julilili42/papers huggingface dataset:
Conformational Sampling by Ab Initio Molecular Dynamics Simulations Improves NMR Chemical Shift Predictions
2013-06-18

Car-Parrinello molecular dynamics simulations were performed for N-methyl acetamide as a small test system for amide groups in protein backbones, and NMR chemical shifts were calculated based on the generated ensemble. If conformational sampling and explicit solvent molecules are taken into account, excellent agreement between the calculated and experimental chemical shifts is obtained. These results represent a landmark improvement over calculations based on classical molecular dynamics (MD) simulations especially for amide protons, which are predicted too high-field shifted based on the latter ensembles. We were able to show that the better results are caused by the solute-solvents interactions forming shorter hydrogen bonds as well as by the internal degrees of freedom of the solute. Inspired by these results, we propose our approach as a new tool for the validation of force fields due to its power of identifying the structural reasons for discrepancies between the experimental and calculated data.
Enhanced Chemokine Receptor Expression on Leukocytes of Patients with Alzheimer's Disease
2013-06-18

Although primarily a neurological complaint, systemic inflammation is present in Alzheimer's Disease, with higher than normal levels of proinflammatory cytokines and chemokines in the periphery as well as the brain. A gradient of these factors may enhance recruitment of activated immune cells into the brain via chemotaxis. Here, we investigated the phenotypes of circulating immune cells in AD patients with multi-colour flow cytometry to determine whether their expression of chemokine receptors is consistent with this hypothesis. In this study, we confirmed our previously reported data on the shift of early- to late-differentiated CD4+ T-cells in AD patients. The percentage of cells expressing CD25, a marker of acute T-cell activation, was higher in patients than in age-matched controls, and percentages of CCR6+ cells were elevated. This chemokine receptor is primarily expressed on pro-inflammatory memory cells and Th17 cells. The proportion of cells expressing CCR4 (expressed on Th2 cells) and CCR5 (Th1 cells and dendritic cells) was also greater in patients, and was more pronounced on CD4+ than CD8+ T-cells. These findings allow a more detailed insight into the systemic immune status of patients with Alzheimer's disease and suggest possible novel targets for immune therapy.
A morphometric approach for the accurate solvation thermodynamics of proteins and ligands
2013-06-18

We have developed a versatile method for calculating solvation thermodynamic quantities for molecules, starting from their atomic coordinates. The contribution of each atom to the thermodynamic quantities is estimated as a linear combination of four fundamental geometric measures of the atomic species, which are defined by Hadwiger's theorem, and the coefficients reflecting their solvation properties. This treatment enables us to calculate the solvation free energy with high accuracy despite of the limited computational load. The method can readily be applied to macromolecules in an all-atom molecular model, allowing the stability of these molecules' structures in solution to be evaluated.
Evaluation on the compliance with secondary prevention and influence factors of ischemic stroke in Hainan province, China
2013-06-18

Survivors of ischemic stroke are still at a significant risk for recurrence. Numerous effective strategies for the secondary prevention of ischemic stroke have now been established; however, these guidelines are not widely known. In this retrospective, a multicenter study was conducted from January 2011 to February 2012 in 10 general hospitals, which included 1300 elderly patients who had previously been diagnosed with ischemic stroke and re-admitted to hospitals. Logistic regression models were fitted to determine the relationship between compliance with secondary prevention therapy and each variable of interest. The treatment rates of antihypertensive, antiplatelet and lipid-lowering therapy were only 56.3%, 48.9% and 19.6%, respectively. Multivariate analysis presented that cardiovascular risk factors would motivate patients with hypertension and hyperlipidemia to receive corresponding treatments. However, it is worth noting that they did not influence the use of antiplatelet therapy. In addition, high education, health education and insurance promote the use of secondary prevention in patients. In conclusion, the importance of antiplatelet therapy should not be ignored any more. Besides, health education will raise patients’ attention to ischemic stroke.
Label-free detection of tumor markers in a colon carcinoma tumor progression model by confocal Raman microspectroscopy
2013-06-18

Living colon carcinoma cells were investigated by confocal Raman microspectroscopy. An in vitro model of tumor progression was established. Evaluation of data sets by cluster analysis reveals that lipid bodies might be a valuable diagnostic parameter for early carcinogenesis.
Gangliosides and Gangliosidoses: Principles of Molecular and Metabolic Pathogenesis
2013-06-19

Gangliosides are the main glycolipids of neuronal plasma membranes. Their surface patterns are generated by coordinated processes, involving biosynthetic pathways of the secretory compartments, catabolic steps of the endolysosomal system, and intracellular trafficking. Inherited defects in ganglioside biosynthesis causing fatal neurodegenerative diseases have been described so far almost exclusively in mouse models, whereas inherited defects in ganglioside catabolism causing various clinical forms of GM1- and GM2-gangliosidoses have long been known. For digestion, gangliosides are endocytosed and reach intra-endosomal vesicles. At the level of late endosomes, they are depleted of membrane-stabilizing lipids like cholesterol and enriched with bis(monoacylglycero)phosphate (BMP). Lysosomal catabolism is catalyzed at acidic pH values by cationic sphingolipid activator proteins (SAPs), presenting lipids to their respective hydrolases, electrostatically attracted to the negatively charged surface of the luminal BMP-rich vesicles. Various inherited defects of ganglioside hydrolases, e.g., of β-galactosidase and β-hexosaminidases, and of GM2-activator protein, cause infantile (with tetraparesis, dementia, blindness) and different protracted clinical forms of GM1- and GM2-gangliosidoses. Mutations yielding proteins with small residual catabolic activities in the lysosome give rise to juvenile and adult clinical forms with a wide range of clinical symptomatology. Apart from patients' differences in their genetic background, clinical heterogeneity may be caused by rather diverse substrate specificities and functions of lysosomal hydrolases, multifunctional properties of SAPs, and the strong regulation of ganglioside catabolism by membrane lipids. Currently, there is no treatment available for neuronal ganglioside storage diseases. Therapeutic approaches in mouse models and patients with juvenile forms of gangliosidoses are discussed.
Exploring the MHC-peptide matrix of central tolerance in the human thymus
2013-06-19

Ever since it was discovered that central tolerance to self is imposed on developing T cells in the thymus through their interaction with self-peptide major histocompatibility complexes on thymic antigen-presenting cells, immunologists have speculated about the nature of these peptides, particularly in humans. Here, to shed light on the so-far unknown human thymic peptide repertoire, we analyse peptides eluted from isolated thymic dendritic cells, dendritic cell-depleted antigen-presenting cells and whole thymus. Bioinformatic analysis of the 842 identified natural major histocompatibility complex I and II ligands reveals significant cross-talk between major histocompatibility complex-class I and II pathways and differences in source protein representation between individuals as well as different antigen-presenting cells. Furthermore, several autoimmune- and tumour-related peptides, from enolase and vimentin for example, are presented in the healthy thymus. 302 peptides are directly derived from negatively selecting dendritic cells, thus providing the first global view of the peptide matrix in the human thymus that imposes self-tolerance in vivo.
A Capacitive Humidity Sensor Suitable for CMOS Integration
2013-06-19

This paper describes the design, fabrication, and performance of a thin film humidity sensor fabricated in standard CMOS process, hence it may be combined with an integrated circuit. The sensor is based on a capacitance between interdigitated electrodes in the top metal layer and water adsorption in the polyimide layer. The design is optimized by analytical and then finite element models which show that, within the constraint of the CMOS structure, the sensitivity can be no greater than one third of the sensitivity of the polyimide alone. Experimental sensors were fabricated in-house before an improved design was fabricated in a commercial foundry. The different behavior of these sensors, despite their similar designs, leads to an investigation into the effects of fabrication process on the sensor linearity. Characterizing the polyimide film by contact angle, AFM and FTIR revealed that the difference in linearity of the response between the two sensors resulted from different etching techniques employed to pattern the film.
The arc space of horospherical varieties and motivic integration
2013-06-19

Abstract For an arbitrary connected reductive group , we consider the motivic integral over the arc space of an arbitrary -Gorenstein horospherical -variety associated with a colored fan and prove a formula for the stringy -function of which generalizes the one for toric varieties. We remark that, in contrast to toric varieties, the stringy -function of a Gorenstein horospherical variety may be not a polynomial if some cones in have nonempty sets of colors. Using the stringy -function, we can formulate and prove a new smoothness criterion for locally factorial horospherical varieties. We expect that this smoothness criterion holds for arbitrary spherical varieties.
Immune Profiling in Blood Identifies sTNF-R1 Performing Comparably Well as Biomarker Panels for Classification of Alzheimer's Disease Patients
2013-06-20

We identified sTNF-R1 from a marker set consisting of 25 inflammatory biomarkers, which allowed SVM-based discrimination of AD patients from healthy controls on a single-subject classification level comparably well as biomarker panels with a clinically relevant accuracy and validity. Although larger sample populations will be needed to confirm this diagnostic accuracy, our study suggests that sTNF-R1 in serum-either as singular marker or incorporated into a biomarker panel-could be a powerful new biomarker for detection of AD. In addition, selective inhibition of TNF-R1 function may represent a new therapeutic approach in AD.
Bevacizumab, irinotecan, and radiotherapy versus standard temozolomide and radiotherapy in newly diagnosed, MGMT-nonmethylated glioblastoma patients: First results from the randomized multicenter GLARIUS trial.
2013-06-20

LBA2000 Background: In patients with MGMT-nonmethylated glioblastoma (GBM), primary chemotherapy with temozolomide (TMZ) is at best moderately effective. There is an urgent need for more effective therapies in this large subgroup of GBM. Since results of phase II trials with the antiangiogenic agent bevacizumab (BEV) +/- irinotecan (IRI) are promising in recurrent GBM, the GLARIUS trial explored the efficacy of BEV/IRI as compared to standard TMZ in the first-line therapy of MGMT-non-methylated GBM. Methods: In the randomized, multicenter, open-label GLARIUS trial, adult patients with newly diagnosed, histologically confirmed and MGMT-non-methylated GBM received local radiotherapy (RT, 30 x 2 Gy) and were randomized (2:1) for experimental therapy with BEV (10 mg/kg q2w) during RT followed by maintenance BEV (10 mg/kg q2w) + IRI (125 mg/m2 q2w (without enzyme-inducing antiepileptic drugs (EIAEDs)) or 340 mg/m2 (with EIAEDs)) or standard therapy with daily TMZ (75 mg/m 2 ) during RT followed by 6 courses of TMZ (150-200 mg/m 2 /day for 5 days q4w). The primary endpoint was progression-free survival rate after 6 months (PFS-6) as determined by central neuroradiological review. Results: The intent-to-treat population included 170 patients (67.1% male, median age 56 years (range 25-78 years), 48.8% complete resection rate, 78.8% of patients with KPS 90% or higher); 116 patients received BEV/IRI, 54 patients had TMZ. The frequencies of adverse events in both arms of the trial were within the expected range. The PFS-6 rate was significantly higher in the BEV/IRI arm (71.1%, 95% CI 58.1-80.8%) than in the TMZ arm (26.2%, 95% CI 13.1-41.4%, p&lt;0.0001 logrank test). Conclusions: The significant and clinically meaningful increase in the primary endpoint PFS-6 upon BEV/IRI chemotherapy suggests that BEV/IRI is superior to standard TMZ therapy in newly diagnosed MGMT-nonmethylated GBM patients. Clinical trial information: 2009-010390-21.
Hablas vielleicht un peu la mia language?A comprehensive overview of the role of language differences in headquarters–subsidiary communication
2013-06-21

The management of human resources in headquarters (HQ)-subsidiary relationships requires intensive communication, but effective communication often depends on having a shared language. Hence, language differences can be a serious threat to the successful management of human resources in multinational corporations (MNCs). In this large-scale quantitative study, encompassing data from more than 800 subsidiaries in thirteen countries, we investigated four related issues.&#13;\\n&#13;\\nFirst, in terms of the importance of language differences, we found that HQ-subsidiary relationships are clearly affected by language differences and that the latter form a distance category of their own, which should not be subsumed under the related, but separate concept of cultural differences. Second, regarding the consequences of language differences for communication outcomes, we found that a lack of a shared language is associated with misunderstanding, conflict and parallel information networks which could harm HQ-subsidiary interactions.&#13;\\n&#13;\\nThird, with regard to the impact of language differences on communication methods, we found that alack of a shared language is associated witha significantly lower level of oral (face-to-face and phone) communication, but not written communication. Fourth, and finally, in terms of a potential solution to communication problems caused by language differences, we found that expatriates can facilitate both communication and knowledge transfer between HQ and subsidiaries.
Palladium-catalyzed synthesis of N-arylated carbazoles using anilines and cyclic diaryliodonium salts
2013-06-21

The direct synthesis of N-arylated carbazoles through a palladium-catalyzed amination of cyclic iodonium salts with anilines is described. In particular, electron-poor aniline derivatives reacted smoothly with only 5 mol % of Pd(OAc) 2 as catalyst to give the desired products in up to 71% yield. Furthermore, the reactivity of cyclic iodonium salts is compared with the reactivity of the corresponding cyclic bromonium analogues.
The Chalcolithic of Northern Iran
2013-06-21

This chapter presents evidence of early villages and towns, such as Tepe Sialk and the Qazvin plain sites, in northern Iran dating from the late sixth to the mid-fourth millennium BC. In addition to reviewing the principal categories of material culture, such as architecture and ceramics, particular attention is paid to the development of pyrotechnology, metallurgy, glyptic, and the circulation of exotic objects and semiprecious stones. Evidence of social ranking is discussed. The beginnings of long-distance contacts and exchange across Iran are treated as well.
Towards quantifying the increase of rainfall interception during secondary forest succession
2013-06-21

Abstract. Large scale forest regrowth is one aspect of modern land-cover change. Yet, despite the importance of understanding the hydrological consequences of land cover dynamics, the relation between forest succession and canopy interception is poorly understood. This lack of knowledge is unfortunate because rainfall interception plays an important role in regional water cycles and needs to be quantified for many modelling purposes. To help close this knowledge gap, we designed a throughfall monitoring study along a secondary succession gradient in a tropical forest region of Panama. The investigated gradient comprises 20 natural forest patches regrowing for 3 up to about 130 yr. We sampled each patch with a minimum of 20 funnel-type throughfall collectors over a continuous two-month period that had nearly 900 mm of rain. At the same time and locations, we acquired forest inventory data and derived several forest structural attributes. We then applied simple and multiple regression models (Bayesian Model Averaging, BMA) and identified those vegetation parameters that have the strongest influence on the variation of canopy interception. Our analyses provide three main findings. First, canopy interception changes rapidly during forest succession. After only a decade, throughfall volumes approach levels that are typical for mature forests. Second, a parsimonious (simple linear regression) model based on the ratio of the basal area of small stems to the total basal area outperformed more complex multivariate models (BMA approach). Third, based on complementary forest inventory data we show that the influence of young secondary forests on interception in real-world fragmented landscapes might be detectable only in regions with a substantial fraction of very young forests. In case entire catchments are subject to forest regrowth, initial stages may be associated with undesirable effects on streamflow generation. Our results further highlight the need to study all forest succession stages, including early ones.
Simulation of Wing Stall
2013-06-22

Simulation capabilities for low-speed aircraft stall prediction are important for determining the limits of safe aircraft operations during design processes. The simulations are extremely demanding in terms of physical models involved, overall computation effort, and the needed efforts for validation. The present paper describes coordinated, fundamental research into new simulation methodologies for wing stall that also include the effects of atmospheric gusts. The research is carried out by the DFG funded Research Unit FOR 1066 composed of German Universities and the German Aerospace Center, DLR. The research Unit investigates advanced models of turbulence, advanced physics-based gust models, and new numerical approaches for gust simulation. These modeling and computational activities are supplemented by an unique validation experiment, that aims at providing stall data on a high-lift wing with well defined, generic distortions of the onset flow.
Combined Flow Cytometric Analysis of Surface and Intracellular Antigens Reveals Surface Molecule Markers of Human Neuropoiesis
2013-06-24

Surface molecule profiles undergo dynamic changes in physiology and pathology, serve as markers of cellular state and phenotype and can be exploited for cell selection strategies and diagnostics. The isolation of well-defined cell subsets is needed for in vivo and in vitro applications in stem cell biology. In this technical report, we present an approach for defining a subset of interest in a mixed cell population by flow cytometric detection of intracellular antigens. We have developed a fully validated protocol that enables the co-detection of cluster of differentiation (CD) surface antigens on fixed, permeabilized neural cell populations defined by intracellular staining. Determining the degree of co-expression of surface marker candidates with intracellular target population markers (nestin, MAP2, doublecortin, TUJ1) on neuroblastoma cell lines (SH-SY5Y, BE(2)-M17) yielded a combinatorial CD49f(-)/CD200(high) surface marker panel. Its application in fluorescence-activated cell sorting (FACS) generated enriched neuronal cultures from differentiated cell suspensions derived from human induced pluripotent stem cells. Our data underlines the feasibility of using the described co-labeling protocol and co-expression analysis for quantitative assays in mammalian neurobiology and for screening approaches to identify much needed surface markers in stem cell biology.
Retinitis Pigmentosa: over‐expression of anti‐ageing protein Klotho in degenerating photoreceptors
2013-06-24

Abstract Retinitis Pigmentosa involves a hereditary degeneration of photoreceptors by as yet unresolved mechanisms. The secretable protein α‐Klotho has a function related to ageing processes, and α‐Klotho‐deficient mice have reduced lifespan and declining functions in several tissues. Here, we studied Klotho in connection with inherited photoreceptor degeneration. Increased nuclear immunostaining for α‐Klotho protein was seen in degenerating photoreceptors in four different Retinitis Pigmentosa models ( rd1 , rd2 mice; P23H , S334ter rhodopsin mutant rats). Correspondingly, in rd1 retina α‐Klotho mRNA expression was significantly up‐regulated. Moreover, immunostaining for another Klotho family protein, β‐Klotho, also co‐localized with degenerating rd1 photoreceptors. The rd1 retina displayed reduced levels of fibroblast growth factor 15, a member of the fibroblast growth factor subfamily for which Klotho acts as a co‐receptor. Exogenous α‐Klotho protein added to retinal explant cultures did not affect cell death in rd1 retinae, but caused a severe layer disordering in wild‐type retinae. Our study suggests Klotho as a novel player in the retina, with a clear connection to photoreceptor cell death as well as with an influence on retinal organization.
Mood and Threat to Attitudinal Freedom
2013-06-24

The present research examined when happy individuals’ processing of a counterattitudinal message is guided by mood-congruent expectancies versus hedonic considerations. Recipients in positive, neutral, or negative mood read a strong or weak counterattitudinal message which either contained a threat to attitudinal freedom or did not contain such a threat. As expected, a freedom-threatening counterattitudinal message was more mood threatening than a counterattitudinal message not threatening freedom. Furthermore, as predicted by the mood-congruent expectancies approach, people in positive mood processed a nonthreatening counterattitudinal message more thoroughly than people in negative mood. Message processing in neutral mood lay in between. In contrast, as predicted by the hedonic-contingency view, a threatening counterattitudinal message was processed less thoroughly in positive mood than in neutral mood. In negative mood, processing of a threatening counterattitudinal message was as low as in positive mood. These findings suggest that message processing is determined by mood congruency unless hedonic considerations override expectancy-based processing inclinations.