julilili42/papers huggingface dataset:
Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease
2014-02-07

Significance Understanding loci nominated by genome-wide association studies (GWASs) is challenging. Here, we show, using the specific example of Parkinson disease, that identification of protein–protein interactions can help determine the most likely candidate for several GWAS loci. This result illustrates a significant general principle that will likely apply across multiple diseases.
Plant diversity effects on pollinating and herbivorous insects can be linked to plant stoichiometry
2014-02-07

Die Artenvielfalt von Pflanzen strukturiert die Gesellschaften höherer trophischer Ebenen und verbessert die Fortpflanzung und Fitness von Pflanzen-assoziierten Insekten. Dieser Einfluss auf höhere trophische Ebenen kann von der Quantität (Verfügbarkeit) und Qualität (Zusammensetzung) der Ressourcen abhängen. Wir untersuchten die Stöchiometrie von Interaktionen zwischen Pflanzen und zwei funktionellen Insektengruppen (Herbivoren, Bestäuber) entlang des experimentellen Pflanzendiversitätsgradienten im „Jena-Experiment“. Wir analysierten den prozentuellen Anteil von Kohlenstoff (C), Stickstoff (N) und Phosphat (P), sowie die entsprechenden molaren Verhältnisse dieser Elemente (C:N, C:P, N:P) bei einer bestäubenden Bienenart (Chelostoma distinctum) und einer herbivoren Heuschreckenart (Chorthippus parallelus), welche wir auf Graslandflächen verschiedener Diversitätsstufen gezüchtet haben. Insekten zeigten höhere prozentuale Anteile in der Trockenmasse (C, N und P) und niedrigere C:N- und C:P-Verhältnisse als Pflanzen. Das C:N-Verhältnis war bei Heuschrecken signifikant höher als bei den Bienen, und in beiden Gruppen bei den Weibchen höher als bei den Männchen. Zunehmende Pflanzenvielfalt erhöhte das C:N-Verhältnis von männlichen Bienen und weiblichen Heuschrecken und die Insektenstöchiometrie beider Gruppen hängte positiv mit der Pflanzenstöchiometrie zusammen (männliche Bienen: C:P und N:P; Heuschrecken: C:N und N:P). Unsere Studie zeigt unterschiedliche Stöchiometrie von antagonistischen und mutualistischen Interaktionen. Daraus ergeben sich verschiedene Schlussfolgerungen für diversitätsgetriebene Veränderungen von der Elementzusammensetzung bei Pflanzen verschiedener trophischer und funktioneller Gruppen.
Quantitative analysis of neuronal response properties in primary and higher‐order auditory cortical fields of awake house mice (Mus musculus)
2014-02-07

Abstract Because of its great genetic potential, the mouse ( M us musculus ) has become a popular model species for studies on hearing and sound processing along the auditory pathways. Here, we present the first comparative study on the representation of neuronal response parameters to tones in primary and higher‐order auditory cortical fields of awake mice. We quantified 12 neuronal properties of tone processing in order to estimate similarities and differences of function between the fields, and to discuss how far auditory cortex (AC) function in the mouse is comparable to that in awake monkeys and cats. Extracellular recordings were made from 1400 small clusters of neurons from cortical layers III / IV in the primary fields AI (primary auditory field) and AAF (anterior auditory field), and the higher‐order fields AII (second auditory field) and DP (dorsoposterior field). Field specificity was shown with regard to spontaneous activity, correlation between spontaneous and evoked activity, tone response latency, sharpness of frequency tuning, temporal response patterns (occurrence of phasic responses, phasic‐tonic responses, tonic responses, and off‐responses), and degree of variation between the characteristic frequency ( CF ) and the best frequency ( BF ) ( CF – BF relationship). Field similarities were noted as significant correlations between CF s and BF s, V ‐shaped frequency tuning curves, similar minimum response thresholds and non‐monotonic rate‐level functions in approximately two‐thirds of the neurons. Comparative and quantitative analyses showed that the measured response characteristics were, to various degrees, susceptible to influences of anesthetics. Therefore, studies of neuronal responses in the awake AC are important in order to establish adequate relationships between neuronal data and auditory perception and acoustic response behavior.
Increased Myeloperoxidase Plasma Levels in Patients with Alzheimer's Disease
2014-02-07

AD patients showed significantly increased plasma levels of MPO, which could be an important molecular link between atherosclerosis and AD. Further studies should evaluate whether MPO may also be a useful biomarker and potential new treatment target in AD.
Magnetostratigraphy of drill-core SG-1b in the western Qaidam Basin (NE Tibetan Plateau) and tectonic implications
2014-02-07

The Qaidam Basin is an ideal archive to study long-term climate and erosion histories at the NE Tibetan Plateau. We present a magnetostratigraphic study of the 723 m deep drill-core SG-1b of lacustrine sediments at the Jianshan anticline in the western Qaidam Basin. The polarity sequence shows 18 normal and 19 reverse polarity zones which can be readily correlated with chrons C1n-C3Br of the Geomagnetic Polarity Time Scale 2004 (GPTS 2004), dating the core at about 7.3-1.6 Ma. The resulting mean sediment accumulation rate (SAR) between polarity boundaries ranges from 6.5 to 30.4 cm ka(-1). High SARs occur within the intervals of &gt; 7.3-6.0, 5.2-4.2 and 3.6-2.6 Ma indicating three episodic phases of higher erosion. From the derived variation of SARs and previous results, we conclude that growth strata at the Jianshan anticline started to develop at similar to 1.6 Ma by limb rotation. All this we relate to pulse tectonic uplift of the NE Tibetan Plateau and fault-propagation-folding in the Qaidam Basin.
Between word formation and meaning change
2014-02-07

In diachronic lexicology, word formation (henceforth: WF) is generally treated as one of three strictly distinct types of processes of lexical innovation, the two others being meaning change (MCh) and borrowing. A unitary theoretical framework based on Construction Grammer and integrating different types of lexical innovation will show that, from an onomasiological point of view, WF and MCh in particular are only two ways of switching from a construction 1 expressing a concept C1 to a formally and semantically related construction 2 expressing a concept C2. From this perspective it is not surprising to find multiple combination, intertwining and interaction between MCh and WF: WF and MCh as subsequent steps in chains of diachronic change; WF and MCh as designative alternatives in lexical innovation; WF and MCh as components of the phenomena of lexical ellipsis and folk-etymology; MCh governing the diachronic evolution of already existing WF devices; MCh creating new WF devices.
Quark gap equation in an external magnetic field
2014-02-10

The nonperturbative quark gap equation under the rainbow truncation and with\\ntwo versions of a phenomenological one-gluon exchange interaction is studied in\\nthe presence of a uniform external magnetic field, with emphasis on the small\\nfield limit. The chiral quark condensate, magnetic moment and susceptibility\\nare calculated and compared to recent lattice data.\\n
Radiation power and linewidth of a semifluxon-based Josephson oscillator
2014-02-10

We demonstrate a high-frequency generator operating at ∼200 GHz based on flipping a semifluxon in a Josephson junction of moderate normalized length. The semifluxon spontaneously appears at the π discontinuity of the Josephson phase artificially created by means of two tiny current injectors. The radiation is detected by an on-chip detector (tunnel junction). The estimated radiation power (at the detector) is ∼8 nW and should be compared with the dc power of ∼100 nW consumed by the generator. The measured radiation linewidth, as low as 1.1 MHz, is typical for geometrical (Fiske) resonances, although we tried to suppress such resonances by placing well-matched microwave transformers at its both ends. Making use of a phase-locking feedback loop, we are able to reduce the radiation linewidth to less than 1 Hz measured relative to the reference oscillator and defined just by the resolution of our measurement setup.
Miles, A. & Mezzich, J.E. (2011). The care of the patient and the soul of the clinic: person-centered medicine as an emergent model of modern clinical practice. International Journal of Person Centered Medicine 1 (2) 207-222
2014-02-10

In recent years, there has undoubtedly been an “over-reliance on science” that has led to an unedifying “scientistic medicine” in patient care of most if not all medical disciplines [1]. Although I would not go so far as to say that these circumstances may lead to “an ethical and moral chaos within clinical practice,” I agree with Miles and Mezzich that “while it is imperative that medicine must be actively and continuously informed by science, science cannot function as the base of medicine.” Evidence generated by clinical or, in the early beginnings of research progress, even non-clinical trials can be very helpful, but to impose study results uncritically upon the individual patient would mean to neglect this person’s individuality. The individual needs may, for example, not be consistent with the inclusion criteria of the very study used as the evidence base for the treatment. I therefore welcome, then, the article by Miles and Mezzich, which discusses the need for a more critical reflection on scientific data before or within clinical use and the demand for more humanity in patient care in terms of a person-centered approach.
Implications of fast recovery after left ventricular assist devices implantation
2014-02-10

Objectives: The treatment of advanced heart failure patients using continuous-flow left ventricular assist devices (CF-LVAD) has become an established therapy with low mortality and morbidity. However the critically ill patients often require long intensive care and recovery periods. We sought to identify determinants of shorter recovery after LVAD implantation.
Biocompatibility profile of the HeartMate II left ventricular assist device and the centrimag adult centrifugal pump
2014-02-10

Objectives: In the management of heart failure patients ECLS/ECMO, as well as LVAD have proofed their clinical benefit. However the development of Sepsis/SIRS in the course of treatment leads to relevant morbidity and mortality. We therefore investigated the biocompatible properties of both devices.
Driving with Binocular Visual Field Loss? A Study on a Supervised On-Road Parcours with Simultaneous Eye and Head Tracking
2014-02-11

Post-chiasmal visual pathway lesions and glaucomatous optic neuropathy cause binocular visual field defects (VFDs) that may critically interfere with quality of life and driving licensure. The aims of this study were (i) to assess the on-road driving performance of patients suffering from binocular visual field loss using a dual-brake vehicle, and (ii) to investigate the related compensatory mechanisms. A driving instructor, blinded to the participants' diagnosis, rated the driving performance (passed/failed) of ten patients with homonymous visual field defects (HP), including four patients with right (HR) and six patients with left homonymous visual field defects (HL), ten glaucoma patients (GP), and twenty age and gender-related ophthalmologically healthy control subjects (C) during a 40-minute driving task on a pre-specified public on-road parcours. In order to investigate the subjects' visual exploration ability, eye movements were recorded by means of a mobile eye tracker. Two additional cameras were used to monitor the driving scene and record head and shoulder movements. Thus this study is novel as a quantitative assessment of eye movements and an additional evaluation of head and shoulder was performed. Six out of ten HP and four out of ten GP were rated as fit to drive by the driving instructor, despite their binocular visual field loss. Three out of 20 control subjects failed the on-road assessment. The extent of the visual field defect was of minor importance with regard to the driving performance. The site of the homonymous visual field defect (HVFD) critically interfered with the driving ability: all failed HP subjects suffered from left homonymous visual field loss (HL) due to right hemispheric lesions. Patients who failed the driving assessment had mainly difficulties with lane keeping and gap judgment ability. Patients who passed the test displayed different exploration patterns than those who failed. Patients who passed focused longer on the central area of the visual field than patients who failed the test. In addition, patients who passed the test performed more glances towards the area of their visual field defect. In conclusion, our findings support the hypothesis that the extent of visual field per se cannot predict driving fitness, because some patients with HVFDs and advanced glaucoma can compensate for their deficit by effective visual scanning. Head movements appeared to be superior to eye and shoulder movements in predicting the outcome of the driving test under the present study scenario.
Flux upper limits for 47 AGN observed with H.E.S.S. in 2004−2011
2014-02-11

About 40% of the observation time of the High Energy Stereoscopic System (H.E.S.S.) is dedicated to studying active galactic nuclei (AGN), with the aim of increasing the sample of known extragalactic very-high-energy (VHE, E&gt;100 GeV) sources and constraining the physical processes at play in potential emitters. H.E.S.S. observations of AGN, spanning a period from April 2004 to December 2011, are investigated to constrain their gamma-ray fluxes. Only the 47 sources without significant excess detected at the position of the targets are presented. Upper limits on VHE fluxes of the targets were computed and a search for variability was performed on the nightly time scale. For 41 objects, the flux upper limits we derived are the most constraining reported to date. These constraints at VHE are compared with the flux level expected from extrapolations of Fermi-LAT measurements in the two-year catalog of AGN. The H.E.S.S. upper limits are at least a factor of two lower than the extrapolated Fermi-LAT fluxes for 11 objects. Taking into account the attenuation by the extragalactic background light reduces the tension for all but two of them, suggesting intrinsic curvature in the high-energy spectra of these two AGN. Compilation efforts led by current VHE instruments are of critical importance for target-selection strategies before the advent of the Cherenkov Telescope Array, CTA.
Cyclophilin A and EMMPRIN (CD147) in cardiovascular diseases
2014-02-11

Cyclophilin A (CyPA) is an abundantly expressed intracellular protein. It exerts a variety of functions due to its peptidyl-prolyl cis-trans isomerase (PPIase) activity. When released into the extracellular space, CyPA binds to its extracellular receptor CD147 (EMMPRIN) and thereby initiates a cascade of inflammatory processes. Recent data indicate that both extra- and intracellular CyPA significantly contribute to cardiovascular inflammation, myocardial ischaemia and reperfusion injury, and myocardial remodelling processes. Thus, CyPA appears to represent a novel target to treat vascular and myocardial inflammation.
Safety and tolerability of carbamylated erythropoietin in Friedreich's ataxia
2014-02-11

ABSTRACT Background Erythropoietin (EPO) derivatives have been found to increase frataxin levels in Friedreich's ataxia (FRDA) in vitro . This multicenter, double‐blind, placebo‐controlled, phase II clinical trial aimed to evaluate the safety and tolerability of Lu AA24493 (carbamylated EPO; CEPO). Methods Thirty‐six ambulatory FRDA patients harboring &gt;400 GAA repeats were 2:1 randomly assigned to either CEPO in a fixed dose (325 μg thrice‐weekly) or placebo. Safety and tolerability were assessed up to 103 days after baseline. Secondary outcome measures of efficacy (exploration of biomarkers and ataxia ratings) were performed up to 43 days after baseline. Results All patients received six doses of study medication. Adverse events were equally distributed between CEPO and placebo. There was no evidence for immunogenicity of CEPO after multiple dosing. Biomarkers, such as frataxin, or measures for oxidative stress and ataxia ratings did not differ between CEPO and placebo. Conclusion CEPO was safe and well tolerated in a 2‐week treatment phase. Secondary outcome measures remained without apparent difference between CEPO and placebo. © 2014 International Parkinson and Movement Disorder Society
Long-Wavelength Limit of Photochemical Energy Conversion in Photosystem I
2014-02-11

In Photosystem I (PS I) long-wavelength chlorophylls (LWC) of the core antenna are known to extend the spectral region up to 750 nm for absorbance of light that drives photochemistry. Here we present clear evidence that even far-red light with wavelengths beyond 800 nm, clearly outside the LWC absorption bands, can still induce photochemical charge separation in PS I throughout the full temperature range from 295 to 5 K. At room temperature, the photoaccumulation of P700(+•) was followed by the absorbance increase at 826 nm. At low temperatures (T < 100 K), the formation of P700(+•)FA/B(-•) was monitored by the characteristic EPR signals of P700(+•) and FA/B(-•) and by the characteristic light-minus-dark absorbance difference spectrum in the QY region. P700 oxidation was observed upon selective excitation at 754, 785, and 808 nm, using monomeric and trimeric PS I core complexes of Thermosynechococcus elongatus and Arthrospira platensis, which differ in the amount of LWC. The results show that the LWC cannot be responsible for the long-wavelength excitation-induced charge separation at low temperatures, where thermal uphill energy transfer is frozen out. Direct energy conversion of the excitation energy from the LWC to the primary radical pair, e.g., via a superexchange mechanism, is excluded, because no dependence on the content of LWC was observed. Therefore, it is concluded that electron transfer through PS I is induced by direct excitation of a proposed charge transfer (CT) state in the reaction center. A direct signature of this CT state is seen in absorbance spectra of concentrated PS I samples, which reveal a weak and featureless absorbance band extending beyond 800 nm, in addition to the well-known bands of LWC (C708, C719 and C740) in the range between 700 and 750 nm. The present findings suggest that nature can exploit CT states for extending the long wavelength limit in PSI even beyond that of LWC. Similar mechanisms may work in other photosynthetic systems and in chemical systems capable of photoinduced electron transfer processes in general.
HESS J1640-465 - an exceptionally luminous TeV -ray supernova remnant
2014-02-11

The results of follow-up observations of the TeV gamma-ray source HESSJ 1640-465 from 2004 to 2011 with the High Energy Stereoscopic System (H.E.S.S.) are reported in this work. The spectrum is well described by an exponential cut-off power law with photon index Gamma=2.11 +/- 0.09_stat +/- 0.10_sys, and a cut-off energy of E_c = (6.0 +2.0 -1.2) TeV. The TeV emission is significantly extended and overlaps with the north-western part of the shell of the SNR G338.3-0.0. The new H.E.S.S. results, a re-analysis of archival XMM-Newton data, and multi-wavelength observations suggest that a significant part of the gamma-ray emission from HESS J1640-465 originates in the SNR shell. In a hadronic scenario, as suggested by the smooth connection of the GeV and TeV spectra, the product of total proton energy and mean target density could be as high as W_p n_H ~ 4 x 10^52 (d/10kpc)^2 erg cm^-3.
Importance models of the physical self: Improved methodology supports a normative‐cultural importance model but not the individual importance model
2014-02-11

Abstract We examine theoretical and methodological issues associated with the roles of individual and group‐normative importance in self‐esteem determination. Critical issues include multicollinearity among the physical self‐subdomains, which may have affected previous results, and the need for a multidimensional perspective on importance models. We apply state‐of‐the‐art methodologies, including exploratory structural equation modelling and the product‐of‐indicators approach to latent interactions. Positive interactions would be required to support the individually importance‐weighted average model, but none were observed in the multidimensional model estimated on the full sample. Nonetheless, some interaction effects were found in the country‐specific version of the model. Rather, we found support for the alternative group importance‐weighted average model. We conclude that domain‐specific self‐concepts are weighted differently and thus differentially affect self‐esteem, but these weights do not seem to depend on individual differences in importance. Although awaiting confirmation from further studies, our results suggest the idea that individuals use mainly normative importance processes based on cultural factors in weighting each domain‐specific component of self‐concept. Copyright © 2014 John Wiley &amp; Sons, Ltd.
Decreased Store Operated Ca2+ Entry in Dendritic Cells Isolated from Mice Expressing PKB/SGK-Resistant GSK3
2014-02-11

Dendritic cells (DCs), key players of immunity, are regulated by glycogen synthase kinase GSK3. GSK3 activity is suppressed by PKB/Akt and SGK isoforms, which are in turn stimulated by the PI3K pathway. Exposure to bacterial lipopolysaccharides increases cytosolic Ca(2+)-concentration ([Ca(2+)]i), an effect augmented in DCs isolated from mutant mice expressing PKB/SGK-resistant GSK3α,β (gsk3(KI) ). Factors affecting [Ca(2+)]i include Ca(2+)-release from intracellular stores (CRIS), store-operated Ca(2+)-entry (SOCE) through STIM1/STIM2-regulated Orai1, K(+)-dependent Na(+)/Ca(2+)-exchangers (NCKX), K(+)-independent Na(+)/Ca(2+)-exchangers (NCX) and calbindin-D28k. The present study explored whether PKB/SGK-dependent GSK3α, β-activity impacts on CRIS, SOCE, NCKX, NCX or calbindin. DCs were isolated from gsk3(KI) mice and respective wild-type mice (gsk3(WT) ), [Ca(2+)]i estimated from Fura2 fluorescence, Orai1, STIM1, STIM2 as well as calbindin-D28k protein abundance determined by Western blotting and mRNA levels quantified by real time PCR. As a result, thapsigargin-induced CRIS and SOCE were significantly blunted by GSK3-inhibitors SB216763 (1-10 μM, 30 min) or GSK-XIII (10 μM, 30 min) but were significantly lower in gsk3(WT) than in gsk3(KI) DCs. Orai1, STIM1 and STIM2 protein abundance was significantly lower and calbindin-D28k abundance significantly higher in gsk3(KI) than in gsk3(WT) DCs. Activity of NCKX and NCX was significantly higher in gsk3(KI) than in gsk3(WT) DCs and was significantly increased by SB216763 (1 μM, 30 min) or GSK-XIII (10 μM, 30 min). Treatment of gsk3(WT) DCs with SB216763 (1 μM, 4-24 h) or GSK-XIII (10 μM, 4-24 h) did not significantly modify the protein abundance of Orai1, STIM1 and STIM2. The present observations point to a dual role of GSK3 in the regulation of Ca(2+) in DCs. Acute inhibition of GSK3 blunted the increase of [Ca(2+)]i following CRIS and SOCE and stimulated NCKX/NCX activity. However, expression of PKB/SGK-resistant GSK3α, β downregulated the increase of [Ca(2+)]i following CRIS and SOCE, an effect at least partially due to downregulation of Orai1, STIM1 and STIM2 expression as well as upregulation of Na(+)/Ca(2+)-exchanger activity and calbindin D28k expression.