108 research outputs found
P04-46. Broadly cross-neutralizing activity in plasma of HIV-1 and HIV-2 infected individuals
A Fluid Dynamics Calculation of Sputtering from a Cylindrical Thermal Spike
The sputtering yield, Y, from a cylindrical thermal spike is calculated using
a two dimensional fluid dynamics model which includes the transport of energy,
momentum and mass. The results show that the high pressure built-up within the
spike causes the hot core to perform a rapid expansion both laterally and
upwards. This expansion appears to play a significant role in the sputtering
process. It is responsible for the ejection of mass from the surface and causes
fast cooling of the cascade. The competition between these effects accounts for
the nearly linear dependence of with the deposited energy per unit depth
that was observed in recent Molecular Dynamics simulations. Based on this we
describe the conditions for attaining a linear yield at high excitation
densities and give a simple model for this yield.Comment: 10 pages, 9 pages (including 9 figures), submitted to PR
Crater formation by fast ions: comparison of experiment with Molecular Dynamics simulations
An incident fast ion in the electronic stopping regime produces a track of
excitations which can lead to particle ejection and cratering. Molecular
Dynamics simulations of the evolution of the deposited energy were used to
study the resulting crater morphology as a function of the excitation density
in a cylindrical track for large angle of incidence with respect to the surface
normal. Surprisingly, the overall behavior is shown to be similar to that seen
in the experimental data for crater formation in polymers. However, the
simulations give greater insight into the cratering process. The threshold for
crater formation occurs when the excitation density approaches the cohesive
energy density, and a crater rim is formed at about six times that energy
density. The crater length scales roughly as the square root of the electronic
stopping power, and the crater width and depth seem to saturate for the largest
energy densities considered here. The number of ejected particles, the
sputtering yield, is shown to be much smaller than simple estimates based on
crater size unless the full crater morphology is considered. Therefore, crater
size can not easily be used to estimate the sputtering yield.Comment: LaTeX, 7 pages, 5 EPS figures. For related figures/movies, see:
http://dirac.ms.virginia.edu/~emb3t/craters/craters.html New version uploaded
5/16/01, with minor text changes + new figure
P04-18. Comparison of HIV neutralization assays for use in vaccine research and clinical trials, phase II: results from the NeutNet working group
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Community Assessment of the Predictability of Cancer Protein and Phosphoprotein Levels from Genomics and Transcriptomics.
Cancer is driven by genomic alterations, but the processes causing this disease are largely performed by proteins. However, proteins are harder and more expensive to measure than genes and transcripts. To catalyze developments of methods to infer protein levels from other omics measurements, we leveraged crowdsourcing via the NCI-CPTAC DREAM proteogenomic challenge. We asked for methods to predict protein and phosphorylation levels from genomic and transcriptomic data in cancer patients. The best performance was achieved by an ensemble of models, including as predictors transcript level of the corresponding genes, interaction between genes, conservation across tumor types, and phosphosite proximity for phosphorylation prediction. Proteins from metabolic pathways and complexes were the best and worst predicted, respectively. The performance of even the best-performing model was modest, suggesting that many proteins are strongly regulated through translational control and degradation. Our results set a reference for the limitations of computational inference in proteogenomics. A record of this paper's transparent peer review process is included in the Supplemental Information
Proteogenomic integration reveals therapeutic targets in breast cancer xenografts
Recent advances in mass spectrometry (MS) have enabled extensive analysis of cancer proteomes. Here, we employed quantitative proteomics to profile protein expression across 24 breast cancer patient-derived xenograft (PDX) models. Integrated proteogenomic analysis shows positive correlation between expression measurements from transcriptomic and proteomic analyses; further, gene expression-based intrinsic subtypes are largely re-capitulated using non-stromal protein markers. Proteogenomic analysis also validates a number of predicted genomic targets in multiple receptor tyrosine kinases. However, several protein/phosphoprotein events such as overexpression of AKT proteins and ARAF, BRAF, HSP90AB1 phosphosites are not readily explainable by genomic analysis, suggesting that druggable translational and/or post-translational regulatory events may be uniquely diagnosed by MS. Drug treatment experiments targeting HER2 and components of the PI3K pathway supported proteogenomic response predictions in seven xenograft models. Our study demonstrates that MS-based proteomics can identify therapeutic targets and highlights the potential of PDX drug response evaluation to annotate MS-based pathway activities
Generation of neutralizing antibodies and divergence of SIVmac239 in cynomolgus macaques following short-term early antiretroviral therapy.
Neutralizing antibodies (NAb) able to react to heterologous viruses are generated during natural HIV-1 infection in some individuals. Further knowledge is required in order to understand the factors contributing to induction of cross-reactive NAb responses. Here a well-established model of experimental pathogenic infection in cynomolgus macaques, which reproduces long-lasting HIV-1 infection, was used to study the NAb response as well as the viral evolution of the highly neutralization-resistant SIVmac239. Twelve animals were infected intravenously with SIVmac239. Antiretroviral therapy (ART) was initiated ten days post-inoculation and administered daily for four months. Viral load, CD4(+) T-cell counts, total IgG levels, and breadth as well as strength of NAb in plasma were compared simultaneously over 14 months. In addition, envs from plasma samples were sequenced at three time points in all animals in order to assess viral evolution. We report here that seven of the 12 animals controlled viremia to below 10(4) copies/ml of plasma after discontinuation of ART and that this control was associated with a low level of evolutionary divergence. Macaques that controlled viral load developed broader NAb responses early on. Furthermore, escape mutations, such as V67M and R751G, were identified in virus sequenced from all animals with uncontrolled viremia. Bayesian estimation of ancestral population genetic diversity (PGD) showed an increase in this value in non-controlling or transient-controlling animals during the first 5.5 months of infection, in contrast to virus-controlling animals. Similarly, non- or transient controllers displayed more positively-selected amino-acid substitutions. An early increase in PGD, resulting in the generation of positively-selected amino-acid substitutions, greater divergence and relative high viral load after ART withdrawal, may have contributed to the generation of potent NAb in several animals after SIVmac239 infection. However, early broad NAb responses correlated with relatively preserved CD4(+) T-cell numbers, low viral load and limited viral divergence
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