julilili42/papers huggingface dataset:
Factors Regulating Stem Cell Biology in Development and Disease
2015-12-20

Stem cells in general are characterized by their ability to self-renew and to differentiate towards various progeny. Great efforts started to give hope since the first discovery of mammalian pluripotency by Stevens and Little, 1954; the field of stem cell research using pluripotent stem cells (PSC) has reached a state of general interest in both science and medicine. Following an overall fast development of in vivo and in vitro research, stem cells are nowadays regularly implied in developmental and pathomechanistical studies. Their unique ability to generate all cell types of the respective organism allows for the directed differentiation of in vitro cultured PSCs into the desired direction. Subsequently, development and function of this differentiated progeny may be investigated in detail. This specifically accounts for the human system where primary materials as well as in vivo studies are strongly limited. In addition, the groundbreaking study describing the generation of PSCs from somatic cells by Takahashi and Yamanaka, served as a lift for unlimited use of individual and patient specific stem cell based investigations. Today, these induced pluripotent stem cells (iPSCs) are amongst others utilized to explicitly study human pathomechanisms in a patient specific setting. Moreover, tissue specific stem cell, for example, serving as a cellular reserve and substitute for decayed cells and degenerated tissue, is discussed as a useful source of human tissue and tissue specific cells. Clearly, these adult stem cells have already been successfully used in therapeutic approaches for decades, such as hematopoietic stem cells in bone marrow transplantations.
Interpreting Thermodynamic Profiles of Aminoadamantane Compounds Inhibiting the M2 Proton Channel of Influenza A by Free Energy Calculations
2015-12-21

The development of novel anti-influenza drugs is of great importance because of the capability of influenza viruses to occasionally cross interspecies barriers and to rapidly mutate. One class of anti-influenza agents, aminoadamantanes, including the drugs amantadine and rimantadine now widely abandoned due to virus resistance, bind to and block the pore of the transmembrane domain of the M2 proton channel (M2TM) of influenza A. Here, we present one of the still rare studies that interprets thermodynamic profiles from isothermal titration calorimetry (ITC) experiments in terms of individual energy contributions to binding, calculated by the computationally inexpensive implicit solvent/implicit membrane molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approach, for aminoadamantane compounds binding to M2TM of the avian "Weybridge" strain. For all eight pairs of aminoadamantane compounds considered, the trend of the predicted relative binding free energies and their individual components, effective binding energies and changes in the configurational entropy, agrees with experimental measures (ΔΔG, ΔΔH, TΔΔS) in 88, 88, and 50% of the cases. In addition, information yielded by the MM-PBSA approach about determinants of binding goes beyond that available in component quantities (ΔH, ΔS) from ITC measurements. We demonstrate how one can make use of such information to link thermodynamic profiles from ITC with structural causes on the ligand side and, ultimately, to guide decision making in lead optimization in a prospective manner, which results in an aminoadamantane derivative with improved binding affinity against M2TM(Weybridge).
Not FLEXible enough: Exploring the temporal dynamics of attentional reallocations with the multiple object tracking paradigm.
2015-12-21

The dynamic environment of human observers requires continuous reallocations of visual attention to compensate for location changes of the attended objects. Particularly, situations with reduced spatial distance between targets and other objects in the display are crucial for keeping track of the target objects. In the present experiments, we explored how the temporal dynamics of such moments of reduced spacing affects the reallocation of visual attention. We asked participants to track 4 targets among indistinguishable distractors. Hereby, we manipulated whether target and distractor objects moved at a constant speed or whether their actual speed followed a sine wave profile. The variable speed oscillated around the constant speed thus maintaining average speed as well as traveled distance and average spatial proximity. We observed inferior tracking performance with variable speed profiles relative to constant speed profiles (Experiments 1a and 1b). When we increased the number of pairs of targets and distractors moving with a variable speed profile (Experiment 2), performance declined continuously. Remarkably, tracking performance also declined when only distractors moved at variable speeds, suggesting that the dynamic changes in interobject spacing rather than the variable speed impairs tracking (Experiment 3). In sum, our results provide evidence for a flexible allocation of the attentional resource toward targets suffering spatial interference by demonstrating the temporal constraints of the reallocation process. (PsycINFO Database Record
Detailed spectral and morphological analysis of the shelltype supernova remnant RCW 86
2015-12-21

Aim. We aim for an understanding of the morphological and spectral properties of the supernova remnant RCW 86 and for insights into the production mechanism leading to the RCW 86 very high-energy γ -ray emission. Methods. We analyzed High Energy Spectroscopic System (H.E.S.S.) data that had increased sensitivity compared to the observations presented in the RCW 86 H.E.S.S. discovery publication. Studies of the morphological correlation between the 0.5–1 keV X-ray band, the 2–5 keV X-ray band, radio, and γ -ray emissions have been performed as well as broadband modeling of the spectral energy distribution with two different emission models. Results. We present the first conclusive evidence that the TeV γ -ray emission region is shell-like based on our morphological studies. The comparison with 2–5 keV X-ray data reveals a correlation with the 0.4–50 TeV γ -ray emission. The spectrum of RCW 86 is best described by a power law with an exponential cutoff at E cut = (3.5 ± 1.2 stat ) TeV and a spectral index of Γ ≈ 1.6 ± 0.2. A static leptonic one-zone model adequately describes the measured spectral energy distribution of RCW 86, with the resultant total kinetic energy of the electrons above 1 GeV being equivalent to ~0.1% of the initial kinetic energy of a Type Ia supernova explosion (10 51 erg). When using a hadronic model, a magnetic field of B ≈ 100 μ G is needed to represent the measured data. Although this is comparable to formerly published estimates, a standard E −2 spectrum for the proton distribution cannot describe the γ -ray data. Instead, a spectral index of Γ p ≈ 1.7 would be required, which implies that ∼7 × 10 49 / n cm −3 has been transferred into high-energy protons with the effective density n cm −3 = n /1 cm −3 . This is about 10% of the kinetic energy of a typical Type Ia supernova under the assumption of a density of 1 cm −3 .
Prefrontal functional connectivity measured with near‐infrared spectroscopy during smoking cue exposure
2015-12-21

Abstract Cue reactivity (CR) is an important concept for relapse in substance use disorders (SUD). Although cue exposure (CE) therapy is discussed as relapse prevention, current approaches still need improvement considering its efficacy. From a neurobiological perspective, CR is related to an over‐activation in sensitized subcortical structures, their projections to motivationally relevant cortical structures (e.g. orbitofrontal cortex, OFC) and deficient prefrontal inhibitory control. Therefore, we analyzed prefrontal cortical activation and its relation to craving during smoking CE. We focused on the OFC—as a projection area of sensitized subcortical structures—due its importance in the processing of reinforcement value and the dorsolateral prefrontal cortex (dlPFC) based on its importance for behavioral inhibition. Functional near‐infrared spectroscopy (fNIRS) was used to assess hemodynamics in prefrontal regions during smoking CE in 24 subjects ( n = 12 occasional smokers, n = 12 controls). Subjective craving intensity (minimum craving as marker of baseline inhibition, range as marker of inhibition time course) was additionally assessed. Craving ratings indicated that CR was elicited solely in smokers, not controls. Those subjective ratings correlated with hemodynamic activity in OFC (craving range) and dlPFC (minimum craving). OFC activation was found earlier throughout the CE in smokers compared to controls. Connectivity (seed‐based correlation) between OFC and dlPFC was increased in smokers. fNIRS can capture prefrontal hemodynamic activity involved in CR elicited during CE and is therefore a promising method to investigate CR and its implications for relapse prevention in SUD.
Prophage-mediated modulation of interaction of Streptococcus thermophilus J34 with human intestinal epithelial cells and its competition against human pathogens
2015-12-21

The human intestinal microbiota plays an important role in human health. While adhesion to gastrointestinal mucosa is a prerequisite for colonisation, inhibition of adhesion is a property which may prevent or reduce infections by food borne pathogens. Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus represent the two lactic bacteria constituting the yoghurt culture. These starter cultures have been claimed to be probiotic. In our study we compared two S. thermophilus strains (i.e. lysogenic strain J34 and corresponding non-lysogenic [prophage-cured] strain J34-6), with respect to (1) their in vitro adhesion properties to HT29 cells and (2) their cell surface hydrophobicities. Effects of the two strains on inhibition of adhesion of the pathogens Listeria monocytogenes Scott A, Staphylococcus aureus 6732 and Salmonella enteritidis S489 were studied in vitro with HT29 cell cultures. Lysogenic strain J34 was shown to be considerably more effective than the non-lysogenic derivative strain J34-6.
Uninformed Decisions? The Online Presentation of Success and Failure of IVF and Related Methods on German IVF Centre Websites
2015-12-21

<b>Background:</b> Patients increasingly use the internet as a source of medical information before initial contact with doctors and during treatment. This applies to reproductive medicine too, where the internet could offer patients the chance to inform themselves in advance about specific procedures and the treatment centres that offer them. In this way it could potentially contribute to informed patient decision-making. This article analyses the web presence of German fertility treatment centres with respect to the provision of information on success rates, risks and side effects of treatment. <b>Methods:</b> Analysis of published success rates and information on the risks and adverse effects of IVF and related methods on German IVF centre websites. <b>Results:</b> Over half of the 129 centres (62.02 %) state a general success rate or their own institution's success rate. Less than a quarter (24.03 %) states their own institution's pregnancy rate and only 7.75 % their own birth rate. The published success rates are mostly pregnancy rates (pregnancy per embryo transfer), which by definition are higher than baby take-home-rates creating unrealistic expectations. Only 61 centres (47.29 %) mention risks and side effects of the procedures offered, and that in varying detail. Only 7 centres (5.43 %) provide information on the risk of psychological stress associated with unsuccessful fertility treatment. <b>Conclusion:</b> There is insufficient opportunity for women and their partners to inform themselves adequately on the internet in advance of treatment about available treatment methods, their success rates and associated risks/side effects; this applies both to specific facilities as well as to the procedures in general. In contrast to other countries, in Germany there is a lack of discussion on content requirements for fertility treatment facility websites.
Windrose Planarity: Embedding Graphs with Direction-Constrained Edges
2015-12-21

Given a planar graph and a partition of the neighbors of each vertex in four sets , , , and , the problem Windrose Planarity asks to decide whether admits a windrose-planar drawing, that is, a planar drawing in which (i) each neighbor is above and to the right of , (ii) each neighbor is above and to the left of , (iii) each neighbor is below and to the left of , (iv) each neighbor is below and to the right of , and (v) edges are represented by curves that are monotone with respect to each axis. By exploiting both the horizontal and the vertical relationship among vertices, windrose-planar drawings allow to simultaneously visualize two partial orders defined by means of the edges of the graph. Although the problem is NP-hard in the general case, we give a polynomial-time algorithm for testing whether there exists a windrose-planar drawing that respects a given combinatorial embedding. This algorithm is based on a characterization of the plane triangulations admitting a windrose-planar drawing. Furthermore, for any embedded graph with vertices that has a windrose-planar drawing, we can construct one with at most one bend per edge and with at most bends in total, which lies on the grid. The latter result contrasts with the fact that straight-line windrose-planar drawings may require exponential area.
Freeze and Thaw of CD4+CD25+Foxp3+ Regulatory T Cells Results in Loss of CD62L Expression and a Reduced Capacity to Protect against Graft-versus-Host Disease
2015-12-22

The adoptive transfer of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in murine models of allogeneic hematopoietic cell transplantation (HCT) has been shown to protect recipient mice from lethal acute graft-versus-host disease (GVHD) and this approach is being actively investigated in human clinical trials. Here, we examined the effects of cryopreservation on Tregs. We found that freeze and thaw of murine and human Tregs is associated with reduced expression of L-selectin (CD62L), which was previously established to be an important factor that contributes to the in vivo protective effects of Tregs. Frozen and thawed murine Tregs showed a reduced capacity to bind to the CD62L binding partner MADCAM1 in vitro as well as an impaired homing to secondary lymphoid organs in vivo. Upon adoptive transfer frozen and thawed Tregs failed to protect against lethal GVHD compared with fresh Tregs in a murine model of allogeneic HCT across major histocompatibility barriers. In summary, the direct administration of adoptively transferred frozen and thawed Tregs adversely affects their immunosuppressive potential which is an important factor to consider in the clinical implementation of Treg immunotherapies.
Intuitive decision making as a gradual process: investigating semantic intuition‐based and priming‐based decisions with fMRI
2015-12-22

Abstract Introduction Intuition has been defined as the instantaneous, experience‐based impression of coherence elicited by cues in the environment. In a context of discovery, intuitive decision‐making processes can be conceptualized as occurring within two stages, the first of which comprises an implicit perception of coherence that is not (yet) verbalizable. Through a process of spreading activation, this initially non‐conscious perception gradually crosses over a threshold of awareness and thereby becomes explicable. Because of its experiential basis, intuition shares conceptual similarities with implicit memory processes. Based on these, the study addresses two research questions: (1) Is the gradual nature of intuitive processes reflected on a neural level? (2) Do intuition‐based decisions differ neurally from priming‐based decisions? Methods To answer these questions, we conducted an fMRI study using the triads task and presented participants with coherent word triads that converge on a common fourth concept, and incoherent word triads that do not converge on a common fourth concept. Participants had to perform semantic coherence judgments as well as to indicate whether they immediately knew the fourth concept. To enable investigating intuition‐based and priming‐based decisions within the same task and with the same participants, we implemented a conceptual priming procedure into the coherence judgment task. We realized this by priming participants with concepts associated with incoherent triads in separate priming blocks prior to the coherence judgments. Results For intuition‐based decisions, imaging results mainly revealed activity within the orbitofrontal cortex, within the inferior frontal gyrus and the middle temporal gyrus. Activity suppression in the right temporo‐occipital complex was observed for priming‐based decisions. Conclusions With respect to research question 1, our data support a continuity model of intuition because the two intuitive stages show quantitatively distinct brain activation patterns. Regarding research question 2, we can draw the preliminary conclusion of a qualitative difference between intuition‐based and priming‐based decisions.
Magnetization reversal of an individual exchange-biased permalloy nanotube
2015-12-22

We investigate the magnetization reversal mechanism in an individual permalloy (Py) nanotube (NT) using a hybrid magnetometer consisting of a nanometer-scale SQUID (nanoSQUID) and a cantilever torque sensor. The Py NT is affixed to the tip of a Si cantilever and positioned in order to optimally couple its stray flux into a Nb nanoSQUID. We are thus able to measure both the NT's volume magnetization by dynamic cantilever magnetometry and its stray flux using the nanoSQUID. We observe a training effect and a temperature dependence in the magnetic hysteresis, suggesting an exchange bias. We find a low blocking temperature T-B = 18 +/- 2 K, indicating the presence of a thin antiferromagnetic native oxide, as confirmed by x-ray absorption spectroscopy on similar samples. Furthermore, we measure changes in the shape of the magnetic hysteresis as a function of temperature and increased training. These observations show that the presence of a thin exchange-coupled native oxide modifies the magnetization reversal process at low temperatures. Complementary information obtained via cantilever and nanoSQUID magnetometry allows us to conclude that, in the absence of exchange coupling, this reversal process is nucleated at the NT's ends and propagates along its length as predicted by theory.
Age-dependent changes of the antioxidant system in rat livers are accompanied by altered MAPK activation and a decline in motor signaling
2015-12-22

Aging is characterized by a progressive decrease of cellular functions, because cells gradually lose their capacity to respond to injury. Increased oxidative stress is considered to be one of the major contributors to age-related changes in all organs including the liver. Our study has focused on elucidating whether important antioxidative enzymes, the mTOR pathway, and MAPKs exhibit age-dependent changes in the liver of rats during aging. We found an age-dependent increase of GSH in the cytosol and mitochondria. The aged liver showed an increased SOD enzyme activity, while the CAT enzyme activity decreased. HO-1 and NOS-2 gene expression was lower in adult rats, but up-regulated in aged rats. Western blot analysis revealed that SOD1, SOD2, GPx, GR, γ-GCL, and GSS were age-dependent up-regulated, while CAT remained constant. We also demonstrated that the phosphorylation of Akt, JNK, p38, and TSC2Ser1254 decreased while ERK1/2 and TSC2Thr1462 increased age-dependently. Furthermore, our data show that the mTOR pathway seems to be activated in livers of aged rats, and hence stimulating cell proliferation/regeneration, as confirmed by an age-dependent increase of PCNA and p-eIF4ESer209 protein expression. Our data may help to explain the fact that liver cells only proliferate in cases of necessity, like injury and damage. In summary, we have demonstrated that, age-dependent changes of the antioxidant system and stress-related signaling pathways occur in the livers of rats, which may help to better understand organ aging.
Factoring lexical and phonetic phylogenetic characters from word lists
2015-12-22

Computational historical linguistics is a young and new field. Among it’s major challenge is the collection and preparation of suitable data resources. Here we present an approach that takes lexical data taken from a large collection of publicly available wordlists as input and infers automatic assessments regarding the cognacy of words and sounds. We illustrate the workflow and test it by comparing the results obtained from the computation of Maximum Likelihood trees with those provided by experts. The results show that our workflow still lags behind simpler approaches which analyze the data within a distance-based framework. However, since distance-based analyses bear a blackbox character, not allowing for a rigorous check of the individual decisions which lead to a certain classification proposal, we think that our experiments are an important contribution towards the establishment of more transparent methods in quantitative historical linguistics.
Determinants of English accents
2015-12-22

In this study we investigate which factors affect the degree of non-native accent of L2 speakers of English who learned English in school and mostly lived for some time in an anglophone setting. We use data from the Speech Accent Archive containing over 700 speakers speaking almost 160 different native languages. We show that besides several important predictors, including the age of English onset and length of anglophone residence, the linguistic distance between the speaker’s native language and English is a significant predictor of the degree of non-native accent in pronunciation. This study extends an earlier study which only focused on Indo-European L2 learners of Dutch and used a general speaking proficiency measure.
Limited influence of Si on the preservation of Fe mineral‐encrusted microbial cells during experimental diagenesis
2015-12-23

Abstract The reconstruction of the history of microbial life since its emergence on early Earth is impaired by the difficulty to prove the biogenicity of putative microfossils in the rock record. While most of the oldest rocks on Earth have been exposed to different grades of diagenetic alterations, little is known about how the remains of micro‐organisms evolve when exposed to pressure (P) and temperature (T) conditions typical of diagenesis. Using spectroscopy and microscopy, we compared morphological, mineralogical, and chemical biosignatures exhibited by Fe mineral‐encrusted cells of the bacterium Acidovorax sp. BoFeN1 after long‐term incubation under ambient conditions and after experimental diagenesis. We also evaluated the effects of Si on the preservation of microbial cells during the whole process. At ambient conditions, Si affected the morphology but not the identity (goethite) of Fe minerals that formed around cells. Fe‐encrusted cells were morphologically well preserved after 1 week at 250 °C‐140 MPa and after 16 weeks at 170 °C‐120 MPa in the presence or in the absence of Si. Some goethite transformed to hematite and magnetite at 250 °C‐140 MPa, but in the presence of Si more goethite was preserved. Proteins—the most abundant cellular components—were preserved over several months at ambient conditions but disappeared after incubations at high temperature and pressure conditions, both in the presence and in the absence of Si. Other organic compounds, such as lipids and extracellular polysaccharides seemed well preserved after exposure to diagenetic conditions. This study provides insights about the composition and potential preservation of microfossils that could have formed in Fe‐ and Si‐rich Precambrian oceans.