Transient domain walls and lepton asymmetry in the Left-Right symmetric model

It is shown that the dynamics of domain walls in Left-Right symmetric models, separating respective regions of unbroken SU(2)_L and SU(2)_R in the early universe, can give rise to baryogenesis via leptogenesis. Neutrinos have a spatially varying complex mass matrix due to CP-violating scalar condensates in the domain wall. The motion of the wall through the plasma generates a flux of lepton number across the wall which is converted to a lepton asymmetry by helicity-flipping scatterings. Subsequent processing of the lepton excess by sphalerons results in the observed baryon asymmetry, for a range of parameters in Left-Right symmetric models.Comment: v2 version accepted for publication in Phys. Rev. D. Discussion in Introduction and Conclusion sharpened. Equation (12) corrected. 16 pages, 3 figure files, RevTeX4 styl

Associations of occupational standing with musculoskeletal symptoms: A systematic review with meta-analysis

Objective Given the high exposure to occupational standing in specific occupations, and recent initiatives to encourage intermittent standing among white-collar workers, a better understanding of the potential health consequences of occupational standing is required. We aimed to review and quantify the epidemiological evidence on associations of occupational standing with musculoskeletal symptoms. Design A systematic review was performed. Data from included articles were extracted and described, and meta-analyses conducted when data were sufficiently homogeneous. Data sources Electronic databases were systematically searched. Eligibility criteria Peer-reviewed articles on occupational standing and musculoskeletal symptoms from epidemiological studies were identified. Results Of the 11 750 articles screened, 50 articles reporting 49 studies were included (45 cross-sectional and 5 longitudinal; n=88 158 participants) describing the associations of occupational standing with musculoskeletal symptoms, including low-back (39 articles), lower extremity (14 articles) and upper extremity (18 articles) symptoms. In the meta-analysis, 'substantial' (>4 hours/workday) occupational standing was associated with the occurrence of low-back symptoms (pooled OR (95% CI) 1.31 (1.10 to 1.56)). Evidence on lower and upper extremity symptoms was too heterogeneous for meta-analyses. The majority of included studies reported statistically significant detrimental associations of occupational standing with lower extremity, but not with upper extremity symptoms. Conclusions The evidence suggests that substantial occupational standing is associated with the occurrence of low-back and (inconclusively) lower extremity symptoms, but there may not be such an association with upper extremity symptoms. However, these conclusions are tentative as only limited evidence was found from high-quality, longitudinal studies with fully adjusted models using objective measures of standing

Selective Depletion of Eosinophils or Neutrophils in Mice Impacts the Efficiency of Apoptotic Cell Clearance in the Thymus

Developing thymocytes undergo a rigorous selection process to ensure that the mature T cell population expresses a T cell receptor (TCR) repertoire that can functionally interact with major histocompatibility complexes (MHC). Over 90% of thymocytes fail this selection process and die. A small number of macrophages within the thymus are responsible for clearing the large number of dying thymocytes that must be continuously cleared. We studied the capacity of thymic macrophages to clear apoptotic cells under acute circumstances. This was done by synchronously inducing cell death in the thymus and then monitoring the clearance of apoptotic thymocytes. Interestingly, acute cell death was shown to recruit large numbers of CD11b+ cells into the thymus. In the absence of a minor CSF-1 dependent population of macrophages, the recruitment of these CD11b+ cells into the thymus was greatly reduced and the clearance of apoptotic cells was disrupted. To assess a possible role for the CD11b+ cells in the clearance of apoptotic cells, we analyzed mice deficient for eosinophils and mice with defective trafficking of neutrophils. Failure to attract either eosinophils or neutrophils to the thymus resulted in the impaired clearance of apoptotic cells. These results suggested that there is crosstalk between cells of the innate immune system that is necessary for maximizing the efficiency of apoptotic cell removal

Successful Expansion but Not Complete Restriction of Tropism of Adeno-Associated Virus by In Vivo Biopanning of Random Virus Display Peptide Libraries

Targeting viral vectors to certain tissues in vivo has been a major challenge in gene therapy. Cell type-directed vector capsids can be selected from random peptide libraries displayed on viral capsids in vitro but so far this system could not easily be translated to in vivo applications. Using a novel, PCR-based amplification protocol for peptide libraries displayed on adeno-associated virus (AAV), we selected vectors for optimized transduction of primary tumor cells in vitro. However, these vectors were not suitable for transduction of the same target cells under in vivo conditions. We therefore performed selections of AAV peptide libraries in vivo in living animals after intravenous administration using tumor and lung tissue as prototype targets. Analysis of peptide sequences of AAV clones after several rounds of selection yielded distinct sequence motifs for both tissues. The selected clones indeed conferred gene expression in the target tissue while gene expression was undetectable in animals injected with control vectors. However, all of the vectors selected for tumor transduction also transduced heart tissue and the vectors selected for lung transduction also transduced a number of other tissues, particularly and invariably the heart. This suggests that modification of the heparin binding motif by target-binding peptide insertion is necessary but not sufficient to achieve tissue-specific transgene expression. While the approach presented here does not yield vectors whose expression is confined to one target tissue, it is a useful tool for in vivo tissue transduction when expression in tissues other than the primary target is uncritical

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum