julilili42/papers huggingface dataset:
Down‐regulation of Na+‐coupled glutamate transporter EAAT3 and EAAT4 by AMP‐activated protein kinase
2010-03-10

J. Neurochem. (2010) 113 , 1426–1435. Abstract The glutamate transporters EAAT3 and EAAT4 are expressed in neurons. They contribute to the cellular uptake of glutamate and aspartate and thus to the clearance of the excitatory transmitters from the extracellular space. During ischemia, extracellular accumulation of glutamate may trigger excitotoxicity. Energy depletion leads to activation of the AMP‐activated protein kinase (AMPK), a kinase enhancing energy production and limiting energy expenditure. The present study thus explored the possibility that AMPK regulates EAAT3 and/or EAAT4. To this end, EAAT3 or EAAT4 were expressed in Xenopus oocytes with or without AMPK and electrogenic glutamate transport determined by dual electrode voltage clamp. In EAAT3‐ and in EAAT4‐expressing oocytes glutamate generated a current ( I g ), which was half maximal ( K M ) at 74 μM (EAAT3) or at 4 μM (EAAT4) glutamate. Co‐expression of constitutively active γR70Q AMPK or of wild type AMPK did not affect K M but significantly decreased the maximal I g in both EAAT3‐ (by 34%) and EAAT4‐ (by 49%) expressing oocytes. Co‐expression of the inactive mutant αK45R AMPK [α1(K45R)β1γ1] did not appreciably affect I g . According to confocal microscopy and chemiluminescence co‐expression of γR70Q AMPK or of wild type AMPK reduced the membrane abundance of EAAT3 and EAAT4. The observations show that AMPK down‐regulates Na + ‐coupled glutamate transport.
PlasmidDNAand MessengerRNAfor Therapy
2010-03-10

Abstract Recent studies performed in animal models and humans show that injection of pDNA or mRNA is safe and can elicit the expected results. Because pDNA and stabilized mRNA have the natural capacity to activate the immune system through the triggering of TLR, pDNA‐ and mRNA‐based therapeutic utilizations are mostly tested in the field of vaccination. This article focuses on therapeutic applications of pDNA‐ and mRNA‐based approaches.
Structural Basis of Cell Wall Cleavage by a Staphylococcal Autolysin
2010-03-11

The major autolysins (Atl) of Staphylococcus epidermidis and S. aureus play an important role in cell separation, and their mutants are also attenuated in virulence. Therefore, autolysins represent a promising target for the development of new types of antibiotics. Here, we report the high-resolution structure of the catalytically active amidase domain AmiE (amidase S. epidermidis) from the major autolysin of S. epidermidis. This is the first protein structure with an amidase-like fold from a bacterium with a gram-positive cell wall architecture. AmiE adopts a globular fold, with several alpha-helices surrounding a central beta-sheet. Sequence comparison reveals a cluster of conserved amino acids that define a putative binding site with a buried zinc ion. Mutations of key residues in the putative active site result in loss of activity, enabling us to propose a catalytic mechanism. We also identified and synthesized muramyltripeptide, the minimal peptidoglycan fragment that can be used as a substrate by the enzyme. Molecular docking and digestion assays with muramyltripeptide derivatives allow us to identify key determinants of ligand binding. This results in a plausible model of interaction of this ligand not only for AmiE, but also for other PGN-hydrolases that share the same fold. As AmiE active-site mutations also show a severe growth defect, our findings provide an excellent platform for the design of specific inhibitors that target staphylococcal cell separation and can thereby prevent growth of this pathogen.
Exploiting plants for glutathione (GSH) production: Uncoupling GSH synthesis from cellular controls results in unprecedented GSH accumulation
2010-03-11

Glutathione (GSH) is a key factor for cellular redox homeostasis and tolerance against abiotic and biotic stress (May et al., 1998; Noctor et al., 1998a). Previous attempts to increase GSH content in plants have met with moderate success (Rennenberg et al., 2007), largely because of tight and multilevel control of its biosynthesis (Rausch et al., 2007). Here, we report the in planta expression of the bifunctional gamma-glutamylcysteine ligase-glutathione synthetase enzyme from Streptococcus thermophilus (StGCL-GS), which is shown to be neither redox-regulated nor sensitive to feedback inhibition by GSH. Transgenic tobacco plants expressing StGCL-GS under control of a constitutive promoter reveal an extreme accumulation of GSH in their leaves (up to 12 micromol GSH/gFW, depending on the developmental stage), which is more than 20- to 30-fold above the levels observed in wild-type (wt) plants and which can be even further increased by additional sulphate fertilization. Surprisingly, this dramatically increased GSH production has no impact on plant growth while enhancing plant tolerance to abiotic stress. Furthermore, StGCL-GS-expressing plants are a novel, cost-saving source for GSH production, being competitive with current yeast-based systems (Li et al., 2004).
Characterization and outcome following Puumala virus infection: a retrospective analysis of 75 cases
2010-03-11

In a majority of cases, PUUV infection results in thrombocytopenic AKI. Fever is a requirement for diagnosis, while elevated LDH and CRP values are also frequently observed. Overall, early renal outcomes were excellent.
Constructing optimal authentication codes with perfect multi-fold secrecy
2010-03-11

We establish a construction of optimal authentication codes achieving perfect multi-fold secrecy by means of combinatorial designs. This continues the author’s work (ISIT 2009, cf. [1]) and answers an open question posed therein. As an application, we present the first infinite class of optimal codes that provide two-fold security against spoofing attacks and at the same time perfect two-fold secrecy.
Method for reliable realization of aφJosephson junction
2010-03-12

We propose a method to realize a Josephson junction by combining alternating 0 and parts (sub junctions) with an intrinsically non-sinusoidal current-phase relation (CPR). Conditions for the realization of the ground state are analyzed. It is shown that taking into account the non-sinusoidal CPR for a "clean junction with a ferromagnetic (F) barrier, one can significantly enlarge the domain (regime of suitable F-layer thicknesses) of the ground state and make the practical realization of Josephson junctions feasible. Such junctions may also have two different stable solutions, such as 0 and , 0 and , or and .
Acute tryptophan depletion increases experimental nausea but also induces hunger in healthy female subjects
2010-03-12

Acute tryptophan depletion is associated with increased symptoms of nausea in healthy female subjects when exposed to body rotation. Acute tryptophan depletion also increases hunger rating. These opposite effects may indicate independent actions of the serotonin on central and peripheral functions.
4-Chloro-7-methoxymethyl-2-phenyl-7H-pyrrolo[2,3-b]pyridine
2010-03-12

In the title compound, C(15)H(13)ClN(2)O, the phenyl group makes a dihedral angle of 7.91 (8)° with the pyrrole ring. The crystal structure forms a three-dimensional network stabilized by π-π inter-actions [centroid-centroid distances = 3.807 (1) Å] between the pyridine and phenyl rings and via inter-molecular C-H⋯O hydrogen bonds.
Total Hemoglobin Mass and Blood Volume of Elite Kenyan Runners
2010-03-13

The oxygen transport of the blood cannot explain the superior endurance performance of Kenyan runners. Most measured parameters are in the same range as those of elite German runners, and tHb-mass even deteriorates after an adaptation to near sea level.
Motion perception during smooth pursuit eye movements: object and background motion perception depend on different non-retinal signals on eye velocity
2010-03-14

The perception of target (=object) motion during steady-state smooth-pursuit eye movements (SPEM) in darkness must rely on non-retinal information on eye velocity (“reference signal”, RS-object) as significant target image slip is missing. On the other hand, an eye movement reference signal (RS-background) is also needed in order to guarantee the perception of a stable background despite pursuit induced background image slip. This is the result of a subtractive comparison of background image slip and RS-b. We have recently shown that RS-b is continuously re-calibrated, based on visual information on its adequacy. Here we used our ability to change the size of RS-b in order to investigate, whether target and background motion perception share a common reference signal. Six human subjects participated in two experiments, in which we compared the perception of pursuit-induced background movement (experiment a) with the perception of object motion (experiment b) during SPEMs. In each experiment, “test” trials, used to measure the percept of object and background motion respectively, were presented randomly interleaved with a much larger number of “constant stimuli” (CS) trials, in which SPEM was carried out over structured backgrounds moving at constant velocities. These CS trials, mimicking a mismatch between RS-b and the retinal signal, allowed us to manipulate the size of RS-b, thereby altering the percept of background motion (Lindner et al. 2000). In accordance with our earlier observations, we found that the velocity of the background associated with subjective stationarity was shifted towards the velocity of the CS, reflecting a change in the size of the RS-b. However, perceived target velocity turned out to be independent of the size and direction of the CS. These findings indicate that the percept of object and background motion during SPEM depends on distinct reference signals. LindnerAHaarmeierTThierP(2000) Psychophysical evidence for an adaptable eye movement reference signal guaranteeing spatial constancy during smooth pursuit eye movements. Society for Neuroscience Abstracts 26, 2, 1716.
Platelet-derived Growth Factor-DD Targeting Arrests Pathological Angiogenesis by Modulating Glycogen Synthase Kinase-3β Phosphorylation
2010-03-15

Platelet-derived growth factor-DD (PDGF-DD) is a recently discovered member of the PDGF family. The role of PDGF-DD in pathological angiogenesis and the underlying cellular and molecular mechanisms remain largely unexplored. In this study, using different animal models, we showed that PDGF-DD expression was up-regulated during pathological angiogenesis, and inhibition of PDGF-DD suppressed both choroidal and retinal neovascularization. We also demonstrated a novel mechanism mediating the function of PDGF-DD. PDGF-DD induced glycogen synthase kinase-3beta (GSK3beta) Ser(9) phosphorylation and Tyr(216) dephosphorylation in vitro and in vivo, leading to increased cell survival. Consistently, GSK3beta activity was required for the antiangiogenic effect of PDGF-DD targeting. Moreover, PDGF-DD regulated the expression of GSK3beta and many other genes important for angiogenesis and apoptosis. Thus, we identified PDGF-DD as an important target gene for antiangiogenic therapy due to its pleiotropic effects on vascular and non-vascular cells. PDGF-DD inhibition may offer new therapeutic options to treat neovascular diseases.
Cancellation of gaze stabilizing mechanisms during human smooth pursuit: Indications for the involvement of an extra-retinal reference
2010-03-15

When our eyes are tracking a target that is moving in front of a structured background, background image motion is induced in the opposite direction. Usually, such global image motion is an appropriate stimulus to drive gaze stabilizing mechanisms, which in turn would counteract the voluntary eye movement. We have previously demonstrated, that during human smooth pursuit eye movements (SPEM) the sensitivity for full-field motion is reduced strongly — but only in the direction opposite to the eye movement (Vision Res. 2001; 41:1685–94). Although these results provided an explanation for the accuracy of SPEM despite self-induced motion the mechanisms underlying this asymmetry in global motion processing remained unclear. To come up with an answer we employed brief and unexpected background motion (20°/s) during horizontal SPEM (10°/s). Background motion could be either ‘in-phase’ or ‘counter-phase’ with respect to the direction of SPEM. In exp. 1 the SOA of background motion was varied between 0, 100 and 200ms with respect to target motion onset (thereby varying relative motion between target and background during SPEM initiation). As in our previous experiments a background induced perturbation in SPEM velocity occurred in ‘in-phase’ conditions, only. Therefore this asymmetry significantly depended on the phase relation between background motion and SPEM direction (p<0.001) but not on the SOAs and related relative motion (p>0.5; ANOVA2). In exp. 2 the pursuit target was briefly extinguished during background motion. Although now any relative motion between target and background was absent the effect of ‘phase’ was still present (p<0.001) and did not significantly differ from trials without target extinction (p>0.5; ANOVA2). The asymmetry in global motion processing cannot solely be attributed to a visual mechanism, i.e. relative motion. This implies that the cancellation of gaze stabilizing mechanisms critically depends on extra-retinal information on SPEM direction.
The spatial tuning of chromatic adaptation
2010-03-15

A central issue for understanding chromatic adaptation is the influence of the spatial complexity of a scene. In previous experiments, we found that the early time-course (0.2–5 sec) of mid-spectral chromatic adaptation is accelerated by a cortical mechanism that responds to contrast in the adaptation-pattern (Werner et al., Vis. Res., 2000 (40): 1101–1113). Our new experiments investigate the properties of this spatial component of chromatic adaptation. The pattern (15.4 × 13.2 deg) was presented on a calibrated colour monitor and consisted of either hexagonal patches or horizontal stripes of different luminances. For the reference condition, ite was achromatic (u′ = 0.197, v′ = 0.468; Lmean = 19.3cd/m2). Chromatic adaptation was measured for the transition from D65 adaptation to a 5s green adaptation-light located in an equiluminant plane in colour space (chromaticities were chosen from cardinal axes after Krauskopf et al., 1982). The effect of chromatic adaptation was measured by a hue cancellation technique, which involved maintaining the achromatic appearance of a central hexagonal test-patch (2.2 × 2.4 deg). Our results show that mid-wavelength adaptation is a function of the magnitude of luminance contrast in the adaptation-pattern, indicating the influence of a mechanism of contrast gain control acting on chromatic adaptation. Furthermore, the contrast component of adaptation responds to the spatial complexity of the adaptation pattern rather than to local contrast per se, indicating a global rather than local mechanism. Finally, chromatic adaptation is selective for the spatial frequency and orientation of the adaptation pattern. The results are interpreted in terms of spatial adaptation gain control and as evidence for the co-processing of form and colour information at a cortical level. A possible relation to contrast gain mechanisms is discussed. This study was supported by DFG SFB 430, Tp A7.
Thousands of Voices for HMM-Based Speech Synthesis–Analysis and Application of TTS Systems Built on Various ASR Corpora
2010-03-16

In conventional speech synthesis, large amounts of phonetically balanced speech data recorded in highly controlled recording studio environments are typically required to build a voice. Although using such data is a straightforward solution for high quality synthesis, the number of voices available will always be limited, because recording costs are high. On the other hand, our recent experiments with HMM-based speech synthesis systems have demonstrated that speaker-adaptive HMM-based speech synthesis (which uses an "average voice model" plus model adaptation) is robust to non-ideal speech data that are recorded under various conditions and with varying microphones, that are not perfectly clean, and/or that lack phonetic balance. This enables us to consider building high-quality voices on "non-TTS" corpora such as ASR corpora. Since ASR corpora generally include a large number of speakers, this leads to the possibility of producing an enormous number of voices automatically. In this paper, we demonstrate the thousands of voices for HMM-based speech synthesis that we have made from several popular ASR corpora such as the Wall Street Journal (WSJ0, WSJ1, and WSJCAM0), Resource Management, Globalphone, and SPEECON databases. We also present the results of associated analysis based on perceptual evaluation, and discuss remaining issues.
Fast and accurate frequency-dependent radiation transport for hydrodynamics simulations in massive star formation
2010-03-16

\\n Context. \\nRadiative feedback plays a crucial role in the formation of massive stars. \\nThe implementation of a fast and accurate description of the proceeding thermodynamics in pre-stellar cores\\nand evolving accretion disks is therefore a main effort in current hydrodynamics simulations.\\n Aims. \\nWe introduce our newly implemented three-dimensional frequency dependent radiation transport algorithm for hydrodynamics simulations of spatial configurations with a dominant central source.\\n Methods. \\nThe module combines the advantage of the speed of an approximate flux limited diffusion (FLD) solver\\nin the one-temperature approach, which is valid in the static diffusion limit,\\nwith the high accuracy of a frequency dependent first order ray-tracing routine. \\nThe ray-tracing routine especially compensates the introduced \\ninaccuracies by standard approximate FLD solvers in transition regions from optically thin to thick and yields the\\ncorrect optical depths for the frequency dependent stellar irradiation. \\nBoth components of our module make use of realistic tabulated dust opacities. \\nThe module is parallelized for distributed memory machines based on the message passing interface standard. We implemented the module in the three-dimensional high-order magneto-hydrodynamics code Pluto. \\n Results. \\nWe prove the viability of the scheme in a standard radiation benchmark test compared to a full frequency dependent Monte-Carlo based radiative transfer code. The setup includes a central star, a circumstellar flared disk,\\nas well as an envelope. The test is performed for different optical depths. \\nConsidering the frequency dependence of the stellar irradiation, \\nthe temperature distributions can be described\\nprecisely in the optically thin, thick, and irradiated transition regions. \\nResulting radiative forces onto dust grains are reproduced with high accuracy. \\nThe achievable parallel speedup of the method imposes no restriction on further radiative (magneto-) hydrodynamics\\nsimulations.\\n Conclusions. The proposed approximate radiation transport method enables frequency dependent radiation hydrodynamics studies of the\\nevolution of pre-stellar cores and circumstellar accretion disks around an evolving massive star in a highly efficient\\nand accurate manner.\\n
Tip‐Enhanced Raman Spectroscopic Studies of the Hydrogen Bonding between Adenine and Thymine Adsorbed on Au (111)
2010-03-16

STM tip-enhanced spectroscopy is employed to study the hydrogen bonding between adenine (A) and thymine (T) at monolayer coverage at a Au(111) surface. The AT base pair adsorbs nearly vertically at Au(111) with A close to the substrate and T exposed away (see picture). In contrast to the observation at neutral pH, no AT hydrogen bonding at pH 1 is found.
Role of center vortices in Gribov’s confinement scenario
2010-03-16

The connection of Gribov's confinement scenario in Coulomb gauge with the\\ncenter vortex picture of confinement is investigated. For this purpose we\\nassume a vacuum wave functional which models the infrared properties of the\\ntheory and in particular shows strict confinement, i.e. an area law of the\\nWilson loop. We isolate the center vortex content of this wave functional by\\nstandard lattice methods and investigate their contributions to various static\\npropagators of the Hamilton approach to Yang-Mills theory in Coulomb gauge. We\\nfind that the infrared properties of these quantities, in particular the\\ninfrared divergence of the ghost form factor, are dominated by center vortices.\\n
Subsumption and complementation as data fusion operators
2010-03-16

The goal of data fusion is to combine several representations of one real world object into a single, consistent representation, e.g., in data integration. A very popular operator to perform data fusion is the minimum union operator. It is defined as the outer union and the subsequent removal of subsumed tuples. Minimum union is used in other applications as well, for instance in database query optimization to rewrite outer join queries, in the semantic web community in implementing Sparql's optional operator, etc. Despite its wide applicability, there are only few efficient implementations, and until now, minimum union is not a relational database primitive.This paper fills this gap as we present implementations of subsumption that serve as a building block for minimum union. Furthermore, we consider this operator as database primitive and show how to perform optimization of query plans in presence of subsumption and minimum union through rule-based plan transformations. Experiments on both artificial and real world data show that our algorithms outperform existing algorithms used for subsumption in terms of runtime and they scale to large volumes of data.In the context of data integration, we observe that performing data fusion calls for more than subsumption and minimum union. Therefore, another contribution of this paper is the definition of the complementation and complement union operators. Intuitively, these allow to merge tuples that have complementing values and thus eliminate unnecessary null-values.
Efficient computation of trade-off skylines
2010-03-16

When selecting alternatives from large amounts of data, trade-offs play a vital role in everyday decision making. In databases this is primarily reflected by the top-k retrieval paradigm. But recently it has been convincingly argued that it is almost impossible for users to provide meaningful scoring functions for top-k retrieval, subsequently leading to the adoption of the skyline paradigm. Here users just specify the relevant attributes in a query and all suboptimal alternatives are filtered following the Pareto semantics. Up to now the intuitive concept of compensation, however, cannot be used in skyline queries, which also contributes to the often unmanageably large result set sizes. In this paper we discuss an innovative and efficient method for computing skylines allowing the use of qualitative trade-offs. Such trade-offs compare examples from the database on a focused subset of attributes. Thus, users can provide information on how much they are willing to sacrifice to gain an improvement in some other attribute(s). Our contribution is the design of the first skyline algorithm allowing for qualitative compensation across attributes. Moreover, we also provide an novel trade-off representation structure to speed up retrieval. Indeed our experiments show efficient performance allowing for focused skyline sets in practical applications. Moreover, we show that the necessary amount of object comparisons can be sped up by an order of magnitude using our indexing techniques.
Let SQL drive the XQuery workhorse (XQuery join graph isolation)
2010-03-16

A purely relational account of the true XQuery semantics can turn any relational database system into an XQuery processor. Compiling nested expressions of the fully compositional XQuery language, however, yields odd algebraic plan shapes featuring scattered distributions of join operators that currently overwhelm commercial SQL query optimizers.