julilili42/papers huggingface dataset:
The dimeric platelet collagen receptor GPVI-Fc reduces platelet adhesion to activated endothelium and preserves myocardial function after transient ischemia in mice
2012-07-20

Platelets play a critical role in the pathophysiology of reperfusion, sepsis, and cardiovascular diseases. In a multiple step process, they adhere to activated endothelium and release proinflammatory cytokines thereby promoting the inflammatory process. Glycoprotein VI (GPVI) is the major collagen receptor on the platelet surface and triggers platelet activation and primary hemostasis. Activation of GPVI leads to stable platelet adhesion and degranulation of platelet granules. However, GPVI is critically involved in platelet adhesion to activated endothelium without exposure of subendothelial matrix. Earlier studies show that the soluble GPVI-Fc binds to collagen and protects mice from atherosclerosis and decreases neointima proliferation after arterial injury. Here, we show for the first time that recombinant GPVI-Fc binds to activated endothelium mainly via vitronectin and prevents platelet/endothelial interaction. Administration of GPVI-Fc reduced infarct size and preserved cardiac function in a mouse model of myocardial infarction. This process was associated with reduced GPVI-induced platelet degranulation and release of proinflammatory cytokines in vitro and in vivo. Taken together, administration of GPVI-Fc offers a novel strategy to control platelet-mediated inflammation and to preserve myocardial function following myocardial infarction.
Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca2+‐permeable TRPC6 channels
2012-07-20

Abstract The standardized extract of the St. John's wort plant ( Hypericum perforatum ) is commonly used to treat mild to moderate depression. Its active constituent is hyperforin, a phloroglucinol derivative that reduces the reuptake of serotonin and norepinephrine by increasing intracellular Na + concentration through the activation of nonselective cationic TRPC6 channels. TRPC6 channels are also Ca 2+ ‐permeable, resulting in intracellular Ca 2+ elevations. Indeed, hyperforin activates TRPC6‐mediated currents and Ca 2+ transients in rat PC12 cells, which induce their differentiation, mimicking the neurotrophic effect of nerve growth factor. Here, we show that hyperforin modulates dendritic spine morphology in CA1 and CA3 pyramidal neurons of hippocampal slice cultures through the activation of TRPC6 channels. Hyperforin also evoked intracellular Ca 2+ transients and depolarizing inward currents sensitive to the TRPC channel blocker La 3+ , thus resembling the actions of the neurotrophin brain‐derived neurotrophic factor (BDNF) in hippocampal pyramidal neurons. These results suggest that the antidepressant actions of St. John's wort are mediated by a mechanism similar to that engaged by BDNF. © 2012 Wiley Periodicals, Inc.
Magnetic hysteresis effects in superconducting coplanar microwave resonators
2012-07-20

We performed transmission spectroscopy experiments on coplanar half\\nwavelength niobium resonators at a temperature T=4.2 K. We observe not only a\\nstrong dependence of the quality factor Q and the resonance frequency f_res on\\nan externally applied magnetic field but also on the magnetic history of our\\nresonators, i.e. on the spatial distribution of trapped Abrikosov vortices in\\nthe device. We find these results to be valid for a broad range of frequencies\\nand angles between the resonator plane and the magnetic field direction as well\\nas for resonators with and without antidots near the edges of the center\\nconductor and the ground planes. In a detailed analysis we show, that\\ncharacteristic features of the experimental data can only be reproduced in\\ncalculations, if a highly inhomogeneous rf-current density and a flux density\\ngradient with maxima at the edges of the superconductor is assumed. We\\nfurthermore demonstrate, that the hysteretic behaviour of the resonator\\nproperties can be used to considerably reduce the vortex induced losses and to\\nfine-tune the resonance frequency by the proper way of cycling to a desired\\nmagnetic field.\\n
Running mass, effective energy, and confinement: The lattice quark propagator in Coulomb gauge
2012-07-20

We calculate the lattice quark propagator in Coulomb gauge both from\\ndynamical and quenched configurations. We show that in the continuum limit both\\nthe static and full quark propagator are multiplicatively renormalizable. From\\nthe propagator we extract the quark renormalization function Z(|p|) and the\\nrunning mass M(|p|) and extrapolate the latter to the chiral limit. We find\\nthat M(|p|) practically coincides with the corresponding Landau gauge function\\nfor small momenta. The computation of M(|p|) can be however made more efficient\\nin Coulomb gauge; this can lead to a better determination of the chiral mass\\nand the quark anomalous dimension. Moreover from the structure of the full\\npropagator we can read off an expression for the dispersion relation of quarks,\\ncompatible with an IR divergent effective energy. If confirmed on larger\\nvolumes this finding would allow to extend the Gribov-Zwanziger confinement\\nmechanism to the fermionic sector of QCD.\\n
The Binding Site of the V-ATPase Inhibitor Apicularen Is in the Vicinity of Those for Bafilomycin and Archazolid
2012-07-20

The investigation of V-ATPases as potential therapeutic drug targets and hence of their specific inhibitors is a promising approach in osteoporosis and cancer treatment because the occurrence of these diseases is interrelated to the function of the V-ATPase. Apicularen belongs to the novel inhibitor family of the benzolactone enamides, which are highly potent but feature the unique characteristic of not inhibiting V-ATPases from fungal sources. In this study we specify, for the first time, the binding site of apicularen within the membrane spanning V(O) complex. By photoaffinity labeling using derivatives of apicularen and of the plecomacrolides bafilomycin and concanamycin, each coupled to (14)C-labeled 4-(3-trifluoromethyldiazirin-3-yl)benzoic acid, we verified that apicularen binds at the interface of the V(O) subunits a and c. The binding site is in the vicinity to those of the plecomacrolides and of the archazolids, a third family of V-ATPase inhibitors. Expression of subunit c homologues from Homo sapiens and Manduca sexta, both species sensitive to benzolactone enamides, in a Saccharomyces cerevisiae strain lacking the corresponding intrinsic gene did not transfer this sensitivity to yeast. Therefore, the binding site of benzolactone enamides cannot be formed exclusively by subunit c. Apparently, subunit a substantially contributes to the binding of the benzolactone enamides.
Detection of linear ego-acceleration from optic flow
2012-07-20

Human observers are able to estimate various ego-motion parameters from optic flow, including rotation, translational heading, time-to-collision (TTC), time-to-passage (TTP), etc. The perception of linear ego-acceleration or deceleration, i.e., changes of translational velocity, is less well understood. While time-to-passage experiments indicate that ego-acceleration is neglected, subjects are able to keep their (perceived) speed constant under changing conditions, indicating that some sense of ego-acceleration or velocity change must be present. In this paper, we analyze the relation of ego-acceleration estimates and geometrical parameters of the environment using simulated flights through cylindrical and conic (narrowing or widening) corridors. Theoretical analysis shows that a logarithmic ego-acceleration parameter, called the acceleration rate ρ, can be calculated from retinal acceleration measurements. This parameter is independent of the geometrical layout of the scene; if veridical ego-motion is known at some instant in time, acceleration rate allows updating of ego-motion without further depth-velocity calibration. Results indicate, however, that subjects systematically confuse ego-acceleration with corridor narrowing and ego-deceleration with corridor widening, while veridically judging ego-acceleration in straight corridors. We conclude that judgments of ego-acceleration are based on first-order retinal flow and do not make use of acceleration rate or retinal acceleration.
Macrocephaly, obesity, mental (intellectual) disability, and ocular abnormalities: Alternative definition and further delineation of MOMO syndrome
2012-07-20

Abstract MOMO syndrome, previously defined as Macrosomia, Obesity, Macrocephaly, and Ocular abnormalities (OMIM 157980) is a rare intellectual disability syndrome of unknown cause. We describe two further patients with MOMO syndrome. Reported data of patients with MOMO syndrome and our own findings indicate that overgrowth does not appear to be a specific feature. We propose to form the acronym “MOMO” from Macrocephaly, Obesity, Mental (intellectual) disability, and Ocular abnormalities, excluding macrosomia from the syndrome name. The combination of obesity, macrocephaly, and colobomas is unique, therefore these features can be used as major diagnostic criteria of MOMO syndrome. © 2012 Wiley Periodicals, Inc.
Does Dose Matter? Effect of Two Different Neoadjuvant Protocols in Advanced NSCLC
2012-07-20

The median survival benefit of 9 months is evident but (probably still) not significant. The more aggressive protocol 2 shows a significant better downstaging effect concerning N- and UICC-stage if R0-resection can be achieved. Insofar dose does matter!
Additive decompositions with interaction effexts
2012-07-21

This paper proposes a comprehensive, path-independent decomposition formula of changes into ceteris paribus effects and interaction effects. The formula implies a reassessment of sequential decomposition methods that are widely used in the literature and that are restrictive in how they treat interaction effects. If counterfactual outcomes are correctly specified, it may also be viewed as a description of certain aspects of causality in the situation where more than one causal influence is present.
Cell Wall Amidase AmiC1 Is Required for Cellular Communication and Heterocyst Development in the Cyanobacterium Anabaena PCC 7120 but Not for Filament Integrity
2012-07-22

ABSTRACT Filamentous cyanobacteria of the order Nostocales display typical properties of multicellular organisms. In response to nitrogen starvation, some vegetative cells differentiate into heterocysts, where fixation of N 2 takes place. Heterocysts provide a micro-oxic compartment to protect nitrogenase from the oxygen produced by the vegetative cells. Differentiation involves fundamental remodeling of the Gram-negative cell wall by deposition of a thick envelope and by formation of a neck-like structure at the contact site to the vegetative cells. Cell wall-hydrolyzing enzymes, like cell wall amidases, are involved in peptidoglycan maturation and turnover in unicellular bacteria. Recently, we showed that mutation of the amidase homologue amiC2 gene in Nostoc punctiforme ATCC 29133 distorts filament morphology and function. Here, we present the functional characterization of two amiC paralogues from Anabaena sp. strain PCC 7120. The amiC1 ( alr0092 ) mutant was not able to differentiate heterocysts or to grow diazotrophically, whereas the amiC2 ( alr0093 ) mutant did not show an altered phenotype under standard growth conditions. In agreement, fluorescence recovery after photobleaching (FRAP) studies showed a lack of cell-cell communication only in the AmiC1 mutant. Green fluorescent protein (GFP)-tagged AmiC1 was able to complement the mutant phenotype to wild-type properties. The protein localized in the septal regions of newly dividing cells and at the neck region of differentiating heterocysts. Upon nitrogen step-down, no mature heterocysts were developed in spite of ongoing heterocyst-specific gene expression. These results show the dependence of heterocyst development on amidase function and highlight a pivotal but so far underestimated cellular process, the remodeling of peptidoglycan, for the biology of filamentous cyanobacteria.
Co-adaptivity in Unsupervised Adaptive Brain-Computer Interfacing: a Simulation Approach
2012-07-22

A Brain-Computer Interface (BCI) allows a user to control a computer by pure brain activity. Due to the non- stationarity of the recorded brain signals, the BCI performance tends to decrease over time. Recently, adaption of the BCI has been proposed as a means to counter non-stationarity and help to stabilize the BCI performance. Since most adaption methods for BCI are analysed in an offline setting, one important factor is not taken into account: that also the user is adapting. While online experiments take into account the adaptive user, a comparison of different classifiers with the same data is always biased towards the method that was used for feedback and thereby does not allow a proper evaluation of the classifier in a co-adaptive environment. To solve this problem, we propose a simulation approach that simulates an adapting BCI user and allows to test and compare different adaptive algorithms considering the co-adaptivity between BCI and user. With this approach we can also show, under which conditions an adaption of the BCI improves performance and when the adaptive BCI and the adaptive user hinder each other and lead to a decrease in BCI performance.
Proton-Binding Capacity of Staphylococcus aureus Wall Teichoic Acid and Its Role in Controlling Autolysin Activity
2012-07-23

Wall teichoic acid (WTA) or related polyanionic cell wall glycopolymers are produced by most gram-positive bacterial species and have been implicated in various cellular functions. WTA and the proton gradient across bacterial membranes are known to control the activity of autolysins but the molecular details of these interactions are poorly understood. We demonstrate that WTA contributes substantially to the proton-binding capacity of Staphylococcus aureus cell walls and controls autolysis largely via the major autolysin AtlA whose activity is known to decline at acidic pH values. Compounds that increase or decrease the activity of the respiratory chain, a main source of protons in the cell wall, modulated autolysis rates in WTA-producing cells but did not affect the augmented autolytic activity observed in a WTA-deficient mutant. We propose that WTA represents a cation-exchanger like mesh in the gram-positive cell envelopes that is required for creating a locally acidified milieu to govern the pH-dependent activity of autolysins.
A smart 19F and 1H MRI probe with self‐immolative linker as a versatile tool for detection of enzymes
2012-07-23

ABSTRACT Here we report on a dual‐modal 19 F and 1 H MRI paramagnetic probe with a self‐immolative linker, Gd–DOMF–Gal. The enzymatic conversion of this probe by β ‐galactosidase resulted in a simultaneous turning on of the fluorine signal and changed ability of the Gd 3+ complex to modulate the 1 H MR signal intensity of the surrounding water molecules. A versatile imaging platform for monitoring a variety of enzymes by 19 F and 1 H MRI using this molecular design is proposed. Copyright © 2012 John Wiley &amp; Sons, Ltd.
MR/PET: A New Challenge in Hybrid Imaging
2012-07-23

Hybrid imaging, the combination of two imaging modalities into one, promises the compensation of specific deficits of the modalities involved. PET/CT has gained wide acceptance for oncologic imaging in recent years; however, MRI has certain advantages that could make combined MR/PET more tempting in various clinical applications. The development of new clinical whole-body MR/PET systems offers new insights in metabolic and functional processes in oncology as well as cardiovascular and neurologic diseases.
Imaging Findings in Tick-Borne Encephalitis With Differential Diagnostic Considerations
2012-07-23

Imaging findings in TBE resemble those of other infections, such as meningoencephalitis. However, a predilection for the thalami, basal ganglia, cerebellum, and anterior horns of the spinal cord suggests the possibility of TBE.
Antitumor activity of zoledronic acid in primary breast cancer cells determined by the ATP tumor chemosensitivity assay
2012-07-23

Abstract Background The NeoAzure study has demonstrated that the use of the bisphosphonate zoledronic acid (Zol) in the neoadjuvant setting increases the rate of complete response in primary breast cancer and therefore indicates direct antitumor activity. The purpose of this study was to compare the antitumor effect of Zol with standard chemotherapy in primary breast cancer cells using ATP-tumor chemosensitivity assay (ATP-TCA). Methods Breast cancer specimens were obtained from patients with breast cancer who underwent primary breast cancer surgery at the Department of Obstetrics and Gynecology, Tübingen, Germany, between 2006 through 2009. Antitumor effects of Zol, TAC (Docetaxel, Adriamycin, Cyclophosphamide) and FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide) were tested in 116 fresh human primary breast cancer specimens using ATP-TCA. ATP-TCA results were analyzed with different cut-off levels for the half maximal inhibitory concentration (IC50), for IC90 and for the sensitivity index (IndexSUM). Each single agent or combination was tested at six doubling dilutions from 6.25, 12.5, 25, 50, 100, and 200% of test drug concentrations (TDC) derived from the plasma peak concentrations determined by pharmacokinetic data. The assay was carried out in duplicate wells with positive and negative controls. Results The median IndexSUM value was lower for Zol than for the combined regimen FEC (36.8%) and TAC (12.9%), respectively, indicating increased antitumor activity of Zol in primary breast cancer cells. The difference regarding Zol and FEC was significant (p &lt; 0.05). The median IC50 value for Zol (8.03% TDC) was significantly lower than the IC50 values for FEC (33.5% TDC) and TAC (19.3% TDC) treatment (p &lt; 0.05). However, the median IC90 value for Zol (152.5% TDC) was significantly higher than the IC90 value obtained with TAC (49.5% TDC; p &lt; 0.05), but similar to the IC90 value for FEC (180.9% TDC). In addition a significant positive correlation was observed for the IndexSum of Zol and the ER status (p &lt; 0.01). Conclusion Zoledronic acid has a strong antitumor effect on primary breast cancer cells in vitro which is equal or superior to commonly used chemotherapeutic regimens for treating breast cancer.
The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease?
2012-07-24

Gut microbiota is a compilation of microorganisms dwelling in the entire mammalian gastrointestinal tract. They display a symbiotic relationship with the host contributing to its intestinal health and disease. Even a slight fluctuation in this equipoise may be deleterious to the host, leading to many pathological conditions like Clostridium difficile infection or inflammatory bowel disease (IBD). In this review, we focus on the role of microbial dysbiosis in initiation of C. difficile infection and IBD, and we also touch upon the role of specific pathogens, particularly C. difficile, as causative agents of IBD. We also discuss the molecular mechanisms activated by C. difficile that contribute to the development and exacerbation of gastrointestinal disorders.
Extracorporeal shockwave lithotripsy vs. percutaneous nephrolithotomy vs. flexible ureterorenoscopy for lower-pole stones
2012-07-24

Considering the currents trends and evidence, the 2012 update of the European Association of Urology Guidelines on Urolithiasis has upgraded the endourological treatment of kidney stones. Individual factors such as body habitus, renal anatomy, costs and patient preference must be considered.
Spatial distribution of glacial erosion rates in the St. Elias range, Alaska, inferred from a realistic model of glacier dynamics
2012-07-24

Glaciers have been principal erosional agents in many orogens throughout much of the recent geological past. A modern example is the St. Elias Mountains in southeastern Alaska; it is a highly convergent, complex orogen, which has been glaciated for much of its history. We examine the Seward‐Malaspina Glacier system, which comprises two of the largest temperate glaciers in the world. We focus on the pattern of erosion within its narrow passage through the St. Elias Mountains, the Seward Throat. Measured glacier surface velocities and elevations provide constraints for a full‐stress numerical flowband model that enables us to quantitatively determine the glacier thickness profile, which is not easily measured on temperate glaciers, and the basal characteristics relevant for erosion. These characteristics at the bed, namely the water pressure, normal and shear stresses, and sliding velocity, are then used to infer the spatial variation in erosion rates using several commonly invoked erosion laws. The calculations show that the geometry of the glacier basin exerts a far stronger control on the spatial variation of erosion rates than does the equilibrium line altitude, which is often assumed to be important in studies of glaciated orogens. The model provides a quantitative basis for understanding why erosion rates are highest around the Seward Throat, which is generally consistent with local and large‐scale geological observations and thermochronologic evidence. Moreover, model results suggest how glacier characteristics could be used to infer zones of active or recent uplift in ice‐mantled orogens.
Swift observations of two supergiant fast X-ray transient prototypes in outburst
2012-07-24

We report on the results from observations of the most recent outbursts of XTE J1739-302 and IGR J17544-2619, which are considered to be the prototypes of the supergiant fast X-ray transient class. They triggered the Swift/Burst Alert Telescope on 2011 February 22 and March 24, respectively, and each time a prompt Swift slew allowed us to obtain the rich broad-band data we present. The X-ray Telescope light curves show the descending portion of very bright flares that reached luminosities of ~2 × 10 36 and ~5 × 10 36ergs -1. The broad-band spectra, when fitted with the usual phenomenological models adopted for accreting neutron stars, yield values of both high-energy cut-off and e-folding energy consistent with those obtained from previously reported outbursts from these sources. In the context of more physical models, the spectra of both sources can be well fitted either with a two-blackbody model or with a single unsaturated Comptonization model. In the latter case, the model can be either a classical static Comptonization model, such as COMPTT, or the recently developed COMPMAG model, which includes thermal and bulk Comptonization for cylindrical accretion on to a magnetized neutron star. We discuss the possible accretion scenarios derived by the different models, and we also emphasize the fact that the electron density derived from the Comptonization models, in the regions where the X-ray spectrum presumably forms, is lower than that estimated using the continuity equation at the magnetospheric radius and the source X-ray luminosity, and we give some possible explanations. © 2012 The Authors Monthly Notices of the Royal Astronomical Society © 2012 RAS.