Alien Registration- Rytky, Esko E. (South Thomaston, Knox County)

https://digitalmaine.com/alien_docs/13115/thumbnail.jp

Brane Decay from the Origin of Time

We present a novel scenario where matter in a spacetime originates from a decaying brane at the origin of time. The decay could be considered as a ``Big Bang''-like event at X^0=0. The closed string interpretation is a time-dependent spacetime with a semi-infinite time direction, with the initial energy of the brane converted into energy flux from the origin. The open string interpretation can be viewed as a string theoretic non-singular initial condition.Comment: 5 pages, 2 eps figure

PinAPL-Py: A comprehensive web-application for the analysis of CRISPR/Cas9 screens.

Large-scale genetic screens using CRISPR/Cas9 technology have emerged as a major tool for functional genomics. With its increased popularity, experimental biologists frequently acquire large sequencing datasets for which they often do not have an easy analysis option. While a few bioinformatic tools have been developed for this purpose, their utility is still hindered either due to limited functionality or the requirement of bioinformatic expertise. To make sequencing data analysis of CRISPR/Cas9 screens more accessible to a wide range of scientists, we developed a Platform-independent Analysis of Pooled Screens using Python (PinAPL-Py), which is operated as an intuitive web-service. PinAPL-Py implements state-of-the-art tools and statistical models, assembled in a comprehensive workflow covering sequence quality control, automated sgRNA sequence extraction, alignment, sgRNA enrichment/depletion analysis and gene ranking. The workflow is set up to use a variety of popular sgRNA libraries as well as custom libraries that can be easily uploaded. Various analysis options are offered, suitable to analyze a large variety of CRISPR/Cas9 screening experiments. Analysis output includes ranked lists of sgRNAs and genes, and publication-ready plots. PinAPL-Py helps to advance genome-wide screening efforts by combining comprehensive functionality with user-friendly implementation. PinAPL-Py is freely accessible at http://pinapl-py.ucsd.edu with instructions and test datasets

Fractional S-branes on a Spacetime Orbifold

Unstable D-branes are central objects in string theory, and exist also in time-dependent backgrounds. In this paper we take first steps to studying brane decay in spacetime orbifolds. As a concrete model we focus on the R^{1,d}/Z_2 orbifold. We point out that on a spacetime orbifold there exist two kinds of S-branes, fractional S-branes in addition to the usual ones. We investigate their construction in the open string and closed string boundary state approach. As an application of these constructions, we consider a scenario where an unstable brane nucleates at the origin of time of a spacetime, its initial energy then converting into energy flux in the form of closed strings. The dual open string description allows for a well-defined description of this process even if it originates at a singular origin of the spacetime.Comment: 22 pages, 6 eps figure

Hepatic heparan sulfate is a master regulator of hepcidin expression and iron homeostasis in human hepatocytes and mice.

Hepcidin is a liver-derived peptide hormone that controls systemic iron homeostasis. Its expression is regulated by the bone morphogenetic protein 6 (BMP6)/SMAD1/5/8 pathway and by the proinflammatory cytokine interleukin 6 (IL6). Proteoglycans that function as receptors of these signaling proteins in the liver are commonly decorated by heparan sulfate, but the potential role of hepatic heparan sulfate in hepcidin expression and iron homeostasis is unclear. Here, we show that modulation of hepatic heparan sulfate significantly alters hepcidin expression and iron metabolism both in vitro and in vivo Specifically, enzymatic removal of heparan sulfate from primary human hepatocytes, CRISPR/Cas9 manipulation of heparan sulfate biosynthesis in human hepatoma cells, or pharmacological manipulation of heparan sulfate-protein interactions using sodium chlorate or surfen dramatically reduced baseline and BMP6/SMAD1/5/8-dependent hepcidin expression. Moreover inactivation of the heparan sulfate biosynthetic gene N-deacetylase and N-sulfotransferase 1 (Ndst1) in murine hepatocytes (Ndst1 f/f AlbCre +) reduced hepatic hepcidin expression and caused a redistribution of systemic iron, leading to iron accumulation in the liver and serum of mice. Manipulation of heparan sulfate had a similar effect on IL6-dependent hepcidin expression in vitro and suppressed IL6-mediated iron redistribution induced by lipopolysaccharide in vivo These results provide compelling evidence that hepatocyte heparan sulfate plays a key role in regulating hepcidin expression and iron homeostasis in mice and in human hepatocytes

Collaboration in electronic resource provision in university libraries: SHEDL, a Scottish case study

This case study examines the growth of collaboration among Scottish higher education institutions. Following a summary of the work of the Scottish Confederation of University and Research Libraries (SCURL), more detailed information is provided on collaboration in the fields of acquisition, licensing, selection, and purchasing. Some of the UK background is outlined, relating to NESLi2 in particular, in order to illuminate the options within Scotland. The origins of negotiations on electronic resource provision within Scotland are described, drawing on developments in other countries including Ireland and Scandinavia. After initial setbacks, the implementation of the Scottish Higher Education Digital Library (SHEDL) from 2007 to 2009 is detailed. Current benefits arising from SHEDL are explained, and some possible future developments are discussed

Disruption of Gastrulation and Heparan Sulfate Biosynthesis in EXT1-Deficient Mice

AbstractMutations in the EXT1 gene are responsible for human hereditary multiple exostosis type 1. The Drosophila EXT1 homologue, tout-velu, regulates Hedgehog diffusion and signaling, which play an important role in tissue patterning during both invertebrate and vertebrate development. The EXT1 protein is also required for the biosynthesis of heparan sulfate glycosaminoglycans that bind Hedgehog. In this study, we generated EXT1-deficient mice by gene targeting. EXT1 homozygous mutants fail to gastrulate and generally lack organized mesoderm and extraembryonic tissues, resulting in smaller embryos compared to normal littermates. RT-PCR analysis of markers for visceral endoderm and mesoderm development indicates the delayed and abnormal development of both of these tissues. Immunohistochemical staining revealed a visceral endoderm pattern of Indian hedgehog (Ihh) in wild-type E6.5 embryos. However, in both EXT1-deficient embryos and wild-type embryos treated with heparitinase I, Ihh failed to associate with the cells. The effect of the EXT1 deletion on heparan sulfate formation was tested by HPLC and cellular glycosyltransferase activity assays. Heparan sulfate synthesis was abolished in EXT1 −/− ES cells and decreased to less than 50% in +/− cell lines. These results indicate that EXT1 is essential for both gastrulation and heparan sulfate biosynthesis in early embryonic development

Increasing the Inflammatory Competence of Macrophages with IL-6 or with Combination of IL-4 and LPS Restrains the Invasiveness of Pancreatic Cancer Cells

Recent studies suggest that pro-inflammatory type M1 macrophages inhibit tumor progression and that anti-inflammatory M2 macrophages enhance it. The aim of this study was to examine the interaction of type M1 and M2 macrophages with pancreatic cancer cells. We studied the migration rate of fluorescein stained pancreatic cancer cells on Matrigel cultured alone or with Granulocyte- Macrophage Colony Stimulating Factor (GM-CSF) differentiated macrophages or with Macrophage Colony Stimulating Factor (M-CSF) differentiated macrophages, skewing the phenotype towards pro- and anti-inflammatory direction, respectively. Macrophage differentiation was assessed with flow cytometry and the cytokine secretion in cell cultures with cytokine array. Both GM-CSF and M-CSF differentiated macrophages increased the migration rate of primary pancreatic adenocarcinoma cell line (MiaPaCa-2) and metastatic cell line (HPAF-II). Stimulation with IL6 or IL4+ LPS reversed the macrophages' increasing effect on the migration rate of Mi-aPaCa-2 completely and partly of HPAF-II. Co-culture with MiaPaCa-2 reduced the inflammatory cytokine secretion of GM-CSF differentiated macrophages. Co-culture of macrophages with pancreatic cancer cells seem to change the inflammatory cytokine profile of GM-CSF differentiated macrophages and this might explain why also GM-CSF differentiated macrophages promoted the invasion. Adding IL6 or IL4+ LPS to the cell culture with MiaPaCa-2 and GM-CSF or M-CSF differentiated macrophages increased the secretion of inflammatory cytokines and this could contribute to the reversion of the macrophage induced increase of cancer cell migration rate.Peer reviewe

37 GHz observations of a large sample of BL Lacertae objects

We present 37 GHz data obtained at Metsahovi Radio Observatory in 2001 December - 2005 April for a large sample of BL Lacertae objects. We also report the mean variability indices and radio spectral indices in frequency intervals 5 - 37 GHz and 37 - 90 GHz. Approximately 34 % of the sample was detected at 37 GHz, 136 BL Lacertae objects in all. A large majority of the detected sources were low-energy BL Lacs (LBLs). The variability index values of the sample were diverse, the mean fractional variability of the sample being \Delta S_2 = 0.31. The spectral indices also varied widely, but the average radio spectrum of the sample sources is flat. Our observations show that many of the high-energy BL Lacs (HBL), which are usually considered radio-quiet, can at times be detected at 37 GHz.Comment: 12 pages, 5 figures + 5 tables. Published in Astronomical Journa

Hawking Radiation from AdS Black Holes

We investigate Hawking radiation from black holes in (d+1)-dimensional anti-de Sitter space. We focus on s-waves, make use of the geometrical optics approximation, and follow three approaches to analyze the radiation. First, we compute a Bogoliubov transformation between Kruskal and asymptotic coordinates and compare the different vacua. Second, following a method due to Kraus, Parikh, and Wilczek, we view Hawking radiation as a tunneling process across the horizon and compute the tunneling probablility. This approach uses an anti-de Sitter version of a metric originally introduced by Painleve for Schwarzschild black holes. From the tunneling probability one also finds a leading correction to the semi-classical emission rate arising from the backreaction to the background geometry. Finally, we consider a spherically symmetric collapse geometry and the Bogoliubov transformation between the initial vacuum state and the vacuum of an asymptotic observer.Comment: 13 pages, latex2e, v2: some clarifications and references adde