julilili42/papers huggingface dataset:
In vivo generalized diffusion tensor imaging (GDTI) using higher‐order tensors (HOT)
2009-12-01

Abstract Generalized diffusion tensor imaging (GDTI) using higher‐order tensor (HOT) statistics generalizes the technique of diffusion tensor imaging by including the effect of nongaussian diffusion on the signal of MRI. In GDTI‐HOT, the effect of nongaussian diffusion is characterized by higher‐order tensor statistics (i.e., the cumulant tensors or the moment tensors), such as the covariance matrix (the second‐order cumulant tensor), the skewness tensor (the third‐order cumulant tensor), and the kurtosis tensor (the fourth‐order cumulant tensor). Previously, Monte Carlo simulations have been applied to verify the validity of this technique in reconstructing complicated fiber structures. However, no in vivo implementation of GDTI‐HOT has been reported. The primary goal of this study is to establish GDTI‐HOT as a feasible in vivo technique for imaging nongaussian diffusion. We show that probability distribution function of the molecular diffusion process can be measured in vivo with GDTI‐HOT and be visualized with three‐dimensional glyphs. By comparing GDTI‐HOT to fiber structures that are revealed by the highest resolution diffusion‐weighted imaging (DWI) possible in vivo, we show that the GDTI‐HOT can accurately predict multiple fiber orientations within one white matter voxel. Furthermore, through bootstrap analysis we demonstrate that in vivo measurement of HOT elements is reproducible, with a small statistical variation that is similar to that of diffusion tensor imaging. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.
Toll-Like Receptor 3 Has No Critical Role During Early Immune Response of Human Monocyte-Derived Dendritic Cells After Infection with the Human Cytomegalovirus Strain TB40E
2009-12-01

Toll-like receptors (TLRs) recognize an increasingly broad range of pathogens, thus demonstrating the importance of these pattern-recognition receptors (PRRs) in host defense. Here, the role of TLR3 in the interaction of monocyte-derived dendritic cells (moDCs) with human cytomegalovirus (HCMV) was investigated by using the TB40E strain, which actively replicates in moDCs. Microarray analysis and quantitative real-time PCR revealed that TB40E infection of moDCs led to changes in the gene expression pattern. A variety of proinflammatory cytokines and chemokines (CXCL10, CXCL11, and CCL5), TLR3, and genes whose products function downstream of the TLR3 signaling pathway (e.g., IFN-alpha and IFN-beta) were significantly upregulated. By silencing TLR3 expression with short interfering RNA (siRNA), and subsequent stimulation with TLR3 ligand poly I:C, expression of IFN-beta was markedly reduced compared to cells transfected with a non-silencing control siRNA. However, expression of IFN-beta induced by HCMV was not diminished when TLR3 was silenced first. Thus the early HCMV-triggered immune response of human moDCs appears to be independent of TLR3 signaling.
Hepatitis C virus core protein induces apoptosis-like caspase independent cell death
2009-12-01

Abstract Background Hepatitis C virus (HCV) associated liver diseases may be related to apoptotic processes. Thus, we investigated the role of different HCV proteins in apoptosis induction as well as their potency to interact with different apoptosis inducing agents. Methods and Results The use of a tightly adjustable tetracycline (Tet)-dependent HCV protein expression cell system with the founder osteosarcoma cell line U-2 OS allowed switch-off and on of the endogenous production of HCV proteins. Analyzed were cell lines expressing the HCV polyprotein, the core protein, protein complexes of the core , envelope proteins E1 , E2 and p7 , and non-structural proteins NS3 and NS4A , NS4B or NS5A and NS5B . Apoptosis was measured mainly by the detection of hypodiploid apoptotic nuclei in the absence or presence of mitomycin C, etoposide, TRAIL and an agonistic anti-CD95 antibody. To further characterize cell death induction, a variety of different methods like fluorescence microscopy, TUNEL (terminal deoxynucleotidyl transferase (TdT)-catalyzed deoxyuridinephosphate (dUTP)-nick end labeling) assay, Annexin V staining, Western blot and caspase activation assays were included into our analysis. Two cell lines expressing the core protein but not the total polyprotein exerted a strong apoptotic effect, while the other cell lines did not induce any or only a slight effect by measuring the hypodiploid nuclei. Cell death induction was caspase-independent since it could not be blocked by zVAD-fmk. Moreover, caspase activity was absent in Western blot analysis and fluorometric assays while typical apoptosis-associated morphological features like the membrane blebbing and nuclei condensation and fragmentation could be clearly observed by microscopy. None of the HCV proteins influenced the apoptotic effect mediated via the mitochondrial apoptosis pathway while only the core protein enhanced death-receptor-mediated apoptosis. Conclusion Our data showed a caspase-independent apoptosis-like effect of the core protein, which seems to be inhibited in the presence of further HCV proteins like the non structural (NS) proteins. This observation could be of relevance for the viral spread since induction of an apoptosis-like cell death by the core protein may have some impact on the release of the HCV particles from the host cell.
Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins
2009-12-01

Abstract Successful establishment and persistence of adenovirus (Ad) infections are facilitated by immunosubversive functions encoded in the early transcription unit 3 (E3). The E3/19K protein has a dual role, preventing cell surface transport of MHC class I/HLA class I (MHC-I/HLA-I) Ags and the MHC-I–like molecules (MHC-I chain-related chain A and B [MICA/B]), thereby inhibiting both recognition by CD8 T cells and NK cells. Although some crucial functional elements in E3/19K have been identified, a systematic analysis of the functional importance of individual amino acids is missing. We now have substituted alanine for each of 21 aas in the luminal domain of Ad2 E3/19K conserved among Ads and investigated the effects on HLA-I downregulation by coimmunoprecipitation, pulse-chase analysis, and/or flow cytometry. Potential structural alterations were monitored using conformation-dependent E3/19K-specific mAbs. The results revealed that only a small number of mutations abrogated HLA-I complex formation (e.g., substitutions W52, M87, and W96). Mutants M87 and W96 were particularly interesting as they exhibited only minimal structural changes suggesting that these amino acids make direct contacts with HLA-I. The considerable number of substitutions with little functional defects implied that E3/19K may have additional cellular target molecules. Indeed, when assessing MICA/B cell-surface expression we found that mutation of T14 and M82 selectively compromised MICA/B downregulation with essentially no effect on HLA-I modulation. In general, downregulation of HLA-I was more severely affected than that of MICA/B; for example, substitutions W52, M87, and W96 essentially abrogated HLA-I modulation while largely retaining the ability to sequester MICA/B. Thus, distinct conserved amino acids seem preferentially important for a particular functional activity of E3/19K.
On the number of allelic types for samples taken from exchangeable coalescents with mutation
2009-12-01

Let K n denote the number of types of a sample of size n taken from an exchangeable coalescent process (Ξ-coalescent) with mutation. A distributional recursion for the sequence ( K n ) n ∈N is derived. If the coalescent does not have proper frequencies, i.e. if the characterizing measure Ξ on the infinite simplex Δ does not have mass at 0 and satisfies ∫ Δ ∣ x ∣Ξ(d x )/( x , x )&lt;∞, where ∣ x ∣:=∑ i =1 ∞ x i and ( x , x )≔∑ i =1 ∞ x i 2 for x =( x 1 , x 2 ,...)∈Δ, then K n / n converges weakly as n →∞ to a limiting variable K that is characterized by an exponential integral of the subordinator associated with the coalescent process. For so-called simple measures Ξ satisfying ∫ Δ Ξ(d x )/( x , x )&lt;∞, we characterize the distribution of K via a fixed-point equation.
Germ-line variation at a functional p53 binding site increases susceptibility to breast cancer development
2009-12-01

Abstract Multiple lines of evidence suggest regulatory variation to play an important role in phenotypic evolution and disease development, but few regulatory polymorphisms have been characterized genetically and molecularly. Recent technological advances have made it possible to identify bona fide regulatory sequences experimentally on a genome-wide scale and opened the window for the biological interrogation of germ-line polymorphisms within these sequences. In this study, through a forward genetic analysis of bona fide p53 binding sites identified by a genome-wide chromatin immunoprecipitation and sequence analysis, we discovered a SNP (rs1860746) within the motif sequence of a p53 binding site where p53 can function as a regulator of transcription. We found that the minor allele (T) binds p53 poorly and has low transcriptional regulation activity as compared to the major allele (G). Significantly, the homozygosity of the minor allele was found to be associated with an increased risk of ER negative breast cancer (OR = 1.47, P = 0.038) from the analysis of five independent breast cancer samples of European origin consisting of 6,127 breast cancer patients and 5,197 controls. rs1860746 resides in the third intron of the PRKAG2 gene that encodes the γ subunit of the AMPK protein, a major sensor of metabolic stress and a modulator of p53 action. However, this gene does not appear to be regulated by p53 in lymphoblastoid cell lines nor in a cancer cell line. These results suggest that either the rs1860746 locus regulates another gene through distant interactions, or that this locus is in linkage disequilibrium with a second causal mutation. This study shows the feasibility of using genomic scale molecular data to uncover disease associated SNPs, but underscores the complexity of determining the function of regulatory variants in human populations.
Use of MT3DMS for Heat Transport Simulation of Shallow Geothermal Systems
2009-12-01

The multi-species transport model MT3DMS is applied to simulate heat transport in shallow confined aquifers. This is done by taking advantage of the mathematical similarities between the description of heat and solute transport. A comprehensive analysis on the applicability of MT3DMS (version 5.2) for heat transport simulation of closed shallow geothermal systems is shown. MT3DMS simulations are compared with results from heat analytical solutions and with those from the established numerical code FEFLOW. Issues regarding the definition of the boundary conditions, as well as the evaluation of the type of the numerical advection solver are investigated. The computed results are examined based on residual errors. The overall agreement of MT3DMS with the analytical solutions and FEFLOW is good. Larger discrepancies are only found close to the heat source, which is due to the inherent differences of the numerical methods used by each code and the boundary conditions required by the analytical solutions. Despite these differences we find that MT3DMS can be successfully applied to simulate heat transport in saturated and confined porous media under the influence of GSHP systems.
Governance in Adult and Further Education
2009-12-01

There is little discussion in Germany on governance of further education. This is surprising for two reasons—first, that the process of German unification should have sparked such a debate, and second, because it was expected that the current international discussions about governance would also reach a scholarly debate on further education. A potential cause for the absent debate on governance might lie in the lack of adequate models to help grasp the diversity of actors, structures, and processes in the field of further education. Against this background and in the context of governance theories in the social sciences, the present article develops a framework model for multilevel analyses of governance of further education. The proposed model might prove stimulating for further research in a synchronic or diachronic perspective as well as in national or international comparisons.
Thienopyridone Antibacterials V [1]. Synthesis of Some N(7)-Azacyclohexyl-4-oxothieno[2,3-b]pyridine-5-carboxylic Acids and Related Congeners
2009-12-01

A series of N(7)-azacyclohexyl-4-oxo-4,7-dihydrothieno[2,3-b]-pyridine-5-carboxylic acids 9a - c, related congeners 9d - g and their methyl esters 8a - g were prepared by cyclization of the respective 2-[(2,5-dichlorothien-3-yl)carbonyl]-3-[(N(7)-azacyclyl/acyclic)amino]acrylates 7a - g. The latter intermediates are accessible from methyl 2-[(2,5-dichlorothien-3-yl)carbonyl]-3-ethoxyacrylate (6). Of the present series, the 7-(N,N-dimethylamino) derivative 9d exhibited good activity, especially against Klebsiella pneumoniae and Salmonella paratyphi A (MIC = 0.5 and 1.0 μgmL −1 , respectively).
A life no longer worth playing: some remarks on in-game suicide
2009-12-01

While references to life and death are often made in texts dealing with video games, and violence in video games is still among the most discussed issues, there are, to date, only a few accounts of the act of virtual self-killing or in-game suicide. In fact, in most video games the player's task is to keep his or her character alive. However, there are some very prominent examples of video games that include the suicide of player and non-player characters. By in-game suicide we refer to any kind of self-harming behaviour with intended lethal outcome for a virtual, human-like character in a game. This article will begin by building a typology of different modes of in-game suicide, before going on to take a closer look at several examples. One major distinction for this research is based on the motivation of the character, whereby we distinguish between game-world's internal motivation and game-world's external motivation. Therefore, some basic considerations on the relationship between player and character are given. In the third section we will analyze three different kinds of games involving suicide: first, we will address games where the act of self-killing is the main task of the player; this is followed by an examination of suicide attackers in video games; and finally, we will address the issue of (attempted) in-game suicide as part of the practice of playing, which includes rituals of self-destruction as well as the dramatic staging of a character's departure from the game's world.
Ethylene-bridged Mesoporous Organosilicas with Hexagonal and Cubic Symmetry
2009-12-01

A series of ordered periodic mesoporous organosilicas (PMOs) with cubic and hexagonal symmetries were fabricated by using divalent surfactants [CH 3 (CH 2 ) 15 NMe 2 (CH 2 ) 3 NMe 3 ] 2+ 2Br − (C 16-3-1 ) or binary surfactant mixtures [CH 3 (CH 2 ) 15 NMe 3 ] + Br − (C 16 TABr) and C 16-3-1 as structure-directing agents (SDAs) and 1,2-bis(triethoxysilyl)ethane (BTEE) as an organosilica source under various basic conditions. The shape/structure of surfactant, molar ratio of binary surfactant mixtures, and base concentration crucially affect the formation of distinct mesophases. Face-centered cubic Fm3̄̅m mesoporous organosilicas can be obtained by using various concentrations of divalent surfactant C 16-3-1 or equimolar mixtures of divalent and monocationic surfactants as SDAs under basic conditions. Cubic Pm3̄̅n or 2D hexagonal p6mm mesophases can be synthesized by changing the molar ratio of the binary surfactant mixtures or the amount of the base NaOH. Use of monocationic C 16 TABr instead of C 16-3-1 as template produced the hexagonal p6mm mesophase exclusively independent of the amount of the surfactant and the base. In addition, use of trimethylbenzene as expander molecule in the aforementioned binary surfactant template system caused a mesophase transformation from cubic Pm3̄̅n to p6mm symmetry. All samples were characterized by powder X-ray diffraction (PXRD) analysis and N2 physisorption. The formation of face-centered cubic Fm ̄3m, primary cubic Pm3̄̅n, and hexagonal p6mm PMOs was also confirmed by transmission electron microscopy (TEM), revealing a good long-range ordering with regular arrays.Moreover, variation of the synthesis parameters resulted in a variety of different PMO morphologies, as ascertained by scanning electron microscopy (SEM). FT-IR and solid-state 13 C and 29 Si NMR spectroscopy further revealed that the organic groups were uniformly incorporated into the framework. The various BET surface areas of the PMOs range from 470 to 780 m 2 g −1 , while the pore diameters lie within a 26 to 30 °A range, as derived from N 2 physisorption
On the number of allelic types for samples taken from exchangeable coalescents with mutation
2009-12-01

Let K n denote the number of types of a sample of size n taken from an exchangeable coalescent process (Ξ-coalescent) with mutation. A distributional recursion for the sequence ( K n ) n ∈N is derived. If the coalescent does not have proper frequencies, i.e. if the characterizing measure Ξ on the infinite simplex Δ does not have mass at 0 and satisfies ∫ Δ ∣ x ∣Ξ(d x )/( x , x )&amp;lt;∞, where ∣ x ∣:=∑ i =1 ∞ x i and ( x , x )≔∑ i =1 ∞ x i 2 for x =( x 1 , x 2 ,...)∈Δ, then K n / n converges weakly as n →∞ to a limiting variable K that is characterized by an exponential integral of the subordinator associated with the coalescent process. For so-called simple measures Ξ satisfying ∫ Δ Ξ(d x )/( x , x )&amp;lt;∞, we characterize the distribution of K via a fixed-point equation.
Prevention of Hot Spot Development on Coarse-Grained Dynamically Reconfigurable Architectures
2009-12-01

With the increasing power density of deep submicron technology, temperature becomes one of the dominating factors for the reliability of integrated circuits. Coarse-grained reconfigurable devices typically exhibit spatially nonuniform activity, which results in areas of localized heating, so called hot spots. In this work we investigate the effects of continuous activity migration in order to prevent hot spots. By applying activity migration we are able to reduce temporal and spatial variations of temperature by up to 87%.
Lehren aus der Krise – Notwendige Änderungen der Finanzmarktregeln und zur Begrenzung systemischer Risiken
2009-12-01

Abstract The latest financial crisis has been caused by a mixture of state and market failure, argues Otmar Issing. To avoid future crises, more transparency is needed - not by gathering more information, but by gathering it systematically and thereby creating “intelligent transparency”. Furthermore, regulation has to be global, he states. The necessary institutions are in place: The International Monetary Fund, the Financial Stability Board and the Bank for International Settlements. Stephany Griffith-Jones and Stefano Pagliari point out, that containing “systemic risk” is one of the most important rationales for regulating financial markets. Our understanding of the sources of systemic risk has repeatedly been challenged by major episodes of financial instability. The crisis that started in the summer of 2007 has been no exception. They discuss how the latest global financial crisis urges analysts and regulators to rethink the origin of systemic risk beyond a narrow focus on the banking sector, beyond the “too big to fail problem”, and beyond a narrow micro-prudential focus. They focus on two regulatory principles: comprehensiveness and countercyclicality. Claudia Buch und Katja Neugebauer review the existing empirical evidence on whether the increase in cross-border activities has allowed banks to diversify risks and to what extent it has increased banks’ exposure to systemic risks.
Outcome Prediction in Node-Negative Breast Cancer Based on ASCO-Recommended Biomarkers uPA/PAI-1 Using the Final 10-Year Analysis of the Randomized Multicenter Chemo N0 Trial Compared to Adjuvant Online™.
2009-12-01

Abstract Background: Based on interim analysis of Chemo N0, the first prospective multicenter randomized clinical trial using biomarkers uPA/PAI-1 for risk stratification and chemotherapy selection in N0 breast cancer, uPA/PAI-1 are now recommended for routine use by ASCO and AGO guidelines. Final 10-year follow-up of Chemo N0 has validated the clinically relevant long-term prognostic and predictive impact of uPA/PAI-1 in N0 breast cancer. To quantify the clinical utility of this impact, outcomes in subgroups defined by these biomarkers were compared to predictions of Adjuvant OnlineTM, the leading validated tool based on established clinical factors. Methods: In Chemo N0, patients (n=647, 1993-98) were prospectively stratified according to uPA/PAI-1: High-risk patients were randomized (6x CMF vs. observation), low-risk patients observed. Retrospectively, we divided recruited patients into two groups (chemotherapy vs. no adjuvant therapy) and stratified using uPA/PAI-1 (low vs. high). Individual 10-year OS was calculated by www.adjuvantonline.org (Version 7.0); these estimated values were compared to the observed Chemo N0 10-year OS. Results: 383/647 patients have complete 10-year follow-up data. Median 10-year OS estimated by Adjuvant OnlineTM was 80.5% taking into account administered adjuvant therapy; 10-year Chemo N0 follow-up revealed observed 10-year OS of 74.7% (97/383 died). 77.8% (298/383) did not receive chemotherapy: In high-risk, untreated patients (n=137), 10-year OS was 72.3% vs. estimated 81.1%. In CMF-treated patients (all high-risk, n=85), observed OS was 61.2% vs. estimated 76.4%. Conclusions: For the first time, risk assessment by novel biomarkers is compared to that by Adjuvant OnlineTM in final data from a randomized prospective clinical trial. In patients with high uPA/PAI-1, the individual 10-year risk calculated by Adjuvant OnlineTM seems to be underestimated compared to observed patient outcome. Tumor-biological information provided by validated biomarkers thus has the potential of enhancing epidemiology-based risk estimation using only established factors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4038.
A Collaborative Self-Monitoring System for highly reliable wireless sensor networks
2009-12-01

Based on a decentralized algorithm that determines dedicated observers for each sensor node we propose a new monitoring approach for highly reliable wireless sensor networks. By disseminating, collecting and evaluating health status information, each node is always well-informed about the health state of its neighbors and can thereby determine its best suited observer by itself. Our monitoring approach offers quick node failure detection and provides tools to arrange counter measures in critical situations for any sensor system.