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Sample records for alamos hiv sequence

  1. HIV Sequence Databases

    PubMed Central

    Kuiken, Carla; Korber, Bette; Shafer, Robert W.

    2008-01-01

    Two important databases are often used in HIV genetic research, the HIV Sequence Database in Los Alamos, which collects all sequences and focuses on annotation and data analysis, and the HIV RT/Protease Sequence Database in Stanford, which collects sequences associated with the development of viral resistance against anti-retroviral drugs and focuses on analysis of those sequences. The types of data and services these two databases offer, the tools they provide, and the way they are set up and operated are described in detail. PMID:12875108

  2. Los Alamos sequence analysis package for nucleic acids and proteins.

    PubMed Central

    Kanehisa, M I

    1982-01-01

    An interactive system for computer analysis of nucleic acid and protein sequences has been developed for the Los Alamos DNA Sequence Database. It provides a convenient way to search or verify various sequence features, e.g., restriction enzyme sites, protein coding frames, and properties of coded proteins. Further, the comprehensive analysis package on a large-scale database can be used for comparative studies on sequence and structural homologies in order to find unnoted information stored in nucleic acid sequences. PMID:6174934

  3. HIV Sequence Compendium 2015

    SciTech Connect

    Foley, Brian Thomas; Leitner, Thomas Kenneth; Apetrei, Cristian; Hahn, Beatrice; Mizrachi, Ilene; Mullins, James; Rambaut, Andrew; Wolinsky, Steven; Korber, Bette Tina Marie

    2015-10-05

    This compendium is an annual printed summary of the data contained in the HIV sequence database. We try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2015. Hence, though it is published in 2015 and called the 2015 Compendium, its contents correspond to the 2014 curated alignments on our website. The number of sequences in the HIV database is still increasing. In total, at the end of 2014, there were 624,121 sequences in the HIV Sequence Database, an increase of 7% since the previous year. This is the first year that the number of new sequences added to the database has decreased compared to the previous year. The number of near complete genomes (>7000 nucleotides) increased to 5834 by end of 2014. However, as in previous years, the compendium alignments contain only a fraction of these. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/ content/sequence/NEWALIGN/align.html As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.

  4. HIV Sequence Compendium 2010

    SciTech Connect

    Kuiken, Carla; Foley, Brian; Leitner, Thomas; Apetrei, Christian; Hahn, Beatrice; Mizrachi, Ilene; Mullins, James; Rambaut, Andrew; Wolinsky, Steven; Korber, Bette

    2010-12-31

    This compendium is an annual printed summary of the data contained in the HIV sequence database. In these compendia we try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2010. Hence, though it is called the 2010 Compendium, its contents correspond to the 2009 curated alignments on our website. The number of sequences in the HIV database is still increasing exponentially. In total, at the time of printing, there were 339,306 sequences in the HIV Sequence Database, an increase of 45% since last year. The number of near complete genomes (>7000 nucleotides) increased to 2576 by end of 2009, reflecting a smaller increase than in previous years. However, as in previous years, the compendium alignments contain only a small fraction of these. Included in the alignments are a small number of sequences representing each of the subtypes and the more prevalent circulating recombinant forms (CRFs) such as 01 and 02, as well as a few outgroup sequences (group O and N and SIV-CPZ). Of the rarer CRFs we included one representative each. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/content/sequence/NEWALIGN/align.html. Reprints are available from our website in the form of both HTML and PDF files. As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.

  5. HIV sequence compendium 2002

    SciTech Connect

    Kuiken, Carla; Foley, Brian; Freed, Eric; Hahn, Beatrice; Marx, Preston; McCutchan, Francine; Mellors, John; Wolinsky, Steven; Korber, Bette

    2002-12-31

    This compendium is an annual printed summary of the data contained in the HIV sequence database. In these compendia we try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Traditionally, we present the sequence data themselves in the form of alignments: Section II, an alignment of a selection of HIV-1/SIVcpz full-length genomes (a lot of LAI-like sequences, for example, have been omitted because they are so similar that they bias the alignment); Section III, a combined HIV-1/HIV-2/SIV whole genome alignment; Sections IV–VI, amino acid alignments for HIV-1/SIV-cpz, HIV-2/SIV, and SIVagm. The HIV-2/SIV and SIVagm amino acid alignments are separate because the genetic distances between these groups are so great that presenting them in one alignment would make it very elongated because of the large number of gaps that have to be inserted. As always, tables with extensive background information gathered from the literature accompany the whole genome alignments. The collection of whole-gene sequences in the database is now large enough that we have abundant representation of most subtypes. For many subtypes, and especially for subtype B, a large number of sequences that span entire genes were not included in the printed alignments to conserve space. A more complete version of all alignments is available on our website, http://hiv-web.lanl.gov/content/hiv-db/ALIGN_CURRENT/ALIGN-INDEX.html. Importantly, all these alignments have been edited to include only one sequence per person, based on phylogenetic trees that were created for all of them, as well as on the literature. Because of the number of sequences available, we have decided to use a different selection principle this year, based on the epidemiological importance of the subtypes. Subtypes A–D and CRFs 01 and 02 are by far the most widespread variants, and for these (when available) we have included 8–10 representatives in the alignments. The other

  6. Integrated sequence and immunology filovirus database at Los Alamos

    DOE PAGES

    Yusim, Karina; Yoon, Hyejin; Foley, Brian; ...

    2016-01-01

    The Ebola outbreak of 2013–15 infected more than 28,000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. We report that as this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount. Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of knownmore » natural diversity in advancing vaccines and therapeutic approaches. To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database. We have integrated and performed baseline analysis of all family Filoviridae sequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis. Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlight the most conserved regions in the proteome that may be useful for a T cell vaccine strategy.« less

  7. Integrated sequence and immunology filovirus database at Los Alamos

    SciTech Connect

    Yusim, Karina; Yoon, Hyejin; Foley, Brian; Feng, Shihai; Macke, Jennifer; Dimitrijevic, Mira; Abfalterer, Werner; Szinger, James; Fischer, Will; Kuiken, Carla; Korber, Bette

    2016-01-01

    The Ebola outbreak of 2013–15 infected more than 28,000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. We report that as this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount. Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of known natural diversity in advancing vaccines and therapeutic approaches. To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database. We have integrated and performed baseline analysis of all family Filoviridae sequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis. Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlight the most conserved regions in the proteome that may be useful for a T cell vaccine strategy.

  8. Integrated sequence and immunology filovirus database at Los Alamos.

    PubMed

    Yusim, Karina; Yoon, Hyejin; Foley, Brian; Feng, Shihai; Macke, Jennifer; Dimitrijevic, Mira; Abfalterer, Werner; Szinger, James; Fischer, Will; Kuiken, Carla; Korber, Bette

    2016-01-01

    The Ebola outbreak of 2013-15 infected more than 28 000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. As this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount. Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of known natural diversity in advancing vaccines and therapeutic approaches. To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database. We have integrated and performed baseline analysis of all family ITALIC! Filoviridaesequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis. Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlight the most conserved regions in the proteome that may be useful for a T cell vaccine strategy.Database URL:www.hfv.lanl.gov.

  9. Therapeutic vaccination reduces HIV sequence variability.

    PubMed

    Hoffmann, Dieter; Seebach, Judith; Cosma, Antonio; Goebel, Frank D; Strimmer, Korbinian; Schätzl, Hermann M; Erfle, Volker

    2008-02-01

    With HIV persisting lifelong in infected persons, therapeutic vaccination is a novel alternative concept to control virus replication. Even though CD8 and CD4 cell responses to such immunizations have been demonstrated, their effects on virus replication are still unclear. In view of this fact, we studied the impact of a therapeutic vaccination with HIV nef delivered by a recombinant modified vaccinia Ankara vector on viral diversity. We investigated HIV sequences derived from chronically infected persons before and after therapeutic vaccination. Before immunization the mean +/- se pairwise variability of patient-derived Nef protein sequences was 0.1527 +/- 0.0041. After vaccination the respective value was 0.1249 +/- 0.0042, resulting in a significant (P<0.0001) difference between the two time points. The genes vif and 5'gag tested in parallel and nef sequences in control persons yielded a constant amino acid sequence variation. The data presented suggest that Nef immunization induced a selective pressure, limiting HIV sequence variability. To our knowledge this is the first report directly linking therapeutic HIV vaccination to decreasing diversity in patient-derived virus isolates.

  10. A Pan-HIV Strategy for Complete Genome Sequencing

    PubMed Central

    Yamaguchi, Julie; Alessandri-Gradt, Elodie; Tell, Robert W.; Brennan, Catherine A.

    2015-01-01

    Molecular surveillance is essential to monitor HIV diversity and track emerging strains. We have developed a universal library preparation method (HIV-SMART [i.e., switching mechanism at 5′ end of RNA transcript]) for next-generation sequencing that harnesses the specificity of HIV-directed priming to enable full genome characterization of all HIV-1 groups (M, N, O, and P) and HIV-2. Broad application of the HIV-SMART approach was demonstrated using a panel of diverse cell-cultured virus isolates. HIV-1 non-subtype B-infected clinical specimens from Cameroon were then used to optimize the protocol to sequence directly from plasma. When multiplexing 8 or more libraries per MiSeq run, full genome coverage at a median ∼2,000× depth was routinely obtained for either sample type. The method reproducibly generated the same consensus sequence, consistently identified viral sequence heterogeneity present in specimens, and at viral loads of ≤4.5 log copies/ml yielded sufficient coverage to permit strain classification. HIV-SMART provides an unparalleled opportunity to identify diverse HIV strains in patient specimens and to determine phylogenetic classification based on the entire viral genome. Easily adapted to sequence any RNA virus, this technology illustrates the utility of next-generation sequencing (NGS) for viral characterization and surveillance. PMID:26699702

  11. A Pan-HIV Strategy for Complete Genome Sequencing.

    PubMed

    Berg, Michael G; Yamaguchi, Julie; Alessandri-Gradt, Elodie; Tell, Robert W; Plantier, Jean-Christophe; Brennan, Catherine A

    2016-04-01

    Molecular surveillance is essential to monitor HIV diversity and track emerging strains. We have developed a universal library preparation method (HIV-SMART [i.e.,switchingmechanismat 5' end ofRNAtranscript]) for next-generation sequencing that harnesses the specificity of HIV-directed priming to enable full genome characterization of all HIV-1 groups (M, N, O, and P) and HIV-2. Broad application of the HIV-SMART approach was demonstrated using a panel of diverse cell-cultured virus isolates. HIV-1 non-subtype B-infected clinical specimens from Cameroon were then used to optimize the protocol to sequence directly from plasma. When multiplexing 8 or more libraries per MiSeq run, full genome coverage at a median ∼2,000× depth was routinely obtained for either sample type. The method reproducibly generated the same consensus sequence, consistently identified viral sequence heterogeneity present in specimens, and at viral loads of ≤4.5 log copies/ml yielded sufficient coverage to permit strain classification. HIV-SMART provides an unparalleled opportunity to identify diverse HIV strains in patient specimens and to determine phylogenetic classification based on the entire viral genome. Easily adapted to sequence any RNA virus, this technology illustrates the utility of next-generation sequencing (NGS) for viral characterization and surveillance.

  12. Sequence conservation, HLA-E-Restricted peptide, and best-defined CTL/CD8+ epitopes in gag P24 (capsid) of HIV-1 subtype B

    NASA Astrophysics Data System (ADS)

    Prasetyo, Afiono Agung; Dharmawan, Ruben; Sari, Yulia; Sariyatun, Ratna

    2017-02-01

    Human immunodeficiency virus type 1 (HIV-1) remains a cause of global health problem. Continuous studies of HIV-1 genetic and immunological profiles are important to find strategies against the virus. This study aimed to conduct analysis of sequence conservation, HLA-E-restricted peptide, and best-defined CTL/CD8+ epitopes in p24 (capsid) of HIV-1 subtype B worldwide. The p24-coding sequences from 3,557 HIV subtype B isolates were aligned using MUSCLE and analysed. Some highly conserved regions (sequence conservation ≥95%) were observed. Two considerably long series of sequences with conservation of 100% was observed at base 349-356 and 550-557 of p24 (HXB2 numbering). The consensus from all aligned isolates was precisely the same as consensus B in the Los Alamos HIV Database. The HLA-E-restricted peptide in amino acid (aa) 14-22 of HIV-1 p24 (AISPRTLNA) was found in 55.9% (1,987/3,557) of HIV-1 subtype B worldwide. Forty-four best-defined CTL/CD8+ epitopes were observed, in which VKNWMTETL epitope (aa 181-189 of p24) restricted by B*4801 was the most frequent, as found in 94.9% of isolates. The results of this study would contribute information about HIV-1 subtype B and benefits for further works willing to develop diagnostic and therapeutic strategies against the virus.

  13. Differentiating founder and chronic HIV envelope sequences.

    PubMed

    Murray, John M; Maher, Stephen; Mota, Talia; Suzuki, Kazuo; Kelleher, Anthony D; Center, Rob J; Purcell, Damian

    2017-01-01

    Significant progress has been made in characterizing broadly neutralizing antibodies against the HIV envelope glycoprotein Env, but an effective vaccine has proven elusive. Vaccine development would be facilitated if common features of early founder virus required for transmission could be identified. Here we employ a combination of bioinformatic and operations research methods to determine the most prevalent features that distinguish 78 subtype B and 55 subtype C founder Env sequences from an equal number of chronic sequences. There were a number of equivalent optimal networks (based on the fewest covarying amino acid (AA) pairs or a measure of maximal covariance) that separated founders from chronics: 13 pairs for subtype B and 75 for subtype C. Every subtype B optimal solution contained the founder pairs 178-346 Asn-Val, 232-236 Thr-Ser, 240-340 Lys-Lys, 279-315 Asp-Lys, 291-792 Ala-Ile, 322-347 Asp-Thr, 535-620 Leu-Asp, 742-837 Arg-Phe, and 750-836 Asp-Ile; the most common optimal pairs for subtype C were 644-781 Lys-Ala (74 of 75 networks), 133-287 Ala-Gln (73/75) and 307-337 Ile-Gln (73/75). No pair was present in all optimal subtype C solutions highlighting the difficulty in targeting transmission with a single vaccine strain. Relative to the size of its domain (0.35% of Env), the α4β7 binding site occurred most frequently among optimal pairs, especially for subtype C: 4.2% of optimal pairs (1.2% for subtype B). Early sequences from 5 subtype B pre-seroconverters each exhibited at least one clone containing an optimal feature 553-624 (Ser-Asn), 724-747 (Arg-Arg), or 46-293 (Arg-Glu).

  14. Differentiating founder and chronic HIV envelope sequences

    PubMed Central

    Maher, Stephen; Mota, Talia; Suzuki, Kazuo; Kelleher, Anthony D.

    2017-01-01

    Significant progress has been made in characterizing broadly neutralizing antibodies against the HIV envelope glycoprotein Env, but an effective vaccine has proven elusive. Vaccine development would be facilitated if common features of early founder virus required for transmission could be identified. Here we employ a combination of bioinformatic and operations research methods to determine the most prevalent features that distinguish 78 subtype B and 55 subtype C founder Env sequences from an equal number of chronic sequences. There were a number of equivalent optimal networks (based on the fewest covarying amino acid (AA) pairs or a measure of maximal covariance) that separated founders from chronics: 13 pairs for subtype B and 75 for subtype C. Every subtype B optimal solution contained the founder pairs 178–346 Asn-Val, 232–236 Thr-Ser, 240–340 Lys-Lys, 279–315 Asp-Lys, 291–792 Ala-Ile, 322–347 Asp-Thr, 535–620 Leu-Asp, 742–837 Arg-Phe, and 750–836 Asp-Ile; the most common optimal pairs for subtype C were 644–781 Lys-Ala (74 of 75 networks), 133–287 Ala-Gln (73/75) and 307–337 Ile-Gln (73/75). No pair was present in all optimal subtype C solutions highlighting the difficulty in targeting transmission with a single vaccine strain. Relative to the size of its domain (0.35% of Env), the α4β7 binding site occurred most frequently among optimal pairs, especially for subtype C: 4.2% of optimal pairs (1.2% for subtype B). Early sequences from 5 subtype B pre-seroconverters each exhibited at least one clone containing an optimal feature 553–624 (Ser-Asn), 724–747 (Arg-Arg), or 46–293 (Arg-Glu). PMID:28187204

  15. Molecular Characterization of Mexican HIV-1 Vif Sequences.

    PubMed

    Guerra-Palomares, Sandra E; Hernandez-Sanchez, Pedro G; Esparza-Perez, Mario A; Arguello, J Rafael; Noyola, Daniel E; Garcia-Sepulveda, Christian A

    2016-03-01

    The viral infectivity factor (Vif) is an HIV accessory protein that counteracts host antiviral proteins of the APOBEC3 family. Accumulating evidence highlights the pivotal role that accessory HIV proteins have on disease pathogenesis, a fact that has made them targets of interest for novel therapeutic and preventive strategies. Little is known about Vif sequence diversity outside of African or white populations. Mexico is home to Americas' third largest HIV-affected population and Mexican Hispanics represent an ever-increasing U.S. minority. This study provides a detailed analysis of the diversity seen in 77 Mexican Vif protein sequences. Phylogenetic analysis shows that most sequences cluster with HIV-1 subtype B, while less than 10% exhibit greater similarity to subtype D and A subtypes. Although most functional motifs are conserved among the Mexican sequences, substantial diversity was seen in some APOBEC binding sites, the nuclear localization inhibitory signal, and the CBFβ interaction sites.

  16. Sequencing of Gag/Env association with HIV genotyping resolution and HIV-related epidemiologic studies of HIV in China.

    PubMed

    Ren, L; Wang, H W; Xu, Y; Feng, Y; Zhang, H F; Wang, K H

    2016-10-24

    HIV genotyping has led to conflicting results between laboratories. Therefore, identifying the most accurate gene combinations to sequence remains a priority. Datasets of Chinese HIV subtypes based on several markers and deposited in PubMed, Metstr, CNKI, and VIP databases between 2000 and 2015 were studied. In total, 9177 cases of amplification-positive samples from 26 provinces of China were collected and used to classify HIV subtypes based on eight individual genes or a combination thereof. CRF01_AE, CRF07_BC, CRF08_BC and B were the prevalent HIV subtypes in China, accounting for 84.07% of all genotypes. Gag/Env sequencing classified a greater number of HIV subtypes compared to other genes or combination of gene fragments. The geographical distribution of Gag and Gag/Env genotypes was similar to that observed with all genetic markers. Further principal component analysis showed a significantly different geographical distribution pattern of HIV in China for HIV genotypes detected with Gag/Env, which was in line with the distribution of all HIV genotypes in China. Gag/Env sequences had the highest diversity of the eight markers studied, followed by Gag and Gag/Pol/Env; Pol/Env polymorphisms were the least divergent. Gag/Env can serve as a high-resolution marker for HIV genotyping.

  17. Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals

    PubMed Central

    Hoehn, Kenneth B.; Gall, Astrid; Bashford-Rogers, Rachael; Fidler, S. J.; Kaye, S.; Weber, J. N.; McClure, M. O.; Kellam, Paul; Pybus, Oliver G.

    2015-01-01

    Advances in immunoglobulin (Ig) sequencing technology are leading to new perspectives on immune system dynamics. Much research in this nascent field has focused on resolving immune responses to viral infection. However, the dynamics of B-cell diversity in early HIV infection, and in response to anti-retroviral therapy, are still poorly understood. Here, we investigate these dynamics through bulk Ig sequencing of samples collected over 2 years from a group of eight HIV-1 infected patients, five of whom received anti-retroviral therapy during the first half of the study period. We applied previously published methods for visualizing and quantifying B-cell sequence diversity, including the Gini index, and compared their efficacy to alternative measures. While we found significantly greater clonal structure in HIV-infected patients versus healthy controls, within HIV patients, we observed no significant relationships between statistics of B-cell clonal expansion and clinical variables such as viral load and CD4+ count. Although there are many potential explanations for this, we suggest that important factors include poor sampling resolution and complex B-cell dynamics that are difficult to summarize using simple summary statistics. Importantly, we find a significant association between observed Gini indices and sequencing read depth, and we conclude that more robust analytical methods and a closer integration of experimental and theoretical work is needed to further our understanding of B-cell repertoire diversity during viral infection. PMID:26194755

  18. An Evaluation of Phylogenetic Methods for Reconstructing Transmitted HIV Variants using Longitudinal Clonal HIV Sequence Data

    PubMed Central

    McCloskey, Rosemary M.; Liang, Richard H.; Harrigan, P. Richard; Brumme, Zabrina L.

    2014-01-01

    ABSTRACT A population of human immunodeficiency virus (HIV) within a host often descends from a single transmitted/founder virus. The high mutation rate of HIV, coupled with long delays between infection and diagnosis, make isolating and characterizing this strain a challenge. In theory, ancestral reconstruction could be used to recover this strain from sequences sampled in chronic infection; however, the accuracy of phylogenetic techniques in this context is unknown. To evaluate the accuracy of these methods, we applied ancestral reconstruction to a large panel of published longitudinal clonal and/or single-genome-amplification HIV sequence data sets with at least one intrapatient sequence set sampled within 6 months of infection or seroconversion (n = 19,486 sequences, median [interquartile range] = 49 [20 to 86] sequences/set). The consensus of the earliest sequences was used as the best possible estimate of the transmitted/founder. These sequences were compared to ancestral reconstructions from sequences sampled at later time points using both phylogenetic and phylogeny-naive methods. Overall, phylogenetic methods conferred a 16% improvement in reproducing the consensus of early sequences, compared to phylogeny-naive methods. This relative advantage increased with intrapatient sequence diversity (P < 10−5) and the time elapsed between the earliest and subsequent samples (P < 10−5). However, neither approach performed well for reconstructing ancestral indel variation, especially within indel-rich regions of the HIV genome. Although further improvements are needed, our results indicate that phylogenetic methods for ancestral reconstruction significantly outperform phylogeny-naive alternatives, and we identify experimental conditions and study designs that can enhance accuracy of transmitted/founder virus reconstruction. IMPORTANCE When HIV is transmitted into a new host, most of the viruses fail to infect host cells. Consequently, an HIV infection tends to be

  19. Computer analysis of HIV epitope sequences

    SciTech Connect

    Gupta, G.; Myers, G.

    1990-01-01

    Phylogenetic tree analysis provide us with important general information regarding the extent and rate of HIV variation. Currently we are attempting to extend computer analysis and modeling to the V3 loop of the type 2 virus and its simian homologues, especially in light of the prominent role the latter will play in animal model studies. Moreover, it might be possible to attack the slightly similar V4 loop by this approach. However, the strategy relies very heavily upon natural'' information and constraints, thus there exist severe limitations upon the general applicability, in addition to uncertainties with regard to long-range residue interactions. 5 refs., 3 figs.

  20. HIV-1 low copy viral sequencing-A prototype assay.

    PubMed

    Mellberg, Tomas; Krabbe, Jon; Gisslén, Magnus; Svennerholm, Bo

    2016-01-01

    In HIV-1 patients with low viral burden, sequencing is often problematic, yet important. This study presents a sensitive, sub-type independent system for sequencing of low level viremia. Sequencing data from 32 HIV-1 infected patients with low level viremia were collected longitudinally. A combination of ViroSeq® HIV-1 Genotyping System and an in-house nesting protocol was used. Eight sub-types were represented. The success-rate of amplification of both PR and RT in the same sample was 100% in samples with viral loads above 100 copies/ml. Below 100 copies/ml, this study managed to amplify both regions in 7/13 (54%) samples. The assays were able to amplify either PR or RT in all sub-types included but one sub-type A specimen. In conclusion, this study presents a promising, simple assay to increase the ability to perform HIV-1 resistance testing at low level viremia. This is a prototype assay and the method needs further testing to evaluate clinical performance.

  1. Sequence determinants of breakpoint location during HIV-1 intersubtype recombination.

    PubMed

    Baird, Heather A; Galetto, Román; Gao, Yong; Simon-Loriere, Etienne; Abreha, Measho; Archer, John; Fan, Jun; Robertson, David L; Arts, Eric J; Negroni, Matteo

    2006-01-01

    Retroviral recombination results from strand switching, during reverse transcription, between the two copies of genomic RNA present in the virus. We analysed recombination in part of the envelope gene, between HIV-1 subtype A and D strains. After a single infection cycle, breakpoints clustered in regions corresponding to the constant portions of Env. With some exceptions, a similar distribution was observed after multiple infection cycles, and among recombinant sequences in the HIV Sequence Database. We compared the experimental data with computer simulations made using a program that only allows recombination to occur whenever an identical base is present in the aligned parental RNAs. Experimental recombination was more frequent than expected on the basis of simulated recombination when, in a region spanning 40 nt from the 5' border of a breakpoint, no more than two discordant bases between the parental RNAs were present. When these requirements were not fulfilled, breakpoints were distributed randomly along the RNA, closer to the distribution predicted by computer simulation. A significant preference for recombination was also observed for regions containing homopolymeric stretches. These results define, for the first time, local sequence determinants for recombination between divergent HIV-1 isolates.

  2. Sequence determinants of breakpoint location during HIV-1 intersubtype recombination

    PubMed Central

    Baird, Heather A.; Galetto, Román; Gao, Yong; Simon-Loriere, Etienne; Abreha, Measho; Archer, John; Fan, Jun; Robertson, David L.; Arts, Eric J.; Negroni, Matteo

    2006-01-01

    Retroviral recombination results from strand switching, during reverse transcription, between the two copies of genomic RNA present in the virus. We analysed recombination in part of the envelope gene, between HIV-1 subtype A and D strains. After a single infection cycle, breakpoints clustered in regions corresponding to the constant portions of Env. With some exceptions, a similar distribution was observed after multiple infection cycles, and among recombinant sequences in the HIV Sequence Database. We compared the experimental data with computer simulations made using a program that only allows recombination to occur whenever an identical base is present in the aligned parental RNAs. Experimental recombination was more frequent than expected on the basis of simulated recombination when, in a region spanning 40 nt from the 5′ border of a breakpoint, no more than two discordant bases between the parental RNAs were present. When these requirements were not fulfilled, breakpoints were distributed randomly along the RNA, closer to the distribution predicted by computer simulation. A significant preference for recombination was also observed for regions containing homopolymeric stretches. These results define, for the first time, local sequence determinants for recombination between divergent HIV-1 isolates. PMID:17003055

  3. [HIV-1 subtype distribution determined by phylogenetic analysis of pol gene sequences and automated subtyping tools among HIV-1 isolates from the Aegian Region of Turkey].

    PubMed

    Uluer Biçeroğlu, Servet; Altuğlu, Imre; Nazli Zeka, Arzu; Gökengin, Deniz; Yazan Sertöz, Rüçhan

    2014-07-01

    Human immunodeficiency virus (HIV) exhibiting remarkable genetic variability, includes two genotypes namely HIV-1 (group M, N, O and P) and HIV-2 (group A-H). HIV-1 group M, which is mainly the cause of the AIDS pandemic, is divided into nine pure subtypes, more than 45 circulating recombinant forms (CRF) and numerous unique recombinant forms (URF). According to the documents of Turkish Government of Health, among a total of 6802 HIV-positive cases, 1096 of them were defined as AIDS as of June 2013 in Turkey. Although subtype B is the predominant subtype, recent studies indicate higher proportion of CRFs similar to their increasing role in the HIV pandemic. The aim of this study was to determine the subtype distribution of HIV-1 strains isolated from 70 patients (61 male, 9 female; age range: 16-73 yrs, mean age: 39.6 yrs) who presented to our institution between April 2008-June 2013. HIV-1 strains were subtyped by phylogenetic analysis of the pol gene region and commonly used automated subtyping tools namely, Stanford HIV db v6.2.0 and Rega v3.0. Pol sequences retrieved from the Los Alamos database and from GeneBank, were trimmed from full-length genomes. Phylogenetic analysis of the 1302 base pair of the pol gene region was performed using Mega v5.2 software. The sequences were aligned using Muscle and phylogenetic distances between sequences were estimated by using Kimura two-parameter model (transition/transversion ratio: 2.0). Tree topology was obtained using neighbour-joining method and bootstrap value was set at 1000. Sixty-one (87.1%) patients were antiretroviral treatment (ART)-naive and nine were on different ART regimens. The subtypes of the isolates according to phylogenetic analysis were found as follows; 31 (44.2%) subtype B, 24 (34.2%) CRF42_BF, 6 (8.5%) B/CRF02_AG recombinants, 5 (7.1%) sub-subtype A1, 1 (1.4%) sub-subtype F1, 1 (%1.4) CRF 25_cpx, 1 (1.4%) CRF02_AG and 1 (1.4%) CRF01_AE. Rega v3.0 subtyping tool produced five discrepant results (4 B

  4. HIV-1 quasispecies delineation by tag linkage deep sequencing.

    PubMed

    Wu, Nicholas C; De La Cruz, Justin; Al-Mawsawi, Laith Q; Olson, C Anders; Qi, Hangfei; Luan, Harding H; Nguyen, Nguyen; Du, Yushen; Le, Shuai; Wu, Ting-Ting; Li, Xinmin; Lewis, Martha J; Yang, Otto O; Sun, Ren

    2014-01-01

    Trade-offs between throughput, read length, and error rates in high-throughput sequencing limit certain applications such as monitoring viral quasispecies. Here, we describe a molecular-based tag linkage method that allows assemblage of short sequence reads into long DNA fragments. It enables haplotype phasing with high accuracy and sensitivity to interrogate individual viral sequences in a quasispecies. This approach is demonstrated to deduce ∼ 2000 unique 1.3 kb viral sequences from HIV-1 quasispecies in vivo and after passaging ex vivo with a detection limit of ∼ 0.005% to ∼ 0.001%. Reproducibility of the method is validated quantitatively and qualitatively by a technical replicate. This approach can improve monitoring of the genetic architecture and evolution dynamics in any quasispecies population.

  5. Proviruses with identical sequences comprise a large fraction of the replication-competent HIV reservoir

    PubMed Central

    Sobolewski, Michele D.; Keele, Brandon F.; Spindler, Jonathan; Wiegand, Ann; Shao, Wei; Hughes, Stephen H.; Coffin, John M.; Kearney, Mary F.; Mellors, John W.

    2017-01-01

    The major obstacle to curing HIV infection is the persistence of cells with intact proviruses that can produce replication-competent virus. This HIV reservoir is believed to exist primarily in CD4+ T-cells and is stable despite years of suppressive antiretroviral therapy. A potential mechanism for HIV persistence is clonal expansion of infected cells, but how often such clones carry replication-competent proviruses has been controversial. Here, we used single-genome sequencing to probe for identical HIV sequence matches among viruses recovered in different viral outgrowth cultures and between the sequences of outgrowth viruses and proviral or intracellular HIV RNA sequences in uncultured blood mononuclear cells from eight donors on suppressive ART with diverse proviral populations. All eight donors had viral outgrowth virus that was fully susceptible to their current ART drug regimen. Six of eight donors studied had identical near full-length HIV RNA sequences recovered from different viral outgrowth cultures, and one of the two remaining donors had identical partial viral sequence matches between outgrowth virus and intracellular HIV RNA. These findings provide evidence that clonal expansion of HIV-infected cells is an important mechanism of reservoir persistence that should be targeted to cure HIV infection. PMID:28328934

  6. Proviruses with identical sequences comprise a large fraction of the replication-competent HIV reservoir.

    PubMed

    Bui, John K; Sobolewski, Michele D; Keele, Brandon F; Spindler, Jonathan; Musick, Andrew; Wiegand, Ann; Luke, Brian T; Shao, Wei; Hughes, Stephen H; Coffin, John M; Kearney, Mary F; Mellors, John W

    2017-03-01

    The major obstacle to curing HIV infection is the persistence of cells with intact proviruses that can produce replication-competent virus. This HIV reservoir is believed to exist primarily in CD4+ T-cells and is stable despite years of suppressive antiretroviral therapy. A potential mechanism for HIV persistence is clonal expansion of infected cells, but how often such clones carry replication-competent proviruses has been controversial. Here, we used single-genome sequencing to probe for identical HIV sequence matches among viruses recovered in different viral outgrowth cultures and between the sequences of outgrowth viruses and proviral or intracellular HIV RNA sequences in uncultured blood mononuclear cells from eight donors on suppressive ART with diverse proviral populations. All eight donors had viral outgrowth virus that was fully susceptible to their current ART drug regimen. Six of eight donors studied had identical near full-length HIV RNA sequences recovered from different viral outgrowth cultures, and one of the two remaining donors had identical partial viral sequence matches between outgrowth virus and intracellular HIV RNA. These findings provide evidence that clonal expansion of HIV-infected cells is an important mechanism of reservoir persistence that should be targeted to cure HIV infection.

  7. HIV type 1 group M subtype G in Cameroon: five genome sequences.

    PubMed

    Yamaguchi, Julie; Ndembi, Nicaise; Ngansop, Charlotte; Mbanya, Dora; Kaptué, Lazare; Gürtler, Lutz G; Devare, Sushil G; Brennan, Catherine A

    2009-04-01

    Near full-length viral genome sequences were obtained for five putative subtype G candidates identified in HIV-infected Cameroonian blood donors, based on partial genome sequences for the gag, pol, and env regions. Phylogenetic analysis of the genome sequences shows that all five strains are pure subtype G with no indication of intersubtype recombination. The Cameroon subtype G sequences did not form a geographically based subcluster and were intermixed within the subtype G branch with isolates from several different countries. HIV-1 group M subtype G accounts for only 4.5% of HIV infections in Cameroon. However, genome segments of subtype G are present in 67% of all infections and 80% of infections due to intersubtype recombinant strains in Cameroon. The addition of five subtype G genome sequences to the HIV database may contribute to a better understanding of the origins and classification of HIV-1 subtypes and CRFs.

  8. Performance characteristics of the TRUGENE HIV-1 Genotyping Kit and the Opengene DNA Sequencing System.

    PubMed

    Kuritzkes, Daniel R; Grant, Robert M; Feorino, Paul; Griswold, Marshal; Hoover, Marie; Young, Russell; Day, Stephen; Lloyd Jr, Robert M; Reid, Caroline; Morgan, Gillian F; Winslow, Dean L

    2003-04-01

    The TRUGENE HIV-1 Genotyping Kit and OpenGene DNA Sequencing System are designed to sequence the protease (PR)- and reverse transcriptase (RT)-coding regions of human immunodeficiency virus type 1 (HIV-1) pol. Studies were undertaken to determine the accuracy of this assay system in detecting resistance-associated mutations and to determine the effects of RNA extraction methods, anticoagulants, specimen handling, and potentially interfering substances. Samples were plasma obtained from HIV-infected subjects or seronegative plasma to which viruses derived from wild-type and mutant infectious molecular clones (IMC) of HIV-1 were added. Extraction methods tested included standard and UltraSensitive AMPLICOR HIV-1 MONITOR, QIAGEN viral RNA extraction mini kit, and QIAGEN Ultra HIV extraction kit, and NASBA manual HIV-1 quantitative NucliSens. Sequence data from test sites were compared to a "gold standard" reference sequence to determine the percent agreement. Comparisons between test and reference sequences at the nucleotide level showed 97.5 to 100% agreement. Similar results were obtained regardless of extraction method, regardless of use of EDTA or acid citrate dextrose as anticoagulant, and despite the presence of triglycerides, bilirubin, hemoglobin, antiretroviral drugs, HIV-2, hepatitis C virus (HCV), HBV, cytomegalovirus, human T-cell leukemia virus type 1 (HTLV-1), or HTLV-2. Samples with HIV-1 RNA titers of >or=1,000 copies/ml gave consistent results. The TRUGENE HIV-1 Genotyping Kit and OpenGene DNA Sequencing System consistently generate highly accurate sequence data when tested with IMC-derived HIV and patient samples.

  9. Quantifying Next Generation Sequencing Sample Pre-Processing Bias in HIV-1 Complete Genome Sequencing.

    PubMed

    Vrancken, Bram; Trovão, Nídia Sequeira; Baele, Guy; van Wijngaerden, Eric; Vandamme, Anne-Mieke; van Laethem, Kristel; Lemey, Philippe

    2016-01-07

    Genetic analyses play a central role in infectious disease research. Massively parallelized "mechanical cloning" and sequencing technologies were quickly adopted by HIV researchers in order to broaden the understanding of the clinical importance of minor drug-resistant variants. These efforts have, however, remained largely limited to small genomic regions. The growing need to monitor multiple genome regions for drug resistance testing, as well as the obvious benefit for studying evolutionary and epidemic processes makes complete genome sequencing an important goal in viral research. In addition, a major drawback for NGS applications to RNA viruses is the need for large quantities of input DNA. Here, we use a generic overlapping amplicon-based near full-genome amplification protocol to compare low-input enzymatic fragmentation (Nextera™) with conventional mechanical shearing for Roche 454 sequencing. We find that the fragmentation method has only a modest impact on the characterization of the population composition and that for reliable results, the variation introduced at all steps of the procedure--from nucleic acid extraction to sequencing--should be taken into account, a finding that is also relevant for NGS technologies that are now more commonly used. Furthermore, by applying our protocol to deep sequence a number of pre-therapy plasma and PBMC samples, we illustrate the potential benefits of a near complete genome sequencing approach in routine genotyping.

  10. Importance of Viral Sequence Length and Number of Variable and Informative Sites in Analysis of HIV Clustering.

    PubMed

    Novitsky, Vlad; Moyo, Sikhulile; Lei, Quanhong; DeGruttola, Victor; Essex, M

    2015-05-01

    To improve the methodology of HIV cluster analysis, we addressed how analysis of HIV clustering is associated with parameters that can affect the outcome of viral clustering. The extent of HIV clustering and tree certainty was compared between 401 HIV-1C near full-length genome sequences and subgenomic regions retrieved from the LANL HIV Database. Sliding window analysis was based on 99 windows of 1,000 bp and 45 windows of 2,000 bp. Potential associations between the extent of HIV clustering and sequence length and the number of variable and informative sites were evaluated. The near full-length genome HIV sequences showed the highest extent of HIV clustering and the highest tree certainty. At the bootstrap threshold of 0.80 in maximum likelihood (ML) analysis, 58.9% of near full-length HIV-1C sequences but only 15.5% of partial pol sequences (ViroSeq) were found in clusters. Among HIV-1 structural genes, pol showed the highest extent of clustering (38.9% at a bootstrap threshold of 0.80), although it was significantly lower than in the near full-length genome sequences. The extent of HIV clustering was significantly higher for sliding windows of 2,000 bp than 1,000 bp. We found a strong association between the sequence length and proportion of HIV sequences in clusters, and a moderate association between the number of variable and informative sites and the proportion of HIV sequences in clusters. In HIV cluster analysis, the extent of detectable HIV clustering is directly associated with the length of viral sequences used, as well as the number of variable and informative sites. Near full-length genome sequences could provide the most informative HIV cluster analysis. Selected subgenomic regions with a high extent of HIV clustering and high tree certainty could also be considered as a second choice.

  11. Use of four next-generation sequencing platforms to determine HIV-1 coreceptor tropism.

    PubMed

    Archer, John; Weber, Jan; Henry, Kenneth; Winner, Dane; Gibson, Richard; Lee, Lawrence; Paxinos, Ellen; Arts, Eric J; Robertson, David L; Mimms, Larry; Quiñones-Mateu, Miguel E

    2012-01-01

    HIV-1 coreceptor tropism assays are required to rule out the presence of CXCR4-tropic (non-R5) viruses prior treatment with CCR5 antagonists. Phenotypic (e.g., Trofile™, Monogram Biosciences) and genotypic (e.g., population sequencing linked to bioinformatic algorithms) assays are the most widely used. Although several next-generation sequencing (NGS) platforms are available, to date all published deep sequencing HIV-1 tropism studies have used the 454™ Life Sciences/Roche platform. In this study, HIV-1 co-receptor usage was predicted for twelve patients scheduled to start a maraviroc-based antiretroviral regimen. The V3 region of the HIV-1 env gene was sequenced using four NGS platforms: 454™, PacBio® RS (Pacific Biosciences), Illumina®, and Ion Torrent™ (Life Technologies). Cross-platform variation was evaluated, including number of reads, read length and error rates. HIV-1 tropism was inferred using Geno2Pheno, Web PSSM, and the 11/24/25 rule and compared with Trofile™ and virologic response to antiretroviral therapy. Error rates related to insertions/deletions (indels) and nucleotide substitutions introduced by the four NGS platforms were low compared to the actual HIV-1 sequence variation. Each platform detected all major virus variants within the HIV-1 population with similar frequencies. Identification of non-R5 viruses was comparable among the four platforms, with minor differences attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used), compared to Trofile (80%) and population sequencing (70%). In conclusion, all four NGS platforms were able to detect minority non-R5 variants at comparable levels suggesting that any NGS-based method can be used to predict HIV-1 coreceptor usage.

  12. Los Alamos National Laboratory.

    ERIC Educational Resources Information Center

    Hammel, Edward F., Jr.

    1982-01-01

    Current and post World War II scientific research at the Los Alamos National Laboratory (New Mexico) is discussed. The operation of the laboratory, the Los Alamos consultant program, and continuation education, and continuing education activities at the laboratory are also discussed. (JN)

  13. Universal amplification, next-generation sequencing, and assembly of HIV-1 genomes.

    PubMed

    Gall, Astrid; Ferns, Bridget; Morris, Clare; Watson, Simon; Cotten, Matthew; Robinson, Mark; Berry, Neil; Pillay, Deenan; Kellam, Paul

    2012-12-01

    Whole HIV-1 genome sequences are pivotal for large-scale studies of inter- and intrahost evolution, including the acquisition of drug resistance mutations. The ability to rapidly and cost-effectively generate large numbers of HIV-1 genome sequences from different populations and geographical locations and determine the effect of minority genetic variants is, however, a limiting factor. Next-generation sequencing promises to bridge this gap but is hindered by the lack of methods for the enrichment of virus genomes across the phylogenetic breadth of HIV-1 and methods for the robust assembly of the virus genomes from short-read data. Here we report a method for the amplification, next-generation sequencing, and unbiased de novo assembly of HIV-1 genomes of groups M, N, and O, as well as recombinants, that does not require prior knowledge of the sequence or subtype. A sensitivity of at least 3,000 copies/ml was determined by using plasma virus samples of known copy numbers. We applied our novel method to compare the genome diversities of HIV-1 groups, subtypes, and genes. The highest level of diversity was found in the env, nef, vpr, tat, and rev genes and parts of the gag gene. Furthermore, we used our method to investigate mutations associated with HIV-1 drug resistance in clinical samples at the level of the complete genome. Drug resistance mutations were detected as both major variant and minor species. In conclusion, we demonstrate the feasibility of our method for large-scale HIV-1 genome sequencing. This will enable the phylogenetic and phylodynamic resolution of the ongoing pandemic and efficient monitoring of complex HIV-1 drug resistance genotypes.

  14. Compromised fronto-striatal functioning in HIV: an fMRI investigation of semantic event sequencing.

    PubMed

    Melrose, Rebecca J; Tinaz, Sule; Castelo, J Mimi Boer; Courtney, Maureen G; Stern, Chantal E

    2008-04-09

    The human immunodeficiency virus (HIV) damages fronto-striatal regions, and is associated with deficits in executive functioning. We recently developed a semantic event sequencing task based on the Picture Arrangement subtest of the Wechsler Adult Intelligence Scale-III for use with functional magnetic resonance imaging (fMRI) and found recruitment of dorsolateral prefrontal cortex and basal ganglia in healthy participants. To assess the impact of HIV on the functioning of the basal ganglia and prefrontal cortex, we administered this task to 11 HIV+ and 11 Control participants matched for age and education. Neuropsychological evaluation demonstrated that the HIV+ group had mild impairment in memory retrieval and motor functioning, but was not demented. Morphometric measurements suggested no atrophy in basal ganglia regions. The results of the fMRI analysis revealed hypoactivation of the left caudate, left dorsolateral prefrontal cortex, and bilateral ventral prefrontal cortex in the HIV+ group. Functional connectivity analysis demonstrated less functional connectivity between the caudate and prefrontal cortex and basal ganglia regions in the HIV+ group. In contrast, the HIV+ group demonstrated increased activation of right postcentral/supramarginal gyrus, and greater connectivity between the caudate and this same anterior parietal region. The results of this study extend previous investigations by demonstrating compromised function of the caudate and connected prefrontal regions in HIV during cognition. This disruption of fronto-striatal circuitry likely precedes the development of cognitive impairment in HIV.

  15. Stockpile Stewardship: Los Alamos

    ScienceCinema

    McMillan, Charlie; Morgan, Nathanial; Goorley, Tom; Merrill, Frank; Funk, Dave; Korzekwa, Deniece; Laintz, Ken

    2016-07-12

    "Heritage of Science" is a short video that highlights the Stockpile Stewardship program at Los Alamos National Laboratory. Stockpile Stewardship was conceived in the early 1990s as a national science-based program that could assure the safety, security, and effectiveness of the U.S. nuclear deterrent without the need for full-scale underground nuclear testing. This video was produced by Los Alamos National Laboratory for screening at the Lab's Bradbury Science Museum in Los Alamos, NM and is narrated by science correspondent Miles O'Brien.

  16. Translating HIV sequences into quantitative fitness landscapes predicts viral vulnerabilities for rational immunogen design.

    PubMed

    Ferguson, Andrew L; Mann, Jaclyn K; Omarjee, Saleha; Ndung'u, Thumbi; Walker, Bruce D; Chakraborty, Arup K

    2013-03-21

    A prophylactic or therapeutic vaccine offers the best hope to curb the HIV-AIDS epidemic gripping sub-Saharan Africa, but it remains elusive. A major challenge is the extreme viral sequence variability among strains. Systematic means to guide immunogen design for highly variable pathogens like HIV are not available. Using computational models, we have developed an approach to translate available viral sequence data into quantitative landscapes of viral fitness as a function of the amino acid sequences of its constituent proteins. Predictions emerging from our computationally defined landscapes for the proteins of HIV-1 clade B Gag were positively tested against new in vitro fitness measurements and were consistent with previously defined in vitro measurements and clinical observations. These landscapes chart the peaks and valleys of viral fitness as protein sequences change and inform the design of immunogens and therapies that can target regions of the virus most vulnerable to selection pressure.

  17. Translating HIV sequences into quantitative fitness landscapes predicts viral vulnerabilities for rational immunogen design

    PubMed Central

    Ferguson, Andrew L.; Mann, Jaclyn K.; Omarjee, Saleha; Ndung’u, Thumbi; Walker, Bruce D.; Chakraborty, Arup K.

    2013-01-01

    Summary A prophylactic or therapeutic vaccine offers the best hope to curb the HIV-AIDS epidemic gripping sub-Saharan Africa, but remains elusive. A major challenge is the extreme viral sequence variability among strains. Systematic means to guide immunogen design for highly variable pathogens like HIV are not available. Using computational models, we have developed an approach to translate available viral sequence data into quantitative landscapes of viral fitness as a function of the amino acid sequences of its constituent proteins. Predictions emerging from our computationally defined landscapes for the proteins of HIV-1 clade B Gag were positively tested against new in vitro fitness measurements, and were consistent with previously defined in vitro measurements and clinical observations. These landscapes chart the peaks and valleys of viral fitness as protein sequences change, and inform the design of immunogens and therapies that can target regions of the virus most vulnerable to selection pressure. PMID:23521886

  18. Reconstructing the Dynamics of HIV Evolution within Hosts from Serial Deep Sequence Data

    PubMed Central

    Poon, Art F. Y.; Swenson, Luke C.; Bunnik, Evelien M.; Edo-Matas, Diana; Schuitemaker, Hanneke; van 't Wout, Angélique B.; Harrigan, P. Richard

    2012-01-01

    At the early stage of infection, human immunodeficiency virus (HIV)-1 predominantly uses the CCR5 coreceptor for host cell entry. The subsequent emergence of HIV variants that use the CXCR4 coreceptor in roughly half of all infections is associated with an accelerated decline of CD4+ T-cells and rate of progression to AIDS. The presence of a ‘fitness valley’ separating CCR5- and CXCR4-using genotypes is postulated to be a biological determinant of whether the HIV coreceptor switch occurs. Using phylogenetic methods to reconstruct the evolutionary dynamics of HIV within hosts enables us to discriminate between competing models of this process. We have developed a phylogenetic pipeline for the molecular clock analysis, ancestral reconstruction, and visualization of deep sequence data. These data were generated by next-generation sequencing of HIV RNA extracted from longitudinal serum samples (median 7 time points) from 8 untreated subjects with chronic HIV infections (Amsterdam Cohort Studies on HIV-1 infection and AIDS). We used the known dates of sampling to directly estimate rates of evolution and to map ancestral mutations to a reconstructed timeline in units of days. HIV coreceptor usage was predicted from reconstructed ancestral sequences using the geno2pheno algorithm. We determined that the first mutations contributing to CXCR4 use emerged about 16 (per subject range 4 to 30) months before the earliest predicted CXCR4-using ancestor, which preceded the first positive cell-based assay of CXCR4 usage by 10 (range 5 to 25) months. CXCR4 usage arose in multiple lineages within 5 of 8 subjects, and ancestral lineages following alternate mutational pathways before going extinct were common. We observed highly patient-specific distributions and time-scales of mutation accumulation, implying that the role of a fitness valley is contingent on the genotype of the transmitted variant. PMID:23133358

  19. Spin models inferred from patient-derived viral sequence data faithfully describe HIV fitness landscapes

    NASA Astrophysics Data System (ADS)

    Shekhar, Karthik; Ruberman, Claire F.; Ferguson, Andrew L.; Barton, John P.; Kardar, Mehran; Chakraborty, Arup K.

    2013-12-01

    Mutational escape from vaccine-induced immune responses has thwarted the development of a successful vaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus' fitness as a function of its proteomic sequence can enable rational design of potent vaccines, as this information can focus vaccine-induced immune responses to target mutational vulnerabilities of the virus. Spin models have been proposed as a means to infer intrinsic fitness landscapes of HIV proteins from patient-derived viral protein sequences. These sequences are the product of nonequilibrium viral evolution driven by patient-specific immune responses and are subject to phylogenetic constraints. How can such sequence data allow inference of intrinsic fitness landscapes? We combined computer simulations and variational theory á la Feynman to show that, in most circumstances, spin models inferred from patient-derived viral sequences reflect the correct rank order of the fitness of mutant viral strains. Our findings are relevant for diverse viruses.

  20. Los Alamos offers Fellowships

    NASA Astrophysics Data System (ADS)

    Los Alamos National Laboratory in New Mexico is calling for applications for postdoctoral appointments and research fellowships. The positions are available in geoscience as well as other scientific disciplines.The laboratory, which is operated by the University of California for the Department of Energy, awards J. Robert Oppenheimer Research Fellowships to scientists that either have or will soon complete doctoral degrees. The appointments are for two years, are renewable for a third year, and carry a stipend of $51,865 per year. Potential applicants should send a resume or employment application and a statement of research goals to Carol M. Rich, Div. 89, Human Resources Development Division, MS P290, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 by mid-November.

  1. Inference of global HIV-1 sequence patterns and preliminary feature analysis.

    PubMed

    Wang, Yan; Rawi, Reda; Hoffmann, Daniel; Sun, Binlian; Yang, Rongge

    2013-08-01

    The epidemiology of HIV-1 varies in different areas of the world, and it is possible that this complexity may leave unique footprints in the viral genome. Thus, we attempted to find significant patterns in global HIV-1 genome sequences. By applying the rule inference algorithm RIPPER (Repeated Incremental Pruning to Produce Error Reduction) to multiple sequence alignments of Env sequences from four classes of compiled datasets, we generated four sets of signature patterns. We found that these patterns were able to distinguish southeastern Asian from nonsoutheastern Asian sequences with 97.5% accuracy, Chinese from non-Chinese sequences with 98.3% accuracy, African from non-African sequences with 88.4% accuracy, and southern African from non-southern African sequences with 91.2% accuracy. These patterns showed different associations with subtypes and with amino acid positions. In addition, some signature patterns were characteristic of the geographic area from which the sample was taken. Amino acid features corresponding to the phylogenetic clustering of HIV-1 sequences were consistent with some of the deduced patterns. Using a combination of patterns inferred from subtypes B, C, and all subtypes chimeric with CRF01_AE worldwide, we found that signature patterns of subtype C were extremely common in some sampled countries (for example, Zambia in southern Africa), which may hint at the origin of this HIV-1 subtype and the need to pay special attention to this area of Africa. Signature patterns of subtype B sequences were associated with different countries. Even more, there are distinct patterns at single position 21 with glycine, leucine and isoleucine corresponding to subtype C, B and all possible recombination forms chimeric with CRF01_AE, which also indicate distinct geographic features. Our method widens the scope of inference of signature from geographic, genetic, and genomic viewpoints. These findings may provide a valuable reference for epidemiological

  2. Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for global HIV-1 vaccine development

    DOE PAGES

    Stephenson, Kathryn E.; Neubauer, George H.; Reimer, Ulf; ...

    2014-11-14

    An effective vaccine against human immunodeficiency virus type 1 (HIV-1) will have to provide protection against a vast array of different HIV-1 strains. Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. Here we describe the development of a global HIV-1 peptide microarray that contains 6564 peptides from across the HIV-1 proteome and covers the majority of HIV-1 sequences in the Los Alamos National Laboratory global HIV-1 sequence database. Using this microarray, we quantified the magnitude, breadth, and depth ofmore » IgG binding to linear HIV-1 sequences in HIV-1-infected humans and HIV-1-vaccinated humans, rhesus monkeys and guinea pigs. The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. Our data suggest that the global HIV-1 peptide microarray may be a useful tool for both preclinical and clinical HIV-1 research.« less

  3. Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for global HIV-1 vaccine development

    SciTech Connect

    Stephenson, Kathryn E.; Neubauer, George H.; Reimer, Ulf; Pawlowski, Nikolaus; Knaute, Tobias; Zerweck, Johannes; Korber, Bette T.; Barouch, Dan H.

    2014-11-14

    An effective vaccine against human immunodeficiency virus type 1 (HIV-1) will have to provide protection against a vast array of different HIV-1 strains. Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. Here we describe the development of a global HIV-1 peptide microarray that contains 6564 peptides from across the HIV-1 proteome and covers the majority of HIV-1 sequences in the Los Alamos National Laboratory global HIV-1 sequence database. Using this microarray, we quantified the magnitude, breadth, and depth of IgG binding to linear HIV-1 sequences in HIV-1-infected humans and HIV-1-vaccinated humans, rhesus monkeys and guinea pigs. The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. Our data suggest that the global HIV-1 peptide microarray may be a useful tool for both preclinical and clinical HIV-1 research.

  4. The Los Alamos primer

    SciTech Connect

    Serber, R.

    1992-01-01

    This book contains the 1943 lecture notes of Robert Serber. Serber was a protege of J. Robert Oppenheimer and member of the team that built the first atomic bomb - reveal what the Los Alamos scientists knew, and did not know, about the terrifying weapon they were building.

  5. Modification of FP-HIV activity by peptide sequences of GB virus C: a biophysical approach.

    PubMed

    Domènech, O; Ortiz, A; Pujol, M; Haro, I; Muñoz, M; Alsina, M A; Prat, J; Busquets, M A; Girona, V

    2014-05-01

    Three synthetic peptide sequences of 18 amino acid each, corresponding to different fragments of the E2 capsid protein of GB virus C (GBV-C): SDRDTVVELSEWGVPCAT (P45), GSVRFPFHRCGAGPKLTK (P58) and RFPFHRCGAGPKLTKDLE (P59) have been characterized in order to find a relationship between their physicochemical properties and the results obtained in cellular models. Experiments were performed in presence and absence of the HIV fusion peptide (FP-HIV) due to the evidences that GBV-C inhibits AIDS progression. P45 peptide showed lower surface activity and less extent of penetration into 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) (3:2, mol/mol) lipid monolayers than P58 and P59. However, P45 peptide presented higher capacity to inhibit FP-HIV induced cell-cell fusion than the other two sequences. These results were supported by fluorescence anisotropy measurements which indicated that P45 had a significant effect on the inhibition of FP-HIV perturbation of liposomes of the same lipid composition. Finally, atomic force microscopy (AFM) studies have evidenced the modification of the changes induced by the FP-HIV in the morphology of lipid bilayers when P45 was present in the medium.

  6. Genome-Wide Association Study of HIV Whole Genome Sequences Validated using Drug Resistance

    PubMed Central

    Power, Robert A.; Davaniah, Siva; Derache, Anne; Wilkinson, Eduan; Tanser, Frank; Pillay, Deenan; de Oliveira, Tulio

    2016-01-01

    Background Genome-wide association studies (GWAS) have considerably advanced our understanding of human traits and diseases. With the increasing availability of whole genome sequences (WGS) for pathogens, it is important to establish whether GWAS of viral genomes could reveal important biological insights. Here we perform the first proof of concept viral GWAS examining drug resistance (DR), a phenotype with well understood genetics. Method We performed a GWAS of DR in a sample of 343 HIV subtype C patients failing 1st line antiretroviral treatment in rural KwaZulu-Natal, South Africa. The majority and minority variants within each sequence were called using PILON, and GWAS was performed within PLINK. HIV WGS from patients failing on different antiretroviral treatments were compared to sequences derived from individuals naïve to the respective treatment. Results GWAS methodology was validated by identifying five associations on a genetic level that led to amino acid changes known to cause DR. Further, we highlighted the ability of GWAS to identify epistatic effects, identifying two replicable variants within amino acid 68 of the reverse transcriptase protein previously described as potential fitness compensatory mutations. A possible additional DR variant within amino acid 91 of the matrix region of the Gag protein was associated with tenofovir failure, highlighting GWAS’s ability to identify variants outside classical candidate genes. Our results also suggest a polygenic component to DR. Conclusions These results validate the applicability of GWAS to HIV WGS data even in relative small samples, and emphasise how high throughput sequencing can provide novel and clinically relevant insights. Further they suggested that for viruses like HIV, population structure was only minor concern compared to that seen in bacteria or parasite GWAS. Given the small genome length and reduced burden for multiple testing, this makes HIV an ideal candidate for GWAS. PMID:27677172

  7. Knowledge discovery in RNA sequence families of HIV using scalable computers

    SciTech Connect

    Hofacker, I.L.; Huynen, M.A.; Stadler, P.F.; Stolorz, P.E.

    1996-12-31

    The prediction of RNA secondary structure on the basis of sequence information is an important tool in biosequence analysis. However, it has typically been restricted to molecules containing no more than 4000 nucleotides due to the computational complexity of the underlying dynamic programming algorithm used. We describe here an approach to RNA sequence analysis based upon scalable computers, which enables molecules containing up to 20,000 nucleotides to be analyzed. We apply the approach to investigation of the entire HIV genome, illustrating the power of these methods to perform knowledge discovery by identification of important secondary structure motifs within RNA sequence families.

  8. Evaluation of GS Junior and MiSeq next-generation sequencing technologies as an alternative to Trugene population sequencing in the clinical HIV laboratory.

    PubMed

    Ram, Daniela; Leshkowitz, Dena; Gonzalez, Dimitri; Forer, Relly; Levy, Itzchak; Chowers, Michal; Lorber, Margalit; Hindiyeh, Musa; Mendelson, Ella; Mor, Orna

    2015-02-01

    Population HIV-1 sequencing is currently the method of choice for the identification and follow-up of HIV-1 antiretroviral drug resistance. It has limited sensitivity and results in a consensus sequence showing the most prevalent nucleotide per position. Moreover concomitant sequencing and interpretation of the results for several samples together is laborious and time consuming. In this study, the practical use of GS Junior and MiSeq bench-top next generation sequencing (NGS) platforms as an alternative to Trugene Sanger-based population sequencing in the clinical HIV laboratory was assessed. DeepChek(®)-HIV TherapyEdge software was used for processing all the protease and reverse transcriptase sequences and for resistance interpretation. Plasma samples from nine HIV-1 carriers, representing the major HIV-1 subtypes in Israel, were compared. The total number of amino acid substitutions identified in the nine samples by GS Junior (232 substitutions) and MiSeq (243 substitutions) was similar and higher than Trugene (181 substitutions), emphasizing the advantage of deep sequencing on population sequencing. More than 80% of the identified substitutions were identical between the GS Junior and MiSeq platforms, most of which (184 of 199) at similar frequency. Low abundance substitutions accounted for 20.9% of the MiSeq and 21.9% of the GS Junior output, the majority of which were not detected by Trugene. More drug resistance mutations were identified by both the NGS platforms, primarily, but not only, at low abundance. In conclusion, in combination with DeepChek, both GS Junior and MiSeq were found to be more sensitive than Trugene and adequate for HIV-1 resistance analysis in the clinical HIV laboratory.

  9. HIV-1 sequence variation between isolates from mother-infant transmission pairs

    SciTech Connect

    Wike, C.M.; Daniels, M.R.; Furtado, M.; Wolinsky, M.; Korber, B.; Hutto, C.; Munoz, J.; Parks, W.; Saah, A.

    1991-01-01

    To examine the sequence diversity of human immunodeficiency virus type 1 (HIV-1) between known transmission sets, sequences from the V3 and V4-V5 region of the env gene from 4 mother-infant pairs were analyzed. The mean interpatient sequence variation between isolates from linked mother-infant pairs was comparable to the sequence diversity found between isolates from other close contacts. The mean intrapatient variation was significantly less in the infants' isolates then the isolates from both their mothers and other characterized intrapatient sequence sets. In addition, a distinct and characteristic difference in the glycosylation pattern preceding the V3 loop was found between each linked transmission pair. These findings indicate that selection of specific genotypic variants, which may play a role in some direct transmission sets, and the duration of infection are important factors in the degree of diversity seen between the sequence sets.

  10. HIV-1 sequence variation between isolates from mother-infant transmission pairs

    SciTech Connect

    Wike, C.M.; Daniels, M.R.; Furtado, M.; Wolinsky, M.; Korber, B.; Hutto, C.; Munoz, J.; Parks, W.; Saah, A.

    1991-12-31

    To examine the sequence diversity of human immunodeficiency virus type 1 (HIV-1) between known transmission sets, sequences from the V3 and V4-V5 region of the env gene from 4 mother-infant pairs were analyzed. The mean interpatient sequence variation between isolates from linked mother-infant pairs was comparable to the sequence diversity found between isolates from other close contacts. The mean intrapatient variation was significantly less in the infants` isolates then the isolates from both their mothers and other characterized intrapatient sequence sets. In addition, a distinct and characteristic difference in the glycosylation pattern preceding the V3 loop was found between each linked transmission pair. These findings indicate that selection of specific genotypic variants, which may play a role in some direct transmission sets, and the duration of infection are important factors in the degree of diversity seen between the sequence sets.

  11. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing

    SciTech Connect

    Wu, Xueling; Zhou, Tongqing; Zhu, Jiang; Zhang, Baoshan; Georgiev, Ivelin; Wang, Charlene; Chen, Xuejun; Longo, Nancy S.; Louder, Mark; McKee, Krisha; O’Dell, Sijy; Perfetto, Stephen; Schmidt, Stephen D.; Shi, Wei; Wu, Lan; Yang, Yongping; Yang, Zhi-Yong; Yang, Zhongjia; Zhang, Zhenhai; Bonsignori, Mattia; Crump, John A.; Kapiga, Saidi H.; Sam, Noel E.; Haynes, Barton F.; Simek, Melissa; Burton, Dennis R.; Koff, Wayne C.; Doria-Rose, Nicole A.; Connors, Mark; Mullikin, James C.; Nabel, Gary J.; Roederer, Mario; Shapiro, Lawrence; Kwong, Peter D.; Mascola, John R.

    2013-03-04

    Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.

  12. Genetic and functional analysis of HIV-1 Rev Responsive Element (RRE) sequences from North-India

    PubMed Central

    2010-01-01

    HIV-1 Rev protein regulates the expression of HIV-1 transcripts by binding to a highly structured stem loop structure called the Rev Responsive Element (RRE) present in the genomic and partially spliced RNAs. Genetic variation in this structure is likely to affect binding of Rev protein and ultimately overall gene expression and replication. We characterized RRE sequences from 13 HIV-1 infected individuals from North India which also included two mother-child pairs following vertical transmission. We observed high degree of conservation of sequences, including the 9-nt (CACUAUGGG) long sequence in stem-loop B, required for efficient binding of Rev protein. All of our 13 RRE sequences possessed G to A (position 66) mutation located in the critical branched-stem-loop B which is not present in consensus C or B sequence. We derived a consensus RRE structure which showed interesting changes in the stem-loop structures including the stem-loop B. Mother-Child RRE sequences showed conservation of unique polymorphisms as well as some new mutations in child RRE sequences. Despite these changes, the ability to form multiple essential stem-loop structures required for Rev binding was conserved. RRE RNA derived from one of the samples, VT5, retained the ability to bind Rev protein under in vitro conditions although it showed alternate secondary structure. This is the first study from India describing the structural and possible functional implications due to very unique RRE sequence heterogeneity and its possible role in vertical transmission and gene expression. PMID:20682034

  13. Using nearly full-genome HIV sequence data improves phylogeny reconstruction in a simulated epidemic

    PubMed Central

    Yebra, Gonzalo; Hodcroft, Emma B.; Ragonnet-Cronin, Manon L.; Pillay, Deenan; Brown, Andrew J. Leigh; Fraser, Christophe; Kellam, Paul; de Oliveira, Tulio; Dennis, Ann; Hoppe, Anne; Kityo, Cissy; Frampton, Dan; Ssemwanga, Deogratius; Tanser, Frank; Keshani, Jagoda; Lingappa, Jairam; Herbeck, Joshua; Wawer, Maria; Essex, Max; Cohen, Myron S.; Paton, Nicholas; Ratmann, Oliver; Kaleebu, Pontiano; Hayes, Richard; Fidler, Sarah; Quinn, Thomas; Novitsky, Vladimir; Haywards, Andrew; Nastouli, Eleni; Morris, Steven; Clark, Duncan; Kozlakidis, Zisis

    2016-01-01

    HIV molecular epidemiology studies analyse viral pol gene sequences due to their availability, but whole genome sequencing allows to use other genes. We aimed to determine what gene(s) provide(s) the best approximation to the real phylogeny by analysing a simulated epidemic (created as part of the PANGEA_HIV project) with a known transmission tree. We sub-sampled a simulated dataset of 4662 sequences into different combinations of genes (gag-pol-env, gag-pol, gag, pol, env and partial pol) and sampling depths (100%, 60%, 20% and 5%), generating 100 replicates for each case. We built maximum-likelihood trees for each combination using RAxML (GTR + Γ), and compared their topologies to the corresponding true tree’s using CompareTree. The accuracy of the trees was significantly proportional to the length of the sequences used, with the gag-pol-env datasets showing the best performance and gag and partial pol sequences showing the worst. The lowest sampling depths (20% and 5%) greatly reduced the accuracy of tree reconstruction and showed high variability among replicates, especially when using the shortest gene datasets. In conclusion, using longer sequences derived from nearly whole genomes will improve the reliability of phylogenetic reconstruction. With low sample coverage, results can be highly variable, particularly when based on short sequences. PMID:28008945

  14. HIV-1 intrapatient sequence diversity in the immunogenic V3 region

    SciTech Connect

    Korber, B.; Myers, G. ); Wolinsky, S.; Kunstman, K.; Levy, R.; Furtado, M.; Otto, P. . Medical School); Haynes, B. . Dept. of Medicine)

    1991-11-12

    The third hypervariable domain (V3) of the human immunodeficiency virus type-1 (HIV-1) envelope protein (env) can serve as an epitope for potent type-specific neutralizing antibodies (NAbs) -- thus short peptides predicted on the most commonly found variants of the antigenic tip of the V3 loop have been considered as potential candidates for an HIV peptide vaccine. To evaluate the extent of intrapatient variation in the immunogenic crest of the V3 loop, sequence sets were analyzed from individuals for whom multiple V3 sequences were available. Several strategies for selecting the best sets of hexapeptides to represent the variable tip of the V3 loop were considered and their effectiveness was evaluated by comparing them with the sequence sets from individuals. Most individuals carried at least one, and frequently many, variants that did not match any of the sequences from among the ten most common hexapeptides. Intrapatient viral sequence variation was increased by including sequences derived from brain biopsy specimens as well as from blood. Additionally, sequences obtained from brain specimens of different individuals had common elements which were not conserved in the corresponding blood samples, suggesting that certain amino acids in the V3 loop may be requisite for viral propagation in the CNS.

  15. Los Alamos Programming Models

    SciTech Connect

    Bergen, Benjamin Karl

    2016-07-07

    This is the PDF of a powerpoint presentation from a teleconference on Los Alamos programming models. It starts by listing their assumptions for the programming models and then details a hierarchical programming model at the System Level and Node Level. Then it details how to map this to their internal nomenclature. Finally, a list is given of what they are currently doing in this regard.

  16. Sensitive Next-Generation Sequencing Method Reveals Deep Genetic Diversity of HIV-1 in the Democratic Republic of the Congo

    PubMed Central

    Wilkinson, Eduan; Vallari, Ana; McArthur, Carole; Sthreshley, Larry; Brennan, Catherine A.; Cloherty, Gavin; de Oliveira, Tulio

    2017-01-01

    ABSTRACT As the epidemiological epicenter of the human immunodeficiency virus (HIV) pandemic, the Democratic Republic of the Congo (DRC) is a reservoir of circulating HIV strains exhibiting high levels of diversity and recombination. In this study, we characterized HIV specimens collected in two rural areas of the DRC between 2001 and 2003 to identify rare strains of HIV. The env gp41 region was sequenced and characterized for 172 HIV-positive specimens. The env sequences were predominantly subtype A (43.02%), but 7 other subtypes (33.14%), 20 circulating recombinant forms (CRFs; 11.63%), and 20 unclassified (11.63%) sequences were also found. Of the rare and unclassified subtypes, 18 specimens were selected for next-generation sequencing (NGS) by a modified HIV-switching mechanism at the 5′ end of the RNA template (SMART) method to obtain full-genome sequences. NGS produced 14 new complete genomes, which included pure subtype C (n = 2), D (n = 1), F1 (n = 1), H (n = 3), and J (n = 1) genomes. The two subtype C genomes and one of the subtype H genomes branched basal to their respective subtype branches but had no evidence of recombination. The remaining 6 genomes were complex recombinants of 2 or more subtypes, including subtypes A1, F, G, H, J, and K and unclassified fragments, including one subtype CRF25 isolate, which branched basal to all CRF25 references. Notably, all recombinant subtype H fragments branched basal to the H clade. Spatial-geographical analysis indicated that the diverse sequences identified here did not expand globally. The full-genome and subgenomic sequences identified in our study population significantly increase the documented diversity of the strains involved in the continually evolving HIV-1 pandemic. IMPORTANCE Very little is known about the ancestral HIV-1 strains that founded the global pandemic, and very few complete genome sequences are available from patients in the Congo Basin, where HIV-1 expanded early in the global pandemic

  17. Sensitive Next-Generation Sequencing Method Reveals Deep Genetic Diversity of HIV-1 in the Democratic Republic of the Congo.

    PubMed

    Rodgers, Mary A; Wilkinson, Eduan; Vallari, Ana; McArthur, Carole; Sthreshley, Larry; Brennan, Catherine A; Cloherty, Gavin; de Oliveira, Tulio

    2017-03-15

    As the epidemiological epicenter of the human immunodeficiency virus (HIV) pandemic, the Democratic Republic of the Congo (DRC) is a reservoir of circulating HIV strains exhibiting high levels of diversity and recombination. In this study, we characterized HIV specimens collected in two rural areas of the DRC between 2001 and 2003 to identify rare strains of HIV. The env gp41 region was sequenced and characterized for 172 HIV-positive specimens. The env sequences were predominantly subtype A (43.02%), but 7 other subtypes (33.14%), 20 circulating recombinant forms (CRFs; 11.63%), and 20 unclassified (11.63%) sequences were also found. Of the rare and unclassified subtypes, 18 specimens were selected for next-generation sequencing (NGS) by a modified HIV-switching mechanism at the 5' end of the RNA template (SMART) method to obtain full-genome sequences. NGS produced 14 new complete genomes, which included pure subtype C (n = 2), D (n = 1), F1 (n = 1), H (n = 3), and J (n = 1) genomes. The two subtype C genomes and one of the subtype H genomes branched basal to their respective subtype branches but had no evidence of recombination. The remaining 6 genomes were complex recombinants of 2 or more subtypes, including subtypes A1, F, G, H, J, and K and unclassified fragments, including one subtype CRF25 isolate, which branched basal to all CRF25 references. Notably, all recombinant subtype H fragments branched basal to the H clade. Spatial-geographical analysis indicated that the diverse sequences identified here did not expand globally. The full-genome and subgenomic sequences identified in our study population significantly increase the documented diversity of the strains involved in the continually evolving HIV-1 pandemic.IMPORTANCE Very little is known about the ancestral HIV-1 strains that founded the global pandemic, and very few complete genome sequences are available from patients in the Congo Basin, where HIV-1 expanded early in the global pandemic. By

  18. Influence of sequence identity and unique breakpoints on the frequency of intersubtype HIV-1 recombination

    PubMed Central

    Baird, Heather A; Gao, Yong; Galetto, Román; Lalonde, Matthew; Anthony, Reshma M; Giacomoni, Véronique; Abreha, Measho; Destefano, Jeffrey J; Negroni, Matteo; Arts, Eric J

    2006-01-01

    Background HIV-1 recombination between different subtypes has a major impact on the global epidemic. The generation of these intersubtype recombinants follows a defined set of events starting with dual infection of a host cell, heterodiploid virus production, strand transfers during reverse transcription, and then selection. In this study, recombination frequencies were measured in the C1-C4 regions of the envelope gene in the presence (using a multiple cycle infection system) and absence (in vitro reverse transcription and single cycle infection systems) of selection for replication-competent virus. Ugandan subtypes A and D HIV-1 env sequences (115-A, 120-A, 89-D, 122-D, 126-D) were employed in all three assay systems. These subtypes co-circulate in East Africa and frequently recombine in this human population. Results Increased sequence identity between viruses or RNA templates resulted in increased recombination frequencies, with the exception of the 115-A virus or RNA template. Analyses of the recombination breakpoints and mechanistic studies revealed that the presence of a recombination hotspot in the C3/V4 env region, unique to 115-A as donor RNA, could account for the higher recombination frequencies with the 115-A virus/template. Single-cycle infections supported proportionally less recombination than the in vitro reverse transcription assay but both systems still had significantly higher recombination frequencies than observed in the multiple-cycle virus replication system. In the multiple cycle assay, increased replicative fitness of one HIV-1 over the other in a dual infection dramatically decreased recombination frequencies. Conclusion Sequence variation at specific sites between HIV-1 isolates can introduce unique recombination hotspots, which increase recombination frequencies and skew the general observation that decreased HIV-1 sequence identity reduces recombination rates. These findings also suggest that the majority of intra- or intersubtype A

  19. HIV-1 Tat and Viral Latency: What We Can Learn from Naturally Occurring Sequence Variations.

    PubMed

    Kamori, Doreen; Ueno, Takamasa

    2017-01-01

    Despite the effective use of antiretroviral therapy, the remainder of a latently HIV-1-infected reservoir mainly in the resting memory CD4(+) T lymphocyte subset has provided a great setback toward viral eradication. While host transcriptional silencing machinery is thought to play a dominant role in HIV-1 latency, HIV-1 protein such as Tat, may affect both the establishment and the reversal of latency. Indeed, mutational studies have demonstrated that insufficient Tat transactivation activity can result in impaired transcription of viral genes and the establishment of latency in cell culture experiments. Because Tat protein is one of highly variable proteins within HIV-1 proteome, it is conceivable that naturally occurring Tat mutations may differentially modulate Tat functions, thereby influencing the establishment and/or the reversal of viral latency in vivo. In this mini review, we summarize the recent findings of Tat naturally occurring polymorphisms associating with host immune responses and we highlight the implication of Tat sequence variations in relation to HIV latency.

  20. HIV-1 conserved-element vaccines: relationship between sequence conservation and replicative capacity.

    PubMed

    Rolland, Morgane; Manocheewa, Siriphan; Swain, J Victor; Lanxon-Cookson, Erinn C; Kim, Moon; Westfall, Dylan H; Larsen, Brendan B; Gilbert, Peter B; Mullins, James I

    2013-05-01

    To overcome the problem of HIV-1 variability, candidate vaccine antigens have been designed to be composed of conserved elements of the HIV-1 proteome. Such candidate vaccines could be improved with a better understanding of both HIV-1 evolutionary constraints and the fitness cost of specific mutations. We evaluated the in vitro fitness cost of 23 mutations engineered in the HIV-1 subtype B Gag-p24 Center-of-Tree (COT) protein through fitness competition assays. While some mutations at conserved sites exacted a high fitness cost, as expected under the assumption that the most conserved residue confers the highest fitness, there was no overall strong relationship between sequence conservation and replicative capacity. By comparing sites that have evolved since the beginning of the epidemic to those that have remain unchanged, we found that sites that have evolved over time were more likely to correspond to HLA-associated sites and that their mutation had limited fitness costs. Our data showed no transcendent link between high conservation and high fitness cost, indicating that merely focusing on conserved segments of HIV-1 would not be sufficient for a successful vaccine strategy. Nonetheless, a subset of sites exacted a high fitness cost upon mutation--these sites have been under selective pressure to change since the beginning of the epidemic but have proved virtually nonmutable and could constitute preferred targets for vaccine design.

  1. HIV-1 Tat and Viral Latency: What We Can Learn from Naturally Occurring Sequence Variations

    PubMed Central

    Kamori, Doreen; Ueno, Takamasa

    2017-01-01

    Despite the effective use of antiretroviral therapy, the remainder of a latently HIV-1-infected reservoir mainly in the resting memory CD4+ T lymphocyte subset has provided a great setback toward viral eradication. While host transcriptional silencing machinery is thought to play a dominant role in HIV-1 latency, HIV-1 protein such as Tat, may affect both the establishment and the reversal of latency. Indeed, mutational studies have demonstrated that insufficient Tat transactivation activity can result in impaired transcription of viral genes and the establishment of latency in cell culture experiments. Because Tat protein is one of highly variable proteins within HIV-1 proteome, it is conceivable that naturally occurring Tat mutations may differentially modulate Tat functions, thereby influencing the establishment and/or the reversal of viral latency in vivo. In this mini review, we summarize the recent findings of Tat naturally occurring polymorphisms associating with host immune responses and we highlight the implication of Tat sequence variations in relation to HIV latency. PMID:28194140

  2. Performance comparison of next-generation sequencing platforms for determining HIV-1 coreceptor use

    PubMed Central

    Raymond, Stéphanie; Nicot, Florence; Jeanne, Nicolas; Delfour, Olivier; Carcenac, Romain; Lefebvre, Caroline; Cazabat, Michelle; Sauné, Karine; Delobel, Pierre; Izopet, Jacques

    2017-01-01

    The coreceptor used by HIV-1 must be determined before a CCR5 antagonist, part of the arsenal of antiretroviral drugs, is prescribed because viruses that enter cells using the CXCR4 coreceptor are responsible for treatment failure. HIV-1 tropism is also correlated with disease progression and so must be determined for virological studies. Tropism can be determined by next-generation sequencing (NGS), but not all of these new technologies have been fully validated for use in clinical practice. The Illumina NGS technology is used in many laboratories but its ability to predict HIV-1 tropism has not been evaluated while the 454 GS-Junior (Roche) is used for routine diagnosis. The genotypic prediction of HIV-1 tropism is based on sequencing the V3 region and interpreting the results with an appropriate algorithm. We compared the performances of the MiSeq (Illumina) and 454 GS-Junior (Roche) systems with a reference phenotypic assay. We used clinical samples for the NGS tropism predictions and assessed their ability to quantify CXCR4-using variants. The data show that the Illumina platform can be used to detect minor CXCR4-using variants in clinical practice but technical optimization are needed to improve quantification. PMID:28186189

  3. Error rates, PCR recombination, and sampling depth in HIV-1 whole genome deep sequencing.

    PubMed

    Zanini, Fabio; Brodin, Johanna; Albert, Jan; Neher, Richard A

    2016-12-27

    Deep sequencing is a powerful and cost-effective tool to characterize the genetic diversity and evolution of virus populations. While modern sequencing instruments readily cover viral genomes many thousand fold and very rare variants can in principle be detected, sequencing errors, amplification biases, and other artifacts can limit sensitivity and complicate data interpretation. For this reason, the number of studies using whole genome deep sequencing to characterize viral quasi-species in clinical samples is still limited. We have previously undertaken a large scale whole genome deep sequencing study of HIV-1 populations. Here we discuss the challenges, error profiles, control experiments, and computational test we developed to quantify the accuracy of variant frequency estimation.

  4. Repair of oxidative DNA base damage in the host genome influences the HIV integration site sequence preference.

    PubMed

    Bennett, Geoffrey R; Peters, Ryan; Wang, Xiao-hong; Hanne, Jeungphill; Sobol, Robert W; Bundschuh, Ralf; Fishel, Richard; Yoder, Kristine E

    2014-01-01

    Host base excision repair (BER) proteins that repair oxidative damage enhance HIV infection. These proteins include the oxidative DNA damage glycosylases 8-oxo-guanine DNA glycosylase (OGG1) and mutY homolog (MYH) as well as DNA polymerase beta (Polβ). While deletion of oxidative BER genes leads to decreased HIV infection and integration efficiency, the mechanism remains unknown. One hypothesis is that BER proteins repair the DNA gapped integration intermediate. An alternative hypothesis considers that the most common oxidative DNA base damages occur on guanines. The subtle consensus sequence preference at HIV integration sites includes multiple G:C base pairs surrounding the points of joining. These observations suggest a role for oxidative BER during integration targeting at the nucleotide level. We examined the hypothesis that BER repairs a gapped integration intermediate by measuring HIV infection efficiency in Polβ null cell lines complemented with active site point mutants of Polβ. A DNA synthesis defective mutant, but not a 5'dRP lyase mutant, rescued HIV infection efficiency to wild type levels; this suggested Polβ DNA synthesis activity is not necessary while 5'dRP lyase activity is required for efficient HIV infection. An alternate hypothesis that BER events in the host genome influence HIV integration site selection was examined by sequencing integration sites in OGG1 and MYH null cells. In the absence of these 8-oxo-guanine specific glycosylases the chromatin elements of HIV integration site selection remain the same as in wild type cells. However, the HIV integration site sequence preference at G:C base pairs is altered at several positions in OGG1 and MYH null cells. Inefficient HIV infection in the absence of oxidative BER proteins does not appear related to repair of the gapped integration intermediate; instead oxidative damage repair may participate in HIV integration site preference at the sequence level.

  5. Molecular Mechanisms of HIV Type 1 Prophylaxis Failure Revealed by Single-Genome Sequencing

    PubMed Central

    Li, Hui; Blair, Lily; Chen, Yalu; Learn, Gerald; Pfafferott, Katja; John, Mina; Bhattacharya, Tanmoy; Hahn, Beatrice H.; Mallal, Simon; Shaw, George M.; Bar, Katharine J.

    2013-01-01

    Trials of human immunodeficiency virus type 1 (HIV) pre- and postexposure prophylaxis show promise. Here, we describe a novel strategy for deciphering mechanisms of prophylaxis failure that could improve therapeutic outcomes. A healthcare worker began antiretroviral prophylaxis immediately after a high-risk needlestick injury but nonetheless became viremic 11 weeks later. Single-genome sequencing of plasma viral RNA identified 15 drug susceptible transmitted/founder HIV genomes responsible for productive infection. Sequences emanating from these genomes exhibited extremely low diversity, suggesting virus sequestration as opposed to low-level replication as the cause of breakthrough infection. Identification of transmitted/founder viruses allows for genome-wide assessment of molecular mechanisms of prophylaxis failure. PMID:24023257

  6. Molecular mechanisms of HIV type 1 prophylaxis failure revealed by single-genome sequencing.

    PubMed

    Li, Hui; Blair, Lily; Chen, Yalu; Learn, Gerald; Pfafferott, Katja; John, Mina; Bhattacharya, Tanmoy; Hahn, Beatrice H; Mallal, Simon; Shaw, George M; Bar, Katharine J

    2013-11-15

    Trials of human immunodeficiency virus type 1 (HIV) pre- and postexposure prophylaxis show promise. Here, we describe a novel strategy for deciphering mechanisms of prophylaxis failure that could improve therapeutic outcomes. A healthcare worker began antiretroviral prophylaxis immediately after a high-risk needlestick injury but nonetheless became viremic 11 weeks later. Single-genome sequencing of plasma viral RNA identified 15 drug susceptible transmitted/founder HIV genomes responsible for productive infection. Sequences emanating from these genomes exhibited extremely low diversity, suggesting virus sequestration as opposed to low-level replication as the cause of breakthrough infection. Identification of transmitted/founder viruses allows for genome-wide assessment of molecular mechanisms of prophylaxis failure.

  7. Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA revealed by in vitro genetic selection.

    PubMed Central

    Purohit, P; Dupont, S; Stevenson, M; Green, M R

    2001-01-01

    The human immunodeficiency virus type-1 matrix protein (HIV-1 MA) is a multifunctional structural protein synthesized as part of the Pr55 gag polyprotein. We have used in vitro genetic selection to identify an RNA consensus sequence that specifically interacts with MA (Kd = 5 x 10(-7) M). This 13-nt MA binding consensus sequence bears a high degree of homology (77%) to a region (nt 1433-1446) within the POL open reading frame of the HIV-1 genome (consensus sequence from 38 HIV-1 strains). Chemical interference experiments identified the nucleotides within the MA binding consensus sequence involved in direct contact with MA. We further demonstrate that this RNA-protein interaction is mediated through a stretch of basic amino acids within MA. Mutations that disrupt the interaction between MA and its RNA binding site within the HIV-1 genome resulted in a measurable decrease in viral replication. PMID:11345436

  8. Prediction of HIV-1 coreceptor usage (tropism) by sequence analysis using a genotypic approach.

    PubMed

    Sierra, Saleta; Kaiser, Rolf; Lübke, Nadine; Thielen, Alexander; Schuelter, Eugen; Heger, Eva; Däumer, Martin; Reuter, Stefan; Esser, Stefan; Fätkenheuer, Gerd; Pfister, Herbert; Oette, Mark; Lengauer, Thomas

    2011-12-01

    Maraviroc (MVC) is the first licensed antiretroviral drug from the class of coreceptor antagonists. It binds to the host coreceptor CCR5, which is used by the majority of HIV strains in order to infect the human immune cells (Fig. 1). Other HIV isolates use a different coreceptor, the CXCR4. Which receptor is used, is determined in the virus by the Env protein (Fig. 2). Depending on the coreceptor used, the viruses are classified as R5 or X4, respectively. MVC binds to the CCR5 receptor inhibiting the entry of R5 viruses into the target cell. During the course of disease, X4 viruses may emerge and outgrow the R5 viruses. Determination of coreceptor usage (also called tropism) is therefore mandatory prior to administration of MVC, as demanded by EMA and FDA. The studies for MVC efficiency MOTIVATE, MERIT and 1029 have been performed with the Trofile assay from Monogram, San Francisco, U.S.A. This is a high quality assay based on sophisticated recombinant tests. The acceptance for this test for daily routine is rather low outside of the U.S.A., since the European physicians rather tend to work with decentralized expert laboratories, which also provide concomitant resistance testing. These laboratories have undergone several quality assurance evaluations, the last one being presented in 2011. For several years now, we have performed tropism determinations based on sequence analysis from the HIV env-V3 gene region (V3). This region carries enough information to perform a reliable prediction. The genotypic determination of coreceptor usage presents advantages such as: shorter turnover time (equivalent to resistance testing), lower costs, possibility to adapt the results to the patients' needs and possibility of analysing clinical samples with very low or even undetectable viral load (VL), particularly since the number of samples analysed with VL < 1000 copies/μl roughly increased in the last years (Fig. 3). The main steps for tropism testing (Fig. 4) demonstrated in

  9. Identification of HIV Mutation as Diagnostic Biomarker through Next Generation Sequencing

    PubMed Central

    Shaw, Wen Hui; Lin, Qianqian; Muhammad, Zikry Zhiwei Bin Roslee; Lee, Jia Jun; Khong, Wei Xin; Ng, Oon Tek; Tan, Eng Lee

    2016-01-01

    Introduction Current clinical detection of Human immunodeficiency virus 1 (HIV-1) is used to target viral genes and proteins. However, the immunoassay, such as viral culture or Polymerase Chain Reaction (PCR), lacks accuracy in the diagnosis, as these conventional assays rely on the stable genome and HIV-1 is a highly-mutated virus. Next generation sequencing (NGS) promises to be transformative for the practice of infectious disease, and the rapidly reducing cost and processing time mean that this will become a feasible technology in diagnostic and research laboratories in the near future. The technology offers the superior sensitivity to detect the pathogenic viruses, including unknown and unexpected strains. Aim To leverage the NGS technology in order to improve current HIV-1 diagnosis and genotyping methods. Materials and Methods Ten blood samples were collected from HIV-1 infected patients which were diagnosed by RT PCR at Singapore Communicable Disease Centre, Tan Tock Seng Hospital from October 2014 to March 2015. Viral RNAs were extracted from blood plasma and reversed into cDNA. The HIV-1 cDNA samples were cleaned up using a PCR purification kit and the sequencing library was prepared and identified through MiSeq. Results Two common mutations were observed in all ten samples. The common mutations were identified at genome locations 1908 and 2104 as missense and silent mutations respectively, conferring S37N and S3S found on aspartic protease and reverse transcriptase subunits. Conclusion The common mutations identified in this study were not previously reported, therefore suggesting the potential for them to be used for identification of viral infection, disease transmission and drug resistance. This was especially the case for, missense mutation S37N which could cause an amino acid change in viral proteases thus reducing the binding affinity of some protease inhibitors. Thus, the unique common mutations identified in this study could be used as diagnostic

  10. Spin models inferred from patient-derived viral sequence data faithfully describe HIV fitness landscapes

    PubMed Central

    Shekhar, Karthik; Ruberman, Claire F.; Ferguson, Andrew L.; Barton, John P.; Kardar, Mehran; Chakraborty, Arup K.

    2017-01-01

    Mutational escape from vaccine-induced immune responses has thwarted the development of a successful vaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus’ fitness as a function of its proteomic sequence can enable rational design of potent vaccines, as this information can focus vaccine-induced immune responses to target mutational vulnerabilities of the virus. Spin models have been proposed as a means to infer intrinsic fitness landscapes of HIV proteins from patient-derived viral protein sequences. These sequences are the product of nonequilibrium viral evolution driven by patient-specific immune responses and are subject to phylogenetic constraints. How can such sequence data allow inference of intrinsic fitness landscapes? We combined computer simulations and variational theory á la Feynman to show that, in most circumstances, spin models inferred from patient-derived viral sequences reflect the correct rank order of the fitness of mutant viral strains. Our findings are relevant for diverse viruses. PMID:24483484

  11. Improving HIV coreceptor usage prediction in the clinic using hints from next-generation sequencing data

    PubMed Central

    Pfeifer, Nico; Lengauer, Thomas

    2012-01-01

    Motivation: Due to the high mutation rate of human immunodeficiency virus (HIV), drug-resistant-variants emerge frequently. Therefore, researchers are constantly searching for new ways to attack the virus. One new class of anti-HIV drugs is the class of coreceptor antagonists that block cell entry by occupying a coreceptor on CD4 cells. This type of drug just has an effect on the subset of HIVs that use the inhibited coreceptor. A good prediction of whether the viral population inside a patient is susceptible to the treatment is hence very important for therapy decisions and pre-requisite to administering the respective drug. The first prediction models were based on data from Sanger sequencing of the V3 loop of HIV. Recently, a method based on next-generation sequencing (NGS) data was introduced that predicts labels for each read separately and decides on the patient label through a percentage threshold for the resistant viral minority. Results: We model the prediction problem on the patient level taking the information of all reads from NGS data jointly into account. This enables us to improve prediction performance for NGS data, but we can also use the trained model to improve predictions based on Sanger sequencing data. Therefore, also laboratories without NGS capabilities can benefit from the improvements. Furthermore, we show which amino acids at which position are important for prediction success, giving clues on how the interaction mechanism between the V3 loop and the particular coreceptors might be influenced. Availability: A webserver is available at http://coreceptor.bioinf.mpi-inf.mpg.de. Contact: nico.pfeifer@mpi-inf.mpg.de PMID:22962486

  12. Interlaboratory concordance of DNA sequence analysis to detect reverse transcriptase mutations in HIV-1 proviral DNA. ACTG Sequencing Working Group. AIDS Clinical Trials Group.

    PubMed

    Demeter, L M; D'Aquila, R; Weislow, O; Lorenzo, E; Erice, A; Fitzgibbon, J; Shafer, R; Richman, D; Howard, T M; Zhao, Y; Fisher, E; Huang, D; Mayers, D; Sylvester, S; Arens, M; Sannerud, K; Rasheed, S; Johnson, V; Kuritzkes, D; Reichelderfer, P; Japour, A

    1998-11-01

    Thirteen laboratories evaluated the reproducibility of sequencing methods to detect drug resistance mutations in HIV-1 reverse transcriptase (RT). Blinded, cultured peripheral blood mononuclear cell pellets were distributed to each laboratory. Each laboratory used its preferred method for sequencing proviral DNA. Differences in protocols included: DNA purification; number of PCR amplifications; PCR product purification; sequence/location of PCR/sequencing primers; sequencing template; sequencing reaction label; sequencing polymerase; and use of manual versus automated methods to resolve sequencing reaction products. Five unknowns were evaluated. Thirteen laboratories submitted 39043 nucleotide assignments spanning codons 10-256 of HIV-1 RT. A consensus nucleotide assignment (defined as agreement among > or = 75% of laboratories) could be made in over 99% of nucleotide positions, and was more frequent in the three laboratory isolates. The overall rate of discrepant nucleotide assignments was 0.29%. A consensus nucleotide assignment could not be made at RT codon 41 in the clinical isolate tested. Clonal analysis revealed that this was due to the presence of a mixture of wild-type and mutant genotypes. These observations suggest that sequencing methodologies currently in use in ACTG laboratories to sequence HIV-1 RT yield highly concordant results for laboratory strains; however, more discrepancies among laboratories may occur when clinical isolates are tested.

  13. STD/HIV prevention in Turkey: planning a sequence of interventions.

    PubMed

    Aral, S O; Fransen, L

    1995-12-01

    This study was initiated to assess which mix of early STD/HIV prevention interventions would potentially be effective, cost-effective and sustainable in Turkey; and to program an intervention sequence to maximize synergy among the interventions. During rapid assessment we: 1) reviewed past issues of 3 leading newspapers; 2) collected information on TV coverage; 3) interviewed key informants including taxicab drivers, hotel employees, grocery store owners, academicians in public health and law, investigators of STD/HIV and reproductive tract infections, and officials in the ministry of health; 4) reviewed available evidence on STD/HIV morbidity, sexual behavior patterns, migration patterns and same/opposite gender sex trade. We found: 1) discrepancies between decision makers' perceptions and social realities with respect to the epidemiology of sexual behavior and STDs, and the state of public health programs; 2) discrepancies between sexual practices and public expression regarding sexual practices; 3) economic, demographic, and political pressures in Turkey and in surrounding countries for the expansion of prostitution; 4) a sexual double standard and gender specific migration patterns which sustain a high demand for commercial sex; 5) patterns of health care seeking behaviors and provision of STD clinical services which indicate other STDs may play a very important role in spread of HIV infection; 6) an important mass media role in opinion formation; 7) consensual denial of risk for the majority based on beliefs embedded in machismo, nationalism and religion, and a resulting marginalization and externalization of STD/HIV risk; 8) high prevalence of syphilis among both Turkish and immigrant female prostitutes in Istanbul (early latent 8 and 13%; late latent 0 and 4%; previous history 9 and 22%) 9) and high rates of syphilis among male prostitutes (early latent 11%, late latent 21% and previous history 58%). We concluded that interventions should initially include

  14. Discontinuous sequence change of human immunodeficiency virus (HIV) type 1 env sequences in plasma viral and lymphocyte-associated proviral populations in vivo: implications for models of HIV pathogenesis.

    PubMed Central

    Simmonds, P; Zhang, L Q; McOmish, F; Balfe, P; Ludlam, C A; Brown, A J

    1991-01-01

    Sequence change in different hypervariable regions of the external membrane glycoprotein (gp120) of human immunodeficiency virus type 1 (HIV-1) was studied. Viral RNA associated with cell-free virus particles circulating in plasma and proviral DNA present in HIV-infected peripheral blood mononuclear cells (PBMCs) were extracted from blood samples of two currently asymptomatic hemophiliac patients over a 5-year period. HIV sequences were amplified by polymerase chain reaction to allow analysis in the V3, V4, and V5 hypervariable regions of gp120. Rapid sequence change, consisting of regular replacements by a succession of distinct viral populations, was found in both plasma virus and PBMC provirus populations. Significant differences between the frequencies of sequence variants in DNA and RNA populations within the same sample were observed, indicating that at any one time point, the predominant plasma virus variants were antigenically distinct from viruses encoded by HIV DNA sequences in PBMCs. How these findings contribute to current models of HIV pathogenesis is discussed. Images PMID:1920632

  15. MinVar: A rapid and versatile tool for HIV-1 drug resistance genotyping by deep sequencing.

    PubMed

    Huber, Michael; Metzner, Karin J; Geissberger, Fabienne D; Shah, Cyril; Leemann, Christine; Klimkait, Thomas; Böni, Jürg; Trkola, Alexandra; Zagordi, Osvaldo

    2017-02-01

    Genotypic monitoring of drug-resistance mutations (DRMs) in HIV-1 infected individuals is strongly recommended to guide selection of the initial antiretroviral therapy (ART) and changes of drug regimens. Traditionally, mutations conferring drug resistance are detected by population sequencing of the reverse transcribed viral RNA encoding the HIV-1 enzymes target by ART, followed by manual analysis and interpretation of Sanger sequencing traces. This process is labor intensive, relies on subjective interpretation from the operator, and offers limited sensitivity as only mutations above 20% frequency can be reliably detected. Here we present MinVar, a pipeline for the analysis of deep sequencing data, which allows reliable and automated detection of DRMs down to 5%. We evaluated MinVar with data from amplicon sequencing of defined mixtures of molecular virus clones with known DRM and plasma samples of viremic HIV-1 infected individuals and we compared it to VirVarSeq, another virus variant detection tool exclusively working on Illumina deep sequencing data. MinVar was designed to be compatible with a diverse range of sequencing platforms and allows the detection of DRMs and insertions/deletions from deep sequencing data without the need to perform additional bioinformatics analysis, a prerequisite to a widespread implementation of HIV-1 genotyping using deep sequencing in routine diagnostic settings.

  16. Los Alamos National Laboratory

    SciTech Connect

    Dogliani, Harold O

    2011-01-19

    The purpose of the briefing is to describe general laboratory technical capabilities to be used for various groups such as military cadets or university faculty/students and post docs to recruit into a variety of Los Alamos programs. Discussed are: (1) development and application of high leverage science to enable effeictive, predictable and reliability outcomes; (2) deter, detect, characterize, reverse and prevent the proliferation of weapons of mass destruction and their use by adversaries and terrorists; (3) modeling and simulation to define complex processes, predict outcomes, and develop effective prevention, response, and remediation strategies; (4) energetic materials and hydrodynamic testing to develop materials for precise delivery of focused energy; (5) materials cience focused on fundamental understanding of materials behaviors, their quantum-molecular properties, and their dynamic responses, and (6) bio-science to rapidly detect and characterize pathogens, to develop vaccines and prophylactic remedies, and to develop attribution forensics.

  17. Short Communication Phylogenetic Characterization of HIV Type 1 CRF01_AE V3 Envelope Sequences in Pregnant Women in Northern Vietnam

    PubMed Central

    Caridha, Rozina; Ha, Tran Thi Thanh; Gaseitsiwe, Simani; Hung, Pham Viet; Anh, Nguyen Mai; Bao, Nguyen Huy; Khang, Dinh Duy; Hien, Nguyen Tran; Cam, Phung Dac; Chiodi, Francesca

    2012-01-01

    Abstract Characterization of HIV-1 strains is important for surveillance of the HIV-1 epidemic. In Vietnam HIV-1-infected pregnant women often fail to receive the care they are entitled to. Here, we analyzed phylogenetically HIV-1 env sequences from 37 HIV-1-infected pregnant women from Ha Noi (n=22) and Hai Phong (n=15), where they delivered in 2005–2007. All carried CRF01_AE in the gp120 V3 region. In 21 women CRF01_AE was also found in the reverse transcriptase gene. We compared their env gp120 V3 sequences phylogenetically in a maximum likelihood tree to those of 198 other CRF01_AE sequences in Vietnam and 229 from neighboring countries, predominantly Thailand, from the HIV-1 database. Altogether 464 sequences were analyzed. All but one of the maternal sequences colocalized with sequences from northern Vietnam. The maternal sequences had evolved the least when compared to sequences collected in Ha Noi in 2002, as shown by analysis of synonymous and nonsynonymous changes, than to other Vietnamese sequences collected earlier and/or elsewhere. Since the HIV-1 epidemic in women in Vietnam may still be underestimated, characterization of HIV-1 in pregnant women is important to observe how HIV-1 has evolved and follow its molecular epidemiology. PMID:21936713

  18. Short communication: phylogenetic characterization of HIV type 1 CRF01_AE V3 envelope sequences in pregnant women in Northern Vietnam.

    PubMed

    Caridha, Rozina; Ha, Tran Thi Thanh; Gaseitsiwe, Simani; Hung, Pham Viet; Anh, Nguyen Mai; Bao, Nguyen Huy; Khang, Dinh Duy; Hien, Nguyen Tran; Cam, Phung Dac; Chiodi, Francesca; Ehrnst, Anneka

    2012-08-01

    Characterization of HIV-1 strains is important for surveillance of the HIV-1 epidemic. In Vietnam HIV-1-infected pregnant women often fail to receive the care they are entitled to. Here, we analyzed phylogenetically HIV-1 env sequences from 37 HIV-1-infected pregnant women from Ha Noi (n=22) and Hai Phong (n=15), where they delivered in 2005-2007. All carried CRF01_AE in the gp120 V3 region. In 21 women CRF01_AE was also found in the reverse transcriptase gene. We compared their env gp120 V3 sequences phylogenetically in a maximum likelihood tree to those of 198 other CRF01_AE sequences in Vietnam and 229 from neighboring countries, predominantly Thailand, from the HIV-1 database. Altogether 464 sequences were analyzed. All but one of the maternal sequences colocalized with sequences from northern Vietnam. The maternal sequences had evolved the least when compared to sequences collected in Ha Noi in 2002, as shown by analysis of synonymous and nonsynonymous changes, than to other Vietnamese sequences collected earlier and/or elsewhere. Since the HIV-1 epidemic in women in Vietnam may still be underestimated, characterization of HIV-1 in pregnant women is important to observe how HIV-1 has evolved and follow its molecular epidemiology.

  19. Near Full-Length Sequence Analysis of HIV Type 1 BF Recombinants from Italy

    PubMed Central

    Foley, Brian T.; Rosi, Andrea; Vicenti, Ilaria; Nannetti, Giulio; Meini, Genny; Razzolini, Francesca; Zazzi, Maurizio

    2012-01-01

    Abstract Recombination between HIV-1 subtypes B and F has generated several circulating and unique recombinant forms, particularly in Latin American areas. In Italy, subtype B is highly prevalent while subtype F is the most common pure non-B subtype. To investigate the recombination pattern in Italian BF recombinant viruses, we characterized full-length sequences derived from 15 adult patients, mostly Italian and infected by the heterosexual route. One of the BF mosaics was a CRF29, three sequences clustered with low bootstrap values with CRF39, CRF40, and CRF42. With the exception of the CRF29-like sequence, the other recombination patterns were unique, but two possible clusters were identified. Analysis of the gp120 V3 domain suggested a possible link with subtype F from Eastern Europe rather than from Latin America, favoring the hypothesis of local recombination between clade B and F viruses over that of import of BF recombinants from Latin America. HIV-1 subtypes B and F appear prone to generation of unique recombinants in Italy, warranting epidemiological surveillance and investigation of a possible clinical significance. PMID:21740272

  20. Attacking HIV-1 RNA versus DNA by sequence-specific approaches: RNAi versus CRISPR-Cas.

    PubMed

    Herrera-Carrillo, Elena; Berkhout, Ben

    2016-10-15

    Human immunodeficiency virus type 1 (HIV-1) infection can be effectively controlled by potent antiviral drugs, but this never results in a cure. The patient should therefore take these drugs for the rest of his/her life, which can cause drug-resistance and adverse effects. Therefore, more durable therapeutic strategies should be considered, such as a stable gene therapy to protect the target T cells against HIV-1 infection. The development of potent therapeutic regimens based on the RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats (CRISPR-Cas) mechanisms will be described, which can be delivered by lentiviral vectors. These mechanisms attack different forms of the viral genome, the RNA and DNA, respectively, but both mechanisms act in a strictly sequence-specific manner. Early RNAi experiments demonstrated profound virus inhibition, but also indicated that viral escape is possible. Such therapy failure can be prevented by the design of a combinatorial RNAi attack on the virus and this gene therapy is currently being tested in a preclinical humanized mouse model. Recent CRISPR-Cas studies also document robust virus inhibition, but suggest a novel viral escape route that is induced by the cellular nonhomologous end joining DNA repair pathway, which is activated by CRISPR-Cas-induced DNA breaks. We will compare these two approaches for durable HIV-1 suppression and discuss the respective advantages and disadvantages. The potential for future clinical applications will be described.

  1. Sequence and structure based models of HIV-1 protease and reverse transcriptase drug resistance

    PubMed Central

    2013-01-01

    Background Successful management of chronic human immunodeficiency virus type 1 (HIV-1) infection with a cocktail of antiretroviral medications can be negatively affected by the presence of drug resistant mutations in the viral targets. These targets include the HIV-1 protease (PR) and reverse transcriptase (RT) proteins, for which a number of inhibitors are available on the market and routinely prescribed. Protein mutational patterns are associated with varying degrees of resistance to their respective inhibitors, with extremes that can range from continued susceptibility to cross-resistance across all drugs. Results Here we implement statistical learning algorithms to develop structure- and sequence-based models for systematically predicting the effects of mutations in the PR and RT proteins on resistance to each of eight and eleven inhibitors, respectively. Employing a four-body statistical potential, mutant proteins are represented as feature vectors whose components quantify relative environmental perturbations at amino acid residue positions in the respective target structures upon mutation. Two approaches are implemented in developing sequence-based models, based on use of either relative frequencies or counts of n-grams, to generate vectors for representing mutant proteins. To the best of our knowledge, this is the first reported study on structure- and sequence-based predictive models of HIV-1 PR and RT drug resistance developed by implementing a four-body statistical potential and n-grams, respectively, to generate mutant attribute vectors. Performance of the learning methods is evaluated on the basis of tenfold cross-validation, using previously assayed and publicly available in vitro data relating mutational patterns in the targets to quantified inhibitor susceptibility changes. Conclusion Overall performance results are competitive with those of a previously published study utilizing a sequence-based strategy, while our structure- and sequence

  2. HIV-1 neutralizing antibody response and viral genetic diversity characterized with next generation sequencing

    PubMed Central

    Carter, Christoph C.; Wagner, Gabriel A.; Hightower, George K.; Caballero, Gemma; Phung, Pham; Richman, Douglas D.; Kosakovsky Pond, Sergei L.; Smith, Davey M.

    2014-01-01

    To better understand the dynamics of HIV-specific neutralizing antibody (NAb), we examined associations between viral genetic diversity and the NAb response against a multi-subtype panel of heterologous viruses in a well-characterized, therapy-naïve primary infection cohort. Using next generation sequencing (NGS), we computed sequence-based measures of diversity within HIV-1 env, gag and pol, and compared them to NAb breadth and potency as calculated by a neutralization score. Contemporaneous env diversity and the neutralization score were positively correlated (p=0.0033), as were the neutralization score and estimated duration of infection (EDI) (p=0.0038), and env diversity and EDI (p=0.0005). Neither early env diversity nor baseline viral load correlated with future NAb breadth and potency (p>0.05). Taken together, it is unlikely that neutralizing capability in our cohort was conditioned on viral diversity, but rather that env evolution was driven by the level of NAb selective pressure. PMID:25463602

  3. Generation and Characterization of HIV-1 Transmitted and Founder Virus Consensus Sequence from Intravenous Drug Users in Xinjiang, China.

    PubMed

    Li, Fan; Ma, Liying; Feng, Yi; Hu, Jing; Ni, Na; Ruan, Yuhua; Shao, Yiming

    2017-03-02

    HIV-1 transmission in intravenous drug users (IDUs) has been characterized by high genetic multiplicity and suggests a greater challenge for HIV-1 infection blocking. We investigated a total of 749 sequences of full-length gp160 gene obtained by single genome sequencing (SGS) from 22 HIV-1 early infected IDUs in Xinjiang province, northwest China, and generated a transmitted and founder virus (T/F virus) consensus sequence (IDU.CON). The T/F virus was classified as subtype CRF07_BC and predicted to be CCR5-tropic virus. The variable region (V1, V2, and V4 loop) of IDU.CON showed length variation compared with the heterosexual T/F virus consensus sequence (HSX.CON) and homosexual T/F virus consensus sequence (MSM.CON). A total of 26 N-linked glycosylation sites were discovered in the IDU.CON sequence, which is less than that of MSM.CON and HSX.CON. Characterization of T/F virus from IDUs highlights the genetic make-up and complexity of virus near the moment of transmission or in early infection preceding systemic dissemination and is important toward the development of an effective HIV-1 preventive methods, including vaccines.

  4. HIV-2 Surveillance with Next-Generation Sequencing Reveals Mutations in a Cytotoxic Lymphocyte-Restricted Epitope Involved in Long-Term Nonprogression.

    PubMed

    Yamaguchi, Julie; Brennan, Catherine A; Alessandri-Gradt, Elodie; Plantier, Jean-Christophe; Cloherty, Gavin A; Berg, Michael G

    2017-04-01

    HIV-2 exhibits a natural history of infection distinct from HIV-1. Primarily found in West Africa and in only 10%-20% of HIV infections in this region, patients with HIV-2 typically exhibit a slower progression to AIDS, lower viral loads, and decreased rates of transmission. Here, we used next-generation sequencing to determine the sequence and phylogenetic classification of nine HIV-2 genomes. We identified a patient with a series of mutations in an invariant cytotoxic lymphocyte (CTL)-restricted gag epitope required for retroviral structure and replication and implicated in long-term nonprogression to AIDS. The presence of wild-type sequence argues these mutations are involved in immune escape, whereas its reversion to a sequence seen only in the sooty mangabey reservoir suggests an alternate means of controlling infection. Surveillance and molecular characterization of circulating strains are essential for continued development of monitoring tools and may provide greater insight into the reduced pathogenicity of HIV-2.

  5. Sequences in gibbon ape leukemia virus envelope that confer sensitivity to HIV-1 accessory protein Vpu.

    PubMed

    Janaka, Sanath Kumar; Lucas, Tiffany M; Johnson, Marc C

    2011-11-01

    HIV-1 efficiently forms pseudotyped particles with many gammaretrovirus glycoproteins, such as Friend murine leukemia virus (F-MLV) Env, but not with the related gibbon ape leukemia virus (GaLV) Env or with a chimeric F-MLV Env with a GaLV cytoplasmic tail domain (CTD). This incompatibility is modulated by the HIV-1 accessory protein Vpu. Because the GaLV Env CTD does not resemble tetherin or CD4, the well-studied targets of Vpu, we sought to characterize the modular sequence in the GaLV Env CTD required for this restriction in the presence of Vpu. Using a systematic mutagenesis scan, we determined that the motif that makes GaLV Env sensitive to Vpu is INxxIxxVKxxVxRxK. This region in the CTD of GaLV Env is predicted to form a helix. Mutations in the CTD that would break this helix abolish sensitivity to Vpu. Although many of these positions can be replaced with amino acids with similar biophysical properties without disrupting the Vpu sensitivity, the final lysine residue is required. This Vpu sensitivity sequence appears to be modular, as the unrelated Rous sarcoma virus (RSV) Env can be made Vpu sensitive by replacing its CTD with the GaLV Env CTD. In addition, F-MLV Env can be made Vpu sensitive by mutating two amino acids in its cytoplasmic tail to make it resemble more closely the Vpu sensitivity motif. Surprisingly, the core components of this Vpu sensitivity sequence are also present in the host surface protein CD4, which is also targeted by Vpu through its CTD.

  6. Multiplexed highly-accurate DNA sequencing of closely-related HIV-1 variants using continuous long reads from single molecule, real-time sequencing.

    PubMed

    Dilernia, Dario A; Chien, Jung-Ting; Monaco, Daniela C; Brown, Michael P S; Ende, Zachary; Deymier, Martin J; Yue, Ling; Paxinos, Ellen E; Allen, Susan; Tirado-Ramos, Alfredo; Hunter, Eric

    2015-11-16

    Single Molecule, Real-Time (SMRT) Sequencing (Pacific Biosciences, Menlo Park, CA, USA) provides the longest continuous DNA sequencing reads currently available. However, the relatively high error rate in the raw read data requires novel analysis methods to deconvolute sequences derived from complex samples. Here, we present a workflow of novel computer algorithms able to reconstruct viral variant genomes present in mixtures with an accuracy of >QV50. This approach relies exclusively on Continuous Long Reads (CLR), which are the raw reads generated during SMRT Sequencing. We successfully implement this workflow for simultaneous sequencing of mixtures containing up to forty different >9 kb HIV-1 full genomes. This was achieved using a single SMRT Cell for each mixture and desktop computing power. This novel approach opens the possibility of solving complex sequencing tasks that currently lack a solution.

  7. Romidepsin-induced HIV-1 viremia during effective antiretroviral therapy contains identical viral sequences with few deleterious mutations

    PubMed Central

    Winckelmann, Anni; Barton, Kirston; Hiener, Bonnie; Schlub, Timothy E.; Shao, Wei; Rasmussen, Thomas A.; Østergaard, Lars; Søgaard, Ole S.; Tolstrup, Martin; Palmer, Sarah

    2017-01-01

    Objective: To investigate the origin of the HIV-1 viremia induced by the latency-reversing agent romidepsin. Design: Six individuals on suppressive antiretroviral therapy received romidepsin administered intravenously once weekly for 3 consecutive weeks. CD4+ T cells were obtained at baseline, following the second and third romidepsin infusion, and 10 weeks after the final romidepsin treatment. Plasma samples were collected 24 and 72 h after romidepsin infusions. Methods: Single-genome sequencing of the env and p24-RT region was used to genetically characterize the virus from proviral DNA, the transcribed cell-associated RNA and the plasma RNA pool. Results: In three of six participants with available plasma samples we identified plasma HIV-1 RNA sequences that were identical to DNA and/or cell-associated RNA sequences from peripheral blood CD4+ T cells. In two participants, plasma RNA sequences contained expansions of identical sequences, corresponding to 62 and 100% of the total sequences, respectively. Plasma HIV-1 RNA had very low amounts of defective viruses compared to cell-associated RNA (odds ratio 20.85, P < 0.001) and to DNA (odds ratio 7.07, P = 0.011) during romidepsin therapy. Conclusions: Romidepsin induced transcription from proviruses in peripheral blood cells, which contributed to viremia in patients on suppressive therapy. The intermingling of these cell-associated HIV-1 RNA with DNA sequences indicates transcription from a diverse range of proviruses, but the expansions of identical viral plasma sequences with few defects indicate that the romidepsin-induced viremia arises from intact proviruses with highly similar or identical genetic backgrounds. PMID:28272134

  8. Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences.

    PubMed

    Tartaglia, Lawrence J; Chang, Hui-Wen; Lee, Benjamin C; Abbink, Peter; Ng'ang'a, David; Boyd, Michael; Lavine, Christy L; Lim, So-Yon; Sanisetty, Srisowmya; Whitney, James B; Seaman, Michael S; Rolland, Morgane; Tovanabutra, Sodsai; Ananworanich, Jintanat; Robb, Merlin L; Kim, Jerome H; Michael, Nelson L; Barouch, Dan H

    2016-02-01

    Simian-human immunodeficiency virus (SHIV) challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need for the field has been the lack of a SHIV challenge stock expressing circulating recombinant form 01_AE (CRF01_AE) env sequences. We therefore sought to develop mucosally transmissible SHIV challenge stocks containing HIV-1 CRF01_AE env derived from acutely HIV-1 infected individuals from Thailand. SHIV-AE6, SHIV-AE6RM, and SHIV-AE16 contained env sequences that were >99% identical to the original HIV-1 isolate and did not require in vivo passaging. These viruses exhibited CCR5 tropism and displayed a tier 2 neutralization phenotype. These challenge stocks efficiently infected rhesus monkeys by the intrarectal route, replicated to high levels during acute infection, and established chronic viremia in a subset of animals. SHIV-AE16 was titrated for use in single, high dose as well as repetitive, low dose intrarectal challenge studies. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines, monoclonal antibodies, and other interventions targeted at preventing HIV-1 CRF01_AE infection.

  9. A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control.

    PubMed

    Bartha, István; Carlson, Jonathan M; Brumme, Chanson J; McLaren, Paul J; Brumme, Zabrina L; John, Mina; Haas, David W; Martinez-Picado, Javier; Dalmau, Judith; López-Galíndez, Cecilio; Casado, Concepción; Rauch, Andri; Günthard, Huldrych F; Bernasconi, Enos; Vernazza, Pietro; Klimkait, Thomas; Yerly, Sabine; O'Brien, Stephen J; Listgarten, Jennifer; Pfeifer, Nico; Lippert, Christoph; Fusi, Nicolo; Kutalik, Zoltán; Allen, Todd M; Müller, Viktor; Harrigan, P Richard; Heckerman, David; Telenti, Amalio; Fellay, Jacques

    2013-10-29

    HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10(-12)). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation for identifying host factors: (1) association signals are much stronger for HIV-1 sequence variants than VL, reflecting the 'intermediate phenotype' nature of viral variation; (2) association testing can be run without any clinical data. The proposed genome-to-genome approach highlights sites of genomic conflict and is a strategy generally applicable to studies of host-pathogen interaction. DOI:http://dx.doi.org/10.7554/eLife.01123.001.

  10. Characterization of HIV type 1 envelope sequence among viral isolates circulating in the northern region of Colombia, South America.

    PubMed

    Villarreal, José-Luis; Gutiérrez, Jaime; Palacio, Lucy; Peñuela, Martha; Hernández, Robin; Lemay, Guy; Cervantes-Acosta, Guillermo

    2012-12-01

    To characterize human immunodeficiency virus (HIV-1) strains circulating in the Northern region of Colombia in South America, sequences of the viral envelope C2V3C3 region were obtained from patients with different high-risk practices. Close to 60% of the sequences were predicted to belong to macrophage-tropic viruses, according to the positions of acidic amino acids and putative N-linked glycosylation sites. This is in agreement with the fact that most of the patients were recently diagnosed individuals. Phylogenic analysis then allowed assignment of all 35 samples to subtype B viruses. This same subtype was found in previous studies carried out in other Colombian regions. This study thus expands previous analyses with previously missing data from the Northern region of the country. The number and the length of the sequences examined also help to provide a clearer picture of the prevailing situation of the present HIV epidemics in this country.

  11. Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling

    PubMed Central

    Campbell, Patrick E.; Isayev, Olexandr; Ali, Syed A.; Roth, William W.; Huang, Ming-Bo; Powell, Michael D.; Leszczynski, Jerzy

    2012-01-01

    The HIV-1 accessory protein Nef plays an active role in the pathogenesis of AIDS by its numerous cellular interactions that facilitate the release of virus particles. This 27 kDa protein is required for maintenance of the viral replication in HIV, and is also known to contribute to immune evasion, blocking of apoptosis in virus-infected cells and enhancement of virus infectivity. Nef has been shown to be secreted and is present on the surface of virus-infected cells. Recent studies from our laboratory have shown that the Nef protein is secreted from nef-transfected and HIV-1-infected cells in small exosome-like vesicles (40–100 nm diam.) that do not contain virions. We have identified three amino-terminal domains of Nef as necessary for secretion: (i) the four arginine residues (17,19,21, 22) comprising the basic region; (ii) the phosphofurin acidic cluster sequence (PACS) composed of four glutamic acid residues (61–64); (iii) a previously unknown motif spanning amino acid residues 65–69 (VGFPV) which we named the secretion modification region (SMR). In this study, we have used population-based phylogeny data and sequence analysis to characterize the conservation of the Nef SMR domain that regulates vesicle secretion. We have performed in silico computational chemistry analysis involving molecular dynamic structure modeling of mutations in the SMR motif. Sequence analysis of Nef from HIV-1-infected patients, including slow progressors (SP), long term progressors (LTP) and long term non-progressors (LTNP) demonstrated 99 % conservation of the Nef SMR motif. Computational analysis including modeling of wild-type HIV-1 Nef and V66A Nef SMR mutant using structural homology and molecular dynamics of ligand-associated interactions indicated significant structural changes in the Nef mutant, thus supporting the importance of the SMR domain for mediating Nef vesicle secretion. PMID:22643973

  12. Comparison of a High-Resolution Melting Assay to Next-Generation Sequencing for Analysis of HIV Diversity

    PubMed Central

    Cousins, Matthew M.; Ou, San-San; Wawer, Maria J.; Munshaw, Supriya; Swan, David; Magaret, Craig A.; Mullis, Caroline E.; Serwadda, David; Porcella, Stephen F.; Gray, Ronald H.; Quinn, Thomas C.; Donnell, Deborah; Eshleman, Susan H.

    2012-01-01

    Next-generation sequencing (NGS) has recently been used for analysis of HIV diversity, but this method is labor-intensive, costly, and requires complex protocols for data analysis. We compared diversity measures obtained using NGS data to those obtained using a diversity assay based on high-resolution melting (HRM) of DNA duplexes. The HRM diversity assay provides a single numeric score that reflects the level of diversity in the region analyzed. HIV gag and env from individuals in Rakai, Uganda, were analyzed in a previous study using NGS (n = 220 samples from 110 individuals). Three sequence-based diversity measures were calculated from the NGS sequence data (percent diversity, percent complexity, and Shannon entropy). The amplicon pools used for NGS were analyzed with the HRM diversity assay. HRM scores were significantly associated with sequence-based measures of HIV diversity for both gag and env (P < 0.001 for all measures). The level of diversity measured by the HRM diversity assay and NGS increased over time in both regions analyzed (P < 0.001 for all measures except for percent complexity in gag), and similar amounts of diversification were observed with both methods (P < 0.001 for all measures except for percent complexity in gag). Diversity measures obtained using the HRM diversity assay were significantly associated with those from NGS, and similar increases in diversity over time were detected by both methods. The HRM diversity assay is faster and less expensive than NGS, facilitating rapid analysis of large studies of HIV diversity and evolution. PMID:22785188

  13. Satellites monitor Los Alamos fires

    NASA Astrophysics Data System (ADS)

    Kalluri, Satya; White, Benjamin

    A man-made fire that was intended to be a “controlled burn” for clearing brush and wilderness at the Bandelier National Monument, New Mexico, became an inferno that devastated significant portions of Los Alamos during the first week of May 2000. Now known as the Cerro Grande fire, it was not confined to Los Alamos alone. The fire spread to 15% of the Santa Clara Indian Reservation and a substantial area of the surrounding national parks and U.S. forests.The National Weather Service estimates that more than 100,000 fires occur in the natural environment each year within the United States alone, of which about 90% are manmade. Remote sensing images from satellites could be used to detect and monitor these active fires and biomass burning. Forest fires have a significant environmental and economic impact, and timely information about their location and magnitude is essential to contain them.

  14. A survey of synthetic HIV-1 peptides with natural and chimeric sequences for differential reactivity with Zimbabwean, Tanzanian and Swedish HIV-1-positive sera.

    PubMed

    Blomberg, J; Lawoko, A; Pipkorn, R; Moyo, S; Malmvall, B E; Shao, J; Dash, R; Tswana, S

    1993-06-01

    The objective of this study was to determine whether the known sequence differences between African and non-African HIV-1 strains are reflected in the serological response. The authors investigated the antibody reactivity of 34 Swedish, 30 Tanzanian, and 42 Zimbabwean HIV-1 positive sera to 67 synthetic peptides with sequences from North American and African HIV-1 isolates, mostly derived from regions of gag and env known to be antigenic. Not all sera were tested against all peptides. The authors noted several results. Differences in frequency of reactivity were noted with peptides covering the entire third variable domain (V3), which is a primary neutralization determinant, and the carboxyl terminus of gp120, in 2 regions of gp41, and the carboxyl terminus of p24. In env, Tanzanian sera reacted preferentially with a V3 peptide from the strain JY1 (Zaire). Gradual substitutions in the central motif in V3 of ELI from GLGQ to GPGR, typical of many non-African strains, led to a gradual increase in reactivity of many Swedish sera, but did not affect Tanzanian and Zimbabwean sera, suggesting that the major epitopes recognized by these African sera are outside GPGR. V3 peptides from the MN and Z3 strains reacted with most sera, but missed 30% of those of Tanzanian origin. In the carboxyl terminus of gp120, both sets of African sera reacted preferentially with peptides from strains JY1 and MAL. Swedish sera reacted strongest with analogues from strains Z321 and HXB2. In gp41, Swedish sera showed a weak preference for reactivity with HXB2-derived peptides in the immunodominant region (amino acids 620-665). The differences in serological reactivity were as great between Zimbabwe and Tanzania as between the 2 African sets and the Swedish. The geographical differences in the pattern of reactivity with HIV peptides probably depend on both host and viral variation and may be developed into a seroepidemiological tool, useful for optimization of future HIV vaccines.

  15. Correlating low-similarity peptide sequences and HIV B-cell epitopes.

    PubMed

    Kanduc, Darja; Serpico, Rosario; Lucchese, Alberta; Shoenfeld, Yehuda

    2008-02-01

    Although a large number of human immunodeficiency virus-1 (HIV-1) derived B-cell epitopes has been experimentally identified, the structural requirements underlying HIV humoral immune response remain unknown. Here, we review the current literature on HIV B-cell epitopes as catalogued in the www.hiv.lanl.gov/content/immunology website, searching for common structural and/or functional immunogenic motifs. The analysis of HIV antibody data documents that the linear determinants recognized by human or murine humoral immune responses, are (or harbor) pentapeptide fragments with no or only very low similarity to the respective host proteome. The present literature analysis provides relevant insights that may be applied to design anti-HCV therapeutic approaches exempt from autoimmune collateral effects.

  16. Los Alamos Science: Number 16

    SciTech Connect

    Cooper, N.G.

    1988-01-01

    It was an unusually stimulating day and a half at Los Alamos when two Nobel Laureates in physiology, a leading paleontologist, and a leading bio-astrophysicist came together to discuss ''Unsolved Problems in the Science of Life,'' the topic of the second in a series of special meetings sponsored by the Fellows of the Laboratory. Just like the first one on ''Creativity in Science,'' this colloquium took us into a broader arena of ideas and viewpoints than is our usual daily fare. To contemplate the evolution and mysteries of intelligent life from the speakers' diverse points of view at one time, in one place was indeed a rare experience.

  17. HIV gp120 H375 is unique to HIV-1 subtype CRF01_AE and confers strong resistance to the entry inhibitor BMS-599793, a candidate microbicide drug.

    PubMed

    Schader, Susan M; Colby-Germinario, Susan P; Quashie, Peter K; Oliveira, Maureen; Ibanescu, Ruxandra-Ilinca; Moisi, Daniela; Mespléde, Thibault; Wainberg, Mark A

    2012-08-01

    BMS-599793 is a small molecule entry inhibitor that binds to human immunodeficiency virus type 1 (HIV-1) gp120, resulting in the inhibition of CD4-dependent entry into cells. Since BMS-599793 is currently considered a candidate microbicide drug, we evaluated its efficacy against a number of primary patient HIV isolates from different subtypes and circulating recombinant forms (CRFs) and showed that activity varied between ∼3 ρM and 7 μM at 50% effective concentrations (EC(50)s). Interestingly, CRF01_AE HIV-1 isolates consistently demonstrated natural resistance against this compound. Genotypic analysis of >1,600 sequences (Los Alamos HIV sequence database) indicated that a single amino acid polymorphism in Env, H375, may account for the observed BMS-599793 resistance in CRF01_AE HIV-1. Results of site-directed mutagenesis experiments confirmed this hypothesis, and in silico drug docking simulations identified a drug resistance mechanism at the molecular level. In addition, CRF01_AE viruses were shown to be resistant to multiple broadly neutralizing monoclonal antibodies. Thus, our results not only provide insight into how Env polymorphisms may contribute to entry inhibitor resistance but also may help to elucidate how HIV can evade some broadly neutralizing antibodies. Furthermore, the high frequency of H375 in CRF01_AE HIV-1, and its apparent nonoccurrence in other subtypes, could serve as a means for rapid identification of CRF01_AE infections.

  18. Intercontinental Dispersal of HIV-1 Subtype B Associated with Transmission among Men Who Have Sex with Men in Japan

    PubMed Central

    Naito, Yuki; Raghwani, Jayna; Fearnhill, Esther; Sano, Takako; Kusagawa, Shigeru; Mbisa, Jean L.; Zhang, Hongyi; Matano, Tetsuro; Leigh Brown, Andrew J.; Pybus, Oliver G.; Dunn, David; Kondo, Makiko

    2014-01-01

    ABSTRACT Transmission clusters of HIV-1 subtype B uniquely associated with the epidemic among men who have sex with men (MSM) in East Asia have recently been identified. Using the Los Alamos HIV sequence database and the UK HIV drug resistance database, we explored possible links between HIV MSM epidemics in East Asia and the rest of the world by using phylogenetic and molecular clock analyses. We found that JP.MSM.B-1, a subtype B MSM variant that accounts for approximately one-third of the infections among Japanese MSM, was detected worldwide, in the United Kingdom (n = 13), mainland China (n = 3), the United States, Germany, Canada, and Taiwan (n = 1 each). Interestingly, 10 United Kingdom samples plus two from Germany and the United States formed a distinct monophyletic subgroup within JP.MSM.B-1. The estimated divergence times of JP.MSM.B-1 and the latter subgroup were ∼1989 and ∼1999, respectively. These dates suggest that JP.MSM.B-1 was circulating for many years in Japan among MSM before disseminating to other countries, most likely through global MSM networks. A significant number of other Asian MSM HIV lineages were also detected in the UK HIV drug resistance database. Our study provides insight into the regional and global dispersal of Asian MSM HIV lineages. Further study of these strains is warranted to elucidate viral migration and the interrelationship of HIV epidemics on a global scale. IMPORTANCE We previously identified several transmission clusters of HIV-1 subtype B uniquely associated with the epidemic among men who have sex with men (MSM) in East Asia. Using the Los Alamos HIV sequence database and the UK HIV drug resistance database, we explored the possible interplay of HIV MSM epidemics in the different geographic regions and found previously unrecognized interrelationships among the HIV-1 epidemics in East Asia, the United Kingdom, and the rest of the world. Our study provides insight into the regional and global dispersal of Asian MSM

  19. Whole Genome Deep Sequencing of HIV-1 Reveals the Impact of Early Minor Variants Upon Immune Recognition During Acute Infection

    PubMed Central

    Henn, Matthew R.; Lennon, Niall J.; Power, Karen A.; Macalalad, Alexander R.; Berlin, Aaron M.; Malboeuf, Christine M.; Ryan, Elizabeth M.; Gnerre, Sante; Zody, Michael C.; Erlich, Rachel L.; Green, Lisa M.; Berical, Andrew; Wang, Yaoyu; Casali, Monica; Streeck, Hendrik; Bloom, Allyson K.; Dudek, Tim; Tully, Damien; Newman, Ruchi; Axten, Karen L.; Gladden, Adrianne D.; Battis, Laura; Kemper, Michael; Zeng, Qiandong; Shea, Terrance P.; Gujja, Sharvari; Zedlack, Carmen; Gasser, Olivier; Brander, Christian; Hess, Christoph; Günthard, Huldrych F.; Brumme, Zabrina L.; Brumme, Chanson J.; Bazner, Suzane; Rychert, Jenna; Tinsley, Jake P.; Mayer, Ken H.; Rosenberg, Eric; Pereyra, Florencia; Levin, Joshua Z.; Young, Sarah K.; Jessen, Heiko; Altfeld, Marcus; Birren, Bruce W.; Walker, Bruce D.; Allen, Todd M.

    2012-01-01

    Deep sequencing technologies have the potential to transform the study of highly variable viral pathogens by providing a rapid and cost-effective approach to sensitively characterize rapidly evolving viral quasispecies. Here, we report on a high-throughput whole HIV-1 genome deep sequencing platform that combines 454 pyrosequencing with novel assembly and variant detection algorithms. In one subject we combined these genetic data with detailed immunological analyses to comprehensively evaluate viral evolution and immune escape during the acute phase of HIV-1 infection. The majority of early, low frequency mutations represented viral adaptation to host CD8+ T cell responses, evidence of strong immune selection pressure occurring during the early decline from peak viremia. CD8+ T cell responses capable of recognizing these low frequency escape variants coincided with the selection and evolution of more effective secondary HLA-anchor escape mutations. Frequent, and in some cases rapid, reversion of transmitted mutations was also observed across the viral genome. When located within restricted CD8 epitopes these low frequency reverting mutations were sufficient to prime de novo responses to these epitopes, again illustrating the capacity of the immune response to recognize and respond to low frequency variants. More importantly, rapid viral escape from the most immunodominant CD8+ T cell responses coincided with plateauing of the initial viral load decline in this subject, suggestive of a potential link between maintenance of effective, dominant CD8 responses and the degree of early viremia reduction. We conclude that the early control of HIV-1 replication by immunodominant CD8+ T cell responses may be substantially influenced by rapid, low frequency viral adaptations not detected by conventional sequencing approaches, which warrants further investigation. These data support the critical need for vaccine-induced CD8+ T cell responses to target more highly constrained

  20. Improvement in the determination of HIV-1 tropism using the V3 gene sequence and a combination of bioinformatic tools.

    PubMed

    Chueca, Natalia; Garrido, Carolina; Alvarez, Marta; Poveda, Eva; de Dios Luna, Juan; Zahonero, Natalia; Hernández-Quero, José; Soriano, Vicente; Maroto, Carmen; de Mendoza, Carmen; García, Federico

    2009-05-01

    Assessment of HIV tropism using bioinformatic tools based on V3 sequences correlates poorly with results provided by phenotypic tropism assays, particularly for recognizing X4 viruses. This may represent an obstacle for the use of CCR5 antagonists. An algorithm combining several bioinformatic tools might improve the correlation with phenotypic tropism results. A total of 200 V3 sequences from HIV-1 subtype B, available in several databases with known phenotypic tropism results, were used to evaluate the sensitivity and specificity of seven different bioinformatic tools (PSSM, SVM, C4.5 decision tree generator and C4.5, PART, Charge Rule, and Geno2pheno). The best predictive bioinformatic tools were identified, and a model combining several of these was built. Using the 200 reference sequences, SVM and geno2-pheno showed the highest sensitivity for detecting X4 viruses (98.8% and 93.7%, respectively); however, their specificity was relatively low (62.5% and 86.6%, respectively). For R5 viruses, PSSM and C4.5 gave the same results and outperformed other bioinformatic tools (95.7% sensitivity, 82% specificity). When results from three out of these four tools were concordant, the sensitivity and specificity, taking as reference the results from phenotypic tropism assays, were over 90% in predicting either R5 or X4 viruses (AUC: 0.9701; 95% CI: 0.9358-0.9889). An algorithm combining four distinct bioinformatic tools (SVM, geno2pheno, PSSM and C4.5), improves the genotypic prediction of HIV tropism, and merits further evaluation, as it might prove useful as a screening strategy in clinical practice.

  1. Whole genome deep sequencing of HIV-1 reveals the impact of early minor variants upon immune recognition during acute infection.

    PubMed

    Henn, Matthew R; Boutwell, Christian L; Charlebois, Patrick; Lennon, Niall J; Power, Karen A; Macalalad, Alexander R; Berlin, Aaron M; Malboeuf, Christine M; Ryan, Elizabeth M; Gnerre, Sante; Zody, Michael C; Erlich, Rachel L; Green, Lisa M; Berical, Andrew; Wang, Yaoyu; Casali, Monica; Streeck, Hendrik; Bloom, Allyson K; Dudek, Tim; Tully, Damien; Newman, Ruchi; Axten, Karen L; Gladden, Adrianne D; Battis, Laura; Kemper, Michael; Zeng, Qiandong; Shea, Terrance P; Gujja, Sharvari; Zedlack, Carmen; Gasser, Olivier; Brander, Christian; Hess, Christoph; Günthard, Huldrych F; Brumme, Zabrina L; Brumme, Chanson J; Bazner, Suzane; Rychert, Jenna; Tinsley, Jake P; Mayer, Ken H; Rosenberg, Eric; Pereyra, Florencia; Levin, Joshua Z; Young, Sarah K; Jessen, Heiko; Altfeld, Marcus; Birren, Bruce W; Walker, Bruce D; Allen, Todd M

    2012-01-01

    Deep sequencing technologies have the potential to transform the study of highly variable viral pathogens by providing a rapid and cost-effective approach to sensitively characterize rapidly evolving viral quasispecies. Here, we report on a high-throughput whole HIV-1 genome deep sequencing platform that combines 454 pyrosequencing with novel assembly and variant detection algorithms. In one subject we combined these genetic data with detailed immunological analyses to comprehensively evaluate viral evolution and immune escape during the acute phase of HIV-1 infection. The majority of early, low frequency mutations represented viral adaptation to host CD8+ T cell responses, evidence of strong immune selection pressure occurring during the early decline from peak viremia. CD8+ T cell responses capable of recognizing these low frequency escape variants coincided with the selection and evolution of more effective secondary HLA-anchor escape mutations. Frequent, and in some cases rapid, reversion of transmitted mutations was also observed across the viral genome. When located within restricted CD8 epitopes these low frequency reverting mutations were sufficient to prime de novo responses to these epitopes, again illustrating the capacity of the immune response to recognize and respond to low frequency variants. More importantly, rapid viral escape from the most immunodominant CD8+ T cell responses coincided with plateauing of the initial viral load decline in this subject, suggestive of a potential link between maintenance of effective, dominant CD8 responses and the degree of early viremia reduction. We conclude that the early control of HIV-1 replication by immunodominant CD8+ T cell responses may be substantially influenced by rapid, low frequency viral adaptations not detected by conventional sequencing approaches, which warrants further investigation. These data support the critical need for vaccine-induced CD8+ T cell responses to target more highly constrained

  2. The HIV-1 repeated sequence R as a robust hot-spot for copy-choice recombination

    PubMed Central

    Moumen, Abdeladim; Polomack, Lucette; Roques, Bernard; Buc, Henri; Negroni, Matteo

    2001-01-01

    Template switching during reverse transcription is crucial for retroviral replication. While strand transfer on the terminal repeated sequence R is essential to achieve reverse transcription, template switching from internal regions of the genome (copy choice) leads to genetic recombination. We have developed an experimental system to study copy-choice recombination in vitro along the HIV-1 genome. We identify here several genomic regions, including the R sequence, where copy choice occurred at high rates. The frequency of copy choice occurring in a given region of template was strongly influenced by the surrounding sequences, an observation that suggests a pivotal role of the folding of template RNA in the process. The sequence R, instead, constituted an exception to this rule since it was a strong hot-spot for copy choice in the different sequence contexts tested. We suggest therefore that the structure of this region has been optimised during viral evolution to ensure efficient template switching independently from the sequences that might surround it. PMID:11557813

  3. Conserved sequences in the current strains of HIV-1 subtype A in Russia are effectively targeted by artificial RNAi in vitro.

    PubMed

    Tchurikov, Nickolai A; Fedoseeva, Daria M; Gashnikova, Natalya M; Sosin, Dmitri V; Gorbacheva, Maria A; Alembekov, Ildar R; Chechetkin, Vladimir R; Kravatsky, Yuri V; Kretova, Olga V

    2016-05-25

    Highly active antiretroviral therapy has greatly reduced the morbidity and mortality of AIDS. However, many of the antiretroviral drugs are toxic with long-term use, and all currently used anti-HIV agents generate drug-resistant mutants. Therefore, there is a great need for new approaches to AIDS therapy. RNAi is a powerful means of inhibiting HIV-1 production in human cells. We propose to use RNAi for gene therapy of HIV/AIDS. Previously we identified a number of new biologically active siRNAs targeting several moderately conserved regions in HIV-1 transcripts. Here we analyze the heterogeneity of nucleotide sequences in three RNAi targets in sequences encoding the reverse transcriptase and integrase domains of current isolates of HIV-1 subtype A in Russia. These data were used to generate genetic constructs expressing short hairpin RNAs 28-30-bp in length that could be processed in cells into siRNAs. After transfection of the constructs we observed siRNAs that efficiently attacked the selected targets. We expect that targeting several viral genes important for HIV-1 reproduction will help overcome the problem of viral adaptation and will prevent the appearance of RNAi escape mutants in current virus strains, an important feature of gene therapy of HIV/AIDS.

  4. High-throughput sequencing identifies HIV-1-replication- and latency-related miRNAs in CD4(+) T cell lines.

    PubMed

    Lu, Xiangyun; Yang, Jin; Wu, Haibo; Yang, Zongxing; Jin, Changzhong; Wang, Juan; Cheng, Linfang; Peng, Xiaorong; Liu, Fumin; Peng, Xiuming; Ji, Sujing; Ou, Huilin; Xie, Tiansheng; Yao, Hangping; Wu, Nanping

    2017-03-16

    MicroRNAs are potent gene expression regulators involved in regulating various biological processes, including host-pathogen interactions. In this study, we used high-throughput sequencing to investigate cellular miRNA signatures related to HIV-1 replication and latent infection in CD4(+) T cell lines, which included HIV-1-replicating H9/HTLV-IIIB, HIV-1-latently-infected CEM-Bru cells, and their parental uninfected H9 and CEM-SS cells. Relatively few miRNAs were found to be modulated by HIV-1 replication or latent infection, while the cell-lineage-specific miRNA difference was more pronounced, irrespective of HIV-1 infection. In silico analysis showed that some of our HIV-1 infection-regulated miRNA profiles echoed previous studies, while others were novel. In addition, some of the miRNAs that were differentially expressed between the productively and latently infected cells seemed to participate in shaping the differential infection state. Thus, the newly identified miRNA profiles related to HIV-1 replication and latency provide information about the interplay between HIV-1 and its host.

  5. Comparative mucosal immunogenicity of HIV gp41 membrane-proximal external region (MPER) containing single and multiple repeats of ELDKWA sequence with defensin peptides.

    PubMed

    Mohan, Teena; Verma, Priyanka; Rao, D N

    2014-04-01

    The MPER of gp41 of HIV-1 has received great attention and is widely recognized as a promising target for the development of AIDS vaccine. We investigated the ability of trirepeat of ELDKWA sequence of gp41 antigen with defensins in liposome using multiple-shot immunization strategy in the mice model. The designed was used to enhance the immunogenicity and exposure of MPER in its native conformation for the induction of MPER-specific HIV-1 neutralizing antibodies. To characterize, we estimated the antibody levels (IgG/IgA) in serum as well as in lung, intestinal, vaginal and rectal washes till day 120 in outbred and inbred (H-2(b) and H-2(d)) mice using liposome as delivery vehicle. The representative sera and washes were also tested for in vitro neutralization with CCR5-tropic Indian HIV-1 primary isolates. We observed that the modified HIV antigen containing trirepeat of ELDKWA with defensins was showing significantly (p<0.001) higher IgG/IgA antibody titre (102,400-204,800) in sera as well as in different mucosal washes (1600-6400) than standard HIV-1 antigen. Furthermore, sera from the modified HIV-1 antigen with defensins found to exhibit higher neutralizing activities (ranging from 59.3% to 84.6%) than the standard HIV-1 antigen. These results show that the induction of MPER-specific HIV-1 neutralizing antibodies could be achieved through a rationally designed vaccine strategy.

  6. Multiplexed next-generation sequencing and de novo assembly to obtain near full-length HIV-1 genome from plasma virus.

    PubMed

    Aralaguppe, Shambhu G; Siddik, Abu Bakar; Manickam, Ashokkumar; Ambikan, Anoop T; Kumar, Milner M; Fernandes, Sunjay Jude; Amogne, Wondwossen; Bangaruswamy, Dhinoth K; Hanna, Luke Elizabeth; Sonnerborg, Anders; Neogi, Ujjwal

    2016-10-01

    Analysing the HIV-1 near full-length genome (HIV-NFLG) facilitates new understanding into the diversity of virus population dynamics at individual or population level. In this study we developed a simple but high-throughput next generation sequencing (NGS) protocol for HIV-NFLG using clinical specimens and validated the method against an external quality control (EQC) panel. Clinical specimens (n=105) were obtained from three cohorts from two highly conserved HIV-1C epidemics (India and Ethiopia) and one diverse epidemic (Sweden). Additionally an EQC panel (n=10) was used to validate the protocol. HIV-NFLG was performed amplifying the HIV-genome (Gag-to-nef) in two fragments. NGS was performed using the Illumina HiSeq2500 after multiplexing 24 samples, followed by de novo assembly in Iterative Virus Assembler or VICUNA. Subtyping was carried out using several bioinformatics tools. Amplification of HIV-NFLG has 90% (95/105) success-rate in clinical specimens. NGS was successful in all clinical specimens (n=45) and EQA samples (n=10) attempted. The mean error for mutations for the EQC panel viruses were <1%. Subtyping identified two as A1C recombinant. Our results demonstrate the feasibility of a simple NGS-based HIV-NFLG that can potentially be used in the molecular surveillance for effective identification of subtypes and transmission clusters for operational public health intervention.

  7. Touchdown digital polymerase chain reaction for quantification of highly conserved sequences in the HIV-1 genome.

    PubMed

    De Spiegelaere, Ward; Malatinkova, Eva; Kiselinova, Maja; Bonczkowski, Pawel; Verhofstede, Chris; Vogelaers, Dirk; Vandekerckhove, Linos

    2013-08-15

    Digital polymerase chain reaction (PCR) is an emerging absolute quantification method based on the limiting dilution principle and end-point PCR. This methodology provides high flexibility in assay design without influencing quantitative accuracy. This article describes an assay to quantify HIV DNA that targets a highly conserved region of the HIV-1 genome that hampers optimal probe design. To maintain high specificity and allow probe binding and hydrolysis of a probe with low melting temperature, a two-stage touchdown PCR was designed with a first round of amplification at high temperature and a subsequent round at low temperature to allow accumulation of fluorescence.

  8. Los Alamos PC estimating system

    SciTech Connect

    Stutz, R.A.; Lemon, G.D.

    1987-01-01

    The Los Alamos Cost Estimating System (QUEST) is being converted to run on IBM personal computers. This very extensive estimating system is capable of supporting cost estimators from many different and varied fields. QUEST does not dictate any fixed method for estimating. QUEST supports many styles and levels of detail estimating. QUEST can be used with or without data bases. This system allows the estimator to provide reports based on levels of detail defined by combining work breakdown structures. QUEST provides a set of tools for doing any type of estimate without forcing the estimator to use any given method. The level of detail in the estimate can be mixed based on the amount of information known about different parts of the project. The system can support many different data bases simultaneously. Estimators can modify any cost in any data base.

  9. Los Alamos Science: The Human Genome Project. Number 20, 1992

    DOE R&D Accomplishments Database

    Cooper, N. G.; Shea, N. eds.

    1992-01-01

    This document provides a broad overview of the Human Genome Project, with particular emphasis on work being done at Los Alamos. It tries to emphasize the scientific aspects of the project, compared to the more speculative information presented in the popular press. There is a brief introduction to modern genetics, including a review of classic work. There is a broad overview of the Genome Project, describing what the project is, what are some of its major five-year goals, what are major technological challenges ahead of the project, and what can the field of biology, as well as society expect to see as benefits from this project. Specific results on the efforts directed at mapping chromosomes 16 and 5 are discussed. A brief introduction to DNA libraries is presented, bearing in mind that Los Alamos has housed such libraries for many years prior to the Genome Project. Information on efforts to do applied computational work related to the project are discussed, as well as experimental efforts to do rapid DNA sequencing by means of single-molecule detection using applied spectroscopic methods. The article introduces the Los Alamos staff which are working on the Genome Project, and concludes with brief discussions on ethical, legal, and social implications of this work; a brief glimpse of genetics as it may be practiced in the next century; and a glossary of relevant terms.

  10. Los Alamos Science: The Human Genome Project. Number 20, 1992

    SciTech Connect

    Cooper, N G; Shea, N

    1992-01-01

    This article provides a broad overview of the Human Genome Project, with particular emphasis on work being done at Los Alamos. It tries to emphasize the scientific aspects of the project, compared to the more speculative information presented in the popular press. There is a brief introduction to modern genetics, including a review of classic work. There is a broad overview of the Genome Project, describing what the project is, what are some of its major five-year goals, what are major technological challenges ahead of the project, and what can the field of biology, as well as society expect to see as benefits from this project. Specific results on the efforts directed at mapping chromosomes 16 and 5 are discussed. A brief introduction to DNA libraries is presented, bearing in mind that Los Alamos has housed such libraries for many years prior to the Genome Project. Information on efforts to do applied computational work related to the project are discussed, as well as experimental efforts to do rapid DNA sequencing by means of single-molecule detection using applied spectroscopic methods. The article introduces the Los Alamos staff which are working on the Genome Project, and concludes with brief discussions on ethical, legal, and social implications of this work; a brief glimpse of genetics as it may be practiced in the next century; and a glossary of relevant terms.

  11. Worldwide genetic features of HIV-1 Env α4β7 binding motif: the Local Dissemination Impact of the LDI tripeptide

    PubMed Central

    Hait, Sabrina H.; Soares, Esmeralda A.; Sprinz, Eduardo; Arthos, James; Machado, Elizabeth S.; Soares, Marcelo A.

    2015-01-01

    Background HIV-1 gp120 binds to integrin α4β7, a homing receptor of lymphocytes to gut-associated lymphoid tissues. This interaction is mediated by the LDI/V tripeptide encoded in the V2-loop. This tripeptide mimics similar motifs in MAdCAM and VCAM, the natural ligands of α4β7. In this study we explored the association of V2-loop LDI/V mimotopes with transmission routes and patterns of disease progression in HIV-infected adult and pediatric patients. HIV-1 env sequences available in the Los Alamos HIV Sequence Database were included in the analyses. Methodology HIV-1 V2-loop sequences generated from infected adults and infants from South and Southeast Brazil, and also retrieved from the Los Alamos Database, were assessed for α4β7 binding tripeptide composition. Chi-Square/Fisher’s Exact test and Mann Whitney U-test were used for tripeptide comparisons. Shannon entropy was assessed for conservancy of the α4β7 tripeptide mimotope. Results We observed no association between the tripeptide composition or conservation and virus transmission route or disease progression. However, LDI was linked to successful epidemic dissemination of HIV-1 subtype C in South America, and further to other expanding non-B subtypes in Europe and Asia. In Africa, subtypes showing increased LDV prevalence evidenced an ongoing process of selection towards LDI expansion, an observation also extended to subtype B in the Americas and Western Europe. Conclusions The V2-loop LDI mimotope was conserved in HIV-1C from South America and other expanding subtypes across the globe, which suggests that LDI may promote successful dissemination of HIV at local geographic levels by means of increased transmission fitness. PMID:26569174

  12. Short Communication: Investigating a Chain of HIV Transmission Events Due to Homosexual Exposure and Blood Transfusion Based on a Next Generation Sequencing Method.

    PubMed

    Zhao, Qi; Zhang, Chen; Jiang, Yan; Wen, Yujie; Pan, Pinliang; Li, Yang; Zhang, Guiyun; Zhang, Lei; Qiu, Maofeng

    2015-12-01

    This study investigates a chain of HIV transmission events due to homosexual exposure and blood transfusion in China. The MiSeq platform, a next generation sequencing (NGS) system, was used to obtain genetic details of the HIV-1 env region (336 base pairs). Evolutionary analysis combined with epidemiologic evidence suggests a transmission chain from patient T3 to T2 through homosexual exposure and subsequently to T1 through blood transfusion. More importantly, a phylogenetic study suggested a likely genetic bottleneck for HIV in homosexual transmission from T3 to T2, while T1 inherited the majority of variants from T2. The result from the MiSeq platform is consistent with findings from the epidemiologic survey. The MiSeq platform is a powerful tool for tracing HIV transmissions and intrapersonal evolution.

  13. Restriction of V3 region sequence divergence in the HIV-1 envelope gene during antiretroviral treatment in a cohort of recent seroconverters

    PubMed Central

    2013-01-01

    Background Dynamic changes in Human Immunodeficiency Virus 1 (HIV-1) sequence diversity and divergence are associated with immune control during primary infection and progression to AIDS. Consensus sequencing or single genome amplification sequencing of the HIV-1 envelope (env) gene, in particular the variable (V) regions, is used as a marker for HIV-1 genome diversity, but population diversity is only minimally, or semi-quantitatively sampled using these methods. Results Here we use second generation deep sequencing to determine inter-and intra-patient sequence heterogeneity and to quantify minor variants in a cohort of individuals either receiving or not receiving antiretroviral treatment following seroconversion; the SPARTAC trial. We show, through a cross-sectional study of sequence diversity of the env V3 in 30 antiretroviral-naive patients during primary infection that considerable population structure diversity exists, with some individuals exhibiting highly constrained plasma virus diversity. Diversity was independent of clinical markers (viral load, time from seroconversion, CD4 cell count) of infection. Serial sampling over 60 weeks of non-treated individuals that define three initially different diversity profiles showed that complex patterns of continuing HIV-1 sequence diversification and divergence could be readily detected. Evidence for minor sequence turnover, emergence of new variants and re-emergence of archived variants could be inferred from this analysis. Analysis of viral divergence over the same time period in patients who received short (12 weeks, ART12) or long course antiretroviral therapy (48 weeks, ART48) and a non-treated control group revealed that ART48 successfully suppressed viral divergence while ART12 did not have a significant effect. Conclusions Deep sequencing is a sensitive and reliable method for investigating the diversity of the env V3 as an important component of HIV-1 genome diversity. Detailed insights into the complex

  14. Bioinformatic analysis of neurotropic HIV envelope sequences identifies polymorphisms in the gp120 bridging sheet that increase macrophage-tropism through enhanced interactions with CCR5

    SciTech Connect

    Mefford, Megan E.; Kunstman, Kevin; Wolinsky, Steven M.; Gabuzda, Dana

    2015-07-15

    Macrophages express low levels of the CD4 receptor compared to T-cells. Macrophage-tropic HIV strains replicating in brain of untreated patients with HIV-associated dementia (HAD) express Envs that are adapted to overcome this restriction through mechanisms that are poorly understood. Here, bioinformatic analysis of env sequence datasets together with functional studies identified polymorphisms in the β3 strand of the HIV gp120 bridging sheet that increase M-tropism. D197, which results in loss of an N-glycan located near the HIV Env trimer apex, was detected in brain in some HAD patients, while position 200 was estimated to be under positive selection. D197 and T/V200 increased fusion and infection of cells expressing low CD4 by enhancing gp120 binding to CCR5. These results identify polymorphisms in the HIV gp120 bridging sheet that overcome the restriction to macrophage infection imposed by low CD4 through enhanced gp120–CCR5 interactions, thereby promoting infection of brain and other macrophage-rich tissues. - Highlights: • We analyze HIV Env sequences and identify amino acids in beta 3 of the gp120 bridging sheet that enhance macrophage tropism. • These amino acids at positions 197 and 200 are present in brain of some patients with HIV-associated dementia. • D197 results in loss of a glycan near the HIV Env trimer apex, which may increase exposure of V3. • These variants may promote infection of macrophages in the brain by enhancing gp120–CCR5 interactions.

  15. Association between a naturally arising polymorphism within a functional region of HIV-1 Nef and disease progression in chronic HIV-1 infection.

    PubMed

    Meribe, Stanley C; Hasan, Zafrul; Mahiti, Macdonald; Mwimanzi, Francis; Toyoda, Mako; Mori, Masahiko; Gatanaga, Hiroyuki; Kikuchi, Tadashi; Miura, Toshiyuki; Kawana-Tachikawa, Ai; Iwamoto, Aikichi; Oka, Shinichi; Ueno, Takamasa

    2015-08-01

    HIV-1 Nef mediates downregulation of HLA class I (HLA-I) through a number of highly conserved sequence motifs. We investigated the in vivo implication(s) of naturally arising polymorphisms in functional motifs in HIV-1 Nef that are associated with HLA-I downregulation, including the acidic cluster, polyproline, di-arginine and Met-20 regions. Plasma samples from treatment-naive, chronically HIV-1 infected subjects were collected after obtaining informed consent, and viral RNA was extracted and amplified by nested RT-PCR. The resultant nef amplicons were sequenced directly, and subtype-B sequences with an intact open reading frame (n = 406) were included in our analyses. There was over-representation of isoleucine at position 20 (Ile-20) in our dataset when compared to sequences in the Los Alamos sequence database (17.7 vs. 6.9 %, p = 0.0309). The presence of having Ile-20 in Nef was found to be associated with higher median plasma viral load (p = 0.013), independent of associated codons or viral lineage effects, whereas no clinical association was found with polymorphisms in the other functional motifs. Moreover, introduction of a Met-20-to-Ile mutation in a laboratory strain SF2 Nef resulted in a modest, albeit not statistically significant, increase in HLA class I downregulation activity (p = 0.06). Taken together, we have identified a naturally arising polymorphism, Ile-20, within HIV-1 subtype B Nef that is associated with poorer disease outcome.

  16. Source identification in two criminal cases using phylogenetic analysis of HIV-1 DNA sequences

    PubMed Central

    Scaduto, Diane I.; Brown, Jeremy M.; Haaland, Wade C.; Zwickl, Derrick J.; Hillis, David M.; Metzker, Michael L.

    2010-01-01

    Phylogenetic analysis has been widely used to test the a priori hypothesis of epidemiological clustering in suspected transmission chains of HIV-1. Among studies showing strong support for relatedness between HIV samples obtained from infected individuals, evidence for the direction of transmission between epidemiologically related pairs has been lacking. During transmission of HIV, a genetic bottleneck occurs, resulting in the paraphyly of source viruses with respect to those of the recipient. This paraphyly establishes the direction of transmission, from which the source can then be inferred. Here, we present methods and results from two criminal cases, State of Washington v Anthony Eugene Whitfield, case number 04-1-0617-5 (Superior Court of the State of Washington, Thurston County, 2004) and State of Texas v Philippe Padieu, case numbers 219-82276-07, 219-82277-07, 219-82278-07, 219-82279-07, 219-82280-07, and 219-82705-07 (219th Judicial District Court, Collin County, TX, 2009), which provided evidence that direction can be established from blinded case samples. The observed paraphyly from each case study led to the identification of an inferred source (i.e., index case), whose identity was revealed at trial to be that of the defendant. PMID:21078965

  17. Sunset at the ALaMO

    NASA Video Gallery

    A new color all-sky camera has opened its eyes at the ALaMO, or Automated Lunar and Meteor Observatory, at NASA's Marshall Space Flight Center in Huntsville, Ala. Watch its inaugural video below, s...

  18. Publications of Los Alamos research 1988

    SciTech Connect

    Varjabedian, K.; Dussart, S.A.; McClary, W.J.; Rich, J.A.

    1989-12-01

    This bibliography lists unclassified publications of work done at the Los Alamos National Laboratory for 1988. The entries, which are subdivided by broad subject categories, are cross-referenced with an author index and a numeric index.

  19. Environmental surveillance at Los Alamos during 1994

    SciTech Connect

    1996-07-01

    This report describes environmental monitoring activities at Los Alamos National Laboratory for 1994. Data were collected to assess external penetrating radiation, airborne emissions, liquid effluents, radioactivity of environmental materials and food stuffs, and environmental compliance.

  20. New Rad Lab for Los Alamos

    ScienceCinema

    None

    2016-07-12

    The topping out ceremony for a key construction stage in the Los Alamos National Laboratory's newest facility, the Radiological Laboratory Utility & Office Building. This is part of the National Nu...  

  1. New Rad Lab for Los Alamos

    SciTech Connect

    2008-08-06

    The topping out ceremony for a key construction stage in the Los Alamos National Laboratory's newest facility, the Radiological Laboratory Utility & Office Building. This is part of the National Nu...  

  2. Edward Teller Returns to LOS Alamos

    NASA Astrophysics Data System (ADS)

    Hecker, Siegfried S.

    2010-01-01

    I was asked to share some reflections of Edward Teller's return to Los Alamos during my directorship. I met Teller late in his life. My comments focus on that time and they will be mostly in the form of stories of my interactions and those of my colleagues with Teller. Although the focus of this symposium is on Teller's contributions to science, at Los Alamos it was never possible to separate Teller's science from policy and controversy ...

  3. Internship at Los Alamos National Laboratory

    SciTech Connect

    Dunham, Ryan Q.

    2012-07-11

    Los Alamos National Laboratory (LANL) is located in Los Alamos, New Mexico. It provides support for our country's nuclear weapon stockpile as well as many other scientific research projects. I am an Undergraduate Student Intern in the Systems Design and Analysis group within the Nuclear Nonproliferation division of the Global Security directorate at LANL. I have been tasked with data analysis and modeling of particles in a fluidized bed system for the capture of carbon dioxide from power plant flue gas.

  4. De novo identification of VRC01 class HIV-1-neutralizing antibodies by next-generation sequencing of B-cell transcripts.

    PubMed

    Zhu, Jiang; Wu, Xueling; Zhang, Baoshan; McKee, Krisha; O'Dell, Sijy; Soto, Cinque; Zhou, Tongqing; Casazza, Joseph P; Mullikin, James C; Kwong, Peter D; Mascola, John R; Shapiro, Lawrence

    2013-10-22

    Next-generation sequencing of antibody transcripts provides a wealth of data, but the ability to identify function-specific antibodies solely on the basis of sequence has remained elusive. We previously characterized the VRC01 class of antibodies, which target the CD4-binding site on gp120, appear in multiple donors, and broadly neutralize HIV-1. Antibodies of this class have developmental commonalities, but typically share only ∼50% amino acid sequence identity among different donors. Here we apply next-generation sequencing to identify VRC01 class antibodies in a new donor, C38, directly from B cell transcript sequences. We first tested a lineage rank approach, but this was unsuccessful, likely because VRC01 class antibody sequences were not highly prevalent in this donor. We next identified VRC01 class heavy chains through a phylogenetic analysis that included thousands of sequences from C38 and a few known VRC01 class sequences from other donors. This "cross-donor analysis" yielded heavy chains with little sequence homology to previously identified VRC01 class heavy chains. Nonetheless, when reconstituted with the light chain from VRC01, half of the heavy chain chimeric antibodies showed substantial neutralization potency and breadth. We then identified VRC01 class light chains through a five-amino-acid sequence motif necessary for VRC01 light chain recognition. From over a million light chain sequences, we identified 13 candidate VRC01 class members. Pairing of these light chains with the phylogenetically identified C38 heavy chains yielded functional antibodies that effectively neutralized HIV-1. Bioinformatics analysis can thus directly identify functional HIV-1-neutralizing antibodies of the VRC01 class from a sequenced antibody repertoire.

  5. Los Alamos Laser Eye Investigation.

    SciTech Connect

    Odom, C. R.

    2005-01-01

    A student working in a laser laboratory at Los Alamos National Laboratory sustained a serious retinal injury to her left eye when she attempted to view suspended particles in a partially evacuated target chamber. The principle investigator was using the white light from the flash lamp of a Class 4 Nd:YAG laser to illuminate the particles. Since the Q-switch was thought to be disabled at the time of the accident, the principal investigator assumed it would be safe to view the particles without wearing laser eye protection. The Laboratory Director appointed a team to investigate the accident and to report back to him the events and conditions leading up to the accident, equipment malfunctions, safety management causal factors, supervisory and management action/inaction, adequacy of institutional processes and procedures, emergency and notification response, effectiveness of corrective actions and lessons learned from previous similar events, and recommendations for human and institutional safety improvements. The team interviewed personnel, reviewed documents, and characterized systems and conditions in the laser laboratory during an intense six week investigation. The team determined that the direct and primary failures leading to this accident were, respectively, the principle investigator's unsafe work practices and the institution's inadequate monitoring of worker performance. This paper describes the details of the investigation, the human and institutional failures, and the recommendations for improving the laser safety program.

  6. Los Alamos Neutron Science Center

    SciTech Connect

    Kippen, Karen Elizabeth

    2016-11-08

    For more than 30 years the Los Alamos Neutron Science Center (LANSCE) has provided the scientific underpinnings in nuclear physics and material science needed to ensure the safety and surety of the nuclear stockpile into the future. In addition to national security research, the LANSCE User Facility has a vibrant research program in fundamental science, providing the scientific community with intense sources of neutrons and protons to perform experiments supporting civilian research and the production of medical and research isotopes. Five major experimental facilities operate simultaneously. These facilities contribute to the stockpile stewardship program, produce radionuclides for medical testing, and provide a venue for industrial users to irradiate and test electronics. In addition, they perform fundamental research in nuclear physics, nuclear astrophysics, materials science, and many other areas. The LANSCE User Program plays a key role in training the next generation of top scientists and in attracting the best graduate students, postdoctoral researchers, and early-career scientists. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA) —the principal sponsor of LANSCE—works with the Office of Science and the Office of Nuclear Energy, which have synergistic long-term needs for the linear accelerator and the neutron science that is the heart of LANSCE.

  7. Next-generation sequencing of small RNAs from HIV-infected cells identifies phased microrna expression patterns and candidate novel microRNAs differentially expressed upon infection.

    PubMed

    Chang, Stewart T; Thomas, Matthew J; Sova, Pavel; Green, Richard R; Palermo, Robert E; Katze, Michael G

    2013-02-05

    HIV infection of CD4(+) T cells induces a range of host transcriptional changes in mRNAs as well as microRNAs that may coordinate changes in mRNAs. To survey these dynamic changes, we applied next-generation sequencing, analyzing the small RNA fraction of HIV-infected cells at 5, 12, and 24 h postinfection (RNA-Seq). These time points afforded a view of the transcriptomic changes occurring both before and during viral replication. In the resulting small RNA-Seq data set, we detected a phased pattern of microRNA expression. Largely distinct sets of microRNAs were found to be suppressed at 5 and 12 h postinfection, and both sets of changes rebounded later in infection. A larger set of microRNA changes was observed at 24 h postinfection. When integrated with mRNA expression data, the small RNA-Seq data indicated a role for microRNAs in transcriptional regulation, T cell activation, and cell cycle during HIV infection. As a unique benefit of next-generation sequencing, we also detected candidate novel host microRNAs differentially expressed during infection, including one whose downregulation at 24 h postinfection may allow full replication of HIV to proceed. Collectively, our data provide a uniquely comprehensive view of the changes in host microRNAs induced by HIV during cellular infection. IMPORTANCE New sequencing technologies allow unprecedented views into changes occurring in virus-infected cells, including comprehensive and largely unbiased measurements of different types of RNA. In this study, we used next-generation sequencing to profile dynamic changes in cellular microRNAs occurring in HIV-infected cells. The sensitivity afforded by sequencing allowed us to detect changes in microRNA expression early in infection, before the onset of viral replication. A phased pattern of expression was evident among these microRNAs, and many that were initially suppressed were later overexpressed at the height of infection, providing unique signatures of infection. By

  8. An amphipathic sequence in the cytoplasmic tail of HIV-1 Env alters cell tropism and modulates viral receptor specificity.

    PubMed

    Vzorov, A N; Yang, C; Compans, R W

    2015-09-01

    The human immunodeficiency virus type 1 (HIV-1) 92UG046 Env protein, obtained from a CD4-independent HIV-1 primary isolate (Zerhouni et al., 2004), has the ability to initiate an infection in HeLa cells expressing CD4 when carrying the full-length (FL) Env, but uses CD8 molecules for receptor-mediated entry when carrying a truncated Env (CT84). To determine whether a specific length or structure in the cytoplasmic tail (CT) is responsible for this alteration of tropism, we compared a series of Env constructs with different CT truncations and the presence or absence of an amphipathic alpha- helical sequence. We found that truncated constructs containing the alpha-helical LLP-2 structure in their CT domains conferred a switch from CD4 to CD8 tropism. The results support the conclusion that the structure of the CT domain can play an important role in determining receptor specificity.

  9. Strategies for recognition of stem-loop RNA structures by synthetic ligands: application to the HIV-1 frameshift stimulatory sequence.

    PubMed

    Palde, Prakash B; Ofori, Leslie O; Gareiss, Peter C; Lerea, Jaclyn; Miller, Benjamin L

    2010-08-26

    Production of the Gag-Pol polyprotein in human immunodeficiency virus (HIV) requires a -1 ribosomal frameshift, which is directed by a highly conserved RNA stem-loop. Building on our discovery of a set of disulfide-containing peptides that bind this RNA, we describe medicinal chemistry efforts designed to begin to understand the structure-activity relationships and RNA sequence-selectivity relationships associated with these compounds. Additionally, we have prepared analogues incorporating an olefin or saturated hydrocarbon bioisostere of the disulfide moiety, as a first step toward enhancing biostability. The olefin-containing compounds exhibit affinity comparable to the lead disulfide and, importantly, have no discernible toxicity when incubated with human fibroblasts at concentrations up to 1 mM.

  10. New anti-HIV aptamers based on tetra-end-linked DNA G-quadruplexes: effect of the base sequence on anti-HIV activity.

    PubMed

    D'Atri, Valentina; Oliviero, Giorgia; Amato, Jussara; Borbone, Nicola; D'Errico, Stefano; Mayol, Luciano; Piccialli, Vincenzo; Haider, Shozeb; Hoorelbeke, Bart; Balzarini, Jan; Piccialli, Gennaro

    2012-10-04

    This communication reports on the synthesis and biophysical, biological and SAR studies of a small library of new anti-HIV aptamers based on the tetra-end-linked G-quadruplex structure. The new aptamers showed EC(50) values against HIV-1 in the range of 0.04-0.15 μM as well as affinities for the HIV-1 gp120 envelope in the same order of magnitude.

  11. Identification of Two New HIV-1 Circulating Recombinant Forms (CRF87_cpx and CRF88_BC) from Reported Unique Recombinant Forms in Asia.

    PubMed

    Hu, Yihong; Wan, Zhenzhou; Zhou, Yan-Heng; Smith, Davey; Zheng, Yong-Tang; Zhang, Chiyu

    2017-04-01

    The on-going generation of HIV-1 intersubtype recombination has led to new circulating recombinant forms (CRFs) and unique recombinant forms (URFs) in Asia. In this study, we evaluated whether previously reported URFs were actually CRFs. All available complete or near full-length HIV-1 URF sequences from Asia were retrieved from the HIV Los Alamos National Laboratory Sequence database, and phylogenetic, transmission cluster, and bootscan analyses were performed using MEGA 6.0, Cluster Picker 1.2.1, and SimPlot3.5.1. According to the criterion of new CRFs, two new HIV-1 CRFs (CRF87_cpx and CRF88_BC) were identified from these available URFs. CRF87_cpx comprised HIV-1 subtypes B, C, and CRF01_AE, and CRF88_BC comprised subtypes B and C. HIV Blast and bootscan analysis revealed that besides the three representative strains, there were two additional CRF87_cpx strains. Furthermore, we defined seven dominant URFs (dURF01-dURF07), each of which contained two strains sharing same recombination map and can be used as sequence references to facilitate the finding of new potential CRFs in future. These results will benefit the molecular epidemiological investigation of HIV-1 in Asia.

  12. Recoding method that removes inhibitory sequences and improves HIV gene expression

    DOEpatents

    Rabadan, Raul; Krasnitz, Michael; Robins, Harlan; Witten, Daniela; Levine, Arnold

    2016-08-23

    The invention relates to inhibitory nucleotide signal sequences or "INS" sequences in the genomes of lentiviruses. In particular the invention relates to the AGG motif present in all viral genomes. The AGG motif may have an inhibitory effect on a virus, for example by reducing the levels of, or maintaining low steady-state levels of, viral RNAs in host cells, and inducing and/or maintaining in viral latency. In one aspect, the invention provides vaccines that contain, or are produced from, viral nucleic acids in which the AGG sequences have been mutated. In another aspect, the invention provides methods and compositions for affecting the function of the AGG motif, and methods for identifying other INS sequences in viral genomes.

  13. Hydrogen Exchange Mass Spectrometry of Related Proteins with Divergent Sequences: A Comparative Study of HIV-1 Nef Allelic Variants

    NASA Astrophysics Data System (ADS)

    Wales, Thomas E.; Poe, Jerrod A.; Emert-Sedlak, Lori; Morgan, Christopher R.; Smithgall, Thomas E.; Engen, John R.

    2016-06-01

    Hydrogen exchange mass spectrometry can be used to compare the conformation and dynamics of proteins that are similar in tertiary structure. If relative deuterium levels are measured, differences in sequence, deuterium forward- and back-exchange, peptide retention time, and protease digestion patterns all complicate the data analysis. We illustrate what can be learned from such data sets by analyzing five variants (Consensus G2E, SF2, NL4-3, ELI, and LTNP4) of the HIV-1 Nef protein, both alone and when bound to the human Hck SH3 domain. Regions with similar sequence could be compared between variants. Although much of the hydrogen exchange features were preserved across the five proteins, the kinetics of Nef binding to Hck SH3 were not the same. These observations may be related to biological function, particularly for ELI Nef where we also observed an impaired ability to downregulate CD4 surface presentation. The data illustrate some of the caveats that must be considered for comparison experiments and provide a framework for investigations of other protein relatives, families, and superfamilies with HX MS.

  14. Status of Monte Carlo at Los Alamos

    SciTech Connect

    Thompson, W.L.; Cashwell, E.D.

    1980-01-01

    At Los Alamos the early work of Fermi, von Neumann, and Ulam has been developed and supplemented by many followers, notably Cashwell and Everett, and the main product today is the continuous-energy, general-purpose, generalized-geometry, time-dependent, coupled neutron-photon transport code called MCNP. The Los Alamos Monte Carlo research and development effort is concentrated in Group X-6. MCNP treats an arbitrary three-dimensional configuration of arbitrary materials in geometric cells bounded by first- and second-degree surfaces and some fourth-degree surfaces (elliptical tori). Monte Carlo has evolved into perhaps the main method for radiation transport calculations at Los Alamos. MCNP is used in every technical division at the Laboratory by over 130 users about 600 times a month accounting for nearly 200 hours of CDC-7600 time.

  15. Publications of Los Alamos research 1980

    SciTech Connect

    Salazar, C.A.; Willis, J.K.

    1981-09-01

    This bibliography is a compilation of unclassified publications of work done at the Los Alamos National Laboratory for 1980. Papers published in 1980 are included regardless of when they were actually written. Publications received too late for inclusion in earlier compilations have also been listed. Declassification of previously classified reports is considered to constitute publication. All classified issuances are omitted-even those papers, themselves unclassified, which were published only as part of a classified document. If a paper was pubished more than once, all places of publication are included. The bibliography includes Los Alamos National Laboratory reports, papers released as non-laboratory reports, journal articles, books, chapters of books, conference papers published either separately or as part of conference proceedings issued as books or reports, papers published in congressional hearings, theses, and US patents. Publications by Los Alamos authors that are not records of Laboratory-sponsored work are included when the Library becomes aware of them.

  16. Publications of Los Alamos Research, 1983

    SciTech Connect

    Sheridan, C.J.; McClary, W.J.; Rich, J.A.; Rodriguez, L.L.

    1984-10-01

    This bibliography is a compilation of unclassified publications of work done at the Los Alamos National Laboratory for 1983. Papers published in 1982 are included regardless of when they were actually written. Publications received too late for inclusion in earlier compilations have also been listed. Declassification of previously classified reports is considered to constitute publication. All classified issuances are omitted - even those papers, themselves unclassified, which were published only as part of a classified document. If a paper was published more than once, all places of publication are included. The bibliography includes Los Alamos National Laboratory reports, papers released as non-Laboratory reports, journal articles, books, chapters of books, conference papers either published separately or as part of conference proceedings issued as books or reports, papers publishd in congressional hearings, theses, and US patents. Publications by Los Alamos authors that are not records of Laboratory-sponsored work are included when the Library becomes aware of them.

  17. Water supply at Los Alamos during 1992

    SciTech Connect

    Purtymun, W.D.; McLin, S.G.; Stoker, A.K.; Maes, M.N.

    1995-09-01

    Municipal potable water supply during 1992 was 1,516 {times} 10{sup 6} gallons from wells in the Guaje and Pajarito well fields. About 13 {times} 10{sup 6} gallons were pumped from the Los Alamos Well Field and used in the construction of State Road 501 adjacent to the Field. The last year the Las Alamos Field was used for municipal supply was 1991. The nonpotable water supply used for steam plant support was about 0.12 {times} 10{sup 6} gallons from the spring gallery in Water Canyon. No nonpotable water was used for irrigation from Guaje and Los Alamos Reservoirs. Thus, the total water usage in 1992 was about 1,529 {times} 10{sup 6} gallons. Neither of the two new wells in the Otowi Well Field were operational in 1992.

  18. Sequence Analysis of In Vivo-Expressed HIV-1 Spliced RNAs Reveals the Usage of New and Unusual Splice Sites by Viruses of Different Subtypes

    PubMed Central

    Vega, Yolanda; Delgado, Elena; de la Barrera, Jorge; Carrera, Cristina; Zaballos, Ángel; Cuesta, Isabel; Mariño, Ana; Ocampo, Antonio; Miralles, Celia; Pérez-Castro, Sonia; Álvarez, Hortensia; López-Miragaya, Isabel; García-Bodas, Elena; Díez-Fuertes, Francisco; Thomson, Michael M.

    2016-01-01

    HIV-1 RNAs are generated through a complex splicing mechanism, resulting in a great diversity of transcripts, which are classified in three major categories: unspliced, singly spliced (SS), and doubly spliced (DS). Knowledge on HIV-1 RNA splicing in vivo and by non-subtype B viruses is scarce. Here we analyze HIV-1 RNA splice site usage in CD4+CD25+ lymphocytes from HIV-1-infected individuals through pyrosequencing. HIV-1 DS and SS RNAs were amplified by RT-PCR in 19 and 12 samples, respectively. 13,108 sequences from HIV-1 spliced RNAs, derived from viruses of five subtypes (A, B, C, F, G), were identified. In four samples, three of non-B subtypes, five 3’ splice sites (3’ss) mapping to unreported positions in the HIV-1 genome were identified. Two, designated A4i and A4j, were used in 22% and 25% of rev RNAs in two viruses of subtypes B and A, respectively. Given their close proximity (one or two nucleotides) to A4c and A4d, respectively, they could be viewed as variants of these sites. Three 3’ss, designated A7g, A7h, and A7i, located 20, 32, and 18 nucleotides downstream of A7, respectively, were identified in a subtype C (A7g, A7h) and a subtype G (A7i) viruses, each in around 2% of nef RNAs. The new splice sites or variants of splice sites were associated with the usual sequence features of 3’ss. Usage of unusual 3’ss A4d, A4e, A5a, A7a, and A7b was also detected. A4f, previously identified in two subtype C viruses, was preferentially used by rev RNAs of a subtype C virus. These results highlight the great diversity of in vivo splice site usage by HIV-1 RNAs. The fact that four of five newly identified splice sites or variants of splice sites were detected in non-subtype B viruses allows anticipating an even greater diversity of HIV-1 splice site usage than currently known. PMID:27355361

  19. Sequence Analysis of In Vivo-Expressed HIV-1 Spliced RNAs Reveals the Usage of New and Unusual Splice Sites by Viruses of Different Subtypes.

    PubMed

    Vega, Yolanda; Delgado, Elena; de la Barrera, Jorge; Carrera, Cristina; Zaballos, Ángel; Cuesta, Isabel; Mariño, Ana; Ocampo, Antonio; Miralles, Celia; Pérez-Castro, Sonia; Álvarez, Hortensia; López-Miragaya, Isabel; García-Bodas, Elena; Díez-Fuertes, Francisco; Thomson, Michael M

    2016-01-01

    HIV-1 RNAs are generated through a complex splicing mechanism, resulting in a great diversity of transcripts, which are classified in three major categories: unspliced, singly spliced (SS), and doubly spliced (DS). Knowledge on HIV-1 RNA splicing in vivo and by non-subtype B viruses is scarce. Here we analyze HIV-1 RNA splice site usage in CD4+CD25+ lymphocytes from HIV-1-infected individuals through pyrosequencing. HIV-1 DS and SS RNAs were amplified by RT-PCR in 19 and 12 samples, respectively. 13,108 sequences from HIV-1 spliced RNAs, derived from viruses of five subtypes (A, B, C, F, G), were identified. In four samples, three of non-B subtypes, five 3' splice sites (3'ss) mapping to unreported positions in the HIV-1 genome were identified. Two, designated A4i and A4j, were used in 22% and 25% of rev RNAs in two viruses of subtypes B and A, respectively. Given their close proximity (one or two nucleotides) to A4c and A4d, respectively, they could be viewed as variants of these sites. Three 3'ss, designated A7g, A7h, and A7i, located 20, 32, and 18 nucleotides downstream of A7, respectively, were identified in a subtype C (A7g, A7h) and a subtype G (A7i) viruses, each in around 2% of nef RNAs. The new splice sites or variants of splice sites were associated with the usual sequence features of 3'ss. Usage of unusual 3'ss A4d, A4e, A5a, A7a, and A7b was also detected. A4f, previously identified in two subtype C viruses, was preferentially used by rev RNAs of a subtype C virus. These results highlight the great diversity of in vivo splice site usage by HIV-1 RNAs. The fact that four of five newly identified splice sites or variants of splice sites were detected in non-subtype B viruses allows anticipating an even greater diversity of HIV-1 splice site usage than currently known.

  20. A short sequence motif in the 5' leader of the HIV-1 genome modulates extended RNA dimer formation and virus replication.

    PubMed

    van Bel, Nikki; Das, Atze T; Cornelissen, Marion; Abbink, Truus E M; Berkhout, Ben

    2014-12-19

    The 5' leader of the HIV-1 RNA genome encodes signals that control various steps in the replication cycle, including the dimerization initiation signal (DIS) that triggers RNA dimerization. The DIS folds a hairpin structure with a palindromic sequence in the loop that allows RNA dimerization via intermolecular kissing loop (KL) base pairing. The KL dimer can be stabilized by including the DIS stem nucleotides in the intermolecular base pairing, forming an extended dimer (ED). The role of the ED RNA dimer in HIV-1 replication has hardly been addressed because of technical challenges. We analyzed a set of leader mutants with a stabilized DIS hairpin for in vitro RNA dimerization and virus replication in T cells. In agreement with previous observations, DIS hairpin stability modulated KL and ED dimerization. An unexpected previous finding was that mutation of three nucleotides immediately upstream of the DIS hairpin significantly reduced in vitro ED formation. In this study, we tested such mutants in vivo for the importance of the ED in HIV-1 biology. Mutants with a stabilized DIS hairpin replicated less efficiently than WT HIV-1. This defect was most severe when the upstream sequence motif was altered. Virus evolution experiments with the defective mutants yielded fast replicating HIV-1 variants with second site mutations that (partially) restored the WT hairpin stability. Characterization of the mutant and revertant RNA molecules and the corresponding viruses confirmed the correlation between in vitro ED RNA dimer formation and efficient virus replication, thus indicating that the ED structure is important for HIV-1 replication.

  1. Sequencing and Phylogenetic Analysis of Near Full-Length HIV-1 Subtypes A, B, G and Unique Recombinant AC and AD Viral Strains Identified in South Africa

    PubMed Central

    Wilkinson, Eduan; Holzmayer, Vera; Jacobs, Graeme B.; de Oliveira, Tulio; Brennan, Catherine A.; Hackett, John; van Rensburg, Estrelita Janse

    2015-01-01

    Abstract By the end of 2012, more than 6.1 million people were infected with HIV-1 in South Africa. Subtype C was responsible for the majority of these infections and more than 300 near full-length genomes (NFLGs) have been published. Currently very few non-subtype C isolates have been identified and characterized within the country, particularly full genome non-C isolates. Seven patients from the Tygerberg Virology (TV) cohort were previously identified as possible non-C subtypes and were selected for further analyses. RNA was isolated from five individuals (TV047, TV096, TV101, TV218, and TV546) and DNA from TV016 and TV1057. The NFLGs of these samples were amplified in overlapping fragments and sequenced. Online subtyping tools REGA version 3 and jpHMM were used to screen for subtypes and recombinants. Maximum likelihood (ML) phylogenetic analysis (phyML) was used to infer subtypes and SimPlot was used to confirm possible intersubtype recombinants. We identified three subtype B (TV016, TV047, and TV1057) isolates, one subtype A1 (TV096), one subtype G (TV546), one unique AD (TV101), and one unique AC (TV218) recombinant form. This is the first NFLG of subtype G that has been described in South Africa. The subtype B sequences described also increased the NFLG subtype B sequences in Africa from three to six. There is a need for more NFLG sequences, as partial HIV-1 sequences may underrepresent viral recombinant forms. It is also necessary to continue monitoring the evolution and spread of HIV-1 in South Africa, because understanding viral diversity may play an important role in HIV-1 prevention strategies. PMID:25492033

  2. Antiretroviral treatment sequencing strategies to overcome HIV type 1 drug resistance in adolescents and adults in low-middle-income countries.

    PubMed

    De Luca, Andrea; Hamers, Raphael L; Schapiro, Jonathan M

    2013-06-15

    Antiretroviral treatment (ART) is expanding to human immunodeficiency virus type 1 (HIV-1)-infected persons in low-middle income countries, thanks to a public health approach. With 3 available drug classes, 2 ART sequencing lines are programmatically foreseen. The emergence and transmission of viral drug resistance represents a challenge to the efficacy of ART. Knowledge of HIV-1 drug resistance selection associated with specific drugs and regimens and the consequent activity of residual drug options are essential in programming ART sequencing options aimed at preserving ART efficacy for as long as possible. This article determines optimal ART sequencing options for overcoming HIV-1 drug resistance in resource-limited settings, using currently available drugs and treatment monitoring opportunities. From the perspective of drug resistance and on the basis of limited virologic monitoring data, optimal sequencing seems to involve use of a tenofovir-containing nonnucleoside reverse-transcriptase inhibitor-based first-line regimen, followed by a zidovudine-containing, protease inhibitor (PI)-based second-line regimen. Other options and their consequences are explored by considering within-class and between-class sequencing opportunities, including boosted PI monotherapies and future options with integrase inhibitors. Nucleoside reverse-transcriptase inhibitor resistance pathways in HIV-1 subtype C suggest an additional reason for accelerating stavudine phase out. Viral load monitoring avoids the accumulation of resistance mutations that significantly reduce the activity of next-line options. Rational use of resources, including broader access to viral load monitoring, will help ensure 3 lines of fully active treatment options, thereby increasing the duration of ART success.

  3. From clinical sample to complete genome: Comparing methods for the extraction of HIV-1 RNA for high-throughput deep sequencing.

    PubMed

    Cornelissen, Marion; Gall, Astrid; Vink, Monique; Zorgdrager, Fokla; Binter, Špela; Edwards, Stephanie; Jurriaans, Suzanne; Bakker, Margreet; Ong, Swee Hoe; Gras, Luuk; van Sighem, Ard; Bezemer, Daniela; de Wolf, Frank; Reiss, Peter; Kellam, Paul; Berkhout, Ben; Fraser, Christophe; van der Kuyl, Antoinette C

    2016-08-04

    The BEEHIVE (Bridging the Evolution and Epidemiology of HIV in Europe) project aims to analyse nearly-complete viral genomes from >3000 HIV-1 infected Europeans using high-throughput deep sequencing techniques to investigate the virus genetic contribution to virulence. Following the development of a computational pipeline, including a new de novo assembler for RNA virus genomes, to generate larger contiguous sequences (contigs) from the abundance of short sequence reads that characterise the data, another area that determines genome sequencing success is the quality and quantity of the input RNA. A pilot experiment with 125 patient plasma samples was performed to investigate the optimal method for isolation of HIV-1 viral RNA for long amplicon genome sequencing. Manual isolation with the QIAamp Viral RNA Mini Kit (Qiagen) was superior over robotically extracted RNA using either the QIAcube robotic system, the mSample Preparation Systems RNA kit with automated extraction by the m2000sp system (Abbott Molecular), or the MagNA Pure 96 System in combination with the MagNA Pure 96 Instrument (Roche Diagnostics). We scored amplification of a set of four HIV-1 amplicons of ∼1.9, 3.6, 3.0 and 3.5kb, and subsequent recovery of near-complete viral genomes. Subsequently, 616 BEEHIVE patient samples were analysed to determine factors that influence successful amplification of the genome in four overlapping amplicons using the QIAamp Viral RNA Kit for viral RNA isolation. Both low plasma viral load and high sample age (stored before 1999) negatively influenced the amplification of viral amplicons >3kb. A plasma viral load of >100,000 copies/ml resulted in successful amplification of all four amplicons for 86% of the samples, this value dropped to only 46% for samples with viral loads of <20,000 copies/ml.

  4. Sequences in Glycoprotein gp41, the CD4 Binding Site, and the V2 Domain Regulate Sensitivity and Resistance of HIV-1 to Broadly Neutralizing Antibodies

    PubMed Central

    O'Rourke, Sara M.; Schweighardt, Becky; Phung, Pham; Mesa, Kathryn A.; Vollrath, Aaron L.; Tatsuno, Gwen P.; To, Briana; Sinangil, Faruk; Limoli, Kay; Wrin, Terri

    2012-01-01

    The swarm of quasispecies that evolves in each HIV-1-infected individual represents a source of closely related Env protein variants that can be used to explore various aspects of HIV-1 biology. In this study, we made use of these variants to identify mutations that confer sensitivity and resistance to the broadly neutralizing antibodies found in the sera of selected HIV-1-infected individuals. For these studies, libraries of Env proteins were cloned from infected subjects and screened for infectivity and neutralization sensitivity. The nucleotide sequences of the Env proteins were then compared for pairs of neutralization-sensitive and -resistant viruses. In vitro mutagenesis was used to identify the specific amino acids responsible for the neutralization phenotype. All of the mutations altering neutralization sensitivity/resistance appeared to induce conformational changes that simultaneously enhanced the exposure of two or more epitopes located in different regions of gp160. These mutations appeared to occur at unique positions required to maintain the quaternary structure of the gp160 trimer, as well as conformational masking of epitopes targeted by neutralizing antibodies. Our results show that sequences in gp41, the CD4 binding site, and the V2 domain all have the ability to act as global regulators of neutralization sensitivity. Our results also suggest that neutralization assays designed to support the development of vaccines and therapeutics targeting the HIV-1 Env protein should consider virus variation within individuals as well as virus variation between individuals. PMID:22933284

  5. Genetic analysis of HIV-1 Circulating Recombinant Form 02_AG, B and C subtype-specific envelope sequences from Northern India and their predicted co-receptor usage

    PubMed Central

    2009-01-01

    HIV-1 epidemic in India is largely driven by subtype C but other subtypes or recombinants have also been reported from several states of India. This is mainly due to the co-circulation of other genetic subtypes that potentially can recombine to generate recombinant/mosaic genomes. In this study, we report detail genetic characterization of HIV-1 envelope sequences from North India (Delhi and neighboring regions). Six of 13 were related to subtype C, one B and the rest six showed relatedness with CRF02_AG strain. The subtype C possessed the highly conserved GPGQ motif but subtype B possessed the GPGR motif in the V3 loop as observed earlier. While most of the sequences suggested CCR5 co-receptor usage, one subtype C sample clearly indicated CXCR4 usage. A successful mother to child transmission was established in two pairs. Thus, co-circulation of multiple subtypes (B and C) and the recombinant CRF02_AG strains in North India suggests a rapidly evolving scenario of HIV-1 epidemic in this region with impact on vaccine formulation. Since this is the first report of CRF02_AG envelope from India, it will be important to monitor the spread of this strain and its impact on HIV-1 transmission in India. PMID:19954551

  6. Induction inserts at the Los Alamos PSR

    SciTech Connect

    King-Yuen Ng

    2002-09-30

    Ferrite-loaded induction tuners installed in the Los Alamos Proton Storage Ring have been successful in compensating space-charge effects. However, the resistive part of the ferrite introduces unacceptable microwave instability and severe bunch lengthening. An effective cure was found by heating the ferrite cores up to {approx} 130 C. An understanding of the instability and cure is presented.

  7. A Sailor in the Los Alamos Navy

    SciTech Connect

    Judd, D. L.

    2016-12-20

    As part of the War Department’s Manhattan Engineer District (MED), Los Alamos was an Army installation during World War II, complete with a base commander and a brace of MPs. But it was a unique Army installation, having more civilian then military personnel. Even more unique was the work performed by the civilian population, work that required highly educated scientists and engineers. As the breadth, scope, and complexity of the Laboratory’s work increased, more and more technically educated and trained personnel were needed. But, the manpower needs of the nation’s war economy had created a shortage of such people. To meet its manpower needs, the MED scoured the ranks of the Army for anyone who had technical training and reassigned these men to its laboratories, including Los Alamos, as part of its Special Engineer Detachment (SED). Among the SEDs assigned to Los Alamos was Val Fitch, who was awarded the Nobel Prize in Physics in 1980. Another was Al Van Vessem, who helped stack the TNT for the 100 ton test, bolted together the Trinity device, and rode shotgun with the bomb has it was driven from Los Alamos to ground zero.

  8. Higher specificity of nucleic acid sequence-based amplification isothermal technology than of real-time PCR for quantification of HIV-1 RNA on dried blood spots.

    PubMed

    Mercier-Delarue, Severine; Vray, Muriel; Plantier, Jean Christophe; Maillard, Theodora; Adjout, Zidan; de Olivera, Fabienne; Schnepf, Nathalie; Maylin, Sarah; Simon, Francois; Delaugerre, Constance

    2014-01-01

    Dried blood spots (DBS) are widely proposed as a plasma surrogate for monitoring antiretroviral treatment efficacy based on the HIV-1 RNA level (viral load [VL]) in resource-limited settings. Interfering coamplification of cell-associated HIV-1 DNA during reverse transcription (RT)-PCR can be avoided by using nucleic acid sequence-based amplification (NASBA) technology, which is based on an RNA template and isothermic conditions. We analyzed VL values obtained with DBS and plasma samples by comparing isothermic NASBA (NucliSENS EasyQ HIV-1 V2.0; bioMérieux) with real-time RT-PCR (Cobas TaqMan HIV-1 V2.0; Roche). Samples from 197 HIV-1-infected patients were tested (non-B subtypes in 51% of the cases). Nucleic acid extractions were performed by use of NucliSENS EasyMAG (bioMérieux) and Cobas AmpliPrep (Roche) before the NASBA and RT-PCR quantifications, respectively. Both quantification assays have lower limits of detection of 20 (1.3) and 800 (2.9) log10 copies/ml (log) in plasma and DBS, respectively. The mean (DBS minus plasma) differences were -0.39 and -0.46 log, respectively, for RT-PCR and NASBA. RT-PCR on DBS identified virological failure in 122 of 126 patients (sensitivity, 97%) and viral suppression in 58 of 70 patients (specificity, 83%), yielding 12 false-positive results (median, 3.2 log). NASBA on DBS identified virological failure in 85 of 96 patients (sensitivity, 89%) and viral suppression in 95 of 97 patients (specificity, 98%) and yielded 2 false-positive results (3.0 log for both). Both technologies detected HIV-1 RNA in DBS at a threshold of 800 copies/ml. This higher specificity of NASBA technology could avoid overestimation of poor compliance or the emergence of resistance when monitoring antiretroviral efficacy with the DBS method.

  9. Genome sequence of a novel HIV-1 circulating recombinant form (CRF64_BC) identified from Yunnan, China.

    PubMed

    Hsi, Jenny; Wei, Huamian; Xing, Hui; Feng, Yi; He, Xiang; Liao, Lingjie; Jia, Manhong; Wang, Nidan; Ning, Chuanyi; Shao, Yiming

    2014-04-01

    We report a novel HIV-1 circulating recombinant form (CRF64_BC) that was isolated from five epidemiologically unlinked HIV-infected persons in Yunnan province. CRF64_BC was composed of subtype B and subtype C, with five short subtype B segments inserted into the subtype C backbone. Phylogenetic analysis demonstrated that the C subregion was correlated with the India C lineage, which was transmitted into China in the early 1990s. The evolutionary history of the B subregion was not as clear as the C subregion, as the short length of this region yielded poor phylogenetic results. Dehong is considered the epicenter of HIV-1 in China, and recombinant strains such as CRF07_BC and CRF08_BC, which also originated from this region, have spread widely in China. The newly emerged CRF64_BC increases the complexity of the HIV epidemic in China and complicates the development of subtype-specific tools against HIV transmission.

  10. Recent Infrasound Calibration Activity at Los Alamos

    NASA Astrophysics Data System (ADS)

    Whitaker, R. W.; Marcillo, O. E.

    2014-12-01

    Absolute infrasound sensor calibration is necessary for estimating source sizes from measured waveforms. This can be an important function in treaty monitoring. The Los Alamos infrasound calibration chamber is capable of absolute calibration. Early in 2014 the Los Alamos infrasound calibration chamber resumed operations in its new location after an unplanned move two years earlier. The chamber has two sources of calibration signals. The first is the original mechanical piston, and the second is a CLD Dynamics Model 316 electro-mechanical unit that can be digitally controlled and provide a richer set of calibration options. During 2008-2010 a number of upgrades were incorporated for improved operation and recording. In this poster we give an overview of recent chamber work on sensor calibrations, calibration with the CLD unit, some measurements with different porous hoses and work with impulse sources.

  11. Nuclear Forensics at Los Alamos National Laboratory

    SciTech Connect

    Podlesak, David W; Steiner, Robert E.; Burns, Carol J.; LaMont, Stephen P.; Tandon, Lav

    2012-08-09

    The overview of this presentation is: (1) Introduction to nonproliferation efforts; (2) Scope of activities at Los Alamos National Laboratory; (3) Facilities for radioanalytical work at LANL; (4) Radiochemical characterization capabilities; and (5) Bulk chemical and materials analysis capabilities. Some conclusions are: (1) Analytical chemistry measurements on plutonium and uranium matrices are critical to numerous defense and non-defense programs including safeguards accountancy verification measurements; (2) Los Alamos National Laboratory operates capable actinide analytical chemistry and material science laboratories suitable for nuclear material forensic characterization; (3) Actinide analytical chemistry uses numerous means to validate and independently verify that measurement data quality objectives are met; and (4) Numerous LANL nuclear facilities support the nuclear material handling, preparation, and analysis capabilities necessary to evaluate samples containing nearly any mass of an actinide (attogram to kilogram levels).

  12. Water Supply at Los Alamos during 1997

    SciTech Connect

    M. N. Maes; S. G. McLin; W. D. Purtymun

    1998-12-01

    Production of potable municipal water supplies during 1997 totaled about 1,285.9 million gallons from wells in the Guaje, Pajarito, and Otowi well fields. There was no water used from the spring gallery in Water Canyon or from Guaje Reservoir during 1997. About 2.4 million gallons of water from Los Alamos Reservoir was used to irrigate public parks and recreational lands. The total water usage in 1997 was about 1,288.3 million gallons, or about 135 gallons per day per person living in Los Alamos County. Groundwater pumpage was down about 82.2 million gallons in 1997 compared with the pumpage in 1996. Four new replacement wells were drilled and cased in Guaje Canyon between October 1997 and March 1998. These wells are currently being developed and aquifer tests are being performed. A special report summarizing the geological, geophysical, and well construction logs will be issued in the near future for these new wells.

  13. Los Alamos Novel Rocket Design Flight Tested

    ScienceCinema

    Tappan, Bryce

    2016-07-12

    Los Alamos National Laboratory scientists recently flight tested a new rocket design that includes a high-energy fuel and a motor design that also delivers a high degree of safety. Researchers will now work to scale-up the design, as well as explore miniaturization of the system, in order to exploit all potential applications that would require high-energy, high-velocity, and correspondingly high safety margins.

  14. Risk management at Los Alamos National Laboratory

    SciTech Connect

    Brooks, D.G.; Stack, D.W.

    1993-11-01

    Los Alamos National Laboratory has risk management programs at a number of administrative levels. Each line organization has responsibility for risk management for routine operations. The Facility Risk Management group (HS-3) is the Los Alamos organization with the primary responsibility for risk management including providing input and expertise to facilities and line managers in the management and documentation of ES&H hazards and risks associated with existing and new activities. One of the major contributions this group has made to laboratory risk management program is to develop and implement a hazard identification and classification methodology that is readily adaptable to continuously changing classification guidelines such as DOE-STD-1027. The increased emphasis on safety at Los Alamos has led to the formation of additional safety oversight organization such as the Integration and Coordination Office (ICO), which is responsible for prioritization of risk management activities. In the fall of 1991, nearly 170 DOE inspectors spent 6 weeks analyzing the environmental, safety, and health activities at Los Alamos. The result of this audit was a list of over 1000 findings, each indicating some deficiency in current Laboratory operations relative to DOE and other government regulation. The audit team`s findings were consolidated and ``action plans`` were developed to address the findings. This resulted in over 200 action plans with a total estimated cost of almost $1 billion. The Laboratory adopted a risk-based prioritization process to attempt to achieve as much risk reduction as possible with the available resources. This paper describes the risk based prioritization model that was developed.

  15. Los Alamos National Laboratory Facility Review

    SciTech Connect

    Nelson, Ronald Owen

    2015-06-05

    This series of slides depicts the Los Alamos Neutron Science Center (LANSCE). The Center's 800-MeV linac produces H+ and H- beams as well as beams of moderated (cold to 1 MeV) and unmoderated (0.1 to 600 MeV) neutrons. Experimental facilities and their capabilities and characteristics are outlined. Among these are LENZ, SPIDER, and DANCE.

  16. Los Alamos Team Demonstrates Bottle Scanner Technology

    SciTech Connect

    Espy, Michelle; Schultz, Larry

    2014-05-06

    Los Alamos scientists are demonstrating a Nuclear Magnetic Resonance Imaging (NMR) technology that may provide a breakthrough for screening liquids at airport security. By adding low-power X-ray data to the NMR mix, scientists believe they have unlocked a new detection technology. Funded in part by the Department of Homeland Security's Science and Technology Directorate, the new technology is called MagRay.

  17. Los Alamos Team Demonstrates Bottle Scanner Technology

    ScienceCinema

    Espy, Michelle; Schultz, Larry

    2016-07-12

    Los Alamos scientists are demonstrating a Nuclear Magnetic Resonance Imaging (NMR) technology that may provide a breakthrough for screening liquids at airport security. By adding low-power X-ray data to the NMR mix, scientists believe they have unlocked a new detection technology. Funded in part by the Department of Homeland Security's Science and Technology Directorate, the new technology is called MagRay.

  18. Amphibians and Reptiles of Los Alamos County

    SciTech Connect

    Teralene S. Foxx; Timothy K. Haarmann; David C. Keller

    1999-10-01

    Recent studies have shown that amphibians and reptiles are good indicators of environmental health. They live in terrestrial and aquatic environments and are often the first animals to be affected by environmental change. This publication provides baseline information about amphibians and reptiles that are present on the Pajarito Plateau. Ten years of data collection and observations by researchers at Los Alamos National Laboratory, the University of New Mexico, the New Mexico Department of Game and Fish, and hobbyists are represented.

  19. Los Alamos Novel Rocket Design Flight Tested

    SciTech Connect

    Tappan, Bryce

    2014-10-23

    Los Alamos National Laboratory scientists recently flight tested a new rocket design that includes a high-energy fuel and a motor design that also delivers a high degree of safety. Researchers will now work to scale-up the design, as well as explore miniaturization of the system, in order to exploit all potential applications that would require high-energy, high-velocity, and correspondingly high safety margins.

  20. Critical partnerships: Los Alamos, universities, and industry

    SciTech Connect

    Berger, C.L.

    1997-04-01

    Los Alamos National Laboratory, situated 35 miles northwest of Santa Fe, NM, is one of the Department of Energy`s three Defense Programs laboratories. It encompasses 43 square miles, employees approximately 10,000 people, and has a budget of approximately $1.1B in FY97. Los Alamos has a strong post-cold war mission, that of reducing the nuclear danger. But even with that key role in maintaining the nation`s security, Los Alamos views partnerships with universities and industry as critical to its future well being. Why is that? As the federal budget for R&D comes under continued scrutiny and certain reduction, we believe that the triad of science and technology contributors to the national system of R&D must rely on and leverage each others capabilities. For us this means that we will rely on these partners to help us in 5 key ways: We expect that partnerships will help us maintain and enhance our core competencies. In doing so, we will be able to attract the best scientists and engineers. To keep on the cutting edge of research and development, we have found that partnerships maintain the excellence of staff through new and exciting challenges. Additionally, we find that from our university and corporate partners we often learn and incorporate {open_quotes}best practices{close_quotes} in organizational management and operations. Finally, we believe that a strong national system of R&D will ensure and enhance our ability to generate revenues.

  1. Los Alamos National Laboratory Building Cost Index

    SciTech Connect

    Orr, H.D.; Lemon, G.D.

    1983-01-01

    The Los Alamos National Laboratory Building Cost Index indicates that actual escalation since 1970 is near 10% per year. Therefore, the Laboratory will continue using a 10% per year escalation rate for construction estimates through 1985 and a slightly lower rate of 8% per year from 1986 through 1990. The computerized program compares the different elements involved in the cost of a typical construction project, which for our purposes, is a complex of office buildings and experimental laboratores. The input data used in the program consist primarily of labor costs and material and equipment costs. The labor costs are the contractural rates of the crafts workers in the Los Alamos area. For the analysis, 12 field-labor draft categories are used; each is weighted corresponding to the labor craft distribution associated with the typical construction project. The materials costs are current Los Alamos prices. Additional information sources include material and equipment quotes obtained through conversations with vendors and from trade publications. The material and equipment items separate into 17 categories for the analysis and are weighted corresponding to the material and equipment distribution associated with the typical construction project. The building cost index is compared to other national building cost indexes.

  2. Los Alamos National Laboratory building cost index

    SciTech Connect

    Orr, H.D.; Lemon, G.D.

    1982-10-01

    The Los Alamos National Laboratory Building Cost Index indicates that actual escalation since 1970 is near 10% per year. Therefore, the Laboratory will continue using a 10% per year escalation rate for construction estimates through 1985 and a slightly lower rate of 8% per year from 1986 through 1990. The computerized program compares the different elements involved in the cost of a typical construction project, which for our purposes, is a complex of office buildings and experimental laboratories. The input data used in the program consist primarily of labor costs and material and equipment costs. The labor costs are the contractual rates of the crafts workers in the Los Alamos area. For the analysis, 12 field-labor craft categories are used; each is weighted corresponding to the labor craft distribution associated with the typical construction project. The materials costs are current Los Alamos prices. Additional information sources include material and equipment quotes obtained through conversations with vendors and from trade publications. The material and equipment items separate into 17 categories for the analysis and are weighted corresponding to the material and equipment distribution associated with the typical construction project. The building cost index is compared to other national building cost indexes.

  3. Short Communication: HIV-1 Subtype B in the Dominican Republic: Evolution and Molecular Epidemiology

    PubMed Central

    López, Pablo; Rivera-Amill, Vanessa; Paulino-Ramirez, Robert

    2015-01-01

    Abstract The Caribbean region has the world second highest incidence rate of acquired immunodeficiency syndrome. The island of Hispaniola is composed of two sovereign nations: the Dominican Republic and Haiti. Together, they account for more than 85% of HIV/AIDS cases in the Caribbean; and the Dominican Republic alone has approximately 46,000 (33,000–59,000) HIV-1-infected adults and children. Despite this, the magnitude of the genetic variability and evolution of the HIV-1 virus in the Dominican Republic is unclear. In the current study, we analyzed 195 reverse transcriptase (RT) sequences obtained from the Los Alamos HIV database. The data were used to assess the course of the viral epidemic over time in the Dominican Republic, using a coalescent approach. Based on the data, we estimated that the timing of the most recent common ancestor (tMRCA) of local HIV-1 subtype B emerged in 1963, approximately. In addition, the Bayesian analysis provided new information that suggests that the epidemic in the Dominican Republic experienced a significant decrease in relative genetic diversity in the past 2 decades. The results suggest that adherence to antiretroviral therapy, adequate prevention campaigns, and better access to health care may be altering the virus's evolution in the Dominican Republic. PMID:25941939

  4. Linkage of viral sequences among HIV-infected village residents in Botswana: estimation of linkage rates in the presence of missing data.

    PubMed

    Carnegie, Nicole Bohme; Wang, Rui; Novitsky, Vladimir; De Gruttola, Victor

    2014-01-01

    Linkage analysis is useful in investigating disease transmission dynamics and the effect of interventions on them, but estimates of probabilities of linkage between infected people from observed data can be biased downward when missingness is informative. We investigate variation in the rates at which subjects' viral genotypes link across groups defined by viral load (low/high) and antiretroviral treatment (ART) status using blood samples from household surveys in the Northeast sector of Mochudi, Botswana. The probability of obtaining a sequence from a sample varies with viral load; samples with low viral load are harder to amplify. Pairwise genetic distances were estimated from aligned nucleotide sequences of HIV-1C env gp120. It is first shown that the probability that randomly selected sequences are linked can be estimated consistently from observed data. This is then used to develop estimates of the probability that a sequence from one group links to at least one sequence from another group under the assumption of independence across pairs. Furthermore, a resampling approach is developed that accounts for the presence of correlation across pairs, with diagnostics for assessing the reliability of the method. Sequences were obtained for 65% of subjects with high viral load (HVL, n = 117), 54% of subjects with low viral load but not on ART (LVL, n = 180), and 45% of subjects on ART (ART, n = 126). The probability of linkage between two individuals is highest if both have HVL, and lowest if one has LVL and the other has LVL or is on ART. Linkage across groups is high for HVL and lower for LVL and ART. Adjustment for missing data increases the group-wise linkage rates by 40-100%, and changes the relative rates between groups. Bias in inferences regarding HIV viral linkage that arise from differential ability to genotype samples can be reduced by appropriate methods for accommodating missing data.

  5. Prevalence of Transmitted Drug-Resistance Mutations and Polymorphisms in HIV-1 Reverse Transcriptase, Protease, and gp41 Sequences Among Recent Seroconverters in Southern Poland

    PubMed Central

    Smoleń-Dzirba, Joanna; Rosińska, Magdalena; Kruszyński, Piotr; Bratosiewicz-Wąsik, Jolanta; Wojtyczka, Robert; Janiec, Janusz; Szetela, Bartosz; Beniowski, Marek; Bociąga-Jasik, Monika; Jabłonowska, Elżbieta; Wąsik, Tomasz J.

    2017-01-01

    Background Monitoring of drug resistance-related mutations among patients with recent HIV-1 infection offers an opportunity to describe current patterns of transmitted drug resistance (TDR) mutations. Material/Methods Of 298 individuals newly diagnosed from March 2008 to February 2014 in southern Poland, 47 were deemed to have recent HIV-1 infection by the limiting antigen avidity immunoassay. Proviral DNA was amplified and sequenced in the reverse transcriptase, protease, and gp41 coding regions. Mutations were interpreted according to the Stanford Database algorithm and/or the International Antiviral Society USA guidelines. TDR mutations were defined according to the WHO surveillance list. Results Among 47 patients with recent HIV-1 infection only 1 (2%) had evidence of TDR mutation. No major resistance mutations were found, but the frequency of strains with ≥1 accessory resistance-associated mutations was high, at 98%. Accessory mutations were present in 11% of reverse transcriptase, 96% of protease, and 27% of gp41 sequences. Mean number of accessory resistance mutations in the reverse transcriptase and protease sequences was higher in viruses with no compensatory mutations in the gp41 HR2 domain than in strains with such mutations (p=0.031). Conclusions Despite the low prevalence of strains with TDR mutations, the frequency of accessory mutations was considerable, which may reflect the history of drug pressure among transmitters or natural viral genetic diversity, and may be relevant for future clinical outcomes. The accumulation of the accessory resistance mutations within the pol gene may restrict the occurrence of compensatory mutations related to enfuvirtide resistance or vice versa. PMID:28167814

  6. Prevalence of Transmitted Drug-Resistance Mutations and Polymorphisms in HIV-1 Reverse Transcriptase, Protease, and gp41 Sequences Among Recent Seroconverters in Southern Poland.

    PubMed

    Smoleń-Dzirba, Joanna; Rosińska, Magdalena; Kruszyński, Piotr; Bratosiewicz-Wąsik, Jolanta; Wojtyczka, Robert; Janiec, Janusz; Szetela, Bartosz; Beniowski, Marek; Bociąga-Jasik, Monika; Jabłonowska, Elżbieta; Wąsik, Tomasz J; The Cascade Collaboration In EuroCoord, And

    2017-02-07

    BACKGROUND Monitoring of drug resistance-related mutations among patients with recent HIV-1 infection offers an opportunity to describe current patterns of transmitted drug resistance (TDR) mutations. MATERIAL AND METHODS Of 298 individuals newly diagnosed from March 2008 to February 2014 in southern Poland, 47 were deemed to have recent HIV-1 infection by the limiting antigen avidity immunoassay. Proviral DNA was amplified and sequenced in the reverse transcriptase, protease, and gp41 coding regions. Mutations were interpreted according to the Stanford Database algorithm and/or the International Antiviral Society USA guidelines. TDR mutations were defined according to the WHO surveillance list. RESULTS Among 47 patients with recent HIV-1 infection only 1 (2%) had evidence of TDR mutation. No major resistance mutations were found, but the frequency of strains with ≥1 accessory resistance-associated mutations was high, at 98%. Accessory mutations were present in 11% of reverse transcriptase, 96% of protease, and 27% of gp41 sequences. Mean number of accessory resistance mutations in the reverse transcriptase and protease sequences was higher in viruses with no compensatory mutations in the gp41 HR2 domain than in strains with such mutations (p=0.031). CONCLUSIONS Despite the low prevalence of strains with TDR mutations, the frequency of accessory mutations was considerable, which may reflect the history of drug pressure among transmitters or natural viral genetic diversity, and may be relevant for future clinical outcomes. The accumulation of the accessory resistance mutations within the pol gene may restrict the occurrence of compensatory mutations related to enfuvirtide resistance or vice versa.

  7. Staphylococcus aureus Leukocidin LukED and HIV-1 gp120 Target Different Sequence Determinants on CCR5

    PubMed Central

    Tam, Kayan; Schultz, Megan; Reyes-Robles, Tamara; Vanwalscappel, Bénédicte; Horton, Joshua; Alonzo, Francis; Wu, Beili

    2016-01-01

    ABSTRACT Leukocidin ED (LukED) is a bicomponent pore-forming toxin produced by Staphylococcus aureus that lyses host cells by targeting the chemokine receptors CC chemokine receptor type 5 (CCR5), CXCR1, CXCR2, and DARC. In addition to its role as a receptor for LukED, CCR5 is the major coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and has been extensively studied. To compare how LukED and HIV-1 target CCR5, we analyzed their respective abilities to use CCR5/CCR2b chimeras to mediate cytotoxicity and virus entry. These analyses showed that the second and third extracellular loops (ECL) of CCR5 are necessary and sufficient for LukED to target the receptor and promote cell lysis. In contrast, the second ECL of CCR5 is necessary but not sufficient for HIV-1 infectivity. The analysis of CCR5 point mutations showed that glycine-163 is critical for HIV-1 infectivity, while arginine-274 and aspartic acid-276 are critical for LukED cytotoxicity. Point mutations in ECL2 diminished both HIV-1 infectivity and LukED cytotoxicity. Treatment of cells with LukED did not interfere with CCR5-tropic HIV-1 infectivity, demonstrating that LukED and the viral envelope glycoprotein use nonoverlapping sites on CCR5. Analysis of point mutations in LukE showed that amino acids 64 to 69 in the rim domain are required for CCR5 targeting and cytotoxicity. Taking the results together, this study identified the molecular basis by which LukED targets CCR5, highlighting the divergent molecular interactions evolved by HIV-1 and LukED to interact with CCR5. PMID:27965453

  8. Staphylococcus aureus Leukocidin LukED and HIV-1 gp120 Target Different Sequence Determinants on CCR5.

    PubMed

    Tam, Kayan; Schultz, Megan; Reyes-Robles, Tamara; Vanwalscappel, Bénédicte; Horton, Joshua; Alonzo, Francis; Wu, Beili; Landau, Nathaniel R; Torres, Victor J

    2016-12-13

    Leukocidin ED (LukED) is a bicomponent pore-forming toxin produced by Staphylococcus aureus that lyses host cells by targeting the chemokine receptors CC chemokine receptor type 5 (CCR5), CXCR1, CXCR2, and DARC. In addition to its role as a receptor for LukED, CCR5 is the major coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and has been extensively studied. To compare how LukED and HIV-1 target CCR5, we analyzed their respective abilities to use CCR5/CCR2b chimeras to mediate cytotoxicity and virus entry. These analyses showed that the second and third extracellular loops (ECL) of CCR5 are necessary and sufficient for LukED to target the receptor and promote cell lysis. In contrast, the second ECL of CCR5 is necessary but not sufficient for HIV-1 infectivity. The analysis of CCR5 point mutations showed that glycine-163 is critical for HIV-1 infectivity, while arginine-274 and aspartic acid-276 are critical for LukED cytotoxicity. Point mutations in ECL2 diminished both HIV-1 infectivity and LukED cytotoxicity. Treatment of cells with LukED did not interfere with CCR5-tropic HIV-1 infectivity, demonstrating that LukED and the viral envelope glycoprotein use nonoverlapping sites on CCR5. Analysis of point mutations in LukE showed that amino acids 64 to 69 in the rim domain are required for CCR5 targeting and cytotoxicity. Taking the results together, this study identified the molecular basis by which LukED targets CCR5, highlighting the divergent molecular interactions evolved by HIV-1 and LukED to interact with CCR5.

  9. Los Alamos National Laboratory computer benchmarking 1982

    SciTech Connect

    Martin, J.L.

    1983-06-01

    Evaluating the performance of computing machinery is a continual effort of the Computer Research and Applications Group of the Los Alamos National Laboratory. This report summarizes the results of the group's benchmarking activities performed between October 1981 and September 1982, presenting compilation and execution times as well as megaflop rates for a set of benchmark codes. Tests were performed on the following computers: Cray Research, Inc. (CRI) Cray-1S; Control Data Corporation (CDC) 7600, 6600, Cyber 73, Cyber 825, Cyber 835, Cyber 855, and Cyber 205; Digital Equipment Corporation (DEC) VAX 11/780 and VAX 11/782; and Apollo Computer, Inc., Apollo.

  10. Los Alamos National Laboratory strategic directions

    SciTech Connect

    Hecker, S.

    1995-10-01

    It is my pleasure to welcome you to Los Alamos. I like the idea of bringing together all aspects of the research community-defense, basic science, and industrial. It is particularly important in today`s times of constrained budgets and in fields such as neutron research because I am convinced that the best science and the best applications will come from their interplay. If we do the science well, then we will do good applications. Keeping our eye focused on interesting applications will spawn new areas of science. This interplay is especially critical, and it is good to have these communities represented here today.

  11. Environmental Programs at Los Alamos National Laboratory

    SciTech Connect

    Jones, Patricia

    2012-07-11

    Summary of this project is: (1) Teamwork, partnering to meet goals - (a) Building on cleanup successes, (b) Solving legacy waste problems, (c) Protecting the area's environment; (2) Strong performance over the past three years - (a) Credibility from four successful Recovery Act Projects, (b) Met all Consent Order milestones, (c) Successful ramp-up of TRU program; (3) Partnership between the National Nuclear Security Administration's Los Alamos Site Office, DOE Carlsbad Field Office, New Mexico Environment Department, and contractor staff enables unprecedented cleanup progress; (4) Continued focus on protecting water resources; and (5) All consent order commitments delivered on time or ahead of schedule.

  12. Biological assessment for the effluent reduction program, Los Alamos National Laboratory, Los Alamos, New Mexico

    SciTech Connect

    Cross, S.P.

    1996-08-01

    This report describes the biological assessment for the effluent recution program proposed to occur within the boundaries of Los Alamos National Laboratory. Potential effects on wetland plants and on threatened and endangered species are discussed, along with a detailed description of the individual outfalls resulting from the effluent reduction program.

  13. LAMPF II workshop, Los Alamos National Laboratory, Los Alamos, New Mexico, February 1-4, 1982

    SciTech Connect

    Thiessen, H.A.

    1982-01-01

    This report contains the proceedings of the first LAMPF II Workshop held at Los Alamos February 1 to 4, 1982. Included are the talks that were available in written form. The conclusion of the participants was that there are many exciting areas of physics that will be addressed by such a machine.

  14. Los Alamos National Laboratory Waste Management Program

    SciTech Connect

    Lopez-Escobedo, G.M.; Hargis, K.M.; Douglass, C.R.

    2007-07-01

    Los Alamos National Laboratory's (LANL) waste management program is responsible for disposition of waste generated by many of the LANL programs and operations. LANL generates liquid and solid waste that can include radioactive, hazardous, and other constituents. Where practical, LANL hazardous and mixed wastes are disposed through commercial vendors; low-level radioactive waste (LLW) and radioactive asbestos-contaminated waste are disposed on site at LANL's Area G disposal cells, transuranic (TRU) waste is disposed at the Waste Isolation Pilot Plant (WIPP), and high-activity mixed wastes are disposed at the Nevada Test Site (NTS) after treatment by commercial vendors. An on-site radioactive liquid waste treatment facility (RLWTF) removes the radioactive constituents from liquid wastes and treated water is released through an NPDES permitted outfall. LANL has a very successful waste minimization program. Routine hazardous waste generation has been reduced over 90% since 1993. LANL has a DOE Order 450.1-compliant environmental management system (EMS) that is ISO 14001 certified; waste minimization is integral to setting annual EMS improvement objectives. Looking forward, under the new LANL management and operating contractor, Los Alamos National Security (LANS) LLC, a Zero Liquid Discharge initiative is being planned that should eliminate flow to the RLWTF NPDES-permitted outfall. The new contractor is also taking action to reduce the number of permitted waste storage areas, to charge generating programs directly for the cost to disposition waste, and to simplify/streamline the waste system. (authors)

  15. Microbiome in HIV infection

    PubMed Central

    Salas, January T.; Chang, Theresa L.

    2014-01-01

    HIV primary infection occurs at mucosa tissues, suggesting an intricate interplay between microbiome and HIV infection. Recent advanced technologies of high-throughput sequencing and bioinformatics allow researchers to explore nonculturable microbes including bacteria, virus and fungi and their association with diseases. HIV/SIV infection is associated with microbiome shifts and immune activation that may affect the outcome of disease progression. Similarly, altered microbiome and inflammation are associated with increased risks of HIV acquisition, suggesting the role of microbiome in HIV transmission. In this review, we will focus on microbiome in HIV infection at various mucosal compartments. Understanding the relationship between microbiome and HIV may offer insights into development of better strategies for HIV prevention and treatment. PMID:25439273

  16. Analysis of HIV type 1 BF recombinant sequences from South America dates the origin of CRF12_BF to a recombination event in the 1970s.

    PubMed

    Dilernia, Dario A; Jones, Leandro R; Pando, Maria A; Rabinovich, Roberto D; Damilano, Gabriel D; Turk, Gabriela; Rubio, Andrea E; Pampuro, Sandra; Gomez-Carrillo, Manuel; Salomón, Horacio

    2011-05-01

    HIV-1 epidemics in South America are believed to have originated in part from the subtype B epidemic initiated in the Caribbean/North America region. However, circulation of BF recombinants in similar proportions was extensively reported. Information currently shows that many BF recombinants share a recombination structure similar to that found in the CRF12_BF. In the present study, analyzing a set of 405 HIV sequences, we identified the most likely origin of the BF epidemic in an early event of recombination. We found that the subtype B epidemics in South America analyzed in the present study were initiated by a founder event that occurred in the early 1970s, a few years after the introduction of these strains in the Americas. Regarding the F/BF recombinant epidemics, by analyzing a subtype F genomic segment within the viral gene gag present in the majority of the BF recombinants, we found evidence of a geographic divergence very soon after the introduction of subtype F strains in South America. Moreover, through analysis of a subtype B segment present in all the CRF12_BF-like recombination structure, we estimated the circulation of the subtype B strain that gave rise to that recombinant structure around the same time period estimated for the introduction of subtype F strains. The HIV epidemics in South America were initiated in part through a founder event driven by subtype B strains coming from the previously established epidemic in the north of the continent. A second introduction driven by subtype F strains is likely to have encountered the incipient subtype B epidemic that soon after their arrival recombined with them, originating the BF epidemic in the region. These results may explain why in South America the majority of F sequences are found as BF recombinants.

  17. DOE Los Alamos National Laboratory – PV Feasibility Assessment, 2015 Update, NREL Final Report

    SciTech Connect

    Dean, Jesse; Witt, Monica Rene

    2016-04-06

    This report summarizes solar and wind potential for Los Alamos National Laboratory (LANL). This report is part of the “Los Alamos National Laboratory and Los Alamos County Renewable Generation” study.

  18. A highly conserved sequence associated with the HIV gp41 loop region is an immunomodulator of antigen-specific T cells in mice.

    PubMed

    Ashkenazi, Avraham; Faingold, Omri; Kaushansky, Nathali; Ben-Nun, Avraham; Shai, Yechiel

    2013-03-21

    Modulation of T-cell responses by HIV occurs via distinct mechanisms, 1 of which involves inactivation of T cells already at the stage of virus-cell fusion. Hydrophobic portions of the gp41 protein of the viral envelope that contributes to membrane fusion may modulate T-cell responsiveness. Here we found a highly conserved sequence (termed "ISLAD") that is associated with the membranotropic gp41 loop region. We showed that ISLAD has the ability to bind the T-cell membrane and to interact with the T-cell receptor (TCR) complex. Furthermore, ISLAD inhibited T-cell proliferation and interferon-γ secretion that resulted from TCR engagement through antigen-presenting cells. Moreover, administering ISLAD (10 µg per mouse) to an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis reduced the severity of the disease. This was related to the inhibition of pathogenic T-cell proliferation and to reduced pro-inflammatory cytokine secretion in the lymph nodes of ISLAD-treated EAE mice. The data suggest that T-cell inactivation by HIV during membrane fusion may lie in part in this conserved sequence associated with the gp41 loop region.

  19. Los Alamos personnel and area criticality dosimeter systems

    SciTech Connect

    Vasilik, D.G.; Martin, R.W.

    1981-06-01

    Fissionable materials are handled and processed at the Los Alamos National Laboratory. Although the probability of a nuclear criticality accident is very remote, it must be considered. Los Alamos maintains a broad spectrum of dose assessment capabilities. This report describes the methods employed for personnel neutron, area neutron, and photon dose evaluations with passive dosimetry systems.

  20. The Climate at Los Alamos; Are we measurement changes?

    SciTech Connect

    Dewart, Jean Marie

    2015-04-16

    A new report shows new graphic displays of the weather trends in Los Alamos, New Mexico, and at the Los Alamos National Laboratory (LANL). The graphs show trends of average, minimum average, and maximum average temperature for summer and winter months going back decades. Records of summer and winter precipitation are also included in the report.

  1. Audit of personal property management at Los Alamos National Laboratory

    SciTech Connect

    Not Available

    1993-12-07

    The Department of Energy`s (Department) Albuquerque Operations Office (Albuquerque) and the Los Alamos National Laboratory (Los Alamos) are responsible for ensuring that Los Alamos maintains an efficient and effective personal property management system that protects, identifies, and controls Government-owned personal property in accordance with applicable regulations. Albuquerque is responsible for reviewing and approving Los Alamos` personal property management system. Los Alamos is responsible for ensuring that personal property is properly protected, identified, and controlled. The audit disclosed that Los Alamos did not have an efficient and effective personal property management system to ensure that personal property was adequately protected, identified, and controlled. In addition, Albuquerque did not approve or disapprove Los Alamos` personal property management system consistent with Federal and Department regulations. Specifically, the audit showed that Los Alamos did not account for $11.6 million of personal property. In addition, $22.2 million of personal property was not properly recorded in the database, $61.7 million of personal property could not be inventoried, and loans to employees and other entities were not adequately justified. As a result, from a total personal property inventory of approximately $1 billion, it is estimated that $100 million of personal property may not be accounted for, and $207 million may not be correctly recorded in the database. Moreover, substantial amounts of personal property on loan to employees and other entities were at risk of unauthorized use. Albuquerque concurred with the finding and agreed to implement the corrective actions recommended in the report.

  2. Portable MRI developed at Los Alamos

    SciTech Connect

    Espy, Michelle

    2015-04-22

    Scientists at Los Alamos National Laboratory are developing an ultra-low-field Magnetic Resonance Imaging (MRI) system that could be low-power and lightweight enough for forward deployment on the battlefield and to field hospitals in the World's poorest regions. "MRI technology is a powerful medical diagnostic tool," said Michelle Espy, the Battlefield MRI (bMRI) project leader, "ideally suited for imaging soft-tissue injury, particularly to the brain." But hospital-based MRI devices are big and expensive, and require considerable infrastructure, such as large quantities of cryogens like liquid nitrogen and helium, and they typically use a large amount of energy. "Standard MRI machines just can't go everywhere," said Espy. "Soldiers wounded in battle usually have to be flown to a large hospital and people in emerging nations just don't have access to MRI at all. We've been in contact with doctors who routinely work in the Third World and report that MRI would be extremely valuable in treating pediatric encephalopathy, and other serious diseases in children." So the Los Alamos team started thinking about a way to make an MRI device that could be relatively easy to transport, set up, and use in an unconventional setting. Conventional MRI machines use very large magnetic fields that align the protons in water molecules to then create magnetic resonance signals, which are detected by the machine and turned into images. The large magnetic fields create exceptionally detailed images, but they are difficult and expensive to make. Espy and her team wanted to see if images of sufficient quality could be made with ultra-low-magnetic fields, similar in strength to the Earth's magnetic field. To achieve images at such low fields they use exquisitely sensitive detectors called Superconducting Quantum Interference Devices, or SQUIDs. SQUIDs are among the most sensitive magnetic field detectors available, so interference with the signal is the primary stumbling block. "SQUIDs are

  3. Portable MRI developed at Los Alamos

    ScienceCinema

    Espy, Michelle

    2016-07-12

    Scientists at Los Alamos National Laboratory are developing an ultra-low-field Magnetic Resonance Imaging (MRI) system that could be low-power and lightweight enough for forward deployment on the battlefield and to field hospitals in the World's poorest regions. "MRI technology is a powerful medical diagnostic tool," said Michelle Espy, the Battlefield MRI (bMRI) project leader, "ideally suited for imaging soft-tissue injury, particularly to the brain." But hospital-based MRI devices are big and expensive, and require considerable infrastructure, such as large quantities of cryogens like liquid nitrogen and helium, and they typically use a large amount of energy. "Standard MRI machines just can't go everywhere," said Espy. "Soldiers wounded in battle usually have to be flown to a large hospital and people in emerging nations just don't have access to MRI at all. We've been in contact with doctors who routinely work in the Third World and report that MRI would be extremely valuable in treating pediatric encephalopathy, and other serious diseases in children." So the Los Alamos team started thinking about a way to make an MRI device that could be relatively easy to transport, set up, and use in an unconventional setting. Conventional MRI machines use very large magnetic fields that align the protons in water molecules to then create magnetic resonance signals, which are detected by the machine and turned into images. The large magnetic fields create exceptionally detailed images, but they are difficult and expensive to make. Espy and her team wanted to see if images of sufficient quality could be made with ultra-low-magnetic fields, similar in strength to the Earth's magnetic field. To achieve images at such low fields they use exquisitely sensitive detectors called Superconducting Quantum Interference Devices, or SQUIDs. SQUIDs are among the most sensitive magnetic field detectors available, so interference with the signal is the primary stumbling block. "SQUIDs are

  4. Los Alamos National Laboratory transuranic database analysis

    SciTech Connect

    Christensen, D.V.; Rogers, P.S.Z.; Kosiewicz, S.T.; LeBrun, D.B.

    1997-02-01

    This paper represents an overview of analyses conducted on the TRU database maintained by the Los Alamos National Laboratory (LANL). This evaluation was conducted to support the ``TRU Waste Workoff Strategies`` document and provides an estimation of the waste volume that potentially could be certified and ready for shipment to (WIPP) in April of 1998. Criteria defined in the WIPP WAC, including container type, weight limits, plutonium fissile gram equivalents and decay heat, were used to evaluated the waste for compliance. LANL evaluated the containers by facility and by waste stream to determining the most efficient plan for characterization and certification of the waste. Evaluation of the waste presently in storage suggested that 40- 60% potentially meets the WIPP WAC Rev. 5 criteria.

  5. Los Alamos Advanced Free-Electron Laser

    SciTech Connect

    Chan, K.C.D.; Kraus, R.H.; Ledford, J.; Meier, K.L.; Meyer, R.E.; Nguyen, D.; Sheffield, R.L.; Sigler, F.L.; Young, L.M.; Wang, T.S.; Wilson, W.L.; Wood, R.L.

    1991-01-01

    At Los Alamos, we are building a free-electron laser (FEL) for industrial, medical, and research applications. This FEL, which will incorporate many of the new technologies developed over the last decade, will be compact in size, robust, and user-friendly. Electrons produced by a photocathode will be accelerated to 20 MeV by a high-brightness accelerator and transported using permanent-magnet quadrupoles and dipoles. They will form an electron beam with an excellent instantaneous beam quality of 10 {pi} mm mrad in transverse emittance and 0.3% in energy spread at a peak current up to 300 A. Including operation at higher harmonics, the laser wavelength extends form 3.7 {mu}m to 0.4 {mu}m. In this paper, we will describe the project and the programs to date. 10 refs., 10 figs., 1 tab.

  6. Environmental surveillance at Los Alamos during 1979

    SciTech Connect

    Not Available

    1980-04-01

    This report documents the environmental surveillance program conducted by the Los Alamos Scientific Laboratory (LASL) in 1979. Routine monitoring for radiation and radioactive or chemical substances was conducted on the Laboratory site and in the surrounding region to determine compliance with appropriate standards and permit early identification of possible undesirable trends. Results and interpretation of the data for 1979 on penetrating radiation, chemical and radiochemical quality of ambient air, surface and ground water, municipal water supply, soils and sediments, food, and airborne and liquid effluents are included. Comparisons with appropriate standards and regulations or with background levels from natural or other non-LASL sources provide a basis for concluding that environmental effects attributable to LASL operations are minor and cannot be considered likely to result in any hazard to the population of the area. Results of several special studies provide documentation of some unique environmental conditions in the LASL environs.

  7. Environmental surveillance at Los Alamos during 1987

    SciTech Connect

    Not Available

    1988-05-01

    This report describes the environmental surveillance program conducted by Los Alamos National Laboratory during 1987. Routine monitoring for radiation and radioactive or chemical materials is conducted on the Laboratory site as well as in the surrounding region. Monitoring results are used to determine compliance with appropriate standards and to permit early identification of potentially undesirable trends. Results and interpretation of data for 1987 cover: external penetrating radiation; quantities of airborne emissions and liquid effluents; concentrations of chemicals and radionuclides in ambient air, surface and ground waters, municipal water supply, soils and sediments, and foodstuffs; and environmental compliance. Comparisons with appropriate standards, regulations, and background levels provide the basis for concluding that environmental effects from Laboratory operations are insignificant and do not pose a threat to the public, Laboratory employees, or the environment. 113 refs., 33 figs., 120 tabs.

  8. Environmental surveillance at Los Alamos during 1989

    SciTech Connect

    Not Available

    1990-12-01

    This report describes the environmental surveillance program conducted by Los Alamos National Laboratory during 1989. Routine monitoring for radiation and radioactive or chemical materials is conducted on the Laboratory site as well as in the surrounding region. Monitoring results are used to determine compliance with appropriate standards and to permit early identification of potentially undesirable trends. Results and interpretation of data for 1989 cover external penetrating radiation; quantities of airborne emissions and effluents; concentrations of chemicals and radionuclides in ambient air, surface and ground waters, municipal water supply, soils and sediments, and foodstuffs; and environmental compliance. Comparisons with appropriate standards, regulations, and background levels provide the basis for concluding that environmental effects from Laboratory operations are small and do not pose a threat to the public, Laboratory employees, or the environment. 58 refs., 31 figs., 39 tabs.

  9. Information about Practicums at Los Alamos

    SciTech Connect

    Bradley, Paul A.

    2012-07-24

    The Los Alamos Neutron Science Center is the premier facility for neutron science experiments ranging from cross section measurements, neutron scattering experiments, proton radiography, cold neutrons, actinide neutronic properties, and many other exciting topics. The National High Magnetic Field Laboratory is home to several powerful magnets, including the one that created the first non-destructive 100 Tesla field in March 2012. They probe the electronic structure of superconductors, magnetic properties of materials (including magneto-quantum effects). Research is also conducted in correlated materials, thermoacoustics, and magnetic properties of actinides. The Trident Laser has a unique niche with very high power, short pulse experiments, with a peak power of 10{sup 20} W in short pulse mode. Discoveries range from production of monoenergetic MeV ion beam, nonlinear kinetic plasma waves, the transition between kinetic and fluid nonlinear behavior and other laser-plasma interaction processes.

  10. Environmental surveillance at Los Alamos during 1995

    SciTech Connect

    1996-10-01

    This report describes the environmental surveillance program at Los Alamos National Laboratory (LANL or the Laboratory) during 1995. The Laboratory routinely monitors for radiation and for radioactive and nonradioactive materials at (or on) Laboratory sites as well as in the surrounding region. LANL uses the monitoring result to determine compliance with appropriate standards and to identify potentially undesirable trends. Data were collected in 1995 to assess external penetrating radiation; quantities of airborne emissions and liquid effluents; concentrations of chemicals and radionuclides in ambient air, surface waters and groundwaters, municipal water supply, soils and sediments, and foodstuffs; and environmental compliance. Using comparisons with standards, regulations, and background levels, this report concludes that environmental effects from Laboratory operations are small and do not pose a demonstrable threat to the public, Laboratory employees, or the environment.

  11. Environmental surveillance at Los Alamos during 1992

    SciTech Connect

    Kohen, K.; Stoker, A.; Stone, G.

    1994-07-01

    This report describes the environmental surveillance program at Los Alamos National Laboratory during 1992. The Laboratory routinely monitors for radiation and for radioactive and nonradioactive materials at (or on) Laboratory sites as well as in the surrounding region. LANL uses the monitoring results to determine compliance with appropriate standards and to identify potentially undesirable trends. Data were collected in 1992 to assess external penetrating radiation; quantities of airborne emissions and liquid effluents; concentrations of chemicals and radionuclides in ambient air, surface waters and groundwaters, municipal water supply, soils and sediments, and foodstuffs; and environmental compliance. Using comparisons with standards, regulations, and background levels, this report concludes that environmental effects from Laboratory operations are small and do not pose a demonstrable threat to the public, laboratory employees, or the environment.

  12. Hot Dry Rock Overview at Los Alamos

    SciTech Connect

    Berger, Michael; Hendron, Robert H.

    1989-03-21

    The Hot Dry Rock (HDR) geothermal energy program is a renewable energy program that can contribute significantly to the nation's balanced and diversified energy mix. Having extracted energy from the first Fenton Hill HDR reservoir for about 400 days, and from the second reservoir for 30 days in a preliminary test, Los Alamos is focusing on the Long Term Flow Test and reservoir studies. Current budget limitations have slowed preparations thus delaying the start date of that test. The test is planned to gather data for more definitive reservoir modeling with energy availability or reservoir lifetime of primary interest. Other salient information will address geochemistry and tracer studies, microseismic response, water requirements and flow impedance which relates directly to pumping power requirements. During this year of ''preparation'' we have made progress in modeling studies, in chemically reactive tracer techniques, in improvements in acoustic or microseismic event analysis.

  13. Environmental surveillance at Los Alamos during 2008

    SciTech Connect

    Fuehne, David; Gallagher, Pat; Hjeresen, Denny; Isaacson, John; Johson, Scot; Morgan, Terry; Paulson, David; Rogers, David

    2009-09-30

    Environmental Surveillance at Los Alamos reports are prepared annually by the Los Alamos National Laboratory (the Laboratory) Environmental Programs Directorate, as required by US Department of Energy Order 450.1, General Environmental Protection Program, and US Department of Energy Order 231.1A, Environment, Safety, and Health Reporting. These annual reports summarize environmental data that are used to determine compliance with applicable federal, state, and local environmental laws and regulations, executive orders, and departmental policies. Additional data, beyond the minimum required, are also gathered and reported as part of the Laboratory’s efforts to ensure public safety and to monitor environmental quality at and near the Laboratory. Chapter 1 provides an overview of the Laboratory’s major environmental programs and explains the risks and the actions taken to reduce risks at the Laboratory from environmental legacies and waste management operations. Chapter 2 reports the Laboratory’s compliance status for 2007. Chapter 3 provides a summary of the maximum radiological dose the public and biota populations could have potentially received from Laboratory operations and discusses chemical exposures. The environmental surveillance and monitoring data are organized by environmental media (Chapter 4, air; Chapters 5 and 6, water and sediments; Chapter 7, soils; and Chapter 8, foodstuffs and biota) in a format to meet the needs of a general and scientific audience. Chapter 9 provides a summary of the status of environmental restoration work around LANL. A glossary and a list of acronyms and abbreviations are in the back of the report. Appendix A explains the standards for environmental contaminants, Appendix B explains the units of measurements used in this report, Appendix C describes the Laboratory’s technical areas and their associated programs, and Appendix D provides web links to more information.

  14. Environmental surveillance at Los Alamos during 2009

    SciTech Connect

    Fuehne, David; Poff, Ben; Hjeresen, Denny; Isaacson, John; Johnson, Scot; Morgan, Terry; Paulson, David; Salzman, Sonja; Rogers, David

    2010-09-30

    Environmental Surveillance at Los Alamos reports are prepared annually by the Los Alamos National Laboratory (the Laboratory) environmental organization, as required by US Department of Energy Order 5400.1, General Environmental Protection Program, and US Department of Energy Order 231.1A, Environment, Safety, and Health Reporting. These annual reports summarize environmental data that are used to determine compliance with applicable federal, state, and local environmental laws and regulations, executive orders, and departmental policies. Additional data, beyond the minimum required, are also gathered and reported as part of the Laboratory’s efforts to ensure public safety and to monitor environmental quality at and near the Laboratory. Chapter 1 provides an overview of the Laboratory’s major environmental programs and explains the risks and the actions taken to reduce risks at the Laboratory from environmental legacies and waste management operations. Chapter 2 reports the Laboratory’s compliance status for 2009. Chapter 3 provides a summary of the maximum radiological dose the public and biota populations could have potentially received from Laboratory operations and discusses chemical exposures. The environmental surveillance and monitoring data are organized by environmental media (air in Chapter 4; water and sediments in Chapters 5 and 6; soils in Chapter 7; and foodstuffs and biota in Chapter 8) in a format to meet the needs of a general and scientific audience. Chapter 9 provides a summary of the status of environmental restoration work around LANL. The new Chapter 10 describes the Laboratory’s environmental stewardship efforts and provides an overview of the health of the Rio Grande. A glossary and a list of acronyms and abbreviations are in the back of the report. Appendix A explains the standards for environmental contaminants, Appendix B explains the units of measurements used in this report, Appendix C describes the Laboratory’s technical

  15. Environmental surveillance at Los Alamos during 2005

    SciTech Connect

    2006-09-30

    Environmental Surveillance at Los Alamos reports are prepared annually by the Los Alamos National Laboratory (LANL or the Laboratory) environmental organization, as required by US Department of Energy Order 5400.1, General Environmental Protection Program, and US Department of Energy Order 231.IA, Environment, Safety, and Health Reporting. These annual reports summarize environmental data that are used to determine compliance with applicable federal, state, and local environmental laws and regulations, executive orders, and departmental policies. Additional data, beyond the minimum required, are also gathered and reported as part of the Laboratory's efforts to ensure public safety and to monitor environmental quality at and near the Laboratory. Chapter 1 provides an overview of the Laboratory's major environmental programs. Chapter 2 reports the Laboratory's compliance status for 2005. Chapter 3 provides a summary of the maximum radiological dose the public and biota populations could have potentially received from Laboratory operations. The environmental surveillance and monitoring data are organized by environmental media (Chapter 4, Air; Chapters 5 and 6, Water and Sediments; Chapter 7, Soils; and Chapter 8, Foodstuffs and Biota) in a format to meet the needs of a general and scientific audience. Chapter 9, new for this year, provides a summary of the status of environmental restoration work around LANL. A glossary and a list ofacronyms and abbreviations are in the back of the report. Appendix A explains the standards for environmental contaminants, Appendix B explains the units of measurements used in this report, Appendix C describes the Laboratory's technical areas and their associated programs, and Appendix D provides web links to more information.

  16. Environmental analysis of Lower Pueblo/Lower Los Alamos Canyon, Los Alamos, New Mexico

    SciTech Connect

    Ferenbaugh, R.W.; Buhl, T.E.; Stoker, A.K.; Becker, N.M.; Rodgers, J.C.; Hansen, W.R.

    1994-12-01

    The radiological survey of the former radioactive waste treatment plant site (TA-45), Acid Canyon, Pueblo Canyon, and Los Alamos Canyon found residual contamination at the site itself and in the channel and banks of Acid, Pueblo, and lower Los Alamos Canyons all the way to the Rio Grande. The largest reservoir of residual radioactivity is in lower Pueblo Canyon, which is on DOE property. However, residual radioactivity does not exceed proposed cleanup criteria in either lower Pueblo or lower Los Alamos Canyons. The three alternatives proposed are (1) to take no action, (2) to construct a sediment trap in lower Pueblo Canyon to prevent further transport of residual radioactivity onto San Ildefonso Indian Pueblo land, and (3) to clean the residual radioactivity from the canyon system. Alternative 2, to cleanup the canyon system, is rejected as a viable alternative. Thousands of truckloads of sediment would have to be removed and disposed of, and this effort is unwarranted by the low levels of contamination present. Residual radioactivity levels, under either present conditions or projected future conditions, will not result in significant radiation doses to persons exposed. Modeling efforts show that future transport activity will not result in any residual radioactivity concentrations higher than those already existing. Thus, although construction of a sediment trap in lower Pueblo Canyon is a viable alternative, this effort also is unwarranted, and the no-action alternative is the preferred alternative.

  17. Detection of HIV-1 Drug Resistance in Women Following Administration of a Single Dose of Nevirapine: Comparison of Plasma RNA to Cellular DNA by Consensus Sequencing and by Oligonucleotide Ligation Assay▿

    PubMed Central

    Wagner, Thor A.; Kress, Catherine M.; Beck, Ingrid; Techapornroong, Malee; Wittayapraparat, Pakorn; Tansuphasawasdikul, Somboon; Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Lallemant, Marc; Frenkel, Lisa M.

    2010-01-01

    A single dose of nevirapine (sdNVP) to prevent mother-to-child transmission of HIV-1 increases the risk of failure of subsequent NVP-containing antiretroviral therapy (ART), especially when initiated within 6 months of sdNVP administration, emphasizing the importance of understanding the decay of nevirapine-resistant mutants. Nevirapine-resistant HIV-1 genotypes (with the mutations K103N, Y181C, and/or G190A) from 21 women were evaluated 10 days and 6 weeks after sdNVP administration and at the initiation of ART. Resistance was assayed by consensus sequencing and by a more sensitive assay (oligonucleotide ligation assay [OLA]) using plasma-derived HIV-1 RNA and cell-associated HIV-1 DNA. OLA detected nevirapine resistance in more specimens than consensus sequencing did (63% versus 33%, P < 0.01). When resistance was detected only by OLA (n = 45), the median mutant concentration was 18%, compared to 61% when detected by both sequencing and OLA (n = 51) (P < 0.0001). The proportion of women whose nevirapine resistance was detected by OLA 10 days after sdNVP administration was higher when we tested their HIV-1 RNA (95%) than when we tested their HIV-1 DNA (88%), whereas at 6 weeks after sdNVP therapy, the proportion was greater with DNA (85%) than with RNA (67%) and remained higher with DNA (33%) than with RNA (11%) at the initiation of antiretroviral treatment (median, 45 weeks after sdNVP therapy). Fourteen women started NVP-ART more than 6 months after sdNVP therapy; resistance was detected by OLA in 14% of the women but only in their DNA. HIV-1 resistance to NVP following sdNVP therapy persists longer in cellular DNA than in plasma RNA, as determined by a sensitive assay using sufficient copies of virus, suggesting that DNA may be superior to RNA for detecting resistance at the initiation of ART. PMID:20181911

  18. DNA-stabilized silver nanoclusters and carbon nanoparticles oxide: A sensitive platform for label-free fluorescence turn-on detection of HIV-DNA sequences.

    PubMed

    Ye, Yu-Dan; Xia, Li; Xu, Dang-Dang; Xing, Xiao-Jing; Pang, Dai-Wen; Tang, Hong-Wu

    2016-11-15

    Based on the remarkable difference between the interactions of carbon nanoparticles (CNPs) oxide with single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), and the fact that fluorescence of DNA-stabilized silver nanoclusters (AgNCs) can be quenched by CNPs oxide, DNA-functionalized AgNCs were applied as label-free fluorescence probes and a novel fluorescence resonance energy transfer (FRET) sensor was successfully constructed for the detection of human immunodeficiency virus (HIV) DNA sequences. CNPs oxide were prepared with the oxidation of candle soot, hence it is simple, time-saving and low-cost. The strategy of dual AgNCs probes was applied to improve the detection sensitivity by using dual- probe capturing the same target DNA in a sandwich mode and as the fluorescence donor, and using CNPs oxide as the acceptor. In the presence of target DNA, a dsDNA hybrid forms, leading to the desorption of the ssDNA-AgNCs probes from CNPs oxide, and the recovering of fluorescence of the AgNCs in a HIV-DNA concentration-dependent manner. The results show that HIV-DNA can be detected in the range of 1-50nM with a detection limit of 0.40nM in aqueous buffer. The method is simple, rapid and sensitive with no need of labeled fluorescent probes, and moreover, the design of fluorescent dual-probe makes full use of the excellent fluorescence property of AgNCs and further improves the detection sensitivity.

  19. Carbon isotope chemostratigraphy and precise dating of middle Frasnian (lower Upper Devonian) Alamo Breccia, Nevada, USA

    USGS Publications Warehouse

    Morrow, J.R.; Sandberg, C.A.; Malkowski, K.; Joachimski, M.M.

    2009-01-01

    At Hancock Summit West, Nevada, western USA, uppermost Givetian (upper Middle Devonian) and lower and middle Frasnian (lower Upper Devonian) rocks of the lower Guilmette Formation include, in stratigraphic sequence, carbonate-platform facies of the conodont falsiovalis, transitans, and punctata Zones; the type Alamo Breccia Member of the middle punctata Zone; and slope facies of the punctata and hassi Zones. The catastrophically deposited Alamo Breccia and related phenomena record the ~ 382??Ma Alamo event, produced by a km-scale bolide impact into a marine setting seaward of an extensive carbonate platform fringing western North America. Re-evaluation of conodonts from the lower Guilmette Formation and Alamo Breccia Member, together with regional sedimentologic and conodont biofacies comparisons, now firmly locates the onset of the Johnson et al. (1985) transgressive-regressive (T-R) cycle IIc, which occurred after the start of the punctata Zone, within a parautochthonous megablock low in the Alamo Breccia. Whole-rock carbon isotope analyses through the lower Guilmette Formation and Alamo Breccia Member reveal two positive ??13Ccarb excursions: (1) a small, 3??? excursion, which is possibly correlative with the falsiovalis Event previously identified from sections in Western Europe and Australia, occurs below the breccia in the Upper falsiovalis Zone to early part of the transitans Zone; and (2) a large, multi-part excursion, dominated by a 6??? positive shift, begins above the start of the punctata Zone and onset of T-R cycle IIc and continues above the Alamo Breccia, ending near the punctata- hassi zonal boundary. This large excursion correlates with the punctata Event, a major positive ??13C excursion previously recognized in eastern Laurussia and northern Gondwana. Consistent with previous studies, at Hancock Summit West the punctata Event is apparently not associated with any regional extinctions or ecosystem reorganizations. In the study area, onset of the

  20. Deep sequencing of RYR3 gene identifies rare and common variants associated with increased carotid intima-media thickness (cIMT) in HIV-infected individuals.

    PubMed

    Zhi, Degui; Shendre, Aditi; Scherzer, Rebecca; Irvin, Marguerite R; Perry, Rodney T; Levy, Shawn; Arnett, Donna K; Grunfeld, Carl; Shrestha, Sadeep

    2015-02-01

    Carotid intima-media thickness (cIMT) is a subclinical measure of atherosclerosis with mounting evidence that higher cIMT confers an increased risk of cardiovascular disease. The ryanodine receptor 3 gene (RYR3) has previously been linked to increased cIMT; however, the causal variants have not yet been localized. Therefore, we sequenced 339,480 bp encompassing 104 exons and 2 kb flanking region of the RYR3 gene in 96 HIV-positive white men from the extremes of the distribution of common cIMT from the Fat Redistribution and Metabolic Changes in HIV infection study (FRAM). We identified 2710 confirmed variants (2414 single-nucleotide polymorphisms (SNPs) and 296 insertion/deletions (indels)), with a mean count of 736 SNPs (ranging from 528 to 1032) and 170 indels (ranging from 128 to 214) distributed in each individual. There were 39 variants in the exons and 15 of these were non-synonymous, of which with only 4 were common variants and the remaining 11 were rare variants, one was a novel SNP. We confirmed that the common variant rs2229116 was significantly associated with cIMT in this design (P<7.9 × 10(-9)), and observed seven other significantly associated SNPs (P<10(-8)). These variants including the private non-synonymous SNPs need to be followed up in a larger sample size and also tested with clinical atherosclerotic outcomes.

  1. Genotyping of Pneumocystis jirovecii isolates from Chinese HIV-infected patients based on nucleotide sequence variations in the internal transcribed spacer regions of rRNA genes.

    PubMed

    Li, Kai; He, Ai; Cai, Wei Ping; Tang, Xiao Ping; Zheng, Xiao Ying; Li, Zhuo Ya; Zhan, Xi Mei

    2013-01-01

    Genetic diversity of Pneumocystis jirovecii isolates based on internal transcribed spacer (ITS) of the nuclear rRNA locus has previously been reported. The information about ITS genotype and epidemiology of this organism in Chinese human immunodeficiency virus-infected patients has not been available. In this study, 12 bronchoalveolar lavage fluid specimens obtained from HIV-infected patients were analyzed by PCR followed by cloning, sequencing and typing. Three ITS1 genotypes (E, B and 'H') and four ITS2 genotypes (b, g, i and r) as previously reported were identified, the most common of which were E, b and i. Five ITS haplotypes (Eg, Eb, Bi, Er and 'H'r) and 19 new combination types were also identified with the most common types being Eg (four of 12 patients, 10 of 60 clones), Eb (three of 12 patients, 11 of 60 clones) and Bi (three of 12 patients, 10 of 60 clones). Nine patients were found to be co-infected with more than one ITS genotype of P. jirovecii. The prevalence of ITS genotypes in HIV patients from one Chinese hospital did not seem to be significantly different when compared to reports from other countries.

  2. Potential impact of viral load and genetic makeup of HIV type 1 on mother-to-child transmission: characterization of env-C2V3C3 and nef sequences.

    PubMed

    Pádua, Elizabeth; Parreira, Ricardo; Tendeiro, Rita; Nunes, Baltazar; Castela, João; Soares, Isabel; Mouzinho, Ana; Reis, Eduarda; Paixão, Maria Teresa

    2009-11-01

    HIV-1 mother-to-child transmission (MTCT) was evaluated in terms of the molecular characterization of the env and nef genomic regions and quantification of maternal RNA viral loads. Assignment of viral subtype was achieved by direct sequencing of PCR 1172 products amplified from proviral DNA in 45 HIV-1-nontransmitting mothers (NTM), along with 13 pairs of HIV-1-transmitting mothers (TM) and their infected children (C). Analysis of the env C2V3C3 and nef sequences revealed that subtypes G and B, and their genetic combinations (AG, BG), accounted for over 84.5% of all viruses identified. The genetic structure form envA-nefG was the most commonly observed, with a lower frequency in the NTM (13.3%) compared to the TM (23.1%) group. A greater number of genetic forms was observed among NTM, namely the presence of sequences assigned to subtypes D and F, as well as the intergenetic A/J, and C/U, recombinant forms, along with a mosaic provirus with a complex putative envA-nefEGE genetic structure. No significant differences were found when RNA viral loads were evaluated as a function of the viral subtypes. Nevertheless, a relatively high quantification of HIV-1 RNA was obtained in the NTM group, emphasizing the importance of the compliance and effectiveness of therapeutic schemes to control viral replication and reduce the risk of HIV vertical transmission. V3 sequences displaying features associated with the R5 phenotype dominated in both groups. Both C2V3C3 and Nef's functional domains were conserved during HIV-1 vertical transmission.

  3. Magic Angle Spinning NMR Reveals Sequence-Dependent Structural Plasticity, Dynamics, and the Spacer Peptide 1 Conformation in HIV-1 Capsid Protein Assemblies

    SciTech Connect

    Han, Yun; Hou, Guangjin; Suiter, Christopher L.; Ahn, Jinwoo; Byeon, In-Ja L.; Lipton, Andrew S.; Burton, Sarah D.; Hung, Ivan; Gorkov, Peter L.; Gan, Zhehong; Brey, William W.; Rice, David M.; Gronenborn, Angela M.; Polenova, Tatyana E.

    2013-11-27

    Maturation of HIV-1 virus into an infectious virion requires cleavage of the Gag polyprotein into its constituent domains and formation of a conical capsid core that encloses viral RNA and a small complement of proteins for replication. The final step of this process is the cleavage of the SP1 peptide from the CA-SP1 maturation intermediate, which triggers the condensation of the CA protein into a conical capsid. The mechanism of this step, including the conformation of the SP1 peptide in CA-SP1, is under intense debate. In this report, we examine the tubular assemblies of CA and the CA-SP1 maturation intermediate using Magic Angle Spinning NMR spectroscopy. At the magnetic fields of 19.9 T and above, tubular CA and CA-SP1 assemblies yield outstanding-quality 2D and 3D MAS NMR spectra, which are amenable to resonance assignments and detailed structural characterization. Dipolar- and scalar-based correlation experiments unequivocally indicate that SP1 peptide is in a random coil conformation and mobile in the assembled CA-SP1. Analysis of two sequence variants reveals that remarkably, the conformation of SP1 tail, of the functionally important CypA loop, and of the loop preceding helix 8 are sequence dependent and modulated by the residue variations at distal sites. These findings challenge the role of SP1 as a conformational switch in the maturation process and establish sequence-dependent conformational plasticity in CA.

  4. Investigation by two-photon fluorescence correlation spectroscopy of the interaction of the nucleocapsid protein of HIV-1 with hairpin loop DNA sequences

    NASA Astrophysics Data System (ADS)

    Mely, Yves; Azoulay, Joel; Beltz, Herve; Clamme, Jean-Pierre; Bernacchi, Serena; Ficheux, Damien; Roques, Bernard P.; Darlix, Jean-Luc

    2004-09-01

    The nucleocapsid protein NCp7 of HIV-1 possesses nucleic acid chaperone properties that are critical for the two strand transfer reactions required during reverse transcription. The first DNA strand transfer relies on the destabilization by NCp7 of double-stranded segments of the transactivation response element, TAR sequence, at the 3' end of the genomic RNA and the complementary sequence cTAR at the 3" terminus of the early product of reverse transcription. To characterize NCp7-mediated nucleic acid destabilization, we investigated by steady-state and time-resolved fluorescence spectroscopy and two photon fluorescence correlation spectroscopy, the interaction of a doubly-labelled cTAR sequence with NCp7. The conformational fluctuations observed in the absence of NCp7 were associated with the rapid opening and closing (fraying) of the double stranded terminal segment of cTAR. NCp7 destabilizes cTAR mainly through a large increase of the opening rate constant. Additionally, the various destabilizing structures (bulges, internal loop, mismatches) spread all over cTAR secondary structure were found to be critical for NCp7 chaperone activity. Taken together, our data enabled us to propose a molecular mechanism for the destabilizing activity of NCp7 on cTAR which is crucial for the formation of the cTAR-TAR complex during the first strand transfer reaction.

  5. IDEPI: Rapid Prediction of HIV-1 Antibody Epitopes and Other Phenotypic Features from Sequence Data Using a Flexible Machine Learning Platform

    PubMed Central

    Hepler, N. Lance; Scheffler, Konrad; Weaver, Steven; Murrell, Ben; Richman, Douglas D.; Burton, Dennis R.; Poignard, Pascal; Smith, Davey M.; Kosakovsky Pond, Sergei L.

    2014-01-01

    Since its identification in 1983, HIV-1 has been the focus of a research effort unprecedented in scope and difficulty, whose ultimate goals — a cure and a vaccine – remain elusive. One of the fundamental challenges in accomplishing these goals is the tremendous genetic variability of the virus, with some genes differing at as many as 40% of nucleotide positions among circulating strains. Because of this, the genetic bases of many viral phenotypes, most notably the susceptibility to neutralization by a particular antibody, are difficult to identify computationally. Drawing upon open-source general-purpose machine learning algorithms and libraries, we have developed a software package IDEPI (IDentify EPItopes) for learning genotype-to-phenotype predictive models from sequences with known phenotypes. IDEPI can apply learned models to classify sequences of unknown phenotypes, and also identify specific sequence features which contribute to a particular phenotype. We demonstrate that IDEPI achieves performance similar to or better than that of previously published approaches on four well-studied problems: finding the epitopes of broadly neutralizing antibodies (bNab), determining coreceptor tropism of the virus, identifying compartment-specific genetic signatures of the virus, and deducing drug-resistance associated mutations. The cross-platform Python source code (released under the GPL 3.0 license), documentation, issue tracking, and a pre-configured virtual machine for IDEPI can be found at https://github.com/veg/idepi. PMID:25254639

  6. Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains.

    PubMed

    Zhu, Jiang; Ofek, Gilad; Yang, Yongping; Zhang, Baoshan; Louder, Mark K; Lu, Gabriel; McKee, Krisha; Pancera, Marie; Skinner, Jeff; Zhang, Zhenhai; Parks, Robert; Eudailey, Joshua; Lloyd, Krissey E; Blinn, Julie; Alam, S Munir; Haynes, Barton F; Simek, Melissa; Burton, Dennis R; Koff, Wayne C; Mullikin, James C; Mascola, John R; Shapiro, Lawrence; Kwong, Peter D

    2013-04-16

    Next-generation sequencing of antibody transcripts from HIV-1-infected individuals with broadly neutralizing antibodies could provide an efficient means for identifying somatic variants and characterizing their lineages. Here, we used 454 pyrosequencing and identity/divergence grid sampling to analyze heavy- and light-chain sequences from donor N152, the source of the broadly neutralizing antibody 10E8. We identified variants with up to 28% difference in amino acid sequence. Heavy- and light-chain phylogenetic trees of identified 10E8 variants displayed similar architectures, and 10E8 variants reconstituted from matched and unmatched phylogenetic branches displayed significantly lower autoreactivity when matched. To test the generality of phylogenetic pairing, we analyzed donor International AIDS Vaccine Initiative 84, the source of antibodies PGT141-145. Heavy- and light-chain phylogenetic trees of PGT141-145 somatic variants also displayed remarkably similar architectures; in this case, branch pairings could be anchored by known PGT141-145 antibodies. Altogether, our findings suggest that phylogenetic matching of heavy and light chains can provide a means to approximate natural pairings.

  7. Mining the antibodyome for HIV-1–neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains

    PubMed Central

    Zhu, Jiang; Ofek, Gilad; Yang, Yongping; Zhang, Baoshan; Louder, Mark K.; McKee, Krisha; Pancera, Marie; Skinner, Jeff; Zhang, Zhenhai; Parks, Robert; Eudailey, Joshua; Lloyd, Krissey E.; Blinn, Julie; Alam, S. Munir; Haynes, Barton F.; Simek, Melissa; Burton, Dennis R.; Koff, Wayne C.; Mullikin, James C.; Mascola, John R.; Shapiro, Lawrence; Kwong, Peter D.; Becker, Jesse; Benjamin, Betty; Blakesley, Robert; Bouffard, Gerry; Brooks, Shelise; Coleman, Holly; Dekhtyar, Mila; Gregory, Michael; Guan, Xiaobin; Gupta, Jyoti; Han, Joel; Hargrove, April; Ho, Shi-ling; Johnson, Taccara; Legaspi, Richelle; Lovett, Sean; Maduro, Quino; Masiello, Cathy; Maskeri, Baishali; McDowell, Jenny; Montemayor, Casandra; Mullikin, James; Park, Morgan; Riebow, Nancy; Schandler, Karen; Schmidt, Brian; Sison, Christina; Stantripop, Mal; Thomas, James; Thomas, Pam; Vemulapalli, Meg; Young, Alice

    2013-01-01

    Next-generation sequencing of antibody transcripts from HIV-1–infected individuals with broadly neutralizing antibodies could provide an efficient means for identifying somatic variants and characterizing their lineages. Here, we used 454 pyrosequencing and identity/divergence grid sampling to analyze heavy- and light-chain sequences from donor N152, the source of the broadly neutralizing antibody 10E8. We identified variants with up to 28% difference in amino acid sequence. Heavy- and light-chain phylogenetic trees of identified 10E8 variants displayed similar architectures, and 10E8 variants reconstituted from matched and unmatched phylogenetic branches displayed significantly lower autoreactivity when matched. To test the generality of phylogenetic pairing, we analyzed donor International AIDS Vaccine Initiative 84, the source of antibodies PGT141–145. Heavy- and light-chain phylogenetic trees of PGT141–145 somatic variants also displayed remarkably similar architectures; in this case, branch pairings could be anchored by known PGT141–145 antibodies. Altogether, our findings suggest that phylogenetic matching of heavy and light chains can provide a means to approximate natural pairings. PMID:23536288

  8. The analysis of near full-length genome sequences of HIV type 1 subtype A viruses from Russia supports the monophyly of major intrasubtype clusters.

    PubMed

    Fernández-García, Aurora; Revilla, Ana; Vázquez-de Parga, Elena; Vinogradova, Anna; Rakhmanova, Aza; Karamov, Eduard; Carrera, Cristina; Delgado, Elena; Pérez-Álvarez, Lucía; Nájera, Rafael; Osmanov, Saladin; Thomson, Michael M

    2012-10-01

    The HIV-1 epidemic in Russia has been insufficiently studied, with only 11 complete genome sequences from this country currently available, only three of which are of the locally predominant genetic form, the former Soviet Union (FSU) subtype A variant (A(FSU)). Here we analyze 10 newly derived A(FSU) near full-length genome sequences from Russia. Samples were selected based on phylogenetic clustering in protease-reverse transcriptase in two of the major A(FSU) clusters, V77I(PR) (n=6), widely circulating in Russia and other FSU countries, and A(SP1) (n=4), predominant in St. Petersburg. The phylogenetic analysis shows that the V77I(PR) genomes group in a monophyletic cluster together with 10 previously obtained A(FSU) genome sequences from Uzbekistan, Kazakhstan, Russia, and Cyprus, all bearing the V77I substitution in protease. Similarly, the four A(SP1) genomes group in a monophyletic cluster. These results therefore show that the monophyly of V77I(PR) and A(SP1) A(FSU) clusters is supported in near complete genomes.

  9. The Analysis of Near Full-Length Genome Sequences of HIV Type 1 Subtype A Viruses from Russia Supports the Monophyly of Major Intrasubtype Clusters

    PubMed Central

    Fernández-García, Aurora; Revilla, Ana; Vázquez-de Parga, Elena; Vinogradova, Anna; Rakhmanova, Aza; Karamov, Eduard; Carrera, Cristina; Delgado, Elena; Pérez-Álvarez, Lucía; Nájera, Rafael; Osmanov, Saladin

    2012-01-01

    Abstract The HIV-1 epidemic in Russia has been insufficiently studied, with only 11 complete genome sequences from this country currently available, only three of which are of the locally predominant genetic form, the former Soviet Union (FSU) subtype A variant (AFSU). Here we analyze 10 newly derived AFSU near full-length genome sequences from Russia. Samples were selected based on phylogenetic clustering in protease-reverse transcriptase in two of the major AFSU clusters, V77IPR (n=6), widely circulating in Russia and other FSU countries, and ASP1 (n=4), predominant in St. Petersburg. The phylogenetic analysis shows that the V77IPR genomes group in a monophyletic cluster together with 10 previously obtained AFSU genome sequences from Uzbekistan, Kazakhstan, Russia, and Cyprus, all bearing the V77I substitution in protease. Similarly, the four ASP1 genomes group in a monophyletic cluster. These results therefore show that the monophyly of V77IPR and ASP1 AFSU clusters is supported in near complete genomes. PMID:22251084

  10. Prevalence and Evolution of Low Frequency HIV Drug Resistance Mutations Detected by Ultra Deep Sequencing in Patients Experiencing First Line Antiretroviral Therapy Failure

    PubMed Central

    Recordon-Pinson, Patricia; Reigadas, Sandrine; Bidet, Yannick; Bruyand, Mathias; Bonnet, Fabrice; Lazaro, Estibaliz; Neau, Didier; Fleury, Hervé; Dabis, François; Morlat, Philippe; Masquelier, Bernard

    2014-01-01

    Objectives Clinical relevance of low-frequency HIV-1 variants carrying drug resistance associated mutations (DRMs) is still unclear. We aimed to study the prevalence of low-frequency DRMs, detected by Ultra-Deep Sequencing (UDS) before antiretroviral therapy (ART) and at virological failure (VF), in HIV-1 infected patients experiencing VF on first-line ART. Methods Twenty-nine ART-naive patients followed up in the ANRS-CO3 Aquitaine Cohort, having initiated ART between 2000 and 2009 and experiencing VF (2 plasma viral loads (VL) >500 copies/ml or one VL >1000 copies/ml) were included. Reverse transcriptase and protease DRMs were identified using Sanger sequencing (SS) and UDS at baseline (before ART initiation) and VF. Results Additional low-frequency variants with PI-, NNRTI- and NRTI-DRMs were found by UDS at baseline and VF, significantly increasing the number of detected DRMs by 1.35 fold (p<0.0001) compared to SS. These low-frequency DRMs modified ARV susceptibility predictions to the prescribed treatment for 1 patient at baseline, in whom low-frequency DRM was found at high frequency at VF, and 6 patients at VF. DRMs found at VF were rarely detected as low-frequency DRMs prior to treatment. The rare low-frequency NNRTI- and NRTI-DRMs detected at baseline that correlated with the prescribed treatment were most often found at high-frequency at VF. Conclusion Low frequency DRMs detected before ART initiation and at VF in patients experiencing VF on first-line ART can increase the overall burden of resistance to PI, NRTI and NNRTI. PMID:24475178

  11. Environmental Surveillance at Los Alamos during 2007

    SciTech Connect

    2008-09-30

    Environmental Surveillance at Los Alamos reports are prepared annually by the Los Alamos National Laboratory (the Laboratory) Environmental Directorate, as required by US Department of Energy Order 450.1, General Environmental Protection Program, and US Department of Energy Order 231.1A, Environment, Safety, and Health Reporting. These annual reports summarize environmental data that are used to determine compliance with applicable federal, state, and local environmental laws and regulations, executive orders, and departmental policies. Additional data, beyond the minimum required, are also gathered and reported as part of the Laboratory’s efforts to ensure public safety and to monitor environmental quality at and near the Laboratory. Chapter 1 provides an overview of the Laboratory’s major environmental programs and explains the risks and the actions taken to reduce risks at the Laboratory from environmental legacies and waste management operations. Chapter 2 reports the Laboratory’s compliance status for 2007. Chapter 3 provides a summary of the maximum radiological dose the public and biota populations could have potentially received from Laboratory operations and discusses chemical exposures. The environmental surveillance and monitoring data are organized by environmental media (Chapter 4, air; Chapters 5 and 6, water and sediments; Chapter 7, soils; and Chapter 8, foodstuffs and biota) in a format to meet the needs of a general and scientific audience. Chapter 9 provides a summary of the status of environmental restoration work around LANL. A glossary and a list of acronyms and abbreviations are in the back of the report. Appendix A explains the standards for environmental contaminants, Appendix B explains the units of measurements used in this report, Appendix C describes the laboratory’s technical areas and their associated programs, and Appendix D provides web links to more information. In printed copies of this report or Executive Summary, we have

  12. Review of liquid metal heat pipe work at Los Alamos

    SciTech Connect

    Reid, R.S.; Merrigan, M.A.; Sena, J.T.

    1990-01-01

    A survey of space-power related liquid metal heat pipe work at Los Alamos National Laboratory is presented. Heat pipe development at Los Alamos has been on-going since 1963. Heat pipes were initially developed for thermionic nuclear-electrical power production in space. Since then Los Alamos has developed liquid metal heat pipes for numerous applications related to high temperature systems in both the space and terrestrial environments. Some of these applications include thermionic electrical generators, thermoelectric energy conversion (both in-core and direct radiation), thermal energy storage, hypersonic vehicle leading edge cooling, and heat pipe vapor laser cells. Some of the work performed at Los Alamos has been documented in internal reports that are often little-known. A representative description and summary of progress in space-related liquid metal heat pipe technology is provided followed by a reference section citing sources where these works may be found. 53 refs.

  13. Review of liquid metal heat pipe work at Los Alamos

    SciTech Connect

    Reid, R.S.; Merrigan, M.A.; Sena, J.T. )

    1991-01-10

    A survey of space-power related liquid metal heat pipe work at Los Alamos National Laboratory is presented. Heat pipe development at Los Alamos has been on-going since 1963. Heat pipes were initially developed for thermionic nuclear-electrical power production in space. Since then Los Alamos has developed liquid metal heat pipes for numerous applications related to high temperature systems in both the space and terrestrial environments. Some of these applications include thermionic electrical generators, thermoelectric energy conversion (both in-core and direct radiation), thermal energy storage, hypersonic vehicle leading edge cooling, and heat pipe vapor laser cells. Some of the work performed at Los Alamos has been documented in internal reports that are often little-known. A representative description and summary of progress in space-related liquid metal heat pipe technology is provided followed by a reference section citing sources where these works may be found.

  14. Los Alamos National Laboratory Prepares for Fire Season

    SciTech Connect

    L’Esperance, Manny

    2016-07-18

    Through the establishment of a Wildland Fire Program Office, and the Interagency Fire Base located on Laboratory property, Los Alamos National Laboratory is continuing and improving a program to prepare for wildland fire.

  15. Explosive Flux Compression: 50 Years of Los Alamos Activities

    SciTech Connect

    Fowler, C.M.; Thomson, D.B.; Garn, W.B.

    1998-10-18

    Los Alamos flux compression activities are surveyed, mainly through references in view of space limitations. However, two plasma physics programs done with Sandia National Laboratory are discussed in more detail.

  16. Los Alamos National Laboratory Prepares for Fire Season

    ScienceCinema

    L’Esperance, Manny

    2016-08-10

    Through the establishment of a Wildland Fire Program Office, and the Interagency Fire Base located on Laboratory property, Los Alamos National Laboratory is continuing and improving a program to prepare for wildland fire.

  17. Explosive Flux Compression:. 50 Years of LOS Alamos Activities

    NASA Astrophysics Data System (ADS)

    Fowler, C.; Thomson, D.; Garn, W.

    2004-11-01

    Los Alamos flux compression activities are surveyed, mainly through references in view of space limitations. However, two plasma physics programs done with Sandia National Laboratory are discussed in more detail.

  18. Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance

    SciTech Connect

    Anastassopoulou, Cleo G.; Ketas, Thomas J.; Sanders, Rogier W.; Johan Klasse, Per; Moore, John P.

    2012-07-05

    A rare pathway of HIV-1 resistance to small molecule CCR5 inhibitors such as Vicriviroc (VCV) involves changes solely in the gp41 fusion peptide (FP). Here, we show that the G516V change is critical to VCV resistance in PBMC and TZM-bl cells, although it must be accompanied by either M518V or F519I to have a substantial impact. Modeling VCV inhibition data from the two cell types indicated that G516V allows both double mutants to use VCV-CCR5 complexes for entry. The model further identified F519I as an independent determinant of preference for the unoccupied, high-VCV affinity form of CCR5. From inhibitor-free reversion cultures, we also identified a substitution in the inner domain of gp120, T244A, which appears to counter the resistance phenotype created by the FP substitutions. Examining the interplay of these changes will enhance our understanding of Env complex interactions that influence both HIV-1 entry and resistance to CCR5 inhibitors.

  19. Strategic defense initiatives at Los Alamos National Laboratory

    SciTech Connect

    Rockwood, S.D.

    1985-01-01

    This presentation reviews the Strategic Defense Initiative (SDI) programs at Los Alamos National Laboratory, noting especially the needs for and applications of optics and optical technologies. Table I lists the various activities at Los Alamos contributing to SDI programs. The principal, nonnuclear SDI programs are: (1) the free-electron laser, and (2) neutral particle beams. Both should be considered as potential long-range-kill systems, but still in the futuristic category.

  20. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) identifies immune-selected HIV variants

    DOE PAGES

    Hraber, Peter; Korber, Bette; Wagh, Kshitij; ...

    2015-10-21

    Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations ofmore » mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. Here, with well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Finally, practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines.« less

  1. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) identifies immune-selected HIV variants

    SciTech Connect

    Hraber, Peter; Korber, Bette; Wagh, Kshitij; Giorgi, Elena; Bhattacharya, Tanmoy; Gnanakaran, S.; Lapedes, Alan S.; Learn, Gerald H.; Kreider, Edward F.; Li, Yingying; Shaw, George M.; Hahn, Beatrice H.; Montefiori, David C.; Alam, S. Munir; Bonsignori, Mattia; Moody, M. Anthony; Liao, Hua-Xin; Gao, Feng; Haynes, Barton

    2015-10-21

    Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations of mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. Here, with well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Finally, practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines.

  2. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants

    PubMed Central

    Hraber, Peter; Korber, Bette; Wagh, Kshitij; Giorgi, Elena E.; Bhattacharya, Tanmoy; Gnanakaran, S.; Lapedes, Alan S.; Learn, Gerald H.; Kreider, Edward F.; Li, Yingying; Shaw, George M.; Hahn, Beatrice H.; Montefiori, David C.; Alam, S. Munir; Bonsignori, Mattia; Moody, M. Anthony; Liao, Hua-Xin; Gao, Feng; Haynes, Barton F.

    2015-01-01

    Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations of mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. With well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines. PMID:26506369

  3. Los Alamos upgrade in metallographic capabilities

    SciTech Connect

    Ledbetter, J.M.; Dowler, K.E.; Cook, J.H.

    1985-01-01

    The Los Alamos Wing 9 Hot Cell Facility is in the process of upgrading their metallographic sample preparation and examination capability. The present capability to grind, polish and etch samples from reactor fuels and materials has been in operation for 18 years. Macro photography and alpha and beta-gamma autoradiography are an important part of this capability. Some of the fast breeder reactor experiments have contained sodium as a coolant. Therefore, the capability to distill sodium from some samples scheduled for microstructural examinations is a requirement. Since the reactor fuel samples are highly radioactive and contain plutonium, either as fabricated or as a result of breeding during reactor service, these samples must be handled in shielded hot cells containing alpha boxes to isolate the plutonium and hazardous fission products from personnel and the environment. The present equipment that was designed and built into those alpha boxes has functioned very well for the past 18 years. During that time the technicians have thought of ways to improve the equipment to do the work faster and safer. These ideas and ideas that have been developed during the design of new alpha boxes and new equipment for microstructural sample preparation have provided the concepts for the capability to perform the work faster and maintain the equipment in a safer manner.

  4. Saving Water at Los Alamos National Laboratory

    ScienceCinema

    Erickson, Andy

    2016-07-12

    Los Alamos National Laboratory decreased its water usage by 26 percent in 2014, with about one-third of the reduction attributable to using reclaimed water to cool a supercomputing center. The Laboratory's goal during 2014 was to use only re-purposed water to support the mission at the Strategic Computing Complex. Using reclaimed water from the Sanitary Effluent Reclamation Facility, or SERF, substantially decreased water usage and supported the overall mission. SERF collects industrial wastewater and treats it for reuse. The reclamation facility contributed more than 27 million gallons of re-purposed water to the Laboratory's computing center, a secured supercomputing facility that supports the Laboratory’s national security mission and is one of the institution’s larger water users. In addition to the strategic water reuse program at SERF, the Laboratory reduced water use in 2014 by focusing conservation efforts on areas that use the most water, upgrading to water-conserving fixtures, and repairing leaks identified in a biennial survey.

  5. Oxidative lime pretreatment of Alamo switchgrass.

    PubMed

    Falls, Matthew; Holtzapple, Mark T

    2011-09-01

    Previous studies have shown that oxidative lime pretreatment is an effective delignification method that improves the enzymatic digestibility of many biomass feedstocks. The purpose of this work is to determine the recommended oxidative lime pretreatment conditions (reaction temperature, time, pressure, and lime loading) for Alamo switchgrass (Panicum virgatum). Enzymatic hydrolysis of glucan and xylan was used to determine the performance of the 52 studied pretreatment conditions. The recommended condition (110°C, 6.89 bar O(2), 240 min, 0.248 g Ca(OH)(2)/g biomass) achieved glucan and xylan overall yields (grams of sugar hydrolyzed/100 g sugar in raw biomass, 15 filter paper units (FPU)/g raw glucan) of 85.9 and 52.2, respectively. In addition, some glucan oligomers (2.6 g glucan recovered/100 g glucan in raw biomass) and significant levels of xylan oligomers (26.0 g xylan recovered/100 g xylan in raw biomass) were recovered from the pretreatment liquor. Combining a decrystallization technique (ball milling) with oxidative lime pretreatment further improved the overall glucan yield to 90.0 (7 FPU/g raw glucan).

  6. Historic Manhattan Project Sites at Los Alamos

    ScienceCinema

    McGehee, Ellen

    2016-07-12

    The Manhattan Project laboratory constructed at Los Alamos, New Mexico, beginning in 1943, was intended from the start to be temporary and to go up with amazing speed. Because most of those WWII-era facilities were built with minimal materials and so quickly, much of the original infrastructure was torn down in the late '40s and early '50s and replaced by more permanent facilities. However, a few key facilities remained, and are being preserved and maintained for historic significance. Four such sites are visited briefly in this video, taking viewers to V-Site, the buildings where the first nuclear explosive device was pre-assembled in preparation for the Trinity Test in Southern New Mexico. Included is another WWII area, Gun Site. So named because it was the area where scientists and engineers tested the so-called "gun method" of assembling nuclear materials -- the fundamental design of the Little Boy weapon that was eventually dropped on Hiroshima. The video also goes to Pajarito Site, home of the "Slotin Building" and "Pond Cabin." The Slotin Building is the place where scientist Louis Slotin conducted a criticality experiment that went awry in early 1946, leading to his unfortunate death, and the Pond Cabin served the team of eminent scientist Emilio Segre who did early chemistry work on plutonium that ultimately led to the Fat Man weapon.

  7. Historic Manhattan Project Sites at Los Alamos

    SciTech Connect

    McGehee, Ellen

    2014-05-22

    The Manhattan Project laboratory constructed at Los Alamos, New Mexico, beginning in 1943, was intended from the start to be temporary and to go up with amazing speed. Because most of those WWII-era facilities were built with minimal materials and so quickly, much of the original infrastructure was torn down in the late '40s and early '50s and replaced by more permanent facilities. However, a few key facilities remained, and are being preserved and maintained for historic significance. Four such sites are visited briefly in this video, taking viewers to V-Site, the buildings where the first nuclear explosive device was pre-assembled in preparation for the Trinity Test in Southern New Mexico. Included is another WWII area, Gun Site. So named because it was the area where scientists and engineers tested the so-called "gun method" of assembling nuclear materials -- the fundamental design of the Little Boy weapon that was eventually dropped on Hiroshima. The video also goes to Pajarito Site, home of the "Slotin Building" and "Pond Cabin." The Slotin Building is the place where scientist Louis Slotin conducted a criticality experiment that went awry in early 1946, leading to his unfortunate death, and the Pond Cabin served the team of eminent scientist Emilio Segre who did early chemistry work on plutonium that ultimately led to the Fat Man weapon.

  8. Saving Water at Los Alamos National Laboratory

    SciTech Connect

    Erickson, Andy

    2015-03-16

    Los Alamos National Laboratory decreased its water usage by 26 percent in 2014, with about one-third of the reduction attributable to using reclaimed water to cool a supercomputing center. The Laboratory's goal during 2014 was to use only re-purposed water to support the mission at the Strategic Computing Complex. Using reclaimed water from the Sanitary Effluent Reclamation Facility, or SERF, substantially decreased water usage and supported the overall mission. SERF collects industrial wastewater and treats it for reuse. The reclamation facility contributed more than 27 million gallons of re-purposed water to the Laboratory's computing center, a secured supercomputing facility that supports the Laboratory’s national security mission and is one of the institution’s larger water users. In addition to the strategic water reuse program at SERF, the Laboratory reduced water use in 2014 by focusing conservation efforts on areas that use the most water, upgrading to water-conserving fixtures, and repairing leaks identified in a biennial survey.

  9. HIV Transmission

    MedlinePlus

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... on HIV Syndicated Content Website Feedback HIV/AIDS HIV Transmission Language: English Transmisión del VIH Recommend on ...

  10. Audit of consultant agreements at Los Alamos National Laboratory

    SciTech Connect

    1996-02-23

    The Department of Energy`s (Department) Albuquerque Operations Office (Albuquerque) and Los Alamos National Laboratory (Los Alamos) are responsible for acquiring consulting services in a manner most advantageous to the Government by ensuring adequate competition. Although the Department prefers competitively awarding subcontracts, including consultant agreements, to ensure the lowest possible cost, it allows sole sourcing a subcontract if the sole source is fully justified. The objective of the audit was to determine whether Los Alamos` consultant agreements contained adequate sole source justifications. The audit showed that Los Alamos may not have acquired some of its consultant agreements at the lowest possible cost because it did not prepare adequate sole source justifications for 17 sole source consultant agreements valued at $842,900. This condition existed because: (1) requesters did not follow policies and procedures when preparing sole source justifications, (2) Los Alamos did not have an internal mechanism to reject consultant agreements that were not adequately justified, and (3) the Department did not review consultant agreements to evaluate the adequacy of sole source justifications. Without adequate justifications, the Department cannot be assured that consultant services were obtained at the lowest possible cost. We therefore recommended that the Manager, Albuquerque Operations Office require Los Alamos to ensure proper sole source justifications and enhance internal controls over consultant agreements. Management agreed to implement the recommendations.

  11. Los Alamos low-level waste performance assessment status

    SciTech Connect

    Wenzel, W.J.; Purtymun, W.D.; Dewart, J.M.; Rodgers, J.E.

    1986-06-01

    This report reviews the documented Los Alamos studies done to assess the containment of buried hazardous wastes. Five sections logically present the environmental studies, operational source terms, transport pathways, environmental dosimetry, and computer model development and use. This review gives a general picture of the Los Alamos solid waste disposal and liquid effluent sites and is intended for technical readers with waste management and environmental science backgrounds but without a detailed familiarization with Los Alamos. The review begins with a wide perspective on environmental studies at Los Alamos. Hydrology, geology, and meteorology are described for the site and region. The ongoing Laboratory-wide environmental surveillance and waste management environmental studies are presented. The next section describes the waste disposal sites and summarizes the current source terms for these sites. Hazardous chemical wastes and liquid effluents are also addressed by describing the sites and canyons that are impacted. The review then focuses on the transport pathways addressed mainly in reports by Healy and Formerly Utilized Sites Remedial Action Program. Once the source terms and potential transport pathways are described, the dose assessment methods are addressed. Three major studies, the waste alternatives, Hansen and Rogers, and the Pantex Environmental Impact Statement, contributed to the current Los Alamos dose assessment methodology. Finally, the current Los Alamos groundwater, surface water, and environmental assessment models for these mesa top and canyon sites are described.

  12. Reconstituting the epidemic history of mono lineage of HIV-1 CRF01_AE in Guizhou province, Southern China.

    PubMed

    Zeng, Haiyan; Sun, Binlian; Li, Lingnuo; Li, Yanpeng; Liu, Yong; Xiao, Yao; Jiang, Yan; Yang, Rongge

    2014-08-01

    Guizhou province, located between border provinces and Central province of China, plays a crucial role in the transmission of HIV-1, implying it is important to monitor the epidemic of HIV-1 in this region. Available HIV-1 infected patients' plasma (n=78) were collected from Tongren city, Eastern Guizhou. Full-length gag, partial pol and env gene sequences were amplified and analyzed using phylogenetic, recombinant and Bayesian molecular clock approaches. Phylogenetic and recombinant analyses showed that CRF01_AE predominated among injecting drug users and heterosexuals in Tongren city with 85.9% proportion, it was followed by B' (5.1%), CRF07_BC (3.8%), CRF08_BC (3.8%), and B (1.3%). Moreover, 98.5% of CRF01_AE strains belonged to the distinct lineage CRF01_AE-v previously found in Guangxi province. To infer the most probable origin of CRF01_AE-v in Guizhou province, we download all available full length of CRF01_AE gag, pol and env gene region sequences from China in Los Alamos HIV sequence database. Phylodynamic and phylogeographic analyses revealed that the expanding CRF01_AE-v epidemic in Guizhou province was the result of local epidemic driven by multiple independent introductions of CRF01_AE-v strains from Guangxi province in early 2000s. High prevalence of CRF01_AE in Guizhou province may bridge the epidemic to Central China. It provides a new insight for the understanding of HIV-1 epidemic in Guizhou province and makes the evolutionary history of CRF01_AE in China more intact.

  13. Drug resistance mutations in HIV pol sequences from Argentinean patients under antiretroviral treatment: subtype, gender, and age issues.

    PubMed

    Jones, Leandro R; Moretti, Franco; Calvo, Andrea Y; Dilernia, Darío A; Manrique, Julieta M; Gómez-Carrillo, Manuel; Salomón, Horacio

    2012-08-01

    We studied drug resistance mutations (DRMs) in 2623 pol sequences. Out of 94,828 amino acid substitutions that were detected, 8749 corresponded to nucleoside reverse transcriptase inhibitor (NRTI), 3765 to nonnucleoside reverse transcriptase inhibitor (NNRTI), and 7141 to protease inhibitor (PI) resistance-associated mutations. The most common DRMs were L10I, I54V, L90M, V82A, A71V, L10V, M46I, M184V, M41L, T215Y, D67N, L210W, K70R, N348I, V118I, K103N, Y181C, G190A, K101E, V108I, L100I, V90I, K101Q, and A98G. As expected, DRMs frequencies depended on viral genotype. The amounts of NRTI and PI resistance mutations among B and BF sequences from children were higher than among sequences from adults. The frequencies of PI and NRTI resistance mutations among B and BF sequences from adult men were higher than among sequences from women. Some of these observations can be explained in light of the available epidemiological information, but some cannot, indicating that further studies are needed to understand the antiretroviral resistance epidemics in Argentina.

  14. Recent UCN source developments at Los Alamos

    SciTech Connect

    Seestrom, S.J.; Anaya, J.M.; Bowles, T.J.

    1998-12-01

    The most intense sources of ultra cold neutrons (UCN) have bee built at reactors where the high average thermal neutron flux can overcome the low UCN production rate to achieve usable densities of UCN. At spallation neutron sources the average flux available is much lower than at a reactor, though the peak flux can be comparable or higher. The authors have built a UCN source that attempts to take advantage of the high peak flux available at the short pulse spallation neutron source at the Los Alamos Neutron Science Center (LANSCE) to generate a useful number of UCN. In the source UCN are produced by Doppler-shifted Bragg scattering of neutrons to convert 400-m/s neutrons down into the UCN regime. This source was initially tested in 1996 and various improvements were made based on the results of the 1996 running. These improvements were implemented and tested in 1997. In sections 2 and 3 they discuss the improvements that have been made and the resulting source performance. Recently an even more interesting concept was put forward by Serebrov et al. This involves combining a solid Deuterium UCN source, previously studied by Serebrov et al., with a pulsed spallation source to achieve world record UCN densities. They have initiated a program of calculations and measurements aimed at verifying the solid Deuterium UCN source concept. The approach has been to develop an analytical capability, combine with Monte Carlo calculations of neutron production, and perform benchmark experiments to verify the validity of the calculations. Based on the calculations and measurements they plan to test a modified version of the Serebrov UCN factory. They estimate that they could produce over 1,000 UCN/cc in a 15 liter volume, using 1 {micro}amp of 800 MeV protons for two seconds every 500 seconds. They will discuss the result UCN production measurements in section 4.

  15. Simulations of flow interactions near Los Alamos

    SciTech Connect

    Costigan, K. R.; Winterkamp, Judy; Bossert, J. E.; Langley, D. L.

    2002-01-01

    The Pajarito Plateau is located on the eastern flank of the Jemez Mountains and the west side of the Rio Grande Valley, in north-central New Mexico, where the river runs roughly north to south. On the Pajarito Plateau, a network of surface meteorological stations has been routinely maintained by Los Alamos National Laboratory. This network includes five instrumented towers, within an approximately 10 km by 15 km area. The towers stand from 23 m to 92 m tall, with multiple wind measurement heights. Investigation of the station records indicates that the wind fields can be quite complicated and may be the result of interactions of thermally and/or dynamically driven flows of many scales. Slope flows are often found on the plateau during the morning and evening transition times, but it is not unusual to find wind directions that are inconsistent with slope flows at some or all of the stations. It has been speculated that valley circulations, as well as synoptically driven winds, interact with the slope flows, but the mesonet measurements alone, with no measurements in the remainder of the valley, were not sufficient to investigate this hypothesis. Thus, during October of 1995, supplemental meteorological instrumentation was placed in the Rio Grande basin to study the complex interaction of flows in the area. A sodar was added near the 92 m tower and a radar wind profiler was placed in the Rio Grande Valley, just east of the plateau and near the river. Measurements were also added at the top of Pajarito Mountain, just west of the plateau, and across the valley, to the east, on top of Tesuque Peak (in the Sangre de Cristo Mountains). Two surface stations were also added to the north-facing slopes of Pajarito Mountain. This paper will present observations from October 1995 and results of simulations of this area that are used in the study of the complex interaction of dynamically and thermally driven flows on multiple scales.

  16. HIV / AIDS

    MedlinePlus

    ... facebook share with twitter share with linkedin HIV/AIDS HIV, or human immunodeficiency virus, is the virus ... HIV/AIDS. Why Is the Study of HIV/AIDS a Priority for NIAID? Nearly 37 million people ...

  17. Simultaneous recognition of HIV-1 TAR RNA bulge and loop sequences by cyclic peptide mimics of Tat protein

    SciTech Connect

    Davidson, Amy; Leeper, Thomas C.; Athanassiou, Zafiria; Patora-Komisarska, Krystyna; Karn, Jonathan; Robinson, John A.; Varani, Gabriele

    2009-07-21

    The interaction of the HIV-1 transactivator protein Tat with its transactivation response (TAR) RNA is an essential step in viral replication and therefore an attractive target for developing antivirals with new mechanisms of action. Numerous compounds that bind to the 3-nt bulge responsible for binding Tat have been identified in the past, but none of these molecules had sufficient potency to warrant pharmaceutical development. We have discovered conformationally-constrained cyclic peptide mimetics of Tat that are specific nM inhibitors of the Tat-TAR interaction by using a structure-based approach. The lead peptides are nearly as active as the antiviral drug nevirapine against a variety of clinical isolates in human lymphocytes. The NMR structure of a peptide–RNA complex reveals that these molecules interfere with the recruitment to TAR of both Tat and the essential cellular cofactor transcription elongation factor-b (P-TEFb) by binding simultaneously at the RNA bulge and apical loop, forming an unusually deep pocket. This structure illustrates additional principles in RNA recognition: RNA-binding molecules can achieve specificity by interacting simultaneously with multiple secondary structure elements and by inducing the formation of deep binding pockets in their targets. It also provides insight into the P-TEFb binding site and a rational basis for optimizing the promising antiviral activity observed for these cyclic peptides.

  18. A zinc(II)-based two-dimensional MOF for sensitive and selective sensing of HIV-1 ds-DNA sequences.

    PubMed

    Zhao, Hai-Qing; Qiu, Gui-Hua; Liang, Zhen; Li, Min-Min; Sun, Bin; Qin, Liang; Yang, Shui-Ping; Chen, Wen-Hua; Chen, Jin-Xiang

    2016-05-30

    Coordination reaction of a known three-dimensional (3D) polymer precursor {Na3[Na9(Cbdcp)6(H2O)18]}n (A, Cbdcp = N-(4-carboxybenzyl)-(3,5-dicarboxyl)pyridinium) with Zn(NO3)2·6H2O in H2O or H2O/DMF at 100 °C and in the presence of aspirin, 5-fluorouracil (5-FU) as modulators, trans-1,2-bis(4-pyridyl)ethylene (bpe) or 1,2-bis(4-pyridyl)ethane (bpea) as ancillary ligands afforded six novel Zn(II)-based metal-organic frameworks (MOFs), that is, {[Zn(Cbdcp)(H2O)3]·H2O}n (1, 1D zigzag chain), {[Zn(HCbdcp)2]·H2O}n (2, 2D sheet), {[Zn(Cbdcp)(bpe)1/2]·2H2O}n (3, 3D polymer), {[Zn(Cbdcp)(bpe)1/2]·2H2O}n (4, 2D network), {[Zn(Cbdcp)(bpea)1/2]·2H2O}n (5, 3D polymer) and {[Zn(Cbdcp)(bpea)1/2]·2H2O}n (6, 2D network). Among them, compound 2 contains aromatic rings, positively charged pyridinium, Zn(2+) cation centers and carboxylic acid groups lined up on the 2D sheet structure with a certain extended surface exposure. The unique structure of 2 facilitates effective association with carboxyfluorescein (FAM) labeled probe single stranded DNA (probe ss-DNA, delineates as P-DNA) to yield a P-DNA@2 system, and leads to fluorescence quenching of FAM via a photoinduced electron transfer process. The P-DNA@2 system is effective and reliable for the detection of human immunodeficiency virus 1 ds-DNA (HIV ds-DNA) sequences and capable of distinguishing complementary HIV ds-DNA from mismatched target sequences with the detection limit as low as 10 pM (S/N = 3).

  19. 1993 Northern goshawk inventory on portions of Los Alamos National Laboratory, Los Alamos, NM. Final report

    SciTech Connect

    Sinton, D.T.; Kennedy, P.L.

    1994-06-01

    Northern goshawks (Accipiter gentilis) (hereafter referred to as goshawk) is a large forest dwelling hawk. Goshawks may be declining in population and reproduction in the southwestern United States. Reasons for the possible decline in goshawk populations include timber harvesting resulting in the loss of nesting habitat, toxic chemicals, and the effects of drought, fire, and disease. Thus, there is a need to determine their population status and assess impacts of management activities in potential goshawk habitat. Inventory for the goshawk was conducted on 2,254 ha of Los Alamos National Laboratory (LANL) to determine the presence of nesting goshawks on LANL lands. This information can be incorporated into LANL`s environmental management program. The inventory was conducted by Colorado State University personnel from May 12 to July 30, 1993. This report summarizes the results of this inventory.

  20. A Highly Conserved Residue in HIV-1 Nef Alpha Helix 2 Modulates Protein Expression

    PubMed Central

    Johnson, Aaron L.; Dirk, Brennan S.; Coutu, Mathieu; Haeryfar, S. M. Mansour; Arts, Eric J.; Finzi, Andrés

    2016-01-01

    ABSTRACT Extensive genetic diversity is a defining characteristic of human immunodeficiency virus type 1 (HIV-1) and poses a significant barrier to the development of an effective vaccine. To better understand the impact of this genetic diversity on the HIV-1 pathogenic factor Nef, we compiled a panel of reference strains from the NIH Los Alamos HIV Database. Initial sequence analysis identified point mutations at Nef residues 13, 84, and 92 in subtype C reference strain C.BR92025 from Brazil. Functional analysis revealed impaired major histocompatibility complex class I and CD4 downregulation of strain C.BR92025 Nef, which corresponded to decreased protein expression. Metabolic labeling demonstrated that strain C.BR92025 Nef has a greater rate of protein turnover than subtype B reference strain B.JRFL that, on the basis of mutational analysis, is related to Nef residue A84. An alanine-to-valine substitution at position 84, located in alpha helix 2 of Nef, was sufficient to alter the rate of turnover of an otherwise highly expressed Nef protein. In conclusion, these findings highlight HIV-1 Nef residue A84 as a major determinant of protein expression that may offer an additional avenue to disrupt or mediate the effects of this key HIV-1 pathogenic factor. IMPORTANCE The HIV-1 Nef protein has been established as a key pathogenic determinant of HIV/AIDS, but there is little knowledge of how the extensive genetic diversity of HIV-1 affects Nef function. Upon compiling a set of subtype-specific reference strains, we identified a subtype C reference strain, C.BR92025, that contained natural polymorphisms at otherwise highly conserved residues 13, 84, and 92. Interestingly, strain C.BR92025 Nef displayed impaired Nef function and had decreased protein expression. We have demonstrated that strain C.BR92025 Nef has a higher rate of protein turnover than highly expressed Nef proteins and that this higher rate of protein turnover is due to an alanine-to-valine substitution

  1. A progress report on UNICOS misuse detection at Los Alamos

    SciTech Connect

    Thompson, J.L.; Jackson, K.A.; Stallings, C.A.; Simmonds, D.D.; Siciliano, C.L.B.; Pedicini, G.A.

    1995-10-01

    An effective method for detecting computer misuse is the automatic monitoring and analysis of on-line user activity. During the past year, Los Alamos enhanced its Network Anomaly Detection and Intrusion Reporter (NADIR) to include analysis of user activity on Los Alamos` UNICOS Crays. In near real-time, NADIR compares user activity to historical profiles and tests activity against expert rules. The expert rules express Los Alamos` security policy and define improper or suspicious behavior. NADIR reports suspicious behavior to security auditors and provides tools to aid in follow-up investigations. This paper describes the implementation to date of the UNICOS component of NADIR, along with the operational experiences and future plans for the system.

  2. Publications of Los Alamos research, 1977-1981

    SciTech Connect

    Sheridan, C.J.; Garcia, C.A.

    1983-03-01

    This bibliography is a compilation of unclassified publications of work done at the Los Alamos National Laboratory for 1977-1981. Papers published in those years are included regardless of when they were actually written. Publications received too late for inclusion in earlier compilations have also been listed. Declassification of previously classified reports is considered to constitute publication. All classified issuances are omitted - even those papers, themselves unclassified, which were published only as part of a classified document. If a paper was published more than once, all places of publication are included. The bibliography includes Los Alamos National Laboratory reports, papers released as non-Laboratory reports, journal articles, books, chapters of books, conference papers either published separately or as part of conference proceedings issued as books or reports, papers published in congressional hearings, theses, and US patents. Publications by Los Alamos authors that are not records of Laboratory-sponsored work are included when the Library becomes aware of them.

  3. Water Supply at Los Alamos 1998-2001

    SciTech Connect

    Richard J. Koch; David B. Rogers

    2003-03-01

    For the period 1998 through 2001, the total water used at Los Alamos from all sources ranged from 1325 million gallons (Mg) in 1999 to 1515 Mg in 2000. Groundwater production ranged from 1323 Mg in 1999 to 1506 Mg in 2000 from the Guaje, Pajarito, and Otowi fields. Nonpotable surface water used from Los Alamos reservoir ranged from zero gallons in 2001 to 9.3 Mg in 2000. For years 1998 through 2001, over 99% of all water used at Los Alamos was groundwater. Water use by Los Alamos National Laboratory (LANL) between 1998 and 2001 ranged from 379 Mg in 2000 to 461 Mg in 1998. The LANL water use in 2001 was 393 Mg or 27% of the total water use at Los Alamos. Water use by Los Alamos County ranged from 872 Mg in 1999 to 1137 Mg in 2000, and averaged 1006 Mg/yr. Four new replacement wells in the Guaje field (G-2A, G-3A, G-4A, and G-5A) were drilled in 1998 and began production in 1999; with existing well G-1A, the Guaje field currently has five producing wells. Five of the old Guaje wells (G-1, G-2, G-4, G-5, and G-6) were plugged and abandoned in 1999, and one well (G-3) was abandoned but remains as an observation well for the Guaje field. The long-term water level observations in production and observation (test) wells at Los Alamos are consistent with the formation of a cone of depression in response to water production. The water level decline is gradual and at most has been about 0.7 to 2 ft per year for production wells and from 0.4 to 0.9 ft/yr for observation (test) wells. The largest water level declines have been in the Guaje field where nonpumping water levels were about 91 ft lower in 2001 than in 1951. The initial water levels of the Guaje replacement wells were 32 to 57 ft lower than the initial water levels of adjacent original Guaje wells. When production wells are taken off-line for pump replacement or repair, water levels have returned to within about 25 ft of initial static levels within 6 to 12 months. Thus, the water-level trends suggest no adverse

  4. HIV RNA and proviral HIV DNA can be detected in semen after 6 months of antiretroviral therapy although HIV RNA is undetectable in blood.

    PubMed

    Du, Peiwei; Liu, An; Jiao, Yanmei; Liu, Cuie; Jiang, Taiyi; Zhu, Weijun; Zhu, Yunxia; Wu, Hao; Sun, Lijun

    2016-03-01

    The risk of sexual transmission of HIV is strongly correlated with amounts of genital HIV RNA. Few studies have reported amounts of HIV RNA and HIV DNA in semen in HIV-infected Chinese patients undergoing antiviral treatment (ART). In this observational study, the amounts of HIV RNA and HIV DNA in semen were assessed after six months of ART in HIV-infected Chinese individuals, when HIV RNA was undetectable in blood . This study included 19 HIV-infected Chinese men undergoing ART for six months. Amounts of HIV in paired semen and blood samples were assessed using real-time PCR. The C2-V5 region of the HIV envelope (env) genes was cloned and sequenced and genotype and co-receptor usage predicted based on the sequence. It was found that HIV RNA was undetectable in the plasma of most patients (17/19), whereas HIV RNA could be detected in the semen of most patients (16/19). HIV DNA could be detected in both semen and blood. Genetic diversity of HIV between the seminal and blood compartments was identified. Thus, amounts of HIV RNA and HIV DNA remain high in semen of HIV-infected Chinese patients after six months of ART treatment, even when HIV RNA was undetectable in blood.

  5. Water supply at Los Alamos during 1993. Progress report

    SciTech Connect

    Purtymun, W.D.; Stoker, A.K.; McLin, S.G.; Maes, M.N.; Glasco, T.A.

    1995-10-01

    This report summarizes production and aquifer conditions for water wells in the Guaje, Pajarito, and Otowi Well Fields. These wells supplied all of the potable water used for municipal and some industrial purposes in Los Alamos County and the Los Alamos National Laboratory during 1993. The wells in the Los Alamos Well Field were transferred to San Ildefonso Pueblo in 1992. Four of the wells in the Los Alamos Well Field were plugged in 1993. One of the two new wells in the Otowi Well Field became operational in 1993. The spring gallery in Water Canyon supplied nonpotable water for industrial use, while surface water from the Los Alamos Reservoir was diverted for irrigation. In 1993 no water was used from the Guaje Reservoir. Due to the maintenance and operating cost of diverting water from the reservoirs, it is not economically feasible to continue their use for irrigation. This report fulfills some of the requirements of the Los Alamos Groundwater Protection Management Program by documenting use of the groundwater for water supply and providing information hydrologic characteristics of the main aquifer. This report is a joint effort between the Laboratory Water Quality and Hydrology Group and the Utilities Department of Johnson Controls World Services Inc. (JCI). The purpose of this report is to ensure a continuing historical record and to provide guidance for management of water resources in long-range planning for the water supply system. We have issued one summary report for the period of 1947 to 1971 and 22 annual reports that contain the results of our studies of these water supplies. An additional report summarized the hydrology of the main aquifer with reference to future development of groundwater supplies. A report was issued in 1988 that examined the status of wells and future water supply.

  6. Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation

    SciTech Connect

    Liu, Donglai; Zuo, Tao; Hora, Bhavna; Song, Hongshuo; Kong, Wei; Yu, Xianghui; Goonetilleke, Nilu; Bhattacharya, Tanmoy; Perelson, Alan S.; Haynes, Barton F.; McMichael, Andrew J.; Gao, Feng

    2014-01-01

    Background: Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses. Results: The T242N mutation resulted in various levels of fitness loss in four different T/F viruses. However, the fitness costs were significantly compromised by preexisting compensatory amino acids in (Isoleucine at position 247) or outside (glutamine at position 219) the CTL epitope. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations. Conclusions: Our results show that the preexisting compensatory amino acids in the majority of circulating HIV-1 strains could significantly compromise the fitness loss due to CTL escape mutations and thus increase challenges for T cell based vaccines.

  7. Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation

    DOE PAGES

    Liu, Donglai; Zuo, Tao; Hora, Bhavna; ...

    2014-01-01

    Background: Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses. Results: The T242N mutation resulted in various levels of fitness loss in four different T/F viruses. However, themore » fitness costs were significantly compromised by preexisting compensatory amino acids in (Isoleucine at position 247) or outside (glutamine at position 219) the CTL epitope. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations. Conclusions: Our results show that the preexisting compensatory amino acids in the majority of circulating HIV-1 strains could significantly compromise the fitness loss due to CTL escape mutations and thus increase challenges for T cell based vaccines.« less

  8. Viral sequence analysis from HIV-infected mothers and infants: molecular evolution, diversity, and risk factors for mother-to-child transmission.

    PubMed

    Bulterys, Philip L; Dalai, Sudeb C; Katzenstein, David A

    2010-12-01

    Great progress has been made in understanding the pathogenesis, treatment, and transmission of HIV and the factors influencing the risk of mother-to-child transmission (MTCT). Many questions regarding the molecular evolution and genetic diversity of HIV in the context of MTCT remain unanswered. Further research to identify the selective factors governing which variants are transmitted, how the compartmentalization of HIV in different cells and tissues contributes to transmission, and the influence of host immunity, viral diversity, and recombination on MTCT may provide insight into new prevention strategies and the development of an effective HIV vaccine.

  9. A physicists guide to The Los Alamos Primer

    NASA Astrophysics Data System (ADS)

    Reed, B. Cameron

    2016-11-01

    In April 1943, a group of scientists at the newly established Los Alamos Laboratory were given a series of lectures by Robert Serber on what was then known of the physics and engineering issues involved in developing fission bombs. Serber’s lectures were recorded in a 24 page report titled The Los Alamos Primer, which was subsequently declassified and published in book form. This paper describes the background to the Primer and analyzes the physics contained in its 22 sections. The motivation for this paper is to provide a firm foundation of the background and contents of the Primer for physicists interested in the Manhattan Project and nuclear weapons.

  10. Fifty-one years of Los Alamos Spacecraft

    SciTech Connect

    Fenimore, Edward E.

    2014-09-04

    From 1963 to 2014, the Los Alamos National Laboratory was involved in at least 233 spacecraft. There are probably only one or two institutions in the world that have been involved in so many spacecraft. Los Alamos space exploration started with the Vela satellites for nuclear test detection, but soon expanded to ionospheric research (mostly barium releases), radioisotope thermoelectric generators, solar physics, solar wind, magnetospheres, astrophysics, national security, planetary physics, earth resources, radio propagation in the ionosphere, and cubesats. Here, we present a list of the spacecraft, their purpose, and their launch dates for use during RocketFest

  11. Los Alamos Using Neutrons to Stop Nuclear Smugglers

    ScienceCinema

    Favalli, Andrea; Swinhoe, Martyn

    2016-07-12

    Los Alamos National Laboratory researchers have successfully demonstrated for the first time that laser-generated neutrons can be enlisted as a useful tool in the War on Terror. The international research team used the short-pulse laser at Los Alamos's TRIDENT facility to generate a neutron beam with novel characteristics that interrogated a closed container to confirm the presence and quantity of nuclear material inside. The successful experiment paves the way for creation of a table-top-sized or truck-mounted neutron generator that could be installed at strategic locations worldwide to thwart smugglers trafficking in nuclear materials.

  12. Los Alamos Using Neutrons to Stop Nuclear Smugglers

    SciTech Connect

    Favalli, Andrea; Swinhoe, Martyn

    2013-06-03

    Los Alamos National Laboratory researchers have successfully demonstrated for the first time that laser-generated neutrons can be enlisted as a useful tool in the War on Terror. The international research team used the short-pulse laser at Los Alamos's TRIDENT facility to generate a neutron beam with novel characteristics that interrogated a closed container to confirm the presence and quantity of nuclear material inside. The successful experiment paves the way for creation of a table-top-sized or truck-mounted neutron generator that could be installed at strategic locations worldwide to thwart smugglers trafficking in nuclear materials.

  13. The development of the atomic bomb, Los Alamos

    SciTech Connect

    Seidel, R.W.

    1993-11-01

    The historical presentation begins with details of the selection of Los Alamos as the site of the Army installation. Wartime efforts of the Army Corps of Engineers, and scientists to include the leader of Los Alamos, Robert Oppenheimer are presented. The layout and construction of the facilities are discussed. The monumental design requirements of the bombs are discussed, including but not limited to the utilization of the second choice implosion method of detonation, and the production of bomb-grade nuclear explosives. The paper ends with a philosophical discussion on the use of nuclear weapons.

  14. Needs assessment for fire department services and resources for the Los Alamos National Laboratory, Los Alamos, New Mexico. Final report

    SciTech Connect

    1995-11-15

    This report has been developed in response to a request from the Los Alamos National Laboratory (LANL) to evaluate the need for fire department services so as to enable the Laboratory to plan effective fire protection and thereby: meet LANL`s regulatory and contractual obligations; interface with the Department of Energy (DOE) and other agencies on matters relating to fire and emergency services; and ensure appropriate protection of the community and environment. This study is an outgrowth of the 1993 Fire Department Needs Assessment (prepared for DOE) but is developed from the LANL perspective. Input has been received from cognizant and responsible representatives at LANL, DOE, Los Alamos County (LAC) and the Los Alamos Fire Department (LAFD).

  15. Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis

    PubMed Central

    Ratmann, Oliver; van Sighem, Ard; Hermanides, Hillegonda S.; Dutilh, Bas E.; Gras, Luuk; Rodrigues Faria, Nuno; van den Hengel, Rob; Duits, Ashley J.; Reiss, Peter; de Wolf, Frank; Fraser, Christophe

    2015-01-01

    Background The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. Methods and Findings As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently

  16. A survey of macromycete diversity at Los Alamos National Laboratory, Bandelier National Monument, and Los Alamos County; A preliminary report

    SciTech Connect

    Jarmie, N.; Rogers, F.J.

    1997-11-01

    The authors have completed a 5-year survey (1991--1995) of macromycetes found in Los Alamos County, Los Alamos National Laboratory, and Bandelier National Monument. The authors have compiled a database of 1,048 collections, their characteristics, and identifications. The database represents 123 (98%) genera and 175 (73%) species reliably identified. Issues of habitat loss, species extinction, and ecological relationships are addressed, and comparisons with other surveys are made. With this baseline information and modeling of this baseline data, one can begin to understand more about the fungal flora of the area.

  17. Working with Fermi at Chicago and Los Alamos

    NASA Astrophysics Data System (ADS)

    Garwin, Richard L.

    2010-02-01

    I discuss my experience with Enrico Fermi as student and fellow faculty member at Chicago and with him as consultants to the Los Alamos Scientific Laboratory in 1950-1952. The talk shares observations about this great physicist and exemplary human being. )

  18. The Controlled-Air Incinerator at Los Alamos

    SciTech Connect

    Newmyer, J.N.

    1994-04-01

    The Controlled-Air Incinerator (CAI) at Los Alamos is being modified and upgraded to begin routine operations treating low-level mixed waste (LLMW), radioactively contaminated polychlorinated biphenyl (PCB) wastes, low-level liquid wastes, and possibly transuranic (TRU) wastes. This paper describes those modifications. Routine waste operations should begin in late FY95.

  19. Mercury: The Los Alamos ICF KrF laser system

    SciTech Connect

    Czuchlewski, S.J.; York, G.W.; Bigio, I.J.; Brucker, J.; Hanson, D.; Honig, E.M.; Kurnit, N.; Leland, W.; McCown, A.W.; McLeod, J.; Rose, E.; Thomas, S.; Thompson, D.

    1993-01-19

    The Mercury KrF laser facility at Los Alamos is being built with the benefit of lessons learned from the Aurora system. An increased understanding of KrF laser engineering, and the designed implementation of system flexibility, will permit Mercury to serve as a tested for a variety of advanced KrF technology concepts.

  20. The Los Alamos nuclear safeguards and nonproliferation technology development program

    SciTech Connect

    Smith, H.A. Jr.; Menlove, H.O.; Reilly, T.D.; Bosler, G.E.; Hakkila, E.A.; Eccleston, G.W.

    1994-04-01

    For nearly three decades, Los Alamos National Laboratory has developed and implemented nuclear measurement technology and training in support of national and international nuclear safeguards. This paper outlines the major elements of those technologies and highlights some of the latest developments.

  1. Plasma and ion beam processing at Los Alamos

    SciTech Connect

    Rej, D.J.; Davis, H.A.; Henins, I.

    1994-07-01

    Efforts are underway at Los Alamos National Laboratory to utilize plasma and intense ion beam science and technology of the processing of advanced materials. A major theme involves surface modification of materials, e.g., etching, deposition, alloying, and implantation. In this paper, we concentrate on two programs, plasma source ion implantation and high-intensity pulsed ion beam deposition.

  2. [Los Alamos National Laboratory industrial applications and technology transfer

    SciTech Connect

    Not Available

    1992-09-30

    In October 1989, the Los Alamos Economic Development Corporation (LAEDC) entered into a contract with the Industrial Applications office (IAO) of Los Alamos National Laboratory (LANL) whereby the LAEDC was to provide support services to IAO. More specifically, according to the Statement of Work in this contract The Los Alamos Economic Development Corporation shall assist the Los Alamos National Laboratory Industrial Applications Office in establishing and strengthening connections between potential entrepreneurs at the Laboratory and the business assistance community throughout New Mexico, directed toward enhancing the number, of successful start up businesses spinning off the Laboratory's technology base.'' As part of this contract and subsequent modifications thereof, the LAEDC was to perform seven tasks: 1. Provide business planning assistance to potential entrepreneurs. 2. (Assist IAO in preparing and distributing) informational materials on technology transfer. 3. (Organize and manage) meetings and seminars on technology transfer and entrepreneurship. 4. Identify new opportunities for technology transfer. 5. (Identify and implement programs for the) recognition of Laboratory Entrepreneurs. 6. Training Lab personnel, in the area of technology transfer and Laboratory industrial interactions. 7. Review and summarize prior New Mexico economic development studies. The purpose of this report, is to summarize the accomplishments of the LAEDC under its contract with IAO, and to fulfill its reporting requirements. This report covers the period from October 1989 to September 1992.

  3. Aqueous Nitrate Recovery Line at Los Alamos National Laboratory

    SciTech Connect

    Finstad, Casey Charles

    2016-06-15

    This powerpoint is part of the ADPSM Plutonium Engineering Lecture Series, which is an opportunity for new hires at LANL to get an overview of work done at TA55. It goes into detail about the aqueous nitrate recovery line at Los Alamos National Laboratory.

  4. Brief review of Rover fuel development at Los Alamos

    NASA Technical Reports Server (NTRS)

    Davidson, Keith V.

    1991-01-01

    A brief review of the graphite matrix uranium fuel development efforts at Los Alamos from 1955 through 1972 is presented. The uses of graphite flour carbon black, various binders, uranium dioxide, coated UC2 particles, and zirconium carbide in this development are described.

  5. Summary of environmental surveillance at Los Alamos during 1995

    SciTech Connect

    1996-10-01

    Linking the Rio Grande Valley and the Jemez Mountains, New Mexico`s Pajarito Plateau is home to a world-class scientific institution. Los Alamos National Laboratory (or the Laboratory), managed by the Regents of the University of California, is a government-owned, Department of Energy-supervised complex investigating all areas of modern science for the purposes of national defense, health, conservation, and ecology. The Laboratory was founded in 1943 as part of the Manhattan Project, whose members assembled to create the first nuclear weapon. Occupying the campus of the Los Alamos Ranch School, American and British scientists gathered on the isolated mesa tops to harness recently discovered nuclear power with the hope of ending World War II. In July 1945, the initial objective of the Laboratory, a nuclear device, was achieved in Los Alamos and tested in White Sands, New Mexico. Today the Laboratory continues its role in defense, particularly in nuclear weapons, including developing methods for safely handling weapons and managing waste. For the past twenty years, the Laboratory has published an annual environmental report. This pamphlet offers a synopsis that briefly explains important concepts, such as radiation and provides a summary of the monitoring results and regulatory compliance status that are explained at length in the document entitled Environmental Surveillance at Los Alamos during 1995.

  6. Airport-Noise Levels and Annoyance Model (ALAMO) system's reference manual

    NASA Technical Reports Server (NTRS)

    Deloach, R.; Donaldson, J. L.; Johnson, M. J.

    1986-01-01

    The airport-noise levels and annoyance model (ALAMO) is described in terms of the constituent modules, the execution of ALAMO procedure files, necessary for system execution, and the source code documentation associated with code development at Langley Research Center. The modules constituting ALAMO are presented both in flow graph form, and through a description of the subroutines and functions that comprise them.

  7. HIV Molecular Immunology 2014

    SciTech Connect

    Yusim, Karina; Korber, Bette Tina Marie; Barouch, Dan; Koup, Richard; de Boer, Rob; Moore, John P.; Brander, Christian; Haynes, Barton F.; Walker, Bruce D.

    2015-02-03

    HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.

  8. Multilocus sequence typing of serially collected isolates of Cryptococcus from HIV-infected patients in South Africa.

    PubMed

    Van Wyk, Marelize; Govender, Nelesh P; Mitchell, Thomas G; Litvintseva, Anastasia P

    2014-06-01

    Patients with cryptococcal meningitis in sub-Saharan Africa frequently relapse following treatment. The natural history and etiology of these recurrent episodes warrant investigation. Here, we used multilocus sequence typing (MLST) to compare the molecular genotypes of strains of Cryptococcus neoformans and Cryptococcus gattii isolated from serial episodes of cryptococcal meningitis that were separated by at least 110 days. The most common MLST genotypes among the isolates were the dominant global clinical genotypes (M5 and M4) of molecular type VNI, as well as the VNI genotypes apparently restricted to southern Africa. In addition, there was considerable genetic diversity among these South African isolates, as 15% of the patients had unique genotypes. Eleven percent of the patients were reinfected with a genetically different strain following their initial diagnosis and treatment. However, the majority of serial episodes (89%) were caused by strains with the same genotype as the original strain. These results indicate that serial episodes of cryptococcosis in South Africa are frequently associated with persistence or relapse of the original infection. Using a reference broth microdilution method, we found that the serial isolates of 11% of the patients infected with strains of C. neoformans var. grubii with identical genotypes exhibited ≥4-fold increases in the MICs to fluconazole. Therefore, these recurrent episodes may have been precipitated by inadequate induction or consolidation of antifungal treatment and occasionally may have been due to increased resistance to fluconazole, which may have developed during the chronic infection.

  9. Environmental assessment for effluent reduction, Los Alamos National Laboratory, Los Alamos, New Mexico

    SciTech Connect

    1996-09-11

    The Department of Energy (DOE) proposes to eliminate industrial effluent from 27 outfalls at Los Alamos National Laboratory (LANL). The Proposed Action includes both simple and extensive plumbing modifications, which would result in the elimination of industrial effluent being released to the environment through 27 outfalls. The industrial effluent currently going to about half of the 27 outfalls under consideration would be rerouted to LANL`s sanitary sewer system. Industrial effluent from other outfalls would be eliminated by replacing once-through cooling water systems with recirculation systems, or, in a few instances, operational changes would result in no generation of industrial effluent. After the industrial effluents have been discontinued, the affected outfalls would be removed from the NPDES Permit. The pipes from the source building or structure to the discharge point for the outfalls may be plugged, or excavated and removed. Other outfalls would remain intact and would continue to discharge stormwater. The No Action alternative, which would maintain the status quo for LANL`s outfalls, was also analyzed. An alternative in which industrial effluent would be treated at the source facilities was considered but dismissed from further analysis because it would not reasonably meet the DOE`s purpose for action, and its potential environmental effects were bounded by the analysis of the Proposed Action and the No Action alternatives.

  10. Environmental Survey preliminary report, Los Alamos National Laboratory, Los Alamos, New Mexico

    SciTech Connect

    Not Available

    1988-01-01

    This report presents the preliminary findings from the first phase of the Environmental Survey of the United States Department of Energy's (DOE) Los Alamos National Laboratory (LANL), conducted March 29, 1987 through April 17, 1987. The Survey is being conducted by an interdisciplinary team of environmental specialists, led and managed by the Office of Environment, Safety and Health's Office of Environmental Audit. Individual team components are outside experts being supplied by a private contractor. The objective of the Survey is to identify environmental problems and areas of environmental risk associated with the LANL. The Survey covers all environmental media and all areas of environmental regulation. It is being performed in accordance with the DOE Environmental Survey Manual. The on-site phase of the Survey involves the review of existing site environmental data, observations of the operations carried on at the LANL, and interviews with site personnel. The Survey team developed Sampling and Analysis Plan to assist in further assessing certain of the environmental problems identified during its on-site activities. The Sampling and Analysis Plan will be executed by the Idaho National Engineering Laboratory. When completed, the results will be incorporated into the LANL Environmental Survey Interim Report. The Interim Report will reflect the final determinations of the Survey for the LANL. 65 refs., 68 figs., 73 tabs.

  11. Monitoring Sensitive Bat Species at Los Alamos National Laboratory

    SciTech Connect

    Schoenberg, Kari M.

    2014-01-15

    Bats play a critical role in ecosystems and are vulnerable to disturbance and disruption by human activities. In recent decades, bat populations in the United States and elsewhere have decreased tremendously. There are 47 different species of bat in the United States and 28 of these occur in New Mexico with 15 different species documented at the Los Alamos National Laboratory (LANL) and surrounding areas. Euderma maculatum(the spotted bat) is listed as “threatened” by the state of New Mexico and is known to occur at LANL. Four other species of bats are listed as “sensitive” and also occur here. In 1995, a four year study was initiated at LANL to assess the status of bat species of concern, elucidate distribution and relative abundance, and obtain information on roosting sites. There have been no definitive studies since then. Biologists in the Environmental Protection Division at LANL initiated a multi-year monitoring program for bats in May 2013 to implement the Biological Resources Management Plan. The objective of this ongoing study is to monitor bat species diversity and seasonal activity over time at LANL. Bat species diversity and seasonal activity were measured using an acoustic bat detector, the Pettersson D500X. This ultrasound recording unit is intended for long-term, unattended recording of bat and other high frequency animal calls. During 2013, the detector was deployed at two locations around LANL. Study sites were selected based on proximity to water where bats may be foraging. Recorded bat calls were analyzed using Sonobat, software that can help determine specific species of bat through their calls. A list of bat species at the two sites was developed and compared to lists from previous studies. Species diversity and seasonal activity, measured as the number of call sequences recorded each month, were compared between sites and among months. A total of 17,923 bat calls were recorded representing 15 species. Results indicate that there is a

  12. HIV infections in otolaryngology

    PubMed Central

    Rzewnicki, Ireneusz; Olszewska, Ewa; Rogowska-Szadkowska, Dorota

    2012-01-01

    Summary HIV (human immunodeficiency virus) infection may produce no clinical symptoms for 10 years on average. However, after many years of infection most people develop symptoms that indicate progression of the disease. There are no regular characteristic symptoms or early stage, and no logical sequence of AIDS indicator disorders has been observed. People who are not aware of the infection are referred to physicians of various specializations, including otolaryngologists. It is on their knowledge about HIV infections, among other factors, that early diagnosis of the disease depends. Appropriate and quick introduction of anti-retroviral drugs may let a person with HIV live decades longer. PMID:22367140

  13. Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G. The WHO and NIAID Networks for HIV Isolation and Characterization.

    PubMed Central

    Gao, F; Morrison, S G; Robertson, D L; Thornton, C L; Craig, S; Karlsson, G; Sodroski, J; Morgado, M; Galvao-Castro, B; von Briesen, H

    1996-01-01

    Present knowledge of human immunodeficiency virus type 1 (HIV-1) envelope immunobiology has been derived almost exclusively from analyses of subtype B viruses, yet such viruses represent only a minority of strains currently spreading worldwide. To generate a more representative panel of genetically diverse envelope genes, we PCR amplified, cloned, and sequenced complete gp160 coding regions of 35 primary (peripheral blood mononuclear cell-propagated) HIV-1 isolates collected at major epicenters of the current AIDS pandemic. Analysis of their deduced amino acid sequences revealed several important differences from prototypic subtype B strains, including changes in the number and distribution of cysteine residues, substantial length differences in hypervariable regions, and premature truncations in the gp41 domain. Moreover, transiently expressed glycoprotein precursor molecules varied considerably in both size and carbohydrate content. Phylogenetic analyses of full-length env sequences indicated that the panel included members of all major sequence subtypes of HIV-1 group M (clades A to G), as well as an intersubtype recombinant (F/B) from an infected individual in Brazil. In addition, all subtype E and three subtype G viruses initially classified on the basis of partial env sequences were found to cluster in subtype A in the 3' half of their gp41 coding region, suggesting that they are also recombinant. The biological activity of PCR-derived env genes was examined in a single-round virus infectivity assay. This analysis identified 20 clones, including 1 from each subtype (or recombinant), which expressed fully functional envelope glycoproteins. One of these, derived from a patient with rapid CD4 cell decline, contained an amino acid substitution in a highly conserved endocytosis signal (Y721C), as mediated virus entry with very poor efficiency, although they did not contain sequence changes predicted to alter protein function. These results indicate that the env

  14. Commercialization of Los Alamos National Laboratory technologies via small businesses. Final report

    SciTech Connect

    Brice, R.; Carton, D.; Rhyne, T.

    1997-06-01

    Appendices are presented from a study performed on a concept model system for the commercialization of Los Alamos National Laboratory technologies via small businesses. Topics include a summary of information from the joint MCC/Los Alamos technology conference; a comparison of New Mexico infrastructure to other areas; a typical licensing agreement; technology screening guides; summaries of specific DOE/UC/Los Alamos documents; a bibliography; the Oak Ridge National Laboratory TCRD; The Ames Center for Advanced Technology Development; Los Alamos licensing procedures; presentation of slides from monthly MCC/Los Alamos review meetings; generalized entrepreneurship model; and a discussion on receiving equity for technology.

  15. Women and HIV

    MedlinePlus

    ... How do you get HIV? How do you get tested for HIV? Is there are cure for HIV? What should pregnant women know about HIV? HIV Quick Facts What is HIV? HIV is the virus that causes AIDS. A person with HIV is called HIV positive (HIV+). HIV ...

  16. Penetrating radiation: applications at Los Alamos National Laboratory

    NASA Astrophysics Data System (ADS)

    Watson, Scott; Hunter, James; Morris, Christopher

    2013-09-01

    Los Alamos has used penetrating radiography extensively throughout its history dating back to the Manhattan Project where imaging dense, imploding objects was the subject of intense interest. This interest continues today as major facilities like DARHT1 have become the mainstay of the US Stockpile Stewardship Program2 and the cornerstone of nuclear weapons certification. Meanwhile, emerging threats to national security from cargo containers and improvised explosive devices (IEDs) have invigorated inspection efforts using muon tomography, and compact x-ray radiography. Additionally, unusual environmental threats, like those from underwater oil spills and nuclear power plant accidents, have caused renewed interest in fielding radiography in severe operating conditions. We review the history of penetrating radiography at Los Alamos and survey technologies as presently applied to these important problems.

  17. The engineering institute of Los Alamos National Laboratory

    SciTech Connect

    Farrar, Charles R; Park, Gyuhae; Cornwell, Phillip J; Todd, Michael D

    2008-01-01

    Los Alamos National Laboratory (LANL) and the University of California, San Diego (UCSD) have taken the unprecedented step of creating a collaborative, multi-disciplinary graduate education program and associated research agenda called the Engineering Institute. The mission of the Engineering Institute is to develop a comprehensive approach for conducting LANL mission-driven, multidisciplinary engineering research and to improve recruiting, revitalization, and retention of the current and future staff necessary to support the LANL' s national security responsibilities. The components of the Engineering Institute are (1) a joint LANL/UCSD degree program, (2) joint LANL/UCSD research projects, (3) the Los Alamos Dynamic Summer School, (4) an annual workshop, and (5) industry short courses. This program is a possible model for future industry/government interactions with university partners.

  18. A NEW GENERATION OF LOS ALAMOS OPACITY TABLES

    SciTech Connect

    Colgan, J.; Kilcrease, D. P.; Magee, N. H.; Sherrill, M. E.; Abdallah, J. Jr.; Hakel, P.; Fontes, C. J.; Guzik, J. A.; Mussack, K. A.

    2016-02-01

    We present a new, publicly available set of Los Alamos OPLIB opacity tables for the elements hydrogen through zinc. Our tables are computed using the Los Alamos ATOMIC opacity and plasma modeling code, and make use of atomic structure calculations that use fine-structure detail for all the elements considered. Our equation of state model, known as ChemEOS, is based on the minimization of free energy in a chemical picture and appears to be a reasonable and robust approach to determining atomic state populations over a wide range of temperatures and densities. In this paper we discuss in detail the calculations that we have performed for the 30 elements considered, and present some comparisons of our monochromatic opacities with measurements and other opacity codes. We also use our new opacity tables in solar modeling calculations and compare and contrast such modeling with previous work.

  19. A New Generation of Los Alamos Opacity Tables

    SciTech Connect

    Colgan, James Patrick; Kilcrease, David Parker; Magee, Jr., Norman H.; Sherrill, Manolo Edgar; Abdallah, Joseph; Hakel, Peter; Fontes, Christopher John; Guzik, Joyce Ann; Mussack Tamashiro, Kathleen Anita

    2016-01-26

    We present a new, publicly available, set of Los Alamos OPLIB opacity tables for the elements hydrogen through zinc. Our tables are computed using the Los Alamos ATOMIC opacity and plasma modeling code, and make use of atomic structure calculations that use fine-structure detail for all the elements considered. Our equation-of-state (EOS) model, known as ChemEOS, is based on the minimization of free energy in a chemical picture and appears to be a reasonable and robust approach to determining atomic state populations over a wide range of temperatures and densities. In this paper we discuss in detail the calculations that we have performed for the 30 elements considered, and present some comparisons of our monochromatic opacities with measurements and other opacity codes. We also use our new opacity tables in solar modeling calculations and compare and contrast such modeling with previous work.

  20. A New Generation of Los Alamos Opacity Tables

    DOE PAGES

    Colgan, James Patrick; Kilcrease, David Parker; Magee, Jr., Norman H.; ...

    2016-01-26

    We present a new, publicly available, set of Los Alamos OPLIB opacity tables for the elements hydrogen through zinc. Our tables are computed using the Los Alamos ATOMIC opacity and plasma modeling code, and make use of atomic structure calculations that use fine-structure detail for all the elements considered. Our equation-of-state (EOS) model, known as ChemEOS, is based on the minimization of free energy in a chemical picture and appears to be a reasonable and robust approach to determining atomic state populations over a wide range of temperatures and densities. In this paper we discuss in detail the calculations thatmore » we have performed for the 30 elements considered, and present some comparisons of our monochromatic opacities with measurements and other opacity codes. We also use our new opacity tables in solar modeling calculations and compare and contrast such modeling with previous work.« less

  1. A new generation of Los Alamos opacity tables

    NASA Astrophysics Data System (ADS)

    Colgan, J.; Kilcrease, D. P.; Magee, N. H.; Abdallah, J.; Sherrill, M. E.; Fontes, C. J.; Hakel, P.; Guzik, J. A.; Mussack, K. A.; Walczak, P.

    2017-03-01

    We review a recently completed set of Los Alamos OPLIB opacity tables for the elements hydrogen through zinc. Our tables have been computed using the Los Alamos ATOMIC code, which makes use of atomic structure calculations that include fine-structure detail for all the elements considered. We utilize an equation-of-state model, known as ChemEOS, that is based on the minimization of free energy in a chemical picture. Recent publications by us have compared our calculations to available experimental opacity data and to other opacity calculations. Our tables are publicly available via our website, and have already been used in solar modeling calculations as well as the modeling of pulsating B-type stars. This proceedings submission will give an overview of our opacity calculations and briefly review the conclusions from the astrophysical modeling.

  2. Tiger Team Assessment of the Los Alamos National Laboratory

    SciTech Connect

    Not Available

    1991-11-01

    This report documents the Tiger Team Assessment of the Los Alamos National Laboratory (LANL) located in Los Alamos, New Mexico. LANL is operated for the US Department of Energy (DOE) by the University of California. The Tiger Team Assessment was conducted from September 23 to November 8, 1991, under the auspices of the DOE Office of Special Projects, Office of Assistant Secretary for Environment, Safety and Health. The assessment was comprehensive, encompassing environmental, safety, and health (ES H) disciplines; management; and contractor and DOE self-assessments. Compliance with applicable Federal, state, and local regulations; applicable DOE Orders; best management practices; and internal LANL site requirements was assessed. In addition, an evaluation of the adequacy and effectiveness of the DOE and the site contractors' management of ES H/quality assurance programs was conducted. This volume discusses findings concerning the environmental assessment.

  3. Airport-Noise Levels and Annoyance Model (ALAMO) user's guide

    NASA Technical Reports Server (NTRS)

    Deloach, R.; Donaldson, J. L.; Johnson, M. J.

    1986-01-01

    A guide for the use of the Airport-Noise Level and Annoyance MOdel (ALAMO) at the Langley Research Center computer complex is provided. This document is divided into 5 primary sections, the introduction, the purpose of the model, and an in-depth description of the following subsystems: baseline, noise reduction simulation and track analysis. For each subsystem, the user is provided with a description of architecture, an explanation of subsystem use, sample results, and a case runner's check list. It is assumed that the user is familiar with the operations at the Langley Research Center (LaRC) computer complex, the Network Operating System (NOS 1.4) and CYBER Control Language. Incorporated within the ALAMO model is a census database system called SITE II.

  4. Los Alamos x-ray characterization facilities for plasma diagnostics

    SciTech Connect

    Day, R.H.; Blake, R.L.; Stradling, G.L.; Trela, W.J.; Bartlett, R.J.

    1986-01-01

    A summary is given of characteristics of x-ray sources used by Los Alamos National Laboratory to calibrate various x-ray diagnostic packages and components. Included are D.C. sourcs in electron impact and fluorescence modes, a pulsed laser source for soft x rays with 100 ps time resolution, Febetron pulsed electron impact sources, and both EUV and x-ray synchrotron beamlines.

  5. Los Alamos National Laboratory's high-performance data system

    SciTech Connect

    Mercier, C.; Chorn, G.; Christman, R.; Collins, B.

    1991-01-01

    Los Alamos National Laboratory is designing a High-Performance Data System (HPDS) that will provide storage for supercomputers requiring large files and fast transfer speeds. The HPDS will meet the performance requirements by managing data transfers from high-speed storage systems connected directly to a high-speed network. File and storage management software will be distributed in workstations. Network protocols will ensure reliable, wide-area network data delivery to support long-distance distributed processing. 3 refs., 2 figs.

  6. Recent results in the Los Alamos compact torus program

    SciTech Connect

    Tuszewski, M.; Armstrong, W.T.; Barnes, C.W.

    1983-01-01

    A Compact Toroid is a toroidal magnetic-plasma-containment geometry in which no conductors or vacuum-chamber walls pass through the hole in the torus. Two types of compact toroids are studied experimentally and theoretically at Los Alamos: spheromaks that are oblate in shape and contain both toroidal and poloidal magnetic fields, and field-reversed configurations (FRC) that are very prolate and contain poloidal field only.

  7. [Los Alamos National Laboratory industrial applications and technology transfer

    SciTech Connect

    Not Available

    1991-10-31

    This report summarizes the accomplishments of the Los Alamos Economic Development Corporation (LAEDC) under its contract with the Industrial Applications Office (IAO). The LAEDC has: provided business planning assistance to potential entrepreneurs, assisted IAO in preparing and distributing informational materials on technology, organized and managed meetings and seminars on technology transfer and entrepreneurship, identified new opportunities for technology transfer, and identified and implemented programs for the recognition of Laboratory entrepreneurs.

  8. Los Alamos Canyon Ice Rink Parking Flood Plain Assessment

    SciTech Connect

    Hathcock, Charles Dean

    2015-02-10

    The project location is in Los Alamos Canyon east of the ice rink facility at the intersection of West and Omega roads (Figure 1). Forty eight parking spaces will be constructed on the north and south side of Omega Road, and a lighted walking path will be constructed to the ice rink. Some trees will be removed during this action. A guardrail of approximately 400 feet will be constructed along the north side of West Road to prevent unsafe parking in that area.

  9. Inertial Confinement Fusion Research at LOS Alamos National Laboratory

    NASA Astrophysics Data System (ADS)

    Batha, S. H.; Albright, B. J.; Alexander, D. J.; Barnes, Cris W.; Bradley, P. A.; Cobble, J. A.; Cooley, J. C.; Cooley, J. H.; Day, R. D.; DeFriend, K. A.; Delamater, N. D.; Dodd, E. S.; Fatherley, V. E.; Fernandez, J. C.; Flippo, K. A.; Grim, G. P.; Goldman, S. R.; Greenfield, S. R.; Herrmann, H. W.; Hoffman, N. M.; Holmes, R. L.; Johnson, R. P.; Keiter, P. A.; Kline, J. L.; Kyrala, G. A.; Lanier, N. E.; Loomis, E.; Lopez, F. E.; Luo, S.; Mack, J. M.; Magelssen, G. R.; Montgomery, D. S.; Nobile, A.; Oertel, J. A.; Reardon, P.; Rose, H. A.; Schmidt, D.; Schmitt, M. J.; Seifter, A.; Shimada, T.; Swift, D. C.; Tierney, T. E.; Welser-Sherrill, L.; Wilke, M. D.; Wilson, D. C.; Workman, J.; Yin, L.

    2009-07-01

    Inertial confinement fusion research at Los Alamos National Laboratory is focused on high-leverage areas of thermonuclear ignition to which LANL can apply its historic strengths and that are complementary to high-energy-density-physics topics. Using the Trident and Omega laser facilities, experiments are pursued in laser-plasma instabilities, symmetry, Be technologies, neutron and fusion-product diagnostics, and defect hydrodynamics.

  10. Overview of laser technology at Los Alamos National Laboratory

    NASA Astrophysics Data System (ADS)

    Lewis, G. K.; Cremers, D. A.

    Los Alamos National Laboratory has had a long history of involvement in laser sciences and has been recognized both for its large laser programs and smaller scale developments in laser technology and applications. The first significant program was with the Rover nuclear-based rocket propulsion system in 1968 to study laser initiated fusion. From here applications spread to programs in laser isotope separation and development of large lasers for fusion. These programs established the technological human resource base of highly trained laser physicists, engineers, and chemists that remain at the Laboratory today. Almost every technical division at Los Alamos now has some laser capability ranging from laser development, applications, studies on nonlinear processes, modeling and materials processing. During the past six years over eight R&D-100 Awards have been received by Los Alamos for development of laser-based techniques and instrumentation. Outstanding examples of technology developed include LIDAR applications to environmental monitoring, single molecule detection using fluorescence spectroscopy, a laser-based high kinetic energy source of oxygen atoms produced by a laser-sustained plasma, laser-induced breakdown spectroscopy (LIBS) for compositional, analysis, thin film high temperature superconductor deposition, multi-station laser welding, and direct metal deposition and build-up of components by fusing powder particles with a laser beam.

  11. Los Alamos, Toshiba probing Fukushima with cosmic rays

    SciTech Connect

    Morris, Christopher

    2014-06-16

    Los Alamos National Laboratory has announced an impending partnership with Toshiba Corporation to use a Los Alamos technique called muon tomography to safely peer inside the cores of the Fukushima Daiichi reactors and create high-resolution images of the damaged nuclear material inside without ever breaching the cores themselves. The initiative could reduce the time required to clean up the disabled complex by at least a decade and greatly reduce radiation exposure to personnel working at the plant. Muon radiography (also called cosmic-ray radiography) uses secondary particles generated when cosmic rays collide with upper regions of Earth's atmosphere to create images of the objects that the particles, called muons, penetrate. The process is analogous to an X-ray image, except muons are produced naturally and do not damage the materials they contact. Muon radiography has been used before in imaginative applications such as mapping the interior of the Great Pyramid at Giza, but Los Alamos's muon tomography technique represents a vast improvement over earlier technology.

  12. Los Alamos, Toshiba probing Fukushima with cosmic rays

    ScienceCinema

    Morris, Christopher

    2016-07-12

    Los Alamos National Laboratory has announced an impending partnership with Toshiba Corporation to use a Los Alamos technique called muon tomography to safely peer inside the cores of the Fukushima Daiichi reactors and create high-resolution images of the damaged nuclear material inside without ever breaching the cores themselves. The initiative could reduce the time required to clean up the disabled complex by at least a decade and greatly reduce radiation exposure to personnel working at the plant. Muon radiography (also called cosmic-ray radiography) uses secondary particles generated when cosmic rays collide with upper regions of Earth's atmosphere to create images of the objects that the particles, called muons, penetrate. The process is analogous to an X-ray image, except muons are produced naturally and do not damage the materials they contact. Muon radiography has been used before in imaginative applications such as mapping the interior of the Great Pyramid at Giza, but Los Alamos's muon tomography technique represents a vast improvement over earlier technology.

  13. Overview of laser technology at Los Alamos National Laboratory

    SciTech Connect

    Lewis, G.K.; Cremers, D.A.

    1994-09-01

    Los Alamos National Laboratory has had a long history of involvement in laser sciences and has been recognized both for its large laser programs and smaller scale developments in laser technology and applications. The first significant program was with the Rover nuclear-based rocket propulsion system in 1968 to study laser initiated fusion. From here applications spread to programs in laser isotope separation and development of large lasers for fusion. These programs established the technological human resource base of highly trained laser physicists, engineers, and chemists that remain at the Laboratory today. Almost every technical division at Los Alamos now has some laser capability ranging from laser development, applications, studies on nonlinear processes, modeling and materials processing. During the past six years over eight R&D-100 Awards have been received by Los Alamos for development of laser-based techniques and instrumentation. Outstanding examples of technology developed include LIDAR applications to environmental monitoring, single molecule detection using fluorescence spectroscopy, a laser-based high kinetic energy source of oxygen atoms produced by a laser-sustained plasma, laser-induced breakdown spectroscopy (LIBS) for compositional, analysis, thin film high temperature superconductor deposition, multi-station laser welding, and direct metal deposition and build-up of components by fusing powder particles with a laser beam.

  14. Water supply at Los Alamos during 1996. Progress report

    SciTech Connect

    McLin, S.G.; Purtymun, W.D.; Maes, M.N.; Longmire, P.A.

    1997-12-01

    Production of potable municipal water supplies during 1996 totaled about 1,368.1 million gallons from wells in the Guaje, Pajarito, and Otowi well fields. There was no water used from either the spring gallery in Water Canyon or from Guaje Reservoir during 1996. About 2.6 million gallons of water from Los Alamos Reservoir was used for lawn irrigation. The total water usage in 1996 was about 1,370.7 million gallons, or about 131 gallons per day per person living in Los Alamos County. Groundwater pumpage was up about 12.0 million gallons in 1996 compared with the pumpage in 1995. This report fulfills requirements specified in US Department of Energy (DOE) Order 5400.1 (Groundwater Protection Management Program), which requires the Los Alamos National Laboratory (LANL) to monitor and document groundwater conditions below Pajarito Plateau and to protect the regional aquifer from contamination associated with Laboratory operations. Furthermore, this report also fulfills special conditions by providing information on hydrologic characteristics of the regional aquifer, including operating conditions of the municipal water supply system.

  15. HIV Molecular Immunology 2015

    SciTech Connect

    Yusim, Karina; Korber, Bette Tina; Brander, Christian; Barouch, Dan; de Boer, Rob; Haynes, Barton F.; Koup, Richard; Moore, John P.; Walker, Bruce D.; Watkins, David

    2016-04-05

    The scope and purpose of the HIV molecular immunology database: HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2015 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/ content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as cross-reactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins

  16. HIV-1 transmission linkage in an HIV-1 prevention clinical trial

    SciTech Connect

    Leitner, Thomas; Campbell, Mary S; Mullins, James I; Hughes, James P; Wong, Kim G; Raugi, Dana N; Scrensen, Stefanie

    2009-01-01

    HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage

  17. Spatio-Temporal History of HIV-1 CRF35_AD in Afghanistan and Iran

    PubMed Central

    Eybpoosh, Sana; Bahrampour, Abbas; Karamouzian, Mohammad; Azadmanesh, Kayhan; Jahanbakhsh, Fatemeh; Mostafavi, Ehsan; Zolala, Farzaneh; Haghdoost, Ali Akbar

    2016-01-01

    HIV-1 Circulating Recombinant Form 35_AD (CRF35_AD) has an important position in the epidemiological profile of Afghanistan and Iran. Despite the presence of this clade in Afghanistan and Iran for over a decade, our understanding of its origin and dissemination patterns is limited. In this study, we performed a Bayesian phylogeographic analysis to reconstruct the spatio-temporal dispersion pattern of this clade using eligible CRF35_AD gag and pol sequences available in the Los Alamos HIV database (432 sequences available from Iran, 16 sequences available from Afghanistan, and a single CRF35_AD-like pol sequence available from USA). Bayesian Markov Chain Monte Carlo algorithm was implemented in BEAST v1.8.1. Between-country dispersion rates were tested with Bayesian stochastic search variable selection method and were considered significant where Bayes factor values were greater than three. The findings suggested that CRF35_AD sequences were genetically similar to parental sequences from Kenya and Uganda, and to a set of subtype A1 sequences available from Afghan refugees living in Pakistan. Our results also showed that across all phylogenies, Afghan and Iranian CRF35_AD sequences formed a monophyletic cluster (posterior clade credibility> 0.7). The divergence date of this cluster was estimated to be between 1990 and 1992. Within this cluster, a bidirectional dispersion of the virus was observed across Afghanistan and Iran. We could not clearly identify if Afghanistan or Iran first established or received this epidemic, as the root location of this cluster could not be robustly estimated. Three CRF35_AD sequences from Afghan refugees living in Pakistan nested among Afghan and Iranian CRF35_AD branches. However, the CRF35_AD-like sequence available from USA diverged independently from Kenyan subtype A1 sequences, suggesting it not to be a true CRF35_AD lineage. Potential factors contributing to viral exchange between Afghanistan and Iran could be injection drug

  18. Signature Peptide-Enabled Metagenomics (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

    ScienceCinema

    McMahon, Ben [LANL

    2016-07-12

    Ben McMahon of Los Alamos National Laboratory (LANL) presents "Signature Peptide-Enabled Metagenomics" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  19. Treatment for HIV

    MedlinePlus

    ... and Public Home » Treatment » Treatment Decisions and HIV HIV/AIDS Menu Menu HIV/AIDS HIV/AIDS Home ... here Enter ZIP code here Treatment Decisions and HIV for Veterans and the Public Treatment for HIV: ...

  20. The C-terminal tail of the gp41 transmembrane envelope glycoprotein of HIV-1 clades A, B, C, and D may exist in two conformations: an analysis of sequence, structure, and function

    SciTech Connect

    Hollier, Mark J.; Dimmock, Nigel J. . E-mail: n.j.dimmock@warwick.ac.uk

    2005-07-05

    In addition to the major ectodomain, the gp41 transmembrane glycoprotein of HIV-1 is now known to have a minor ectodomain that is part of the long C-terminal tail. Both ectodomains are highly antigenic, carry neutralizing and non-neutralizing epitopes, and are involved in virus-mediated fusion activity. However, data have so far been biologically based, and derived solely from T cell line-adapted (TCLA), B clade viruses. Here we have carried out sequence and theoretically based structural analyses of 357 gp41 C-terminal sequences of mainly primary isolates of HIV-1 clades A, B, C, and D. Data show that all these viruses have the potential to form a tail loop structure (the minor ectodomain) supported by three, {beta}-sheet, membrane-spanning domains (MSDs). This means that the first (N-terminal) tyrosine-based sorting signal of the gp41 tail is situated outside the cell membrane and is non-functional, and that gp41 that reaches the cell surface may be recycled back into the cytoplasm through the activity of the second tyrosine-sorting signal. However, we suggest that only a minority of cell-associated gp41 molecules - those destined for incorporation into virions - has 3 MSDs and the minor ectodomain. Most intracellular gp41 has the conventional single MSD, no minor ectodomain, a functional first tyrosine-based sorting signal, and in line with current thinking is degraded intracellularly. The gp41 structural diversity suggested here can be viewed as an evolutionary strategy to minimize HIV-1 envelope glycoprotein expression on the cell surface, and hence possible cytotoxicity and immune attack on the infected cell.

  1. Audit Report, "Fire Protection Deficiencies at Los Alamos National Laboratory"

    SciTech Connect

    2009-06-01

    The Department of Energy's Los Alamos National Laboratory (Los Alamos) maintains some of the Nation's most important national security assets, including nuclear materials. Many of Los Alamos' facilities are located in close proximity to one another, are occupied by large numbers of contract and Federal employees, and support activities ranging from nuclear weapons design to science-related activities. Safeguarding against fires, regardless of origin, is essential to protecting employees, surrounding communities, and national security assets. On June 1, 2006, Los Alamos National Security, LLC (LANS), became the managing and operating contractor for Los Alamos, under contract with the Department's National Nuclear Security Administration (NNSA). In preparation for assuming its management responsibilities at Los Alamos, LANS conducted walk-downs of the Laboratory's facilities to identify pre-existing deficiencies that could give rise to liability, obligation, loss or damage. The walk-downs, which identified 812 pre-existing fire protection deficiencies, were conducted by subject matter professionals, including fire protection experts. While the Los Alamos Site Office has overall responsibility for the effectiveness of the fire protection program, LANS, as the Laboratory's operating contractor, has a major, day-to-day role in minimizing fire-related risks. The issue of fire protection at Los Alamos is more than theoretical. In May 2000, the 'Cerro Grande' fire burned about 43,000 acres, including 7,700 acres of Laboratory property. Due to the risk posed by fire to the Laboratory's facilities, workforce, and surrounding communities, we initiated this audit to determine whether pre-existing fire protection deficiencies had been addressed. Our review disclosed that LANS had not resolved many of the fire protection deficiencies that had been identified in early 2006: (1) Of the 296 pre-existing deficiencies we selected for audit, 174 (59 percent) had not been corrected

  2. Probabilistic risk assessment for the Los Alamos Meson Physics Facility worst-case design-basis accident

    SciTech Connect

    Sharirli, M.; Butner, J.M.; Rand, J.L.; Macek, R.J. ); McKinney, S.J. ); Roush, M.L. . Center for Reliability Engineering)

    1992-01-01

    This paper presents results from a Los Alamos National Laboratory Engineering and Safety Analysis Group assessment of the worse-case design-basis accident associated with the Clinton P. Anderson Meson Physics Facility (LAMPF)/Weapons Neutron Research (WNR) Facility. The primary goal of the analysis was to quantify the accident sequences that result in personnel radiation exposure in the WNR Experimental Hall following the worst-case design-basis accident, a complete spill of the LAMPF accelerator 1L beam. This study also provides information regarding the roles of hardware systems and operators in these sequences, and insights regarding the areas where improvements can increase facility-operation safety. Results also include confidence ranges to incorporate combined effects of uncertainties in probability estimates and importance measures to determine how variations in individual events affect the frequencies in accident sequences.

  3. Probabilistic risk assessment for the Los Alamos Meson Physics Facility worst-case design-basis accident

    SciTech Connect

    Sharirli, M.; Butner, J.M.; Rand, J.L.; Macek, R.J.; McKinney, S.J.; Roush, M.L.

    1992-12-01

    This paper presents results from a Los Alamos National Laboratory Engineering and Safety Analysis Group assessment of the worse-case design-basis accident associated with the Clinton P. Anderson Meson Physics Facility (LAMPF)/Weapons Neutron Research (WNR) Facility. The primary goal of the analysis was to quantify the accident sequences that result in personnel radiation exposure in the WNR Experimental Hall following the worst-case design-basis accident, a complete spill of the LAMPF accelerator 1L beam. This study also provides information regarding the roles of hardware systems and operators in these sequences, and insights regarding the areas where improvements can increase facility-operation safety. Results also include confidence ranges to incorporate combined effects of uncertainties in probability estimates and importance measures to determine how variations in individual events affect the frequencies in accident sequences.

  4. HIV Type 1 Molecular Epidemiology in pol and gp41 Genes Among Naive Patients from Mato Grosso do Sul State, Central Western Brazil

    PubMed Central

    da Silveira, Alexsander Augusto; Cardoso, Ludimila Paula Vaz; Francisco, Roberta Barbosa Lopes

    2012-01-01

    Abstract Antiretroviral naive patients (n=49) were recruited in central western Brazil (Campo Grande City/Mato Grosso do Sul State, located across the Bolivia and Paraguay borders). HIV-1 protease (PR), reverse transcriptase (RT), and env gp41 HR1 fragments were sequenced. Genetic diversity was analyzed by REGA/phylogenetic analyses. Intersubtype recombinants were identified by SimPlot/phylogenetic trees. PR/RT resistance was analyzed by Calibrated Population Resistance/Stanford databases. T-20 resistance in gp41 was assessed by Stanford, Los Alamos, and other sources. Of HIV-1 subtypes 65.3% were BPRBRT, 10.2% were CPRCRT, and 8.2% were F1PRF1RT. Intersubtype recombinants were 16.3%: four B/F1 and four B/C (two were “CRF31_BC-like”). The Pol-RT V75M mutation was detected in two homosexual partners; one patient had the T215S revertant mutation. T-20/gp41 resistance mutations were L44M (n=2) and V38A (n=1). The high percentage of non-B isolates (∼35%) highlights the importance of molecular surveillance studies in settings distant from the origin of the epidemic. Our data help elaborate the molecular epidemiological map of HIV-1 in Brazil. PMID:21790471

  5. [Coreceptors of HIV infection and the development of HIV entry inhibitors: overview and targets].

    PubMed

    Hoshino, Hiroo

    2002-01-01

    In 1996 CXCR4 was identified as a coreceptor for HIV-1. This finding has lead to further identification of more than ten G-protein-coupled receptors (GPCRs) as coreceptors for HIV/SIV. Cell tropisms and coreceptor uses of HIV during the course of HIV infection are summarized. Promiscuous properties of correlations between chemokines and their chemokine receptor uses and also between variable amino acid sequences in the V3 region of HIV gp120 Env and HIV coreceptor uses are discussed. This promiscuous property of HIV-1 is claimed to be a possible cause of a difficulty in developing highly effective entry inhibitors and in addition to allow rapid appearance of immune escape HIV mutants. Representative agents that inhibit HIV entry with a special reference to inhibitors of coreceptor use and gp41 function are summarized. gp41 is discussed as a promising target for the development of effective entry inhibitors.

  6. Groundwater level status report for 2009, Los Alamos National Laboratory

    SciTech Connect

    Koch, Richard J.; Schmeer, Sarah

    2010-03-01

    The status of groundwater level monitoring at Los Alamos National Laboratory in 2009 is provided in this report. This report summarizes groundwater level data for 179 monitoring wells, including 55 regional aquifer wells (including 11 regional/intermediate wells), 26 intermediate wells, 98 alluvial wells, and 12 water supply wells. Pressure transducers were installed in 161 monitoring wells for continuous monitoring of groundwater levels. Time-series hydrographs of groundwater level data are presented along with pertinent construction and location information for each well. The report also summarizes the groundwater temperatures recorded in intermediate and regional aquifer monitoring wells.

  7. Los Alamos National Laboratory Economic Analysis Capability Overview

    SciTech Connect

    Boero, Riccardo; Edwards, Brian Keith; Pasqualini, Donatella; Rivera, Michael Kelly

    2016-04-19

    Los Alamos National Laboratory has developed two types of models to compute the economic impact of infrastructure disruptions. FastEcon is a fast running model that estimates first-­order economic impacts of large scale events such as hurricanes and floods and can be used to identify the amount of economic activity that occurs in a specific area. LANL’s Computable General Equilibrium (CGE) model estimates more comprehensive static and dynamic economic impacts of a broader array of events and captures the interactions between sectors and industries when estimating economic impacts.

  8. Bradbury science museum: your window to Los Alamos National Laboratory

    SciTech Connect

    Deck, Linda Theresa

    2009-03-05

    The Bradbury Science Museum is the public's window to Los Alamos National Laboratory and supports the Community Program Office's mission to develop community support to accomplish LANL's national security and science mission. It does this by stimulating interest in and increasing basic knowledge of science and technology in northern New Mexico audiences, and increasing public understanding and appreciation of how LANL science and technology solve our global problems. In performing these prime functions, the Museum also preserves the history of scientific accomplishment at the Lab by collecting and preserving artifacts of scientific and historical importance.

  9. Groundwater level status report for 2010, Los Alamos National Laboratory

    SciTech Connect

    Koch, Richard J.; Schmeer, Sarah

    2011-03-01

    The status of groundwater level monitoring at Los Alamos National Laboratory in 2010 is provided in this report. This report summarizes groundwater level data for 194 monitoring wells, including 63 regional aquifer wells (including 10 regional/intermediate wells), 34 intermediate wells, 97 alluvial wells, and 12 water supply wells. Pressure transducers were installed in 162 monitoring wells for continuous monitoring of groundwater levels. Time-series hydrographs of groundwater level data are presented along with pertinent construction and location information for each well. The report also summarizes the groundwater temperatures recorded in intermediate and regional aquifer monitoring wells and seasonal responses to snowmelt runoff observed in intermediate wells.

  10. Tiger Team Assessment of the Los Alamos National Laboratory

    SciTech Connect

    Not Available

    1991-11-01

    The purpose of the safety and health assessment was to determine the effectiveness of representative safety and health programs at the Los Alamos National Laboratory (LANL). Within the safety and health programs at LANL, performance was assessed in the following technical areas: Organization and Administration, Quality Verification, Operations, Maintenance, Training and Certification, Auxiliary Systems, Emergency Preparedness, Technical Support, Packaging and Transportation, Nuclear Criticality Safety, Security/Safety Interface, Experimental Activities, Site/Facility Safety Review, Radiological Protection, Personnel Protection, Worker Safety and Health (OSHA) Compliance, Fire Protection, Aviation Safety, Explosives Safety, Natural Phenomena, and Medical Services.

  11. Recent developments in the Los Alamos radiation transport code system

    SciTech Connect

    Forster, R.A.; Parsons, K.

    1997-06-01

    A brief progress report on updates to the Los Alamos Radiation Transport Code System (LARTCS) for solving criticality and fixed-source problems is provided. LARTCS integrates the Diffusion Accelerated Neutral Transport (DANT) discrete ordinates codes with the Monte Carlo N-Particle (MCNP) code. The LARCTS code is being developed with a graphical user interface for problem setup and analysis. Progress in the DANT system for criticality applications include a two-dimensional module which can be linked to a mesh-generation code and a faster iteration scheme. Updates to MCNP Version 4A allow statistical checks of calculated Monte Carlo results.

  12. Groundwater level status report for 2008, Los Alamos National Laboratory

    SciTech Connect

    Koch, Richard J.; Schmeer, Sarah

    2009-03-01

    The status of groundwater level monitoring at Los Alamos National Laboratory in 2008 is provided in this report. This report summarizes groundwater level data for 179 monitoring wells, including 45 regional aquifer wells, 28 intermediate wells, 8 regional/intermediate wells, 106 alluvial wells, and 12 water supply wells. Pressure transducers were installed in 166 monitoring wells for continuous monitoring of groundwater levels. Time-series hydrographs of groundwater level data are presented along with pertinent construction and location information for each well. The report also summarizes the groundwater temperatures recorded in intermediate and regional aquifer monitoring wells.

  13. Groundwater Level Status Report for 2005 Los Alamos National Laboratory

    SciTech Connect

    S.P. Allen; R.J. Koch

    2006-05-15

    The status of groundwater level monitoring at Los Alamos National Laboratory (LANL) in 2005 is provided in this report. The Groundwater Level Monitoring Project was instituted in 2005 to provide a framework for the collection and processing of quality controlled groundwater level data. This report summarizes groundwater level data for 137 monitoring wells, including 41 regional aquifer wells, 22 intermediate wells, and 74 alluvial wells. Pressure transducers were installed in 118 monitoring wells for continuous monitoring of groundwater levels. Time-series hydrographs of groundwater level data are presented along with pertinent construction and location information for each well.

  14. The Los Alamos National Laboratory Nuclear Vision Project

    SciTech Connect

    Arthur, E.D.; Wagner, R.L. Jr.

    1996-09-01

    Los Alamos National Laboratory has initiated a project to examine possible futures associated with the global nuclear enterprise over the course of the next 50 years. All major components are included in this study--weapons, nonproliferation, nuclear power, nuclear materials, and institutional and public factors. To examine key issues, the project has been organized around three main activity areas--workshops, research and analyses, and development of linkages with other synergistic world efforts. This paper describes the effort--its current and planned activities--as well as provides discussion of project perspectives on nuclear weapons, nonproliferation, nuclear energy, and nuclear materials focus areas.

  15. Los Alamos Science, Number 25 -- 1997: Celebrating the Neutrino

    DOE R&D Accomplishments Database

    Cooper, N. G. ed.

    1997-01-01

    This issue is devoted to the neutrino and its remaining mysteries. It is divided into the following areas: (1) The Reines-Cowan experiment -- detecting the poltergeist; (2) The oscillating neutrino -- an introduction to neutrino masses and mixing; (3) A brief history of neutrino experiments at LAMPF; (4) A thousand eyes -- the story of LSND (Los Alamos neutrino oscillation experiment); (5) The evidence for oscillations; (6) The nature of neutrinos in muon decay and physics beyond the Standard Model; (7) Exorcising ghosts -- in pursuit of the missing solar neutrinos; (8) MSW -- a possible solution to the solar neutrino problem; (8) Neutrinos and supernovae; and (9) Dark matter and massive neutrinos.

  16. Mac configuration management at the Los Alamos National Laboratory

    SciTech Connect

    Marcus, Allan B

    2010-01-01

    The Los Alamos National Laboratory (LANL) had a need for central configuration management of non-Windows computers. LANL has three to five thousand Macs and an equal number of Linux based systems. The primary goal was to be able to inventory all non-windows systems and patch Mc OS X systems. LANL examined a number of commercial and open source solutions and ultimately selected Puppet. This paper will discuss why we chose Puppet, how we implemented it, and some lessons we learned along the way.

  17. Los Alamos Science, Number 25 -- 1997: Celebrating the neutrino

    SciTech Connect

    Cooper, N.G.

    1997-12-31

    This issue is devoted to the neutrino and its remaining mysteries. It is divided into the following areas: (1) The Reines-Cowan experiment -- detecting the poltergeist; (2) The oscillating neutrino -- an introduction to neutrino masses and mixing; (3) A brief history of neutrino experiments at LAMPF; (4) A thousand eyes -- the story of LSND (Los Alamos neutrino oscillation experiment); (5) The evidence for oscillations; (6) The nature of neutrinos in muon decay and physics beyond the Standard Model; (7) Exorcising ghosts -- in pursuit of the missing solar neutrinos; (8) MSW -- a possible solution to the solar neutrino problem; (8) Neutrinos and supernovae; and (9) Dark matter and massive neutrinos.

  18. Los Alamos safeguards program overview and NDA in safeguards

    SciTech Connect

    Keepin, G.R.

    1988-01-01

    Over the years the Los Alamos safeguards program has developed, tested, and implemented a broad range of passive and active nondestructive analysis (NDA) instruments (based on gamma and x-ray detection and neutron counting) that are now widely employed in safeguarding nuclear materials of all forms. Here very briefly, the major categories of gamma ray and neutron based NDA techniques, give some representative examples of NDA instruments currently in use, and cite a few notable instances of state-of-the-art NDA technique development. Historical aspects and a broad overview of the safeguards program are also presented.

  19. Water supply at Los Alamos during 1995. Progress report

    SciTech Connect

    McLin, S.G.; Purtymun, W.D.; Maes, M.N.

    1997-04-01

    Production of potable municipal water supplies during 1995 totaled about 1,356.1 million gallons from wells in the Guaje and Pajarito well fields. Wells in the Otowi field were not operational during 1995. The nonpotable water supply for industrial use was about 1.6 million gallons from the spring gallery in Water Canyon, and another 1.6 million gallons from Los Alamos Reservoir was used for lawn irrigation. There was no water used from Guaje Reservoir in 1995. The total water usage in 1995 was about 1,359.3 million gallons. Groundwater pumpage during 1995 was the lowest on record since 1966.

  20. Water supply at Los Alamos during 1985: Progress report

    SciTech Connect

    Purtymun, W.D.; Becker, N.M.; Maes, M.N.

    1986-10-01

    Well field operations during 1985 were satisfactory with municipal and industrial supplies consisting of 1587 x 10/sup 6/ gal from wells in three well fields and 37 x 10/sup 6/ gal from the gallery in Water Canyon. About 2.8 x 10/sup 6/ gal of water from Guaje Reservoir and 0.9 x 10/sup 6/ gal from Los Alamos Reservoir were used for irrigation; thus the total water usage in 1985 was about 1628 x 10/sup 6/ gal. Primary and secondary chemical quality of water in the distribution system is in compliance with federal regulations.

  1. The Epidemic Dynamics of Four Major Lineages of HIV-1 CRF01_AE Strains After Their Introduction into China.

    PubMed

    Zeng, Haiyan; Li, Tingting; Wang, Yan; Sun, Binlian; Yang, Rongge

    2016-05-01

    The epidemic of HIV-1 CRF01_AE in China was driven by multiple lineages of HIV-1 viruses introduced in the 1990s and increasing; it is important to investigate their epidemic status in China. In this study, we download all available CRF01_AE sequences (n = 2,931) from China and their associated epidemiological information in the Los Alamos HIV database for our analysis to explore their epidemic status in China. The results showed there were 11 distinct clusters of CRF01_AE strains in China, and 4 major clusters that accounted for 80.0% (1,793/2,241) of Chinese CRF01_AE strains in total had led a real epidemic. Clusters 1 and 2 were epidemic among heterosexuals and injecting drug users in southern and southwestern China, while Clusters 3 and 4 were predominant among homosexuals in eastern and central China and northeastern China, respectively. HIV-1 CRF01_AE strains detected in heterosexuals had the most complex characteristic, underscoring its important role in the occurrence of multiple CRF01_AE lineages. Furthermore, epidemic history reconstruction analysis using the birth-death susceptible-infected-removed package revealed that the four clusters had gone through varying epidemic stages. Clusters 2 and 3 were near the peak of the local epidemic, while Clusters 1 and 4 were just in the very early stage of their epidemic. The epidemic status of CRF01_AE clusters in the future is mainly determined by the effect of prevention and control. Our study provides new insights into the understanding of the epidemic dynamics of CRF01_AE in China.

  2. Disentangling the impact of within-host evolution and transmission dynamics on the tempo of HIV-1 evolution

    PubMed Central

    Vrancken, Bram; Baele, Guy; Vandamme, Anne-Mieke; Van Laethem, Kristel; Suchard, Marc A.; Lemey, Philippe

    2017-01-01

    Background Although evidence exists for a selective component at transmission, it is clear that HIV-1 transmission is also to a large extent driven by drift. The variation in inoculum size among different risk groups therefore implies that the adaptation rate of HIV may vary between epidemics with different risk group compositions. Furthermore, factors that govern the rate of within-host evolution may also vary by risk group and therefore contribute to evolutionary differences at the epidemic level. Methods We adopted a population genetic approach to test whether the different proportions of multi-variant transmissions are reflected by varying proportions of transmitted diversity between men-having-sex-with-men (MSM), heterosexual (HET) and direct blood contact (BC) sub-populations. To this purpose, we collected all available transmission chain clonal sequence data sets (n = 70) available at the Los Alamos HIV website and through an extensive literature search. To assess evolutionary rate differences among different risk groups, we compiled risk group datasets for several subtypes and directly compared the absolute substitution rate and its synonymous and non-synonymous components. Results There was sufficient demographic signal to inform the transmission model in BEAST using env data to compare the transmission bottleneck size between the MSM and HET risk groups, i.e. the largest contributors to HIV spread. We find no indications for a different proportion of transmitted genetic diversity at the population level between these groups. In the direct rate comparisons between risk groups, however, we consistently recover a higher evolutionary rate in the male dominated risk group compared to the HET datasets. Conclusions We find that the risk group composition impacts the viral evolutionary rate and therefore potentially also the adaptation rate. In particular, risk group-specific sex ratios, and the variation in within-host evolutionary rates between males and

  3. HIV Prevention

    MedlinePlus

    ... medicines to treat HIV (called antiretroviral therapy, or ART) the right way, every day. They can keep ... to treat HIV infection (called antiretroviral therapy, or ART) the right way, every day and his or ...

  4. Coreceptor usage of Chinese HIV-1 and impact of X4/DM transmission clusters among recently infected men who have sex with men

    PubMed Central

    Li, Xiaoshan; Zhu, Kexin; Li, Wei; Fang, Kun; Musa, Taha Hussein; Song, Yue; Du, Guoping; Gao, Rong; Guo, Yan; Yan, Wenjuan; Xuan, Yang; Zhong, Ping; Wei, Pingmin

    2016-01-01

    Abstract To characterize the current frequency of HIV-1 coreceptor usage in China and assess the candidacy of CCR5 antagonists for treatment of HIV infections. In addition, we aimed to evaluate the potential of X4/DM virus transmission in recently infected men who have sex with men (MSM) individuals. Viral tropism testing was performed on samples from 399 MSM individuals and on 2408 available Chinese HIV-1 V3 sequences downloaded from the Los Alamos database using Geno2pheno and WebPSSM in combination. The transmission clusters were evaluated using pol sequences from 291 recently infected MSM with a maximum likelihood, maximum pairwise distance, and Bayesian inference. A higher prevalence of X4/DM viruses was observed in individuals infected with CRF01_AE strains than with subtype B (27.8% vs 12.2%, P < 0.001) and CRF07_BC/CRF08_BC/C (27.8% vs 1.0%, P < 0.001). Seven clusters containing only X4/DM viruses were detected in 40 transmission clusters. No significant difference in proportions between clustered X4/DM viruses and R5 viruses was found (P = 0.683). The high proportion of CXCR4 usage for CRF01_AE strains may result in the loss of susceptibility to maraviroc since CRF01_AE has become the most prevalent strains in China. The high prevalence of X4/DM viruses among recently CRF01_AE-infected individuals may be attributed to the stochasticity of HIV transmission, which implied that the early viral tropism screening and treatment would be the key for controlling the epidemic of CRF01_AE strains in China. PMID:27684870

  5. Coreceptor usage of Chinese HIV-1 and impact of X4/DM transmission clusters among recently infected men who have sex with men.

    PubMed

    Li, Xiaoshan; Zhu, Kexin; Li, Wei; Fang, Kun; Musa, Taha Hussein; Song, Yue; Du, Guoping; Gao, Rong; Guo, Yan; Yan, Wenjuan; Xuan, Yang; Zhong, Ping; Wei, Pingmin

    2016-09-01

    To characterize the current frequency of HIV-1 coreceptor usage in China and assess the candidacy of CCR5 antagonists for treatment of HIV infections. In addition, we aimed to evaluate the potential of X4/DM virus transmission in recently infected men who have sex with men (MSM) individuals.Viral tropism testing was performed on samples from 399 MSM individuals and on 2408 available Chinese HIV-1 V3 sequences downloaded from the Los Alamos database using Geno2pheno and WebPSSM in combination. The transmission clusters were evaluated using pol sequences from 291 recently infected MSM with a maximum likelihood, maximum pairwise distance, and Bayesian inference.A higher prevalence of X4/DM viruses was observed in individuals infected with CRF01_AE strains than with subtype B (27.8% vs 12.2%, P < 0.001) and CRF07_BC/CRF08_BC/C (27.8% vs 1.0%, P < 0.001). Seven clusters containing only X4/DM viruses were detected in 40 transmission clusters. No significant difference in proportions between clustered X4/DM viruses and R5 viruses was found (P = 0.683).The high proportion of CXCR4 usage for CRF01_AE strains may result in the loss of susceptibility to maraviroc since CRF01_AE has become the most prevalent strains in China. The high prevalence of X4/DM viruses among recently CRF01_AE-infected individuals may be attributed to the stochasticity of HIV transmission, which implied that the early viral tropism screening and treatment would be the key for controlling the epidemic of CRF01_AE strains in China.

  6. Industrial application for the Los Alamos Materials Modeling Platform

    SciTech Connect

    Lesar, R.; Charbon, C.; Kothe, D.; Wu, D.; Reddy, A.

    1996-09-01

    This is the final report of a one-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Casting and solidification of molten metals and metal alloys is a critical step in the production of high-quality metal stock and in the fabrication of finished parts. Control of the casting process can be the determining factor in both the quality and cost of the final metal product. Major problems with the quality of cast stock or finished parts can arise because of the difficulty of preventing variations in the alloy content, the generation of porosity or poor surface finish, and the loss of microstructure controlled strength and toughness resulting from the poor understanding and design of the mold filling and solidification processes. In this project, we sought to develop a new set of applications focused on adding the ability to accurately model solidification and grain growth to casting simulations. We implemented these applications within the Los Alamos Materials Modeling Platform, LAMMP, a graphical-based materials, and materials modeling environment being created at the Computational Testbed for Industry.

  7. Exploding metallic foil fuse modeling at Los Alamos

    SciTech Connect

    Lindemuth, I.R.; Reinovsky, R.E.; Goforth, J.H.

    1989-01-01

    A ''first-principles'' computational model of exploding metallic foil behavior has been developed at Los Alamos. The model couples zero-dimensional magnetohydrodynamics with ohmic heating and electrical circuit equations and uses the Los Alamos SESAME atomic data base computer library to determine the foil material's temperature- and density-dependent pressure, specific energy, and electrical conductivity. The model encompasses many previously successful empirical models and offers plausible physical explanations of phenomena not treated by the empirical models. In addition to addressing the electrical circuit performance of an exploding foil, the model provides information on the temporal evolution of the foil material's density, temperature, pressure, electrical conductivity, and expansion and translational velocities. In this paper, we report the physical insight gained by computational studies of two opening switch concepts being developed for application in an FCG-driven 1-MJ-class imploding plasma z-pinch experiment. The first concept considered is a ''conventional'' electrically exploded fuse, which has been demonstrated to operate at 16 MA driven by the 15-MJ-class FCG to be used in the 1 MJ implosion experiment. The second concept considered is a Type 2 explosively formed fuse (EFF), which has been demonstrated to operate at the 8 MA level by a 1-MJ-class FCG.

  8. An organizational survey of the Los Alamos Site

    SciTech Connect

    Shurberg, D.A.; Haber, S.B.

    1991-11-01

    An Organizational Survey (OS) was administered at the Los Alamos Site that queried employees on the subjects of organizational culture, various aspects of communications, employee commitment, work group cohesion, coordination of work, environmental, safety, and health concern, hazardous nature of work, safety and overall job satisfaction. The purpose of the OS is to measure in a quantitative and objective way the notion of culture;'' that is, the values, attitudes, and beliefs of the individuals working within the organization. In addition, through the OS, a broad sample of individuals can be reached that would probably not be interviewed or observed during the course of a typical assessment. The OS also provides a descriptive profile of the organization at one point in time that can then be compared to a profile taken at a different point in time to assess changes in the culture of the organization. While comparisons among groups are made, it is not the purpose of this report to make evaluative statements of which profile may be positive or negative. However, using the data presented in this report in conjunction with other evaluative activities, may provide useful insight into the organization. The OS administration at the Los Alamos Site was the ninth to occur at a Department of Energy (DOE) facility. All data from the OS is presented in group summaries, by organization, department or directorate within organization, supervisory level both overall and within organization, and staff classification within organization. Statistically significant differences between groups are identified and discussed. 9 refs., 94 figs., 11 tabs.

  9. An organizational survey of the Los Alamos Site

    SciTech Connect

    Shurberg, D.A.; Haber, S.B.

    1991-11-01

    An Organizational Survey (OS) was administered at the Los Alamos Site that queried employees on the subjects of organizational culture, various aspects of communications, employee commitment, work group cohesion, coordination of work, environmental, safety, and health concern, hazardous nature of work, safety and overall job satisfaction. The purpose of the OS is to measure in a quantitative and objective way the notion of ``culture;`` that is, the values, attitudes, and beliefs of the individuals working within the organization. In addition, through the OS, a broad sample of individuals can be reached that would probably not be interviewed or observed during the course of a typical assessment. The OS also provides a descriptive profile of the organization at one point in time that can then be compared to a profile taken at a different point in time to assess changes in the culture of the organization. While comparisons among groups are made, it is not the purpose of this report to make evaluative statements of which profile may be positive or negative. However, using the data presented in this report in conjunction with other evaluative activities, may provide useful insight into the organization. The OS administration at the Los Alamos Site was the ninth to occur at a Department of Energy (DOE) facility. All data from the OS is presented in group summaries, by organization, department or directorate within organization, supervisory level both overall and within organization, and staff classification within organization. Statistically significant differences between groups are identified and discussed. 9 refs., 94 figs., 11 tabs.

  10. Fuels Inventories in the Los Alamos National Laboratory Region: 1997

    SciTech Connect

    Balice, R.G.; Oswald, B.P.; Martin, C.

    1999-03-01

    Fifty-four sites were surveyed for fuel levels, vegetational structures, and topographic characteristics. Most of the surveyed sites were on Los Alamos National Laboratory property, however, some surveys were also conducted on U.S. Forest Service property. The overall vegetation of these sites ranged from pinon-juniper woodlands to ponderosa pine forests to mixed conifer forests, and the topographic positions included canyons, mesas, and mountains. The results of these surveys indicate that the understory fuels are the greatest in mixed conifer forests and that overstory fuels are greatest in both mixed conifer forests and ponderosa pine forests on mesas. The geographic distribution of these fuels would suggest a most credible wildfire scenario for the Los Alamos region. Three major fires have occurred since 1954 and these fires behaved in a manner that is consistent with this scenario. The most credible wildfire scenario was also supported by the results of BEHAVE modeling that used the fuels inventory data as inputs. Output from the BEHAVE model suggested that catastrophic wildfires would continue to occur during any season with sufficiently dry, windy weather.

  11. Cleanup at Los Alamos National Laboratory - the challenges - 9493

    SciTech Connect

    Stiger, Susan G; Hargis, Kenneth M; Graham, Michael J; Rael, George J

    2008-01-01

    This paper provides an overview of environmental cleanup at the Los Alamos National Laboratory (LANL) and some of the unique aspects and challenges. Cleanup of the 65-year old Department of Energy Laboratory is being conducted under a RCRA Consent Order with the State of New Mexico. This agreement is one of the most recent cleanup agreements signed in the DOE complex and was based on lessons learned at other DOE sites. A number of attributes create unique challenges for LANL cleanup -- the proximity to the community and pueblos, the site's topography and geology, and the nature of LANL's on-going missions. This overview paper will set the stage for other papers in this session, including papers that present: Plans to retrieve buried waste at Material Disposal Area B, across the street from oen of Los Alamos' commercial districts and the local newspaper; Progress to date and joint plans with WIPP for disposal of the remaining inventory of legacy transuranic waste; Reviews of both groundwater and surface water contamination and the factors complicating both characterization and remediation; Optimizing the disposal of low-level radioactive waste from ongoing LANL missions; A stakeholder environmental data transparency project (RACER), with full public access to all available information on contamination at LANL, and A description of the approach to waste processing cost recovery from the programs that generate hazardous and radioactive waste at LANL.

  12. The Los Alamos suite of relativistic atomic physics codes

    DOE PAGES

    Fontes, C. J.; Zhang, H. L.; Jr, J. Abdallah; ...

    2015-05-28

    The Los Alamos SuitE of Relativistic (LASER) atomic physics codes is a robust, mature platform that has been used to model highly charged ions in a variety of ways. The suite includes capabilities for calculating data related to fundamental atomic structure, as well as the processes of photoexcitation, electron-impact excitation and ionization, photoionization and autoionization within a consistent framework. These data can be of a basic nature, such as cross sections and collision strengths, which are useful in making predictions that can be compared with experiments to test fundamental theories of highly charged ions, such as quantum electrodynamics. The suitemore » can also be used to generate detailed models of energy levels and rate coefficients, and to apply them in the collisional-radiative modeling of plasmas over a wide range of conditions. Such modeling is useful, for example, in the interpretation of spectra generated by a variety of plasmas. In this work, we provide a brief overview of the capabilities within the Los Alamos relativistic suite along with some examples of its application to the modeling of highly charged ions.« less

  13. Recent progress in the Los Alamos KrF Program

    SciTech Connect

    McDonald, T.E.; Cartwright, D.C.; Coggeshall, S.V.; Fenstermacher, C.A.; Figueira, J.F.; Foreman, L.R.; Goldstone, P.D.; Hanson, D.E.; Harris, D.B.; Hauer, A.A.

    1988-01-01

    The goal of the Inertial Confinement Fusion Program (ICF) is to develop the ability to ignite and burn small masses of thermonuclear fuel. Although the present near-term objectives of the program are directed toward defense applications, ICF research continues to be carried out with a view to the longer term goal of commercial power production. The characteristics of a KrF laser make it an attractive candidate as an ICF driver. The KrF wavelength of 248 nm provides a target coupling that is very high at intensities of 10/sup 14/w/cm/sup 2/. In addition, the KrF laser can be repetitively operated at frequencies appropriate for a power reactor and has an intrinsically high efficiency, which allows projections to the long-term goal of energy production. The ICF program at Los Alamos consists of driver development, target design and fabrication, and target experimentation. The major effort at present is the investigation and development of KrF technology to determine its applicability for use in a laboratory driver at Los Alamos. Such a driver would be used in defense related technology studies and in areas of scientific study such as highly ionized materials and high-energy-density physics.

  14. The Los Alamos universe: Using multimedia to promote laboratory capabilities

    SciTech Connect

    Kindel, J.

    2000-03-01

    This project consists of a multimedia presentation that explains the technological capabilities of Los Alamos National Laboratory. It takes the form of a human-computer interface built around the metaphor of the universe. The project is intended promote Laboratory capabilities to a wide audience. Multimedia is simply a means of communicating information through a diverse set of tools--be they text, sound, animation, video, etc. Likewise, Los Alamos National Laboratory is a collection of diverse technologies, projects, and people. Given the ample material available at the Laboratory, there are tangible benefits to be gained by communicating across media. This paper consists of three parts. The first section provides some basic information about the Laboratory, its mission, and its needs. The second section introduces this multimedia presentation and the metaphor it is based on along with some basic concepts of color and user interaction used in the building of this project. The final section covers construction of the project, pitfalls, and future improvements.

  15. Investigation of excess thyroid cancer incidence in Los Alamos County

    SciTech Connect

    Athas, W.F.

    1996-04-01

    Los Alamos County (LAC) is home to the Los Alamos National Laboratory, a U.S. Department of Energy (DOE) nuclear research and design facility. In 1991, the DOE funded the New Mexico Department of Health to conduct a review of cancer incidence rates in LAC in response to citizen concerns over what was perceived as a large excess of brain tumors and a possible relationship to radiological contaminants from the Laboratory. The study found no unusual or alarming pattern in the incidence of brain cancer, however, a fourfold excess of thyroid cancer was observed during the late-1980`s. A rapid review of the medical records for cases diagnosed between 1986 and 1990 failed to demonstrate that the thyroid cancer excess had resulted from enhanced detection. Surveillance activities subsequently undertaken to monitor the trend revealed that the excess persisted into 1993. A feasibility assessment of further studies was made, and ultimately, an investigation was conducted to document the epidemiologic characteristics of the excess in detail and to explore possible causes through a case-series records review. Findings from the investigation are the subject of this report.

  16. The Los Alamos suite of relativistic atomic physics codes

    SciTech Connect

    Fontes, C. J.; Zhang, H. L.; Jr, J. Abdallah; Clark, R. E. H.; Kilcrease, D. P.; Colgan, J.; Cunningham, R. T.; Hakel, P.; Magee, N. H.; Sherrill, M. E.

    2015-05-28

    The Los Alamos SuitE of Relativistic (LASER) atomic physics codes is a robust, mature platform that has been used to model highly charged ions in a variety of ways. The suite includes capabilities for calculating data related to fundamental atomic structure, as well as the processes of photoexcitation, electron-impact excitation and ionization, photoionization and autoionization within a consistent framework. These data can be of a basic nature, such as cross sections and collision strengths, which are useful in making predictions that can be compared with experiments to test fundamental theories of highly charged ions, such as quantum electrodynamics. The suite can also be used to generate detailed models of energy levels and rate coefficients, and to apply them in the collisional-radiative modeling of plasmas over a wide range of conditions. Such modeling is useful, for example, in the interpretation of spectra generated by a variety of plasmas. In this work, we provide a brief overview of the capabilities within the Los Alamos relativistic suite along with some examples of its application to the modeling of highly charged ions.

  17. Water supply at Los Alamos during 1994. Progress report

    SciTech Connect

    McLin, S.G.; Purtymun, W.D.; Stoker, A.K.; Maes, M.N.

    1996-10-01

    Production of potable municipal water supplies during 1994 totaled about 1,426.6 million gallons of wells in the Guaje, Pajarito, and Otowi Fields. The non-potable water supply for industrial use was about 11.6 million gallons from the spring gallery in Water Canyon. There was no water used for irrigation from Guaje or Los Alamos Reservoirs; thus, the total water usage in 1994 was about 1,438.2 million gallons. Pumps in Guaje Well 5 and Otowi Well 4 failed during the year and were not operational by the end of 1994. Water production resumed in Pajarito Well 3 in June. Wells in the Los Alamos Field, on Pueblo Land, were plugged and abandoned in 1992, or were transferred to San Ildefonso Pueblo. This report fulfills requirements which require the Laboratory to monitor and document groundwater conditions below Pajarito Plateau, and to protect the main aquifer from contamination associated with Laboratory operations by providing information on hydrologic characteristics of the main aquifer, including operating conditions of the municipal water supply system.

  18. Mixed low-level waste minimization at Los Alamos

    SciTech Connect

    Starke, T.P.

    1998-12-01

    During the first six months of University of California 98 Fiscal Year (July--December) Los Alamos National Laboratory has achieved a 57% reduction in mixed low-level waste generation. This has been accomplished through a systems approach that identified and minimized the largest MLLW streams. These included surface-contaminated lead, lead-lined gloveboxes, printed circuit boards, and activated fluorescent lamps. Specific waste minimization projects have been initiated to address these streams. In addition, several chemical processing equipment upgrades are being implemented. Use of contaminated lead is planned for several high energy proton beam stop applications and stainless steel encapsulated lead is being evaluated for other radiological control area applications. INEEL is assisting Los Alamos with a complete systems analysis of analytical chemistry derived mixed wastes at the CMR building and with a minimum life-cycle cost standard glovebox design. Funding for waste minimization upgrades has come from several sources: generator programs, waste management, the generator set-aside program, and Defense Programs funding to INEEL.

  19. Plutonium scrap processing at the Los Alamos Scientific Laboratory

    SciTech Connect

    Nixon, A.E.; McKerley, B.J.; Christensen, E.L.

    1980-01-01

    The Los Alamos Scientific Laboratory currently has the newest plutonium handling facility in the nation. Los Alamos has been active in the processing of plutonium almost since the discovery of this man-made element in 1941. One of the functions of the new facility is the processing of plutonium scrap generated at LASL and other sites. The feed for the scrap processing program is extremely varied, and a wide variety of contaminants are often encountered. Depending upon the scrap matrix and contaminants present, the majority of material receives a nitric acid/hydrofluoric acid or nitric acid/calcium fluoride leach. The plutonium nitrate solutions are then loaded onto an anion exchange column charged with DOWEX 1 x 4, 50 to 100 mesh, nitrate form resin. The column is eluted with 0.48 M hydroxyl amine nitrate. The Pu(NO/sub 3/)/sub 3/ is then precipitated as plutonium III oxalate which is calcined at 450 to 500/sup 0/C to yield a purified PuO/sub 2/ product.

  20. Recollections of a very junior physicist at Los Alamos, 1944-1946

    NASA Astrophysics Data System (ADS)

    French, Anthony P.

    2008-04-01

    The author came to Los Alamos as a member of the British Mission after two years of making fission cross section measurements at the Cavendish Laboratory. He worked in a group headed by Egon Bretscher in Enrico Fermi's F Division. The talk presents his personal memories and experiences at Los Alamos as compared to his life and work in wartime Britain.

  1. 75 FR 1793 - Study Team for the Los Alamos Historical Document Retrieval and Assessment (LAHDRA) Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ... HUMAN SERVICES Centers for Disease Control and Prevention Study Team for the Los Alamos Historical...: Public Meeting of the Study Team for the Los Alamos Historical Document Retrieval and Assessment Project...://www.ohkay.com/contactus.html . Status: Open to the public, limited only by the space available....

  2. Office of Inspector General report on audit of environmental restoration at the Los Alamos National Laboratory

    SciTech Connect

    1997-07-01

    Los Alamos` Environmental Restoration Program is charged with cost effectively remediating contaminated sites. To monitor progress toward this goal, the University of California, the contractor operating Los Alamos, and the Department negotiated eight performance measures. The objective of this audit was to determine whether the contract performance criteria were reasonable, measurable, and complete, thereby allowing the Department to determine if Los Alamos had expeditiously and cost effectively remediated contaminated sites. The audit determined that Los Alamos did not generate the information needed to assess the cost effectiveness of remediation on a site-by-site basis. This situation occurred because the performance criteria used to evaluate cost effectiveness were not always reasonable, measurable, and complete. As a result, neither Los Alamos nor the Department could evaluate the cost effectiveness or progress of the remediation program or accurately budget for upcoming remediation activities. The audit also determined that Los Alamos` sample validation procedures were too costly because Los Alamos validated more samples than called for by Federal and New Mexico standard practices. While the Office of Inspector General recognizes the importance of prudent sample validation, Los Alamos paid $540,000 more than necessary to validate sample results. These funds could have been used to remediate contaminated sites.

  3. Bulk processing of radionuclide generator parents at the Los Alamos Hot Cell Facility

    SciTech Connect

    Fassbender, M. E.; Nortier, F. M.; Phillips, Dennis R.; Peterson, E. J.

    2004-01-01

    Bulk radionuclide processing at Los Alamos includes isotopes with short-lived radioactive daughter nuclides ('generator parents') for medical applications. The generator radionuclide parents {sup 68}Ge, {sup 82}Sr, {sup 88}Zr and {sup 109}Cd are regularly processed at the Los Alamos Hot Cell Facility. Nuclear chemical aspects related to the production and processing of these generator parents are briefly outlined.

  4. 75 FR 72829 - Los Alamos Historical Document Retrieval and Assessment (LAHDRA) Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Los Alamos Historical Document Retrieval and... Los Alamos Historical Document Retrieval and Assessment (LAHDRA)Project. Time and Date: 5 p.m.-7...

  5. Los Alamos strategic defense research and the ABM (Anti-Ballistic Missile) Treaty

    SciTech Connect

    Morales, R.; Pendley, R.E.

    1988-04-01

    This report reviews the restrictions placed on Los Alamos strategic defense by current arms control treaty agreements, including controversies about the correct interpretation of the major treaty at issue, the Anti-Ballistic Missile Treaty; and it assesses the current status of the most significant Los Alamos strategic defense programs in terms of their compliance with that Treaty, and others. 7 tabs.

  6. HIV-1 and HIV-2 LTR nucleotide sequences: assessment of the alignment by N-block presentation, "retroviral signatures" of overrepeated oligonucleotides, and a probable important role of scrambled stepwise duplications/deletions in molecular evolution.

    PubMed

    Laprevotte, I; Pupin, M; Coward, E; Didier, G; Terzian, C; Devauchelle, C; Hénaut, A

    2001-07-01

    Previous analyses of retroviral nucleotide sequences, suggest a so-called "scrambled duplicative stepwise molecular evolution" (many sectors with successive duplications/deletions of short and longer motifs) that could have stemmed from one or several starter tandemly repeated short sequence(s). In the present report, we tested this hypothesis by focusing on the long terminal repeats (LTRs) (and flanking sequences) of 24 human and 3 simian immunodeficiency viruses. By using a calculation strategy applicable to short sequences, we found consensus overrepresented motifs (often containing CTG or CAG) that were congruent with the previously defined "retroviral signature." We also show many local repetition patterns that are significant when compared with simply shuffled sequences. First- and second-order Markov chain analyses demonstrate that a major portion of the overrepresented oligonucleotides can be predicted from the dinucleotide compositions of the sequences, but by no means can biological mechanisms be deduced from these results: some of the listed local repetitions remain significant against dinucleotide-conserving shuffled sequences; together with previous results, this suggests that interspersed and/or local mononucleotide and oligonucleotide repetitions could have biased the dinucleotide compositions of the sequences. We searched for suggestive evolutionary patterns by scrutinizing a reliable multiple alignment of the 27 sequences. A manually constructed alignment based on homology blocks was in good agreement with the polypeptide alignment in the coding sectors and has been exhaustively assessed by using a multiplied alphabet obtained by the promising mathematical strategy called the N-block presentation (taking into account the environment of each nucleotide in a sequence). Sector by sector, we hypothesize many successive duplication/deletion scenarios that fit our previous evolutionary hypotheses. This suggests an important duplication/deletion role for

  7. Impact of sampling density on the extent of HIV clustering.

    PubMed

    Novitsky, Vlad; Moyo, Sikhulile; Lei, Quanhong; DeGruttola, Victor; Essex, Myron

    2014-12-01

    Identifying and monitoring HIV clusters could be useful in tracking the leading edge of HIV transmission in epidemics. Currently, greater specificity in the definition of HIV clusters is needed to reduce confusion in the interpretation of HIV clustering results. We address sampling density as one of the key aspects of HIV cluster analysis. The proportion of viral sequences in clusters was estimated at sampling densities from 1.0% to 70%. A set of 1,248 HIV-1C env gp120 V1C5 sequences from a single community in Botswana was utilized in simulation studies. Matching numbers of HIV-1C V1C5 sequences from the LANL HIV Database were used as comparators. HIV clusters were identified by phylogenetic inference under bootstrapped maximum likelihood and pairwise distance cut-offs. Sampling density below 10% was associated with stochastic HIV clustering with broad confidence intervals. HIV clustering increased linearly at sampling density >10%, and was accompanied by narrowing confidence intervals. Patterns of HIV clustering were similar at bootstrap thresholds 0.7 to 1.0, but the extent of HIV clustering decreased with higher bootstrap thresholds. The origin of sampling (local concentrated vs. scattered global) had a substantial impact on HIV clustering at sampling densities ≥10%. Pairwise distances at 10% were estimated as a threshold for cluster analysis of HIV-1 V1C5 sequences. The node bootstrap support distribution provided additional evidence for 10% sampling density as the threshold for HIV cluster analysis. The detectability of HIV clusters is substantially affected by sampling density. A minimal genotyping density of 10% and sampling density of 50-70% are suggested for HIV-1 V1C5 cluster analysis.

  8. Natural Attenuation of Anthropogenic Chromium in Selected Puye Formation in Regional Aquifer System of LOS Alamos, New Mexico

    NASA Astrophysics Data System (ADS)

    Brown, D. B.; Ding, M.; WoldeGabriel, G. W.; Cheshire, M.; Rearick, M.; Conradson, S.; Kluk, E.; Katzman, D.

    2014-12-01

    Routine groundwater monitoring conducted in 2005 revealed significant chromium (Cr) contamination in regional groundwater in Los Alamos, New Mexico. Previous use of potassium dichromate (K2Cr2O7) in cooling towers at Los Alamos National Laboratory's main power plant is believed to be the source of the elevated chromium levels. From 1956 to 1972 between 31,000 and 72,000 Kg of toxic Cr(IV) was released into Sandia Canyon. Initial investigations of the vadose zone using chromium isotopes indicated that reduction of anthropogenic Cr(IV) had occurred. However, to justify the use of Monitoring Natural Attenuation (MNA) as a valid remediation strategy, the Cr attenuation mechanism and the reduction capacity of the regional aquifer needs to be determined. Conventional batch sorption and synchrotron-based X-ray absorption spectroscopy studies were performed. Two samples were selected from the Puye formation, a silicoclastic sedimentary rock sequence located within the contaminated aquifer. Additionally, two Los Alamos Puye outcrop samples with no chromium exposure were selected for comparison. Each sample was subsequently sorted based on grain size, magnetic, and clay fractions. Groundwater with a known concentration of Cr(IV) was used in the batch experiments. Spectroscopy measurements of Puye samples before and after exposure to the same contaminated groundwater were conducted at the Stanford Synchrotron Radiation Lightsource (SSRL). Batch sorption results indicated little to no attenuation, as indicated by the small measured sorption coefficient (Kd < 5 Kg/L). Spectroscopic measurements suggest that attenuation of hexavalent chromium in groundwater is due to reduction of Cr(VI) to Cr(III) in the Puye and may be attributed almost exclusively to the clay fraction. These results indicate that the tested Puye sediments occurring in the regional aquifer have minor ability to naturally attenuate anthropogenic Cr(IV), with the clay fraction dominating the reduction process

  9. Genetic variability between isolates of human immunodeficiency virus (HIV) type 2 is comparable to the variability among HIV type 1.

    PubMed Central

    Zagury, J F; Franchini, G; Reitz, M; Collalti, E; Starcich, B; Hall, L; Fargnoli, K; Jagodzinski, L; Guo, H G; Laure, F

    1988-01-01

    The isolation from macaques of retroviruses related to human immunodeficiency virus (HIV) led to the identification of a second group of human retroviruses (termed HIV-2), which are prevalent in West Africa and closely related to the simian immunodeficiency virus (SIV). We have cloned and determined the complete nucleotide sequence of the human West African retrovirus HIV-2NIH-Z and compared it to that of a previously described strain of HIV-2 (HIV-2ROD) as well as to SIV and HIV-1. We have reached the following conclusions: (i) The HIV-2 isolates are (slightly) more closely related to each other than to SIV, compatible with their isolation from different species. (ii) The variability between HIV-2 isolates is similar in degree and kind to that found among HIV-1 isolates. The equivalent degrees of intragroup divergence suggest that HIV-1 and HIV-2 have existed in their present ranges in Africa for approximately equal lengths of time. The fact that acquired immunodeficiency syndrome is widespread in regions where HIV-1 is prevalent but not in regions where HIV-2 is prevalent suggests a substantial difference in the morbidity rates associated with HIV-1 vs. HIV-2 infection. (iii) HIV-2 and SIV are related to each other more closely than they are to HIV-1. PMID:3261862

  10. HIV-1 subtypes in Yugoslavia.

    PubMed

    Stanojevic, Maja; Papa, Anna; Papadimitriou, Evagelia; Zerjav, Sonja; Jevtovic, Djordje; Salemovic, Dubravka; Jovanovic, Tanja; Antoniadis, Antonis

    2002-05-01

    To gain insight concerning the genetic diversity of HIV-1 viruses associated with the HIV-1 epidemic in Yugoslavia, 45 specimens from HIV-1-infected individuals were classified into subtypes by sequence-based phylogenetic analysis of the polymerase (pol) region of the viral genome. Forty-one of 45 specimens (91.2%) were identified as pol subtype B, 2 of 45 as subtype C (4.4%), 1 of 45 as CRF01_AE (2.2%), and 1 as CRF02_AG recombinant (2.2%). Nucleotide divergence among subtype B sequences was 4.8%. Results of this study show that among HIV-1-infected patients in Yugoslavia subtype B predominates (91.5%), whereas non-B subtypes are present at a low percentage, mostly related to travel abroad.

  11. Nearly Finished Genomes Produced Using Gel Microdroplet Culturing (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

    ScienceCinema

    Fitzsimmons, Michael [LANL

    2016-07-12

    Michael Fitzsimmons from Los Alamos National Laboratory gives a talk titled "Nearly Finished Genomes Produced Using Gel Microdroplet Culturing" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  12. HIV Treatment: The Basics

    MedlinePlus

    HIV Treatment HIV Treatment: The Basics (Last updated 2/24/2017; last reviewed 2/24/2017) Key Points Antiretroviral therapy (ART) ... reduces the risk of HIV transmission . How do HIV medicines work? HIV attacks and destroys the infection- ...

  13. Vaccination With Heterologous HIV-1 Envelope Sequences and Heterologous Adenovirus Vectors Increases T-Cell Responses to Conserved Regions: HVTN 083

    PubMed Central

    Walsh, Stephen R.; Moodie, Zoe; Fiore-Gartland, Andrew J.; Morgan, Cecilia; Wilck, Marissa B.; Hammer, Scott M.; Buchbinder, Susan P.; Kalams, Spyros A.; Goepfert, Paul A.; Mulligan, Mark J.; Keefer, Michael C.; Baden, Lindsey R.; Swann, Edith M.; Grant, Shannon; Ahmed, Hasan; Li, Fusheng; Hertz, Tomer; Self, Steven G.; Friedrich, David; Frahm, Nicole; Liao, Hua-Xin; Montefiori, David C.; Tomaras, Georgia D.; McElrath, M. Juliana; Hural, John; Graham, Barney S.; Jin, Xia

    2016-01-01

    Background. Increasing the breadth of human immunodeficiency virus type 1 (HIV-1) vaccine-elicited immune responses or targeting conserved regions may improve coverage of circulating strains. HIV Vaccine Trials Network 083 tested whether cellular immune responses with these features are induced by prime-boost strategies, using heterologous vectors, heterologous inserts, or a combination of both. Methods. A total of 180 participants were randomly assigned to receive combinations of adenovirus vectors (Ad5 or Ad35) and HIV-1 envelope (Env) gene inserts (clade A or B) in a prime-boost regimen. Results. T-cell responses to heterologous and homologous insert regimens targeted a similar number of epitopes (ratio of means, 1.0; 95% confidence interval [CI], .6–1.6; P = .91), but heterologous insert regimens induced significantly more epitopes that were shared between EnvA and EnvB than homologous insert regimens (ratio of means, 2.7; 95% CI, 1.2–5.7; P = .01). Participants in the heterologous versus homologous insert groups had T-cell responses that targeted epitopes with greater evolutionary conservation (mean entropy [±SD], 0.32 ± 0.1 bits; P = .003), and epitopes recognized by responders provided higher coverage (49%; P = .035). Heterologous vector regimens had higher numbers of total, EnvA, and EnvB epitopes than homologous vector regimens (P = .02, .044, and .045, respectively). Conclusions. These data demonstrate that vaccination with heterologous insert prime boosting increased T-cell responses to shared epitopes, while heterologous vector prime boosting increased the number of T-cell epitopes recognized. Clinical Trials Registration. NCT01095224. PMID:26475930

  14. Common ground: An environmental ethic for Los Alamos National Laboratory

    SciTech Connect

    Menlove, F.L.

    1991-01-01

    Three predominant philosophies have characterized American business ethical thinking over the past several decades. The first phase is the ethics of self-interest'' which argues that maximizing self-interest coincidentally maximizes the common good. The second phase is legality ethics.'' Proponents argue that what is important is knowing the rules and following them scrupulously. The third phase might be called stake-holder ethics.'' A central tenant is that everyone affected by a decision has a moral hold on the decision maker. This paper will discuss one recent initiative of the Los Alamos National Laboratory to move beyond rules and regulations toward an environmental ethic that integrates the values of stakeholder ethics'' into the Laboratory's historical culture and value systems. These Common Ground Principles are described. 11 refs.

  15. The legacy and future of CFD at Los Alamos

    SciTech Connect

    Johnson, N.L.

    1996-06-01

    The early history is presented of the prolific development of CFD methods in the Fluid Dynamics Group (T-3) at Los Alamos National Laboratory in the years from 1958 to the late 1960`s. Many of the currently used numerical methods--PIC, MAC, vorticity-stream-function, ICE, ALE methods and the {kappa}-{var_epsilon} method for turbulence--originated during this time. The rest of the paper summarizes the current research in T-3 for CFD, turbulence and solids modeling. The research areas include reactive flows, multimaterial flows, multiphase flows and flows with spatial discontinuities. Also summarized are modern particle methods and techniques developed for large scale computing on massively parallel computing platforms and distributed processors.

  16. Los Alamos Guns Take Aim at Material's Mysteries

    SciTech Connect

    Byers, Mark; Moore, David; Dimarino, Steve

    2014-04-14

    Los Alamos National Laboratory scientists and technicians conduct thousands of experiments a year, delving into the fundamental nature of everything from supernovas to subatomic particles. One set of instruments used to better understand the fundamental nature of various materials are 10 scientific gun systems that fire various projectiles at high-tech targets to create enormous velocities, pressures, and temperatures - and using laser, x-ray, and other diagnostics - explore the very nature of metals and other materials. The hundreds of gun-based experiments conducted every year at the Laboratory require a highly-skilled staff of scientists and technicians, and has given rise to a special organization called the "gun working group" to foster open communications, cooperation, problem-solving, and a healthy safety culture.

  17. Environmental surveillance and compliance at Los Alamos during 1996

    SciTech Connect

    1997-09-01

    This report presents environmental data that characterize environmental performance and addresses compliance with environmental standards and requirements at Los Alamos National Laboratory (LANL or the Laboratory) during 1996. The Laboratory routinely monitors for radiation and for radioactive nonradioactive materials at Laboratory sites as well as in the surrounding region. LANL uses the monitoring results to determine compliance with appropriate standards and to identify potentially undesirable trends. Data were collected in 1996 to assess external penetrating radiation; quantities of airborne emissions; and concentrations of chemicals and radionuclides in ambient air, surface waters and groundwaters, the municipal water supply, soils and sediments, and foodstuffs. Using comparisons with standards and regulations, this report concludes that environmental effects from Laboratory operations are small and do not pose a demonstrable threat to the public, Laboratory employees, or the environment. Laboratory operations were in compliance with all major environmental regulations.

  18. Root lengths of plants on Los Alamos National Laboratory lands

    SciTech Connect

    Tierney, G.D.; Foxx, T.S.

    1987-01-01

    Maximum root lengths of 22 plant species occurring on Los Alamos National Laboratory lands were measured. An average of two longest roots from each species were dug up and their lengths, typical shapes, and qualitative morphologics were noted along with the overstory dimensions of the plant individual with which the roots were associated. Maximum root lengths were compared with overstory (height times width) dimensions. Among the life forms studied, the shrubs tend to show the longest roots in relation to overstory size. Forbs show the shortest roots in relation to overstory size. Measurements of tree roots suggest only that immature trees on the Pajarito Plateau may have root-length to overstory-size ratios near one. 30 refs., 14 figs., 2 tabs.

  19. Los Alamos Discovers Super Efficient Solar Using Perovskite Crystals

    ScienceCinema

    Mohite, Aditya; Nie, Wanyi

    2016-07-12

    State-of-the-art photovoltaics using high-purity, large-area, wafer-scale single-crystalline semiconductors grown by sophisticated, high temperature crystal-growth processes offer promising routes for developing low-cost, solar-based clean global energy solutions for the future. Solar cells composed of the recently discovered material organic-inorganic perovskites offer the efficiency of silicon, yet suffer from a variety of deficiencies limiting the commercial viability of perovskite photovoltaic technology. In research to appear in Science, Los Alamos National Laboratory researchers reveal a new solution-based hot-casting technique that eliminates these limitations, one that allows for the growth of high-quality, large-area, millimeter-scale perovskite crystals and demonstrates that highly efficient and reproducible solar cells with reduced trap assisted recombination can be realized.

  20. Los Alamos National Laboratory capability reviews - FY 2011 status

    SciTech Connect

    Springer, Everett P

    2011-01-12

    Capability reviews are the Los Alamos National Laboratory approach to assess the quality of its science, technology, and engineering (STE), and its integration across the Laboratory. There are seven capability reviews in FY 2011 reviews. The Weapons Science and Engineering review will be replaced by the National Nuclear Security Administration's Predictive Science Panel for 2011 . Beginning in 2011, third-year LORD projects will be reviewed by capability review committees rather than the first-year LORD projects that have been performed for the last three years. This change addresses concerns from committees about reviewing a project before it had made any substantive progress. The current schedule, and chairs for the 2011 capability reviews is presented. The three-year cycle (2011-2013) for capability reviews are presented for planning purposes.

  1. Plans for an Ultra Cold Neutron source at Los Alamos

    SciTech Connect

    Seestrom, S.J.; Bowles, T.J.; Hill, R.; Greene, G.L.

    1996-10-01

    Ultra Cold Neutrons (UCN) can be produced at spallation sources using a variety of techniques. To date the technique used has been to Bragg scatter and Doppler shift cold neutrons into UCN from a moving crystal. This is particularly applicable to short-pulse spallation sources. We are presently constructing a UCN source at LANSCE using this method. In addition, large gains in UCN density should be possible using cryogenic UCN sources. Research is under way at Gatchina to demonstrate technical feasibility of a frozen deuterium source. If successful, a source of this type could be implemented at future spallation source, such as the long pulse source being planned at Los Alamos, with a UCN density that may be two orders of magnitude higher than that presently available at reactors.

  2. Los Alamos Neutron Science Center (LANSCE) Nuclear Science Facilities

    SciTech Connect

    Nelson, Ronald Owen; Wender, Steve

    2015-06-19

    The Los Alamos Neutron Science Center (LANSCE) facilities for Nuclear Science consist of a high-energy "white" neutron source (Target 4) with 6 flight paths, three low-energy nuclear science flight paths at the Lujan Center, and a proton reaction area. The neutron beams produced at the Target 4 complement those produced at the Lujan Center because they are of much higher energy and have shorter pulse widths. The neutron sources are driven by the 800-MeV proton beam of the LANSCE linear accelerator. With these facilities, LANSCE is able to deliver neutrons with energies ranging from a milli-electron volt to several hundreds of MeV, as well as proton beams with a wide range of energy, time and intensity characteristics. The facilities, instruments and research programs are described briefly.

  3. Neutron Capture Experiments Using the DANCE Array at Los Alamos

    NASA Astrophysics Data System (ADS)

    Dashdorj, D.; Mitchell, G. E.; Baramsai, B.; Chyzh, A.; Walker, C.; Agvaanluvsan, U.; Becker, J. A.; Parker, W.; Sleaford, B.; Wu, C. Y.; Bredeweg, T. A.; Couture, A.; Haight, R. C.; Jandel, M.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wouters, J. M.; Krtička, M.; Bečvář, F.

    2009-03-01

    The Detector for Advanced Neutron Capture Experiments (DANCE) is designed for neutron capture measurements on very small and/or radioactive targets. The DANCE array of 160 BaF2 scintillation detectors is located at the Lujan Center at the Los Alamos Neutron Science Center (LANSCE). Accurate measurements of neutron capture data are important for many current applications as well as for basic understanding of neutron capture. The gamma rays following neutron capture reactions have been studied by the time-of-flight technique using the DANCE array. The high granularity of the array allows measurements of the gamma-ray multiplicity. The gamma-ray multiplicities and energy spectra for different multiplicities can be measured and analyzed for spin and parity determination of the resolved resonances.

  4. Los Alamos Explosives Performance Key to Stockpile Stewardship

    ScienceCinema

    Dattelbaum, Dana

    2016-07-12

    As the U.S. Nuclear Deterrent ages, one essential factor in making sure that the weapons will continue to perform as designed is understanding the fundamental properties of the high explosives that are part of a nuclear weapons system. As nuclear weapons go through life extension programs, some changes may be advantageous, particularly through the addition of what are known as "insensitive" high explosives that are much less likely to accidentally detonate than the already very safe "conventional" high explosives that are used in most weapons. At Los Alamos National Laboratory explosives research includes a wide variety of both large- and small-scale experiments that include small contained detonations, gas and powder gun firings, larger outdoor detonations, large-scale hydrodynamic tests, and at the Nevada Nuclear Security Site, underground sub-critical experiments.

  5. HELIOS: applications at the Los Alamos National Laboratory

    SciTech Connect

    Perry, R.T.; Mosteller, R.D.; Chodak, Paul III; Charlton, W.; Adams, B.T.

    1997-10-01

    The Los Alamos National Laboratory (LANL) is involved in the analysis of many different types of nuclear systems. The nuclear systems that we have analyzed have included subcritical accelerator driven systems for the transmutation of waste, fusion systems, critical experiment systems, and space propulsion and power systems. We have also analyzed special purpose reactors such as the LANL Omega West reactor, production reactors, and conventional commercial light- and heavy-water reactors. Thus the systems that we analyze and the type of results desired, often vary considerably from those of a power company normally analyzing their PWR or BWR for fissile fuel burnup and production. The reactor geometries that we model are often quite complicated such as those of an RBMK or Savannah River Production Reactor. Rather than fissile fuel production and burnup, the goal of a calculation could be the production rate of some obscure isotope which has medical applications.

  6. Experiments on planar plasma flow switches at Los Alamos

    SciTech Connect

    Benage, J.F. Jr.; Wysocki, F.J.; Bowers, R.; Oona, H.

    1997-12-01

    The authors have performed a series of experiments on the Colt facility at Los Alamos to study the performance of plasma flow switches and to understand the important physics issues which affect that performance. These experiments were done in planar geometry on a small machine to allow for better diagnostic access and a higher repetition rate. The Colt facility is a capacitor bank which stores 300 kJ at maximum charge and produced a peak current of 1.1 MA in 2.0 microseconds for these experiments. The diagnostics used for these experiments included an array of b-dot probes, visible framing pictures, visible spectroscopy, and laser interferometry. Characteristics of the switch are determined from spatial and temporal profiles of the magnetic field and the spatial profile and temperature of the switch plasma. Here the authors present results from experiments for a variety of switch conditions.

  7. Tiger Team Assessment of the Los Alamos National Laboratory

    SciTech Connect

    Not Available

    1991-11-01

    The Management Subteam conducted a management and organization assessment of environment, safety, and health (ES H) activities performed by the Los Alamos National Laboratory (LANL) and onsite contractor personnel. The objectives of the assessment were to (1) evaluate the effectiveness of management systems and practices in terms of ensuring environmental compliance and the safety and health of workers and the general public, (2) identify key findings, and (3) identify root causes for all ES H findings and concerns. The scope of the assessment included examinations of the following from an ES H perspective: (1) strategic and program planning; (2) organizational structure and management configuration; (3) human resource management, including training and staffing; (4) management systems, including performance monitoring and assessment; (5) conduct of operations; (6) public and institutional interactions; and (7) corporate'' parent support.

  8. Smoking patterns among Los Alamos National Laboratory employees

    SciTech Connect

    Mahoney, M.C.; Wilkinson, G.S.

    1987-06-01

    Smoking patterns among 5507 employees at Los Alamos National Laboratory were investigated for those who underwent physical examinations by occupational physicians from 1978 to 1983. More male than female employees smoked, although differences in smoking rates between the sexes were not as large as differences observed for national smoking rates. Employees over 40 were more likely to smoke than younger employees, males consumed more cigarettes than did females, and Anglo employees smoked more cigarettes than did Hispanic employees. Highly educated employees smoked less than did less-educated workers, and staff members exhibited the lowest rates of smoking. Smoking cessation programs for Laboratory employees should be directed toward those subpopulations with the highest rates of smoking. 31 refs., 8 figs., 1 tab.

  9. Operational status of the Los Alamos neutron science center (LANSCE)

    SciTech Connect

    Jones, Kevin W; Erickson, John L; Schoenberg, Kurt F

    2010-01-01

    The Los Alamos Neutron Science Center (LANSCE) accelerator and beam delivery complex generates the proton beams that serve three neutron production sources; the thermal and cold source for the Manuel Lujan Jr. Neutron Scattering Center, the Weapons Neutron Research (WNR) high-energy neutron source, and a pulsed Ultra-Cold Neutron Source. These three sources are the foundation of strong and productive multi-disciplinary research programs that serve a diverse and robust user community. The facility also provides multiplexed beams for the production of medical radioisotopes and proton radiography of dynamic events. The recent operating history of these sources will be reviewed and plans for performance improvement will be discussed, together with the underlying drivers for the proposed LANSCE Refurbishment project. The details of this latter project are presented in a separate contribution.

  10. LANSCE (Los Alamos Neutron Scattering Center) target data collection system

    SciTech Connect

    Kernodle, A.K. )

    1988-01-01

    The Los Alamos Neutron Scattering Center (LANSCE) Target Data Collection System is the result of an effort to provide a base of information from which to draw conclusions on the performance and operational condition of the overall LANSCE target system. During the conceptualization of the system several purposes and goals were defined. A survey was made of custom as well as off the shelf hardware and software which was capable of meeting these goals. The first stage of this system was successfully implemented for the LANSCE run cycle 52. From the operational experience gained thus far with the LANSCE Target Data Collection System, it would appear as though this system will indeed meet all of the previously defined requirements that seem to develop after a new system is installed.

  11. Los Alamos National Laboratory support to IAEA environmental safeguards

    SciTech Connect

    Steiner, Robert E; Dry, Don E; Roensch, Fred R; Kinman, Will S; Roach, Jeff L; La Mont, Stephen P

    2010-12-01

    The nuclear and radiochemistry group provides sample preparation and analysis support to the International Atomic Energy Agency (IAEA) Network of Analytical Laboratories (NWAL). These analyses include both non-destructive (alpha and gamma-ray spectrometry) and destructive (thermal ionization mass spectrometry and inductively coupled plasma mass spectrometry) methods. On a bi-annual basis the NWAL laboratories are invited to meet to discuss program evolution and issues. During this meeting each participating laboratory summarizes their efforts over the previous two years. This presentation will present Los Alamos National Laboratories efforts in support of this program. Data showing results from sample and blank analysis will be presented along with capability enhancement and issues that arose over the previous two years.

  12. The Laser Safety Program at Los Alamos National Laboratory

    SciTech Connect

    Hyer, R.

    1997-02-01

    The Laser Safety Program at the Los Alamos National Laboratory was formalized in April, 1991, with the publication of a document, {open_quotes}Lasers,{close_quotes} modeled on the ANSIZ136.1 standard. This program has received such wide acceptance by the laser community and line managers that the original Laser Safety Program document has become a Laboratory standard on lasers. As a benchmark of the success of this program is that the Laboratory has experienced no disabling eye injuries because of laser operations since July, 1990, to be compared with a disabling laser eye injury that used to average one every eighteen months prior to the time the formal program was established. The Laboratory Laser Safety Program and program elements will be presented and discussed.

  13. Los Alamos Explosives Performance Key to Stockpile Stewardship

    SciTech Connect

    Dattelbaum, Dana

    2014-11-03

    As the U.S. Nuclear Deterrent ages, one essential factor in making sure that the weapons will continue to perform as designed is understanding the fundamental properties of the high explosives that are part of a nuclear weapons system. As nuclear weapons go through life extension programs, some changes may be advantageous, particularly through the addition of what are known as "insensitive" high explosives that are much less likely to accidentally detonate than the already very safe "conventional" high explosives that are used in most weapons. At Los Alamos National Laboratory explosives research includes a wide variety of both large- and small-scale experiments that include small contained detonations, gas and powder gun firings, larger outdoor detonations, large-scale hydrodynamic tests, and at the Nevada Nuclear Security Site, underground sub-critical experiments.

  14. Decommissioning the UHTREX Reactor Facility at Los Alamos, New Mexico

    SciTech Connect

    Salazar, M.; Elder, J.

    1992-08-01

    The Ultra-High Temperature Reactor Experiment (UHTREX) facility was constructed in the late 1960s to advance high-temperature and gas-cooled reactor technology. The 3-MW reactor was graphite moderated and helium cooled and used 93% enriched uranium as its fuel. The reactor was run for approximately one year and was shut down in February 1970. The decommissioning of the facility involved removing the reactor and its associated components. This document details planning for the decommissioning operations which included characterizing the facility, estimating the costs of decommissioning, preparing environmental documentation, establishing a system to track costs and work progress, and preplanning to correct health and safety concerns in the facility. Work to decommission the facility began in 1988 and was completed in September 1990 at a cost of $2.9 million. The facility was released to Department of Energy for other uses in its Los Alamos program.

  15. Los Alamos Discovers Super Efficient Solar Using Perovskite Crystals

    SciTech Connect

    Mohite, Aditya; Nie, Wanyi

    2015-01-29

    State-of-the-art photovoltaics using high-purity, large-area, wafer-scale single-crystalline semiconductors grown by sophisticated, high temperature crystal-growth processes offer promising routes for developing low-cost, solar-based clean global energy solutions for the future. Solar cells composed of the recently discovered material organic-inorganic perovskites offer the efficiency of silicon, yet suffer from a variety of deficiencies limiting the commercial viability of perovskite photovoltaic technology. In research to appear in Science, Los Alamos National Laboratory researchers reveal a new solution-based hot-casting technique that eliminates these limitations, one that allows for the growth of high-quality, large-area, millimeter-scale perovskite crystals and demonstrates that highly efficient and reproducible solar cells with reduced trap assisted recombination can be realized.

  16. Los Alamos Guns Take Aim at Material's Mysteries

    ScienceCinema

    Byers, Mark; Moore, David; Dimarino, Steve

    2016-07-12

    Los Alamos National Laboratory scientists and technicians conduct thousands of experiments a year, delving into the fundamental nature of everything from supernovas to subatomic particles. One set of instruments used to better understand the fundamental nature of various materials are 10 scientific gun systems that fire various projectiles at high-tech targets to create enormous velocities, pressures, and temperatures - and using laser, x-ray, and other diagnostics - explore the very nature of metals and other materials. The hundreds of gun-based experiments conducted every year at the Laboratory require a highly-skilled staff of scientists and technicians, and has given rise to a special organization called the "gun working group" to foster open communications, cooperation, problem-solving, and a healthy safety culture.

  17. Initial performance of Los Alamos Advanced Free Electron Laser

    SciTech Connect

    Nguyen, D.C.; Austin, R.H.; Chan, K.C.D.

    1993-09-01

    The Los Alamos compact Advanced FEL has lased at 4.7 and 5.2 {mu}m with a 1-cm period wiggler and a high-brightness electron beam at 16.8 and 15.8 MeV, respectively. The measured electron beam normalized emittance is 1.7 {pi}{center_dot}mm{center_dot}mrad at a peak current of 100 A, corresponding to a beam brightness greater than 2 {times} 10{sup 12} A/m{sup 2}rad{sup 2}. Initial results indicate that the AFEL small signal gain is {approximately}8% at 0.3 nC (30 A peak). The maximum output energy is 7 mJ over a 2-{mu}s macropulse. The AFEL performance can be significantly enhanced by improvements in the rf and drive laser stability.

  18. Recent progress of the Los Alamos advanced free electron laser

    SciTech Connect

    Nguyen, D.C.; Austin, R.H.; Chan, K.C.D.; Feldman, D.W.; Goldstein, J.C.; Gierman, S.M.; Kinross-Wright, J.M.; Kong, S.H.; Plato, J.G.; Russell, S.J.

    1994-05-01

    Many industrial and research applications can benefit from the availability of a compact, user-friendly, broadly tunable and high average power free electron laser (FEL). Over the past four years, the Los Alamos Advanced FEL has been built with these design goals. The key to a compact FEL is the integration of advanced beam technologies such as a high-brightness photoinjector, a high-gradient compact linac, and permanent magnet beamline components. These technologies enable the authors to shrink the FEL size yet maintain its high average power capability. The Advanced FEL has been in operation in the near ir (4-6 {mu}m) since early 1993. Recent results of the Advanced FEL lasing at saturation and upgrades to improve its average power are presented.

  19. Environmental surveillance at Los Alamos during 1991. Environmental protection group

    SciTech Connect

    Dewart, J.; Kohen, K.L.

    1993-08-01

    This report describes the environmental surveillance program conducted by Los Alamos National Laboratory during 1991. Routine monitoring for radiation and for radioactive and chemical materials is conducted on the Laboratory site as well as in the surrounding region. Monitoring results are used to determine compliance with appropriate standards and to permit early identification of potentially undesirable trends. Results and interpretation of data for 1991 cover external penetrating radiation; quantities of airborne emissions and effluents; concentrations of chemicals and radionuclides in ambient air, surface waters and groundwaters, municipal water supply, soils and sediments, and foodstuffs; and environmental compliance. Comparisons with appropriate standards, regulations, and background levels provide the basis for concluding that environmental effects from Laboratory operations are small and do not pose a threat to the public, Laboratory employees, or the environment.

  20. The Los Alamos Scientific Laboratory - An Isolated Nuclear Research Establishment

    SciTech Connect

    Bradbury, Norris E.; Meade, Roger Allen

    2016-09-23

    Early in his twenty-five year career as the Director of the Los Alamos Scientific Laboratory, Norris Bradbury wrote at length about the atomic bomb and the many implications the bomb might have on the world. His themes were both technical and philosophical. In 1963, after nearly twenty years of leading the nation’s first nuclear weapons laboratory, Bradbury took the opportunity to broaden his writing. In a paper delivered to the International Atomic Energy Agency’s symposium on the “Criteria in the Selection of Sites for the Construction of Reactors and Nuclear Research Centers,” Bradbury took the opportunity to talk about the business of nuclear research and the human component of operating a scientific laboratory. This report is the transcript of his talk.

  1. Neutron Capture Experiments Using the DANCE Array at Los Alamos

    SciTech Connect

    Dashdorj, D.; Mitchell, G. E.; Baramsai, B.; Chyzh, A.; Walker, C.; Agvaanluvsan, U.; Becker, J. A.; Parker, W.; Sleaford, B.; Wu, C. Y.; Bredeweg, T. A.; Couture, A.; Haight, R. C.; Jandel, M.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wouters, J. M.; Krticka, M.; Becvar, F.

    2009-03-31

    The Detector for Advanced Neutron Capture Experiments (DANCE) is designed for neutron capture measurements on very small and/or radioactive targets. The DANCE array of 160 BaF{sub 2} scintillation detectors is located at the Lujan Center at the Los Alamos Neutron Science Center (LANSCE). Accurate measurements of neutron capture data are important for many current applications as well as for basic understanding of neutron capture. The gamma rays following neutron capture reactions have been studied by the time-of-flight technique using the DANCE array. The high granularity of the array allows measurements of the gamma-ray multiplicity. The gamma-ray multiplicities and energy spectra for different multiplicities can be measured and analyzed for spin and parity determination of the resolved resonances.

  2. Study of polyelectrolytes for Los Alamos National Laboratory. Final report

    SciTech Connect

    Labonne, N.

    1994-11-01

    To assess the safety of a potential radioactive waste repository, analysis of the fluid solution containing low levels of activity need to be performed. In some cases, the radioactivity would be so weak (3--30 pCi/L) that the solution must be concentrated for measurement. For this purpose, Los Alamos National Laboratory scientists are synthesizing some water soluble polyelectrolytes, which, because they are strong complexing agents for inorganic cations, can concentrate the radioelements in solution. To assist in characterization of these polyelectrolytes, the author has performed experiments to determine physico-chemical constants, such as pKa values and stability constants. The complexation constants between both polyelectrolytes and europium were determined by two methods: solvent extraction and ion exchange. Results are presented.

  3. 2016 Los Alamos National Laboratory Hazardous Waste Minimization Report

    SciTech Connect

    Salzman, Sonja L.; English, Charles Joe

    2016-12-02

    Waste minimization and pollution prevention are goals within the operating procedures of Los Alamos National Security, LLC (LANS). The US Department of Energy (DOE), inclusive of the National Nuclear Security Administration (NNSA) and the Office of Environmental Management, and LANS are required to submit an annual hazardous waste minimization report to the New Mexico Environment Department (NMED) in accordance with the Los Alamos National Laboratory (LANL or the Laboratory) Hazardous Waste Facility Permit. The report was prepared pursuant to the requirements of Section 2.9 of the LANL Hazardous Waste Facility Permit. This report describes the hazardous waste minimization program, which is a component of the overall Pollution Prevention (P2) Program, administered by the Environmental Stewardship Group (EPC-ES). This report also supports the waste minimization and P2 goals of the Associate Directorate of Environmental Management (ADEM) organizations that are responsible for implementing remediation activities and describes its programs to incorporate waste reduction practices into remediation activities and procedures. This report includes data for all waste shipped offsite from LANL during fiscal year (FY) 2016 (October 1, 2015 – September 30, 2016). LANS was active during FY2016 in waste minimization and P2 efforts. Multiple projects were funded that specifically related to reduction of hazardous waste. In FY2016, there was no hazardous, mixed-transuranic (MTRU), or mixed low-level (MLLW) remediation waste shipped offsite from the Laboratory. More non-remediation hazardous waste and MLLW was shipped offsite from the Laboratory in FY2016 compared to FY2015. Non-remediation MTRU waste was not shipped offsite during FY2016. These accomplishments and analysis of the waste streams are discussed in much more detail within this report.

  4. 2013 Los Alamos National Laboratory Hazardous Waste Minimization Report

    SciTech Connect

    Salzman, Sonja L.; English, Charles J.

    2015-08-24

    Waste minimization and pollution prevention are inherent goals within the operating procedures of Los Alamos National Security, LLC (LANS). The US Department of Energy (DOE) and LANS are required to submit an annual hazardous waste minimization report to the New Mexico Environment Department (NMED) in accordance with the Los Alamos National Laboratory (LANL or the Laboratory) Hazardous Waste Facility Permit. The report was prepared pursuant to the requirements of Section 2.9 of the LANL Hazardous Waste Facility Permit. This report describes the hazardous waste minimization program (a component of the overall Waste Minimization/Pollution Prevention [WMin/PP] Program) administered by the Environmental Stewardship Group (ENV-ES). This report also supports the waste minimization and pollution prevention goals of the Environmental Programs Directorate (EP) organizations that are responsible for implementing remediation activities and describes its programs to incorporate waste reduction practices into remediation activities and procedures. LANS was very successful in fiscal year (FY) 2013 (October 1-September 30) in WMin/PP efforts. Staff funded four projects specifically related to reduction of waste with hazardous constituents, and LANS won four national awards for pollution prevention efforts from the National Nuclear Security Administration (NNSA). In FY13, there was no hazardous, mixedtransuranic (MTRU), or mixed low-level (MLLW) remediation waste generated at the Laboratory. More hazardous waste, MTRU waste, and MLLW was generated in FY13 than in FY12, and the majority of the increase was related to MTRU processing or lab cleanouts. These accomplishments and analysis of the waste streams are discussed in much more detail within this report.

  5. Pinon Pine Tree Study, Los Alamos National Laboratory: Source document

    SciTech Connect

    P. R. Fresquez; J. D. Huchton; M. A. Mullen; L. Naranjo, Jr.

    2000-01-01

    One of the dominant tree species growing within and around Los Alamos National Laboratory (LANL), Los Alamos, NM, lands is the pinon pine (Pinus edulis) tree. Pinon pine is used for firewood, fence posts, and building materials and is a source of nuts for food--the seeds are consumed by a wide variety of animals and are also gathered by people in the area and eaten raw or roasted. This study investigated the (1) concentration of {sup 3}H, {sup 137}Cs, {sup 90}Sr, {sup tot}U, {sup 238}Pu, {sup 239,240}Pu, and {sup 241}Am in soils (0- to 12-in. [31 cm] depth underneath the tree), pinon pine shoots (PPS), and pinon pine nuts (PPN) collected from LANL lands and regional background (BG) locations, (2) concentrations of radionuclides in PPN collected in 1977 to present data, (3) committed effective dose equivalent (CEDE) from the ingestion of nuts, and (4) soil to PPS to PPN concentration ratios (CRs). Most radionuclides, with the exception of {sup 3}H in soils, were not significantly higher (p < 0.10) in soils, PPS, and PPN collected from LANL as compared to BG locations, and concentrations of most radionuclides in PPN from LANL have decreased over time. The maximum net CEDE (the CEDE plus two sigma minus BG) at the most conservative ingestion rate (10 lb [4.5 kg]) was 0.0018 mrem (0.018 {micro}Sv). Soil-to-nut CRs for most radionuclides were within the range of default values in the literature for common fruits and vegetables.

  6. Post-Cold War Science and Technology at Los Alamos

    NASA Astrophysics Data System (ADS)

    Browne, John C.

    2002-04-01

    Los Alamos National Laboratory serves the nation through the development and application of leading-edge science and technology in support of national security. Our mission supports national security by: ensuring the safety, security, and reliability of the U.S. nuclear stockpile; reducing the threat of weapons of mass destruction in support of counter terrorism and homeland defense; and solving national energy, environment, infrastructure, and health security problems. We require crosscutting fundamental and advanced science and technology research to accomplish our mission. The Stockpile Stewardship Program develops and applies, advanced experimental science, computational simulation, and technology to ensure the safety and reliability of U.S. nuclear weapons in the absence of nuclear testing. This effort in itself is a grand challenge. However, the terrorist attack of September 11, 2001, reminded us of the importance of robust and vibrant research and development capabilities to meet new and evolving threats to our national security. Today through rapid prototyping we are applying new, innovative, science and technology for homeland defense, to address the threats of nuclear, chemical, and biological weapons globally. Synergistically, with the capabilities that we require for our core mission, we contribute in many other areas of scientific endeavor. For example, our Laboratory has been part of the NASA effort on mapping water on the moon and NSF/DOE projects studying high-energy astrophysical phenomena, understanding fundamental scaling phenomena of life, exploring high-temperature superconductors, investigating quantum information systems, applying neutrons to condensed-matter and nuclear physics research, developing large-scale modeling and simulations to understand complex phenomena, and exploring nanoscience that bridges the atomic to macroscopic scales. In this presentation, I will highlight some of these post-cold war science and technology advances

  7. SNM holdup assessment of Los Alamos exhaust ducts. Final report

    SciTech Connect

    Marshall, R.S.

    1994-02-01

    Fissile material holdup in glovebox and fume hood exhaust ducting has been quantified for all Los Alamos duct systems. Gamma-based, nondestructive measurements were used to quantify holdup. The measurements were performed during three measurement campaigns. The first campaign, Phase I, provided foot-by-foot, semiquantitative measurement data on all ducting. These data were used to identify ducting that required more accurate (quantitative) measurement. Of the 280 duct systems receiving Phase I measurements, 262 indicated less than 50 g of fissile holdup and 19 indicated fissile holdup of 50 or more grams. Seven duct systems were measured in a second campaign, called Series 1, Phase II. Holdup estimates on these ducts ranged from 421 g of {sup 235}U in a duct servicing a shut-down uranium-machining facility to 39 g of {sup 239}Pu in a duct servicing an active plutonium-processing facility. Measurements performed in the second campaign proved excessively laborious, so a third campaign was initiated that used more efficient instrumentation at some sacrifice in measurement quality. Holdup estimates for the 12 duct systems measured during this third campaign ranged from 70 g of {sup 235}U in a duct servicing analytical laboratories to 1 g of {sup 235}U and 1 g of {sup 239}Pu in a duct carrying exhaust air to a remote filter building. These quantitative holdup estimates support the conclusion made at the completion of the Phase I measurements that only ducts servicing shut-down uranium operations contain about 400 g of fissile holdup. No ventilation ducts at Los Alamos contain sufficient fissile material holdup to present a criticality safety concern.

  8. Environmental Assessment for Electrical Power System Upgrades at Los Alamos National Laboratory, Los Alamos, New Mexico - Final Document

    SciTech Connect

    N /A

    2000-03-09

    The ''National Environmental Policy Act of 1969'' (NEPA) requires Federal agency officials to consider the environmental consequences of their proposed actions before decisions are made. In complying with NEPA, the United States (U.S.) Department of Energy (DOE) follows the Council on Environmental Quality (CEQ) regulations (40 Code of Federal Regulations [CFR] 1500-1508) and DOE's NEPA implementing procedures (10 CFR 1021). The purpose of an Environmental Assessment (EA) is to provide Federal decision makers with sufficient evidence and analysis to determine whether to prepare an Environmental Impact Statement (EIS) or issue a Finding of No Significant Impact. In this case, the DOE decision to be made is whether to construct and operate a 19.5-mile (mi) (31-kilometer [km]) electric transmission line (power line) reaching from the Norton Substation, west across the Rio Grande, to locations within the Los Alamos National Laboratory (LANL) Technical Areas (TAs) 3 and 5 at Los Alamos, New Mexico. The construction of one electric substation at LANL would be included in the project as would the construction of two line segments less than 1,200 feet (ft) (366 meters [m]) long that would allow for the uncrossing of a portion of two existing power lines. Additionally, a fiber optics communications line would be included and installed concurrently as part of the required overhead ground conductor for the power line. The new power line would improve the reliability of electric service in the LANL and Los Aktrnos County areas as would the uncrossing of the crossed segments of the existing lines. Additionally, installation of the new power line would enable the LANL and the Los Alamos County electric grid, which is a shared resource, to be adapted to accommodate the future import of increased power when additional power service becomes available in the northern New Mexico area. Similarly, the fiber optics line would allow DOE to take advantage of future opportunities in

  9. 1993 Annual PCB Document for Los Alamos National Laboratory EPA Region VI, January 1, 1993 through December 31, 1993

    SciTech Connect

    Wechsler, R.J.; Sandoval, T.M.; Bryant, D.E.; Hupke, L.; Esquibel, L.

    1995-12-31

    This document, the {open_quotes}1993 Annual PCB Document for Los Alamos National Laboratory{close_quotes} was prepared to fulffill the requirements of the federal PCB (Polychlorinated Biphenyl) regulation: 40 CFR 761 Subpart J General Records and Reports. The PCB Management Program at Los Alamos National Laboratory (LANL), Environmental Protection Group, compiled this 1993 Annual PCB Document. The overall format generally follows the sequence of the applicable regulations. Subsection 1.2 cross references those regulatory requirements with the applicable Document Section. The scope of this document also includes status summaries of various aspects of LANL`s PCB Management Program. The intent of this approach to the Annual Document is to provide an overview of LANL`s PCB Management Program and to increase the usefulness of this document as a management tool. Section 2.0, {open_quotes}Status of the PCB Management Program{close_quotes}, discusses the use, generation of waste, and storage of PCBs at LANL. Section 3.0 is the 1993 Annual Document Log required by 761.180(a). This Section also discusses the PCB Management Program`s policies for reporting under those regulatory requirements. Sections 4.0 and 5.0 contain the 1993 Annual Records for off-site and on-site disposal as required by 761.180(b). There is a tab for each manifest and its associated continuation sheets, receipt letters, and certificates of disposal.

  10. Ecological baseline studies in Los Alamos and Guaje Canyons County of Los Alamos, New Mexico. A two-year study

    SciTech Connect

    Foxx, T.S.

    1995-11-01

    During the summers of 1993 and 1994, the Biological Resource Evaluations Team (BRET) of the Environmental Protection Group (ESH-8) conducted baseline studies within two canyon systems, Los Alamos and Guaje Canyons. Biological data was collected within each canyon to provide background and baseline information for Ecological Risk models. Baseline studies included establishment of permanent vegetation plots within each canyon along the elevational gradient. Then, in association with the various vegetation types, surveys were conducted for ground dwelling insects, birds, and small mammals. The stream channels associated with the permanent vegetation plots were characterized and aquatic macroinvertebrates collected within the stream monthly throughout a six-month period. The Geographic Position System (GPS) in combination with ARC INFO was used to map the study areas. Considerable data was collected during these surveys and are summarized in individual chapters.

  11. NEPA and NHPA- successful decommissioning of historic Manhattan Project properties at Los Alamos National Laboratory, Los Alamos, New Mexico

    SciTech Connect

    McGehee, E.D.; Pendergrass, A.K.

    1997-05-21

    This paper describes experiences at Los Alamos National Laboratory during the process of planning and executing decommissioning and decontamination activities on a number of properties constructed as part of the Manhattan project. Many of these buildings had been abandoned for many years and were in deteriorating condition, in addition to being contaminated with asbestos, lead based paints and high explosive residues. Due to the age and use of the structures they were evaluated against criteria for the National Register of Historic Places. This process is briefly reviewed, along with the results, as well as actions implemented as a result of the condition and safety of the structures. A number of the structures have been decontaminated and demolished. Planning is still ongoing for the renovation of one structure, and the photographic and drawing records of the properties is near completion.

  12. Radionuclide concentrations in pinto beans, sweet corn, and zucchini squash grown in Los Alamos Canyon at Los Alamos National Laboratory

    SciTech Connect

    Fresquez, P.R.; Mullen, M.A.; Naranjo, L. Jr.; Armstrong, D.R.

    1997-05-01

    Pinto beans, sweet corn, and zucchini squash (Cucurbita pepo var. black beauty) were grown in a randomized complete-block field/pot experiment at a site that contained the highest observed levels of surface gross gamma radioactivity within Los Alamos Canyon (LAC) at Los Alamos National Laboratory. Soils as well as washed edible and nonedible crop tissues were analyzed for various radionuclides and heavy metals . Most radionuclides, with the exception of {sup 3}H and {sup tot}U, in soil from LAC were detected in significantly higher concentrations (p <0.01) than in soil collected from regional background (RBG) locations. Similarly, most radionuclides in edible crop portions of beans, squash, and corn were detected in significantly higher (p <0.01 and 0.05) concentrations than RBG. Most soil-to-plant concentration ratios for radionuclides in edible and nonedible crop tissues from LAC were within the default values given by the Nuclear Regulatory Commission and Environmental Protection Agency. All heavy metals in soils, as well as edible and nonedible crop tissues grown in soils from LAC, were within RBG concentrations. Overall, the total maximum net positive committed effective dose equivalent (CEDE)--the CEDE plus two sigma for each radioisotope minus background and then all positive doses summed--to a hypothetical 50-year resident that ingested 160 kg of beans, corn, and squash in equal proportions, was 74 mrem y{sup -1}. This dose was below the International Commission on Radiological Protection permissible dose limit (PDL) of 100 mrem y{sup -1} from all pathways; however, the addition of other internal and external exposure route factors may increase the overall dose over the PDL. Also, the risk of an excess cancer fatality, based on 74 mrem y{sup -1}, was 3.7 x 10{sup -5} (37 in a million), which is above the Environmental Protection Agency`s (acceptable) guideline of one in a million. 31 refs., 15 tabs.

  13. Audit of the radioactive liquid waste treatment facility operations at the Los Alamos National Laboratory

    SciTech Connect

    1997-11-19

    Los Alamos National Laboratory (Los Alamos) generates radioactive and liquid wastes that must be treated before being discharged to the environment. Presently, the liquid wastes are treated in the Radioactive Liquid Waste Treatment Facility (Treatment Facility), which is over 30 years old and in need of repair or replacement. However, there are various ways to satisfy the treatment need. The objective of the audit was to determine whether Los Alamos cost effectively managed its Treatment Facility operations. The audit determined that Los Alamos` treatment costs were significantly higher when compared to similar costs incurred by the private sector. This situation occurred because Los Alamos did not perform a complete analysis of privatization or prepare a {open_quotes}make-or-buy{close_quotes} plan for its treatment operations, although a {open_quotes}make-or-buy{close_quotes} plan requirement was incorporated into the contract in 1996. As a result, Los Alamos may be spending $2.15 million more than necessary each year and could needlessly spend $10.75 million over the next five years to treat its radioactive liquid waste. In addition, Los Alamos has proposed to spend $13 million for a new treatment facility that may not be needed if privatization proves to be a cost effective alternative. We recommended that the Manager, Albuquerque Operations Office (Albuquerque), (1) require Los Alamos to prepare a {open_quotes}make-or-buy{close_quotes} plan for its radioactive liquid waste treatment operations, (2) review the plan for approval, and (3) direct Los Alamos to select the most cost effective method of operations while also considering other factors such as mission support, reliability, and long-term program needs. Albuquerque concurred with the recommendations.

  14. The Role of HIV-1 gp41 Glycoprotein in Infectious Tropism Inferred from Physico-Chemical Properties of its Amino Acid Sequence

    NASA Astrophysics Data System (ADS)

    Figueroa, E.; Villarreal, C.; Huerta, L.; Cocho, G.

    2006-09-01

    We performed a statistical analysis of the amino acid sequence of the gp41 ectodomain of the Human Immunodeficiency Virus type 1. We found strong correlations between physicochemical properties of highly variable residues and the viral infectious tropism.

  15. Los Alamos National Laboratory: 21st century solutions to urgent national challenges

    SciTech Connect

    Mcbranch, Duncan

    2008-01-01

    Los Alamos National Laboratory has been called upon to meet urgent national challenges for more than 65 years. The people, tools, and technologies at Los Alamos are a world class resource that has proved decisive through our history, and are needed in the future. We offer expertise in nearly every science, technology, and engineering discipline, a unique integrated capability for large-scale computing and experimentation, and the proven ability to deliver solutions involving the most complex and difficult technical systems. This white paper outlines some emerging challenges and why the nation needs Los Alamos, the premier National Security Science Laboratory, to meet these challenges.

  16. Linear induction accelerators at the Los Alamos National Laboratory DARHT facility

    SciTech Connect

    Nath, Subrata

    2010-09-07

    The Dual-Axis Radiographic Hydrodynamic Test Facility (DARHT) at Los Alamos National Laboratory consists of two linear induction accelerators at right angles to each other. The First Axis, operating since 1999, produces a nominal 20-MeV, 2-kA single beam-pulse with 60-nsec width. In contrast, the DARHT Second Axis, operating since 2008, produces up to four pulses in a variable pulse format by slicing micro-pulses out of a longer {approx}1.6-microseconds (flat-top) pulse of nominal beam-energy and -current of 17 MeV and 2 kA respectively. Bremsstrahlung x-rays, shining on a hydro-dynamical experimental device, are produced by focusing the electron beam-pulses onto a high-Z target. Variable pulse-formats allow for adjustment of the pulse-to-pulse doses to record a time sequence of x-ray images of the explosively driven imploding mock device. Herein, we present a sampling of the numerous physics and engineering aspects along with the current status of the fully operational dual axes capability. First successful simultaneous use of both the axes for a hydrodynamic experiment was achieved in 2009.

  17. Uncertainty quantification and global sensitivity analysis of the Los Alamos sea ice model

    SciTech Connect

    Urrego-Blanco, Jorge Rolando; Urban, Nathan Mark; Hunke, Elizabeth Clare; Turner, Adrian Keith; Jeffery, Nicole

    2016-04-01

    Changes in the high-latitude climate system have the potential to affect global climate through feedbacks with the atmosphere and connections with midlatitudes. Sea ice and climate models used to understand these changes have uncertainties that need to be characterized and quantified. We present a quantitative way to assess uncertainty in complex computer models, which is a new approach in the analysis of sea ice models. We characterize parametric uncertainty in the Los Alamos sea ice model (CICE) in a standalone configuration and quantify the sensitivity of sea ice area, extent, and volume with respect to uncertainty in 39 individual model parameters. Unlike common sensitivity analyses conducted in previous studies where parameters are varied one at a time, this study uses a global variance-based approach in which Sobol' sequences are used to efficiently sample the full 39-dimensional parameter space. We implement a fast emulator of the sea ice model whose predictions of sea ice extent, area, and volume are used to compute the Sobol' sensitivity indices of the 39 parameters. Main effects and interactions among the most influential parameters are also estimated by a nonparametric regression technique based on generalized additive models. A ranking based on the sensitivity indices indicates that model predictions are most sensitive to snow parameters such as snow conductivity and grain size, and the drainage of melt ponds. Lastly, it is recommended that research be prioritized toward more accurately determining these most influential parameter values by observational studies or by improving parameterizations in the sea ice model.

  18. Specific sequences commonly found in the V3 domain of HIV-1 subtype C isolates affect the overall conformation of native Env and induce a neutralization-resistant phenotype independent of V1/V2 masking.

    PubMed

    Salomon, Aidy; Krachmarov, Chavdar; Lai, Zhong; Honnen, William; Zingman, Barry S; Sarlo, Julie; Gorny, Miroslaw K; Zolla-Pazner, Susan; Robinson, James E; Pinter, Abraham

    2014-01-05

    Primary HIV-1 isolates are relatively resistant to neutralization by antibodies commonly induced after infection or vaccination. This is generally attributed to masking of sensitive epitopes by the V1/V2 domain and/or glycans situated at various positions in Env. Here we identified a novel masking effect mediated by subtype C-specific V3 sequences that contributes to the V1/V2-independent and glycan-independent neutralization resistance of chimeric and primary Envs to antibodies directed against multiple neutralization domains. Positions at several conserved charged and hydrophobic sites in the V3 crown and stem were also shown to affect neutralization phenotype. These results indicated that substitutions typically present in subtype C and related V3 sequences influence the overall conformation of native Env in a way that occludes multiple neutralization targets located both within and outside of the V3 domain, and may reflect an alternative mechanism for neutralization resistance that is particularly active in subtype C and related isolates.

  19. The Los Alamos Science Pillars The Science of Signatures

    SciTech Connect

    Smith, Joshua E.; Peterson, Eugene J.

    2012-09-13

    As a national security science laboratory, Los Alamos is often asked to detect and measure the characteristics of complex systems and to use the resulting information to quantify the system's behavior. The Science of Signatures (SoS) pillar is the broad suite of technical expertise and capability that we use to accomplish this task. With it, we discover new signatures, develop new methods for detecting or measuring signatures, and deploy new detection technologies. The breadth of work at Los Alamos National Laboratory (LANL) in SoS is impressive and spans from the initial understanding of nuclear weapon performance during the Manhattan Project, to unraveling the human genome, to deploying laser spectroscopy instrumentation on Mars. Clearly, SoS is a primary science area for the Laboratory and we foresee that as it matures, new regimes of signatures will be discovered and new ways of extracting information from existing data streams will be developed. These advances will in turn drive the development of sensing instrumentation and sensor deployment. The Science of Signatures is one of three science pillars championed by the Laboratory and vital to supporting our status as a leading national security science laboratory. As with the other two pillars, Materials for the Future and Information Science and Technology for Predictive Science (IS&T), SoS relies on the integration of technical disciplines and the multidisciplinary science and engineering that is our hallmark to tackle the most difficult national security challenges. Over nine months in 2011 and 2012, a team of science leaders from across the Laboratory has worked to develop a SoS strategy that positions us for the future. The crafting of this strategy has been championed by the Chemistry, Life, and Earth Sciences Directorate, but as you will see from this document, SoS is truly an Institution-wide effort and it has engagement from every organization at the Laboratory. This process tapped the insight and

  20. A Journey From Sandia To Los Alamos - 12465

    SciTech Connect

    Goyal, K.K.; Humphrey, B.J.; Krause, T.J.; Gluth, J.W.; Kiefer, M.L.; Haynes, S.

    2012-07-01

    The U.S. Department of Energy (DOE) relies on laboratory experiments and computer-based models to verify the reliability of the nation's nuclear stockpile. Sandia National Laboratories/New Mexico (SNL/NM) tests various materials in extreme environments designed to mimic those of nuclear explosions using the Z machine. The Z machine is a key tool in the National Nuclear Security Administration's (NNSA) stockpile stewardship mission and is used to study the dynamic properties of nuclear weapon materials. In 2006, SNL/NM and Los Alamos National Laboratory (LANL) signed a Memorandum of Understanding (MOU) defining experiments to be conducted in the Z machine involving plutonium (Pu) provided by LANL. Five Pu experiments have been completed with as many as 20 more planned through 2016. The experimental containment vessel used for the experiment and containing the Pu residues, becomes transuranic (TRU) waste after the experiment and termination of safeguards and is considered a LANL waste stream. Each containment vessel is placed in a 55-gallon Type A drum or standard waste box (SWB) for shipment back to LANL for final certification and eventual disposal at the Waste Isolation Pilot Plant (WIPP). The experimental containment vessels are greater than 99% metallic materials (ferrous and non-ferrous metals). In addition to the Pu targets, detonators with high explosives (HE) are used in the experiments to isolate the containment vessel from the Z machine as energy is delivered to the Pu samples. The characterization requirements, transportation issues, required documentation, and the approvals needed before shipments were challenging and required close coordination between SNL/NM, Sandia Site Office, LANL, Los Alamos Site Office, Washington TRU Solutions, Inc., the Central Characterization Project, and the Carlsbad Field Office. Between 2006 and 2010, representatives from SNL/NM and LANL worked to develop an approved path forward to meet the requirements of all stakeholders

  1. 2015 Los Alamos Space Weather Summer School Research Reports

    SciTech Connect

    Cowee, Misa; Chen, Yuxi; Desai, Ravindra; Hassan, Ehab; Kalmoni, Nadine; Lin, Dong; Depascuale, Sebastian; Hughes, Randall Scott; Zhou, Hong

    2015-11-24

    The fifth Los Alamos Space Weather Summer School was held June 1st - July 24th, 2015, at Los Alamos National Laboratory (LANL). With renewed support from the Institute of Geophysics, Planetary Physics, and Signatures (IGPPS) and additional support from the National Aeronautics and Space Administration (NASA) and the Department of Energy (DOE) Office of Science, we hosted a new class of five students from various U.S. and foreign research institutions. The summer school curriculum includes a series of structured lectures as well as mentored research and practicum opportunities. Lecture topics including general and specialized topics in the field of space weather were given by a number of researchers affiliated with LANL. Students were given the opportunity to engage in research projects through a mentored practicum experience. Each student works with one or more LANL-affiliated mentors to execute a collaborative research project, typically linked with a larger ongoing research effort at LANL and/or the student’s PhD thesis research. This model provides a valuable learning experience for the student while developing the opportunity for future collaboration. This report includes a summary of the research efforts fostered and facilitated by the Space Weather Summer School. These reports should be viewed as work-in-progress as the short session typically only offers sufficient time for preliminary results. At the close of the summer school session, students present a summary of their research efforts. Titles of the papers included in this report are as follows: Full particle-in-cell (PIC) simulation of whistler wave generation, Hybrid simulations of the right-hand ion cyclotron anisotropy instability in a sub-Alfvénic plasma flow, A statistical ensemble for solar wind measurements, Observations and models of substorm injection dispersion patterns, Heavy ion effects on Kelvin-Helmholtz instability: hybrid study, Simulating plasmaspheric electron densities with a two

  2. Small Mammal Sampling in Mortandad and Los Alamos Canyons, 2005

    SciTech Connect

    Bennett, Kathy; Sherwood, Sherri; Robinson, Rhonda

    2006-08-15

    As part of an ongoing ecological field investigation at Los Alamos National Laboratory, a study was conducted that compared measured contaminant concentrations in sediment to population parameters for small mammals in the Mortandad Canyon watershed. Mortandad Canyon and its tributary canyons have received contaminants from multiple solid waste management units and areas of concern since establishment of the Laboratory in the 1940s. The study included three reaches within Effluent and Mortandad canyons (E-1W, M-2W, and M-3) that had a spread in the concentrations of metals and radionuclides and included locations where polychlorinated biphenyls and perchlorate had been detected. A reference location, reach LA-BKG in upper Los Alamos Canyon, was also included in the study for comparison purposes. A small mammal study was initiated to assess whether potential adverse effects were evident in Mortandad Canyon due to the presence of contaminants, designated as contaminants of potential ecological concern, in the terrestrial media. Study sites, including the reference site, were sampled in late July/early August. Species diversity and the mean daily capture rate were the highest for E-1W reach and the lowest for the reference site. Species composition among the three reaches in Mortandad was similar with very little overlap with the reference canyon. Differences in species composition and diversity were most likely due to differences in habitat. Sex ratios, body weights, and reproductive status of small mammals were also evaluated. However, small sample sizes of some species within some sites affected the analysis. Ratios of males to females by species of each site (n = 5) were tested using a Chi-square analysis. No differences were detected. Where there was sufficient sample size, body weights of adult small mammals were compared between sites. No differences in body weights were found. Reproductive status of species appears to be similar across sites. However, sample

  3. Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy.

    PubMed

    Imamichi, Hiromi; Dewar, Robin L; Adelsberger, Joseph W; Rehm, Catherine A; O'Doherty, Una; Paxinos, Ellen E; Fauci, Anthony S; Lane, H Clifford

    2016-08-02

    Despite years of plasma HIV-RNA levels <40 copies per milliliter during combination antiretroviral therapy (cART), the majority of HIV-infected patients exhibit persistent seropositivity to HIV-1 and evidence of immune activation. These patients also show persistence of proviruses of HIV-1 in circulating peripheral blood mononuclear cells. Many of these proviruses have been characterized as defective and thus thought to contribute little to HIV-1 pathogenesis. By combining 5'LTR-to-3'LTR single-genome amplification and direct amplicon sequencing, we have identified the presence of "defective" proviruses capable of transcribing novel unspliced HIV-RNA (usHIV-RNA) species in patients at all stages of HIV-1 infection. Although these novel usHIV-RNA transcripts had exon structures that were different from those of the known spliced HIV-RNA variants, they maintained translationally competent ORFs, involving elements of gag, pol, env, rev, and nef to encode a series of novel HIV-1 chimeric proteins. These novel usHIV-RNAs were detected in five of five patients, including four of four patients with prolonged viral suppression of HIV-RNA levels <40 copies per milliliter for more than 6 y. Our findings suggest that the persistent defective proviruses of HIV-1 are not "silent," but rather may contribute to HIV-1 pathogenesis by stimulating host-defense pathways that target foreign nucleic acids and proteins.

  4. Advertising HIV.

    PubMed

    Mougenez, Stephane; Chad, N'Djamena; Howe, John

    1995-04-05

    Think of advertising and what comes to mind, soap powders, motor cars, baked beans? All of these, of course, are heavily advertised, but what about HIV? Among the most durable of the government's advertisement campaigns have been the ones concerning HIV. Tens of millions of pounds have been spent telling the public of the presence and dangers of the virus.

  5. Los Alamos National Laboratory Science Education Programs. Quarterly progress report, April 1--June 30, 1995

    SciTech Connect

    Gill, D.

    1995-09-01

    This report is quarterly progress report on the Los Alamos National Laboratory Science Education Programs. Included in the report are dicussions on teacher and faculty enhancement, curriculum improvement, student support, educational technology, and institutional improvement.

  6. Architect and engineering costs at Los Alamos and Sandia National Laboratories

    SciTech Connect

    1998-08-01

    The objective of this audit was to determine whether architect and engineering (A-E) costs at Los Alamos National Laboratory and Sandia National Laboratories were reasonable in comparison with industry standards.

  7. Disposal of tritium residues at the Los Alamos National Laboratory. Audit repost

    SciTech Connect

    1998-07-01

    The objective of this audit was to determine whether Los Alamos disposed of wastewater containing tritium residues in a safe and cost-effective manner subsequent to an October 1991 report reviewing tritium facility management practices.

  8. Isentropic Compression Studies at the Los Alamos National High Magnetic Field Laboratory

    DTIC Science & Technology

    2011-06-01

    actinide samples in extremes of high magnetic field (to 300 Tesla) [1, 2]. A simple modification to the single-turn magnet has converted it to a fast...Isentropic Compression Studies At The Los Alamos National High Magnetic Field Laboratory 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT ...Laboratory (NHMFL) at Los Alamos was originally designed to study actinide samples in extremes of high magnetic field (to 300 Tesla) [1, 2]. A simple

  9. An Archaeological Sample Survey of the Alamo Reservoir Mohave and Yuma Counties, Arizona,

    DTIC Science & Technology

    1977-09-01

    about one-thid of the annual rainfall. This rainfall pattern is characteristic of the Lover Colorado section of the Sonoran Desert (Love 1964:24). 3Ř...Vegetation The Alamo Lake area is characterized by Southwestern Desert Scrub vegetation (Lowe 1964:18). Such vegetation occurs in the Lower Sonoran life...zone, an association covering elevations ranging up to 1220 a (4,000 ft). Alamo Lake is located in the Sonoran Desert, the hot desert covering most of

  10. Surface water data at Los Alamos National Laboratory: 1995 water year. Progress report

    SciTech Connect

    Barks, R.; Shaull, D.A.; Alexander, M.R.; Reynolds, R.P.

    1996-08-01

    The principle investigators collected and computed surface water discharge data from 15 stream-gaging stations that cover most of Los Alamos National Laboratory. The United States Department of Interior Geological Survey, Water Resources Division, operates two of the stations under a subcontract; these are identified in the station manuscripts. Included in this report are data from one seepage run conducted in Los Alamos Canyon during the 1995 water year.

  11. The Los Alamos Reservoir: A Gauge for Increased Erosion after the Cerro Grande Fire, Los Alamos, New Mexico

    NASA Astrophysics Data System (ADS)

    Lavine, A.; Katzman, D.; Reneau, S. L.; Kuyumjian, G. A.; Gardner, J. N.; Malmon, D. V.

    2001-12-01

    The Cerro Grande fire of May 2000 burned approximately 17,400 ha in the eastern Jemez Mountains in the vicinity of Los Alamos, New Mexico. Changes in surface characteristics caused by the fire, including the development of hydrophobic soils and the loss of vegetation and litter layers, resulted in major increases in runoff and erosion relative to pre-fire conditions. This study documents sedimentation in the Los Alamos reservoir, located in upper Los Alamos Canyon, providing a unique datum for estimating pre- and post-fire erosion rates in a montane watershed. The reservoir was built in 1943 for water storage, and had a maximum holding capacity of ~42,000 m3. The drainage basin upstream from the reservoir has an area of 16.5 km2, ranges in elevation from 2320 to 3180 m, and largely supported a mixed conifer forest prior to the fire. Thirty percent of the basin experienced moderate to high severity burn during the Cerro Grande fire, including some of the steepest parts of the basin; 33% experienced low severity burn and 37% was unburned. Draining of the reservoir to mitigate the potential for flooding down-canyon allowed for detailed surveying of the top of pre- and post-fire sediments. A total station survey in June 2000, following a single post-fire flood, showed a holding capacity of ~34,500 m3. The post-fire deposits in the reservoir were less than 0.3 m thick, and comprised ~1200 m3 of sediment deposited during 1 event. This yields an estimate of ~6200 m3 of sediment accumulation in 57 years, or an average of ~110 m3/yr prior to the fire, equivalent to an average basin-wide denudation rate of ~ 0.007 mm/yr. This low rate is consistent with the well-vegetated nature of the basin prior to the fire, and the absence of evidence for extensive surface runoff and erosion. When the total station survey was repeated in June 2001, a large delta front consisting of gravels and sands had formed a subaerial platform at the head of the reservoir. The post-fire deposits also

  12. The NHMFL Pulsed Field Facility at Los Alamos National Lab

    NASA Astrophysics Data System (ADS)

    Mielke, Chuck

    2014-03-01

    National user facilities provide scientists and industrial development companies with access to specialized experimental capabilities to enable development of materials and solve long standing technical problems. Magnetic fields have become an indispensable tool for researchers to better understand and manipulate ground states of electronic materials. As magnetic field intensities are increased the quantum nature of these materials become exponentially more likely to be observed and this is but one of the drivers to go further in high magnetic field generation. At the Los Alamos branch of the National High Magnetic Field Laboratory we have significant efforts in extremely high magnetic field generation and experimentation. In direct opposition with our efforts are the tremendous electro-mechanical forces exerted on our magnets and the electromagnetic interference that couples to the sample under study and the diagnostic equipment. Challenges in magnetic field generation and research will be presented. Various methods of pulsed high magnetic field generation and experimentation capabilities will be reviewed, including our recent ``World Record'' for the highest non-destructive magnetic field. NSF-DMR 1157490.

  13. Los Alamos High-Brightness Accelerator FEL (HIBAF) facility

    SciTech Connect

    Cornelius, W.D.; Bender, S.; Meier, K.; Thode, L.E.; Watson, J.M.

    1989-01-01

    The 10-/mu/m Los Alamos free-electron laser (FEL) facility is being upgraded. The conventional electron gun and bunchers have been replaced with a much more compact 6-MeV photoinjector accelerator. By adding existing parts from previous experiments, the primary beam energy will be doubled to 40 MeV. With the existing 1-m wiggler (/lambda//sub w/ = 2.7 cm) and resonator, the facility can produce photons with wavelengths from 3 to 100 /mu/m when lasing on the fundamental mode and produce photons in the visible spectrum with short-period wigglers or harmonic operation. After installation of a 150/degree/ bend, a second wiggler will be added as an amplifier. The installation of laser transport tubes between the accelerator vault and an upstairs laboratory will provide experimenters with a radiation-free environment for experiments. Although the initial experimental program of the upgraded facility will be to test the single accelerator-master oscillator/power amplifier configuration, some portion of the operational time of the facility can be dedicated to user experiments. 13 refs., 5 figs., 6 tabs.

  14. Chemical decontamination technical resources at Los Alamos National Laboratory (2008)

    SciTech Connect

    Moore, Murray E

    2008-01-01

    This document supplies information resources for a person seeking to create planning or pre-planning documents for chemical decontamination operations. A building decontamination plan can be separated into four different sections: Pre-planning, Characterization, Decontamination (Initial response and also complete cleanup), and Clearance. Of the identified Los Alamos resources, they can be matched with these four sections: Pre-planning -- Dave Seidel, EO-EPP, Emergency Planning and Preparedness; David DeCroix and Bruce Letellier, D-3, Computational fluids modeling of structures; Murray E. Moore, RP-2, Aerosol sampling and ventilation engineering. Characterization (this can include development projects) -- Beth Perry, IAT-3, Nuclear Counterterrorism Response (SNIPER database); Fernando Garzon, MPA-11, Sensors and Electrochemical Devices (development); George Havrilla, C-CDE, Chemical Diagnostics and Engineering; Kristen McCabe, B-7, Biosecurity and Public Health. Decontamination -- Adam Stively, EO-ER, Emergency Response; Dina Matz, IHS-IP, Industrial hygiene; Don Hickmott, EES-6, Chemical cleanup. Clearance (validation) -- Larry Ticknor, CCS-6, Statistical Sciences.

  15. Population Files for use with CAP88 at Los Alamos

    SciTech Connect

    McNaughton, Michael W; Brock, Burgandy R

    2012-07-10

    CAP88 (Clean Air Act Assessment Package 1988) is a computer model developed for the US Environmental Protection Agency to assess the potential dose from radionuclide emissions to air and to demonstrate compliance with the Clean Air Act. It has options to calculate either individual doses, in units of mrem, or a collective dose, also called population dose, in units of person-rem. To calculate the collective dose, CAP88 uses a population file such as LANL.pop, that lists the number of people in each sector (N, NNE, NE, etc.) as a function of distance (1 to 2 km, etc.) out to a maximum radius of 80 km. Early population files are described in the Los Alamos National Laboratory (LANL) Environmental Reports for 1985 (page 14) and subsequent years. LA-13469-MS describes a population file based on the 1990 census. These files have been updated several times, most recently in 2006 for CAP88 version 3. The 2006 version used the US census for 2000. The present paper describes the 2012 updates, using the 2010 census.

  16. HELIOSEISMIC TESTS OF THE NEW LOS ALAMOS OPACITIES

    SciTech Connect

    J. GUZIK; ET AL

    2001-01-01

    We compare the helioseismic properties of two solar models, one calibrated with the OPAL opacities and the other with the recent Los Alamos LEDCOP opacities. We show that, in the radiative interior of the Sun, the small differences between the two sets of opacities (up to 6% near the base of the convection zone) lead to noticeable differences in the solar structure (up to 0.4% in sound speed), with the OPAL model being the closest to the helioseismic data. More than half of the difference between the two opacity sets results from the interpolation scheme and from the relatively widely spaced temperature grids used in the tables. The remaining 3% intrinsic difference between the OPAL and the LEDCOP opacities in the radiative interior of the Sun is well within the error bars on the opacity calculations resulting from the uncertainties on the physics. We conclude that the OPAL and LEDCOP opacity sets do about as well in the radiative interior of the Sun.

  17. Organizational cultural survey of the Los Alamos Site

    SciTech Connect

    Not Available

    1991-11-01

    An Organizational Survey (OS) was administered at the Los Alamos Site that queried employees on the subjects of organizational culture, various aspects of communications, employee commitment, work group cohesion, coordination of work, environmental, safety, and health concerns, hazardous nature of work, safety and overall job satisfaction. The purpose of the OS is to measure in a quantitative and objective way the notion of culture;'' that is, the values, attitudes, and beliefs of the individuals working within the organization. In addition, through the OS, a broad sample of individuals can be reached that would probably not be interviewed or observed during the course of a typical assessment. The OS also provides a descriptive profile of the organization at one point in time that can then be compared to a profile taken at a different point in time to assess changes in the culture of the organization. While comparisons among groups are made, it is not the purpose of this report to make evaluative statements of which profile may be positive or negative. However, using the data presented in this report in conjunction with other evaluative activities, may provide useful insight into the organization.

  18. Organizational cultural survey of the Los Alamos Site

    SciTech Connect

    Not Available

    1991-11-01

    An Organizational Survey (OS) was administered at the Los Alamos Site that queried employees on the subjects of organizational culture, various aspects of communications, employee commitment, work group cohesion, coordination of work, environmental, safety, and health concerns, hazardous nature of work, safety and overall job satisfaction. The purpose of the OS is to measure in a quantitative and objective way the notion of ``culture;`` that is, the values, attitudes, and beliefs of the individuals working within the organization. In addition, through the OS, a broad sample of individuals can be reached that would probably not be interviewed or observed during the course of a typical assessment. The OS also provides a descriptive profile of the organization at one point in time that can then be compared to a profile taken at a different point in time to assess changes in the culture of the organization. While comparisons among groups are made, it is not the purpose of this report to make evaluative statements of which profile may be positive or negative. However, using the data presented in this report in conjunction with other evaluative activities, may provide useful insight into the organization.

  19. Progress on the Los Alamos heavy-ion injector

    SciTech Connect

    Wilson, D.C.; Riepe, K.B.; Ballard, E.O.; Meyer, E.A.; Shurter, R.P.; Van Haaften, F.W.; Humphries, S. Jr.

    1986-01-01

    Heavy-ion fusion using an induction linac requires injection of multiple high-current beams from a pulsed electrostatic accelerator at as high a voltage as practical. Los Alamos National Laboratory is developing a 16-beam, 2-MeV, pulsed electrostatic accelerator for Al/sup +/ ions. The ion source will use a pulsed metal vapor arc plasma. A biased grid will control plasma flux into the ion extraction region. This source has achieved a normalized emittance of epsilon/sub n/ < 3.10/sup -7/..pi..-m-rad with Al/sup +/ ions. An 800 kV Marx prototype with a laser fired diverter is being assembled. The ceramic accelerating column sections have been brazed and leak tested. Voltage hold off on a brazed sample was more than doubled by selective removal of the Ticusil braze fillet extending along the ceramic. A scaled test module held 250 kV for 50 ..mu..s, giving confidence that the full module can hold 175 kV per section. The pressure vessel should be received in June 1986. High-voltage testing of a 1 MV column will begin by early 1987.

  20. Factors affecting radionuclide availability to vegetables grown at Los Alamos

    SciTech Connect

    White, G.C.; Hakonson, T.E.; Ahlquist, A.J.

    1981-07-01

    A field study was conducted in 1977 on /sup 238/ /sup 239/Pu and /sup 137/Cs availability to zucchini squash (Curcurbita melopepo, hybrid seneca) and green bush beans (Phaseolus vulgaris, Landreths stringless) grown under home-garden conditions in an area at Los Alamos National Laboratory used for treated radioactive liquid waste disposal. Radionuclide concentrations were measured as a function of tissue type, height above the soil, fertilization regime, and for the squash, food-cleansing procedures. Analysis of variance procedures was used to analyze the data. Ratios of the concentration of a radionuclide in oven-dried vegetation to dry soil ranged from 0.0004 to 0.116 for the Pu isotopes, and from 0.051 to 0.255 for /sup 137/Cs. Fertilization with cattle manure reduced the Pu concentration ratios by 30% and /sup 137/Cs by 50%. Vegetative parts sampled within 20 cm of the ground surface were contaminated about four times as much as those parts growing further from the ground surface. About 65% of the contamination was removed by washing, indicating the presence of surficial contamination. The 50-year radiation dose commitment to humans consuming vegetables from the garden plot would be less than 0.05 mrem and would be due almost entirely to /sup 137/Cs.

  1. ACCELERATION OF LOS ALAMOS NATIONAL LABORATORY TRANSURANIC WASTE DISPOSITION

    SciTech Connect

    O'LEARY, GERALD A.

    2007-01-04

    One of Los Alamos National Laboratory's (LANL's) most significant risks is the site's inventory of transuranic waste retrievably stored above and below-ground in Technical Area (TA) 54 Area G, particularly the dispersible high-activity waste stored above-ground in deteriorating facilities. The high activity waste represents approximately 50% (by activity) of the total 292,000 PE-Ci inventory remaining to be disposed. The transuramic waste inventory includes contact-handled and remote-handled waste packaged in drums, boxes, and oversized containers which are retrievably stored both above and below-ground. Although currently managed as transuranic waste, some of the inventory is low-level waste that can be disposed onsite or at approved offsite facilities. Dispositioning the transuranic waste inventory requires retrieval of the containers from above and below-ground storage, examination and repackaging or remediation as necessary, characterization, certification and loading for shipment to the Waste Isolation Pilot Plant in Carlsbad New Mexico, all in accordance with well-defined requirements and controls. Although operations are established to process and characterize the lower-activity contact-handled transuranic waste containers, LAN L does not currently have the capability to repack high activity contact-handled transuranic waste containers (> 56 PE-Ci) or to process oversized containers with activity levels over 0.52 PE-Ci. Operational issues and compliance requirements have resulted in less than optimal processing capabilities for lower activity contact-handled transuranic waste containers, limiting preparation and reducing dependability of shipments to the Waste Isolation Pilot Plant. Since becoming the Los Alamos National Laboratory contract in June 2006, Los Alamos National Security (LANS) L.L.C. has developed a comprehensive, integrated plan to effectively and efficiently disposition the transuranic waste inventory, working in concert with the Department of

  2. Electron clearing in the Los Alamos Proton Storage Ring

    SciTech Connect

    Plum, M.A.; Allen, J.; Borden, M.J.; Fitzgerald, D.H.; Macek, R.J.; Wang, T.S.

    1995-05-01

    The instability observed in the Los Alamos Proton Storage Ring (PSR) has been tentatively identified as an electron-proton instability. A source of electrons must exist for this instability to occur. The PSR injection section contains the stripper foil, and therefore provides several strong sources of electrons. An electron clearing system was installed in the injection section to clear out these electrons. The system comprised: (1) a foil biasing system to clear the SEM and thermionic electrons, (2) a pair of low-field bending magnets with a Faraday cup to clear the convoy electrons, and (3) two pairs of clearing electrodes, one upstream and one downstream of the stripper foil, to clear the remaining electrons. This paper discusses the design and performance of the Electron Clearing System, and its effect on the instability. Also presented are some results from other charge-collection experiments that suggest there is also substantial electron production in parts of the ring other than the injection section.

  3. Carbon stripper foils used in the Los Alamos PSR

    SciTech Connect

    Borden, M.J.; Plum, M.A.; Sugai, I.

    1997-12-01

    Carbon stripper foils produced by the modified controlled ACDC arc discharge method (mCADAD) at the Institute for Nuclear Study have been tested and used for high current 800-MeV beam production in the Proton Storage Ring (PSR) since 1993. Two foils approximately 110 {mu}g/cm{sup 2} each are sandwiched together to produce an equivalent 220 {mu}g/cm{sup 2} foil. The foil sandwitch is supported by 4-5 {mu}m diameter carbon filters attached to an aluminum frame. These foils have survived as long as five months during PSR normal beam production of near 70 {mu}A average current on target. Typical life-times of other foils vary from seven to fourteen days with lower on-target average current. Beam loss data also indicate that these foils have slower shrinkage rates than standard foils. Equipment has been assembled and used to produce foils by the mCADAD method at Los Alamos. These foils will be tested during 1997 operation.

  4. Los Alamos high-current proton storage ring

    NASA Astrophysics Data System (ADS)

    Lawrence, G. P.; Hardekopf, R. A.; Jason, A. J.; Clout, P. N.; Sawyer, G. A.

    1985-05-01

    The Proton Storage Ring (PSR), whose installation was recently completed at Los Alamos, is a fast-cycling high-current accumulator designed to produce intense 800 MeV proton pulses for driving a spallation neutron source. The ring converts long beam pulses from the LAMPF linear accelerator into short bunches well matched to requirements of a high-resolution neutron-scattering materials science program. The initial performance goal for this program is to provide 100-(MU)A average current at the neutron production target within a 12-Hz pulse rate. Operation at 20 (MU)A is scheduled for September 1985, with full intensity within the next year. The storage ring was originally designed to function in a second mode in which six 1-ns bunches are accumulated and separately extracted every LAMPF macropulse. Implementation of this mode, which would serve a fast-neutron nuclear-physics program, was deferred in favor of initial concentration on the neutron-scattering program. The PSR design and status is summarized. Unique machine features include high peak current, two-step charge-stripping injection, a low-impedance buncher amplifier to counter beam-loading, and a high-repetition-rate strip-line extraction kicker.

  5. Los Alamos Shows Airport Security Technology at Work

    ScienceCinema

    Espy, Michelle; Schultz, Larry; Hunter, James

    2016-07-12

    Los Alamos scientists have advanced a Magnetic Resonance Imaging (MRI) technology that may provide a breakthrough for screening liquids at airport security. They've added low-power X-ray data to the mix, and as a result have unlocked a new detection technology. Funded in part by the Department of Homeland Security's Science and Technology Directorate, the new system is named MagRay. The goal is to quickly and accurately distinguish between liquids that visually appear identical. For example, what appears to be a bottle of white wine could potentially be nitromethane, a liquid that could be used to make an explosive. Both are clear liquids, one would be perfectly safe on a commercial aircraft, the other would be strictly prohibited. How to tell them apart quickly without error at an airport security area is the focus of Michelle Espy, Larry Schultz and their team. In this video, Espy and the MagRay team explain how the new technology works, how they've developed an easy operator interface, and what the next steps might be in transitioning this technology to the private sector.

  6. Wildlife use of NPDES outfalls at Los Alamos National Laboratory

    SciTech Connect

    Foxx, T.; Blea-Edeskuty, B.

    1995-09-01

    From July through October of 1991, the Biological Resources Evaluation Team (BRET) surveyed 133 of the 140 National Pollutant Discharge and Elimination System outfalls at Los Alamos National Laboratory (LANL). The purpose of the survey was to determine the use of these wastewater outfalls by wildlife. BRET observed wildlife or evidence of wildlife (scat, tracks, or bedding) by 35 vertebrate species in the vicinity of the outfalls, suggesting these animals could be using water from outfalls. Approximately 56% of the outfalls are probably used or are suitable for use by large mammals as sources of drinking water. Additionally, hydrophytic vegetation grows in association with approximately 40% of the outfalls-a characteristic that could make these areas eligible for wetland status. BRET recommends further study to accurately characterize the use of outfalls by small and medium-sized mammals and amphibians. The team also recommends systematic aquatic macroinvertebrate studies to provide information on resident communities and water quality. Wetland assessments may be necessary to ensure compliance with wetland regulations if LANL activities affect any of the outfalls supporting hydrophytic vegetation.

  7. Atomic Structure Calculations from the Los Alamos Atomic Physics Codes

    DOE Data Explorer

    Cowan, R. D.

    The well known Hartree-Fock method of R.D. Cowan, developed at Los Alamos National Laboratory, is used for the atomic structure calculations. Electron impact excitation cross sections are calculated using either the distorted wave approximation (DWA) or the first order many body theory (FOMBT). Electron impact ionization cross sections can be calculated using the scaled hydrogenic method developed by Sampson and co-workers, the binary encounter method or the distorted wave method. Photoionization cross sections and, where appropriate, autoionizations are also calculated. Original manuals for the atomic structure code, the collisional excitation code, and the ionization code, are available from this website. Using the specialized interface, you will be able to define the ionization stage of an element and pick the initial and final configurations. You will be led through a series of web pages ending with a display of results in the form of cross sections, collision strengths or rates coefficients. Results are available in tabular and graphic form.

  8. Explorer at Los Alamos: A library for the future

    SciTech Connect

    Waters, M.; McDonald, J.

    1998-03-01

    Since 1993, Los Alamos National Laboratory, has been developing World Wide Web (WWW) applications to facilitate access to vast quantities of information critical to the successful operation of a nuclear weapons facility Explorer is a web-based tool that integrates full-text search and retrieval technology, custom user in interface faces, user-friendly navigation tools, extremely large document collections, and data collection and workflow applications. Explorer`s first major thrust was to enable quick access to regulatory and policy information used by Department of Energy facilities throughout the country. Today, Explorer users can easily search document collections containing, millions of pages of information scattered across Web sites around the country. Over fifteen large applications containing multiple collections are searchable through Explorer, and the subject areas range from DOE regulations to quality management-related resources to technology transfer opportunities. Explorer has succeeded because it provides quick and easy access to stored data across the Web; it saves time and reduces costs in comparison with traditional information distribution, access, and retrieval methods.

  9. World's Largest Gold Crystal Studied at Los Alamos

    ScienceCinema

    Vogel, Sven; Nakotte, Heinz

    2016-07-12

    When geologist John Rakovan needed better tools to investigate whether a dazzling 217.78-gram piece of gold was in fact the world's largest single-crystal specimen - a distinguishing factor that would not only drastically increase its market value but also provide a unique research opportunity - he traveled to Los Alamos National Laboratory's Lujan Neutron Scattering Center to peer deep inside the mineral using neutron diffractometry. Neutrons, different from other probes such as X-rays and electrons, are able to penetrate many centimeters deep into most materials. Revealing the inner structure of a crystal without destroying the sample - imperative, as this one is worth an estimated $1.5 million - would allow Rakovan and Lujan Center collaborators Sven Vogel and Heinz Nakotte to prove that this exquisite nugget, which seemed almost too perfect and too big to be real, was a single crystal and hence a creation of nature. Its owner, who lives in the United States, provided the samples to Rakovan to assess the crystallinity of four specimens, all of which had been found decades ago in Venezuela.

  10. Response of `Alamo` switchgrass (Panicum virgatum) to weed management practices

    SciTech Connect

    Sledge, S.L.; Walker, R.H.

    1995-11-01

    Field studies were conducted in 1992 and 1994 to evaluate herbicides that would provide weed control and biomass yield of `Alamo` switchgrass during the year of establishment. For grass weed control, bensulide was applied preplant incorporated (PPI) at 4.4 kg ai ha{sup -1}, while MSMA was applied postemergence over the top (POST) at 2.2 kg ai ha{sup -1} to switchgrass that had two to four leaves. Herbicides applied POST for control of broadleaf weed species included 2,4-D at 0.6 kg ai ha{sup -1} or metsulfuron at 0.02 kg ai ha{sup -1}. Herbicide treatments included bensulide and MSMA applied alone or in combination with s,3-D or metsulfuron. They were arranged in a randomized complete block design and replicated four times. Weed control, crop tolerance and yield data were taken over time. Bensulide or MSMA applied alone provided 80% or greater control of large crabgrass, broadleaf signalgrass and fall panicum for the two years. The addition of metsulfuron or 2,4-D provided acceptable control of smooth pigweed, prickly sida, pitted morningglory and sicklepod. MSMA treatments produced slight PANVI injury that ranged from 20 to 36%. Bensulide injury was mostly moderate ranging from 19 to 88%. Although less injury was recorded with MSMA treatments, bensulide treatments trended higher for establishment-year biomass production that averaged 5123 kg ha{sup -1} as compared to 4239 kg ha{sup -1} for MSMA treatments.

  11. Los Alamos Shows Airport Security Technology at Work

    SciTech Connect

    Espy, Michelle; Schultz, Larry; Hunter, James

    2013-11-25

    Los Alamos scientists have advanced a Magnetic Resonance Imaging (MRI) technology that may provide a breakthrough for screening liquids at airport security. They've added low-power X-ray data to the mix, and as a result have unlocked a new detection technology. Funded in part by the Department of Homeland Security's Science and Technology Directorate, the new system is named MagRay. The goal is to quickly and accurately distinguish between liquids that visually appear identical. For example, what appears to be a bottle of white wine could potentially be nitromethane, a liquid that could be used to make an explosive. Both are clear liquids, one would be perfectly safe on a commercial aircraft, the other would be strictly prohibited. How to tell them apart quickly without error at an airport security area is the focus of Michelle Espy, Larry Schultz and their team. In this video, Espy and the MagRay team explain how the new technology works, how they've developed an easy operator interface, and what the next steps might be in transitioning this technology to the private sector.

  12. Los Alamos National Laboratory 1995 self assessment report

    SciTech Connect

    1995-06-30

    The Los Alamos National Laboratory (LANL) Safeguards and Security (S and S) Assurance Program (AP) is designed to ensure the adequacy and effectiveness of the LANL S and S program. The Assurance Program provides a mechanism for discovering deficiencies, determining causes, conducting risk assessments, implementing corrective actions, and documenting the assessment process. Selection of organizations for self assessments is based on the criteria established in the LANL S and S Assurance Program. For FY 1995, 12 organizations were selected for self assessments, these organizations are identified fin the schedule at Appendix A. The S and S topical areas selected for review in each organization varied depending on their security interests and included: Program Planning and Management (PPM); Protection Program Operations (PPO); Material Control and Accountability (MC and A); Computer and Communications Security (COMPSEC and COMSEC); Information Security (INFOSEC); Personnel Security (PERSEC); and Operational Security (OPSEC). The objective was to ascertain the effectiveness of S and S programs in each organization, its formality of operations, and its integration with the overall Laboratory S and S program. The goal was to meet both the DOE self-assessment requirements and the UC performance criteria and document the results.

  13. Lessons learned from decommissioning projects at Los Alamos National Laboratory

    SciTech Connect

    Salazar, M.

    1995-09-01

    This paper describes lessons learned over the last 20 years from 12 decommissioning projects at Los Alamos National Laboratory. These lessons relate both to overall program management and to management of specific projects during the planning and operations phases. The issues include waste management; the National Environmental Policy Act (NEPA); the Resource Conservation and Recovery Act (RCRA); the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA); contracting; public involvement; client/customer interface; and funding. Key elements of our approach are to be proactive; follow the observation method; perform field activities concurrently; develop strategies to keep reportable incidents from delaying work; seek and use programs, methods, etc., in existence to shorten learning curves; network to help develop solutions; and avoid overstudying and overcharacterizing. This approach results in preliminary plans that require very little revision before implementation, reasonable costs and schedules, early acquisition of permits and NEPA documents, preliminary characterization reports, and contracting documents. Our track record is good -- the last four projects (uranium and plutonium-processing facility and three research reactors) have been on budget and on schedule.

  14. Los Alamos National Laboratory compliance with cultural resource management legislation

    SciTech Connect

    Olinger, C.E.; Rea, K.H.

    1984-01-01

    Cultural resources management is one aspect of NEPA-induced legislation increasingly affecting federal land managers. A number of regulations, some of them recent, outline management criteria for protecting cultural resources on federal land. Nearly all construction projects at the 11,135 hectare Los Alamos National Laboratory in northern New Mexico are affected by cultural resource management requirements. A substantial prehistoric Puebloan population occupied the Laboratory area from the 13th to the early 16th centuries. Grazing, timbering, and homesteading followed Indian occupation. Therefore, archaeological and historical ruins and artifacts are abundant. The Laboratory has developed a cultural resources management program which meets both legal and project planning requirements. The program operates in coordination with the New Mexico State Historical Preservation Office. Major elements of the Laboratory program are illustrated by a current project involving relocation of a homesteader's cabin located on land required for a major new facility. The Laboratory cultural resource management program couples routine oversight of all engineering design projects with onsite resource surveys and necessary mitigation prior to construction. The Laboratory has successfully protected major archaeological and historical ruins, although some problems remain. The cultural resource program is intended to be adjustable to new needs. A cultural resource management plan will provide long-term management guidance.

  15. Results from the Argonne, Los Alamos, JAERI collaboration

    SciTech Connect

    Meadows, J.; Smith, D.; Greenwood, L.; Haight, R.; Ikeda, Y.; Konno, C.

    1993-07-01

    Four sample packets containing elemental Ti, Fe, Ni, Cu, Nb, Ag, Eu, Tb and Hf have been irradiated in three distinct accelerator neutron fields, at Argonne National Laboratory and Los Alamos National Laboratory, USA, and Japan Atomic Energy Research Institute, Tokai, Japan. The acquired experimental data include differential cross sections and integral cross sections for the continuum neutron spectrum produced by 7-MeV deuterons incident on thick Be-metal target. The U-238(n,f) cross section was also measured at 10.3 MeV as a consistency check on the experimental technique. This the third progress report on a project which has been carried out under the auspices of an IAEA Coordinated Research Program entitled ``Activation Cross Sections for the Generation Of Long-lived Radionuclides of Importance in Fusion Reactor Technology``. The present report provides the latest results from this work. Comparison is made between the 14.7-MeV cross-section values obtained from the separate investigations at Argonne and JAERI. Generally, good agreement observed within the experimental errors when consistent sample parameters, radioactivity decay data and reference cross values are employed. A comparison is also made between the experimental results and those derived from calculations using a nuclear model. Experimental neutron information on the Be(d,n) neutron spectrum was incorporated in the comparisons for the integral results. The agreement is satisfactory considering the various uncertainties that are involved.

  16. Los Alamos Plutonium Facility newly generated TRU waste certification

    SciTech Connect

    Gruetzmacher, K.; Montoya, A.; Sinkule, B.; Maez, M.

    1997-02-01

    This paper presents an overview of the activities being planned and implemented to certify newly generated contact handled transuranic (TRU) waste produced by Los Alamos National Laboratory`s (LANL`s) Plutonium Facility. Certifying waste at the point of generation is the most important cost and labor saving step in the WIPP certification process. The pedigree of a waste item is best known by the originator of the waste and frees a site from expensive characterization activities such as those associated with legacy waste. Through a cooperative agreement with LANLs Waste Management Facility and under the umbrella of LANLs WIPP-related certification and quality assurance documents, the Plutonium Facility will be certifying its own newly generated waste. Some of the challenges faced by the Plutonium Facility in preparing to certify TRU waste include the modification and addition of procedures to meet WIPP requirements, standardizing packaging for TRU waste, collecting processing documentation from operations which produce TRU waste, and developing ways to modify waste streams which are not certifiable in their present form.

  17. World's Largest Gold Crystal Studied at Los Alamos

    SciTech Connect

    Vogel, Sven; Nakotte, Heinz

    2014-04-03

    When geologist John Rakovan needed better tools to investigate whether a dazzling 217.78-gram piece of gold was in fact the world's largest single-crystal specimen - a distinguishing factor that would not only drastically increase its market value but also provide a unique research opportunity - he traveled to Los Alamos National Laboratory's Lujan Neutron Scattering Center to peer deep inside the mineral using neutron diffractometry. Neutrons, different from other probes such as X-rays and electrons, are able to penetrate many centimeters deep into most materials. Revealing the inner structure of a crystal without destroying the sample - imperative, as this one is worth an estimated $1.5 million - would allow Rakovan and Lujan Center collaborators Sven Vogel and Heinz Nakotte to prove that this exquisite nugget, which seemed almost too perfect and too big to be real, was a single crystal and hence a creation of nature. Its owner, who lives in the United States, provided the samples to Rakovan to assess the crystallinity of four specimens, all of which had been found decades ago in Venezuela.

  18. Use Of Lasers At The Los Alamos Hot Cell Facility

    NASA Astrophysics Data System (ADS)

    Lazarus, Michael E.

    1983-11-01

    An optical profilometer that uses a Techmet LaserMike scanning, focused, laser-beam, optical micrometer is installed in a remote alpha-gamma containment cell at the Los Alamos Hot-Cell Facility.1 A hot-cell extension chamber provides the nominal 30-cm (12-in.) working distance required by the LaserMike and, at the same time, keeps the LaserMike components outside the high-radiation-containment environment. This system provides measurement accu-racy better than±5 pm (0.0002 in.) on diameters between 2 and 13 mm (0.08 and 0.5 in.) at a rate of 33 measurements per second. The Hot-Cell Facility also uses a Korad 20-J-output ruby pulsed laser to drill a hole in reactor fuel element cladding to sample fission gas. The laser is then used to reweld the hole so that the fuel element will not be contaminated and may be stored without an alpha-containment barrier. The wall thickness of the fuel elements sampled varies from 0.25 to 0.50 mm (0.010 to 0.020 in.).

  19. Final Progress Report: Internship at Los Alamos National Laboratory

    SciTech Connect

    Dunham, Ryan Q.

    2012-08-10

    Originally I was tasked fluidized bed modeling, however, I changed projects. While still working with ANSYS Fluent, I performed a study of particle tracks in glove boxes. This is useful from a Health-Physics perspective, dealing respirable particles that can be hazardous to the human body. I iteratively tested different amounts of turbulent particles in a steady-state flow. The goal of this testing was to discover how Fluent handles built-in Rosin-Rammler distributions for particle injections. I worked on the health physics flow problems and distribution analysis under the direction of two mentors, Bruce Letellier and Dave Decroix. I set up and ran particle injection calculations using Fluent. I tried different combinations of input parameters to produce sets of 500,000, 1 million, and 1.5 million particles to determine what a good test case would be for future experiments. I performed a variety of tasks in my work as an Undergraduate Student Intern at LANL this summer, and learned how to use a powerful CFD application in addition to expanding my skills in MATLAB. I enjoyed my work at LANL and hope to be able to use the experience here to further my career in the future working in a security-conscious environment. My mentors provided guidance and help with all of my projects and I am grateful for the opportunity to work at Los Alamos National Laboratory.

  20. Los Alamos climatology summary including latest normals from 1961--1990

    SciTech Connect

    Bowen, B.M.

    1992-03-01

    This report contains a summary of Los Alamos climate and analyses of basic weather variables from late 1910 through 1991. The first few sections offer a description of the local geography and large-scale weather patterns that affect Los Alamos. Temperature and precipitation analyses are presented in the next few sections. Updated 30-year temperature and precipitation normals ending in 1990 are shown for Los Alamos and White Rock. Normal snowfall is also shown for Los Alamos. Extremes of temperature, precipitation, and snowfall and averages of weather variables are also given. A section then discusses the changes of the latest 30-year normals. Another section describes the winds in Los Alamos. Brief descriptions of, humidity, sunshine, atmospheric pressure, and pollutant dispersal appear in the following sections. The report ends with brief descriptions of other weather phenomena that occur in Los Alamos. Appendices include locations of weather stations, normal heating and cooling degree-days, growing-season data, and English/metric unit conversions.

  1. Frequency and implications of HIV superinfection.

    PubMed

    Redd, Andrew D; Quinn, Thomas C; Tobian, Aaron A R

    2013-07-01

    HIV superinfection occurs when an individual with HIV is infected with a new distinct HIV viral strain. Superinfection has been reported throughout the world, and studies have recorded incidence rates of 0-7·7% per year. Use of next-generation sequencing has improved detection of superinfection, which can be transmitted by injecting drug use and sexual intercourse. Superinfection might have incidence rates comparable to those of initial HIV infection. Clinicians should encourage safe sexual and injecting drug use practices for HIV-infected patients because superinfection has detrimental effects on clinical outcomes and could pose a concern for large-scale antiretroviral treatment plans. The occurrence of superinfection has implications for vaccine research, since it seems initial HIV infection is not fully protective against a subsequent infection. Additional collaborative research could benefit care of patients and inform future vaccine design.

  2. [Analysis of genetic recombination between human immunodeficiency virus type 1 (HIV-1) and HIV-2].

    PubMed

    Motomura, Kazushi

    2009-03-01

    It is estimated that one million people are dually infected with Human Immunodeficiency Virus type-I (HIV-1) and type-II (HIV-2) in West Africa and parts of India. HIV-1 and HIV-2 use the same receptor and coreceptors for entry into cells, and thus target the same cell populations in the host. Additionally, we first examined whether RNAs from HIV-1 and HIV-2 can be copackaged into the same virion. Therefore these properties suggest that in the dually infected population, it is likely that some cells can be infected by both HIV-1 and HIV-2, thereby providing opportunities for these two viruses to interact with each other. We constructed recombination assay system for measurement recombination frequencies and analyzed recombination rate between HIV-1 and HIV-2. We used modified near-full-length viruses that each contained a green fluorescent protein gene (gfp) with a different inactivating mutation. Thus, a functional gfp could be reconstituted via recombination, which was used to detect copackaging of HIV-1 and HIV-2 RNAs. In this study, approximately 0.2% of infection events generated the GFP phenotype. Therefore, the appearance of the GFP+ phenotype in the current system is approximately 35-fold lower than that between two homologous HIV-1 or HIV-2 viruses. We then mapped the general structures of the recombinant viruses and characterized the recombination junctions by DNA sequencing. We observed several different recombination patterns including those only had crossovers in gfp. The most common hybrid genomes had heterologous LTRs. Although infrequent, crossovers were also identified in the viral sequences. Such chimeric HIV-1 and HIV-2 viruses have yet to be observed in the infected population. It is unclear whether the lack of observed chimeras is due to the divergence between HIV-1 and HIV-2 being too great for such an event to occur, or whether such events could occur but have not yet been observed. Given the number of coinfected people, the potential for

  3. Unique C2V3 Sequence in HIV-1 Envelope Obtained from Broadly Neutralizing Plasma of a Slow Progressing Patient Conferred Enhanced Virus Neutralization

    PubMed Central

    Ringe, Rajesh; Das, Lipsa; Choudhary, Ipsita; Sharma, Deepak; Paranjape, Ramesh; Chauhan, Virander Singh; Bhattacharya, Jayanta

    2012-01-01

    Broadly neutralizing antibodies to HIV-1 usually develops in chronic infections. Here, we examined the basis of enhanced sensitivity of an env clone amplified from cross neutralizing plasma of an antiretroviral naïve chronically infected Indian patient (ID50 >600-fold higher compared to other autologous env clones). The enhanced autologous neutralization of pseudotyped viruses expressing the sensitive envelope (Env) was associated with increased sensitivity to reagents and monoclonal antibodies targeting distinct sites in Env. Chimeric viruses constructed by swapping fragments of sensitive Env into resistant Env backbone revealed that the presence of unique residues within C2V3 region of gp120 governed increased neutralization. The enhanced virus neutralization was also associated with low CD4 dependence as well as increased binding of Env trimers to IgG1b12 and CD4-IgG2 and was independent of gp120 shedding. Our data highlighted vulnerabilities in the Env obtained from cross neutralizing plasma associated with the exposure of discontinuous neutralizing epitopes and enhanced autologous neutralization. Such information may aid in Env-based vaccine immunogen design. PMID:23056416

  4. Children and HIV

    MedlinePlus

    ... National HIV/AIDS and Aging Awareness Day National Gay Men's HIV/AIDS Awareness Day National Latinx AIDS ... who have lived with HIV since they were born are living productive and healthy lives. Can HIV ...

  5. Environmental assessment for the proposed CMR Building upgrades at the Los Alamos National Laboratory, Los Alamos, New Mexico. Final document

    SciTech Connect

    1997-02-04

    In order to maintain its ability to continue to conduct uninterrupted radioactive and metallurgical research in a safe, secure, and environmentally sound manner, the US Department of Energy (DOE) proposes to upgrade the Los Alamos National Laboratory (LANL) Chemistry and Metallurgy Research (CMR) Building. The building was built in the early 1950s to provide a research and experimental facility for analytical chemistry, plutonium and uranium chemistry, and metallurgy. Today, research and development activities are performed involving nuclear materials. A variety of radioactive and chemical hazards are present. The CMR Building is nearing the end of its original design life and does not meet many of today`s design codes and standards. The Proposed Action for this Environmental Assessment (EA) includes structural modifications to some portions of the CMR Building which do not meet current seismic criteria for a Hazard Category 2 Facility. Also included are upgrades and improvements in building ventilation, communications, monitoring, and fire protection systems. This EA analyzes the environmental effects of construction of the proposed upgrades. The Proposed Action will have no adverse effects upon agricultural and cultural resources, wetlands and floodplains, endangered and threatened species, recreational resources, or water resources. The Proposed Action would have negligible effects on human health and transportation, and would not pose a disproportionate adverse health or environmental impact on minority or low-income populations within an 80 kilometer (50 mile) radius of the CMR Building.

  6. Geology and physical properties of the near-surface rocks of Mesita de los Alamos, Los Alamos County, New Mexico

    USGS Publications Warehouse

    Purtymun, W.D.

    1967-01-01

    The surface of Mesita de los Alamos is formed by units 2b and 3 of the Tshirege Member of the Bandelier Tuff. These units dip gently east-southeastward at 3 to 6 degrees. The units are faulted near the center of the mesa by a north-south trending normal strike slip fault, that is downthrown about 14 feet to the east. The units east of the fault have moved about 14 feet south relative to the units on the west side of the fault. Units 2b and 3 have bulk density values ranging from 80 to 120 pounds per cubic foot. The moisture content of the tuff below the soil zone and near surface tuff was less than 5 percent by volume in five of the 25 test holes drilled during a foundation investigation for the Meson Facility. The temperature of the tuff in the bottom of three test holes (depth 16 to 43 feet) varied from 50?F to 54?F. Temperature variations were a function of density and amount of solar radiation.

  7. Environmental assessment for the scintillation vial crusher TA-54, Area L, Los Alamos National Laboratory, Los Alamos, New Mexico

    SciTech Connect

    Not Available

    1992-07-01

    Research and development projects conducted at the Los Alamos National Laboratory produce scintillation vials as waste from normal operations. These vials contain radioisotopes such as tritium, carbon-14, and isotopes of transuranic elements such as americium-241, plutonium-238 and -239. The scintillation fluids contain some solvents defined as hazardous waste. The vials are thus classed as mixed waste under the Resource Conservation and Recovery Act (RCRA). The Laboratory has in storage some 520 drums of stored vials and is accumulating some 70 to 140 more drums annually. The drained vial fragments can be disposed of at TA-54 as low-level radioactive waste (LLW). The bulked liquid will be stored at TA-54 as RCRA mixed waste until treatment/disposal options are developed. Other waste from the vial crushing operation will also be stored at TA-54 as mixed waste. By operating the scintillation vial crusher, the storage space needed for this RCRA mixed waste stream can be reduced to about 5% of that currently being used. The other 95% will be vial fragments that can be disposed immediately as LLW.

  8. Temporal association of HLA-B*81:01- and HLA-B*39:10-mediated HIV-1 p24 sequence evolution with disease progression.

    PubMed

    Ntale, R S; Chopera, D R; Ngandu, N K; Assis de Rosa, D; Zembe, L; Gamieldien, H; Mlotshwa, M; Werner, L; Woodman, Z; Mlisana, K; Abdool Karim, S; Gray, C M; Williamson, C

    2012-11-01

    HLA-B*81:01 and HLA-B*39:10 alleles have been associated with viremic control in HIV-1 subtype C infection. Both alleles restrict the TL9 epitope in p24 Gag, and cytotoxic-T-lymphocyte (CTL)-mediated escape mutations in this epitope have been associated with an in vitro fitness cost to the virus. We investigated the timing and impact of mutations in the TL9 epitope on disease progression in five B*81:01- and two B*39:10-positive subtype C-infected individuals. Whereas both B*39:10 participants sampled at 2 months postinfection had viruses with mutations in the TL9 epitope, in three of the five (3/5) B*81:01 participants, TL9 escape mutations were only detected 10 months after infection, taking an additional 10 to 15 months to reach fixation. In the two remaining B*81:01 individuals, one carried a TL9 escape variant at 2 weeks postinfection, whereas no escape mutations were detected in the virus from the other participant for up to 33 months postinfection, despite CTL targeting of the epitope. In all participants, escape mutations in TL9 were linked to coevolving residues in the region of Gag known to be associated with host tropism. Late escape in TL9, together with coevolution of putative compensatory mutations, coincided with a spontaneous increase in viral loads in two individuals who were otherwise controlling the infection. These results provide in vivo evidence of the detrimental impact of B*81:01-mediated viral evolution, in a single Gag p24 epitope, on the control of viremia.

  9. Human immunodeficiency virus (HIV) transcripts identified in HIV-related psoriasis and Kaposi's sarcoma lesions.

    PubMed Central

    Mahoney, S E; Duvic, M; Nickoloff, B J; Minshall, M; Smith, L C; Griffiths, C E; Paddock, S W; Lewis, D E

    1991-01-01

    Persons with HIV infection sometimes develop aggressive psoriasis or Kaposi's sarcoma (KS) not usually seen in other immunosuppressed patients. However, a specific and direct pathophysiological role for HIV-1 in these AIDS-associated disorders remains unclear since HIV has not been easily detected in these skin lesions. By combining in situ hybridization with the sensitive detection technique of confocal laser scanning microscopy, we have demonstrated HIV RNA transcripts in 5 of 15 lesional skin biopsies from HIV-infected psoriasis patients, and in 3 of 8 Kaposi's sarcoma biopsies from HIV-infected patients. HIV transcripts were not detected in normal appearing skin from HIV-infected patients or in psoriatic and normal skin biopsies from uninfected individuals (P = 0.006). Although previous attempts to demonstrate viral sequences in psoriasis and KS lesions have been unsuccessful, in situ hybridization with confocal microscopy has shown the presence of HIV RNA transcripts predominantly within CD4+, Factor XIIIa positive dermal dendrocytes. HIV or cytokines produced by infected cells in skin lesions may therefore play a direct role in the pathogenesis of HIV-associated psoriasis and KS. Images PMID:1676036

  10. An aerial radiological survey of Technical Areas 2, 21, and 53 and surroundings, Los Alamos National Laboratory, Los Alamos, New Mexico

    SciTech Connect

    Fritzsche, A.E.

    1990-09-01

    An aerial radiological survey of the entire Los Alamos National Laboratory was flown in September 1982. The data from a part of the survey, Technical Areas 2, 21, and 53, are presented here along with pertinent data from an October 1975 survey of limited areas of Los Alamos. The data from Technical Area 15, another part of the survey, will be published in another report. Contour maps of the gamma survey data show some Cs-137 activity in Los Alamos Canyon as well as in DP Canyon beside TA-21. Some Be-7, Sb-124, and Co-58 apparently exist in the canyon immediately below the Los Alamos Meson Physics Facility (LAMPF) ponds. Estimates on the Cs-137 inventory in the canyons range from 210 mCi to 1270 mCi. An exposure rate contour map at 1 meter above ground level (AGL) was constructed from the gamma data and overlaid on an aerial photograph and map of the area. The terrestrial exposure rates ranged from 6{mu}R/h to about 18{mu}R/h. 25 figs., 3 tabs.

  11. Living with HIV

    MedlinePlus

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Syndicated Content Website Feedback HIV/AIDS Living With HIV Language: English Spanish Recommend on Facebook Tweet Share ...

  12. HIV Among Asians

    MedlinePlus

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Among Asians Format: Select One File [143K] Recommend ...

  13. Los Alamos National Laboratory W76 Pit Tube Lifetime Study

    SciTech Connect

    Abeln, Terri G.

    2012-04-25

    A metallurgical study was requested as part of the Los Alamos National Laboratory (LANL) W76-1 life-extension program (LEP) involving a lifetime analysis of type 304 stainless steel pit tubes subject to repeat bending loads during assembly and disassembly operations at BWXT/Pantex. This initial test phase was completed during the calendar years of 2004-2006 and the report not issued until additional recommended tests could be performed. These tests have not been funded to this date and therefore this report is considered final. Tubes were reportedly fabricated according to Rocky Flats specification P14548 - Seamless Type 304 VIM/VAR Stainless Steel Tubing. Tube diameter was specified as 0.125 inches and wall thickness as 0.028 inches. A heat treat condition is not specified and the hardness range specification can be characteristic of both 1/8 and 1/4 hard conditions. Properties of all tubes tested were within specification. Metallographic analysis could not conclusively determine a specified limit to number of bends allowable. A statistical analysis suggests a range of 5-7 bends with a 99.95% confidence limit. See the 'Statistical Analysis' section of this report. The initial phase of this study involved two separate sets of test specimens. The first group was part of an investigation originating in the ESA-GTS [now Gas Transfer Systems (W-7) Group]. After the bend cycle test parameters were chosen (all three required bends subjected to the same amount of bend cycles) and the tubes bent, the investigation was transferred to Terri Abeln (Metallurgical Science and Engineering) for analysis. Subsequently, another limited quantity of tubes became available for testing and were cycled with the same bending fixture, but with different test parameters determined by T. Abeln.

  14. Los Alamos National Laboratory considers the use of biodiesel.

    SciTech Connect

    Matlin, M. K.

    2002-01-01

    A new EPA-approved alternative fuel, called biodiesel, may soon be used at Los Alamos National Laboratory in everything from diesel trucks to laboratory equipment. Biodiesel transforms vegetable oils into a renewable, cleaner energy source that can be used in any machinery that uses diesel fuel. For the past couple years, the Laboratory has been exploring the possibility of switching over to soybean-based biodiesel. This change could lead to many health and environmental benefits, as well as help reduce the nation's dependence on foreign oil. Biodiesel is a clean, renewable diesel fuel substitute made from soybean and other vegetable oil crops, as well as from recycled cooking oils. A chemical process breaks down the vegetable oil into a usable form. Vegetable oil has a chain of about 18 carbons and ordinary diesel has about 12 or 13 carbons. The process breaks the carbon chains of the vegetable oil and separates out the glycerin (a fatty substance used in creams and soaps). The co-product of glycerin can be used by pharmaceutical and cosmetic companies, as well as many other markets. Once the chains are shortened and the glycerin is removed from the oil, the remaining liquid is similar to petroleum diesel fuel. It can be burned in pure form or in a blend of any proportion with petroleum diesel. To be considered an alternative fuel source by the EPA, the blend must be at least 20 percent biodiesel (B20). According to the U.S. Department of Energy (DOE), biodiesel is America's fastest growing alternative fuel.

  15. ZERT Final Scientific Report Los Alamos National Laboratory

    SciTech Connect

    Pawar, Rajesh J.

    2011-01-01

    Los Alamos National Laboratory's (LANL) activities for the Center for Zero Emission Research and Technology (ZERT) have fallen into three broad research areas: (1) How do you reduce uncertainty in assuring prior to operation that an engineered geologic site will meet a specific performance goal (e.g., <0.01% leak per year)? (2) What are key monitoring needs for verifying that an engineered geologic site is meeting a performance goal? (3) What are potential vulnerabilities for breeches in containment of CO{sub 2}, and how could they be mitigated either prior to operation or in the event that a threshold is exceeded? We have utilized LANL's multi-disciplinary expertise and an integrated approach combining laboratory experiments, field observations and numerical simulations to address various research issues related to above-mentioned areas. While there have been a number of major milestones achieved as described in past quarterly reports, two of the major accomplishments resulting from LANL's efforts include: (1) Development of the CO{sub 2}-PENS systems framework for long-term performance analysis of geologic CO{sub 2} sequestration sites. CO{sub 2}-PENS is first-ever systems analysis tool designed for assessment of CO{sub 2} sequestration sites. (2) One of the few field studies to-date focused on understanding impact of CO{sub 2} leakage on shallow groundwater chemistry. Two major conclusions of the study are as follows: the impact of co-contaminants transported with deeper brine on shallow groundwater quality is likely to be much larger than that of the CO{sub 2} and CO{sub 2}-induced geochemical reactions and in certain geochemical environment the reactivity of pure CO{sub 2} will not be sufficient to mobilize metals beyond background levels.

  16. 2011 Los Alamos National Laboratory Riparian Inventory Results

    SciTech Connect

    Norris, Elizabeth J.; Hansen, Leslie A.; Hathcock, Charles D.; Keller, David C.; Zemlick, Catherine M.

    2012-03-29

    A total length of 36.7 kilometers of riparian habitat were inventoried within LANL boundaries between 2007 and 2011. The following canyons and lengths of riparian habitat were surveyed and inventoried between 2007 and 2011. Water Canyon (9,669 m), Los Alamos Canyon (7,131 m), Pajarito Canyon (6,009 m), Mortandad Canyon (3,110 m), Two-Mile Canyon (2,680 m), Sandia Canyon (2,181 m), Three-Mile Canyon (1,883 m), Canyon de Valle (1,835 m), Ancho Canyon (1,143 m), Canada del Buey (700 m), Sandia Canyon (221 m), DP Canyon (159 m) and Chaquehui Canyon (50 m). Effluent Canyon, Fence Canyon and Potrillo Canyon were surveyed but no areas of riparian habitat were found. Stretches of inventoried riparian habitat were classified for prioritization of treatment, if any was recommended. High priority sites included stretches of Mortandad Canyon, LA Canyon, Pajarito Canyon, Two-Mile Canyon, Sandia Canyon and Water Canyon. Recommended treatment for high priority sites includes placement of objects into the stream channel to encourage sediment deposition, elimination of channel incision, and to expand and slow water flow across the floodplain. Additional stretches were classified as lower priority, and, for other sites it was recommended that feral cattle and exotic plants be removed to aid in riparian habitat recovery. In June 2011 the Las Conchas Wildfire burned over 150,000 acres of land in the Jemez Mountains and surrounding areas. The watersheds above LA Canyon, Water Canyon and Pajarito Canyon were burned in the Las Conchas Wildfire and flooding and habitat alteration were observed in these canyon bottoms (Wright 2011). Post fire status of lower priority areas may change to higher priority for some of the sites surveyed prior to the Las Conchas Wildfire, due to changes in vegetation cover in the adjacent upland watershed.

  17. Initial performance of Los Alamos Advanced Free Electron Laser

    SciTech Connect

    Nguyen, D.C.; Baca, D.M.; Chan, K.C.D.; Cheairs, R.B.; Fortgang, C.M.; Gierman, S.M.; Johnson, W.J.D.; Holcomb, D.E.; Kinross-Wright, J.; McCann, S.W.; Meier, K.L.; Plato, J.G.; Sheffield, R.L.; Sherwood, B.A.; Sigler, F.E.; Timmer, C.A.; Warren, R.W.; Weber, M.E.; Wilson, W.L.

    1992-09-01

    We report recent results on the high-brightness electron linac and initial performance of the Advanced FEL at Los Alamos. The design and construction of the Advanced FEL beamline are based upon integration of advanced technologies such as high-brightness photoinjector, high-gradient compact linac, and permanent-magnet beamline components. With the use of microwiggler, both permanent magnet and pulsed electromagnet, and compact optical resonator, the Advanced FEL will be the first of its kind small enough to be mounted on an optical table and yet capable of providing highpower optical output spanning the near-ir and visible regions. A schematic of the Advanced FEL is shown in. The source of high-current electron pulses is a laser-gated photoelectron injector which forms-an integral part of a high-gradient 1.2-m long rf linear accelerator. The latter is capable of accelerating electrons up to 20 MeV with room temperature operation and 25 MeV at 77K. The electrons are produced in 10-ps pulses with peak currents as high as 300 A. These electron pulses are transported in a brightness-preserving beamline consisting of permanent magnet dipoles and quadrupoles. The beamline has three 30{degrees} bends. The first bend allows for the photocathode drive laser input; the second allows for the FEL output and the third turns the electron beam into the floor for safety reasons. Additional information on the design physics of the Advanced FEL can be found elsewhere.

  18. Initial performance of Los Alamos Advanced Free Electron Laser

    SciTech Connect

    Nguyen, D.C.; Baca, D.M.; Chan, K.C.D.; Cheairs, R.B.; Fortgang, C.M.; Gierman, S.M.; Johnson, W.J.D.; Holcomb, D.E.; Kinross-Wright, J.; McCann, S.W.; Meier, K.L.; Plato, J.G.; Sheffield, R.L.; Sherwood, B.A.; Sigler, F.E.; Timmer, C.A.; Warren, R.W.; Weber, M.E.; Wilson, W.L.

    1992-01-01

    We report recent results on the high-brightness electron linac and initial performance of the Advanced FEL at Los Alamos. The design and construction of the Advanced FEL beamline are based upon integration of advanced technologies such as high-brightness photoinjector, high-gradient compact linac, and permanent-magnet beamline components. With the use of microwiggler, both permanent magnet and pulsed electromagnet, and compact optical resonator, the Advanced FEL will be the first of its kind small enough to be mounted on an optical table and yet capable of providing highpower optical output spanning the near-ir and visible regions. A schematic of the Advanced FEL is shown in. The source of high-current electron pulses is a laser-gated photoelectron injector which forms-an integral part of a high-gradient 1.2-m long rf linear accelerator. The latter is capable of accelerating electrons up to 20 MeV with room temperature operation and 25 MeV at 77K. The electrons are produced in 10-ps pulses with peak currents as high as 300 A. These electron pulses are transported in a brightness-preserving beamline consisting of permanent magnet dipoles and quadrupoles. The beamline has three 30{degrees} bends. The first bend allows for the photocathode drive laser input; the second allows for the FEL output and the third turns the electron beam into the floor for safety reasons. Additional information on the design physics of the Advanced FEL can be found elsewhere.

  19. HIV Drug Resistance Surveillance Among Jamaican Men Who Have Sex with Men Should Be Prioritized for Reducing HIV Transmission

    PubMed Central

    Dennis, Ann M.; Nelson, Julie A.E.; Weir, Sharon S.; Figueroa, J. Peter

    2015-01-01

    Abstract The prevalence of human immunodeficiency virus type 1 (HIV-1) is highest among men who have sex with men (MSM) in Jamaica but no genotypic data are available on the virus strains that are responsible for the epidemic among this key population. HIV-1 polymerase (pol) genes from 65 MSM were sequenced and used to predict drug resistance mutations. An HIV drug resistance prevalence of 28% (minimum 13%) was observed among this cohort, with the most frequent mutations conferring resistance to efavirenz, nevirapine, and lamivudine. Phylogenetic analysis of the sequences revealed 10 times the number of linked HIV infections among this cohort than respondent reporting. HIV treatment and prevention efforts in Jamaica could benefit significantly from Pol genotyping of the HIV strains infecting socially vulnerable MSM prior to initiating antiretroviral therapy (ART), as this would guide suppressive ART and unearth HIV transmission clusters to enable more effective delivery of treatment and prevention programs. PMID:26133540

  20. Production of the p24 capsid protein from HIV-1 subtype C in Arabidopsis thaliana and Daucus carota using an endoplasmic reticulum-directing SEKDEL sequence in protein expression constructs.

    PubMed

    Lindh, Ingrid; Wallin, Anita; Kalbina, Irina; Sävenstrand, Helena; Engström, Peter; Andersson, Sören; Strid, Ake

    2009-07-01

    An optimized gene expression construct was designed in order to increase the accumulation of the HIV-1 subtype C p24 protein in Arabidopsis thaliana and carrot (Daucus carota) plants. An ER retention signal was introduced into the genetic construct generating a p24 protein containing a SEKDEL amino acid sequence at its C-terminus. Mature A. thaliana plants and carrot cells were transformed using Agrobacterium tumefaciens carrying the improved pGreen0229/p24_SEKDEL vector. Several transgenic plant lines were obtained from both plant species by growth on selective medium and confirmed by PCR. Transformed lines were analyzed for p24 protein content by western blotting using anti-p24-specific antibodies and by Southern blotting to establish the number of copies of the insert in the plant nuclear genome. To estimate the accumulation levels of p24 protein in the plants, ELISA was run using soluble plant extracts. By comparing these results with our previous findings, the ER retention signal increased the level of p24 protein fivefold in the A. thaliana plants. In carrot taproot, the content of p24_SEKDEL protein was approximately half of that in Arabidopsis on a fresh weight basis and was stable in planta for several months. However, on a total soluble protein basis, carrots produced considerable higher levels of the p24_SEKDEL protein than Arabidopsis.

  1. HIV Testing

    MedlinePlus

    ... the right way, every day. If you have health insurance, your insurer is required to cover some medicines ... to treat HIV. If you don’t have health insurance, or you’re unable to afford your co- ...

  2. Multimedia contaminant environmental exposure assessment methodology as applied to Los Alamos, New Mexico

    SciTech Connect

    Whelan, G.; Thompson, F.L.; Yabusaki, S.B.

    1983-02-01

    The MCEA (Multimedia Contaminant Environmental Exposure Assessment) methodology assesses exposures to air, water, soil, and plants from contaminants released into the environment by simulating dominant mechanisms of contaminant migration and fate. The methodology encompasses five different pathways (i.e., atmospheric, terrestrial, overland, subsurface, and surface water) and combines them into a highly flexible tool. The flexibility of the MCEA methodology is demonstrated by encompassing two of the pathways (i.e., overland and surface water) into an effective tool for simulating the migration and fate of radionuclides released into the Los Alamos, New Mexico region. The study revealed that: (a) the /sup 239/Pu inventory in lower Los Alamos Canyon increased by approximately 1.1 times for the 50-y flood event; (b) the average contaminant /sup 239/Pu concentrations (i.e., weighted according to the depth of the respective bed layer) in lower Los Alamos Canyon for the 50-y flood event decreased by 5.4%; (c) approx. 27% of the total /sup 239/Pu contamination resuspended from the entire bed (based on the assumed cross sections) for the 50-y flood event originated from lower Pueblo Canyon; (d) an increase in the /sup 239/Pu contamination of the bed followed the general deposition patterns experienced by the sediment in Pueblo-lower Los Alamos Canyon; likewise, a decrease in the /sup 239/Pu contamination of the bed followed general sediment resuspension patterns in the canyon; (e) 55% of the /sup 239/Pu reaching the San Ildefonso Pueblo in lower Los Alamos Canyon originated from lower Los Alamos Canyon; and (f) 56% of the /sup 239/Pu contamination reaching the San Ildefonso Pueblo in lower Los Alamos Canyon was carried through towards the Rio Grande. 47 references, 41 figures, 29 tables.

  3. The design of a peptide sequence to inhibit HIV replication: a search algorithm combining Monte Carlo and self-consistent mean field techniques.

    PubMed

    Xiao, Xingqing; Hall, Carol K; Agris, Paul F

    2014-01-01

    We developed a search algorithm combining Monte Carlo (MC) and self-consistent mean field techniques to evolve a peptide sequence that has good binding capability to the anticodon stem and loop (ASL) of human lysine tRNA species, tRNA(Lys3), with the ultimate purpose of breaking the replication cycle of human immunodeficiency virus-1. The starting point is the 15-amino-acid sequence, RVTHHAFLGAHRTVG, found experimentally by Agris and co-workers to bind selectively to hypermodified tRNA(Lys3). The peptide backbone conformation is determined via atomistic simulation of the peptide-ASL(Lys3) complex and then held fixed throughout the search. The proportion of amino acids of various types (hydrophobic, polar, charged, etc.) is varied to mimic different peptide hydration properties. Three different sets of hydration properties were examined in the search algorithm to see how this affects evolution to the best-binding peptide sequences. Certain amino acids are commonly found at fixed sites for all three hydration states, some necessary for binding affinity and some necessary for binding specificity. Analysis of the binding structure and the various contributions to the binding energy shows that: 1) two hydrophilic residues (asparagine at site 11 and the cysteine at site 12) "recognize" the ASL(Lys3) due to the VDW energy, and thereby contribute to its binding specificity and 2) the positively charged arginines at sites 4 and 13 preferentially attract the negatively charged sugar rings and the phosphate linkages, and thereby contribute to the binding affinity.

  4. Sequence-conserved and antibody-accessible sites in the V1V2 domain of HIV-1 gp120 envelope protein.

    PubMed

    Shmelkov, Evgeny; Grigoryan, Arsen; Krachmarov, Chavdar; Abagyan, Ruben; Cardozo, Timothy

    2014-09-01

    The immune-correlates analysis of the RV144 trial suggested that epitopes targeted by protective antibodies (Abs) reside in the V1V2 domain of gp120. We mapped V1V2 positional sequence variation onto the conserved V1V2 structural fold and showed that while most of the solvent-accessible V1V2 amino acids vary between strains, there are two accessible molecular surface regions that are conserved and also naturally antigenic. These sites may contain epitopes targeted by broadly cross-reactive anti-V1V2 antibodies.

  5. HIV-1 molecular epidemiology among newly diagnosed HIV-1 individuals in Hebei, a low HIV prevalence province in China

    PubMed Central

    Lu, Xinli; Kang, Xianjiang; Liu, Yongjian; Cui, Ze; Guo, Wei; Zhao, Cuiying; Li, Yan; Chen, Suliang; Li, Jingyun; Zhang, Yuqi; Zhao, Hongru

    2017-01-01

    New human immunodeficiency virus type 1 (HIV-1) diagnoses are increasing rapidly in Hebei. The aim of this study presents the most extensive HIV-1 molecular epidemiology investigation in Hebei province in China thus far. We have carried out the most extensive systematic cross-sectional study based on newly diagnosed HIV-1 positive individuals in 2013, and characterized the molecular epidemiology of HIV-1 based on full length gag-partial pol gene sequences in the whole of Hebei. Nine HIV-1 genotypes based on full length gag-partial pol gene sequence were identified among 610 newly diagnosed naïve individuals. The four main genotypes were circulating recombinant form (CRF)01_AE (53.4%), CRF07_BC (23.4%), subtype B (15.9%), and unique recombinant forms URFs (4.9%). Within 1 year, three new genotypes (subtype A1, CRF55_01B, CRF65_cpx), unknown before in Hebei, were first found among men who have sex with men (MSM). All nine genotypes were identified in the sexually contracted HIV-1 population. Among 30 URFs, six recombinant patterns were revealed, including CRF01_AE/BC (40.0%), CRF01_AE/B (23.3%), B/C (16.7%), CRF01_AE/C (13.3%), CRF01_AE/B/A2 (3.3%) and CRF01_AE/BC/A2 (3.3%), plus two potential CRFs. This study elucidated the complicated characteristics of HIV-1 molecular epidemiology in a low HIV-1 prevalence northern province of China and revealed the high level of HIV-1 genetic diversity. All nine HIV-1 genotypes circulating in Hebei have spread out of their initial risk groups into the general population through sexual contact, especially through MSM. This highlights the urgency of HIV prevention and control in China. PMID:28178737

  6. Environmental Assessment for Proposed Access Control and Traffic Improvements at Los Alamos National Laboratory, Los Alamos, New Mexico

    SciTech Connect

    N /A

    2002-08-23

    The National Nuclear Security Administration (NNSA) has assigned a continuing role to Los Alamos National Laboratory (LANL) in carrying out NNSA's national security mission. It is imperative that LANL continue this enduring responsibility and that NNSA adequately safeguard LANL capabilities. NNSA has identified the need to restrict vehicular access to certain areas within LANL for the purpose of permanently enhancing the physical security environment at LANL. It has also identified the need to change certain traffic flow patterns for the purpose of enhancing physical safety at LANL. The Proposed Action would include the construction of eastern and western bypass roads around the LANL Technical Area (TA) 3 area and the installation of vehicle access controls and related improvements to enhance security along Pajarito Road and in the LANL core area. This Proposed Action would modify the current roadway network and traffic patterns. It would also result in traversing Areas of Environmental Interest identified in the LANL Habitat Management Plan, demolition of part of an historic structure at Building 3-40, and traversing several potential release sites and part of the Los Alamos County landfill. The No Action Alternative was also considered. Under this alternative NNSA would not construct the eastern or western bypass roads, any access-control stations, or related improvements. Diamond Drive would continue to serve as the primary conduit for most vehicle traffic within the LANL core area regardless of actual trip destinations. The No Action Alternative does not meet NNSA's purpose and need for action. The proposed bypass road corridors traverse both developed and undeveloped areas. Several potential release sites are present. These would either be sampled and remediated in accordance with New Mexico Environment Department requirements before construction or avoided to allow for future remediation. In some cases, contaminant levels may fall below remediation thresholds

  7. Uncertainty quantification and global sensitivity analysis of the Los Alamos sea ice model

    DOE PAGES

    Urrego-Blanco, Jorge Rolando; Urban, Nathan Mark; Hunke, Elizabeth Clare; ...

    2016-04-01

    Changes in the high-latitude climate system have the potential to affect global climate through feedbacks with the atmosphere and connections with midlatitudes. Sea ice and climate models used to understand these changes have uncertainties that need to be characterized and quantified. We present a quantitative way to assess uncertainty in complex computer models, which is a new approach in the analysis of sea ice models. We characterize parametric uncertainty in the Los Alamos sea ice model (CICE) in a standalone configuration and quantify the sensitivity of sea ice area, extent, and volume with respect to uncertainty in 39 individual modelmore » parameters. Unlike common sensitivity analyses conducted in previous studies where parameters are varied one at a time, this study uses a global variance-based approach in which Sobol' sequences are used to efficiently sample the full 39-dimensional parameter space. We implement a fast emulator of the sea ice model whose predictions of sea ice extent, area, and volume are used to compute the Sobol' sensitivity indices of the 39 parameters. Main effects and interactions among the most influential parameters are also estimated by a nonparametric regression technique based on generalized additive models. A ranking based on the sensitivity indices indicates that model predictions are most sensitive to snow parameters such as snow conductivity and grain size, and the drainage of melt ponds. Lastly, it is recommended that research be prioritized toward more accurately determining these most influential parameter values by observational studies or by improving parameterizations in the sea ice model.« less

  8. Risk management for operations of the Los Alamos critical experiments facility

    SciTech Connect

    Paternoster, R.; Butterfield, K.

    1998-12-31

    The Los Alamos Critical Experiments Facility (LACEF) currently operates two burst reactors (Godiva-IV and Skua), one solution assembly (SHEBA 2--Solution high-Energy Burst Assembly), two fast-spectrum benchmark assemblies (Flattop and Big Ten), and five general-purpose remote assembly machines which may be configured with nuclear materials and assembled by remote control. SNM storage vaults support these and other operations at the site. With this diverse set of operations, several approaches are possible in the analysis and management of risk. The most conservative approach would be to write a safety analysis report (SAR) for each assembly and experiment. A more cost-effective approach is to analyze the probability and consequences of several classes of operations representative of operations on each critical assembly machine and envelope the bounding case accidents. Although the neutron physics of these machines varies widely, the operations performed at LACEF fall into four operational modes: steady-state mode, approach-to-critical mode, prompt burst mode, and nuclear material operations which can include critical assembly fuel loading. The operational sequences of each mode are very nearly the same, whether operated on one assembly machine or another. The use of an envelope approach to accident analysis is facilitated by the use of classes of operations and the use of bounding case consequence analysis. A simple fault tree analysis of operational modes helps resolve which operations are sensitive to human error and which are initiated by hardware of software failures. Where possible, these errors and failures are blocked by TSR LCOs.

  9. Environmental Assessment for the High Explosives Wastewater Treatment Facility, Los Alamos National Laboratory, Los Alamos, New Mexico

    SciTech Connect

    1995-08-03

    The Department of Energy (DOE) has identified a need to improve the management of wastewater resulting from high explosives (HE) research and development work at Los Alamos National Laboratory (LANL). LANL`s current methods off managing HE-contaminated wastewater cannot ensure that discharged HE wastewater would consistently meet the Environmental Protection Agency`s (EPA`s) standards for wastewater discharge. The DOE needs to enhance He wastewater management to e able to meet both present and future regulatory standards for wastewater discharge. The DOE also proposes to incorporate major pollution prevention and waste reduction features into LANL`s existing HE production facilities. Currently, wastewater from HE processing buildings at four Technical Areas (TAs) accumulates in sumps where particulate HE settles out and barium is precipitated. Wastewater is then released from the sumps to the environment at 15 permitted outfalls without treatment. The released water may contain suspended and dissolved contaminants, such as HE and solvents. This Environmental Assessment (EA) analyzes two alternatives, the Proposed Action and the Alternative Action, that would meet the purpose and need for agency action. Both alternatives would treat all HE process wastewater using sand filters to remove HE particulates and activated carbon to adsorb organic solvents and dissolved HE. Under either alternative, LANL would burn solvents and flash dried HE particulates and spent carbon following well-established procedures. Burning would produce secondary waste that would be stored, treated, and disposed of at TA-54, Area J. This report contains the Environmental Assessment, as well as the Finding of No Significant Impact and Floodplain Statement of Findings for the High Explosives Wastewater Treatment Facility.

  10. Perspectives of Genome-Editing Technologies for HIV Therapy

    PubMed Central

    Ebina, Hirotaka; Gee, Peter; Koyanagi, Yoshio

    2016-01-01

    Background: Current HIV antiretroviral therapies potently suppress virus replication and prevent patients from progressing to AIDS but are unable to completely eliminate HIV due to the existence of dormant viral reservoirs which threaten to reemerge at anytime. Recently, genome-editing technologies that can recognize specific DNA sequences, including viral DNA, are being touted as promising tools for curing HIV, owing to their specificity, ease of use, and ability to be custom designed. Conclusion: Here, we introduce several novel strategies aimed at eradicating HIV proviruses with state-of-the-art genome-editing technologies and discuss perspectives of these approaches for curing HIV. PMID:26255882

  11. RCRA facility investigation for the townsite of Los Alamos, New Mexico

    SciTech Connect

    Dorries, A.M.; Conrad, R.C.; Nonno, L.M.

    1992-01-01

    During World War II, Los Alamos, New Mexico was established as an ideal location for the secrecy and safety needed for the research and development required to design a nuclear fission bomb. Experiments carried out in the 1940s generated both radioactive and hazardous waste constituents on what is presently part of the Los Alamos townsite. Under the RCRA permit issued to Los alamos national Laboratory in 1990, the Laboratory is scheduled for investigation of its solid waste management units (SWMUs). The existing information on levels of radioactivity on the townsite is principally data from soil samples taken during the last site decontamination in 1976, little information on the presence of hazardous constituents exists today. This paper addresses pathway analysis and a preliminary risk assessment for current residents of the Los Alamos townsite. The estimated dose levels, in mrem per year, show that the previously decontaminated SWMU areas on the Los Alamos townsite will not contribute a radiation dose of any concern to the current residents.

  12. Los Alamos contribution to target diagnostics on the National Ignition Facility

    SciTech Connect

    Mack, J.M.; Baker, D.A.; Caldwell, S.E.

    1994-07-01

    The National Ignition Facility (NIF) will have a large suite of sophisticated target diagnostics. This will allow thoroughly diagnosed experiments to be performed both at the ignition and pre-ignition levels. As part of the national effort Los Alamos National Laboratory will design, construct and implement a number of diagnostics for the NIF. This paper describes Los Alamos contributions to the ``phase I diagnostics.`` Phase I represents the most fundamental and basic measurement systems that will form the core for most work on the NIF. The Los Alamos effort falls into four categories: moderate to hard X-ray (time resolved imaging neutron spectroscopy- primarily with neutron time of flight devices; burn diagnostics utilizing gamma ray measurements; testing measurement concepts on the TRIDENT laser system at Los Alamos. Because of the high blast, debris and radiation environment, the design of high resolution X-ray imaging systems present significant challenges. Systems with close target proximity require special protection and methods for such protection is described. The system design specifications based on expected target performance parameters is also described. Diagnosis of nuclear yield and burn will be crucial to the NIF operation. Nuclear reaction diagnosis utilizing both neutron and gamma ray detection is discussed. The Los Alamos TRIDENT laser system will be used extensively for the development of new measurement concepts and diagnostic instrumentation. Some its potential roles in the development of diagnostics for NIF are given.

  13. Evaluation of Macroinvertebrate Communities and Habitat for Selected Stream Reaches at Los Alamos National Laboratory

    SciTech Connect

    L.J. Henne; K.J. Buckley

    2005-08-12

    This is the second aquatic biological monitoring report generated by Los Alamos National Laboratory's (LANL's) Water Quality and Hydrology Group. The study has been conducted to generate impact-based assessments of habitat and water quality for LANL waterways. The monitoring program was designed to allow for the detection of spatial and temporal trends in water and habitat quality through ongoing, biannual monitoring of habitat characteristics and benthic aquatic macroinvertebrate communities at six key sites in Los Alamos, Sandia, Water, Pajarito, and Starmer's Gulch Canyons. Data were collected on aquatic habitat characteristics, channel substrate, and macroinvertebrate communities during 2001 and 2002. Aquatic habitat scores were stable between 2001 and 2002 at all locations except Starmer's Gulch and Pajarito Canyon, which had lower scores in 2002 due to low flow conditions. Channel substrate changes were most evident at the upper Los Alamos and Pajarito study reaches. The macroinvertebrate Stream Condition Index (SCI) indicated moderate to severe impairment at upper Los Alamos Canyon, slight to moderate impairment at upper Sandia Canyon, and little or no impairment at lower Sandia Canyon, Starmer's Gulch, and Pajarito Canyon. Habitat, substrate, and macroinvertebrate data from the site in upper Los Alamos Canyon indicated severe impacts from the Cerro Grande Fire of 2000. Impairment in the macroinvertebrate community at upper Sandia Canyon was probably due to effluent-dominated flow at that site. The minimal impairment SCI scores for the lower Sandia site indicated that water quality improved with distance downstream from the outfall at upper Sandia Canyon.

  14. Enabling completion of the material disposition area G closure at the Los Alamos National Laboratory

    SciTech Connect

    Blankenhorn, James Allen; Bishop, Milton L

    2010-01-01

    Los Alamos National Security, LLC (LANS) and the Los Alamos Site Office (LASO) have developed and are implementing an integrated strategy to accelerate the disposition of Los Alamos National Laboratory (LANL) legacy transuranic waste inventory currently stored in Technical Area 54, Material Disposition Area (MDA) G. As that strategy has been implemented the easier waste streams have been certified and shipped leaving the harder more challenging wastes to be dispositioned. Lessons learned from around the complex and a partnership with the National Transuranic Program located in Carlsbad, New Mexico, are enabling this acceleration. The Waste Disposition Program is responsible for the removal of both the above ground and below grade, retrievably stored transuranic waste in time to support the negotiated consent order with the State of New Mexico which requires closure of MDA G by the year 2015. The solutions and strategy employed at LANL are applicable to any organization that is currently managing legacy transuranic waste.

  15. Los Alamos National Laboratory Human and Intellectual Capital for Sustaining Nuclear Deterrence

    SciTech Connect

    McAlpine, Bradley

    2015-04-01

    This paper provides an overview of the current human and intellectual capital at Los Alamos National Laboratory, through specific research into the statistics and demographics as well as numerous personal interviews at all levels of personnel. Based on this information, a series of recommendations are provided to assist Los Alamos National Laboratory in ensuring the future of the human and intellectual capital for the nuclear deterrence mission. While the current human and intellectual capital is strong it stands on the precipice and action must be taken to ensure Los Alamos National Laboratory maintains leadership in developing and sustaining national nuclear capabilities. These recommendations may be applicable to other areas of the nuclear enterprise, including the Air Force, after further research and study.

  16. Wide-area Gigabit networking: Los Alamos HIPPI-SONET Gateway

    SciTech Connect

    St. John, W.B.; DuBois, D.H.

    1995-05-01

    This paper describes a HIPPI-SONET Gateway which has been designed by members of the Computer Network Engineering Group at Los Alamos National Laboratory. The Gateway has been used in the CASA Gigabit Testbed at Caltech, Los Alamos National Laboratory, and the San Diego Supercomputer Center to provide communications between the sites. This paper will also make some qualitative statements as to lessons learned during the deployment and maintenance of this wide area network. We report record throughput for transmission of data across a wide area network. We have sustained data rates using the TCP/IP protocol of 550 Mbits/second and the rate of 792 Mbits/second for raw HIPPI data transfer over the 2,000 kilometers from the San Diego Supercomputer Center to the Los Alamos National Laboratory.

  17. HIV infection en route to endogenization: two cases

    PubMed Central

    Colson, P; Ravaux, I; Tamalet, C; Glazunova, O; Baptiste, E; Chabriere, E; Wiedemann, A; Lacabaratz, C; Chefrour, M; Picard, C; Stein, A; Levy, Y; Raoult, D

    2014-01-01

    The long-term spontaneous evolution of humans and the human immunodeficiency virus (HIV) is not well characterized; many vertebrate species, including humans, exhibit remnants of other retroviruses in their genomes that question such possible endogenization of HIV. We investigated two HIV-infected patients with no HIV-related disease and no detection with routine tests of plasma HIV RNA or cell-associated HIV DNA. We used Sanger and deep sequencing to retrieve HIV DNA sequences integrated in the human genome and tested the host humoral and cellular immune responses. We noticed that viruses from both patients were inactivated by the high prevalence of the transformation of tryptophan codons into stop codons (25% overall (3–100% per gene) and 24% overall (0–50% per gene)). In contrast, the humoral and/or cellular responses were strong for one patient and moderate for the other, indicating that a productive infection occurred at one stage of the infection. We speculate that the stimulation of APOBEC, the enzyme group that exchanges G for A in viral nucleic acids and is usually inhibited by the HIV protein Vif, has been amplified and made effective from the initial stage of the infection. Furthermore, we propose that a cure for HIV may occur through HIV endogenization in humans, as observed for many other retroviruses in mammals, rather than clearance of all traces of HIV from human cells, which defines viral eradication. PMID:25366539

  18. Los Alamos Controlled Air Incinerator for radioactive waste. Volume I. Rationale, process, equipment, performance, and recommendations

    SciTech Connect

    Neuls, A.S.; Draper, W.E.; Koenig, R.A.; Newmyer, J.M.; Warner, C.L.

    1982-08-01

    This two-volume report is a detailed design and operating documentation of the Los Alamos National Laboratory Controlled Air Incinerator (CAI) and is an aid to technology transfer to other Department of Energy contractor sites and the commercial sector. Volume I describes the CAI process, equipment, and performance, and it recommends modifications based on Los Alamos experience. It provides the necessary information for conceptual design and feasibility studies. Volume II provides descriptive engineering information such as drawing, specifications, calculations, and costs. It aids duplication of the process at other facilities.

  19. Los Alamos Controlled Air Incinerator for radioactive waste. Volume II. Engineering design reference manual

    SciTech Connect

    Koenig, R.A.; Draper, W.E.; Newmyer, J.M.; Warner, C.L.

    1982-10-01

    This two-volume report is a detailed design and operating documentation of the Los Alamos National Laboratory Controlled Air Incinerator (CAI) and is an aid to technology transfer to other Department of Energy contractor sites and the commercial sector. Volume I describes the CAI process, equipment, and performance, and it recommends modifications based on Los Alamos experience. It provides the necessary information for conceptual design and feasibility studies. Volume II provides descriptive engineering information such as drawings, specifications, calculations, and costs. It aids duplication of the process at other facilities.

  20. Concentration Ratios for Cesium and Strontium in Produce Near Los Alamos

    SciTech Connect

    S. Salazar, M.McNaughton, P.R. Fresquez

    2006-03-01

    The ratios of the concentrations of radionuclides in produce (fruits, vegetables, and grains) to the concentrations in the soil have been measured for cesium and strontium at locations near Los Alamos. The Soil, Foodstuffs, and Biota Team of the Meteorology and Air Quality Group of the Los Alamos National Laboratory (LANL) obtained the data at locations within a radius of 50 miles of LANL. The concentration ratios are in good agreement with previous measurements: 0.01 to 0.06 for cesium-137 and 0.1 to 0.5 for strontium-90 (wet-weight basis).

  1. Los Alamos DP West Plutonium Facility decontamination project, 1978-1981

    SciTech Connect

    Garde, R.; Cox, E.J.; Valentine, A.M.

    1982-09-01

    The DP West Plutonium Facility operated by the Los Alamos National Laboratory, Los Alamos, New Mexico was decontaminated between April 1978 and April 1981. The facility was constructed in 1944 to 1945 to produce plutonium metal and fabricate parts for nuclear weapons. It was continually used as a plutonium processing and research facility until mid-1978. Decontamination operations included dismantling and removing gloveboxes and conveyor tunnels; removing process systems, utilities, and exhaust ducts; and decontaminating all remaining surfaces. This report describes glovebox and conveyor tunnel separations, decontamination techniques, health and safety considerations, waste management procedures, and costs of the operation.

  2. Los Alamos Air Monitoring Data Related to the Fukushima Daiichi Reactor

    SciTech Connect

    McNaughton, Michael

    2011-01-01

    In response to the disasters in Japan on March 11, 2011, Los Alamos National Laboratory (LANL) is collecting air data and analyzing the data for fission products. At present, we report preliminary data from three high-volume air samplers and one stack sampler. Iodine-131 (I-131) is not optimally measured by our standard polypropylene filters. In addition to the filter data, we have one measurement obtained from a charcoal cartridge. These data, together with measurements of other radionuclides are adequate for a preliminary assessment and assure us that radionuclides from Fukushima Daiichi do not present a threat to human health at or near Los Alamos.

  3. Measurements at Los Alamos National Laboratory Plutonium Facility in Support of Global Security Mission Space

    SciTech Connect

    Stange, Sy; Mayo, Douglas R.; Herrera, Gary D.; McLaughlin, Anastasia D.; Montoya, Charles M.; Quihuis, Becky A.; Trujillo, Julio B.; Van Pelt, Craig E.; Wenz, Tracy R.

    2012-07-13

    The Los Alamos National Laboratory Plutonium Facility at Technical Area (TA) 55 is one of a few nuclear facilities in the United States where Research & Development measurements can be performed on Safeguards Category-I (CAT-I) quantities of nuclear material. This capability allows us to incorporate measurements of CAT-IV through CAT-I materials as a component of detector characterization campaigns and training courses conducted at Los Alamos. A wider range of measurements can be supported. We will present an overview of recent measurements conducted in support of nuclear emergency response, nuclear counterterrorism, and international and domestic safeguards. This work was supported by the NNSA Office of Counterterrorism.

  4. Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART

    PubMed Central

    Vazquez-Guillen, Jose Manuel; Palacios-Saucedo, Gerardo C.; Rivera-Morales, Lydia G.; Garcia-Campos, Jorge; Ortiz-Lopez, Rocio; Noguera-Julian, Marc; Paredes, Roger; Vielma-Ramirez, Herlinda J.; Ramirez, Teresa J.; Chavez-Garcia, Marcelino; Lopez-Guillen, Paulo; Briones-Lara, Evangelina; Sanchez-Sanchez, Luz M.; Vazquez-Martinez, Carlos A.; Rodriguez-Padilla, Cristina

    2016-01-01

    Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM’s) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM’s in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM’s during STI. PMID:26807922

  5. HIV Life Cycle

    MedlinePlus

    HIV Overview The HIV Life Cycle (Last updated 9/13/2016; last reviewed 9/8/2016) Key Points HIV gradually destroys the immune ... life cycle. What is the connection between the HIV life cycle and HIV medicines? Antiretroviral therapy (ART) ...

  6. Near Full-Length Genome Sequence of a Novel HIV-1 Recombinant Form (CRF01_AE/B) Detected Among Men Who Have Sex with Men in Jilin Province, China

    PubMed Central

    Li, Xingguang; Feng, Yi; Yang, Yao; Chen, Yanli; Guo, Qi; Sun, Liuyan; Zang, Xihui; Xing, Hui

    2014-01-01

    Abstract We report here a novel HIV-1 recombinant form (CRF01_AE/B) detected from a comprehensive HIV-1 molecular epidemiologic study among men who have sex with men (MSM) in Jilin province of northeastern China. The near full-length genome (NFLG) analyses showed that the novel HIV-1 recombinant isolate (JL.RF07) was composed of CRF01_AE cluster 5 (northeastern China origin) and subtype B (U.S. and European origin), with six recombinant breakpoints observed in the pol, vif, tat, rev, and env gene regions. To the best of our knowledge, this is the first detection of a novel HIV-1 recombinant form (CRF01_AE/B) in Jilin, which may indicate an active transmission network of HIV-1 infection among MSM in the region. Further studies of the molecular epidemiology of the HIV-1 epidemic among MSM in northeastern China are necessary to gain a fuller understanding of the transmission network and potential public health impact of HIV-1 among MSM in this region. PMID:24521207

  7. Near full-length genome sequence of a novel HIV-1 recombinant form (CRF01_AE/B) detected among men who have sex with men in Jilin Province, China.

    PubMed

    Li, Xingguang; Feng, Yi; Yang, Yao; Chen, Yanli; Guo, Qi; Sun, Liuyan; Zang, Xihui; Xing, Hui; Shao, Yiming

    2014-07-01

    We report here a novel HIV-1 recombinant form (CRF01_AE/B) detected from a comprehensive HIV-1 molecular epidemiologic study among men who have sex with men (MSM) in Jilin province of northeastern China. The near full-length genome (NFLG) analyses showed that the novel HIV-1 recombinant isolate (JL.RF07) was composed of CRF01_AE cluster 5 (northeastern China origin) and subtype B (U.S. and European origin), with six recombinant breakpoints observed in the pol, vif, tat, rev, and env gene regions. To the best of our knowledge, this is the first detection of a novel HIV-1 recombinant form (CRF01_AE/B) in Jilin, which may indicate an active transmission network of HIV-1 infection among MSM in the region. Further studies of the molecular epidemiology of the HIV-1 epidemic among MSM in northeastern China are necessary to gain a fuller understanding of the transmission network and potential public health impact of HIV-1 among MSM in this region.

  8. Fabrication of Optical Fiber Mechanical Shock Sensors for the Los Alamos HERT (High Explosive Radio Telemetry) Project

    SciTech Connect

    P. E. Klingsporn

    2005-11-14

    This document lists the requirements for the fiber optic mechanical shock sensor for the Los Alamos HERT (High Explosive Radio Telemetry) project and provides detailed process steps for fabricating, testing, and assembling the fiber shock sensors for delivery to Los Alamos.

  9. HIV-1 replication.

    PubMed

    Freed, E O

    2001-11-01

    surface (SU) Env glycoprotein gp120 and the transmembrane (TM) glycoprotein gp41. gp120 contains the determinants that interact with receptor and coreceptor, while gp41 not only anchors the gp120/gp41 complex in the membrane (Fig. 2), but also contains domains that are critical for catalyzing the membrane fusion reaction between viral and host lipid bilayers during virus entry. Comparison of env sequences from a large number of virus isolates revealed that gp120 is organized into five conserved regions (C1-C5) and five highly variable domains (V1-V5). The variable regions tend to be located in disulfide-linked loops. gp41 is composed of three major domains: the ectodomain (which contains determinants essential for membrane fusion), the transmembrane anchor sequence, and the cytoplasmic tail. In addition to the gag, pol, and env genes, HIV-1 also encodes a number of regulatory and accessory proteins. Tat is critical for transcription from the HIV-1 LTR and Rev plays a major [figure: see text] role in the transport of viral RNAs from the nucleus to the cytoplasm. Vpu, Vif, Vpr and Nef have been termed "accessory" or "auxiliary" proteins to reflect the fact that they are not uniformly required for virus replication. The functions of these very interesting proteins will be discussed in more detail at the end of this chapter. HIV replication proceeds in a series of events that can be divided into two overall phases: "early" and "late" (Fig. 3). Although some events occur in a concerted or simultaneous fashion, the replication cycle can be viewed most simply as proceeding in an ordered, step-wise manner. In this chapter, each step in virus replication will be considered; additional information can be obtained from the more detailed reviews and primary references that are cited.

  10. HIV Medicines and Side Effects

    MedlinePlus

    ... on a person’s individual needs. Can HIV medicines cause side effects? HIV medicines help people with HIV live longer, healthier lives. Sometimes HIV medicines can also cause side effects. Most side effects from HIV medicines are manageable, ...

  11. Cyclophilin B enhances HIV-1 infection

    SciTech Connect

    DeBoer, Jason; Madson, Christian J.; Belshan, Michael

    2016-02-15

    Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. - Highlights: • CypB has been identified in several proteomic studies of HIV-1 infection. • CypB expression is upregulated in activated and infected T-cells. • Over-expression of CypB enhances HIV nuclear import and infection. • The N-terminus of CypB is necessary for these effects.

  12. HIV classification using coalescent theory

    SciTech Connect

    Zhang, Ming; Letiner, Thomas K; Korber, Bette T

    2008-01-01

    Algorithms for subtype classification and breakpoint detection of HIV-I sequences are based on a classification system of HIV-l. Hence, their quality highly depend on this system. Due to the history of creation of the current HIV-I nomenclature, the current one contains inconsistencies like: The phylogenetic distance between the subtype B and D is remarkably small compared with other pairs of subtypes. In fact, it is more like the distance of a pair of subsubtypes Robertson et al. (2000); Subtypes E and I do not exist any more since they were discovered to be composed of recombinants Robertson et al. (2000); It is currently discussed whether -- instead of CRF02 being a recombinant of subtype A and G -- subtype G should be designated as a circulating recombination form (CRF) nd CRF02 as a subtype Abecasis et al. (2007); There are 8 complete and over 400 partial HIV genomes in the LANL-database which belong neither to a subtype nor to a CRF (denoted by U). Moreover, the current classification system is somehow arbitrary like all complex classification systems that were created manually. To this end, it is desirable to deduce the classification system of HIV systematically by an algorithm. Of course, this problem is not restricted to HIV, but applies to all fast mutating and recombining viruses. Our work addresses the simpler subproblem to score classifications of given input sequences of some virus species (classification denotes a partition of the input sequences in several subtypes and CRFs). To this end, we reconstruct ancestral recombination graphs (ARG) of the input sequences under restrictions determined by the given classification. These restritions are imposed in order to ensure that the reconstructed ARGs do not contradict the classification under consideration. Then, we find the ARG with maximal probability by means of Markov Chain Monte Carlo methods. The probability of the most probable ARG is interpreted as a score for the classification. To our

  13. Travelers' Health: HIV Infection

    MedlinePlus

    ... AGENT HIV, a single-stranded, positive-sense, enveloped RNA virus in the genus Lentivirus. TRANSMISSION HIV can ... be diagnosed is approximately 9 days, when HIV RNA becomes detectable in blood; however, tests needed to ...

  14. HIV Antibody Test

    MedlinePlus

    ... test is performed that detects the genetic material ( RNA ) of the virus. An HIV RNA test will detect HIV in most people by ... next test to perform is an HIV-1 RNA test (nucleic acid amplification test, NAAT). If the ...

  15. HIV/AIDS Basics

    MedlinePlus

    ... Enter ZIP code or city Follow Act Against AIDS Act Against AIDS @talkHIV Act Against AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets HIV/ ...

  16. HIV/AIDS

    MedlinePlus

    ... at risk for serious infections and certain cancers. AIDS stands for acquired immunodeficiency syndrome. It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV most often spreads through unprotected sex with ...

  17. HIV/AIDS

    MedlinePlus

    ... yeast infection (thrush) Shingles (herpes zoster) Progression to AIDS If you receive no treatment for your HIV ... childbirth or breast-feeding. How does HIV become AIDS? HIV destroys CD4 cells — a specific type of ...

  18. HIV and AIDS

    MedlinePlus

    ... dientes Video: Getting an X-ray HIV and AIDS KidsHealth > For Kids > HIV and AIDS Print A ... serious infection. continue How Many People Have HIV/AIDS? Since the discovery of the virus in 1983, ...

  19. HIV/AIDS Coinfection

    MedlinePlus

    ... Laotian Mongolian Spanish Turkish Vietnamese Hindi Subscribe HIV/AIDS Coinfection Approximately 10% of the HIV-infected population ... Control and Prevention website to learn about HIV/AIDS and Viral Hepatitis guidelines and resources. Home About ...

  20. HIV migration between blood plasma and cellular subsets before and after HIV therapy.

    PubMed

    Choi, Jun Yong; Chaillon, Antoine; Oh, Jin Ok; Ahn, Jin Young; Ann, Hae Won; Jung, In Young; Ahn, Mi-Young; Jeon, Yong Duk; Ku, Nam Su; Smith, Davey M; Kim, June Myung

    2016-04-01

    The cellular source of HIV RNA circulating in blood plasma remains unclear. Here, we investigated whether sequence analysis of HIV RNA populations circulating before combination antiretroviral therapy (cART) and HIV DNA populations in cellular subsets (CS) after cART could identify the cellular sources of circulating HIV RNA. Blood was collected from five subjects at cART initiation and again 6 months later. Naïve CD4+ T cells, resting central memory and effector memory CD4+ T cells, activated CD4+ T cells, monocytes, and natural killer cells were sorted using a fluorescence-activated cell sorter. HIV-1 env C2V3 sequences from HIV RNA in blood plasma and HIV DNA in CSs were generated using single genome sequencing. Sequences were evaluated for viral compartmentalization (Fst test) and migration events (MEs; Slatkin Maddison and cladistic measures) between blood plasma and each CS. Viral compartmentalization was observed in 88% of all cellular subset comparisons (range: 77-100% for each subject). Most observed MEs were directed from blood plasma to CSs (52 MEs, 85.2%). In particular, there was only viral movement from plasma to NK cells (15 MEs), monocytes (seven MEs), and naïve cells (five ME). We observed a total of nine MEs from activated CD4 cells (2/9 MEs), central memory T cells (3/9 MEs), and effector memory T cells (4/9 MEs) to blood plasma. Our results revealed that the HIV RNA population in blood plasma plays an important role in seeding various cellular reservoirs and that the cellular source of the HIV RNA population is activated central memory and effector memory T cells.