sup 232/Th, and /sup 226/Ra into crops from soils. Also examined was plant uptake of radionuclides originating from the fertilizers. Raising the phosphate content by incorporating the fertilizers into certain soils changed the ratio of the amount of radionuclide available to a plant to that fixed in the soil. A specific case was the addition of 4000 kg/ha of ammophos to soddy podzolic soils, which raised the thorium isotope buildup factor by 2 to 3. The uptake of thorium from ammophosmore » by plants, as measured by the entry ratio, was a hundred times lower than from the soils.« less

24-Month-Old Children with Larger Oral Vocabularies Display Greater Academic and Behavioral Functioning at Kindergarten Entry

PubMed Central

Morgan, Paul L.; Farkas, George; Hillemeier, Marianne M.; Hammer, Carol Scheffner; Maczuga, Steve

2015-01-01

Data were analyzed from a population-based, longitudinal sample of 8,650 U.S. children to (a) identify factors associated with or predictive of oral vocabulary size at 24 months of age and (b) evaluate whether oral vocabulary size is uniquely predictive of academic and behavioral functioning at kindergarten entry. Children from higher socioeconomic status households, females, and those experiencing higher-quality parenting had larger oral vocabularies. Children born with very low birth weight or from households where the mother had health problems had smaller oral vocabularies. Even after extensive covariate adjustment, 24-month-old children with larger oral vocabularies displayed greater reading and mathematics achievement, increased behavioral self-regulation, and fewer externalizing and internalizing problem behaviors at kindergarten entry. PMID:26283023

Entry of Porphyromonas gingivalis outer membrane vesicles into epithelial cells causes cellular functional impairment.

PubMed

Furuta, Nobumichi; Takeuchi, Hiroki; Amano, Atsuo

2009-11-01

Porphyromonas gingivalis, a periodontal pathogen, secretes outer membrane vesicles (MVs) that contain major virulence factors, including proteases termed gingipains (Arg-gingipain [Rgp] and Lys-gingipain [Kgp]). We recently showed that P. gingivalis MVs swiftly enter host epithelial cells via an endocytosis pathway and are finally sorted to lytic compartments. However, it remains unknown whether MV entry impairs cellular function. Herein, we analyzed cellular functional impairment following entry of P. gingivalis into epithelial cells, including HeLa and immortalized human gingival epithelial (IHGE) cells. After being taken up by endocytic vacuoles, MVs degraded the cellular transferrin receptor (TfR) and integrin-related signaling molecules, such as paxillin and focal adhesion kinase (FAK), which resulted in depletion of intracellular transferrin and inhibition of cellular migration. Few Rgp-null MVs entered the cells, and these negligibly degraded TfR, whereas paxillin and FAK degradation was significant. In contrast, Kgp-null MVs clearly entered the cells and degraded TfR, while they scarcely degraded paxillin and FAK. In addition, both wild-type and Kgp-null MVs significantly impaired cellular migration, whereas the effect of Rgp-null MVs was limited. Our findings suggest that, following entry of P. gingivalis MVs into host cells, MV-associated gingipains degrade cellular functional molecules such as TfR and paxillin/FAK, resulting in cellular impairment, indicating that P. gingivalis MVs are potent vehicles for transmission of virulence factors into host cells and are involved in the etiology of periodontitis.

Entry of Porphyromonas gingivalis Outer Membrane Vesicles into Epithelial Cells Causes Cellular Functional Impairment▿

PubMed Central

Furuta, Nobumichi; Takeuchi, Hiroki; Amano, Atsuo

2009-01-01

Porphyromonas gingivalis, a periodontal pathogen, secretes outer membrane vesicles (MVs) that contain major virulence factors, including proteases termed gingipains (Arg-gingipain [Rgp] and Lys-gingipain [Kgp]). We recently showed that P. gingivalis MVs swiftly enter host epithelial cells via an endocytosis pathway and are finally sorted to lytic compartments. However, it remains unknown whether MV entry impairs cellular function. Herein, we analyzed cellular functional impairment following entry of P. gingivalis into epithelial cells, including HeLa and immortalized human gingival epithelial (IHGE) cells. After being taken up by endocytic vacuoles, MVs degraded the cellular transferrin receptor (TfR) and integrin-related signaling molecules, such as paxillin and focal adhesion kinase (FAK), which resulted in depletion of intracellular transferrin and inhibition of cellular migration. Few Rgp-null MVs entered the cells, and these negligibly degraded TfR, whereas paxillin and FAK degradation was significant. In contrast, Kgp-null MVs clearly entered the cells and degraded TfR, while they scarcely degraded paxillin and FAK. In addition, both wild-type and Kgp-null MVs significantly impaired cellular migration, whereas the effect of Rgp-null MVs was limited. Our findings suggest that, following entry of P. gingivalis MVs into host cells, MV-associated gingipains degrade cellular functional molecules such as TfR and paxillin/FAK, resulting in cellular impairment, indicating that P. gingivalis MVs are potent vehicles for transmission of virulence factors into host cells and are involved in the etiology of periodontitis. PMID:19737899

Linear model analysis of the influencing factors of boar longevity in Southern China.

PubMed

Wang, Chao; Li, Jia-Lian; Wei, Hong-Kui; Zhou, Yuan-Fei; Jiang, Si-Wen; Peng, Jian

2017-04-15

This study aimed to investigate the factors influencing the boar herd life month (BHLM) in Southern China. A total of 1630 records of culling boars from nine artificial insemination centers were collected from January 2013 to May 2016. A logistic regression model and two linear models were used to analyze the effects of breed, housing type, age at herd entry, and seed stock herd on boar removal reason and BHLM, respectively. Boar breed and the age at herd entry had significant effects on the removal reasons (P < 0.001). Results of the two linear models (with or without removal reason including) showed boars raised individually in stalls exhibited shorter BHLM than those raised in pens (P < 0.001). Boars aged 5 and 6 months at herd entry (44.6%) showed shorter BHLM than those aged 8 and 9 months at herd entry (P < 0.05). Approximately 95% boars were culled for different reasons other than old age, and the BHLM of these boars was at least 12.3 months longer than that of boars culled for other reasons (P < 0.001). In conclusion, abnormal elimination in boars is serious and it had a negative effect on boar BHLM. Boar removal reason and BHLM can be affected by breed, housing type, and seed stock herd. Importantly, 8 months is suggested as the most suitable age for boar introduction. Copyright © 2017. Published by Elsevier Inc.

Mental health selection and income support dynamics: multiple spell discrete-time survival analyses of welfare receipt.

PubMed

Kiely, Kim M; Butterworth, Peter

2014-04-01

The higher occurrence of common psychiatric disorders among welfare recipients has been attributed to health selection, social causation and underlying vulnerability. The aims of this study were to test for the selection effects of mental health problems on entry and re-entry to working-age welfare payments in respect to single parenthood, unemployment and disability. Nationally representative longitudinal data were drawn from the Household Income and Labour Dynamics in Australia survey. Multiple spell discrete-time survival analyses were conducted using multinomial logistic regression models to test if pre-existing mental health problems predicted transitions to welfare. Analyses were stratified by sex and multivariate adjusted for mental health problems, father's occupation, socioeconomic position, marital status, employment history, smoking status and alcohol consumption, physical function and financial hardship. All covariates were modelled as either lagged effects or when a respondent was first observed to be at risk of income support. Mental health problems were associated with increased risk of entry and re-entry to disability, unemployment and single parenting payments for women, and disability and unemployment payments for men. These associations were attenuated but remained significant after adjusting for contemporaneous risk factors. Although we do not control for reciprocal causation, our findings are consistent with a health selection hypothesis and indicate that mental illness may be a contributing factor to later receipt of different types of welfare payments. We argue that mental health warrants consideration in the design and targeting of social and economic policies.

Psychosocial Screening and Assessment Practice within Cardiac Rehabilitation: A Survey of Cardiac Rehabilitation Coordinators in Australia.

PubMed

Jackson, Alun C; Le Grande, Michael R; Higgins, Rosemary O; Rogerson, Michelle; Murphy, Barbara M

2017-01-01

Many cardiac rehabilitation (CR) guidelines and position statements recommend screening for psychosocial risk factors, although there is wide variation in the recommended factors and recommended screening tools. Little is known about screening in CR in Australia. Cardiac rehabilitation coordinators at the 314 CR programs operating across Australia, drawn from the 2014 Australian Directory of Cardiac Rehabilitation Services were invited to participate in an online survey. Of 165 complete responses, 157 (95%) CR coordinators indicated that they screened at entry with 132 (80%) screening on exit. At CR entry, programs screened for - depression (83%), anxiety (75%), stress (75%), and sleep disturbance (57%). The use of standardised instruments by those screening at entry varied from 89% for depression to only 9% for sleep disturbance. Organisational, resource and personal barriers inhibited the routine screening for many psychosocial factors. Surveys such as this are useful for monitoring the rate of adoption of guideline recommendations and identifying barriers to implementation. Findings can also inform discussions about what should be included in minimum data sets for CR programs, and the identification of brief screening tools that have been validated not just in the general population but in cardiac patients. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Multicenter Phase II Trial of Temsirolimus and Bevacizumab in Pancreatic Neuroendocrine Tumors

PubMed Central

Hobday, Timothy J.; Qin, Rui; Reidy-Lagunes, Diane; Moore, Malcolm J.; Strosberg, Jonathan; Kaubisch, Andreas; Shah, Manisha; Kindler, Hedy Lee; Lenz, Heinz-Josef; Chen, Helen; Erlichman, Charles

2015-01-01

Purpose There are few effective therapies for pancreatic neuroendocrine tumors (PNETs). Recent placebo-controlled phase III trials of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the vascular endothelial growth factor (VEGF)/platelet-derived growth factor receptor inhibitor sunitinib have noted improved progression-free survival (PFS). Preclinical studies have suggested enhanced antitumor effects with combined mTOR and VEGF pathway–targeted therapy. We conducted a clinical trial to evaluate combination therapy against these targets in PNETs. Patients and Methods We conducted a two-stage single-arm phase II trial of the mTOR inhibitor temsirolimus 25 mg intravenously (IV) once per week and the VEGF-A monoclonal antibody bevacizumab 10 mg/kg IV once every 2 weeks in patients with well or moderately differentiated PNETs and progressive disease by RECIST within 7 months of study entry. Coprimary end points were tumor response rate and 6-month PFS. Results A total of 58 patients were enrolled, and 56 patients were eligible for response assessment. Confirmed response rate (RR) was 41% (23 of 56 patients). PFS at 6 months was 79% (44 of 56). Median PFS was 13.2 months (95% CI, 11.2 to 16.6). Median overall survival was 34 months (95% CI, 27.1 to not reached). For evaluable patients, the most common grade 3 to 4 adverse events attributed to therapy were hypertension (21%), fatigue (16%), lymphopenia (14%), and hyperglycemia (14%). Conclusion The combination of temsirolimus and bevacizumab had substantial activity and reasonable tolerability in a multicenter phase II trial, with RR of 41%, well in excess of single targeted agents in patients with progressive PNETs. Six-month PFS was a notable 79% in a population of patients with disease progression by RECIST criteria within 7 months of study entry. On the basis of this trial, continued evaluation of combination mTOR and VEGF pathway inhibitors is warranted. PMID:25488966

Contemporary Constructivist Practices in Higher Education Settings and Academic Motivational Factors

ERIC Educational Resources Information Center

Alt, Dorit

2016-01-01

This study was aimed at assessing the relationships between college students' pre-entry factors, self-efficacy and motivation for learning, and the perceived constructivist learning in traditional lecture-based courses and seminars (SM). The study included 411 undergraduate third-year college students. Several scales were administered to the…

In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence

PubMed Central

Figueira, T. N.; Palermo, L. M.; Veiga, A. S.; Huey, D.; Alabi, C. A.; Santos, N. C.; Welsch, J. C.; Mathieu, C.; Niewiesk, S.; Moscona, A.

2016-01-01

ABSTRACT Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo. We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. IMPORTANCE Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides. PMID:27733647

In Vivo Efficacy of Measles Virus Fusion Protein-Derived Peptides Is Modulated by the Properties of Self-Assembly and Membrane Residence.

PubMed

Figueira, T N; Palermo, L M; Veiga, A S; Huey, D; Alabi, C A; Santos, N C; Welsch, J C; Mathieu, C; Horvat, B; Niewiesk, S; Moscona, A; Castanho, M A R B; Porotto, M

2017-01-01

Measles virus (MV) infection is undergoing resurgence and remains one of the leading causes of death among young children worldwide despite the availability of an effective measles vaccine. MV infects its target cells by coordinated action of the MV hemagglutinin (H) and fusion (F) envelope glycoproteins; upon receptor engagement by H, the prefusion F undergoes a structural transition, extending and inserting into the target cell membrane and then refolding into a postfusion structure that fuses the viral and cell membranes. By interfering with this structural transition of F, peptides derived from the heptad repeat (HR) regions of F can inhibit MV infection at the entry stage. In previous work, we have generated potent MV fusion inhibitors by dimerizing the F-derived peptides and conjugating them to cholesterol. We have shown that prophylactic intranasal administration of our lead fusion inhibitor efficiently protects from MV infection in vivo We show here that peptides tagged with lipophilic moieties self-assemble into nanoparticles until they reach the target cells, where they are integrated into cell membranes. The self-assembly feature enhances biodistribution and the half-life of the peptides, while integration into the target cell membrane increases fusion inhibitor potency. These factors together modulate in vivo efficacy. The results suggest a new framework for developing effective fusion inhibitory peptides. Measles virus (MV) infection causes an acute illness that may be associated with infection of the central nervous system (CNS) and severe neurological disease. No specific treatment is available. We have shown that fusion-inhibitory peptides delivered intranasally provide effective prophylaxis against MV infection. We show here that specific biophysical properties regulate the in vivo efficacy of MV F-derived peptides. Copyright © 2016 American Society for Microbiology.

Sources of international migration statistics in Africa.

PubMed

1984-01-01

The sources of international migration data for Africa may be classified into 2 main categories: administrative records and 2) censuses and survey data. Both categories are sources for the direct measurement of migration, but the 2nd category can be used for the indirect estimation of net international migration. The administrative records from which data on international migration may be derived include 1) entry/departure cards or forms completed at international borders, 2) residence/work permits issued to aliens, and 3) general population registers and registers of aliens. The statistics derived from the entry/departure cards may be described as 1) land frontier control statistics and 2) port control statistics. The former refer to data derived from movements across land borders and the latter refer to information collected at international airports and seaports. Other administrative records which are potential sources of statistics on international migration in some African countries include some limited population registers, records of the registration of aliens, and particulars of residence/work permits issued to aliens. Although frontier control data are considered the most important source of international migration statistics, in many African countries these data are too deficient to provide a satisfactory indication of the level of international migration. Thus decennial population censuses and/or sample surveys are the major sources of the available statistics on the stock and characteristics of international migration. Indirect methods can be used to supplement census data with intercensal estimates of net migration using census data on the total population. This indirect method of obtaining information on migration can be used to evaluate estimates derived from frontier control records, and it also offers the means of obtaining alternative information on international migration in African countries which have not directly investigated migration topics in their censuses or surveys.

Determination of Barometric Altimeter Errors for the Orion Exploration Flight Test-1 Entry

NASA Technical Reports Server (NTRS)

Brown, Denise L.; Munoz, Jean-Philippe; Gay, Robert

2011-01-01

The EFT-1 mission is the unmanned flight test for the upcoming Multi-Purpose Crew Vehicle (MPCV). During entry, the EFT-1 vehicle will trigger several Landing and Recovery System (LRS) events, such as parachute deployment, based on onboard altitude information. The primary altitude source is the filtered navigation solution updated with GPS measurement data. The vehicle also has three barometric altimeters that will be used to measure atmospheric pressure during entry. In the event that GPS data is not available during entry, the altitude derived from the barometric altimeter pressure will be used to trigger chute deployment for the drogues and main parachutes. Therefore it is important to understand the impact of error sources on the pressure measured by the barometric altimeters and on the altitude derived from that pressure. There are four primary error sources impacting the sensed pressure: sensor errors, Analog to Digital conversion errors, aerodynamic errors, and atmosphere modeling errors. This last error source is induced by the conversion from pressure to altitude in the vehicle flight software, which requires an atmosphere model such as the US Standard 1976 Atmosphere model. There are several secondary error sources as well, such as waves, tides, and latencies in data transmission. Typically, for error budget calculations it is assumed that all error sources are independent, normally distributed variables. Thus, the initial approach to developing the EFT-1 barometric altimeter altitude error budget was to create an itemized error budget under these assumptions. This budget was to be verified by simulation using high fidelity models of the vehicle hardware and software. The simulation barometric altimeter model includes hardware error sources and a data-driven model of the aerodynamic errors expected to impact the pressure in the midbay compartment in which the sensors are located. The aerodynamic model includes the pressure difference between the midbay compartment and the free stream pressure as a function of altitude, oscillations in sensed pressure due to wake effects, and an acoustics model capturing fluctuations in pressure due to motion of the passive vents separating the barometric altimeters from the outside of the vehicle.

HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor.

PubMed

Bashir, Tahir; Patgaonkar, Mandar; Kumar, Selvaa C; Pasi, Achhelal; Reddy, Kudumula Venkata Rami

2015-01-01

Human Immunodeficiency Virus (HIV-1) poses a serious threat to the developing world and sexual transmission continues to be the major source of new infections. Therefore, the development of molecules, which prevent new HIV-1 infections, is highly warranted. In the present study, a panel of human hemoglobin (Hb)-α subunit derived peptides and their analogues, with an ability to bind gp120, were designed in-silico and their anti-HIV-1 activity was evaluated. Of these peptides, HbAHP-25, an analogue of Hb-α derived peptide, demonstrated significant anti-HIV-1 activity. HbAHP-25 was found to be active against CCR5-tropic HIV-1 strains (ADA5 and BaL) and CXCR4-tropic HIV-1 strains (IIIB and NL4-3). Surface plasmon resonance (SPR) and ELISA revealed direct interaction between HbAHP-25 and HIV-1 envelope protein, gp120. The peptide prevented binding of CD4 to gp120 and blocked subsequent steps leading to entry and/or fusion or both. Anti-HIV activity of HbAHP-25 appeared to be specific as it failed to inhibit the entry of HIV-1 pseudotyped virus (HIV-1 VSV). Further, HbAHP-25 was found to be non-cytotoxic to TZM-bl cells, VK2/E6E7 cells, CEM-GFP cells and PBMCs, even at higher concentrations. Moreover, HbAHP-25 retained its anti-HIV activity in presence of seminal plasma and vaginal fluid. In brief, the study identified HbAHP-25, a novel anti-HIV peptide, which directly interacts with gp120 and thus has a potential to inhibit early stages of HIV-1 infection.

Occludin-Knockout Human Hepatic Huh7.5.1-8-Derived Cells Are Completely Resistant to Hepatitis C Virus Infection.

PubMed

Shirasago, Yoshitaka; Shimizu, Yoshimi; Tanida, Isei; Suzuki, Tetsuro; Suzuki, Ryosuke; Sugiyama, Kazuo; Wakita, Takaji; Hanada, Kentaro; Yagi, Kiyohito; Kondoh, Masuo; Fukasawa, Masayoshi

2016-05-01

It is well known that occludin (OCLN) is involved in hepatitis C virus (HCV) entry into hepatocytes, but there has been no conclusive evidence that OCLN is essential for HCV infection. In this study, we first established an OCLN-knockout cell line derived from human hepatic Huh7.5.1-8 cells using the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 system, in which two independent targeting plasmids expressing single-guide RNAs were used. One established cell clone, named OKH-4, had the OCLN gene truncated in the N-terminal region, and a complete defect of the OCLN protein was shown using immunoblot analysis. Infection of OKH-4 cells with various genotypes of HCV was abolished, and exogenous expression of the OCLN protein in OKH-4 cells completely reversed permissiveness to HCV infection. In addition, using a co-culture system of HCV-infected Huh7.5.1-8 cells with OKH-4 cells, we showed that OCLN is also critical for cell-to-cell HCV transmission. Thus, we concluded that OCLN is essential for HCV infection of human hepatic cells. Further experiments using HCV genomic RNA-transfected OKH-4 cells or HCV subgenomic replicon-harboring OKH-4 cells suggested that OCLN is mainly involved in the entry step of the HCV life cycle. It was also demonstrated that the second extracellular loop of OCLN, especially the two cysteine residues, is critical for HCV infection of hepatic cells. OKH-4 cells may be a useful tool for understanding not only the entire mechanism of HCV entry, but also the biological functions of OCLN.

HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor

PubMed Central

Bashir, Tahir; Patgaonkar, Mandar; Kumar C, Selvaa; Pasi, Achhelal; Reddy, Kudumula Venkata Rami

2015-01-01

Human Immunodeficiency Virus (HIV-1) poses a serious threat to the developing world and sexual transmission continues to be the major source of new infections. Therefore, the development of molecules, which prevent new HIV-1 infections, is highly warranted. In the present study, a panel of human hemoglobin (Hb)-α subunit derived peptides and their analogues, with an ability to bind gp120, were designed in-silico and their anti-HIV-1 activity was evaluated. Of these peptides, HbAHP-25, an analogue of Hb-α derived peptide, demonstrated significant anti-HIV-1 activity. HbAHP-25 was found to be active against CCR5-tropic HIV-1 strains (ADA5 and BaL) and CXCR4-tropic HIV-1 strains (IIIB and NL4-3). Surface plasmon resonance (SPR) and ELISA revealed direct interaction between HbAHP-25 and HIV-1 envelope protein, gp120. The peptide prevented binding of CD4 to gp120 and blocked subsequent steps leading to entry and/or fusion or both. Anti-HIV activity of HbAHP-25 appeared to be specific as it failed to inhibit the entry of HIV-1 pseudotyped virus (HIV-1 VSV). Further, HbAHP-25 was found to be non-cytotoxic to TZM-bl cells, VK2/E6E7 cells, CEM-GFP cells and PBMCs, even at higher concentrations. Moreover, HbAHP-25 retained its anti-HIV activity in presence of seminal plasma and vaginal fluid. In brief, the study identified HbAHP-25, a novel anti-HIV peptide, which directly interacts with gp120 and thus has a potential to inhibit early stages of HIV-1 infection. PMID:25915507

Risk Factors for Delayed Entrance into Care after Diagnosis among Patients with Late-Stage HIV Disease in Southern Vietnam

PubMed Central

Rangarajan, Suresh; Tram, Hoang Nguyen Bao; Todd, Catherine S.; Thinh, Tran; Hung, Van; Hieu, Pham Thanh; Hanh, Tran My; Chau, Khong Minh; Lam, Nguyen Danh; Hung, Pham Tri; West, Gary; Colby, Donn

2014-01-01

Background We surveyed HIV patients with late-stage disease in southern Vietnam to determine if barriers to access and service quality resulted in late HIV testing and delays from initial diagnosis to entry into HIV care. Methodology 196 adult patients at public HIV clinics with CD4 counts less than 250 cells/mm3 completed a standardized questionnaire. We used multivariate analysis to determine risk factors for delayed entry into care, defined as >3 months time from diagnosis to registration. Results Common reasons for delayed testing were feeling healthy (71%), fear of stigma and discrimination in the community (43%), time conflicts with work or school (31%), did not want to know if infected (30%), and fear of lack of confidentiality (27%). Forty-five percent of participants delayed entry into care with a median CD4 count of 65 cells/mm3. The most common reasons for delayed entry were feeling healthy (51%), fear of stigma and discrimination in the community (41%), time conflicts with work or school (33%), and fear of lack of confidentiality (26%). Independent predictors for delayed entry were feeling healthy (aOR 3.7, 95% CI 1.5–9.1), first positive HIV test at other site (aOR 2.9, CI 1.2–7.1), history of injection drug use (IDU) (aOR 2.9, 95% CI 1.1–7.9), work/school conflicts (aOR 4.3, 95% CI 1.7–10.8), prior registration at another clinic (aOR 77.4, 95% CI 8.6–697), detention or imprisonment (aOR 10.3, 95% CI 1.8–58.2), and perceived distance to clinic (aOR 3.7, 95% CI 1.0–13.7). Conclusion Delayed entry into HIV care in Vietnam is common and poses a significant challenge to preventing AIDS and opportunistic infections, decreasing mortality, and reducing HIV transmission. Improved linkages between testing and care are needed, particularly for patients who feel healthy, as well as incarcerated and drug-using populations who may face structural and social barriers to accessing care. PMID:25330196

Re-refinement from deposited X-ray data can deliver improved models for most PDB entries.

PubMed

Joosten, Robbie P; Womack, Thomas; Vriend, Gert; Bricogne, Gérard

2009-02-01

The deposition of X-ray data along with the customary structural models defining PDB entries makes it possible to apply large-scale re-refinement protocols to these entries, thus giving users the benefit of improvements in X-ray methods that have occurred since the structure was deposited. Automated gradient refinement is an effective method to achieve this goal, but real-space intervention is most often required in order to adequately address problems detected by structure-validation software. In order to improve the existing protocol, automated re-refinement was combined with structure validation and difference-density peak analysis to produce a catalogue of problems in PDB entries that are amenable to automatic correction. It is shown that re-refinement can be effective in producing improvements, which are often associated with the systematic use of the TLS parameterization of B factors, even for relatively new and high-resolution PDB entries, while the accompanying manual or semi-manual map analysis and fitting steps show good prospects for eventual automation. It is proposed that the potential for simultaneous improvements in methods and in re-refinement results be further encouraged by broadening the scope of depositions to include refinement metadata and ultimately primary rather than reduced X-ray data.

Entry inhibitors: New advances in HCV treatment

PubMed Central

Qian, Xi-Jing; Zhu, Yong-Zhe; Zhao, Ping; Qi, Zhong-Tian

2016-01-01

Hepatitis C virus (HCV) infection affects approximately 3% of the world's population and causes chronic liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. Although current antiviral therapy comprising direct-acting antivirals (DAAs) can achieve a quite satisfying sustained virological response (SVR) rate, it is still limited by viral resistance, long treatment duration, combined adverse reactions, and high costs. Moreover, the currently marketed antivirals fail to prevent graft reinfections in HCV patients who receive liver transplantations, probably due to the cell-to-cell transmission of the virus, which is also one of the main reasons behind treatment failure. HCV entry is a highly orchestrated process involving initial attachment and binding, post-binding interactions with host cell factors, internalization, and fusion between the virion and the host cell membrane. Together, these processes provide multiple novel and promising targets for antiviral therapy. Most entry inhibitors target host cell components with high genetic barriers and eliminate viral infection from the very beginning of the viral life cycle. In future, the addition of entry inhibitors to a combination of treatment regimens might optimize and widen the prevention and treatment of HCV infection. This review summarizes the molecular mechanisms and prospects of the current preclinical and clinical development of antiviral agents targeting HCV entry. PMID:26733381

Experimental energy resolution of a paracentric hemispherical deflector analyzer for different entry positions and bias

NASA Astrophysics Data System (ADS)

Dogan, M.; Ulu, M.; Gennarakis, G. G.; Zouros, T. J. M.

2013-04-01

A specially designed hemispherical deflector analyzer (HDA) with 5-element input lens having a movable entry position R0 suitable for electron energy analysis in atomic collisions was constructed and tested. The energy resolution of the HDA was experimentally determined for three different entry positions R0 = 84, 100, 112 mm as a function of the nominal entry potential V(R0) under pre-retardation conditions. The resolution for the (conventional) entry at the mean radius R0 = 100 mm was found to be a factor of 1.6-2 times worse than the resolution for the two (paracentric) positions R0 = 84 and 112 mm at particular values of V(R0). These results provide the first experimental verification and a proof of principle of the utility of such a paracentric HDA, while demonstrating its advantages over the conventional HDA: greater dispersion with reduced angular aberrations resulting in better energy resolution without the use of any additional fringing field correction electrodes. Supporting simulations of the entire lens plus HDA spectrometer are also provided and mostly found to be within 20%-30% of experimental values. The paracentric HDA is expected to provide a lower cost and/or more compact alternative to the conventional HDA particularly useful in modern applications utilizing a position sensitive detector.

Experimental energy resolution of a paracentric hemispherical deflector analyzer for different entry positions and bias.

PubMed

Dogan, M; Ulu, M; Gennarakis, G G; Zouros, T J M

2013-04-01

A specially designed hemispherical deflector analyzer (HDA) with 5-element input lens having a movable entry position R0 suitable for electron energy analysis in atomic collisions was constructed and tested. The energy resolution of the HDA was experimentally determined for three different entry positions R0 = 84, 100, 112 mm as a function of the nominal entry potential V(R0) under pre-retardation conditions. The resolution for the (conventional) entry at the mean radius R0 = 100 mm was found to be a factor of 1.6-2 times worse than the resolution for the two (paracentric) positions R0 = 84 and 112 mm at particular values of V(R0). These results provide the first experimental verification and a proof of principle of the utility of such a paracentric HDA, while demonstrating its advantages over the conventional HDA: greater dispersion with reduced angular aberrations resulting in better energy resolution without the use of any additional fringing field correction electrodes. Supporting simulations of the entire lens plus HDA spectrometer are also provided and mostly found to be within 20%-30% of experimental values. The paracentric HDA is expected to provide a lower cost and∕or more compact alternative to the conventional HDA particularly useful in modern applications utilizing a position sensitive detector.

Sulphate absorption across biological membranes.

PubMed

Mitchell, Stephen C; Waring, Rosemary H

2016-01-01

1. Sulphonation is unusual amongst the common Phase II (condensation; synthetic) reactions experienced by xenobiotics, in that the availability of the conjugating agent, sulphate, may become a rate-limiting factor. This sulphate is derived within the body via the oxygenation of sulphur moieties liberated from numerous ingested compounds including the sulphur-containing amino acids. Preformed inorganic sulphate also makes a considerable contribution to this pool. 2. There has been a divergence of opinion as to whether or not inorganic sulphate may be readily absorbed from the gastrointestinal tract and this controversy still continues in some quarters. Even more so, is the vexing question of potential absorption of inorganic sulphate via the lungs and through the skin. 3. This review examines the relevant diverse literature and concludes that sulphate ions may move across biological membranes by means of specific transporters and, although the gastrointestinal tract is by far the major portal of entry, some absorption across the lungs and the skin may take place under appropriate circumstances.

Studying medicine – a cross-sectional questionnaire-based analysis of the motivational factors which influence graduate and undergraduate entrants in Ireland

PubMed Central

Sulong, Saadah; McGrath, Deirdre; Finucane, Paul; Horgan, Mary; O’Flynn, Siún

2014-01-01

Summary Objectives The number of places available in Ireland for graduate entry to medical school has steadily increased since 2006. Few studies have, however, characterized the motivational factors underlying decision to study medicine via this route. We compared the factors motivating graduate entrants versus undergraduate entry (UGE) students to choose medicine as a course of study. Design The present study was a quantitative cross-sectional questionnaire-based investigation. Setting The study was conducted in University College Cork and University of Limerick, Ireland. Participants It involved 185 graduate entry (GE) and 120 UGE students. Outcome measures Questionnaires were distributed to students addressing the following areas: demographic/academic characteristics; factors influencing the selection of academic institution and motivation to study medicine; and the role of career guidance in choice of study. Results When asked to list reasons for selecting medicine, both groups listed a wish to help and work with people, and a desire to prevent and cure disease. UGE students were significantly more motivated by intellectual satisfaction, encouragement by family/friends, financial reasons, and professional independence. Approximately half of GE students selected their first degree with a view to potentially studying medicine in the future. GE and UGE students differed significantly with respect to sources consulted for career guidance and source of study information. Conclusions This study is the first systematic examination of study and career motivation in GE medical students since the programme was offered by Irish universities and provides insight into the reasons why graduate entrants in Ireland choose to study medicine via this route. PMID:25057383

Patterns of post-acute health care utilization after a severe traumatic brain injury: Results from the PariS-TBI cohort.

PubMed

Jourdan, Claire; Bayen, Eleonore; Darnoux, Emmanuelle; Ghout, Idir; Azerad, Sylvie; Ruet, Alexis; Vallat-Azouvi, Claire; Pradat-Diehl, Pascale; Aegerter, Philippe; Weiss, Jean-Jacques; Azouvi, Philippe

2015-01-01

To assess brain injury services utilization and their determinants using Andersen's model. Prospective follow-up of the PariS-TBI inception cohort. Out of 504 adults with severe traumatic brain injury (TBI), 245 survived and 147 received a 4-year outcome assessment (mean age 33 years, 80% men). Provision rates of medical, rehabilitation, social and re-entry services and their relations to patients' characteristics were assessed. Following acute care discharge, 78% of patients received physiotherapy, 61% speech/cognitive therapy, 50% occupational therapy, 41% psychological assistance, 63% specialized medical follow-up, 21% community re-entry assistance. Health-related need factors, in terms of TBI severity, were the main predictors of services. Provision of each therapy was significantly associated with corresponding speech, motor and psychological impairments. However, care provision did not depend on cognitive impairments and cognitive therapy was related to pre-disposing and geographical factors. Community re-entry assistance was provided to younger and more independent patients. These quantitative findings illustrate strengths and weaknesses of late brain injury care provision in urban France and highlight the need to improve treatment of cognitive impairments.

Curve fits of predicted inviscid stagnation-point radiative heating rates, cooling factors, and shock standoff distances for hyperbolic earth entry

NASA Technical Reports Server (NTRS)

Suttles, J. T.; Sullivan, E. M.; Margolis, S. B.

1974-01-01

Curve-fit formulas are presented for the stagnation-point radiative heating rate, cooling factor, and shock standoff distance for inviscid flow over blunt bodies at conditions corresponding to high-speed earth entry. The data which were curve fitted were calculated by using a technique which utilizes a one-strip integral method and a detailed nongray radiation model to generate a radiatively coupled flow-field solution for air in chemical and local thermodynamic equilibrium. The range of free-stream parameters considered were altitudes from about 55 to 70 km and velocities from about 11 to 16 km.sec. Spherical bodies with nose radii from 30 to 450 cm and elliptical bodies with major-to-minor axis ratios of 2, 4, and 6 were treated. Powerlaw formulas are proposed and a least-squares logarithmic fit is used to evaluate the constants. It is shown that the data can be described in this manner with an average deviation of about 3 percent (or less) and a maximum deviation of about 10 percent (or less). The curve-fit formulas provide an effective and economic means for making preliminary design studies for situations involving high-speed earth entry.

Host cell virus entry mediated by Australian bat lyssavirus G envelope glycoprotein occurs through a clathrin-mediated endocytic pathway that requires actin and Rab5.

PubMed

Weir, Dawn L; Laing, Eric D; Smith, Ina L; Wang, Lin-Fa; Broder, Christopher C

2014-02-27

Australian bat lyssavirus (ABLV), a rhabdovirus of the genus Lyssavirus which circulates in both pteropid fruit bats and insectivorous bats in mainland Australia, has caused three fatal human infections, the most recent in February 2013, manifested as acute neurological disease indistinguishable from clinical rabies. Rhabdoviruses infect host cells through receptor-mediated endocytosis and subsequent pH-dependent fusion mediated by their single envelope glycoprotein (G), but the specific host factors and pathways involved in ABLV entry have not been determined. ABLV internalization into HEK293T cells was examined using maxGFP-encoding recombinant vesicular stomatitis viruses (rVSV) that express ABLV G glycoproteins. A combination of chemical and molecular approaches was used to investigate the contribution of different endocytic pathways to ABLV entry. Dominant negative Rab GTPases were used to identify the endosomal compartment utilized by ABLV to gain entry into the host cell cytosol. Here we show that ABLV G-mediated entry into HEK293T cells was significantly inhibited by the dynamin-specific inhibitor dynasore, chlorpromazine, a drug that blocks clathrin-mediated endocytosis, and the actin depolymerizing drug latrunculin B. Over expression of dominant negative mutants of Eps15 and Rab5 also significantly reduced ABLV G-mediated entry into HEK293T cells. Chemical inhibitors of caveolae-dependent endocytosis and macropinocytosis and dominant negative mutants of Rab7 and Rab11 had no effect on ABLV entry. The predominant pathway utilized by ABLV for internalization into HEK293T cells is clathrin-and actin-dependent. The requirement of Rab5 for productive infection indicates that ABLV G-mediated fusion occurs within the early endosome compartment.

Potential predictors of susceptibility to occupational stress in Japanese novice nurses - a pilot study.

PubMed

Okita, Shinobu; Daitoku, Satoshi; Abe, Masaharu; Arimura, Emi; Setoyama, Hitoshi; Koriyama, Chihaya; Ushikai, Miharu; Kawaguchi, Hiroaki; Horiuchi, Masahisa

2017-04-04

Occupational stress is a known factor behind employee resignations; thus, early identification of individuals prone to such stress is important. Accordingly, in this pilot study we evaluated potential predictors of susceptibility to occupational stress in Japanese novice nurses. Forty-two female novice nurses at Kagoshima University Hospital were recruited for the study population. Each underwent physical health and urinary examinations, and completed a lifestyle questionnaire at the time of job entry. Each also completed a Brief Job Stress Questionnaire (BJSQ), related to mental health status, at job entry and 5 months post-entry. Psychological stress, somatic symptoms, and combined BJSQ scores were determined for each time point. All three stress condition scores had significantly decreased at 5 months post-entry, suggesting occupational stress. Systolic blood pressure (r = -0.324, p < 0.05) and urinary sodium (r = -0.313, p < 0.05) were significantly negatively correlated with combined BJSQ score at 5 months post-entry. Post-entry stress condition scores were significantly low in subjects reporting substantial 1-year body weight change (≤ ± 3 kg) and short times between dinner and bedtimes (≤2 h), though baseline stress condition scores were not. Urinary sodium concentration, 1-year body weight change, and pre-sleep evening meals were then targeted for multivariate analysis, and confirmed as independent explanatory variables for post-entry stress condition scores. One-year body weight change, times between dinner and bedtimes, and urinary sodium concentration are promising potential predictors of susceptibility to occupational stress, and should be further investigated in future research. ISRCTN ISRCTN17516023. Retrospectively registered 7 December 2016.

Step test performance and risk of stress fractures among female army trainees.

PubMed

Cowan, David N; Bedno, Sheryl A; Urban, Nadia; Lee, Dara S; Niebuhr, David W

2012-06-01

Stress fractures and other musculoskeletal injuries are major sources of morbidity among female military trainees. Several risk factors have been postulated, particularly pre-existing fitness, usually assessed with post-entry run time for ≥ 1.0 mile. Physical fitness is not formally evaluated prior to Army entry. If a valid and simple test that identified women at increased risk of stress fracture were available and could be applied prior to entry, it would facilitate cost-benefit studies of deferral or interventions. These analyses were undertaken to determine if a 5-minute step test conducted before entry identified women at increased risk. A prospective study was conducted of weight-qualified women entering the Army in 2005-2006, with analyses completed in 2011. At the pre-entry examination, information was collected on age, BMI, smoking, race, and activity level. Everyone took the step test. All outpatient medical encounters were captured, and stress fractures and other musculoskeletal injuries identified. Women with stress fractures and those with other musculoskeletal injuries were evaluated separately. 1568 women were included in the study; 109 developed stress fractures and 803 other musculoskeletal injury. Women who failed the step test had a 76% higher stress fracture incidence and a 35% higher incidence of other musculoskeletal injuries. There was effect modification between age and test failure for stress fracture. A step test that can be administered before military entry identifies women with increased incidence of stress fracture and other musculoskeletal injury. This test could be used pre-entry to defer or target high-risk recruits for tailored fitness training before or after military entrance. Copyright © 2012 American Journal of Preventive Medicine. All rights reserved.

Icm/Dot-Independent Entry of Legionella pneumophila into Amoeba and Macrophage Hosts

PubMed Central

Bandyopadhyay, Purnima; Xiao, Huifang; Coleman, Hope A.; Price-Whelan, Alexa; Steinman, Howard M.

2004-01-01

Legionella pneumophila, the causative agent of Legionnaires' disease, expresses a type IVB secretion apparatus that translocates bacterial proteins into amoeba and macrophage hosts. When stationary-phase cultures are used to infect hosts, the type IVB apparatus encoded by the icm/dot genes is required for entry, delay of phagosome-lysosome fusion, and intracellular multiplication within host cells. Null mutants with mutations in icm/dot genes are defective in these phenotypes. Here a new model is described in which hosts are infected with stationary-phase cultures that have been incubated overnight in pH 6.5 buffer. This model is called Ers treatment because it enhances the resistance to acid, hydrogen peroxide, and antibiotic stress beyond that of stationary-phase cultures. Following Ers treatment entry into amoeba and macrophage hosts does not require dotA, which is essential for Legionella virulence phenotypes when hosts are infected with stationary-phase cultures, dotB, icmF, icmV, or icmX. Defective host entry is also suppressed for null mutants with mutations in the KatA and KatB catalase-peroxidase enzymes, which are required for proper intracellular growth in amoeba and macrophage hosts. Ers treatment-induced suppression of defective entry is not associated with increased bacterial adhesion to host cells or with morphological changes in the bacterial envelope but is dependent on protein expression during Ers treatment. By using proteomic analysis, Ers treatment was shown to induce a protein predicted to contain eight tetratricopeptide repeats, a motif previously implicated in enhanced entry of L. pneumophila. Characterization of Ers treatment-dependent changes in expression is proposed as an avenue for identifying icm/dot-independent factors that function in the entry of Legionella into amoeba and macrophage hosts. PMID:15271914

Prediction of the Aerothermodynamic Environment of the Huygens Probe

NASA Technical Reports Server (NTRS)

Hollis, Brian R.; Striepe, Scott A.; Wright, Michael J.; Bose, Deepak; Sutton, Kenneth; Takashima, Naruhisa

2005-01-01

An investigation of the aerothermodynamic environment of the Huygens entry probe has been conducted. A Monte Carlo simulation of the trajectory of the probe during entry into Titan's atmosphere was performed to identify a worst-case heating rate trajectory. Flowfield and radiation transport computations were performed at points along this trajectory to obtain convective and radiative heat-transfer distributions on the probe's heat shield. This investigation identified important physical and numerical factors, including atmospheric CH4 concentration, transition to turbulence, numerical diffusion modeling, and radiation modeling, which strongly influenced the aerothermodynamic environment.

Space shuttle entry terminal area energy management

NASA Technical Reports Server (NTRS)

Moore, Thomas E.

1991-01-01

A historical account of the development for Shuttle's Terminal Area Energy Management (TAEM) is presented. A derivation and explanation of logic and equations are provided as a supplement to the well documented guidance computation requirements contained within the official Functional Subsystem Software Requirements (FSSR) published by Rockwell for NASA. The FSSR contains the full set of equations and logic, whereas this document addresses just certain areas for amplification.

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

Walton, B.T.

In the present study, acute and chronic toxicities of five PAHs (naphthalene, anthracene, benz(a)anthracene, pyrene, and benzo(a)pyrene) and an oxygenated PAH derivative (anthrone) were determined in a terrestrial insect, Acheta domesticus (L.), with emphasis on the influence of route of entry on toxicity. Hexamethylphosphoric triamide (hempa) was included in the chronic tests since this chemosterilant is a useful reference compound for investigations of reproductive effects of chemicals in insects.

Viral Entry of Hepatitis B and D Viruses and Bile Salts Transportation Share Common Molecular Determinants on Sodium Taurocholate Cotransporting Polypeptide

PubMed Central

Yan, Huan; Peng, Bo; Liu, Yang; Xu, Guangwei; He, Wenhui; Ren, Bijie; Jing, Zhiyi; Sui, Jianhua

2014-01-01

ABSTRACT The liver bile acids transporter sodium taurocholate cotransporting polypeptide (NTCP) is responsible for the majority of sodium-dependent bile salts uptake by hepatocytes. NTCP also functions as a cellular receptor for viral entry of hepatitis B virus (HBV) and hepatitis D virus (HDV) through a specific interaction between NTCP and the pre-S1 domain of HBV large envelope protein. However, it remains unknown if these two functions of NTCP are independent or if they interfere with each other. Here we show that binding of the pre-S1 domain to human NTCP blocks taurocholate uptake by the receptor; conversely, some bile acid substrates of NTCP inhibit HBV and HDV entry. Mutations of NTCP residues critical for bile salts binding severely impair viral infection by HDV and HBV; to a lesser extent, the residues important for sodium binding also inhibit viral infection. The mutation S267F, corresponding to a single nucleotide polymorphism (SNP) found in about 9% of the East Asian population, renders NTCP without either taurocholate transporting activity or the ability to support HBV or HDV infection in cell culture. These results demonstrate that molecular determinants critical for HBV and HDV entry overlap with that for bile salts uptake by NTCP, indicating that viral infection may interfere with the normal function of NTCP, and bile acids and their derivatives hold the potential for further development into antiviral drugs. IMPORTANCE Human hepatitis B virus (HBV) and its satellite virus, hepatitis D virus (HDV), are important human pathogens. Available therapeutics against HBV are limited, and there is no drug that is clinically available for HDV infection. A liver bile acids transporter (sodium taurocholate cotransporting polypeptide [NTCP]) critical for maintaining homeostasis of bile acids serves as a functional receptor for HBV and HDV. We report here that the NTCP-binding lipopeptide that originates from the first 47 amino acids of the pre-S1 domain of the HBV L protein blocks taurocholate transport. Some bile salts dose dependently inhibit HBV and HDV infection mediated by NTCP; molecular determinants of NTCP critical for HBV and HDV entry overlap with that for bile acids transport. This work advances our understanding of NTCP-mediated HBV and HDV infection in relation to NTCP's physiological function. Our results also suggest that bile acids or their derivatives hold potential for development into novel drugs against HBV and HDV infection. PMID:24390325

The characteristics of registered nurses whose licenses expire: why they leave nursing and implications for retention and re-entry.

PubMed

Skillman, Susan M; Palazzo, Lorella; Hart, L Gary; Keepnews, David

2010-01-01

Little is known about RNs who drop their licenses and their potential re-entry into the nursing workforce. The results of this study provide insight into reasons nurses leave their careers and the barriers to re-entry, all important indicators of the current professional climate for nursing. While representing only one state, these findings suggest that RNs who allow their licenses to expire do so because they have reached retirement age or, among those who do not cite age as a factor, because many are unable or unwilling to work in the field. Inactive nurses who might otherwise appear to be likely candidates for re-entry into the profession may not be easily encouraged to practice nursing again without significant changes in their personal circumstances or the health care work environment. Effective ways to address current and pending RN workforce shortages include expanding RN education capacity to produce more RNs who can contribute to the workforce across the coming decades, and promote work environments in which RNs want to, and are able to, practice across a long nursing career.

Enhanced Inhibition of Human Immunodeficiency Virus Type 1 by Met-Stromal-Derived Factor 1β Correlates with Down-Modulation of CXCR4

PubMed Central

Yang, Otto O.; Swanberg, Stephen L.; Lu, Zhijian; Dziejman, Michelle; McCoy, John; Luster, Andrew D.; Walker, Bruce D.; Herrmann, Steven H.

1999-01-01

CXCR4 is a chemokine receptor used by some strains of HIV-1 as an entry coreceptor in association with cell surface CD4 on human cells. In human immunodeficiency virus type 1 (HIV-1)-infected individuals, the appearance of viral isolates with a tropism for CXCR4 (T tropic) has been correlated with late disease progression. The presumed natural ligands for CXCR4 are SDF-1α and SDF-1β, which are proposed to play a role in blocking T-tropic HIV-1 cell entry. Here, we demonstrate that addition of an N-terminal methionine residue to SDF-1β (Met-SDF-1β) results in a dramatically enhanced functional activity compared to that of native SDF-1β. Equivalent concentrations of Met-SDF-1β are markedly more inhibitory for T-tropic HIV-1 replication than SDF-1β. A comparison of the biological activities of these two forms of SDF-1β reveals that Met-SDF-1β induces a more pronounced intracellular calcium flux yet binds with slightly lower affinity to CXCR4 than SDF-1β. Down-modulation of CXCR4 is similar after exposure of cells to either chemokine form for 2 h. However, after a 48-h incubation, the surface expression of CXCR4 is much lower for cells treated with Met-SDF-1β. The enhanced blocking of T-tropic HIV-1 by Met-SDF-1β appears to be related to prolonged CXCR4 down-modulation. PMID:10233917

Ceramic Foams for TPS Applications

NASA Technical Reports Server (NTRS)

Stockpoole, Mairead

2003-01-01

Ceramic foams have potential in many areas of Thermal Protection Systems (TPS) including acreage and tile leading edges as well as being suitable as a repair approach for re-entry vehicles. NASA Ames is conducting ongoing research in developing lower-density foams from pre-ceramic polymer routes. One of the key factors to investigate, when developing new materials for re-entry applications, is their oxidation behavior in the appropriate re-entry environment which can be simulated using ground based arc jet (plasma jet) testing. Arc jet testing is required to provide the appropriate conditions (stagnation pressures, heat fluxes, enthalpies, heat loads and atmospheres) encountered during flight. This work looks at the response of ceramic foams (Si systems) exposed to simulated reentry environments and investigates the influence of microstructure and composition on the material? response. Other foam properties (mechanical and thermal) will also be presented.

Implementing computerized physician order entry: the importance of special people.

PubMed

Ash, Joan S; Stavri, P Zoë; Dykstra, Richard; Fournier, Lara

2003-03-01

To articulate important lessons learned during a study to identify success factors for implementing computerized physician order entry (CPOE) in inpatient and outpatient settings. Qualitative study by a multidisciplinary team using data from observation, focus groups, and both formal and informal interviews. Data were analyzed using a grounded approach to develop a taxonomy of patterns and themes from the transcripts and field notes. The theme we call Special People is explored here in detail. A taxonomy of types of Special People includes administrative leaders, clinical leaders (champions, opinion leaders, and curmudgeons), and bridgers or support staff who interface directly with users. The recognition and nurturing of Special People should be among the highest priorities of those implementing computerized physician order entry. Their education and training must be a goal of teaching programs in health administration and medical informatics.

Analytical design of sensors for measuring during terminal phase of atmospheric temperature planetary entry

NASA Technical Reports Server (NTRS)

Millard, J. P.; Green, M. J.; Sommer, S. C.

1972-01-01

An analytical study was conducted to develop a sensor for measuring the temperature of a planetary atmosphere from an entry vehicle traveling at supersonic speeds and having a detached shock. Such a sensor has been used in the Planetary Atmosphere Experiments Test Probe (PAET) mission and is planned for the Viking-Mars mission. The study specifically considered butt-welded thermocouple sensors stretched between two support posts; however, the factors considered are sufficiently general to apply to other sensors as well. This study included: (1) an investigation of the relation between sensor-measured temperature and free-stream conditions; (2) an evaluation of the effects of extraneous sources of heat; (3) the development of a computer program for evaluating sensor response during entry; and (4) a parametric study of sensor design characteristics.

The ectodomain of a novel member of the immunoglobulin subfamily related to the poliovirus receptor has the attributes of a bona fide receptor for herpes simplex virus types 1 and 2 in human cells.

PubMed

Cocchi, F; Menotti, L; Mirandola, P; Lopez, M; Campadelli-Fiume, G

1998-12-01

We report on the functional cloning of a hitherto unknown member of the immunoglobulin (Ig) superfamily selected for its ability to confer susceptibility to herpes simplex virus (HSV) infection on a highly resistant cell line (J1.1-2 cells), derived by exposure of BHKtk- cells to a recombinant HSV-1 expressing tumor necrosis factor alpha (TNF-alpha). The sequence of herpesvirus Ig-like receptor (HIgR) predicts a transmembrane protein with an ectodomain consisting of three cysteine-bracketed domains, one V-like and two C-like. HIgR shares its ectodomain with and appears to be an alternative splice variant of the previously described protein PRR-1 (poliovirus receptor-related protein). Both HIgR and PRR-1 conferred on J1.1-2 cells susceptibility to HSV-1, HSV-2, and bovine herpesvirus 1. The viral ligand of HIgR and PRR-1 is glycoprotein D, a constituent of the virion envelope long known to mediate viral entry into cells through interaction with cellular receptor molecules. Recently, PRR-1, renamed HveC (herpesvirus entry mediator C), and the related PRR-2, renamed HveB, were reported to mediate the entry of HSV-1, HSV-2, and bovine herpesvirus 1, and the homologous poliovirus receptor was reported to mediate the entry of pseudorabies virus (R. J. Geraghty, C. Krummenacher, G. H. Cohen, R. J. Eisenberg, and P. G. Spear, Science 280:1618-1620, 1998; M. S. Warner, R. J. Geraghty, W. M. Martinez, R. I. Montgomery, J. C. Whitbeck, R. Xu, R. J. Eisenberg, G. H. Cohen, and P. G. Spear, Virology 246:179-189, 1998). Here we further show that HIgR or PRR-1 proteins detected by using a monoclonal antibody to PRR-1 are widely distributed among human cell lines susceptible to HSV infection and commonly used for HSV studies. The monoclonal antibody neutralized virion infectivity in cells transfected with HIgR or PRR-1 cDNA, as well as in the human cell lines, indicating a direct interaction of virions with the receptor molecule, and preliminarily mapping this function to the ectodomain of HIgR and PRR-1. Northern blot analysis showed that HIgR or PRR-1 mRNAs were expressed in human tissues, with the highest expression being detected in nervous system samples. HIgR adds a novel member to the cluster of Ig superfamily members able to mediate the entry of alphaherpesviruses into cells. The wide distribution of HIgR or PRR-1 proteins among human cell lines susceptible to HSV infection, coupled with the neutralizing activity of the antibody in the same cells, provides direct demonstration of the actual use of this cluster of molecules as HSV-1 and HSV-2 entry receptors in human cell lines. The high level of expression in samples from nervous system makes the use of these proteins in human tissues very likely. This cluster of molecules may therefore be considered to constitute bona fide receptors for HSV-1 and HSV-2.

Space shuttle post-entry and landing analysis. Volume 1: Candidate system evaluations

NASA Technical Reports Server (NTRS)

Crawford, B. S.; Duiven, E. M.

1973-01-01

The general purpose of this study is to aid in the evaluation and design of multi-sensor navigation schemes proposed for the orbiter. The scope of the effort is limited to the post-entry, energy management, and approach and landing mission phases. One candidate system based on conventional navigation aids is illustrated including two DME (Distance Measuring Equipment) stations and ILS (Instrument Landing System) glide slope and localizer antennas. Some key elements of the system not shown are the onboard IMUs (Inertial Measurement Units), altimeters, and a computer. The latter is programmed to mix together (filter) the IMU data and the externally-derived data. A completely automatic, all-weather landing capability is required. Since no air-breathing engines will be carried on orbital flights, there will be no chance to go around and try again following a missed approach.

Ultrasound beam transmission using a discretely orthogonal Gaussian aperture basis

NASA Astrophysics Data System (ADS)

Roberts, R. A.

2018-04-01

Work is reported on development of a computational model for ultrasound beam transmission at an arbitrary geometry transmission interface for generally anisotropic materials. The work addresses problems encountered when the fundamental assumptions of ray theory do not hold, thereby introducing errors into ray-theory-based transmission models. Specifically, problems occur when the asymptotic integral analysis underlying ray theory encounters multiple stationary phase points in close proximity, due to focusing caused by concavity on either the entry surface or a material slowness surface. The approach presented here projects integrands over both the transducer aperture and the entry surface beam footprint onto a Gaussian-derived basis set, thereby distributing the integral over a summation of second-order phase integrals which are amenable to single stationary phase point analysis. Significantly, convergence is assured provided a sufficiently fine distribution of basis functions is used.

US photovoltaic patents: 1991-1993

NASA Astrophysics Data System (ADS)

Pohle, L.

1995-03-01

This document contains US patents on terrestrial photovoltaic (PV) power applications, including systems, components, and materials as well as manufacturing and support functions. The patent entries in this document were issued from 1991 to 1993. The entries were located by searching USPA, the database of the US Patent Office. The final search retrieved all patents under the class 'Batteries, Thermoelectric and Photoelectric' and the subclasses 'Photoelectric,' 'Testing,' and 'Applications.' The search also located patents that contained the words 'photovoltaic(s)' or 'solar cell(s)' and their derivatives. After the initial list was compiled, most of the patents on the following subjects were excluded: space photovoltaic technology, use of the photovoltaic effect for detectors, and subjects only peripherally concerned with photovoltaic. Some patents on these three subjects were included when ft appeared that those inventions might be of use in terrestrial PV power technologies.

Atmospheric Chemistry of Micrometeoritic Organic Compounds

NASA Technical Reports Server (NTRS)

Kress, M. E.; Belle, C. L.; Pevyhouse, A. R.; Iraci, L. T.

2011-01-01

Micrometeorites approx.100 m in diameter deliver most of the Earth s annual accumulation of extraterrestrial material. These small particles are so strongly heated upon atmospheric entry that most of their volatile content is vaporized. Here we present preliminary results from two sets of experiments to investigate the fate of the organic fraction of micrometeorites. In the first set of experiments, 300 m particles of a CM carbonaceous chondrite were subject to flash pyrolysis, simulating atmospheric entry. In addition to CO and CO2, many organic compounds were released, including functionalized benzenes, hydrocarbons, and small polycyclic aromatic hydrocarbons. In the second set of experiments, we subjected two of these compounds to conditions that simulate the heterogeneous chemistry of Earth s upper atmosphere. We find evidence that meteor-derived compounds can follow reaction pathways leading to the formation of more complex organic compounds.

Palladium-Copper Catalyzed Alkyne Activation as an Entry to Multicomponent Syntheses of Heterocycles

NASA Astrophysics Data System (ADS)

Müller, Thomas J. J.

Alkynones and chalcones are of paramount importance in heterocyclic chemistry as three-carbon building blocks. In a very efficient manner, they can be easily generated by palladium-copper catalyzed reactions: ynones are formed from acid chlorides and terminal alkynes, and chalcones are synthesized in the sense of a coupling-isomerization (CI) sequence from (hetero)aryl halides and propargyl alcohols. Mild reaction conditions now open entries to sequential and consecutive transformations to heterocycles, such as furans, 3-halo furans, pyrroles, pyrazoles, substituted and annelated pyridines, annelated thiopyranones, pyridimines, meridianins, benzoheteroazepines and tetrahydro-β-carbolines, by consecutive coupling-cyclocondensation or CI-cyclocondensation sequences, as new diversity oriented routes to heterocycles. Domino reactions based upon the coupling-isomerization reaction (CIR) have been probed in the synthesis of antiparasital 2-substituted quinoline derivatives and highly luminescent spiro-benzofuranones and spiro-indolones.

Micro Weather Stations for Mars

NASA Technical Reports Server (NTRS)

Crisp, David; Kaiser, William J.; VanZandt, Thomas R.; Hoenk, Michael E.; Tillman, James E.

1995-01-01

A global network of weather stations will be needed to characterize the near-surface environment on Mars. Here, we review the scientific and measurement objectives of this network. We also show how these objectives can be met within the cost-constrained Mars Surveyor Program by augmenting the Mars Pathfinder-derived landers with large numbers of very small (less than 5 liter), low-mass (less than 5 kg), low-power, low-cost Mini-meteorological stations. Each station would include instruments for measuring atmospheric. pressures, temperatures, wind velocities, humidity, and airborne dust abundance. They would also include a data handling, telemetry, power, atmospheric entry, and deployment systems in a rugged package capable of direct entry and a high-impact landing. In this paper, we describe these systems and summarize the data-taking strategies and data volumes needed to achieve the surface meteorology objectives for Mars.

Regolith-Derived Heat Shield for Planetary Body Entry and Descent System with In Situ Fabrication

NASA Technical Reports Server (NTRS)

Hogue, Michael D.; Mueller, Robert P.; Rasky, Daniel; Hintze, Paul; Sibille, Laurent

2012-01-01

In this paper we will discuss a new mass-efficient and innovative way of protecting high-mass spacecraft during planetary Entry, Descent & Landing (EDL). Heat shields fabricated in situ can provide a thermal-protection system (TPS) for spacecraft that routinely enter a planetary atmosphere. By fabricating the heat shield with space resources from regolith materials available on moons and asteroids, it is possible to avoid launching the heat-shield mass from Earth. Two regolith processing and manufacturing methods will be discussed: 1) Compression and sintering of the regolith to yield low density materials; 2) Formulations of a High-temperature silicone RTV (Room Temperature Vulcanizing) compound are used to bind regolith particles together. The overall positive results of torch flame impingement tests and plasma arc jet testing on the resulting samples will also be discussed.

Validating Emergency Department Vital Signs Using a Data Quality Engine for Data Warehouse

PubMed Central

Genes, N; Chandra, D; Ellis, S; Baumlin, K

2013-01-01

Background : Vital signs in our emergency department information system were entered into free-text fields for heart rate, respiratory rate, blood pressure, temperature and oxygen saturation. Objective : We sought to convert these text entries into a more useful form, for research and QA purposes, upon entry into a data warehouse. Methods : We derived a series of rules and assigned quality scores to the transformed values, conforming to physiologic parameters for vital signs across the age range and spectrum of illness seen in the emergency department. Results : Validating these entries revealed that 98% of free-text data had perfect quality scores, conforming to established vital sign parameters. Average vital signs varied as expected by age. Degradations in quality scores were most commonly attributed logging temperature in Fahrenheit instead of Celsius; vital signs with this error could still be transformed for use. Errors occurred more frequently during periods of high triage, though error rates did not correlate with triage volume. Conclusions : In developing a method for importing free-text vital sign data from our emergency department information system, we now have a data warehouse with a broad array of quality-checked vital signs, permitting analysis and correlation with demographics and outcomes. PMID:24403981

Validating emergency department vital signs using a data quality engine for data warehouse.

PubMed

Genes, N; Chandra, D; Ellis, S; Baumlin, K

2013-01-01

Vital signs in our emergency department information system were entered into free-text fields for heart rate, respiratory rate, blood pressure, temperature and oxygen saturation. We sought to convert these text entries into a more useful form, for research and QA purposes, upon entry into a data warehouse. We derived a series of rules and assigned quality scores to the transformed values, conforming to physiologic parameters for vital signs across the age range and spectrum of illness seen in the emergency department. Validating these entries revealed that 98% of free-text data had perfect quality scores, conforming to established vital sign parameters. Average vital signs varied as expected by age. Degradations in quality scores were most commonly attributed logging temperature in Fahrenheit instead of Celsius; vital signs with this error could still be transformed for use. Errors occurred more frequently during periods of high triage, though error rates did not correlate with triage volume. In developing a method for importing free-text vital sign data from our emergency department information system, we now have a data warehouse with a broad array of quality-checked vital signs, permitting analysis and correlation with demographics and outcomes.

Extraterrestrial Regolith Derived Atmospheric Entry Heat Shields

NASA Technical Reports Server (NTRS)

Hogue, Michael D.; Mueller, Robert P.; Sibille, Laurent; Hintze, Paul E.; Rasky, Daniel J.

2016-01-01

High-mass planetary surface access is one of NASAs technical challenges involving entry, descent and landing (EDL). During the entry and descent phase, frictional interaction with the planetary atmosphere causes a heat build-up to occur on the spacecraft, which will rapidly destroy it if a heat shield is not used. However, the heat shield incurs a mass penalty because it must be launched from Earth with the spacecraft, thus consuming a lot of precious propellant. This NASA Innovative Advanced Concept (NIAC) project investigated an approach to provide heat shield protection to spacecraft after launch and prior to each EDL thus potentially realizing significant launch mass savings. Heat shields fabricated in situ can provide a thermal-protection system for spacecraft that routinely enter a planetary atmosphere. By fabricating the heat shield with space resources from materials available on moons and asteroids, it is possible to avoid launching the heat-shield mass from Earth. Regolith has extremely good insulating properties and the silicates it contains can be used in the fabrication and molding of thermal-protection materials. In this paper, we will describe three types of in situ fabrication methods for heat shields and the testing performed to determine feasibility of this approach.

Resistance of human plasmacytoid dendritic CAL-1 cells to infection with lymphocytic choriomeningitis virus (LCMV) is caused by restricted virus cell entry, which is overcome by contact of CAL-1 cells with LCMV-infected cells.

PubMed

Iwasaki, Masaharu; Sharma, Siddhartha M; Marro, Brett S; de la Torre, Juan C

2017-11-01

Plasmacytoid dendritic cells (pDCs), a main source of type I interferon in response to viral infection, are an early cell target during lymphocytic choriomeningitis virus (LCMV) infection, which has been associated with the LCMV's ability to establish chronic infections. Human blood-derived pDCs have been reported to be refractory to ex vivo LCMV infection. In the present study we show that human pDC CAL-1 cells are refractory to infection with cell-free LCMV, but highly susceptible to infection with recombinant LCMVs carrying the surface glycoprotein of VSV, indicating that LCMV infection of CAL-1 cells is restricted at the cell entry step. Co-culture of uninfected CAL-1 cells with LCMV-infected HEK293 cells enabled LCMV to infect CAL-1 cells. This cell-to-cell spread required direct cell-cell contact and did not involve exosome pathway. Our findings indicate the presence of a novel entry pathway utilized by LCMV to infect pDC. Copyright © 2017. Published by Elsevier Inc.

Murine Leukemia Virus (MLV)-based Coronavirus Spike-pseudotyped Particle Production and Infection

PubMed Central

Millet, Jean Kaoru; Whittaker, Gary R.

2016-01-01

Viral pseudotyped particles (pp) are enveloped virus particles, typically derived from retroviruses or rhabdoviruses, that harbor heterologous envelope glycoproteins on their surface and a genome lacking essential genes. These synthetic viral particles are safer surrogates of native viruses and acquire the tropism and host entry pathway characteristics governed by the heterologous envelope glycoprotein used. They have proven to be very useful tools used in research with many applications, such as enabling the study of entry pathways of enveloped viruses and to generate effective gene-delivery vectors. The basis for their generation lies in the capacity of some viruses, such as murine leukemia virus (MLV), to incorporate envelope glycoproteins of other viruses into a pseudotyped virus particle. These can be engineered to contain reporter genes such as luciferase, enabling quantification of virus entry events upon pseudotyped particle infection with susceptible cells. Here, we detail a protocol enabling generation of MLV-based pseudotyped particles, using the Middle East respiratory syndrome coronavirus (MERS-CoV) spike (S) as an example of a heterologous envelope glycoprotein to be incorporated. We also describe how these particles are used to infect susceptible cells and to perform a quantitative infectivity readout by a luciferase assay. PMID:28018942

Post-entry and volcanic contaminant abundances of zinc, copper, selenium, germanium and gallium in stratospheric micrometeorites

NASA Technical Reports Server (NTRS)

Rietmeijer, Frans J. M.

1995-01-01

Some fraction of Zn, Cu, Se, Ga and Ge in chondritic interplanetary dust particles (IDPs) collected in the lower stratosphere between 1981 May and 1984 June has a volcanic origin. I present a method to evaluate the extent of this unavoidable type of stratospheric contamination for individual particles. The mass-normalized abundances for Cu and Ge as a function of mass-normalized stratospheric residence time show their time-integrated stratospheric aerosol abundances. The Zn, Se and Ga abundances show a subdivision into two groups that span approximately two-year periods following the eruptions of the Mount St. Helens (1980 May) and El Chichon (1982 April) volcanoes. Elemental abundances in particles collected at the end of each two-year period indicate low, but not necessarily ambient, volcanic stratospheric abundances. Using this time-integrated baseline, I calculate the straospheric contaminant fractions in nine IDPs and show that Zn, SE and Ga abundances in chondritic IDPs derive in part from stratospheric aerosol contaminants. Post-entry elemental abundances (i.e., the amount that survived atmospheric entry heating of the IDP) show enrichments relative to the CI abundances but in a smaller number of particles than previously suggested.

Twinning of amphibian embryos by centrifugation

NASA Technical Reports Server (NTRS)

Black, S. D.

1984-01-01

In the frog Xenopus laevis, the dorsal structures of the embryonic body axis normally derive from the side of the egg opposite the side of sperm entry. However, if the uncleaved egg is inclined at lg or centrifuged in an inclined position, this topographic relationship is overridden: the egg makes its dorsal axial structures according to its orientation in the gravitational/centrifugal field, irrespective of the position of sperm entry. Certain conditions of centrifugation cause eggs to develop into conjoined twins with two sets of axial structures. A detailed analysis of twinning provided some insight into experimental axis orientation. First, as with single-axis embryos, both axes in twins are oriented according to the direction of centrifugation. One axis forms at the centripetal side of the egg and the other forms at the centrifugal side, even when the side of sperm entry is normal to the centrifugal force vector. Second, if eggs are centrifuged to give twins, but are inclined at lg to prevent post-centrifugation endoplasmic redistributions, only single-axis embryos develop. Thus, a second redistribution is required for high-frequency secondary axis formation. This can be accomplished by lg (as in the single centrifugations) or by a second centrifugation directed along the egg's animal-vegetal axis.

Psychosocial Risk Factors for Future Adolescent Suicide Attempts.

ERIC Educational Resources Information Center

Lewinsohn, Peter M.; And Others

1994-01-01

Examined psychosocial risk factors for attempting suicide in 1,508 high school students, 26 of whom attempted suicide during year following entry into study. Strongest predictors of future suicide attempt were history of past attempt, current suicidal ideation and depression, recent attempt by friend, low self-esteem, and having been born to…

Productive vs non-productive infection by cell-free Varicella zoster virus of human neurons derived from embryonic stem cells is dependent upon infectious viral dose

PubMed Central

Sloutskin, Anna; Kinchington, Paul R.; Goldstein, Ronald S.

2013-01-01

Varicella Zoster virus (VZV) productively infects humans causing varicella upon primary infection and herpes zoster upon reactivation from latency in neurons. In-vitro studies using cell-associated VZV infection have demonstrated productive VZV-infection, while a few recent studies of human neurons derived from stem cells incubated with cell-free, vaccine-derived VZV did not result in generation of infectious virus. In the present study, 90%-pure human embryonic stem cell-derived neurons were incubated with recombinant cell-free pOka-derived made with an improved method or with VZV vaccine. We found that cell-free pOka and vOka at higher multiplicities of infection elicited productive infection in neurons followed by spread of infection, cytopathic effect and release of infectious virus into the medium. These results further validate the use of this unlimited source of human neurons for studying unexplored aspects of VZV interaction with neurons such as entry, latency and reactivation. PMID:23769240

Exploring transduction mechanisms of protein transduction domains (PTDs) in living cells utilizing single-quantum dot tracking (SQT) technology.

PubMed

Suzuki, Yasuhiro

2012-01-01

Specific protein domains known as protein transduction domains (PTDs) can permeate cell membranes and deliver proteins or bioactive materials into living cells. Various approaches have been applied for improving their transduction efficacy. It is, therefore, crucial to clarify the entry mechanisms and to identify the rate-limiting steps. Because of technical limitations for imaging PTD behavior on cells with conventional fluorescent-dyes, how PTDs enter the cells has been a topic of much debate. Utilizing quantum dots (QDs), we recently tracked the behavior of PTD that was derived from HIV-1 Tat (TatP) in living cells at the single-molecule level with 7-nm special precision. In this review article, we initially summarize the controversy on TatP entry mechanisms; thereafter, we will focus on our recent findings on single-TatP-QD tracking (SQT), to identify the major sequential steps of intracellular delivery in living cells and to discuss how SQT can easily provide direct information on TatP entry mechanisms. As a primer for SQT study, we also discuss the latest findings on single particle tracking of various molecules on the plasma membrane. Finally, we discuss the problems of QDs and the challenges for the future in utilizing currently available QD probes for SQT. In conclusion, direct identification of the rate-limiting steps of PTD entry with SQT should dramatically improve the methods for enhancing transduction efficiency.

Factors Influencing Clinical Performance of Baccalaureate Nursing Majors: A Retrospective Audit.

PubMed

Johnston, Sandra; Fox, Amanda; Coyer, Fiona Maree

2018-06-01

Transition of nursing student to new graduate depends on successful completion of clinical work placement during an undergraduate course. Supporting students during the clinical placement is imperative. This study examined associations between grade point average, domestic or international status, course entry qualification, and single or dual nursing degree to successful completion of clinical placement. A retrospective audit of 665 students in a baccalaureate nursing program was conducted to examine factors influencing clinical performance of baccalaureate nursing students. A significant association between entry qualification, lower grade point average, international status, and receipt of a constructive note was found: χ 2 = 8.678, df = 3, p = .034, t(3.862), df = 663, p ⩽ .001, and Fisher's exact test = 8.581, df = 1, p = .003, respectively. Understanding factors that affect clinical performance may help early identification of students at risk and allow for supportive intervention during placement and subsequent program completion. [J Nurs Educ. 2018;57(6):333-338.]. Copyright 2018, SLACK Incorporated.

The molecular network governing nodule organogenesis and infection in the model legume Lotus japonicus.

PubMed

Madsen, Lene H; Tirichine, Leïla; Jurkiewicz, Anna; Sullivan, John T; Heckmann, Anne B; Bek, Anita S; Ronson, Clive W; James, Euan K; Stougaard, Jens

2010-04-12

Bacterial infection of interior tissues of legume root nodules is controlled at the epidermal cell layer and is closely coordinated with progressing organ development. Using spontaneous nodulating Lotus japonicus plant mutants to uncouple nodule organogenesis from infection, we have determined the role of 16 genes in these two developmental processes. We show that host-encoded mechanisms control three alternative entry processes operating in the epidermis, the root cortex and at the single cell level. Single cell infection did not involve the formation of trans-cellular infection threads and was independent of host Nod-factor receptors and bacterial Nod-factor signals. In contrast, Nod-factor perception was required for epidermal root hair infection threads, whereas primary signal transduction genes preceding the secondary Ca2+ oscillations have an indirect role. We provide support for the origin of rhizobial infection through direct intercellular epidermal invasion and subsequent evolution of crack entry and root hair invasions observed in most extant legumes.

Venus Atmospheric Maneuverable Platform (VAMP) - A Low Cost Venus Exploration Concept

NASA Astrophysics Data System (ADS)

Lee, G.; Polidan, R. S.; Ross, F.

2015-12-01

The Northrop Grumman Aerospace Systems and L-Garde team has been developing an innovative mission concept: a long-lived, maneuverable platform to explore the Venus upper atmosphere. This capability is an implementation of our Lifting Entry Atmospheric Flight (LEAF) system concept, and the Venus implementation is called the Venus Atmospheric Maneuverable Platform (VAMP). The VAMP concept utilizes an ultra-low ballistic coefficient (< 50 Pa), semi-buoyant aircraft that deploys prior to entering the Venus atmosphere, enters without an aeroshell, and provides a long-lived (months to a year) maneuverable vehicle capable of carrying science instruments to explore the Venus upper atmosphere. In this presentation we provide an update on the air vehicle design and a low cost pathfinder mission concept that can be implemented in the near-term. The presentation also provides an overview of our plans for future trade studies, analyses, and prototyping to advance and refine the concept. We will discuss the air vehicle's entry concepts of operations (CONOPs) and atmospheric science operations. We will present a strawman concept of a VAMP pathfinder, including ballistic coefficient, planform area, percent buoyancy, wing span, vehicle mass, power supply, propulsion, materials considerations, structural elements, and instruments accommodation. In this context, we will discuss the following key factors impacting the design and performance of VAMP: Entry into the Venus atmosphere, including descent profile, heating rate, total heat load, stagnation, and acreage temperatures Impact of maximum altitude on air vehicle design and entry heating Candidate thermal protection system (TPS) requirements We will discuss the interdependencies of the above factors and the manner in which the VAMP pathfinder concept's characteristics affect the CONOPs and the science objectives. We will show how the these factors provide constraints as well as enable opportunities for novel long duration scientific studies of the Venus upper atmosphere that support Venus science goals. We will also discuss how the VAMP platform itself can facilitate some of these science measurements.

Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture.

PubMed

Muir, Peter; Hans, Eric C; Racette, Molly; Volstad, Nicola; Sample, Susannah J; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L; Bloom, Debra D; Bleedorn, Jason A; Hao, Zhengling; Amene, Ermias; Suresh, M; Hematti, Peiman

2016-01-01

Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response associated with cranial cruciate ligament matrix degeneration or damage.

Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture

PubMed Central

Muir, Peter; Hans, Eric C.; Racette, Molly; Volstad, Nicola; Sample, Susannah J.; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L.; Bloom, Debra D.; Bleedorn, Jason A.; Hao, Zhengling; Amene, Ermias; Suresh, M.; Hematti, Peiman

2016-01-01

Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response associated with cranial cruciate ligament matrix degeneration or damage. PMID:27575050

Alcohol Detoxification Completion, Acceptance of Referral to Substance Abuse Treatment, and Entry into Substance Abuse Treatment Among Alaska Native People

PubMed Central

Bear, Ursula Running; Beals, Janette; Novins, Douglas K.; Manson, Spero M.

2016-01-01

Background Little is known about factors associated with detoxification treatment completion and the transition to substance abuse treatment following detoxification among Alaska Native people. This study examined 3 critical points on the substance abuse continuum of care (alcohol detoxification completion, acceptance of referral to substance abuse treatment, entry into substance abuse treatment following detoxification). Methods The retrospective cohort included 383 adult Alaska Native patients admitted to a tribally owned and managed inpatient detoxification unit. Three multiple logistic regression models estimated the adjusted associations of each outcome separately with demographic/psychosocial characteristics, clinical characteristics, use related behaviors, and health care utilization. Results Seventy-five percent completed detoxification treatment. Higher global assessment functioning scores, longer lengths of stay, and older ages of first alcohol use were associated with completing detoxification. A secondary drug diagnosis was associated with not completing detoxification. Thirty-six percent accepted a referral to substance abuse treatment following detoxification. Men, those with legal problems, and those with a longer length of stay were more likely to accept a referral to substance abuse treatment. Fifty-eight percent had a confirmed entry into a substance abuse treatment program at discharge. Length of stay was the only variable associated with substance abuse treatment entry. Conclusions Services like motivational interviewing, counseling, development of therapeutic alliance, monetary incentives, and contingency management are effective in linking patients to services after detoxification. These should be considered, along with the factors associated with each point on the continuum of care when linking patients to follow-up services. PMID:27705843

General physicians: born or made? The use of a tracking database to answer medical workforce questions.

PubMed

Poole, P; McHardy, K; Janssen, A

2009-07-01

The aim of the study was to use a tracking database to investigate the perceived influence of various factors on career choices of New Zealand medical graduates and to examine specifically whether experiences at medical school may have an effect on a decision to become a general physician. Questionnaires were distributed to medical students in the current University of Auckland programme at entry and exit points. The surveys have been completed by two entry cohorts and an exit one since 2006. The response rates were 70 and 88% in the entry and exit groups, respectively. More than 75% of exiting students reported an interest in pursuing a career in general internal medicine. In 42%, this is a 'strong interest' in general medicine compared with 23% in the entry cohort (P < 0.0001). There is correlation between a positive experience in a clinical rotation and the reported level of interest in that specialty with those indicating a good experience likely to specify career intentions in that area. Having a positive experience in a clinical rotation, positive role models and flexibility in training are the most influential factors affecting career decisions in Auckland medical students. Only 11% of study respondents reported that student loan burden has a significant influence on career decisions. Quality experiences on attachments seem essential for undergraduates to promote interest in general medicine. There is potential for curriculum design and clinical experiences to be formulated to promote the 'making' of these doctors. Tracking databases will assist in answering some of these questions.

Second-chance university admission, the theory of planned behaviour and student achievement

NASA Astrophysics Data System (ADS)

Alas, Yabit; Anshari, Muhammad; Sabtu, Norakmarul Ihsan; Yunus, Norazmah

2016-06-01

The theory of planned behaviour attempts to explain factors which influence behaviour. One of these factors is intention. Positive or negative intentions are formed by a person's impression of the way other people would perceive similar behaviour (external forces). The authors of this study used the theory of planned behaviour to examine, compare and interpret the academic performance of students entering a university either via direct intake or via a bridging programme. This study focuses on the UniBridge programme offered by Universiti Brunei Darussalam (UBD), which is an intensive one-semester course that prepares students for undergraduate-level study. While direct-intake applicants pass minimum requirements for entry and are able to enrol directly into an undergraduate programme, applicants who do not meet these minimum requirements can join this bridging programme which is designed to be a "second-chance" entry option. Using a mixed-methods approach, the authors subjected student performance data of both direct-intake and bridge-programme undergraduates to statistical analyses, carried out interviews and then used the theoretical framework of planned behaviour to pinpoint individual attitudes and social pressures which form an intention to prepare for entry examinations. The results were mostly consistent and showed that the two groups were competitive in terms of undergraduate academic achievement, thus proving the second-chance programme to be effective in enabling students with poor A-Level results to experience academic confidence at university level. On the strength of these findings, the authors conclude their paper with recommendations for tertiary institutions to support lifelong learning initiatives through the use of multiple channels of entry.

Age of Entry to Kindergarten and Children’s Academic Achievement and Socioemotional Development

PubMed Central

2007-01-01

Research Findings Data on more than 900 children participating in the National Institute of Child Health and Human Development Study of Early Child Care were analyzed to examine the effect of age of entry to kindergarten on children’s functioning in early elementary school. Children’s academic achievement and socioemotional development were measured repeatedly from the age of 54 months through 3rd grade. With family background factors and experience in child care in the first 54 months of life controlled, hierarchical linear modeling (growth curve) analysis revealed that children who entered kindergarten at younger ages had higher (estimated) scores in kindergarten on the Woodcock-Johnson (W-J) Letter-Word Recognition subtest but received lower ratings from kindergarten teachers on Language and Literacy and Mathematical Thinking scales. Furthermore, children who entered kindergarten at older ages evinced greater increases over time on 4 W-J subtests (i.e., Letter-Word Recognition, Applied Problems, Memory for Sentences, Picture Vocabulary) and outperformed children who started kindergarten at younger ages on 2 W-J subtests in 3rd grade (i.e., Applied Problems, Picture Vocabulary). Age of entry proved unrelated to socioemotional functioning. Practice The fact that age-of-entry effects were small in magnitude and dwarfed by other aspects of children’s family and child care experiences suggests that age at starting school should not be regarded as a major determinant of children’s school achievement, but that it may merit consideration in context with other probably more important factors (e.g., child’s behavior and abilities). PMID:18084635

An explanation of the relationship between mass, metabolic rate and characteristic length for placental mammals

PubMed Central

2015-01-01

The Mass, Metabolism and Length Explanation (MMLE) was advanced in 1984 to explain the relationship between metabolic rate and body mass for birds and mammals. This paper reports on a modernized version of MMLE. MMLE deterministically computes the absolute value of Basal Metabolic Rate (BMR) and body mass for individual animals. MMLE is thus distinct from other examinations of these topics that use species-averaged data to estimate the parameters in a statistically best fit power law relationship such as BMR = a(bodymass)b. Beginning with the proposition that BMR is proportional to the number of mitochondria in an animal, two primary equations are derived that compute BMR and body mass as functions of an individual animal’s characteristic length and sturdiness factor. The characteristic length is a measureable skeletal length associated with an animal’s means of propulsion. The sturdiness factor expresses how sturdy or gracile an animal is. Eight other parameters occur in the equations that vary little among animals in the same phylogenetic group. The present paper modernizes MMLE by explicitly treating Froude and Strouhal dynamic similarity of mammals’ skeletal musculature, revising the treatment of BMR and using new data to estimate numerical values for the parameters that occur in the equations. A mass and length data set with 575 entries from the orders Rodentia, Chiroptera, Artiodactyla, Carnivora, Perissodactyla and Proboscidea is used. A BMR and mass data set with 436 entries from the orders Rodentia, Chiroptera, Artiodactyla and Carnivora is also used. With the estimated parameter values MMLE can calculate characteristic length and sturdiness factor values so that every BMR and mass datum from the BMR and mass data set can be computed exactly. Furthermore MMLE can calculate characteristic length and sturdiness factor values so that every body mass and length datum from the mass and length data set can be computed exactly. Whether or not MMLE can calculate a sturdiness factor value so that an individual animal’s BMR and body mass can be simultaneously computed given its characteristic length awaits analysis of a data set that simultaneously reports all three of these items for individual animals. However for many of the addressed MMLE homogeneous groups, MMLE can predict the exponent obtained by regression analysis of the BMR and mass data using the exponent obtained by regression analysis of the mass and length data. This argues that MMLE may be able to accurately simultaneously compute BMR and mass for an individual animal. PMID:26355655

Bypass Flow Resistance in Prismatic Gas-Cooled Nuclear Reactors

DOE PAGES

McEligot, Donald M.; Johnson, Richard W.

2016-12-20

Available computational fluid dynamics (CFD) predictions of pressure distributions in the vertical bypass flow between blocks in a prismatic gas-cooled reactor (GCR) have been analyzed to deduce apparent friction factors and loss coefficients for systems and network codes. We performed calculations for vertical gap spacings "s" of 2, 6 and 10 mm, horizontal gaps between the blocks of two mm and two flow rates, giving a range of gap Reynolds numbers Re Dh of about 40 to 5300. Laminar predictions of the fully-developed friction factor f fd were about three to ten per cent lower than the classical infinitely-wide channelmore » In the entry region, the local apparent friction factor was slightly higher than the classic idealized case but the hydraulic entry length L hy was approximately the same. The per cent reduction in flow resistance was greater than the per cent increase in flow area at the vertical corners of the blocks. The standard k-ϵ model was employed for flows expected to be turbulent. Its predictions of f fd and flow resistance were significantly higher than direct numerical simulations for the classic case; the value of L hy was about thirty gap spacings. Initial quantitative information for entry coefficients and loss coefficients for the expansion-contraction junctions between blocks is also presented. Our study demonstrates how CFD predictions can be employed to provide integral quantities needed in systems and network codes.« less

Bypass Flow Resistance in Prismatic Gas-Cooled Nuclear Reactors

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

McEligot, Donald M.; Johnson, Richard W.

Available computational fluid dynamics (CFD) predictions of pressure distributions in the vertical bypass flow between blocks in a prismatic gas-cooled reactor (GCR) have been analyzed to deduce apparent friction factors and loss coefficients for systems and network codes. We performed calculations for vertical gap spacings "s" of 2, 6 and 10 mm, horizontal gaps between the blocks of two mm and two flow rates, giving a range of gap Reynolds numbers Re Dh of about 40 to 5300. Laminar predictions of the fully-developed friction factor f fd were about three to ten per cent lower than the classical infinitely-wide channelmore » In the entry region, the local apparent friction factor was slightly higher than the classic idealized case but the hydraulic entry length L hy was approximately the same. The per cent reduction in flow resistance was greater than the per cent increase in flow area at the vertical corners of the blocks. The standard k-ϵ model was employed for flows expected to be turbulent. Its predictions of f fd and flow resistance were significantly higher than direct numerical simulations for the classic case; the value of L hy was about thirty gap spacings. Initial quantitative information for entry coefficients and loss coefficients for the expansion-contraction junctions between blocks is also presented. Our study demonstrates how CFD predictions can be employed to provide integral quantities needed in systems and network codes.« less

Contribution of manipulable and non-manipulable environmental factors to trapping efficiency of invasive sea lamprey

USGS Publications Warehouse

Dawson, Heather A.; Bravener, Gale; Beaulaurier, Joshua; Johnson, Nicholas S.; Twohey, Michael; McLaughlin, Robert L.; Brenden, Travis O.

2017-01-01

We identified aspects of the trapping process that afforded opportunities for improving trap efficiency of invasive sea lamprey (Petromyzon marinus) in a Great Lake's tributary. Capturing a sea lamprey requires it to encounter the trap, enter, and be retained until removed. Probabilities of these events depend on the interplay between sea lamprey behavior, environmental conditions, and trap design. We first tested how strongly seasonal patterns in daily trap catches (a measure of trapping success) were related to nightly rates of trap encounter, entry, and retention (outcomes of sea lamprey behavior). We then tested the degree to which variation in rates of trap encounter, entry, and retention were related to environmental features that control agents can manipulate (attractant pheromone addition, discharge) and features agents cannot manipulate (water temperature, season), but could be used as indicators for when to increase trapping effort. Daily trap catch was most strongly associated with rate of encounter. Relative and absolute measures of predictive strength for environmental factors that managers could potentially manipulate were low, suggesting that opportunities to improve trapping success by manipulating factors that affect rates of encounter, entry, and retention are limited. According to results at this trap, more sea lamprey would be captured by increasing trapping effort early in the season when sea lamprey encounter rates with traps are high. The approach used in this study could be applied to trapping of other invasive or valued species.

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.

Mars Sample Return Using Commercial Capabilities: Propulsive Entry, Descent, and Landing of a Capsule Form Vehicle

NASA Technical Reports Server (NTRS)

Gonzales, Andrew A.; Lemke, Lawrence G.; Huynh, Loc C.

2014-01-01

This paper describes a critical portion of the work that has been done at NASA, Ames Research Center regarding the use of the commercially developed Dragon capsule as a delivery vehicle for the elements of a high priority Mars Sample Return mission. The objective of the investigation was to determine entry and landed mass capabilities that cover anticipated mission conditions. The "Red Dragon", Mars configuration, uses supersonic retro-propulsion, with no required parachute system, to perform Entry, Descent, and Landing (EDL) maneuvers. The propulsive system proposed for use is the same system that will perform an abort, if necessary, for a human rated version of the Dragon capsule. Standard trajectory analysis tools are applied to publically available information about Dragon and other legacy capsule forms in order to perform the investigation. Trajectory simulation parameters include entry velocity, flight path angle, lift to drag Ratio (L/D), landing site elevation, atmosphere density, and total entry mass, in addition engineering assumptions for the performance of the propulsion system are stated. Mass estimates for major elements of the overall proposed architecture are coupled to this EDL analysis to close the overall architecture. Three synodic launch opportunities, beginning with the 2022 opportunity, define the arrival conditions. Results state the relations between the analysis parameters as well as sensitivities to those parameters. The EDL performance envelope includes landing altitudes between 0 and -4 km referenced to the Mars Orbiter Laser Altimeter datum as well as minimum and maximum atmosphere density. Total entry masses between 7 and 10 mt are considered with architecture closure occurring between 9.0 and 10 mt. Propellant mass fractions for each major phase of the EDL - Entry, Terminal Descent, and Hazard Avoidance - have been derived. An assessment of the effect of the entry conditions on the Thermal Protection System (TPS) currently in use for Dragon missions shows no significant stressors. A useful payload mass of 2.0 mt is provided and includes mass and grow allowance for a Mars Ascent Vehicle (MAV), Earth Return Vehicle (ERV), and mission unique equipment. The useful payload supports an architecture that receives a sample from another surface asset and sends it directly back to Earth for recovery in a high Earth orbit. The work shows that emerging commercial capabilities as well as previously studied EDL methodologies can be used to efficiently support an important planetary science objective. The work also has applications for human exploration missions that will also use propulsive EDL techniques

Advances in Procedural Techniques - Antegrade

PubMed Central

Wilson, William; Spratt, James C.

2014-01-01

There have been many technological advances in antegrade CTO PCI, but perhaps most importantly has been the evolution of the “hybrid’ approach where ideally there exists a seamless interplay of antegrade wiring, antegrade dissection re-entry and retrograde approaches as dictated by procedural factors. Antegrade wire escalation with intimal tracking remains the preferred initial strategy in short CTOs without proximal cap ambiguity. More complex CTOs, however, usually require either a retrograde or an antegrade dissection re-entry approach, or both. Antegrade dissection re-entry is well suited to long occlusions where there is a healthy distal vessel and limited “interventional” collaterals. Early use of a dissection re-entry strategy will increase success rates, reduce complications, and minimise radiation exposure, contrast use as well as procedural times. Antegrade dissection can be achieved with a knuckle wire technique or the CrossBoss catheter whilst re-entry will be achieved in the most reproducible and reliable fashion by the Stingray balloon/wire. It should be avoided where there is potential for loss of large side branches. It remains to be seen whether use of newer dissection re-entry strategies will be associated with lower restenosis rates compared with the more uncontrolled subintimal tracking strategies such as STAR and whether stent insertion in the subintimal space is associated with higher rates of late stent malapposition and stent thrombosis. It is to be hoped that the algorithms, which have been developed to guide CTO operators, allow for a better transfer of knowledge and skills to increase uptake and acceptance of CTO PCI as a whole. PMID:24694104

Cell cycle re-entry sensitizes podocytes to injury induced death.

PubMed

Hagen, Manuel; Pfister, Eva; Kosel, Andrea; Shankland, Stuart; Pippin, Jeffrey; Amann, Kerstin; Daniel, Christoph

2016-07-17

Podocytes are terminally differentiated renal cells, lacking the ability to regenerate by proliferation. However, during renal injury, podocytes re-enter into the cell cycle but fail to divide. Earlier studies suggested that re-entry into cell cycle results in loss of podocytes, but a direct evidence for this is lacking. Therefore, we established an in vitro model to test the consequences of re-entry into the cell cycle on podocyte survival. A mouse immortalized podocyte cell line was differentiated to non-permissive podocytes and stimulated with e.g. growth factors. Stimulated cells were analyzed for mRNA-expression or stained for cell cycle analysis using flow cytometry and immunocytofluorescence microscopy. After stimulation to re-entry into cell cycle, podocytes were stressed with puromycin aminonucleoside (PAN) and analyzed for survival. During permissive stage more than 40% of immortalized podocytes were in the S-phase. In contrast, S-phase in non-permissive differentiated podocytes was reduced to 5%. Treatment with b-FGF dose dependently induced re-entry into cell cycle increasing the number of podocytes in the S-phase to 10.7% at an optimal bFGF dosage of 10 ng/ml. Forty eight hours after stimulation with bFGF the number of bi-nucleated podocytes significantly increased. A secondary injury stimulus significantly reduced podocyte survival preferentially in bi-nucleated podocytes In conclusion, stimulation of podocytes using bFGF was able to induce re-entry of podocytes into the cell cycle and to sensitize the cells for cell death by secondary injuries. Therefore, this model is appropriate for testing new podocyte protective substances that can be used for therapy.

The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry.

PubMed

Gehring, Gerrit; Rohrmann, Katrin; Atenchong, Nkacheh; Mittler, Eva; Becker, Stephan; Dahlmann, Franziska; Pöhlmann, Stefan; Vondran, Florian W R; David, Sascha; Manns, Michael P; Ciesek, Sandra; von Hahn, Thomas

2014-08-01

Filoviruses such as Ebola virus and Marburg virus cause a severe haemorrhagic fever syndrome in humans for which there is no specific treatment. Since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties. We used authentic filoviruses and lentiviral particles pseudotyped with filoviral glycoproteins to identify and characterize such compounds. We discovered that amiodarone, a multi-ion channel inhibitor and adrenoceptor antagonist, is a potent inhibitor of filovirus cell entry at concentrations that are routinely reached in human serum during anti-arrhythmic therapy. A similar effect was observed with the amiodarone-related agent dronedarone and the L-type calcium channel blocker verapamil. Inhibition by amiodarone was concentration dependent and similarly affected pseudoviruses as well as authentic filoviruses. Inhibition of filovirus entry was observed with most but not all cell types tested and was accentuated by the pre-treatment of cells, indicating a host cell-directed mechanism of action. The New World arenavirus Guanarito was also inhibited by amiodarone while the Old World arenavirus Lassa and members of the Rhabdoviridae (vesicular stomatitis virus) and Bunyaviridae (Hantaan) families were largely resistant. The ion channel blockers amiodarone, dronedarone and verapamil inhibit filoviral cell entry. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Developing a primary dental care outreach (PDCO) course--part 2: perceptions of dental students.

PubMed

Maguire, A; Hind, V; Waterhouse, P J; Tabari, D; Steen, I N; Lloyd, J

2009-11-01

The perspective of participating students in a primary dental care outreach (PDCO) course, with regard to clinical and educational value, has informed course development and delivery. To evaluate students' perception of the PDCO experience including clinical experience gained, teaching and learning and the teaching environment. Likert Scale-based questionnaires were completed: (A) prior to the start of PDCO teaching, (B1) after one term, (B2) after one year and (C) for entry year 2001 students at completion. Additionally, a cohort of entry year 2000 students with no PDCO experience was surveyed at the end of their 4th year. Factor Analysis with Crohnbach's alpha was used to investigate perception of (i) confidence and skills in treating child patients, (ii) confidence and skills in treating adult patients; (iii) general clinical skills and experience; (iv) team working. Data from entry years 2000-2003 were analysed using ANOVA and independent sample t-tests. For entry years 2001 and 2002, perceived confidence and skills in treating child patients and general clinical experience increased, although for entry year 2002 students the levels of perceived general confidence and skills achieved after 1 year were similar to the entry year 2000 cohort who had received no PDCO teaching. There was consistently high satisfaction with teamworking. After 2 years in PDCO, 11 of the 13 overall satisfaction scores were over 70%. The majority of students perceive PCDO as a valuable component of professional training and development. Further evaluation, including analysis of value for money, would help to inform funding decisions and further curriculum development.

Distinct Patterns of IFITM-Mediated Restriction of Filoviruses, SARS Coronavirus, and Influenza A Virus

PubMed Central

Huang, I-Chueh; Bailey, Charles C.; Weyer, Jessica L.; Radoshitzky, Sheli R.; Becker, Michelle M.; Chiang, Jessica J.; Brass, Abraham L.; Ahmed, Asim A.; Chi, Xiaoli; Dong, Lian; Longobardi, Lindsay E.; Boltz, Dutch; Kuhn, Jens H.; Elledge, Stephen J.; Bavari, Sina; Denison, Mark R.; Choe, Hyeryun; Farzan, Michael

2011-01-01

Interferon-inducible transmembrane proteins 1, 2, and 3 (IFITM1, 2, and 3) are recently identified viral restriction factors that inhibit infection mediated by the influenza A virus (IAV) hemagglutinin (HA) protein. Here we show that IFITM proteins restricted infection mediated by the entry glycoproteins (GP1,2) of Marburg and Ebola filoviruses (MARV, EBOV). Consistent with these observations, interferon-β specifically restricted filovirus and IAV entry processes. IFITM proteins also inhibited replication of infectious MARV and EBOV. We observed distinct patterns of IFITM-mediated restriction: compared with IAV, the entry processes of MARV and EBOV were less restricted by IFITM3, but more restricted by IFITM1. Moreover, murine Ifitm5 and 6 did not restrict IAV, but efficiently inhibited filovirus entry. We further demonstrate that replication of infectious SARS coronavirus (SARS-CoV) and entry mediated by the SARS-CoV spike (S) protein are restricted by IFITM proteins. The profile of IFITM-mediated restriction of SARS-CoV was more similar to that of filoviruses than to IAV. Trypsin treatment of receptor-associated SARS-CoV pseudovirions, which bypasses their dependence on lysosomal cathepsin L, also bypassed IFITM-mediated restriction. However, IFITM proteins did not reduce cellular cathepsin activity or limit access of virions to acidic intracellular compartments. Our data indicate that IFITM-mediated restriction is localized to a late stage in the endocytic pathway. They further show that IFITM proteins differentially restrict the entry of a broad range of enveloped viruses, and modulate cellular tropism independently of viral receptor expression. PMID:21253575

Subintimal angioplasty with the aid of a re-entry device for TASC C and D lesions of the SFA.

PubMed

Setacci, C; Chisci, E; de Donato, G; Setacci, F; Iacoponi, F; Galzerano, G

2009-07-01

The aim of this prospective study was to assess the clinical effectiveness and related midterm patency of subintimal angioplasty (SAP) in patients suffering from critical limb ischaemia (CLI) in a single tertiary care university centre. The secondary aim was to evaluate the safety and clinical effectiveness of using a re-entry device when re-canalisation by SAP was unsuccessful. From January 2005 to December 2007, consecutive patients suffering from CLI (Rutherford clinical categories: 4-6) were treated with SAP. All patients included in the study had occluded SFA (TASC C and D) and underwent clinical and ultrasound follow-up examinations at day 30 and at 3, 6, 9 and 12 months, and then yearly. A re-entry device (Outback, Cordis Corporation, Miami Lakes, Florida, USA in all cases) was only used when re-canalisation by simple SAP was unsuccessful, and stenting was used when residual stenosis was >30% or there was a flow-limiting dissection. Factors that could modify the outcome were analysed. In this study, 145 patients were treated, with a technical success rate of 83.5% (121 of 145) for simple SAP. Stenting was performed in 43% (n=62) of successful SAP procedures. No death occurred in the perioperative period, while the 30-day mortality was 4.8% (7 of 145). The re-entry device (Outback) was used in 24 cases (16.5%). The technical success of the re-entry device was 79% (19 of 24), with a 90% success rate of stent placement at the site of re-entry. Complications occurred in 6.2% of all procedures (n=9) (three arterial perforations (2.1%), three distal embolisations (2.1%), two femoral artery pseudo-aneurysms (1.4%) and one arterio-venous fistula (0.7%)). Factors capable of independently affecting the patency were renal insufficiency (p=0.03), current smoking (p=0.01) and diabetes (p=0.04). The primary patency at 1 and 3 years was 70% and 34% and the secondary patency at 1 and 3 years was 77% and 43%, respectively. At the same time intervals, the limb-salvage rate was 88% and 49%. SAP with the aid of a re-entry device for TASC C and D lesions of the SFA seems to be safe and clinically effective in patients suffering from CLI, according to the experience at our centre. Further follow-up and more data are necessary to confirm these findings.

Thai Vocabulary. American Council of Learned Societies Program in Oriental Languages, Publications Series A - Texts - Number 2.

ERIC Educational Resources Information Center

Haas, Mary R.

This dictionary is intended to serve an interim need as a short dictionary of the Thai language. It contains vocabulary entries derived from the "Thai Reader" and a selection of words and examples from other sources, including (1) the words and expressions found in "Spoken Thai" (Haas and Subhanka, Henry Holt and Co.) and (2) McFarland's list of…

A new entry to azomethine ylides from allylic amines and glyoxals: shifting the reliance on amino ester precursors.

PubMed

Machamer, Natalie K; Liu, Xiaoxi; Waters, Stephen P

2014-10-03

The first examples of azomethine ylides derived from allylic amine and glyoxal precursors are reported. The condensation of primary allylic and α-aryl amines with glyoxylates or α-aryl glyoxals affords conjugated azomethine ylides that undergo facile [3 + 2] cycloaddition, providing 5-alkenyl pyrrolidine cycloadducts that cannot be accessed through the classical use of amino esters as ylide precursors.

Drug Abuse in the Military Impacts National Security.

DTIC Science & Technology

1988-03-30

types of drugs - cannabis , hallucinogens, opiates, stimulants, hypnotics, and cocaine. Subscores were derived for each drug, based upon the product of a...he was interviewed by medical personnel. The soldiers who were Judged to be not drug dependent continued their military service. Soldiers who were...separated as "not meeting the medical 8 fitness standards at time of entry. These separated soldiers along with all others with medical and non

Documentation of computer program VS2D to solve the equations of fluid flow in variably saturated porous media

USGS Publications Warehouse

Lappala, E.G.; Healy, R.W.; Weeks, E.P.

1987-01-01

This report documents FORTRAN computer code for solving problems involving variably saturated single-phase flow in porous media. The flow equation is written with total hydraulic potential as the dependent variable, which allows straightforward treatment of both saturated and unsaturated conditions. The spatial derivatives in the flow equation are approximated by central differences, and time derivatives are approximated either by a fully implicit backward or by a centered-difference scheme. Nonlinear conductance and storage terms may be linearized using either an explicit method or an implicit Newton-Raphson method. Relative hydraulic conductivity is evaluated at cell boundaries by using either full upstream weighting, the arithmetic mean, or the geometric mean of values from adjacent cells. Nonlinear boundary conditions treated by the code include infiltration, evaporation, and seepage faces. Extraction by plant roots that is caused by atmospheric demand is included as a nonlinear sink term. These nonlinear boundary and sink terms are linearized implicitly. The code has been verified for several one-dimensional linear problems for which analytical solutions exist and against two nonlinear problems that have been simulated with other numerical models. A complete listing of data-entry requirements and data entry and results for three example problems are provided. (USGS)

Inhibition of Nipah virus infection in vivo: targeting an early stage of paramyxovirus fusion activation during viral entry.

PubMed

Porotto, Matteo; Rockx, Barry; Yokoyama, Christine C; Talekar, Aparna; Devito, Ilaria; Palermo, Laura M; Liu, Jie; Cortese, Riccardo; Lu, Min; Feldmann, Heinz; Pessi, Antonello; Moscona, Anne

2010-10-28

In the paramyxovirus cell entry process, receptor binding triggers conformational changes in the fusion protein (F) leading to viral and cellular membrane fusion. Peptides derived from C-terminal heptad repeat (HRC) regions in F have been shown to inhibit fusion by preventing formation of the fusogenic six-helix bundle. We recently showed that the addition of a cholesterol group to HRC peptides active against Nipah virus targets these peptides to the membrane where fusion occurs, dramatically increasing their antiviral effect. In this work, we report that unlike the untagged HRC peptides, which bind to the postulated extended intermediate state bridging the viral and cell membranes, the cholesterol tagged HRC-derived peptides interact with F before the fusion peptide inserts into the target cell membrane, thus capturing an earlier stage in the F-activation process. Furthermore, we show that cholesterol tagging renders these peptides active in vivo: the cholesterol-tagged peptides cross the blood brain barrier, and effectively prevent and treat in an established animal model what would otherwise be fatal Nipah virus encephalitis. The in vivo efficacy of cholesterol-tagged peptides, and in particular their ability to penetrate the CNS, suggests that they are promising candidates for the prevention or therapy of infection by Nipah and other lethal paramyxoviruses.

Measuring performance in off-patent drug markets: a methodological framework and empirical evidence from twelve EU Member States.

PubMed

Kanavos, Panos

2014-11-01

This paper develops a methodological framework to help evaluate the performance of generic pharmaceutical policies post-patent expiry or after loss of exclusivity in non-tendering settings, comprising five indicators (generic availability, time delay to and speed of generic entry, number of generic competitors, price developments, and generic volume share evolution) and proposes a series of metrics to evaluate performance. The paper subsequently tests this framework across twelve EU Member States (MS) by using IMS data on 101 patent expired molecules over the 1998-2010 period. Results indicate that significant variation exists in generic market entry, price competition and generic penetration across the study countries. Size of a geographical market is not a predictor of generic market entry intensity or price decline. Regardless of geographic or product market size, many off patent molecules lack generic competitors two years after loss of exclusivity. The ranges in each of the five proposed indicators suggest, first, that there are numerous factors--including institutional ones--contributing to the success of generic entry, price decline and market penetration and, second, MS should seek a combination of supply and demand-side policies in order to maximise cost-savings from generics. Overall, there seems to be considerable potential for faster generic entry, uptake and greater generic competition, particularly for molecules at the lower end of the market. Copyright © 2014. Published by Elsevier Ireland Ltd.

Re-refinement from deposited X-ray data can deliver improved models for most PDB entries

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

Joosten, Robbie P.; Womack, Thomas; Vriend, Gert, E-mail: vriend@cmbi.ru.nl

2009-02-01

An evaluation of validation and real-space intervention possibilities for improving existing automated (re-)refinement methods. The deposition of X-ray data along with the customary structural models defining PDB entries makes it possible to apply large-scale re-refinement protocols to these entries, thus giving users the benefit of improvements in X-ray methods that have occurred since the structure was deposited. Automated gradient refinement is an effective method to achieve this goal, but real-space intervention is most often required in order to adequately address problems detected by structure-validation software. In order to improve the existing protocol, automated re-refinement was combined with structure validation andmore » difference-density peak analysis to produce a catalogue of problems in PDB entries that are amenable to automatic correction. It is shown that re-refinement can be effective in producing improvements, which are often associated with the systematic use of the TLS parameterization of B factors, even for relatively new and high-resolution PDB entries, while the accompanying manual or semi-manual map analysis and fitting steps show good prospects for eventual automation. It is proposed that the potential for simultaneous improvements in methods and in re-refinement results be further encouraged by broadening the scope of depositions to include refinement metadata and ultimately primary rather than reduced X-ray data.« less

Impaired Calcium Entry into Cells Is Associated with Pathological Signs of Zinc Deficiency12

PubMed Central

O’Dell, Boyd L.; Browning, Jimmy D.

2013-01-01

Zinc is an essential trace element whose deficiency gives rise to specific pathological signs. These signs occur because an essential metabolic function is impaired as the result of failure to form or maintain a specific metal-ion protein complex. Although zinc is a component of many essential metalloenzymes and transcription factors, few of these have been identified with a specific sign of incipient zinc deficiency. Zinc also functions as a structural component of other essential proteins. Recent research with Swiss murine fibroblasts, 3T3 cells, has shown that zinc deficiency impairs calcium entry into cells, a process essential for many cell functions, including proliferation, maturation, contraction, and immunity. Impairment of calcium entry and the subsequent failure of cell proliferation could explain the growth failure associated with zinc deficiency. Defective calcium uptake is associated with impaired nerve transmission and pathology of the peripheral nervous system, as well as the failure of platelet aggregation and the bleeding tendency of zinc deficiency. There is a strong analogy between the pathology of genetic diseases that result in impaired calcium entry and other signs of zinc deficiency, such as decreased and cyclic food intake, taste abnormalities, abnormal water balance, skin lesions, impaired reproduction, depressed immunity, and teratogenesis. This analogy suggests that failure of calcium entry is involved in these signs of zinc deficiency as well. PMID:23674794

Paths, Patterns and Factors That Influence the Entry of University Graduates into the Labour Market

ERIC Educational Resources Information Center

Jimenez Vivas, Amparo; Menendez Alvarez-Hevia, David

2017-01-01

This article provides an overview of the literature that contributes to the study of the key factors that explain the process by which university graduates enter the labour market. It is approached from the standpoint of the Spanish experience but also discussesother European initiatives. Understanding this process is paramount for the…

7 CFR 51.628 - Tolerances.

Code of Federal Regulations, 2011 CFR

2011-01-01

...—Shipping Point 1 (A) For 1 through 20 Samples Factor Grades AL 2 Number of 33-count samples 3 1 2 3 4 5 6 7.... 2 Russet. Table I—Shipping Point 1 (Continued) (B) For 21 through 40 Samples Factor Grades AL 2... outside the continental United States, the port of entry into the United States. 2 AL—Absolute limit...

7 CFR 51.628 - Tolerances.

Code of Federal Regulations, 2012 CFR

2012-01-01

...—Shipping Point 1 (A) For 1 through 20 Samples Factor Grades AL 2 Number of 33-count samples 3 1 2 3 4 5 6 7.... 2 Russet. Table I—Shipping Point 1 (Continued) (B) For 21 through 40 Samples Factor Grades AL 2... outside the continental United States, the port of entry into the United States. 2 AL—Absolute limit...

7 CFR 51.628 - Tolerances.

Code of Federal Regulations, 2010 CFR

2010-01-01

...—Shipping Point 1 (A) For 1 through 20 Samples Factor Grades AL 2 Number of 33-count samples 3 1 2 3 4 5 6 7.... 2 Russet. Table I—Shipping Point 1 (Continued) (B) For 21 through 40 Samples Factor Grades AL 2... outside the continental United States, the port of entry into the United States. 2 AL—Absolute limit...

Developmental dyslexia: predicting individual risk

PubMed Central

Thompson, Paul A; Hulme, Charles; Nash, Hannah M; Gooch, Debbie; Hayiou-Thomas, Emma; Snowling, Margaret J

2015-01-01

Background Causal theories of dyslexia suggest that it is a heritable disorder, which is the outcome of multiple risk factors. However, whether early screening for dyslexia is viable is not yet known. Methods The study followed children at high risk of dyslexia from preschool through the early primary years assessing them from age 3 years and 6 months (T1) at approximately annual intervals on tasks tapping cognitive, language, and executive-motor skills. The children were recruited to three groups: children at family risk of dyslexia, children with concerns regarding speech, and language development at 3;06 years and controls considered to be typically developing. At 8 years, children were classified as ‘dyslexic’ or not. Logistic regression models were used to predict the individual risk of dyslexia and to investigate how risk factors accumulate to predict poor literacy outcomes. Results Family-risk status was a stronger predictor of dyslexia at 8 years than low language in preschool. Additional predictors in the preschool years include letter knowledge, phonological awareness, rapid automatized naming, and executive skills. At the time of school entry, language skills become significant predictors, and motor skills add a small but significant increase to the prediction probability. We present classification accuracy using different probability cutoffs for logistic regression models and ROC curves to highlight the accumulation of risk factors at the individual level. Conclusions Dyslexia is the outcome of multiple risk factors and children with language difficulties at school entry are at high risk. Family history of dyslexia is a predictor of literacy outcome from the preschool years. However, screening does not reach an acceptable clinical level until close to school entry when letter knowledge, phonological awareness, and RAN, rather than family risk, together provide good sensitivity and specificity as a screening battery. PMID:25832320

Oocyte Activation and Fertilisation: Crucial Contributors from the Sperm and Oocyte.

PubMed

Yeste, Marc; Jones, Celine; Amdani, Siti Nornadhirah; Coward, Kevin

2017-01-01

This chapter intends to summarise the importance of sperm- and oocyte-derived factors in the processes of sperm-oocyte binding and oocyte activation. First, we describe the initial interaction between sperm and the zona pellucida, with particular regard to acrosome exocytosis. We then describe how sperm and oocyte membranes fuse, with special reference to the discovery of the sperm protein IZUMO1 and its interaction with the oocyte membrane receptor JUNO. We then focus specifically upon oocyte activation, the fundamental process by which the oocyte is alleviated from metaphase II arrest by a sperm-soluble factor. The identity of this sperm factor has been the source of much debate recently, although mounting evidence, from several different laboratories, provides strong support for phospholipase C ζ (PLCζ), a sperm-specific phospholipase. Herein, we discuss the evidence in support of PLCζ and evaluate the potential role of other candidate proteins, such as post-acrosomal WW-binding domain protein (PAWP/WBP2NL). Since the cascade of downstream events triggered by the sperm-borne oocyte activation factor heavily relies upon specialised cellular machinery within the oocyte, we also discuss the critical role of oocyte-borne factors, such as the inositol trisphosphate receptor (IP 3 R), protein kinase C (PKC), store-operated calcium entry (SOCE) and calcium/calmodulin-dependent protein kinase II (CaMKII), during the process of oocyte activation. In order to place the implications of these various factors and processes into a clinical context, we proceed to describe their potential association with oocyte activation failure and discuss how clinical techniques such as the in vitro maturation of oocytes may affect oocyte activation ability. Finally, we contemplate the role of artificial oocyte activating agents in the clinical rescue of oocyte activation deficiency and discuss options for more endogenous alternatives.

A Systematic Review of the Epidemiology of Echinococcosis in Domestic and Wild Animals

PubMed Central

Otero-Abad, Belen; Torgerson, Paul R.

2013-01-01

Background Human echinococcosis is a neglected zoonosis caused by parasites of the genus Echinococcus. The most frequent clinical forms of echinococcosis, cystic echinococcosis (CE) and alveolar echinococcosis (AE), are responsible for a substantial health and economic burden, particularly to low-income societies. Quantitative epidemiology can provide important information to improve the understanding of parasite transmission and hence is an important part of efforts to control this disease. The purpose of this review is to give an insight on factors associated with echinococcosis in animal hosts by summarising significant results reported from epidemiological studies identified through a systematic search. Methodology and Principal Findings The systematic search was conducted mainly in electronic databases but a few additional records were obtained from other sources. Retrieved entries were examined in order to identify available peer-reviewed epidemiological studies that found significant risk factors for infection using associative statistical methods. One hundred studies met the eligibility criteria and were suitable for data extraction. Epidemiological factors associated with increased risk of E. granulosus infection in dogs included feeding with raw viscera, possibility of scavenging dead animals, lack of anthelmintic treatment and owners' poor health education and indicators of poverty. Key factors associated with E. granulosus infection in intermediate hosts were related to the hosts' age and the intensity of environmental contamination with parasite eggs. E. multilocularis transmission dynamics in animal hosts depended on the interaction of several ecological factors, such as hosts' population densities, host-prey interactions, landscape characteristics, climate conditions and human-related activities. Conclusions/Significance Results derived from epidemiological studies provide a better understanding of the behavioural, biological and ecological factors involved in the transmission of this parasite and hence can aid in the design of more effective control strategies. PMID:23755310

STS-114: Discovery Post Landing Press Briefing from JSC

NASA Technical Reports Server (NTRS)

2005-01-01

LeRoy Cain, STS-114 Ascent/Entry Flight Director, takes a solo stand with the Press in this briefing. He noted that the successful flight and return of Discovery is another important milestone, a fresh start, and a new beginning as part of NASA's commitment to the President's vision of man's return to the Moon, Mars and beyond. From this successful test flight, NASA will have a lot of learning and hard work to do in preparation for the next flight. Weather factors, safe landing, touch down, communications, re-entry, the Columbia, were some topics covered with the News media.

HBV life cycle is restricted in mouse hepatocytes expressing human NTCP.

PubMed

Li, Hanjie; Zhuang, Qiuyu; Wang, Yuze; Zhang, Tianying; Zhao, Jinghua; Zhang, Yali; Zhang, Junfang; Lin, Yi; Yuan, Quan; Xia, Ningshao; Han, Jiahuai

2014-03-01

Recent studies have revealed that human sodium taurocholate cotransporting polypeptide (SLC10A1 or NTCP) is a functional cellular receptor for hepatitis B virus (HBV). However, whether human NTCP can support HBV infection in mouse hepatocyte cell lines has not been clarified. Because an HBV-permissible mouse model would be helpful for the study of HBV pathogenesis, it is necessary to investigate whether human NTCP supports the susceptibility of mouse hepatocyte cell lines to HBV. The results show that exogenous human NTCP expression can render non-susceptible HepG2 (human), Huh7 (human), Hepa1-6 (mouse), AML-12 (mouse) cell lines and primary mouse hepatocyte (PMH) cells susceptible to hepatitis D virus (HDV) which employs HBV envelope proteins. However, human NTCP could only introduce HBV susceptibility in human-derived HepG2 and Huh7 cells, but not in mouse-derived Hepa1-6, AML-12 or PMH cells. These data suggest that although human NTCP is a functional receptor that mediates HBV infection in human cells, it cannot support HBV infection in mouse hepatocytes. Our study indicated that the restriction of HBV in mouse hepatocytes likely occurs after viral entry but prior to viral transcription. We have excluded the role of mouse hepatocyte nuclear factors in the restriction of the HBV life cycle and showed that knockdown or inhibition of Sting, TBK1, IRF3 or IRF7, the components of the anti-viral signaling pathways, had no effect on HBV infection in mouse hepatocytes. Therefore, murine restriction factors that limit HBV infection need to be identified before a HBV-permissible mouse line can be created.

Longitudinal assessment of brain-derived neurotrophic factor in Sardinian psychotic patients (LABSP): a protocol for a prospective observational study

PubMed Central

Primavera, Diego; Deriu, Luca; Collu, Roberto; Scherma, Maria; Fadda, Paola; Fratta, Walter; Carpiniello, Bernardo

2017-01-01

Introduction Brain-derived neurotrophic factor (BDNF) plays a crucial role in neurodevelopment, synaptic plasticity and neuronal function and survival. Serum and plasma BDNF levels are moderately, but consistently, decreased in patients with schizophrenia (SCZ) compared with healthy controls. There is a lack of knowledge, however, on the temporal manifestation of this decline. Clinical, illness course and treatment factors might influence the variation of BDNF serum levels in patients with psychosis. In this context, we propose a longitudinal study of a cohort of SCZ and schizophrenic and schizoaffective disorder (SAD) Sardinian patients with the aim of disentangling the relationship between peripheral BDNF serum levels and changes of psychopathology, cognition and drug treatments. Methods and analysis Longitudinal assessment of BDNF in Sardinian psychotic patients (LABSP) is a 24-month observational prospective cohort study. Patients with SAD will be recruited at the Psychiatry Research Unit of the Department of Medical Science and Public Health, University of Cagliari and University of Cagliari Health Agency, Cagliari, Italy. We will collect BDNF serum levels as well as sociodemographic, psychopathological and neurocognitive measures. Structured, semistructured and self-rating assessment tools, such as the Positive and Negative Syndrome Scale for psychopathological measures and the Brief Assessment of Cognition in Schizophrenia for cognitive function, will be used. Ethics and dissemination This study protocol was approved by the University of Cagliari Health Agency Ethics Committee (NP2016/5491). The study will be conducted in accordance with the principles of good clinical practice, in the Declaration of Helsinki in compliance with the regulations. Participation will be voluntary and written informed consent will be obtained for each participant upon entry into the study. We plan to disseminate the results of our study through conference presentations and publication in international peer-reviewed journals. Access to raw data will be available in anonymised form upon request to the corresponding author. PMID:28550022

Treatment concept of chronic subdural haematoma according to an algorithm using evidence-based medicine-derived key factors: A prospective controlled study.

PubMed

Weigel, Ralf; Schlickum, Linda; Weisser, Gerald; Krauss, Joachim K

2015-01-01

Surgical treatment for chronic subdural haematoma (CSH) has been analysed by applying evidence-based medicine (EBM) criteria earlier. Whether implementation of EBM-derived key factors into an optimised treatment algorithm would improve outcome, however, needs to be clarified. Symptomatic patients with CSH who fulfilled the inclusion criteria were either assigned to an optimised treatment algorithm (OA-EBM group) or to a control group treated by the standard departmental surgical technique (SDST group) in a prospective design. For the OA-EBM algorithm only one burr hole, extensive intraoperative irrigation and a closed system drainage with meticulous avoidance of entry of air was mandatory. A two-catheter technique was used to reduce intracavital air. Final endpoints were neurological outcome (Markwalder Score), recurrence and the amount of intracranial air. A total of 93 out of 117 patients were evaluated accounting for 113 cases because 20 patients had bilateral haematomas. Demographic data of 68 cases in the SDST group did not differ from 45 cases in the OA-EBM group. The Markwalder Score showed greater improvement in the OA-EBM group (0.5 ± 0.6 vs. 1.0 ± 1.0, p = 0.003). The recurrence rate was 18% (12 patients) in the SDST group versus 2% (1 patient) in the OA-EBM group (p < 0.05). The amount of intracranial air was significantly lower in the OA-EBM group (3.3 ± 5.0 cm(3) vs. 5.2 ± 7.7 cm(3)) with p = 0.04. In the standard group computerised tomography scanning was performed slightly earlier (3 ± 1.7 days vs. 3.6 ± 1.4 days). When comparing only non-recurrent cases in both groups no significant difference was apparent. Implementation of EBM key factors into a treatment algorithm for CSH can improve neurological outcome in a typical neurosurgical department, reduce recurrence and minimise the amount of postoperative air within the haematoma cavity.

Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration.

PubMed

Kempuraj, Duraisamy; Thangavel, Ramasamy; Selvakumar, Govindhasamy P; Zaheer, Smita; Ahmed, Mohammad E; Raikwar, Sudhanshu P; Zahoor, Haris; Saeed, Daniyal; Natteru, Prashant A; Iyer, Shankar; Zaheer, Asgar

2017-01-01

Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions. In addition, inflammatory mediators released from activated glial cells induce neurodegeneration in the brain. Systemic inflammation-derived proinflammatory cytokines/chemokines and other factors cause a breach in the blood brain-barrier (BBB) thereby allowing for the entry of immune/inflammatory cells including mast cell progenitors, mast cells and proinflammatory cytokines and chemokines into the brain. These peripheral-derived factors and intrinsically generated cytokines/chemokines, α-synuclein, corticotropin-releasing hormone (CRH), substance P (SP), beta amyloid 1-42 (Aβ1-42) peptide and amyloid precursor proteins can activate glial cells, T-cells and mast cells in the brain can induce additional release of inflammatory and neurotoxic molecules contributing to chronic neuroinflammation and neuronal death. The glia maturation factor (GMF), a proinflammatory protein discovered in our laboratory released from glia, activates mast cells to release inflammatory cytokines and chemokines. Chronic increase in the proinflammatory mediators induces neurotoxic Aβ and plaque formation in AD brains and neurodegeneration in PD brains. Glial cells, mast cells and T-cells can reactivate each other in neuroinflammatory conditions in the brain and augment neuroinflammation. Further, inflammatory mediators from the brain can also enter into the peripheral system through defective BBB, recruit immune cells into the brain, and exacerbate neuroinflammation. We suggest that mast cell-associated inflammatory mediators from systemic inflammation and brain could augment neuroinflammation and neurodegeneration in the brain. This review article addresses the role of some atypical inflammatory mediators that are associated with mast cell inflammation and their activation of glial cells to induce neurodegeneration.

Desiccant Cooling Poised for Entry into Mainstream Markets

Science.gov Websites

annual sales if costs can be lowered to competitive levels. Near-term markets include hospitals, nursing , which measures wheel performance factors with high accuracy in accordance with American Society for

Methodology Development for the Reconstruction of the ESA Huygens Probe Entry and Descent Trajectory

NASA Astrophysics Data System (ADS)

Kazeminejad, B.

2005-01-01

The European Space Agency's (ESA) Huygens probe performed a successful entry and descent into Titan's atmosphere on January 14, 2005, and landed safely on the satellite's surface. A methodology was developed, implemented, and tested to reconstruct the Huygens probe trajectory from its various science and engineering measurements, which were performed during the probe's entry and descent to the surface of Titan, Saturn's largest moon. The probe trajectory reconstruction is an essential effort that has to be done as early as possible in the post-flight data analysis phase as it guarantees a correct and consistent interpretation of all the experiment data and furthermore provides a reference set of data for "ground-truthing" orbiter remote sensing measurements. The entry trajectory is reconstructed from the measured probe aerodynamic drag force, which also provides a means to derive the upper atmospheric properties like density, pressure, and temperature. The descent phase reconstruction is based upon a combination of various atmospheric measurements such as pressure, temperature, composition, speed of sound, and wind speed. A significant amount of effort was spent to outline and implement a least-squares trajectory estimation algorithm that provides a means to match the entry and descent trajectory portions in case of discontinuity. An extensive test campaign of the algorithm is presented which used the Huygens Synthetic Dataset (HSDS) developed by the Huygens Project Scientist Team at ESA/ESTEC as a test bed. This dataset comprises the simulated sensor output (and the corresponding measurement noise and uncertainty) of all the relevant probe instruments. The test campaign clearly showed that the proposed methodology is capable of utilizing all the relevant probe data, and will provide the best estimate of the probe trajectory once real instrument measurements from the actual probe mission are available. As a further test case using actual flight data the NASA Mars Pathfinder entry and descent trajectory and the space craft attitude was reconstructed from the 3-axis accelerometer measurements which are archived on the Planetary Data System. The results are consistent with previously published reconstruction efforts.

The design and realisation of the IXV Mission Analysis and Flight Mechanics

NASA Astrophysics Data System (ADS)

Haya-Ramos, Rodrigo; Blanco, Gonzalo; Pontijas, Irene; Bonetti, Davide; Freixa, Jordi; Parigini, Cristina; Bassano, Edmondo; Carducci, Riccardo; Sudars, Martins; Denaro, Angelo; Angelini, Roberto; Mancuso, Salvatore

2016-07-01

The Intermediate eXperimental Vehicle (IXV) is a suborbital re-entry demonstrator successfully launched in February 2015 focusing on the in-flight demonstration of a lifting body system with active aerodynamic control surfaces. This paper presents an overview of the Mission Analysis and Flight Mechanics of the IXV vehicle, which comprises computation of the End-to-End (launch to splashdown) design trajectories, characterisation of the Entry Corridor, assessment of the Mission Performances through Monte Carlo campaigns, contribution to the aerodynamic database, analysis of the Visibility and link budget from Ground Stations and GPS, support to safety analyses (off nominal footprints), specification of the Centre of Gravity box, selection of the Angle of Attack trim line to be flown and characterisation of the Flying Qualities performances. An initial analysis and comparison with the raw flight data obtained during the flight will be discussed and first lessons learned derived.

Aerodynamic Analysis of Tektites and Their Parent Bodies

NASA Technical Reports Server (NTRS)

Adams, E. W.; Huffaker, R. M.

1962-01-01

Experiment and analysis indicate that the button-type australites were derived from glassy spheres which entered or re-entered the atmosphere as cold solid bodies; in case of average-size specimens, the entry direction was nearly horizontal and the entry speed between 6.5 and 11.2 km/sec. Terrestrial origin of such spheres is impossible because of extremely high deceleration rates at low altitudes. The limited extension of the strewn fields rules out extraterrestrial origin of clusters of such spheres because of stability considerations for clusters in space. However, tektites may have been released as liquid droplets from glassy parent bodies ablating in the atmosphere of the earth. The australites then have skipped together with the parent body in order to re-enter as cold spheres. Terrestrial origin of a parent body would require an extremely violent natural event. Ablation analysis shows that fusion of opaque siliceous stone into glass by aerodynamic heating is impossible.

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

Deng,Y.; Liu, J.; Zheng, Q.

Entry of SARS coronavirus into its target cell requires large-scale structural transitions in the viral spike (S) glycoprotein in order to induce fusion of the virus and cell membranes. Here we describe the identification and crystal structures of four distinct a-helical domains derived from the highly conserved heptad-repeat (HR) regions of the S2 fusion subunit. The four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-helix bundle that is likely the final fusogenic form of the protein. When considered together, the structural and thermodynamic features of the four domains suggest amore » possible mechanism whereby the HR regions, initially sequestered in the native S glycoprotein spike, are released and refold sequentially to promote membrane fusion. Our results provide a structural framework for understanding the control of membrane fusion and should guide efforts to intervene in the SARS coronavirus entry process.« less

Autonomous atmospheric entry on mars: Performance improvement using a novel adaptive control algorithm

NASA Astrophysics Data System (ADS)

Ulrich, Steve; de Lafontaine, Jean

2007-12-01

Upcoming landing missions to Mars will require on-board guidance and control systems in order to meet the scientific requirement of landing safely within hundreds of meters to the target of interest. More specifically, in the longitudinal plane, the first objective of the entry guidance and control system is to bring the vehicle to its specified velocity at the specified altitude (as required for safe parachute deployment), while the second objective is to reach the target position in the longitudinal plane. This paper proposes an improvement to the robustness of the constant flight path angle guidance law for achieving the first objective. The improvement consists of combining this guidance law with a novel adaptive control scheme, derived from the so-called Simple Adaptive Control (SAC) technique. Monte-Carlo simulation results are shown to demonstrate the accuracy and the robustness of the proposed guidance and adaptive control system.

US photovoltaic patents: 1991--1993

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

Pohle, L

1995-03-01

This document contains US patents on terrestrial photovoltaic (PV) power applications, including systems, components, and materials as well as manufacturing and support functions. The patent entries in this document were issued from 1991 to 1993. The entries were located by searching USPA, the database of the US Patent Office. The final search retrieved all patents under the class ``Batteries, Thermoelectric and Photoelectric`` and the subclasses ``Photoelectric,`` ``Testing,`` and ``Applications.`` The search also located patents that contained the words ``photovoltaic(s)`` or ``solar cell(s)`` and their derivatives. After the initial list was compiled, most of the patents on the following subjects weremore » excluded: space photovoltaic technology, use of the photovoltaic effect for detectors, and subjects only peripherally concerned with photovoltaic. Some patents on these three subjects were included when ft appeared that those inventions might be of use in terrestrial PV power technologies.« less

Space shuttle entry and landing navigation analysis

NASA Technical Reports Server (NTRS)

Jones, H. L.; Crawford, B. S.

1974-01-01

A navigation system for the entry phase of a Space Shuttle mission which is an aided-inertial system which uses a Kalman filter to mix IMU data with data derived from external navigation aids is evaluated. A drag pseudo-measurement used during radio blackout is treated as an additional external aid. A comprehensive truth model with 101 states is formulated and used to generate detailed error budgets at several significant time points -- end-of-blackout, start of final approach, over runway threshold, and touchdown. Sensitivity curves illustrating the effect of variations in the size of individual error sources on navigation accuracy are presented. The sensitivity of the navigation system performance to filter modifications is analyzed. The projected overall performance is shown in the form of time histories of position and velocity error components. The detailed results are summarized and interpreted, and suggestions are made concerning possible software improvements.

Role of magnolol in the proliferation of vascular smooth muscle cells.

PubMed

Wu, L; Zou, H; Xia, W; Dong, Q; Wang, L

2015-05-01

Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of vascular remodeling. Recently, magnolol has been reported to have a potential role in regulating tumor necrosis factor α-induced proliferation of VSMCs. However, the role of magnolol in platelet-derived growth factor (PDGF)-induced proliferation of VSMCs remains unknown. Our purpose was to elucidate the effect of magnolol on the proliferation of VSMCs induced by PDGF-BB and to investigate the underlying molecular mechanisms. Our data demonstrated that magnolol inhibited rat VSMC proliferation and DNA synthesis stimulated by 20 ng/ml PDGF-BB without causing cell cytotoxicity. Flow cytometric analysis showed that magnolol inhibited S-phase entry of VSMCs. We also demonstrated that magnolol caused this effect by inhibiting the mRNA and protein expression of cyclin D1, cyclin E, and cyclin-dependent kinases 2 and 4 in PDGF-BB-stimulated VSMCs. Further analysis showed that the inhibitory effect of magnolol on the proliferation of VSMCs was associated with the inhibition of the PDGF-BB-stimulated production of intracellular reactive oxygen species (ROS) and Ras, MEK, and ERK1/2 activation. These results demonstrate that magnolol can block the proliferation of VSMCs through inhibition of intracellular ROS production and Ras-MEK-ERK1/2 pathways. Magnolol, therefore, has a potential application in preventing atherosclerosis and restenosis.

High-resolution crystal structure of copper amine oxidase from Arthrobacter globiformis: assignment of bound diatomic molecules as O2.

PubMed

Murakawa, Takeshi; Hayashi, Hideyuki; Sunami, Tomoko; Kurihara, Kazuo; Tamada, Taro; Kuroki, Ryota; Suzuki, Mamoru; Tanizawa, Katsuyuki; Okajima, Toshihide

2013-12-01

The crystal structure of a copper amine oxidase from Arthrobacter globiformis was determined at 1.08 Å resolution with the use of low-molecular-weight polyethylene glycol (LMW PEG; average molecular weight ∼200) as a cryoprotectant. The final crystallographic R factor and Rfree were 13.0 and 15.0%, respectively. Several molecules of LMW PEG were found to occupy cavities in the protein interior, including the active site, which resulted in a marked reduction in the overall B factor and consequently led to a subatomic resolution structure for a relatively large protein with a monomer molecular weight of ∼70,000. About 40% of the presumed H atoms were observed as clear electron densities in the Fo - Fc difference map. Multiple minor conformers were also identified for many residues. Anisotropic displacement fluctuations were evaluated in the active site, which contains a post-translationally derived quinone cofactor and a Cu atom. Furthermore, diatomic molecules, most likely to be molecular oxygen, are bound to the protein, one of which is located in a region that had previously been proposed as an entry route for the dioxygen substrate from the central cavity of the dimer interface to the active site.

JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles

PubMed Central

Portales-Casamar, Elodie; Thongjuea, Supat; Kwon, Andrew T.; Arenillas, David; Zhao, Xiaobei; Valen, Eivind; Yusuf, Dimas; Lenhard, Boris; Wasserman, Wyeth W.; Sandelin, Albin

2010-01-01

JASPAR (http://jaspar.genereg.net) is the leading open-access database of matrix profiles describing the DNA-binding patterns of transcription factors (TFs) and other proteins interacting with DNA in a sequence-specific manner. Its fourth major release is the largest expansion of the core database to date: the database now holds 457 non-redundant, curated profiles. The new entries include the first batch of profiles derived from ChIP-seq and ChIP-chip whole-genome binding experiments, and 177 yeast TF binding profiles. The introduction of a yeast division brings the convenience of JASPAR to an active research community. As binding models are refined by newer data, the JASPAR database now uses versioning of matrices: in this release, 12% of the older models were updated to improved versions. Classification of TF families has been improved by adopting a new DNA-binding domain nomenclature. A curated catalog of mammalian TFs is provided, extending the use of the JASPAR profiles to additional TFs belonging to the same structural family. The changes in the database set the system ready for more rapid acquisition of new high-throughput data sources. Additionally, three new special collections provide matrix profile data produced by recent alternative high-throughput approaches. PMID:19906716

Zika virus crosses an in vitro human blood brain barrier model.

PubMed

Alimonti, Judie B; Ribecco-Lutkiewicz, Maria; Sodja, Caroline; Jezierski, Anna; Stanimirovic, Danica B; Liu, Qing; Haqqani, Arsalan S; Conlan, Wayne; Bani-Yaghoub, Mahmud

2018-05-15

Zika virus (ZIKV) is a flavivirus that is highly neurotropic causing congenital abnormalities and neurological damage to the central nervous systems (CNS). In this study, we used a human induced pluripotent stem cell (iPSC)-derived blood brain barrier (BBB) model to demonstrate that ZIKV can infect brain endothelial cells (i-BECs) without compromising the BBB barrier integrity or permeability. Although no disruption to the BBB was observed post-infection, ZIKV particles were released on the abluminal side of the BBB model and infected underlying iPSC-derived neural progenitor cells (i-NPs). AXL, a putative ZIKV cellular entry receptor, was also highly expressed in ZIKV-susceptible i-BEC and i-NPs. This iPSC-derived BBB model can help elucidate the mechanism by which ZIKV can infect BECs, cross the BBB and gain access to the CNS.

Chemical suppressors of mlo-mediated powdery mildew resistance

PubMed Central

Wu, Hongpo; Kwaaitaal, Mark; Strugala, Roxana; Schaffrath, Ulrich; Bednarek, Paweł

2017-01-01

Loss-of-function of barley mildew locus o (Mlo) confers durable broad-spectrum penetration resistance to the barley powdery mildew pathogen, Blumeria graminis f. sp. hordei (Bgh). Given the importance of mlo mutants in agriculture, surprisingly few molecular components have been identified to be required for this type of resistance in barley. With the aim to identify novel cellular factors contributing to mlo-based resistance, we devised a pharmacological inhibitor screen. Of the 41 rationally chosen compounds tested, five caused a partial suppression of mlo resistance in barley, indicated by increased levels of Bgh host cell entry. These chemicals comprise brefeldin A (BFA), 2′,3′-dideoxyadenosine (DDA), 2-deoxy-d-glucose, spermidine, and 1-aminobenzotriazole. Further inhibitor analysis corroborated a key role for both anterograde and retrograde endomembrane trafficking in mlo resistance. In addition, all four ribonucleosides, some ribonucleoside derivatives, two of the five nucleobases (guanine and uracil), some guanine derivatives as well as various polyamines partially suppress mlo resistance in barley via yet unknown mechanisms. Most of the chemicals identified to be effective in partially relieving mlo resistance in barley also to some extent compromised powdery mildew resistance in an Arabidopsis mlo2 mlo6 double mutant. In summary, our study identified novel suppressors of mlo resistance that may serve as valuable probes to unravel further the molecular processes underlying this unusual type of disease resistance. PMID:29127104

Eukaryotic translation initiation factor 3 plays distinct roles at the mRNA entry and exit channels of the ribosomal preinitiation complex

PubMed Central

Aitken, Colin Echeverría; Beznosková, Petra; Vlčkova, Vladislava; Chiu, Wen-Ling; Zhou, Fujun; Valášek, Leoš Shivaya; Hinnebusch, Alan G; Lorsch, Jon R

2016-01-01

Eukaryotic translation initiation factor 3 (eIF3) is a central player in recruitment of the pre-initiation complex (PIC) to mRNA. We probed the effects on mRNA recruitment of a library of S. cerevisiae eIF3 functional variants spanning its 5 essential subunits using an in vitro-reconstituted system. Mutations throughout eIF3 disrupt its interaction with the PIC and diminish its ability to accelerate recruitment to a native yeast mRNA. Alterations to the eIF3a CTD and eIF3b/i/g significantly slow mRNA recruitment, and mutations within eIF3b/i/g destabilize eIF2•GTP•Met-tRNAi binding to the PIC. Using model mRNAs lacking contacts with the 40S entry or exit channels, we uncovered a critical role for eIF3 requiring the eIF3a NTD, in stabilizing mRNA interactions at the exit channel, and an ancillary role at the entry channel requiring residues of the eIF3a CTD. These functions are redundant: defects at each channel can be rescued by filling the other channel with mRNA. DOI: http://dx.doi.org/10.7554/eLife.20934.001 PMID:27782884

A Dual Microscopy-Based Assay To Assess Listeria monocytogenes Cellular Entry and Vacuolar Escape.

PubMed

Quereda, Juan J; Pizarro-Cerdá, Javier; Balestrino, Damien; Bobard, Alexandre; Danckaert, Anne; Aulner, Nathalie; Shorte, Spencer; Enninga, Jost; Cossart, Pascale

2016-01-01

Listeria monocytogenes is a Gram-positive bacterium and a facultative intracellular pathogen that invades mammalian cells, disrupts its internalization vacuole, and proliferates in the host cell cytoplasm. Here, we describe a novel image-based microscopy assay that allows discrimination between cellular entry and vacuolar escape, enabling high-content screening to identify factors specifically involved in these two steps. We first generated L. monocytogenes and Listeria innocua strains expressing a β-lactamase covalently attached to the bacterial cell wall. These strains were then incubated with HeLa cells containing the Förster resonance energy transfer (FRET) probe CCF4 in their cytoplasm. The CCF4 probe was cleaved by the bacterial surface β-lactamase only in cells inoculated with L. monocytogenes but not those inoculated with L. innocua, thereby demonstrating bacterial access to the host cytoplasm. Subsequently, we performed differential immunofluorescence staining to distinguish extracellular versus total bacterial populations in samples that were also analyzed by the FRET-based assay. With this two-step analysis, bacterial entry can be distinguished from vacuolar rupture in a single experiment. Our novel approach represents a powerful tool for identifying factors that determine the intracellular niche of L. monocytogenes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Exotic Dance in Baltimore: From Entry to STI/HIV Risk.

PubMed

Lilleston, Pamela S; Reuben, Jacqueline; Sherman, Susan G

2015-01-01

Research has documented health risks associated with sex work, but few U.S. studies have focused on the exotic dance industry. We undertook this study to describe the factors that influenced women's entry into exotic dance and explored the relation of these forces to their subsequent sexually transmitted infection (STI)/HIV risk trajectory. Qualitative interviews (N = 25) were conducted with female exotic dancers from June through August 2009. Data were analyzed through Atlas-ti using an inductive approach. Economic vulnerability was the primary force behind women's initiation into the profession. Drug use, physical abuse, and enjoyment of dancing were often concurrent with economic need and provided a further push toward exotic dance. Social networks facilitated entry by normalizing the profession and presenting it as a solution to financial hardship. Characteristics of exotic dance clubs, such as immediate hire and daily pay, attracted women in a state of financial vulnerability. Women's motivations for dancing, including economic vulnerability and drug use practices, shaped their STI/HIV risk once immersed in the club environment, with social networks often facilitating sexual risk behavior. Understanding the factors that drive women to exotic dance and influence risk behavior in the club may assist in the development of targeted harm reduction interventions for exotic dancers.

Exotic Dance in Baltimore: From Entry to STI/HIV Risk

PubMed Central

Reuben, Jacqueline; Sherman, Susan G.

2015-01-01

Research has documented health risks associated with sex work, but few U.S. studies have focused on the exotic dance industry. We undertook to describe the factors that influenced women's entry into exotic dance and explored the relation of these forces to their subsequent Sexually Transmitted Infection (STI)/HIV risk trajectory. Qualitative interviews (N=25) were conducted with female exotic dancers from June through August, 2009. Data were analyzed through Atlas-ti using an inductive approach. Economic vulnerability was the primary force behind women's initiation into the profession. Drug use, physical abuse, and enjoyment of dancing were often concurrent with economic need and provided a further push toward exotic dance. Social networks facilitated entry by normalizing the profession and presenting it as a solution to financial hardship. Characteristics of exotic dance clubs, such as immediate hire and daily pay, attracted women in a state of financial vulnerability. Women's motivations for dancing, including economic vulnerability and drug use practices, shaped their STI/HIV risk once immersed in the club environment, with social networks often facilitating sexual risk behavior. Understanding the factors that drive women to exotic dance and influence risk behavior in the club may assist in the development of targeted harm reduction interventions for exotic dancers. PMID:25807063

Key Attributes of a Successful Physician Order Entry System Implementation in a Multi-hospital Environment

PubMed Central

Ahmad, Asif; Teater, Phyllis; Bentley, Thomas D.; Kuehn, Lynn; Kumar, Rajee R.; Thomas, Andrew; Mekhjian, Hagop S.

2002-01-01

The benefits of computerized physician order entry have been widely recognized, although few institutions have successfully installed these systems. Obstacles to successful implementation are organizational as well as technical. In the spring of 2000, following a 4-year period of planning and customization, a 9-month pilot project, and a 14-month hiatus for year 2000, the Ohio State University Health System extensively implemented physician order entry across inpatient units. Implementation for specialty and community services is targeted for completion in 2002. On implemented units, all orders are processed through the system, with 80 percent being entered by physicians and the rest by nursing or other licensed care providers. The system is deployable across diverse clinical environments, focused on physicians as the primary users, and accepted by clinicians. These are the three criteria by which the authors measured the success of their implementation. They believe that the availability of specialty-specific order sets, the engagement of physician leadership, and a large-scale system implementation were key strategic factors that enabled physician-users to accept a physician order entry system despite significant changes in workflow. PMID:11751800

Parametric entry corridors for lunar/Mars aerocapture missions

NASA Technical Reports Server (NTRS)

Ling, Lisa M.; Baseggio, Franco M.; Fuhry, Douglas P.

1991-01-01

Parametric atmospheric entry corridor data are presented for Earth and Mars aerocapture. Parameter ranges were dictated by the range of mission designs currently envisioned as possibilities for the Human Exploration Initiative (HEI). This data, while not providing a means for exhaustive evaluation of aerocapture performance, should prove to be a useful aid for preliminary mission design and evaluation. Entry corridors are expressed as ranges of allowable vacuum periapse altitude of the planetary approach hyperbolic orbit, with chart provided for conversion to an approximate flight path angle corridor at entry interface (125 km altitude). The corridor boundaries are defined by open-loop aerocapture trajectories which satisfy boundary constraints while utilizing the full aerodynamic control capability of the vehicle (i.e., full lift-up or full lift-down). Parameters examined were limited to those of greatest importance from an aerocapture performance standpoint, including the approach orbit hyperbolic excess velocity, the vehicle lift to drag ratio, maximum aerodynamic load factor limit, and the apoapse of the target orbit. The impact of the atmospheric density bias uncertainties are also included. The corridor data is presented in graphical format, and examples of the utilization of these graphs for mission design and evaluation are included.

TrSDB: a proteome database of transcription factors

PubMed Central

Hermoso, Antoni; Aguilar, Daniel; Aviles, Francesc X.; Querol, Enrique

2004-01-01

TrSDB—TranScout Database—(http://ibb.uab.es/trsdb) is a proteome database of eukaryotic transcription factors based upon predicted motifs by TranScout and data sources such as InterPro and Gene Ontology Annotation. Nine eukaryotic proteomes are included in the current version. Extensive and diverse information for each database entry, different analyses considering TranScout classification and similarity relationships are offered for research on transcription factors or gene expression. PMID:14681387

Transfer of intestine-derived diamines into tumour cells during treatment of Ehrlich-ascites--carcinoma-bearing mice with polyamine anti-metabolites.

PubMed Central

Kallio, A; Nikula, P; Jänne, J

1984-01-01

Treatment of Ehrlich-ascites-carcinoma-bearing mice with methylglyoxal bis(guanylhydrazone) alone or in combination with 2-difluoromethylornithine greatly enhanced the transfer of intragastrically administered radioactive putrescine and cadaverine into the carcinoma cells. Difluoromethylornithine alone did not have any effect on the accumulation of intestine-derived diamines in the tumour cells. The frequently reported restoration of difluoromethylornithine-induced polyamine depletion on administration of methylglyoxal bis(guanylhydrazone) is in all likelihood attributable to a profound inhibition of intestinal diamine oxidase (EC 1.4.3.6), resulting in an enhanced entry of intestinal (bacterial) diamines into general circulation and finally into tumour cells. PMID:6424664

Inhibition of Vaccinia virus entry by a broad spectrum antiviral peptide

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

Altmann, S.E.; Jones, J.C.; Schultz-Cherry, S.

2009-06-05

Concerns about the possible use of Variola virus, the causative agent of smallpox, as a weapon for bioterrorism have led to renewed efforts to identify new antivirals against orthopoxviruses. We identified a peptide, EB, which inhibited infection by Vaccinia virus with an EC{sub 50} of 15 muM. A control peptide, EBX, identical in composition to EB but differing in sequence, was inactive (EC{sub 50} > 200 muM), indicating sequence specificity. The inhibition was reversed upon removal of the peptide, and EB treatment had no effect on the physical integrity of virus particles as determined by electron microscopy. Viral adsorption wasmore » unaffected by the presence of EB, and the addition of EB post-entry had no effect on viral titers or on early gene expression. The addition of EB post-adsorption resulted in the inhibition of beta-galactosidase expression from an early viral promoter with an EC{sub 50} of 45 muM. A significant reduction in virus entry was detected in the presence of the peptide when the number of viral cores released into the cytoplasm was quantified. Electron microscopy indicated that 88% of the virions remained on the surface of cells in the presence of EB, compared to 37% in the control (p < 0.001). EB also blocked fusion-from-within, suggesting that virus infection is inhibited at the fusion step. Analysis of EB derivatives suggested that peptide length may be important for the activity of EB. The EB peptide is, to our knowledge, the first known small molecule inhibitor of Vaccinia virus entry.« less

IFITM3 Restricts Human Metapneumovirus Infection.

PubMed

McMichael, Temet M; Zhang, Yu; Kenney, Adam D; Zhang, Lizhi; Zani, Ashley; Lu, Mijia; Chemudupati, Mahesh; Li, Jianrong; Yount, Jacob S

2018-06-15

Human metapneumovirus (hMPV) utilizes a bifurcated cellular entry strategy, fusing either with the plasma membrane or, after endocytosis, with the endosome membrane. Whether cellular factors restrict or enhance either entry pathway is largely unknown. We found that the interferon-induced transmembrane protein 3 (IFITM3) inhibits hMPV infection to an extent similar to endocytosis-inhibiting drugs, and an IFITM3 variant that accumulates at the plasma membrane in addition to its endosome localization provided increased virus restriction. Mechanistically, IFITM3 blocks hMPV F protein-mediated membrane fusion, and inhibition of infection was reversed by the membrane destabilizing drug amphotericin B. Conversely, we found that infection by some hMPV strains is enhanced by the endosomal protein Toll-like receptor 7 (TLR7), and that IFITM3 retains the ability to restrict hMPV infection even in cells expressing TLR7. Overall, our results identify IFITM3 as an endosomal restriction factor that limits hMPV infection of cells.

Cyclophilin A Associates with Enterovirus-71 Virus Capsid and Plays an Essential Role in Viral Infection as an Uncoating Regulator

PubMed Central

Huang, Jiaoyan; Yan, Wenzhong; Wang, Jinglan; Su, Dan; Ni, Cheng; Li, Jian; Rao, Zihe; Liu, Lei; Lou, Zhiyong

2014-01-01

Viruses utilize host factors for their efficient proliferation. By evaluating the inhibitory effects of compounds in our library, we identified inhibitors of cyclophilin A (CypA), a known immunosuppressor with peptidyl-prolyl cis-trans isomerase activity, can significantly attenuate EV71 proliferation. We demonstrated that CypA played an essential role in EV71 entry and that the RNA interference-mediated reduction of endogenous CypA expression led to decreased EV71 multiplication. We further revealed that CypA directly interacted with and modified the conformation of H-I loop of the VP1 protein in EV71 capsid, and thus regulated the uncoating process of EV71 entry step in a pH-dependent manner. Our results aid in the understanding of how host factors influence EV71 life cycle and provide new potential targets for developing antiviral agents against EV71 infection. PMID:25275585

Comparison of the time-to-indexing in PubMed between biomedical journals according to impact factor, discipline, and focus.

PubMed

Irwin, Adriane N; Rackham, Daniel

Practicing evidence-based medicine requires health care professionals to efficiently retrieve relevant and current literature. The purpose of this study was to compare the time interval between PubMed entry and indexing with Medical Subject Headings (MeSH) between biomedical journals with varying impact factors, focus areas, and health care discipline representation. This was a cross-sectional study of articles entered into PubMed database between January 1 and December 31, 2012. The primary endpoint was the number of days between PubMed entry and indexing with MeSH terms. A total of 7906 articles were reviewed across 18 journals. In the first comparison, the time-to-indexing was 177 ± 100 days, 111 ± 69 days, and 23 ± 40 days for articles published in journals with impact factors of 2.0-2.5, 4.5-6.5, and >25, respectively (P ≤ 0.001). In the second comparison, the time-to-indexing was 111 ± 69 days for general medicine versus 170 ± 74 days for specialty journals (P ≤ 0.001). In the third comparison, the overall time-to-indexing was 177 ± 100 days, 234 ± 107 days, and 163 ± 58 days for medicine, nursing, and pharmacy journals, respectively (P ≤ 0.001). Study results identified a significant delay between entry of articles into the PubMed database and time-to-indexing with MeSH terms across journals of varying impact factor, discipline, and focus. Results suggest that there may be factors that influence the priority by which articles are indexed with MeSH terms. Future research should focus on determining those journal characteristics and any impact of this delay on clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Simian hemorrhagic fever virus cell entry is dependent on CD163 and uses a clathrin-mediated endocytosis-like pathway.

PubMed

Caì, Yíngyún; Postnikova, Elena N; Bernbaum, John G; Yú, Shu Qìng; Mazur, Steven; Deiuliis, Nicole M; Radoshitzky, Sheli R; Lackemeyer, Matthew G; McCluskey, Adam; Robinson, Phillip J; Haucke, Volker; Wahl-Jensen, Victoria; Bailey, Adam L; Lauck, Michael; Friedrich, Thomas C; O'Connor, David H; Goldberg, Tony L; Jahrling, Peter B; Kuhn, Jens H

2015-01-01

Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques but is thought to be nonpathogenic for humans. To date, the SHFV life cycle is almost completely uncharacterized on the molecular level. Here, we describe the first steps of the SHFV life cycle. Our experiments indicate that SHFV enters target cells by low-pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-β-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knockout study and electron microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, α-chymotrypsin, and trypsin) abrogated entry, indicating that the SHFV cell surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component. Simian hemorrhagic fever virus (SHFV) causes highly lethal disease in Asian macaques resembling human illness caused by Ebola or Lassa virus. However, little is known about SHFV's ecology and molecular biology and the mechanism by which it causes disease. The results of this study shed light on how SHFV enters its target cells. Using electron microscopy and inhibitors for various cellular pathways, we demonstrate that SHFV invades cells by low-pH-dependent, actin-independent endocytosis, likely with the help of a cellular surface protein. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Huygens probe entry, descent, and landing trajectory reconstruction using the Program to Optimize Simulated Trajectories II

NASA Astrophysics Data System (ADS)

Striepe, Scott Allen

The objectives of this research were to develop a reconstruction capability using the Program to Optimize Simulated Trajectories II (POST2), apply this capability to reconstruct the Huygens Titan probe entry, descent, and landing (EDL) trajectory, evaluate the newly developed POST2 reconstruction module, analyze the reconstructed trajectory, and assess the pre-flight simulation models used for Huygens EDL simulation. An extended Kalman filter (EKF) module was developed and integrated into POST2 to enable trajectory reconstruction (especially when using POST2-based mission specific simulations). Several validation cases, ranging from a single, constant parameter estimate to multivariable estimation cases similar to an actual mission flight, were executed to test the POST2 reconstruction module. Trajectory reconstruction of the Huygens entry probe at Titan was accomplished using accelerometer measurements taken during flight to adjust an estimated state (e.g., position, velocity, parachute drag, wind velocity, etc.) in a POST2-based simulation developed to support EDL analyses and design prior to entry. Although the main emphasis of the trajectory reconstruction was to evaluate models used in the NASA pre-entry trajectory simulation, the resulting reconstructed trajectory was also assessed to provide an independent evaluation of the ESA result. Major findings from this analysis include: Altitude profiles from this analysis agree well with other NASA and ESA results but not with Radar data, whereas a scale factor of about 0.93 would bring the radar measurements into compliance with these results; entry capsule aerodynamics predictions (axial component only) were well within 3-sigma bounds established pre-flight for most of the entry when compared to reconstructed values; Main parachute drag of 9% to 19% above ESA model was determined from the reconstructed trajectory; based on the tilt sensor and accelerometer data, the conclusion from this assessment was that the probe was tilted about 10 degrees during the Drogue parachute phase.

Aviation Security: Biometric Technology and Risk Based Security Aviation Passenger Screening Program

DTIC Science & Technology

2012-12-01

distribution is unlimited 12b. DISTRIBUTION CODE A 13. ABSTRACT (maximum 200 words ) Since 9/11, the Transportation Security Administration (TSA...Council POE Point Of Entry RBS Risk-Based Security SENTRI Secure Electronic Network for Travelers Rapid Inspection SFPD Secure Flight Passenger...Committee on Biometrics provides the origins of biometrics; the term “biometrics” is derived from the Greek words “bio” (life) and “metrics” (to measure

Flow-field measurements in the windward surface shock layer of space shuttle orbiter configurations at Mach number 8. [wind tunnel tests of scale models

NASA Technical Reports Server (NTRS)

Martindale, W. R.; Carter, L. D.

1975-01-01

Pitot pressure and total-temperature measurements were made in the windward surface shock layer of two 0.0175-scale space shuttle orbiter models at simulated re-entry conditions. Corresponding surface static pressure measurements were also made. Flow properties at the edge of the model boundary layer were derived from these measurements and compared with values calculated using conventional methods.

Anaphase-Promoting Complex/Cyclosome-Cdh1-Mediated Proteolysis of the Forkhead Box M1 Transcription Factor Is Critical for Regulated Entry into S Phase▿

PubMed Central

Park, Hyun Jung; Costa, Robert H.; Lau, Lester F.; Tyner, Angela L.; Raychaudhuri, Pradip

2008-01-01

The forkhead box M1 (FoxM1) transcription factor is overexpressed in many cancers, and in mouse models it is required for tumor progression. FoxM1 activates expression of the cell cycle genes required for both S and M phase progression. Here we demonstrate that FoxM1 is degraded in late mitosis and early G1 phase by the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. FoxM1 interacts with the APC/C complex and its adaptor, Cdh1. Expression of Cdh1 stimulated degradation of the FoxM1 protein, and depletion of Cdh1 resulted in stabilization of the FoxM1 protein in late mitosis and in early G1 phase of the cell cycle. Cdh1 has been implicated in regulating S phase entry. We show that codepletion of FoxM1 inhibits early S phase entry observed in Cdh1-depleted cells. The N-terminal region of FoxM1 contains both destruction box (D box) and KEN box sequences that are required for targeting by Cdh1. Mutation of either the D box sequence or the KEN box sequence stabilized FoxM1 and blocked Cdh1-induced proteolysis. Cells expressing a nondegradable form of FoxM1 entered S phase rapidly following release from M phase arrest. Together, our observations show that FoxM1 is one of the targets of Cdh1 in late M or early G1 phase and that its proteolysis is important for regulated entry into S phase. PMID:18573889

Anaphase-promoting complex/cyclosome-CDH1-mediated proteolysis of the forkhead box M1 transcription factor is critical for regulated entry into S phase.

PubMed

Park, Hyun Jung; Costa, Robert H; Lau, Lester F; Tyner, Angela L; Raychaudhuri, Pradip

2008-09-01

The forkhead box M1 (FoxM1) transcription factor is overexpressed in many cancers, and in mouse models it is required for tumor progression. FoxM1 activates expression of the cell cycle genes required for both S and M phase progression. Here we demonstrate that FoxM1 is degraded in late mitosis and early G(1) phase by the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. FoxM1 interacts with the APC/C complex and its adaptor, Cdh1. Expression of Cdh1 stimulated degradation of the FoxM1 protein, and depletion of Cdh1 resulted in stabilization of the FoxM1 protein in late mitosis and in early G(1) phase of the cell cycle. Cdh1 has been implicated in regulating S phase entry. We show that codepletion of FoxM1 inhibits early S phase entry observed in Cdh1-depleted cells. The N-terminal region of FoxM1 contains both destruction box (D box) and KEN box sequences that are required for targeting by Cdh1. Mutation of either the D box sequence or the KEN box sequence stabilized FoxM1 and blocked Cdh1-induced proteolysis. Cells expressing a nondegradable form of FoxM1 entered S phase rapidly following release from M phase arrest. Together, our observations show that FoxM1 is one of the targets of Cdh1 in late M or early G(1) phase and that its proteolysis is important for regulated entry into S phase.

Calling Orientations of Junior Doctors and Medical Interns in India: Cultural, Occupational and Relational Perspectives

ERIC Educational Resources Information Center

Nath, Vandana

2017-01-01

This study examines the factors that shape calling orientations within the Indian context. Based on the narratives of 72 junior doctors and medical interns, it is found that participants identify with harbouring a calling both prior and subsequent to occupational entry. Although factors such as self-recognition of talent and sensemaking of work as…

An Exploratory Study of the Factors Influencing Undergraduate Student Choice: The Case of Higher Education in Scotland

ERIC Educational Resources Information Center

Briggs, Senga

2006-01-01

This article explores the factors influencing student choice at six contrasting universities in Scotland to establish if there is value in developing a model for predicting institutional choice for Scottish undergraduate entry. It is based on a survey of 651 students in two undergraduate disciplines, accountancy and engineering, across the six…

An Analysis of the External Environmental and Internal Organizational Factors Associated with Adoption of the Electronic Health Record

ERIC Educational Resources Information Center

Kruse, Clemens Scott

2013-01-01

Despite a Presidential Order in 2004 that launched national incentives for the use of health information technology, specifically the Electronic Health Record (EHR), adoption of the EHR has been slow. This study attempts to quantify factors associated with adoption of the EHR and Computerized Provider Order Entry (CPOE) by combining multiple…

Syncytial Mutations Do Not Impair the Specificity of Entry and Spread of a Glycoprotein D Receptor-Retargeted Herpes Simplex Virus

PubMed Central

Okubo, Yu; Wakata, Aika; Suzuki, Takuma; Shibata, Tomoko; Ikeda, Hitomi; Yamaguchi, Miki; Cohen, Justus B.; Glorioso, Joseph C.; Tagaya, Mitsuo; Hamada, Hirofumi; Tahara, Hideaki

2016-01-01

ABSTRACT Membrane fusion, which is the key process for both initial cell entry and subsequent lateral spread of herpes simplex virus (HSV), requires the four envelope glycoproteins gB, gD, gH, and gL. Syncytial mutations, predominantly mapped to the gB and gK genes, confer hyperfusogenicity on HSV and cause multinucleated giant cells, termed syncytia. Here we asked whether interaction of gD with a cognate entry receptor remains indispensable for initiating membrane fusion of syncytial strains. To address this question, we took advantage of mutant viruses whose viral entry into cells relies on the uniquely specific interaction of an engineered gD with epidermal growth factor receptor (EGFR). We introduced selected syncytial mutations into gB and/or gK of the EGFR-retargeted HSV and found that these mutations, especially when combined, enabled formation of extensive syncytia by human cancer cell lines that express the target receptor; these syncytia were substantially larger than the plaques formed by the parental retargeted HSV strain. We assessed the EGFR dependence of entry and spread separately by using direct entry and infectious center assays, respectively, and we found that the syncytial mutations did not override the receptor specificity of the retargeted viruses at either stage. We discuss the implications of these results for the development of more effective targeted oncolytic HSV vectors. IMPORTANCE Herpes simplex virus (HSV) is investigated not only as a human pathogen but also as a promising agent for oncolytic virotherapy. We previously showed that both the initial entry and subsequent lateral spread of HSV can be retargeted to cells expressing tumor-associated antigens by single-chain antibodies fused to a receptor-binding-deficient envelope glycoprotein D (gD). Here we introduced syncytial mutations into the gB and/or gK gene of gD-retargeted HSVs to determine whether viral tropism remained dependent on the interaction of gD with the target receptor. Entry and spread profiles of the recombinant viruses indicated that gD retargeting does not abolish the hyperfusogenic activity of syncytial mutations and that these mutations do not eliminate the dependence of HSV entry and spread on a specific gD-receptor interaction. These observations suggest that syncytial mutations may be valuable for increasing the tumor-specific spreading of retargeted oncolytic HSV vectors. PMID:27707922

Activity of the HIV-1 Attachment Inhibitor BMS-626529, the Active Component of the Prodrug BMS-663068, against CD4-Independent Viruses and HIV-1 Envelopes Resistant to Other Entry Inhibitors

PubMed Central

Li, Zhufang; Zhou, Nannan; Sun, Yongnian; Ray, Neelanjana; Lataillade, Max; Hanna, George J.

2013-01-01

BMS-626529 is a novel small-molecule HIV-1 attachment inhibitor active against both CCR5- and CXCR4-tropic viruses. BMS-626529 functions by preventing gp120 from binding to CD4. A prodrug of this compound, BMS-663068, is currently in clinical development. As a theoretical resistance pathway to BMS-663068 could be the development of a CD4-independent phenotype, we examined the activity of BMS-626529 against CD4-independent viruses and investigated whether resistance to BMS-626529 could be associated with a CD4-independent phenotype. Finally, we evaluated whether cross-resistance exists between BMS-626529 and other HIV-1 entry inhibitors. Two laboratory-derived envelopes with a CD4-independent phenotype (one CXCR4 tropic and one CCR5 tropic), five envelopes from clinical isolates with preexisting BMS-626529 resistance, and several site-specific mutant BMS-626529-resistant envelopes were examined for their dependence on CD4 for infectivity or susceptibility to BMS-626529. Viruses resistant to other entry inhibitors (enfuvirtide, maraviroc, and ibalizumab) were also examined for susceptibility to BMS-626529. Both CD4-independent laboratory isolates retained sensitivity to BMS-626529 in CD4− cells, while HIV-1 envelopes from viruses resistant to BMS-626529 exhibited no evidence of a CD4-independent phenotype. BMS-626529 also exhibited inhibitory activity against ibalizumab- and enfuvirtide-resistant envelopes. While there appeared to be some association between maraviroc resistance and reduced susceptibility to BMS-626529, an absolute correlation cannot be presumed, since some CCR5-tropic maraviroc-resistant envelopes remained sensitive to BMS-626529. Clinical use of the prodrug BMS-663068 is unlikely to promote resistance via generation of CD4-independent virus. No cross-resistance between BMS-626529 and other HIV entry inhibitors was observed, which could allow for sequential or concurrent use with different classes of entry inhibitors. PMID:23774428

Lifespan Extension in a Semelparous Chordate Occurs via Developmental Growth Arrest Just Prior to Meiotic Entry

PubMed Central

Subramaniam, Gunasekaran; Campsteijn, Coen; Thompson, Eric M.

2014-01-01

It is proposed that the ageing process is linked to signaling from the germline such that the rate of ageing can be adjusted to the state of the reproductive system, allowing these two processes to co-evolve. Mechanistic insight into this link has been primarily derived from iteroparous reproductive models, the nematode C. elegans, and the arthropod Drosophila. Here, we examined to what extent these mechanisms are evolutionarily conserved in a semelparous chordate, Oikopleura dioica, where we identify a developmental growth arrest (GA) in response to crowded, diet-restricted conditions, which can extend its lifespan at least three-fold. Under nutritional stress, the iteroparative models sacrifice germ cells that have entered meiosis, while maintaining a reduced pool of active germline stem cells (GSCs). In contrast, O. dioica only entered GA prior to meiotic entry. Stress conditions encountered after this point led to maturation in a normal time frame but with reduced reproductive output. During GA, TOR signaling was inhibited, whereas MAPK, ERK1/2 and p38 pathways were activated, and under such conditions, activation of these pathways was shown to be critical for survival. Direct inhibition of TOR signaling alone was sufficient to prevent meiotic entry and germline differentiation. This inhibition activated the p38 pathway, but did not activate the ERK1/2 pathway. Thus, the link between reproductive status and lifespan extension in response to nutrient-limited conditions is interpreted in a significantly different manner in these iteroparative versus semelparous models. In the latter case, meiotic entry is a definitive signal that lifespan extension can no longer occur, whereas in the former, meiotic entry is not a unique chronological event, and can be largely erased during lifespan extension in response to nutrient stress, and reactivated from a pool of maintained GSCs when conditions improve. PMID:24695788

Cell cycle re-entry sensitizes podocytes to injury induced death

PubMed Central

Hagen, Manuel; Pfister, Eva; Kosel, Andrea; Shankland, Stuart; Pippin, Jeffrey; Amann, Kerstin; Daniel, Christoph

2016-01-01

ABSTRACT Podocytes are terminally differentiated renal cells, lacking the ability to regenerate by proliferation. However, during renal injury, podocytes re-enter into the cell cycle but fail to divide. Earlier studies suggested that re-entry into cell cycle results in loss of podocytes, but a direct evidence for this is lacking. Therefore, we established an in vitro model to test the consequences of re-entry into the cell cycle on podocyte survival. A mouse immortalized podocyte cell line was differentiated to non-permissive podocytes and stimulated with e.g. growth factors. Stimulated cells were analyzed for mRNA-expression or stained for cell cycle analysis using flow cytometry and immunocytofluorescence microscopy. After stimulation to re-entry into cell cycle, podocytes were stressed with puromycin aminonucleoside (PAN) and analyzed for survival. During permissive stage more than 40% of immortalized podocytes were in the S-phase. In contrast, S-phase in non-permissive differentiated podocytes was reduced to 5%. Treatment with b-FGF dose dependently induced re-entry into cell cycle increasing the number of podocytes in the S-phase to 10.7% at an optimal bFGF dosage of 10 ng/ml. Forty eight hours after stimulation with bFGF the number of bi-nucleated podocytes significantly increased. A secondary injury stimulus significantly reduced podocyte survival preferentially in bi-nucleated podocytes In conclusion, stimulation of podocytes using bFGF was able to induce re-entry of podocytes into the cell cycle and to sensitize the cells for cell death by secondary injuries. Therefore, this model is appropriate for testing new podocyte protective substances that can be used for therapy. PMID:27232327

Health literacy and task environment influence parents' burden for data entry on child-specific health information: randomized controlled trial.

PubMed

Porter, Stephen C; Guo, Chao-Yu; Bacic, Janine; Chan, Eugenia

2011-01-26

Health care systems increasingly rely on patients' data entry efforts to organize and assist in care delivery through health information exchange. We sought to determine (1) the variation in burden imposed on parents by data entry efforts across paper-based and computer-based environments, and (2) the impact, if any, of parents' health literacy on the task burden. We completed a randomized controlled trial of parent-completed data entry tasks. Parents of children with attention deficit hyperactivity disorder (ADHD) were randomized based on the Test of Functional Health Literacy in Adults (TOFHLA) to either a paper-based or computer-based environment for entry of health information on their children. The primary outcome was the National Aeronautics and Space Administration Task Load Index (TLX) total weighted score. We screened 271 parents: 194 (71.6%) were eligible, and 180 of these (92.8%) constituted the study cohort. We analyzed 90 participants from each arm. Parents who completed information tasks on paper reported a higher task burden than those who worked in the computer environment: mean (SD) TLX scores were 22.8 (20.6) for paper and 16.3 (16.1) for computer. Assignment to the paper environment conferred a significant risk of higher task burden (F(1,178) = 4.05, P = .046). Adequate literacy was associated with lower task burden (decrease in burden score of 1.15 SD, P = .003). After adjusting for relevant child and parent factors, parents' TOFHLA score (beta = -.02, P = .02) and task environment (beta = .31, P = .03) remained significantly associated with task burden. A tailored computer-based environment provided an improved task experience for data entry compared to the same tasks completed on paper. Health literacy was inversely related to task burden.

Optimization of a Hot Structure Aeroshell and Nose Cap for Mars Atmospheric Entry

NASA Technical Reports Server (NTRS)

Langston, Sarah L.; Lang, Christapher G.; Samareh, Jamshid A.; Daryabeigi, Kamran

2016-01-01

The National Aeronautics and Space Administration (NASA) is preparing to send humans beyond Low Earth Orbit and eventually to the surface of Mars. As part of the Evolvable Mars Campaign, different vehicle configurations are being designed and considered for delivering large payloads to the surface of Mars. Weight and packing volume are driving factors in the vehicle design, and the thermal protection system (TPS) for planetary entry is a technology area which can offer potential weight and volume savings. The feasibility and potential benefits of a ceramic matrix composite hot structure concept for different vehicle configurations are explored in this paper, including the nose cap for a Hypersonic Inflatable Aerodynamic Decelerator (HIAD) and an aeroshell for a mid lift-to-drag (Mid L/D) concept. The TPS of a planetary entry vehicle is a critical component required to survive the severe aerodynamic heating environment during atmospheric en- try. The current state-of-the-art is an ablative material to protect the vehicle from the heat load. The ablator is bonded to an underlying structure, which carries the mechanical loads associated with entry. The alternative hot structure design utilizes an advanced carbon-carbon material system on the outer surface of the vehicle, which is exposed to the severe heating and acts as a load carrying structure. The preliminary design using the hot structure concept and the ablative concept is determined for the spherical nose cap of the HIAD entry vehicle and the aeroshell of the Mid L/D entry vehicle. The results of the study indicate that the use of hot structures for both vehicle concepts leads to a feasible design with potential weight and volume savings benefits over current state-of-the-art TPS technology that could enable future missions.