On the Heterotic World-sheet Instanton Superpotential and its individual Contributions

For supersymmetric heterotic string compactifications on a Calabi-Yau threefold $X$ endowed with a vector bundle $V$ the world-sheet superpotential $W$ is a sum of contributions from isolated rational curves \C in $X$; the individual contribution is given by an exponential in the K\"ahler class of the curve times a prefactor given essentially by the Pfaffian which depends on the moduli of $V$ and the complex structure moduli of $X$. Solutions of $DW=0$ (or even of $DW=W=0$) can arise either by nontrivial cancellations between the individual terms in the summation over all contributing curves or because each of these terms is zero already individually. Concerning the latter case conditions on the moduli making a single Pfaffian vanish (for special moduli values) have been investigated. However, even if corresponding moduli - fulfilling these constraints - for the individual contribution of one curve are known it is not at all clear whether {\em one} choice of moduli exists which fulfills the corresponding constraints {\em for all contributing curves simultaneously}. Clearly this will in general happen only if the conditions on the 'individual zeroes' had already a conceptual origin which allows them to fit together consistently. We show that this happens for a class of cases. In the special case of spectral cover bundles we show that a relevant solution set has an interesting location in moduli space and is related to transitions which change the generation number.Comment: 47 page

Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes

Crown Lengthening Revisited

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141178/1/cap0233.pd

Quiver Structure of Heterotic Moduli

We analyse the vector bundle moduli arising from generic heterotic compactifications from the point of view of quiver representations. Phenomena such as stability walls, crossing between chambers of supersymmetry, splitting of non-Abelian bundles and dynamic generation of D-terms are succinctly encoded into finite quivers. By studying the Poincar\'e polynomial of the quiver moduli space using the Reineke formula, we can learn about such useful concepts as Donaldson-Thomas invariants, instanton transitions and supersymmetry breaking.Comment: 38 pages, 5 figures, 1 tabl

On Instanton Effects in F-theory

We revisit the issue of M5-brane instanton corrections to the superpotential in F-theory compactifications on elliptically fibered Calabi-Yau fourfolds. Elaborating on concrete geometries, we compare the instanton zero modes for non-perturbative F-theory models with the zero modes in their perturbative Sen limit. The fermionic matter zero modes localized on the intersection of the instanton with the space-time filling D7-branes show up in a geometric way in F-theory. Methods for their computation are developed and, not surprisingly, exceptional gauge group structures do appear. Finally, quite intriguing geometrical aspects of the one-loop determinant are discussed.Comment: 52 pages, 8 figures, 13 tables; v2: extended discussion of matter zero modes, refs added; v3: sections 3.3 + 4.1 restructure

Fast empirical Bayesian LASSO for multiple quantitative trait locus mapping

<p>Abstract</p> <p>Background</p> <p>The Bayesian shrinkage technique has been applied to multiple quantitative trait loci (QTLs) mapping to estimate the genetic effects of QTLs on quantitative traits from a very large set of possible effects including the main and epistatic effects of QTLs. Although the recently developed empirical Bayes (EB) method significantly reduced computation comparing with the fully Bayesian approach, its speed and accuracy are limited by the fact that numerical optimization is required to estimate the variance components in the QTL model.</p> <p>Results</p> <p>We developed a fast empirical Bayesian LASSO (EBLASSO) method for multiple QTL mapping. The fact that the EBLASSO can estimate the variance components in a closed form along with other algorithmic techniques render the EBLASSO method more efficient and accurate. Comparing with the EB method, our simulation study demonstrated that the EBLASSO method could substantially improve the computational speed and detect more QTL effects without increasing the false positive rate. Particularly, the EBLASSO algorithm running on a personal computer could easily handle a linear QTL model with more than 100,000 variables in our simulation study. Real data analysis also demonstrated that the EBLASSO method detected more reasonable effects than the EB method. Comparing with the LASSO, our simulation showed that the current version of the EBLASSO implemented in Matlab had similar speed as the LASSO implemented in Fortran, and that the EBLASSO detected the same number of true effects as the LASSO but a much smaller number of false positive effects.</p> <p>Conclusions</p> <p>The EBLASSO method can handle a large number of effects possibly including both the main and epistatic QTL effects, environmental effects and the effects of gene-environment interactions. It will be a very useful tool for multiple QTL mapping.</p

Comprehensive analysis of human microRNA target networks

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) mediate posttranscriptional regulation of protein-coding genes by binding to the 3' untranslated region of target mRNAs, leading to translational inhibition, mRNA destabilization or degradation, depending on the degree of sequence complementarity. In general, a single miRNA concurrently downregulates hundreds of target mRNAs. Thus, miRNAs play a key role in fine-tuning of diverse cellular functions, such as development, differentiation, proliferation, apoptosis and metabolism. However, it remains to be fully elucidated whether a set of miRNA target genes regulated by an individual miRNA in the whole human microRNAome generally constitute the biological network of functionally-associated molecules or simply reflect a random set of functionally-independent genes.</p> <p>Methods</p> <p>The complete set of human miRNAs was downloaded from miRBase Release 16. We explored target genes of individual miRNA by using the Diana-microT 3.0 target prediction program, and selected the genes with the miTG score ≧ 20 as the set of highly reliable targets. Then, Entrez Gene IDs of miRNA target genes were uploaded onto KeyMolnet, a tool for analyzing molecular interactions on the comprehensive knowledgebase by the neighboring network-search algorithm. The generated network, compared side by side with human canonical networks of the KeyMolnet library, composed of 430 pathways, 885 diseases, and 208 pathological events, enabled us to identify the canonical network with the most significant relevance to the extracted network.</p> <p>Results</p> <p>Among 1,223 human miRNAs examined, Diana-microT 3.0 predicted reliable targets from 273 miRNAs. Among them, KeyMolnet successfully extracted molecular networks from 232 miRNAs. The most relevant pathway is transcriptional regulation by transcription factors RB/E2F, the disease is adult T cell lymphoma/leukemia, and the pathological event is cancer.</p> <p>Conclusion</p> <p>The predicted targets derived from approximately 20% of all human miRNAs constructed biologically meaningful molecular networks, supporting the view that a set of miRNA targets regulated by a single miRNA generally constitute the biological network of functionally-associated molecules in human cells.</p

Neutrophils in cancer: neutral no more

Neutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view. The traditionally held belief that neutrophils are inert bystanders is being challenged by the recent literature. Emerging evidence indicates that tumours manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumour behaviour. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets

Higgs Multiplets in Heterotic GUT Models

For supersymmetric GUT models from heterotic string theory, built from a stable holomorphic SU(n) vector bundle $V$ on a Calabi-Yau threefold $X$, the net amount of chiral matter can be computed by a Chern class computation. Corresponding computations for the number $N_H$ of Higgses lead for the phenomenologically relevant cases of GUT group SU(5) or SO(10) to consideration of the bundle \La^2 V. In a class of bundles where everything can be computed explicitly (spectral bundles on elliptic $X$) we find that the computation for $N_H$ gives a result which is in conflict with expectations. We argue that this discrepancy has its origin in the subtle geometry of the spectral data for \La^2 V and that taking this subtlety into account properly should resolve the problem.Comment: 29 pages; comments and references adde