220 research outputs found
A Flexible and Modular Framework for Implementing Infrastructures for Global Computing
We present a Java software framework for building infrastructures to support the development of applications for systems where mobility and network awareness are key issues. The framework is particularly useful to develop run-time support for languages oriented towards global computing. It enables platform designers to customize communication protocols and network architectures and guarantees transparency of name management and code mobility in distributed environments. The key features are illustrated by means of a couple of simple case studies
DâAgents: Security in a Multiple-Language, Mobile-Agent System
Abstract. Mobile-agent systems must address three security issues: protecting an individual machine, protecting a group of machines, and protecting an agent. In this chapter, we discuss these three issues in the context of DâAgents, a mobile-agent system whose agents can be written in Tcl, Java and Scheme. (DâAgents was formerly known as Agent Tcl.) First we discuss mechanisms existing in DâAgents for protecting an individual machine: (1) cryptographic authentication of the agentâs owner, (2) resource managers that make policy decisions based on the ownerâs identity, and (3) secure execution environments for each language that enforce the decisions of the resource managers. Then we discuss our planned market-based approach for protecting machine groups. Finally we consider several (partial) solutions for protecting an agent from a malicious machine.
Emerging Insights into Keratin 16 Expression during Metastatic Progression of Breast Cancer.
Keratins are the main identification markers of circulating tumor cells (CTCs); however, whether their deregulation is associated with the metastatic process is largely unknown. Previously we have shown by in silico analysis that keratin 16 (KRT16) mRNA upregulation might be associated with more aggressive cancer. Therefore, in this study, we investigated the biological role and the clinical relevance of K16 in metastatic breast cancer. By performing RT-qPCR, western blot, and immunocytochemistry, we investigated the expression patterns of K16 in metastatic breast cancer cell lines and evaluated the clinical relevance of K16 expression in CTCs of 20 metastatic breast cancer patients. High K16 protein expression was associated with an intermediate mesenchymal phenotype. Functional studies showed that K16 has a regulatory effect on EMT and overexpression of K16 significantly enhanced cell motility (p < 0.001). In metastatic breast cancer patients, 64.7% of the detected CTCs expressed K16, which was associated with shorter relapse-free survival (p = 0.0042). Our findings imply that K16 is a metastasis-associated protein that promotes EMT and acts as a positive regulator of cellular motility. Furthermore, determining K16 status in CTCs provides prognostic information that helps to identify patients whose tumors are more prone to metastasize
Microphytobenthos of Arctic Kongsfjorden (Svalbard, Norway): biomass and potential primary production along the shore line
During summer 2007, Arctic microphytobenthic potential primary production was measured at several stations around the coastline of Kongsfjorden (Svalbard, Norway) at ?5 m water depth and at two stations at five different water depths (5, 10, 15, 20, 30 m). Oxygen planar optode sensor spots were used ex situ to determine oxygen exchange in the overlying water of intact sediment cores under controlled light (ca. 100 ?mol photons m?2 s?1) and temperature (2â4°C) conditions. Patches of microalgae (mainly diatoms) covering sandy sediments at water depths down to 30 m showed high biomass of up to 317 mg chl a m?2. In spite of increasing water depth, no significant trend in âphotoautotrophic active biomassâ (chl a, ratio living/dead cells, cell sizes) and, thus, in primary production was measured at both stations. All sites from ?5 to 30 m water depth exhibited variable rates of net production from ?19 to +40 mg O2 m?2 h?1 (?168 to +360 mg C m?2 day?1) and gross production of about 2â62 mg O2 m?2 h?1 (17â554 mg C m?2 day?1), which is comparable to other polar as well as temperate regions. No relation between photoautotrophic biomass and gross/net production values was found. Microphytobenthos demonstrated significant rates of primary production that is comparable to pelagic production of Kongsfjorden and, hence, emphasised the importance as C source for the zoobenthos
PRMT5-Selective Inhibitors Suppress Inflammatory T Cell Responses and Experimental Autoimmune Encephalomyelitis
In the autoimmune disease multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), expansion of pathogenic, myelin-specific Th1 cell populations drives active disease; selectively targeting this process may be the basis for a new therapeutic approach. Previous studies have hinted at a role for protein arginine methylation in immune responses, including T cellâmediated autoimmunity and EAE. However, a conclusive role for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lacking. PRMT5 is the main PRMT responsible for symmetric dimethylation of arginine residues of histones and other proteins. PRMT5 drives embryonic development and cancer, but its role in T cells, if any, has not been investigated. In this article, we show that PRMT5 is an important modulator of CD4+ T cell expansion. PRMT5 was transiently upregulated during maximal proliferation of mouse and human memory Th cells. PRMT5 expression was regulated upstream by the NF-ÎșB pathway, and it promoted IL-2 production and proliferation. Blocking PRMT5 with novel, highly selective small molecule PRMT5 inhibitors severely blunted memory Th expansion, with preferential suppression of Th1 cells over Th2 cells. In vivo, PRMT5 blockade efficiently suppressed recall T cell responses and reduced inflammation in delayed-type hypersensitivity and clinical disease in EAE mouse models. These data implicate PRMT5 in the regulation of adaptive memory Th cell responses and suggest that PRMT5 inhibitors may be a novel therapeutic approach for T cellâmediated inflammatory disease
Different osteosyntheses for Colles' fracture: A mechanical study in 42 cadaver bones
Background and purpose In recent years several different plate designs for internal fixation of fractures of the distal radius have been developed. However, few biomechanical studies have been performed to compare these new implants. The purpose of this study was to compare the mechanical properties of 5 different commercially available plates (3 volar and 2 dorsal) with standard K-wire fixation using a distal radial cadaver model
Circulating extracellular DNA is an independent predictor of mortality in elderly patients with venous thromboembolism.
Venous thromboembolism (VTE) is a major cause of morbidity and mortality in elderly patients. Extracellular DNA is a pro-inflammatory and pro-thrombotic mediator in vitro and in animal models. Levels of circulating extracellular DNA (ceDNA) are increased in VTE patients, but the association of ceDNA with VTE extent and clinical outcome is poorly understood.
We analyzed the association of ceDNA with the extent of VTE, categorized as distal and proximal deep vein thrombosis and pulmonary embolism, and with the clinical outcomes VTE recurrence and mortality.
We quantified ceDNA by a fluorescent probe, as well as circulating nucleosomes and neutrophil extracellular traps (NETs) by ELISA in plasma from 611 patients aged â„ 65 years with acute VTE of a prospective cohort study (SWITCO65+).
Levels of ceDNA and nucleosomes, but not NETs, correlated with VTE extent. Infectious comorbidities independently increased ceDNA levels in VTE. CeDNA strongly correlated with C-reactive protein and leukocytosis, suggesting an association of ceDNA with inflammation in VTE patients. CeDNA furthermore predicted PE-related and all-cause mortality, but not VTE recurrence, during a 3-year follow-up.
Our study suggests that ceDNA levels in VTE patients reflect the degree of inflammation and may serve as a biomarker to stratify VTE patients at risk for mortality
Front Immunol
NK cells are phenotypically and functionally diverse lymphocytes due to variegated expression of a large array of receptors. NK-cell activity is tightly regulated through integration of receptor-derived inhibitory and activating signals. Thus, the receptor profile of each NK cell ultimately determines its ability to sense aberrant cells and subsequently mediate anti-viral or anti-tumor responses. However, an in-depth understanding of how different receptor repertoires enable distinct immune functions of NK cells is lacking. Therefore, we investigated the phenotypic diversity of primary human NK cells by performing extensive phenotypic characterization of 338 surface molecules using flow cytometry (n = 18). Our results showed that NK cells express at least 146 receptors on their surface. Of those, 136 (>90%) exhibited considerable inter-donor variability. Moreover, comparative analysis of CD56bright and CD56dim NK cells identified 70 molecules with differential expression between the two major NK-cell subsets and allowed discrimination of these subsets via unsupervised hierarchical clustering. These receptors were associated with a broad range of NK-cell functions and multiple molecules were not previously associated with predominant expression on either subset (e.g. CD82 and CD147). Altogether, our study contributes to an improved understanding of the phenotypic diversity of NK cells and its potential functional implications on a cellular and population level. While the identified distinct signatures in the receptor repertoires provide a molecular basis for the differential immune functions exerted by CD56bright and CD56dim NK cells, the observed inter-individual differences in the receptor repertoire of NK cells may contribute to a diverging ability to control certain diseases
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Addressing the Black Box of AI â A Model and Research Agenda on the Co-Constitution of Aging and Artificial Intelligence
Algorithmic technologies and (large) data infrastructures, often referred to as Artificial Intelligence (AI), have received increasing attention from gerontological research in the last decade. While there is much literature that dissects and explores the development, application, and evaluation of AI relevant for gerontology, this article makes a novel contribution by critically engaging with the theorizing in this growing field of research. We observe that gerontologyâs engagement with AI is shaped by an interventionist logic that situates AI as a black box for gerontological research. We demonstrate how this black box logic has neglected many aspects of AI as a research topic for gerontology and discuss three classical concepts in gerontology to show how they can be used to open various black boxes of aging and AI in the areas: a) the datafication of aging, b) the political economy of AI and aging, and c) everyday engagements and embodiments of AI in later life. In the final chapter, we propose a model of the co-constitution of aging and AI that makes theoretical propositions to study the relational terrain between aging and AI and hence aims to open the black box of AI in gerontology beyond an interventionist logic.Vera Gallistlâs work on this paper has been funded by the Vienna Science and Technology Fund (WWTF) and by the State of Lower Austria through project ICT20-055 (Grant-ID: 10.47379/ICT20055). Barbara Marshallâs work on this paper has been funded by the Social Science and Humanities Research Council of Canada (435-2017-1343) and the Canadian Institute for Health Research (155188). We acknowledge support by Open Access Publishing Fund of Karl Landsteiner University of Health Sciences, Krems, Austria
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