Информационные интеллектуальные системы и семантический веб

В учебном пособии рассматриваются основные составляющие технологии семантического веба: XML, пространство имен, универсальный идентификатор ресурсов URI, XML Schema, XSL, RDF, RDF Schema и OWL. Особое внимание уделяется использованию DTD и XML Schema, а также модели DOM XML. Материал проиллюстрирован наглядными практическими примерами, разделы включают лабораторные работы. Предназначено для студентов специальностей "Прикладная лингвистика", "Прикладная информатика" и других информационных и компьютерных направлений

GridLabs: Facilitating collaborative access to remote laboratories

eScience is usually characterized by the cooperation of distributed groups of researchers who share data and computing environments and perform experiments together. Often immense data sets that were produced by expensive equipments need to be accessed and evaluated. Such eScience scenarios require both, support for collaboration of researchers at distant locations and also the remote control of the shared laboratory devices. However, this type of remote experimentation and collaboration must be taught during university education. In this paper, we propose a framework that supports the training of above practices through the provision of a dedicated collaboration environment. It extends current approaches with support for a life cycle of remote labs, including scheduling the access to remote labs as well as defining access permissions. Our experiences in teaching lab courses suggest that the approach is also applicable in eScience scenarios

Asymmetric simple exclusion process in one-dimensional chains with long-range links

We study the boundary-driven asymmetric simple exclusion process (ASEP) in a one-dimensional chain with long-range links. Shortcuts are added to a chain by connecting $pL$ different pairs of sites selected randomly where $L$ and $p$ denote the chain length and the shortcut density, respectively. Particles flow into a chain at one boundary at rate $\alpha$ and out of a chain at the other boundary at rate $\beta$, while they hop inside a chain via nearest-neighbor bonds and long-range shortcuts. Without shortcuts, the model reduces to the boundary-driven ASEP in a one-dimensional chain which displays the low density, high density, and maximal current phases. Shortcuts lead to a drastic change. Numerical simulation studies suggest that there emerge three phases; an empty phase with $\rho = 0$, a jammed phase with $\rho = 1$, and a shock phase with $0<\rho<1$ where $\rho$ is the mean particle density. The shock phase is characterized with a phase separation between an empty region and a jammed region with a localized shock between them. The mechanism for the shock formation and the non-equilibrium phase transition is explained by an analytic theory based on a mean-field approximation and an annealed approximation.Comment: revised version (16 pages and 6 eps figures

Loss of APC induces polyploidy as a result of a combination of defects in mitosis and apoptosis

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene initiate a majority of colorectal cancers. Acquisition of chromosomal instability is an early event in these tumors. We provide evidence that the loss of APC leads to a partial loss of interkinetochore tension at metaphase and alters mitotic progression. Furthermore, we show that inhibition of APC in U2OS cells compromises the mitotic spindle checkpoint. This is accompanied by a decrease in the association of the checkpoint proteins Bub1 and BubR1 with kinetochores. Additionally, APC depletion reduced apoptosis. As expected from this combination of defects, tetraploidy and polyploidy are consequences of APC inhibition in vitro and in vivo. The removal of APC produced the same defects in HCT116 cells that have constitutively active β-catenin. These data show that the loss of APC immediately induces chromosomal instability as a result of a combination of mitotic and apoptotic defects. We suggest that these defects amplify each other to increase the incidence of tetra- and polyploidy in early stages of tumorigenesis

From Cancer to Immune-Mediated Diseases and Tolerance Induction: Lessons Learned From Immune Oncology and Classical Anti-cancer Treatment

Success in cancer treatment over the last four decades has ranged from improvements in classical drug therapy to immune oncology. Anti-cancer drugs have also often proven beneficial for the treatment of inflammatory and autoimmune diseases. In this review, we report on challenging examples that bridge between treatment of cancer and immune-mediated diseases, addressing mechanisms and experimental models as well as clinical investigations. Patient-derived tumor xenograft (PDX) (humanized) mouse models represent useful tools for preclinical evaluation of new therapies and biomarker identification. However, new developments using human ex vivo approaches modeling cancer, for example in microfluidic human organs-on-chips, promise to identify key molecular, cellular and immunological features of human cancer progression in a fully human setting. Classical drugs which bridge the gap, for instance, include cytotoxic drugs, proteasome inhibitors, PI3K/mTOR inhibitors and metabolic inhibitors. Biologicals developed for cancer therapy have also shown efficacy in the treatment of autoimmune diseases. In immune oncology, redirected chimeric antigen receptor (CAR) T cells have achieved spectacular remissions in refractory B cell leukemia and lymphoma and are currently under development for tolerance induction using cell-based therapies such as CAR Tregs or NK cells. Finally, a brief outline will be given of the lessons learned from bridging cancer and autoimmune diseases as well as tolerance induction

The double Ringel-Hall algebra on a hereditary abelian finitary length category

In this paper, we study the category $\mathscr{H}^{(\rho)}$ of semi-stable coherent sheaves of a fixed slope $\rho$ over a weighted projective curve. This category has nice properties: it is a hereditary abelian finitary length category. We will define the Ringel-Hall algebra of $\mathscr{H}^{(\rho)}$ and relate it to generalized Kac-Moody Lie algebras. Finally we obtain the Kac type theorem to describe the indecomposable objects in this category, i.e. the indecomposable semi-stable sheaves.Comment: 29 page

Skin-impedance in Fabry Disease: A prospective, controlled, non-randomized clinical study

<p>Abstract</p> <p>Background</p> <p>We previously demonstrated improved sweating after enzyme replacement therapy (ERT) in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating), has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM) system.</p> <p>Methods</p> <p>We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive) and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1) moisture reading of the 100^threpetitive reading, 2) rate of change, 3) average of 60–110^threading and 4) overall average of all readings.</p> <p>Results</p> <p>All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p < 0.0001). There was no difference between Fabry patients on ERT and patients naïve to ERT. Increased skin-impedance values for the four skin-impedance outcome measures were found in a small number of dermatome test-sites two days post-enzyme infusions.</p> <p>Conclusion</p> <p>The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool.</p

Co-administration With the Pharmacological Chaperone AT1001 Increases Recombinant Human α-Galactosidase A Tissue Uptake and Improves Substrate Reduction in Fabry Mice

Fabry disease is an X-linked lysosomal storage disorder (LSD) caused by mutations in the gene (GLA) that encodes the lysosomal hydrolase α-galactosidase A (α-Gal A), and is characterized by pathological accumulation of the substrate, globotriaosylceramide (GL-3). Regular infusion of recombinant human α-Gal A (rhα-Gal A), termed enzyme replacement therapy (ERT), is the primary treatment for Fabry disease. However, rhα-Gal A has low physical stability, a short circulating half-life, and variable uptake into different disease-relevant tissues. We hypothesized that coadministration of the orally available, small molecule pharmacological chaperone AT1001 (GR181413A, 1-deoxygalactonojirimycin, migalastat hydrochloride) may improve the pharmacological properties of rhα-Gal A via binding and stabilization. AT1001 prevented rhα-Gal A denaturation and activity loss in vitro at neutral pH and 37 °C. Coincubation of Fabry fibroblasts with rhα-Gal A and AT1001 resulted in up to fourfold higher cellular α-Gal A and ~30% greater GL-3 reduction compared to rhα-Gal A alone. Furthermore, coadministration of AT1001 to rats increased the circulating half-life of rhα-Gal A by >2.5-fold, and in GLA knockout mice resulted in up to fivefold higher α-Gal A levels and fourfold greater GL-3 reduction than rhα-Gal A alone. Collectively, these data highlight the potentially beneficial effects of AT1001 on rhα-Gal A, thus warranting clinical investigation