S/360 TELOR3 program description test, edit, and list and ORB3A tape

IBM 360 TELOR3 program for testing, editing, and listing information on ORB3A tap

Population history from the Neolithic to present on the Mediterranean island of Sardinia: an ancient DNA perspective

Recent ancient DNA studies of western Eurasia have revealed a dynamic history of admixture, with evidence for major migrations during the Neolithic and Bronze Age. The population of the Mediterranean island of Sardinia has been notable in these studies –} Neolithic individuals from mainland Europe cluster more closely with Sardinian individuals than with all other present-day Europeans. The current model to explain this result is that Sardinia received an initial influx of Neolithic ancestry and then remained relatively isolated from expansions in the later Neolithic and Bronze Age that took place in continental Europe. To test this model, we generated genome-wide capture data (approximately 1.2 million variants) for 43 ancient Sardinian individuals spanning the Neolithic through the Bronze Age, including individuals from Sardinia{’}s Nuragic culture, which is known for the construction of numerous large stone towers throughout the island. We analyze these new samples in the context of previously generated genome-wide ancient DNA data from 972 ancient individuals across western Eurasia and whole-genome sequence data from approximately 1,500 modern individuals from Sardinia. The ancient Sardinian individuals show a strong affinity to western Mediterranean Neolithic populations and we infer a high degree of genetic continuity on the island from the Neolithic (around fifth millennium BCE) through the Nuragic period (second millennium BCE). In particular, during the Bronze Age in Sardinia, we do not find significant levels of the {“}Steppe{” ancestry that was spreading in many other parts of Europe at that time. We also characterize subsequent genetic influx between the Nuragic period and the present. We detect novel, modest signals of admixture between 1,000 BCE and present-day, from ancestry sources in the eastern and northern Mediterranean. Within Sardinia, we confirm that populations from the more geographically isolated mountainous provinces have experienced elevated levels of genetic drift and that northern and southwestern regions of the island received more gene flow from outside Sardinia. Overall, our genetic analysis sheds new light on the origin of Neolithic settlement on Sardinia, reinforces models of genetic continuity on the island, and provides enhanced power to detect post-Bronze-Age gene flow. Together, these findings offer a refined demographic model for future medical genetic studies in Sardinia

Homological Type of Geometric Transitions

The present paper gives an account and quantifies the change in topology induced by small and type II geometric transitions, by introducing the notion of the \emph{homological type} of a geometric transition. The obtained results agree with, and go further than, most results and estimates, given to date by several authors, both in mathematical and physical literature.Comment: 36 pages. Minor changes: A reference and a related comment in Remark 3.2 were added. This is the final version accepted for publication in the journal Geometriae Dedicat

Elucidating glycosaminoglycan–protein–protein interactions using carbohydrate microarray and computational approaches

Glycosaminoglycan polysaccharides play critical roles in many cellular processes, ranging from viral invasion and angiogenesis to spinal cord injury. Their diverse biological activities are derived from an ability to regulate a remarkable number of proteins. However, few methods exist for the rapid identification of glycosaminoglycan–protein interactions and for studying the potential of glycosaminoglycans to assemble multimeric protein complexes. Here, we report a multidisciplinary approach that combines new carbohydrate microarray and computational modeling methodologies to elucidate glycosaminoglycan–protein interactions. The approach was validated through the study of known protein partners for heparan and chondroitin sulfate, including fibroblast growth factor 2 (FGF2) and its receptor FGFR1, the malarial protein VAR2CSA, and tumor necrosis factor-α (TNF-α). We also applied the approach to identify previously undescribed interactions between a specific sulfated epitope on chondroitin sulfate, CS-E, and the neurotrophins, a critical family of growth factors involved in the development, maintenance, and survival of the vertebrate nervous system. Our studies show for the first time that CS is capable of assembling multimeric signaling complexes and modulating neurotrophin signaling pathways. In addition, we identify a contiguous CS-E-binding site by computational modeling that suggests a potential mechanism to explain how CS may promote neurotrophin-tyrosine receptor kinase (Trk) complex formation and neurotrophin signaling. Together, our combined microarray and computational modeling methodologies provide a general, facile means to identify new glycosaminoglycan–protein–protein interactions, as well as a molecular-level understanding of those complexes

The N-terminal intrinsically disordered domain of mgm101p is localized to the mitochondrial nucleoid.

The mitochondrial genome maintenance gene, MGM101, is essential for yeasts that depend on mitochondrial DNA replication. Previously, in Saccharomyces cerevisiae, it has been found that the carboxy-terminal two-thirds of Mgm101p has a functional core. Furthermore, there is a high level of amino acid sequence conservation in this region from widely diverse species. By contrast, the amino-terminal region, that is also essential for function, does not have recognizable conservation. Using a bioinformatic approach we find that the functional core from yeast and a corresponding region of Mgm101p from the coral Acropora millepora have an ordered structure, while the N-terminal domains of sequences from yeast and coral are predicted to be disordered. To examine whether ordered and disordered domains of Mgm101p have specific or general functions we made chimeric proteins from yeast and coral by swapping the two regions. We find, by an in vivo assay in S.cerevisiae, that the ordered domain of A.millepora can functionally replace the yeast core region but the disordered domain of the coral protein cannot substitute for its yeast counterpart. Mgm101p is found in the mitochondrial nucleoid along with enzymes and proteins involved in mtDNA replication. By attaching green fluorescent protein to the N-terminal disordered domain of yeast Mgm101p we find that GFP is still directed to the mitochondrial nucleoid where full-length Mgm101p-GFP is targeted

On nonsupersymmetric \BC^4/\BZ_N, tachyons, terminal singularities and flips

We investigate nonsupersymmetric \BC^4/\BZ_N orbifold singularities using their description in terms of the string worldsheet conformal field theory and its close relation with the toric geometry description of these singularities and their possible resolutions. Analytic and numerical study strongly suggest the absence of nonsupersymmetric Type II terminal singularities (i.e. with no marginal or relevant blowup modes) so that there are always moduli or closed string tachyons that give rise to resolutions of these singularities, although supersymmetric and Type 0 terminal singularities do exist. Using gauged linear sigma models, we analyze the phase structure of these singularities, which often involves 4-dimensional flip transitions, occurring between resolution endpoints of distinct topology. We then discuss 4-dim analogs of unstable conifold-like singularities that exhibit flips, in particular their Type II GSO projection and the phase structure. We also briefly discuss aspects of M2-branes stacked at such singularities and nonsupersymmetric AdS_4\times S^7/\BZ_N backgrounds.Comment: Latex, 43pgs incl. appendices, 2 eps figs, v2. minor clarifications added, to appear in JHE

High- and Low-Affinity Epidermal Growth Factor Receptor-Ligand Interactions Activate Distinct Signaling Pathways

Signaling mediated by the Epidermal Growth Factor Receptor (EGFR) is crucial in normal development, and aberrant EGFR signaling has been implicated in a wide variety of cancers. Here we find that the high- and low-affinity interactions between EGFR and its ligands activate different signaling pathways. While high-affinity ligand binding is sufficient for activation of most canonical signaling pathways, low-affinity binding is required for the activation of the Signal transducers and activators of transcription (Stats) and Phospholipase C-gamma 1 (PLCγ1). As the Stat proteins are involved in many cellular responses including proliferation, migration and apoptosis, these results assign a function to low-affinity interactions that has been omitted from computational models of EGFR signaling. The existence of receptors with distinct signaling properties provides a way for EGFR to respond to different concentrations of the same ligand in qualitatively different ways

An Invitation to Higher Gauge Theory

In this easy introduction to higher gauge theory, we describe parallel transport for particles and strings in terms of 2-connections on 2-bundles. Just as ordinary gauge theory involves a gauge group, this generalization involves a gauge '2-group'. We focus on 6 examples. First, every abelian Lie group gives a Lie 2-group; the case of U(1) yields the theory of U(1) gerbes, which play an important role in string theory and multisymplectic geometry. Second, every group representation gives a Lie 2-group; the representation of the Lorentz group on 4d Minkowski spacetime gives the Poincar\'e 2-group, which leads to a spin foam model for Minkowski spacetime. Third, taking the adjoint representation of any Lie group on its own Lie algebra gives a 'tangent 2-group', which serves as a gauge 2-group in 4d BF theory, which has topological gravity as a special case. Fourth, every Lie group has an 'inner automorphism 2-group', which serves as the gauge group in 4d BF theory with cosmological constant term. Fifth, every Lie group has an 'automorphism 2-group', which plays an important role in the theory of nonabelian gerbes. And sixth, every compact simple Lie group gives a 'string 2-group'. We also touch upon higher structures such as the 'gravity 3-group' and the Lie 3-superalgebra that governs 11-dimensional supergravity.Comment: 60 pages, based on lectures at the 2nd School and Workshop on Quantum Gravity and Quantum Geometry at the 2009 Corfu Summer Institut

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity