julilili42/papers huggingface dataset:
Intraspecific Variation in Cellular and Biochemical Heat Response Strategies of Mediterranean Xeropicta derbentina [Pulmonata, Hygromiidae]
2014-01-27

Dry and hot environments challenge the survival of terrestrial snails. To minimize overheating and desiccation, physiological and biochemical adaptations are of high importance for these animals. In the present study, seven populations of the Mediterranean land snail species Xeropicta derbentina were sampled from their natural habitat in order to investigate the intraspecific variation of cellular and biochemical mechanisms, which are assigned to contribute to heat resistance. Furthermore, we tested whether genetic parameters are correlated with these physiological heat stress response patterns. Specimens of each population were individually exposed to elevated temperatures (25 to 52°C) for 8 h in the laboratory. After exposure, the health condition of the snails' hepatopancreas was examined by means of qualitative description and semi-quantitative assessment of histopathological effects. In addition, the heat-shock protein 70 level (Hsp70) was determined. Generally, calcium cells of the hepatopancreas were more heat resistant than digestive cells - this phenomenon was associated with elevated Hsp70 levels at 40°C.We observed considerable variation in the snails' heat response strategy: Individuals from three populations invested much energy in producing a highly elevated Hsp70 level, whereas three other populations invested energy in moderate stress protein levels - both strategies were in association with cellular functionality. Furthermore, one population kept cellular condition stable despite a low Hsp70 level until 40°C exposure, whereas prominent cellular reactions were observed above this thermal limit. Genetic diversity (mitochondrial cytochrome c oxidase subunit I gene) within populations was low. Nevertheless, when using genetic indices as explanatory variables in a multivariate regression tree (MRT) analysis, population structure explained mean differences in cellular and biochemical heat stress responses, especially in the group exposed to 40°C. Our study showed that, even in similar habitats within a close range, populations of the same species use different stress response strategies that all rendered survival possible.
Electromagnetic structure of the nucleon and the Roper resonance in a light-front quark approach
2014-01-27

A relativistic light-front quark model is used to describe both the elastic nucleon and nucleon-Roper transition form factors in a large Q2 range, up to 35 GeV2 for the elastic and up to 12 GeV2 for the resonance case. Relativistic three-quark configurations satisfying the Pauli exclusion principle on the light-front are used for the derivation of the current matrix elements. The Roper resonance is considered as a mixed state of a three-quark core configuration and a molecular N+sigma hadron component. Based on this ansatz we obtain a realistic description of both processes, elastic and inelastic, and show that existing experimental data are indicative of a composite structure of the Roper resonance.
Up-Regulation of hERG K+ Channels by B-RAF
2014-01-27

Human ether-a-go-go related-gene K+ channels (hERG) participate in the regulation of tumor cell proliferation and apoptosis. HERG channel activity is up-regulated by growth factors. Kinases sensitive to growth factor signaling include the serine/threonine protein kinase B-RAF. The present study thus explored whether B-RAF influences hERG channel expression and activity. To this end, hERG channels were expressed in Xenopus oocytes with or without wild-type B-RAF, hERG channel activity was determined utilizing dual-electrode voltage clamp and hERG protein abundance in the cell membrane was analyzed utilizing confocal microscopy as well as chemiluminescence. Moreover, in rhabdomyosarcoma RD cells the effect of B-RAF inhibitor PLX-4720 on hERG-mediated current was quantified by whole-cell patch clamp and hERG cell surface protein abundance by utilizing biotinylation of cell surface proteins as well as flow cytometry. As a result, co-expression of wild-type B-RAF in hERG-expressing Xenopus oocytes significantly increased hERG channel activity and hERG channel protein abundance in the cell membrane. Treatment for 24 hours of B-RAF and hERG-expressing Xenopus oocytes with B-RAF inhibitor PLX-4720 (10 μM) significantly decreased hERG-mediated current and hERG cell surface expression. Similarly, in rhabdomyosarcoma RD cells, treatment for 24 hours with B-RAF inhibitor PLX-4720 significantly decreased hERG cell membrane protein abundance and hERG-mediated current. In conclusion, B-RAF is a powerful regulator of hERG channel activity and cell surface hERG protein abundance.
Cold Bose atoms around the crossing of quantum waveguides
2014-01-27

We show that massive low energy particles traversing a branching zone or a\\ncrossing of quantum waveguides may experience a non standard trapping force\\nthat cannot be derived from a potential. For interacting cold Bose atoms we\\nreport on the formation of a localised Hartree ground state for three prototype\\nwaveguide geometries with broken translational symmetry: a cranked L-shaped\\nwaveguide L, a T-shaped waveguide T, and the crossing C of two quantum\\nwaveguides. The phenomenon is kinetic energy driven and cannot be described\\nwithin the Thomas-Fermi approximation. Depending on the ratio of joining\\nlateral tube diameters of the respective waveguides C,L,T delocalisation\\ncommences when the particle number N approaches a critical value. For the case\\nof a binary mixture of two different Bose atom species A and B we observe non\\nstandard trapping of both atom species for subcritical particle numbers. A\\nsudden demixing quantum transition takes place as the total particle number\\nN=N_{A}+N_{B} is increased at fixed mixing ratio N_{A}/N_{B}. Depending on the\\nmass ratio m_{A}/m_{B} the heavier atom species delocalises first for a wide\\nrange of interaction parameters. The numerical calculations are based on a\\nsplitting scheme involving an analytic approximation to the short time\\nasymptotics of the imaginary time quantum propagator of a single particle\\nobeying to Dirichlet boundary conditions at the walls inside the respective\\nwaveguides.\\n
Managerial versus Production Wages: Offshoring, Country Size, and Endowments
2014-01-27

Abstract We explore the role of trade in differentiated final goods as well as offshoring of tasks for inequality both within and between countries, emphasizing the distinction between managerial and production labour. We extend Grossman and Rossi‐Hansberg (2012), where task trade is driven by external economies of scale, by considering asymmetric endowments. Identifying possible equilibrium patterns of task trade, we find little scope for two‐way trade if endowments are asymmetric. Our numerical simulations identify non‐monotonicities between the level of offshoring and measures of within‐country as well as between‐country inequality.
Elucidation of the molecular mechanism and the efficacyin vivoof a novel 1,4‐benzoquinone that inhibits 5‐lipoxygenase
2014-01-28

Background and Purpose 1,4‐Benzoquinones are well‐known inhibitors of 5‐lipoxygenase (5‐ LOX , the key enzyme in leukotriene biosynthesis), but the molecular mechanisms of 5‐ LOX inhibition are not completely understood. Here we investigated the molecular mode of action and the pharmacological profile of the novel 1,4‐benzoquinone derivative 3‐((decahydronaphthalen‐6‐yl)methyl)‐2,5‐dihydroxycyclohexa‐2,5‐diene‐1,4‐dione ( RF ‐ I d) in vitro and its effectiveness in vivo . Experimental Approach Mechanistic investigations in cell‐free assays using 5‐ LOX and other enzymes associated with eicosanoid biosynthesis were conducted, along with cell‐based studies in human leukocytes and whole blood. Molecular docking of RF ‐ I d into the 5‐ LOX structure was performed to illustrate molecular interference with 5‐ LOX . The effectiveness of RF ‐ I d in vivo was also evaluated in two murine models of inflammation. Key Results RF ‐ I d consistently suppressed 5‐ LOX product synthesis in human leukocytes and human whole blood. RF ‐ I d also blocked COX ‐2 activity but did not significantly inhibit COX ‐1, microsomal PGE 2 synthase‐1, cytosolic PLA 2 or 12‐ and 15‐ LOX . Although RF ‐ I d lacked radical scavenging activity, reducing conditions facilitated its inhibitory effect on 5‐ LOX whereas cell stress impaired its efficacy. The reduced hydroquinone form of RF ‐ I d ( RED ‐ RF ‐ I d) was a more potent inhibitor of 5‐ LOX as it had more bidirectional hydrogen bonds within the 5‐ LOX substrate binding site. Finally, RF ‐ I d had marked anti‐inflammatory effects in mice in vivo . Conclusions and Implications RF ‐ I d represents a novel anti‐inflammatory 1,4‐benzoquinone that potently suppresses LT biosynthesis by direct inhibition of 5‐ LOX with effectiveness in vivo . Mechanistically, RF ‐ I d inhibits 5‐ LOX in a non‐redox manner by forming discrete molecular interactions within the active site of 5‐ LOX .
Modeling of Compound Profiling Experiments Using Support Vector Machines
2014-01-28

Profiling of compounds against target families has become an important approach in pharmaceutical research for the identification of hits and analysis of selectivity and promiscuity patterns. We report on modeling of profiling experiments involving 429 potential inhibitors and a panel of 24 different kinases using support vector machine ( SVM ) techniques and naïve Bayesian classification. The experimental matrix contained many different activity profiles. SVM predictions achieved overall high accuracy due to consistently low false‐positive and consistently high true‐negative rates. However, predictions for promiscuous inhibitors were affected by false‐negative rates. Combined target‐based SVM classifiers reached or exceeded the performance of SVM profile prediction methods and were superior to Bayesian classification. The classifiers displayed different prediction characteristics including diverse combinations of false‐positive and true‐negative rates. Predicted and experimentally observed compound activity profiles were compared in detail, revealing activity patterns modeled with different accuracy.
An empirical test of marginal productivity theory
2014-01-28

We explore an hitherto unused approach to testing marginal productivity theory. Our method rests on the simple idea that, under the assumption of a linear homogeneous production function, residual profits are informative about the discrepancies between factor payments and marginal products. Our empirical application using data on manufacturing plants in Chile suggest moderate deviations from marginal productivity theory which depend on firm size.
Back Cover: Design and Synthesis of Tricyclic JAK3 Inhibitors with Picomolar Affinities as Novel Molecular Probes (ChemMedChem 2/2014)
2014-01-28

The back cover picture shows the design of a novel class of tricyclic Janus kinase 3 (JAK3) inhibitors. By freezing the current gold standard, tofacitinib, into its binding conformation, extremely potent inhibitors with improved selectivity for JAK3 and intracellular activity were developed. These compounds may serve as tools and probes for pharmacodynamic studies. For more details, see the Communication by Stefan A. Laufer et al. on p. 277 ff.
The Big-Fish-Little-Pond Effect in Mathematics
2014-01-29

This substantive-methodological synergy demonstrates evolving multilevel latent-variable models for cross-cultural data. Using Trends in International Mathematics and Science Study (TIMSS) 2007 data for U.S. and Saudi Arabian eighth grade students, we evaluate the psychometric properties (measurement invariance, method effects, and gender differences) of math self-concept, positive affect, coursework aspirations, and achievement. Extending the studies of the “paradoxical cross-cultural self-concept effect” largely based on U.S.-Asian comparisons, country-level differences strongly favored the United States for achievement test scores, but favored Saudi Arabia for self-concept and aspirations. Latent mean gender differences, of particular interest because of Saudi Arabia’s single-sex school system, interacted with country for all constructs. The largest interaction was for achievement test scores; there were no significant gender differences for U.S. students (in coed schools), but in single-sex Saudi schools, Saudi girls performed substantially better than Saudi boys. Consistently with previous (mostly Western) research, but not previously evaluated with TIMSS, in each of the four (2 gender × 2 country) groups all three outcomes (self-concept, affect, and aspiration) were positively influenced by individual student achievement but negatively influenced by class-average achievement (the Big-Fish-Little-Pond Effect: BFLPE). BFLPEs were similar in size for boys and girls in coeducational (United States) and in single-sex (Saudi) classrooms.
Dynamically phase‐cycled radial balanced SSFP imaging for efficient banding removal
2014-01-29

Purpose Balanced steady‐state free precession (bSSFP) imaging suffers from banding artifacts due to its inherent sensitivity to inhomogeneities in the main magnetic field. These artifacts can be removed by the acquisition of multiple images at different frequency offsets. However, conventional phase‐cycling is hindered by a long scan time. The purpose of this work is to present a novel approach for efficient banding removal in bSSFP imaging. Theory and Methods To this end, the phase‐cycle during a single‐shot radial acquisition of an image was dynamically changed. Thus, each projection is acquired with a different frequency offset. Using conventional radial gridding, an artifact‐free image can be reconstructed out of this dataset. Results The approach is validated at clinical field strength [3.0 Tesla (T)] as well as at ultrahigh field (9.4T). Robust elimination of banding artifacts was obtained for different imaging regions, including brain imaging at ultrahigh field with an in‐plane resolution of 0.25 × 0.25 mm 2 . Besides banding artifact‐free imaging, the applicability of the proposed technique for fat‐water separation is demonstrated. Conclusion Dynamically phase‐cycled radial bSSFP has the potential for banding‐free bSSFP imaging in a short scan time, in the presence of severe field inhomogeneities and at high resolution. Magn Reson Med 73:182–194, 2015. © 2014 Wiley Periodicals, Inc.
An efficient approach for glomerular filtration rate assessment in older adults
2014-01-29

Aims Assessment of glomerular filtration rate ( GFR ) is crucial because the GFR value defines the stage of chronic kidney disease and determines the adjustment of drug dosage. The aim was to investigate a new method for the accurate determination of GFR in older adults based on the combination of an exogenous filtration marker, iohexol, and an endogenous marker, serum creatinine or cystatin C . Methods We combined variables for the estimation of GFR with a reduced set of measurements of the marker iohexol. In a population‐based sample of 570 subjects (≥70 years old) from the B erlin I nitiative S tudy ( BIS ), we investigated the following: (i) the BIS 1 and BIS 2 equations based on age, gender and serum creatinine with or without serum cystatin C ; (ii) equations based on one or two iohexol measurements; and (iii) equations based on the combination of variables from BIS 1 or BIS 2 with iohexol measurements. The reference standard was based on eight iohexol measurements. The cut‐off value of 60 ml min −1 (1.73 m) −2 was chosen to assess accuracy. Equations were constructed using a learning sample ( n = 285) and an independent validation sample ( n = 285). Results Misclassification rates were 17.2% ( BIS 1), 11.6% ( BIS 2), 14.7% [iohexol measurement at 240 min (iohexol 240 )], 7.0% (iohexol 240 combined with variables included in BIS 1) and 6.7% (iohexol 240 combined with variables included in BIS 2). Misclassification rates did not decrease significantly after inclusion of two or three iohexol measurements. Conclusions Combined strategies for the determination of GFR lead to a relevant increase of diagnostic validity.
Lower Limb Movement Preparation in Chronic Stroke
2014-01-30

Background. Thus far, most of the brain–computer interfaces (BCIs) developed for motor rehabilitation used electroencephalographic signals to drive prostheses that support upper limb movement. Only few BCIs used hemodynamic signals or were designed to control lower extremity prostheses. Recent technological developments indicate that functional near-infrared spectroscopy (fNIRS)-BCI can be exploited in rehabilitation of lower limb movement due to its great usability and reduced sensitivity to head motion artifacts. Objective. The aim of this proof of concept study was to assess whether hemodynamic signals underlying lower limb motor preparation in stroke patients can be reliably measured and classified. Methods. fNIRS data were acquired during preparation of left and right hip movement in 7 chronic stroke patients. Results. Single-trial analysis indicated that specific hemodynamic changes associated with left and right hip movement preparation can be measured with fNIRS. Linear discriminant analysis classification of totHB signal changes in the premotor cortex and/or posterior parietal cortex indicated above chance accuracy in discriminating paretic from nonparetic movement preparation trials in most of the tested patients. Conclusion. The results provide first evidence that fNIRS can detect brain activity associated with single-trial lower limb motor preparation in stroke patients. These findings encourage further investigation of fNIRS suitability for BCI applications in rehabilitation of patients with lower limb motor impairment after stroke.
Claudin-3 and Claudin-5 Protein Folding and Assembly into the Tight Junction Are Controlled by Non-conserved Residues in the Transmembrane 3 (TM3) and Extracellular Loop 2 (ECL2) Segments
2014-01-30

The mechanism of tight junction (TJ) assembly and the structure of claudins (Cldn) that form the TJ strands are unclear. This limits the molecular understanding of paracellular barriers and strategies for drug delivery across tissue barriers. Cldn3 and Cldn5 are both common in the blood-brain barrier but form TJ strands with different ultrastructures. To identify the molecular determinants of folding and assembly of these classic claudins, Cldn3/Cldn5 chimeric mutants were generated and analyzed by cellular reconstitution of TJ strands, live cell confocal imaging, and freeze-fracture electron microscopy. A comprehensive screening was performed on the basis of the rescue of mutants deficient for strand formation. Cldn3/Cldn5 residues in transmembrane segment 3, TM3 (Ala-127/Cys-128, Ser-136/Cys-137, Ser-138/Phe-139), and the transition of TM3 to extracellular loop 2, ECL2 (Thr-141/Ile-142) and ECL2 (Asn-148/Asp-149, Leu-150/Thr-151, Arg-157/Tyr-158), were identified to be involved in claudin folding and/or assembly. Blue native PAGE and FRET assays revealed 1% n-dodecyl β-d-maltoside-resistant cis-dimerization for Cldn5 but not for Cldn3. This homophilic interaction was found to be stabilized by residues in TM3. The resulting subtype-specific cis-dimer is suggested to be a subunit of polymeric TJ strands and contributes to the specific ultrastructure of the TJ detected by freeze-fracture electron microscopy. In particular, the Cldn5-like exoplasmic face-associated and particle-type strands were found to be related to cis-dimerization. These results provide new insight into the mechanisms of paracellular barrier formation by demonstrating that defined non-conserved residues in TM3 and ECL2 of classic claudins contribute to the formation of TJ strands with differing ultrastructures.
Singlet Exciton Diffusion in Organic Crystals Based on Marcus Transfer Rates
2014-01-30

Exciton diffusion is a critical step for energy conversion in optoelectronic devices. This spawns the desire for theoretical approaches that allow for fast but reliable determinations of the material-dependent exciton transport parameters. For this purpose, the Marcus theory, which is widely used in the context of charge transport, is adapted to exciton diffusion. In contrast to the common approach of calculating the exciton hopping rate via the coupling and the spectral overlap, this alternative approach is less costly, because, instead of the spectral overlap, only the reorganization energy is needed. To demonstrate the capability of the approach, the diffusion constants for naphthalene, anthracene, and diindenoperylene crystals are calculated and compared with both calculations conducted with the well-established exciton hopping rate, including coupling and spectral overlap, and with experimental data. These test calculations show that Marcus-based exciton diffusion properties tend to be too small but are qualitatively correct (i.e., they seem to be useful to predict trends). Nevertheless, for reliable results, high-level quantum chemical approaches are necessary for the computation of the reorganization energies. However, they have to be calculated only once. Coupling constants, which are needed for all pairs of monomers, have a considerably smaller influence, i.e., they can be computed by a lower level approach, which makes the method even less costly.
Copper(I) Complexes of Phenanthro‐Annulated N‐Heterocyclic Carbenes: Synthesis and Transmetalation Reactions
2014-01-30

Abstract Copper(I) complexes with phenanthro‐annulated N‐heterocyclic carbene ligands were prepared by reaction of imidazolium salts with copper(I) oxide. Transmetalation of the copper complexes with [RhCl(cod)] 2 in usual solvents like CH 2 Cl 2 led to an equilibrium between the reactants and the products. For rhodium complexes 4 and 5 this equilibrium could be shifted to the product side by carrying out the reaction in acetonitrile. The ester functionalized rhodium complex 6 was prepared in a two phase mixture of chloroform and aqueous CaCl 2 starting from copper complex 3c . The rhodium complexes were characterized by NMR and X‐ray measurements.
Hypothermia inhibits expression of CD11b (MAC-1) and CD162 (PSGL-1) on monocytes during extracorporeal circulation.
2014-01-30

Expression of CD11b and CD162 on monocytes has a temperature-dependent regulation, with decreased expression during hypothermia, which may result in an inhibition of leukocyte-endothelial and leukocyte-platelet interaction. This beneficial effect may influence the extracorporeal circulation-related inflammatory response and tissue damage.
Coding of melodic gestalt in human auditory cortex
2014-01-30

The perception of a melody is invariant to the absolute properties of its constituting notes, but depends on the relation between them—the melody's relative pitch profile. In fact, a melody's “Gestalt” is recognized regardless of the instrument or key used to play it. Pitch processing in general is assumed to occur at the level of the auditory cortex. However, it is unknown whether early auditory regions are able to encode pitch sequences integrated over time (i.e., melodies) and whether the resulting representations are invariant to specific keys. Here, we presented participants different melodies composed of the same 4 harmonic pitches during functional magnetic resonance imaging recordings. Additionally, we played the same melodies transposed in different keys and on different instruments. We found that melodies were invariantly represented by their blood oxygen level–dependent activation patterns in primary and secondary auditory cortices across instruments, and also across keys. Our findings extend common hierarchical models of auditory processing by showing that melodies are encoded independent of absolute pitch and based on their relative pitch profile as early as the primary auditory cortex.