Restriction of HIV-1 Genotypes in Breast Milk Does Not Account for the Population Transmission Genetic Bottleneck That Occurs following Transmission

BACKGROUND. Breast milk transmission of HIV-1 remains a major route of pediatric infection. Defining the characteristics of viral variants to which breastfeeding infants are exposed is important for understanding the genetic bottleneck that occurs in the majority of mother-to-child transmissions. The blood-milk epithelial barrier markedly restricts the quantity of HIV-1 in breast milk, even in the absence of antiretroviral drugs. The basis of this restriction and the genetic relationship between breast milk and blood variants are not well established. METHODOLOGY/PRINCIPAL FINDINGS. We compared 356 HIV-1 subtype C gp160 envelope (env) gene sequences from the plasma and breast milk of 13 breastfeeding women. A trend towards lower viral population diversity and divergence in breast milk was observed, potentially indicative of clonal expansion within the breast. No differences in potential N-linked glycosylation site numbers or in gp160 variable loop amino acid lengths were identified. Genetic compartmentalization was evident in only one out of six subjects in whom contemporaneously obtained samples were studied. However, in samples that were collected 10 or more days apart, six of seven subjects were classified as having compartmentalized viral populations, highlighting the necessity of contemporaneous sampling for genetic compartmentalization studies. We found evidence of CXCR4 co-receptor using viruses in breast milk and blood in nine out of the thirteen subjects, but no evidence of preferential localization of these variants in either tissue. CONCLUSIONS/SIGNIFICANCE. Despite marked restriction of HIV-1 quantities in milk, our data indicate intermixing of virus between blood and breast milk. Thus, we found no evidence that a restriction in viral genotype diversity in breast milk accounts for the genetic bottleneck observed following transmission. In addition, our results highlight the rapidity of HIV-1 env evolution and the importance of sample timing in analyses of gene flow.National Institute of Child Health and Human Development; National Institutes of Health (R01 HD 39611, R01 HD 40777); International Maternal Pediatric Adolescent AIDS Clinical Trials Group (U01 AI068632-01); National Institutes of Health Cellular, Biochemical; Molecular Sciences Training Program Grant (T 32 067587

On the breaking of a plasma wave in a thermal plasma: I. The structure of the density singularity

The structure of the singularity that is formed in a relativistically large amplitude plasma wave close to the wavebreaking limit is found by using a simple waterbag electron distribution function. The electron density distribution in the breaking wave has a typical "peakon" form. The maximum value of the electric field in a thermal breaking plasma is obtained and compared to the cold plasma limit. The results of computer simulations for different initial electron distribution functions are in agreement with the theoretical conclusions.Comment: 21 pages, 12 figure

The potential to narrow uncertainty in projections of stratospheric ozone over the 21st century

Future stratospheric ozone concentrations will be determined both by changes in the concentration of ozone depleting substances (ODSs) and by changes in stratospheric and tropospheric climate, including those caused by changes in anthropogenic greenhouse gases (GHGs). Since future economic development pathways and resultant emissions of GHGs are uncertain, anthropogenic climate change could be a significant source of uncertainty for future projections of stratospheric ozone. In this pilot study, using an "ensemble of opportunity" of chemistry-climate model (CCM) simulations, the contribution of scenario uncertainty from different plausible emissions pathways for ODSs and GHGs to future ozone projections is quantified relative to the contribution from model uncertainty and internal variability of the chemistry-climate system. For both the global, annual mean ozone concentration and for ozone in specific geographical regions, differences between CCMs are the dominant source of uncertainty for the first two-thirds of the 21st century, up-to and after the time when ozone concentrations return to 1980 values. In the last third of the 21st century, dependent upon the set of greenhouse gas scenarios used, scenario uncertainty can be the dominant contributor. This result suggests that investment in chemistry-climate modelling is likely to continue to refine projections of stratospheric ozone and estimates of the return of stratospheric ozone concentrations to pre-1980 levels

Decoherence in rf SQUID Qubits

We report measurements of coherence times of an rf SQUID qubit using pulsed microwaves and rapid flux pulses. The modified rf SQUID, described by an double-well potential, has independent, in situ, controls for the tilt and barrier height of the potential. The decay of coherent oscillations is dominated by the lifetime of the excited state and low frequency flux noise and is consistent with independent measurement of these quantities obtained by microwave spectroscopy, resonant tunneling between fluxoid wells and decay of the excited state. The oscillation's waveform is compared to analytical results obtained for finite decay rates and detuning and averaged over low frequency flux noise.Comment: 24 pages, 13 figures, submitted to the journal Quantum Information Processin

Strain-Rate Effects on Microstructural Deformation in Irradiated 316 SS

A series of studies have been performed to investigate the post-irradiation deformation and failure behavior of 12% cold-worked 316 stainless steel following irradiation to variety of doses and temperatures in the outer rows of the experimental breeder reactor II (EBR-II). In the current phase of these studies, three sets of samples with different radiation induced microstructures have been characterized with transmission electron microscopy (TEM) following tensile testing to failure at a ‘fast’ strain-rate (1 x 10-3 s-1) and a ‘slow’ strain-rate (1 x 10-7 s-1). The samples were irradiated to doses between 9 and 41 dpa at temperatures between 383 and 443 degrees C. Tensile tests were conducted at a temperature of 430 degrees C and only regions outside of the necked region were examined. Over the parameters tested, strain-rate had a negligible effect on the deformation microstructure. In addition, there was no clear evidence of localized deformation behavior and the deformation appeared relatively homogeneous, characterized by unfaulting and incorporation of faulted dislocation loops into the general dislocation network structure. The influence of the defect microstructures and strain-rate on deformation behavior is discussed

Breast milk and in utero transmission of HIV-1 select for envelope variants with unique molecular signatures

Additional file 5: Figure S5. Representative CD4 infectivity curves using Affinofile cells for IUT (top) and BMT (bottom) maternal–infant pairs. Affinofile cells were induced to generate a 100-fold range of CD4 surface density (ABS/cell) and infected with 2000 IU pseudotyped virus. Percent infection was measured as the percent luciferase relative to infected and maximally induced Affinofile cells. Data shown are representative curves among 3–4 experimental replicates

Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab.

Cluster of differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and autoimmune disorders but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX, revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs), each of which engages a composite epitope and an extensive homotypic Fab:Fab interface. Our data suggest that RTX cross-links CD20 into circular assemblies and lead to a structural model for complement recruitment. Our results further highlight the potential relevance of homotypic Fab:Fab interactions in targeting oligomeric cell-surface markers

Holographic Roberge-Weiss Transitions

We investigate N=4 SYM coupled to fundamental flavours at nonzero imaginary quark chemical potential in the strong coupling and large N limit, using gauge/gravity duality applied to the D3-D7 system, treating flavours in the probe approximation. The interplay between Z(N) symmetry and the imaginary chemical potential yields a series of first-order Roberge-Weiss transitions. An additional thermal transition separates phases where quarks are bound/unbound into mesons. This results in a set of Roberge-Weiss endpoints: we establish that these are triple points, determine the Roberge-Weiss temperature, give the curvature of the phase boundaries and confirm that the theory is analytic in mu^2 when mu^2~0.Comment: 37 pages, 13 figures; minor comments added, to appear in JHE

Improving the sensitivity of Higgs boson searches in the golden channel

Leptonic decays of the Higgs boson in the ZZ* channel yield what is known as the golden channel due to its clean signature and good total invariant mass resolution. In addition, the full kinematic distribution of the decay products can be reconstructed, which, nonetheless, is not taken into account in traditional search strategy relying only on measurements of the total invariant mass. In this work we implement a type of multivariate analysis known as the matrix element method, which exploits differences in the full production and decay matrix elements between the Higgs boson and the dominant irreducible background from q bar{q} -> ZZ*. Analytic expressions of the differential distributions for both the signal and the background are also presented. We perform a study for the Large Hadron Collider at sqrt{s}=7 TeV for Higgs masses between 175 and 350 GeV. We find that, with an integrated luminosity of 2.5 fb^-1 or higher, improvements in the order of 10 - 20 % could be obtained for both discovery significance and exclusion limits in the high mass region, where the differences in the angular correlations between signal and background are most pronounced.Comment: 31 pages, 8 figures. v2: Minus signs in definitions of angles corrected. Typos fixed. Reference added. Cosmetic changes to Figure 4. Additional sentence added for clarificatio

Precision measurements of the top quark mass from the Tevatron in the pre-LHC era

The top quark is the heaviest of the six quarks of the Standard Model. Precise knowledge of its mass is important for imposing constraints on a number of physics processes, including interactions of the as yet unobserved Higgs boson. The Higgs boson is the only missing particle of the Standard Model, central to the electroweak symmetry breaking mechanism and generation of particle masses. In this Review, experimental measurements of the top quark mass accomplished at the Tevatron, a proton-antiproton collider located at the Fermi National Accelerator Laboratory, are described. Topologies of top quark events and methods used to separate signal events from background sources are discussed. Data analysis techniques used to extract information about the top mass value are reviewed. The combination of several most precise measurements performed with the two Tevatron particle detectors, CDF and \D0, yields a value of \Mt = 173.2 \pm 0.9 GeV/$c^2$.Comment: This version contains the most up-to-date top quark mass averag