julilili42/papers huggingface dataset:
Pulse phase and precession phase resolved spectroscopy of Hercules X-1: studying a representative Main-On with RXTE
2012-12-26

\\n Aims. We performed a detailed pulse phase resolved spectroscopy of the\\n accreting binary X-ray pulsar Her X-1 in the energy range 3.5–75 keV and have established\\n pulse phase profiles for all spectral parameters. For three parameters, the centroid\\n energy of the cyclotron line, the photon index and the flux of the 6.4 keV iron line, we\\n have studied the variation as a function of 35 d phase.\\n Methods. We analyzed RXTE observations of the Main-On of November 2002\\n using data from the PCA and the HEXTE instruments. Four different time intervals of about\\n ~1 d duration were selected to provide a good coverage of a complete Main-On. The\\n intervals are centered at 35 d phases 0.03, 0.10, 0.15, and 0.20, respectively.\\n Results. All spectral parameters show a strong modulation with pulse\\n phase. While the centroid energy of the cyclotron line follows roughly the shape of the\\n pulse profile, showing higher values close to the peak of the X-ray pulse, both the photon\\n index and the iron line intensity exhibit distinct minima around the peak of the X-ray\\n pulse. With respect to variations of the observed profiles with 35 d phase, we find that\\n there is a clear evolution of the shape of the pulse profiles (flux versus pulse phase), a\\n moderate increase of the maximum cyclotron line energy (found around pulse phase 0.7), but\\n no significant evolution of the shape of the pulse phase profiles of the cyclotron line\\n energy, the spectral power law index or the iron line intensity. \\n Conclusions. The variation of spectral parameters as a function of the\\n pulse phase provides important information about the system: i. the disappearance of the\\n Fe line flux near the highest continuum flux may be an indication of a hollow cone\\n geometry of the accretion structure; ii. the apparent non-dependence of the cyclotron line\\n energy profiles on 35 d phase provides a new possibility to test the model of free\\n precession of the neutron star, proposed to be responsible for the systematic variations\\n in the pulse profiles.\\n
Binding Pocket Optimization by Computational Protein Design
2012-12-27

Engineering specific interactions between proteins and small molecules is extremely useful for biological studies, as these interactions are essential for molecular recognition. Furthermore, many biotechnological applications are made possible by such an engineering approach, ranging from biosensors to the design of custom enzyme catalysts. Here, we present a novel method for the computational design of protein-small ligand binding named PocketOptimizer. The program can be used to modify protein binding pocket residues to improve or establish binding of a small molecule. It is a modular pipeline based on a number of customizable molecular modeling tools to predict mutations that alter the affinity of a target protein to its ligand. At its heart it uses a receptor-ligand scoring function to estimate the binding free energy between protein and ligand. We compiled a benchmark set that we used to systematically assess the performance of our method. It consists of proteins for which mutational variants with different binding affinities for their ligands and experimentally determined structures exist. Within this test set PocketOptimizer correctly predicts the mutant with the higher affinity in about 69% of the cases. A detailed analysis of the results reveals that the strengths of PocketOptimizer lie in the correct introduction of stabilizing hydrogen bonds to the ligand, as well as in the improved geometric complemetarity between ligand and binding pocket. Apart from the novel method for binding pocket design we also introduce a much needed benchmark data set for the comparison of affinities of mutant binding pockets, and that we use to asses programs for in silico design of ligand binding.
Dibenzosuberones as p38 Mitogen-Activated Protein Kinase Inhibitors with Low ATP Competitiveness and Outstanding Whole Blood Activity
2012-12-27

p38α mitogen-activated protein (MAP) kinase is a main target in drug research concerning inflammatory diseases. Nevertheless, no inhibitor of p38α MAP kinase has been introduced to the market. This might be attributed to the fact that there is no inhibitor which combines outstanding activity in biological systems and selectivity. Herein an approach to the development of such inhibitors on the basis of the highly selective molecular probe Skepinone-L is described. Introduction of a "deep pocket" moiety addressing the DFG motif led to an increased activity of the compounds. Hydrophilic moieties, addressing the solvent-exposed area adjacent to hydrophilic region II, conserved a high activity of the compounds in a whole blood assay. Combined with their outstanding selectivity and low ATP competitiveness, these inhibitors are very interesting candidates for use in biological systems and in therapy.
Effective Combination of Photodynamic Therapy and Imiquimod 5% Cream in the Treatment of Actinic Keratoses: Three Cases
2012-12-27

Background . The therapy for actinic keratoses includes photodynamic therapy (PDT) and imiquimod 5% cream. The sequential use of both could result in better clinical outcomes. Objectives . To enhance efficacy of therapies while improving tolerability, convenience, and patient adherence with a scheme combining two concomitant or sequential AK treatments. Methods . All patients underwent one session of conventional PDT. Two weeks after, the PDT imiquimod 5% cream was applied to the treatment area once daily for three days per week. One course continued for four weeks followed by a clinical evaluation and decision about further treatment. Patients who had not cleared all of their AK lesions in the treatment area in course 1 participated in a second 4-week course of treatment. Limitations . Small size of population. Results . Three participants were enrolled. Two patients showed complete clinical clearance of AKs. The effect was also noted after long-term followup, at months seven and eleven. No subject discontinued for an adverse event. There were severe local skin reactions in two participants which were severe erythema, scaling, and crusting. One patient showed no response to the therapy. Conclusions . Photodynamic therapy followed by imiquimod was well tolerated and improved reduction of actinic keratoses. This initial proof-of-concept should be studied in larger clinical trials.
cGMP-Dependent Protein Kinase Contributes to Hydrogen Sulfide-Stimulated Vasorelaxation
2012-12-28

A growing body of evidence suggests that hydrogen sulfide (H2S) is a signaling molecule in mammalian cells. In the cardiovascular system, H2S enhances vasodilation and angiogenesis. H2S-induced vasodilation is hypothesized to occur through ATP-sensitive potassium channels (K(ATP)); however, we recently demonstrated that it also increases cGMP levels in tissues. Herein, we studied the involvement of cGMP-dependent protein kinase-I in H2S-induced vasorelaxation. The effect of H2S on vessel tone was studied in phenylephrine-contracted aortic rings with or without endothelium. cGMP levels were determined in cultured cells or isolated vessel by enzyme immunoassay. Pretreatment of aortic rings with sildenafil attenuated NaHS-induced relaxation, confirming previous findings that H2S is a phosphodiesterase inhibitor. In addition, vascular tissue levels of cGMP in cystathionine gamma lyase knockouts were lower than those in wild-type control mice. Treatment of aortic rings with NaHS, a fast releasing H2S donor, enhanced phosphorylation of vasodilator-stimulated phosphoprotein in a time-dependent manner, suggesting that cGMP-dependent protein kinase (PKG) is activated after exposure to H2S. Incubation of aortic rings with a PKG-I inhibitor (DT-2) attenuated NaHS-stimulated relaxation. Interestingly, vasodilatory responses to a slowly releasing H2S donor (GYY 4137) were unaffected by DT-2, suggesting that this donor dilates mouse aorta through PKG-independent pathways. Dilatory responses to NaHS and L-cysteine (a substrate for H2S production) were reduced in vessels of PKG-I knockout mice (PKG-I−/−). Moreover, glibenclamide inhibited NaHS-induced vasorelaxation in vessels from wild-type animals, but not PKG-I−/−, suggesting that there is a cross-talk between K(ATP) and PKG. Our results confirm the role of cGMP in the vascular responses to NaHS and demonstrate that genetic deletion of PKG-I attenuates NaHS and L-cysteine-stimulated vasodilation.
First test of Lorentz violation with a reactor-based antineutrino experiment
2012-12-28

We present a search for Lorentz violation with 8249 candidate electron antineutrino events taken by the Double Chooz experiment in 227.9 live days of running. This analysis, featuring a search for a sidereal time dependence of the events, is the first test of Lorentz invariance using a reactor-based antineutrino source. No sidereal variation is present in the data and the disappearance results are consistent with sidereal time independent oscillations. Under the Standard-Model Extension, we set the first limits on 14 Lorentz violating coefficients associated with transitions between electron and tau flavor, and set two competitive limits associated with transitions between electron and muon flavor.
A Variant In the Abo Gene Explains the Variation in Soluble E-Selectin Levels—Results from Dense Genotyping in Two Independent Populations
2012-12-28

Our findings in two independent samples indicate that the genetic variants at the ABO locus affect sE-selectin levels. Since distinct genome-wide association studies linked the ABO gene with myocardial infarction (MI) in the presence of coronary atherosclerosis and with coronary artery disease, these findings may not only enhance our understanding of adhesion molecule biology, but may also provide a focus for several novel research avenues.
Ray Tracing Rational B-Spline Patches in VLSI
2012-12-30

Rational B-spline surfaces make it possible to merge the concepts of freeform surfaces and that of surfaces described by rational polynomials especially conic sections. For ray tracing it is crucial to determine the intersection between ray and object. Therefore an algorithm is developed that is suitable for a VLSI implementation. Some alternatives for the implementation of this algorithm are presented and discussed. The paper concludes with a discussion of some problems and possible further developments.
Parallel Subpixel Scanconversion
2012-12-30

IntroductionComputer graphics and its subsections image processing, image analysis and image generation are known to be a wide field for the application of parallel architectures. While in image processing and analysis the demand for "real time" computation is in the center of discussion, it becomes more and more important in the field of image generation, too. Some applications, like sequences of realistic appearing images raise highest demands on algorithm and architecture as well.
Towards a Taxonomy for Display Processors
2012-12-30

Image generation for raster displays proceeds in two main steps: geometry processing and pixel processing. The snbsystem performing the pixel processing is called display processor.In the paper a model for the displa.y processor is developed that takes into account both function and timing properties. The model identifies scan conversion, hidden surface removal, shading and anti-aliasing as tile key functions of the display processor. The timing model is expressed in an inequation being fundamental for all display processor architectures.On the basis of that model a taxonomy is presented which classifies display processors according to four main criteria: function, partitioning, a.rchitecture and performance.The taxonomy is applied to five real display processors: Pixel-planes, SLAM, PROOF, the Ray-Casting Machine and the Structured Frame Store System.Investigation of existing display processor architectures on the basis of the devel oped taxonomy revealed a potential new architecture. This architecture partitions the image generation process ill image space and employs a. tree topology.
In Vivo Imaging Enables High Resolution Preclinical Trials on Patients’ Leukemia Cells Growing in Mice
2012-12-31

Xenograft mouse models represent helpful tools for preclinical studies on human tumors. For modeling the complexity of the human disease, primary tumor cells are by far superior to established cell lines. As qualified exemplary model, patients' acute lymphoblastic leukemia cells reliably engraft in mice inducing orthotopic disseminated leukemia closely resembling the disease in men. Unfortunately, disease monitoring of acute lymphoblastic leukemia in mice is hampered by lack of a suitable readout parameter.
Optimized recuperation strategy for (Hybrid) Electric Vehicles based on intelligent sensors
2012-12-31

The limited range of Battery Electric Vehicles (BEV) is a major restraint for their market acceptance. This paper shows that efficiency — hence range — increase can be achieved by optimal distribution of driving and braking torque to the electric machines of an EV. Furthermore, a novel strategy for efficient recuperation of kinetic energy during the braking process of a (H)EV based on intelligent sensors is introduced. Both mentioned approaches take a detailed model of the vehicle's dynamics and powertrain characteristics into account. The strategy is utilized in an Advanced Driver Assistance System, which enables guided anticipatory driving for the driver. It is shown that the proposed semi-automatic process allows increased recuperation capabilities compared to state-of-the-art regenerative braking with torque blending. An improvement of energy regeneration efficiency of 31.7 percentage points compared to a standard serial regenerative braking system is achieved in a typical braking scenario.
Structural Requirements for Cub Domain Containing Protein 1 (CDCP1) and Src Dependent Cell Transformation
2012-12-31

Cub domain containing protein 1 (CDCP1) is strongly expressed in tumors derived from lung, colon, ovary, or kidney. It is a membrane protein that is phosphorylated and then bound by Src family kinases. Although expression and phosphorylation of CDCP1 have been investigated in many tumor cell lines, the CDCP1 features responsible for transformation have not been fully evaluated. This is in part due to the lack of an experimental system in which cellular transformation depends on expression of exogenous CDCP1 and Src. Here we use retrovirus mediated co-overexpression of c-Src and CDCP1 to induce focus formation of NIH3T3 cells. Employing different mutants of CDCP1 we show that for a full transformation capacity, the intact amino- and carboxy-termini of CDCP1 are essential. Mutation of any of the core intracellular tyrosine residues (Y734, Y743, or Y762) abolished transformation, and mutation of a palmitoylation motif (C689,690G) strongly reduced it. Src kinase binding to CDCP1 was not required since Src with a defective SH2 domain generated even more CDCP1 dependent foci whereas Src myristoylation was necessary. Taken together, the focus formation assay allowed us to define structural requirements of CDCP1/Src dependent transformation and to characterize the interaction of CDCP1 and Src.
Down-Regulation of Na+/K+ATPase Activity by Human Parvovirus B19 Capsid Protein VP1
2013-01-01

To investigate the molecular mechanisms of the inhibition of Na+,K(+)-adenosine triphosphatase (Na+,K(+)-ATPase) in diabetes mellitus, we incubated Na+,K(+)-ATPase purified from human placenta of six healthy nondiabetic women with plasma from six insulin-dependent diabetic (IDDM) men and six healthy controls and with different concentrations of lysophosphatidylcholine (LPC). We determined the enzyme activity, anthroyl ouabain-binding capacity, dissociation constant (Kd), and average lifetime values (tau) by the static and dynamic fluorescence of anthroyl ouabain. The lipid annulus of the enzyme was studied by static and dynamic fluorescence of 1-(4-trimethylamino-phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH). Moreover, we studied the lipid microenvironment surrounding the Na+,K(+)-ATPase purified from the placentas of six healthy women and six insulin-dependent diabetic women, determining the percent composition of phospholipids of the lipid annulus. The addition of total and protein-free IDDM plasma to normal Na+,K(+)-ATPase significantly inhibited the enzymatic activity even at the lowest concentration studied (1: 100), whereas the ouabain-binding capacity, Kd, and tau were not affected by IDDM plasma. The fluorescence polarization and lifetime values of TMA-DPH were significantly decreased by diabetic plasma. The incubation of Na+,K(+)-ATPase with LPC caused an inhibition of the enzymatic activity without modifications of the anthroyl ouabain-binding capacity and dissociation constant. The fluorescence polarization and lifetime values of TMA-DPH were significantly decreased by 5 mumol/L LPC. The study of the phospholipids surrounding Na+,K(+)-ATPase demonstrated a significant increase in the percent LPC content in IDDM patients compared with controls together with a concomitant decrease in phosphatidylcholine. These observations indicate that the inhibition caused by diabetic plasma on Na+,K(+)-ATPase is not dependent on a modification of the ouabain-binding site and that it seems to mimic the effect of LPC addition. A link between modification of the lipid moiety of the enzyme and Na+,K(+)-ATPase inhibition might be hypothesized.
Bat guilds, a concept to classify the highly diverse foraging and echolocation behaviors of microchiropteran bats
2013-01-01

Throughout evolution the foraging and echolocation behaviors as well as the motor systems of bats have been adapted to the tasks they have to perform while searching and acquiring food. When bats exploit the same class of environmental resources in a similar way, they perform comparable tasks and thus share similar adaptations independent of their phylogeny. Species with similar adaptations are assigned to guilds or functional groups. Habitat type and foraging mode mainly determine the foraging tasks and thus the adaptations of bats. Therefore, we use habitat type and foraging mode to define seven guilds. The habitat types open, edge and narrow space are defined according to the bats' echolocation behavior in relation to the distance between bat and background or food item and background. Bats foraging in the aerial, trawling, flutter detecting, or active gleaning mode use only echolocation to acquire their food. When foraging in the passive gleaning mode bats do not use echolocation but rely on sensory cues from the food item to find it. Bat communities often comprise large numbers of species with a high diversity in foraging areas, foraging modes, and diets. The assignment of species living under similar constraints into guilds identifies patterns of community structure and helps to understand the factors that underlie the organization of highly diverse bat communities. Bat species from different guilds do not compete for food as they differ in their foraging behavior and in the environmental resources they use. However, sympatric living species belonging to the same guild often exploit the same class of resources. To avoid competition they should differ in their niche dimensions. The fine grain structure of bat communities below the rather coarse classification into guilds is determined by mechanisms that result in niche partitioning.
Human T Cell Aging and the Impact of Persistent Viral Infections
2013-01-01

Aging is associated with a dysregulation of the immune response, loosely termed "immunosenescence." Each part of the immune system is influenced to some extent by the aging process. However, adaptive immunity seems more extensively affected and among all participating cells it is the T cells that are most altered. There is a large body of experimental work devoted to the investigation of age-associated differences in T cell phenotypes and functions in young and old individuals, but few longitudinal studies in humans actually delineating changes at the level of the individual. In most studies, the number and proportion of late-differentiated T cells, especially CD8+ T cells, is reported to be higher in the elderly than in the young. Limited longitudinal studies suggest that accumulation of these cells is a dynamic process and does indeed represent an age-associated change. Accumulations of such late-stage cells may contribute to the enhanced systemic pro-inflammatory milieu commonly seen in older people. We do not know exactly what causes these observed changes, but an understanding of the possible causes is now beginning to emerge. A favored hypothesis is that these events are at least partly due to the effects of the maintenance of essential immune surveillance against persistent viral infections, notably Cytomegalovirus (CMV), which may exhaust the immune system over time. It is still a matter of debate as to whether these changes are compensatory and beneficial or pathological and detrimental to the proper functioning of the immune system and whether they impact longevity. Here, we will review present knowledge of T cell changes with aging and their relation to chronic viral and possibly other persistent infections.
The contribution of transcranial magnetic stimulation in the functional evaluation of microcircuits in human motor cortex
2013-01-01

Although transcranial magnetic stimulation (TMS) activates a number of different neuron types in the cortex, the final output elicited in corticospinal neurones is surprisingly stereotyped. A single TMS pulse evokes a series of descending corticospinal volleys that are separated from each other by about 1.5 ms (i.e., ~670 Hz). This evoked descending corticospinal activity can be directly recorded by an epidural electrode placed over the high cervical cord. The earliest wave is thought to originate from the direct activation of the axons of fast-conducting pyramidal tract neurones (PTN) and is therefore termed "D" wave. The later waves are thought to originate from indirect, trans-synaptic activation of PTNs and are termed "I" waves. The anatomical and computational characteristics of a canonical microcircuit model of cerebral cortex composed of layer II and III and layer V excitatory pyramidal cells, inhibitory interneurons, and cortico-cortical and thalamo-cortical inputs can account for the main characteristics of the corticospinal activity evoked by TMS including its regular and rhythmic nature, the stimulus intensity-dependence and its pharmacological modulation. In this review we summarize present knowledge of the physiological basis of the effects of TMS of the human motor cortex describing possible interactions between TMS and simple canonical microcircuits of neocortex. According to the canonical model, a TMS pulse induces strong depolarization of the excitatory cells in the superficial layers of the circuit. This leads to highly synchronized recruitment of clusters of excitatory neurons, including layer V PTNs, and of inhibitory interneurons producing a high frequency (~670 Hz) repetitive discharge of the corticospinal axons. The role of the inhibitory circuits is crucial to entrain the firing of the excitatory networks to produce a high-frequency discharge and to control the number and magnitude of evoked excitatory discharge in layer V PTNs. In summary, simple canonical microcircuits of neocortex can explain activation of corticospinal neurons in human motor cortex by TMS.