julilili42/papers huggingface dataset:
Clinical, pathophysiological and genetic features of motor symptoms in autosomal dominant Alzheimer’s disease
2019-02-25

Aβ deposition in the basal ganglia is common in autosomal dominant Alzheimer’s disease. Vöglein et al. report an increased severity of motor symptoms in autosomal dominant versus sporadic disease in advanced disease stages. Motor symptoms are more severe in post-codon 200 presenilin 1 mutation carriers and correlate with basal ganglia Aβ.
DeepCEST: 9.4 T Chemical exchange saturation transfer MRI contrast predicted from 3 T data – a proof of concept study
2019-02-25

Purpose To determine the feasibility of employing the prior knowledge of well‐separated chemical exchange saturation transfer (CEST) signals in the 9.4 T Z‐spectrum to separate overlapping CEST signals acquired at 3 T, using a deep learning approach trained with 3 T and 9.4 T CEST spectral data from brains of the same subjects. Methods Highly spectrally resolved Z‐spectra from the same volunteer were acquired by 3D‐snapshot CEST MRI at 3 T and 9.4 T at low saturation power of B 1 = 0.6 μT. The volume‐registered 3 T Z‐spectra‐stack was then used as input data for a three layer deep neural network with the volume‐registered 9.4 T fitted parameter stack as target data. Results An optimized neural net architecture could be found and verified in healthy volunteers. The gray‐/white‐matter contrast of the different CEST effects was predicted with only small deviations (Pearson R = 0.89). The 9.4 T prediction was less noisy compared to the directly measured CEST maps, although at the cost of slightly lower tissue contrast. Application to an unseen tumor patient measured at 3 T and 9.4 T revealed that tumorous tissue Z‐spectra and corresponding hyper‐/hypointensities of different CEST effects can also be predicted (Pearson R = 0.84). Conclusion The 9.4 T CEST signals acquired at low saturation power can be accurately estimated from CEST imaging at 3 T using a neural network trained with coregistered 3 T and 9.4 T data of healthy subjects. The deepCEST approach generalizes to Z‐spectra of tumor areas and might indicate whether additional ultrahigh‐field (UHF) scans will be beneficial.
Pathophysiology of Autoimmune Thrombocytopenia: Current Insight with a Focus on Thrombopoiesis
2019-02-25

Abstract Immune thrombocytopenia (ITP) is an autoimmune disease characterized by a significant reduction in the number of circulating platelets which is frequently associated with bleeding. The total count of platelets in the body is finely regulated by the balance between platelet production and destruction. Although the pathogenesis of ITP is still not completely elucidated, it is largely recognized that the low platelet count observed in ITP patients is due to alterations of both mechanisms. An abnormal proliferation of autoreactive T cells leading to the breakdown of immune tolerance to platelet antigens is suggested to be responsible for the up-regulated proliferation of autoantibody producing B cells. Consequently, the immune response induces enhanced T cell-mediated cytotoxicity and antibody-mediated platelet destruction through phagocytosis, complement activation and apoptosis. An additional contribution to the pathophysiology of ITP is given by alterations of thrombopoiesis caused by platelet-reactive autoantibodies or cytotoxic T cells leading to impaired megakaryocyte differentiation and platelet production. All these processes involved in ITP pathophysiology account for the complexity and heterogeneity in the clinical manifestation and therapy responsiveness of this disorder. For this reason, a better understanding of the different underlying mechanisms in ITP is necessary to develop more efficient therapeutic treatments in the future. In this review, we will provide an update on the pathophysiology of ITP with a particular focus on the impact of impaired thrombopoiesis.
Organic Matter Complexation Promotes Fe(II) Oxidation by the Photoautotrophic Fe(II)-Oxidizer Rhodopseudomonas palustris TIE-1
2019-02-25

Fe(II)–organic matter (Fe(II)–OM) complexes are present in the photic zone of aquatic environments and due to their reactivity may play an important role in biogeochemical cycling. Complexation of Fe has been shown to influence the rates and extent of many chemical and microbial redox reactions. However, it is currently unknown whether, how fast, and to which extent Fe(II)–OM complexes can be oxidized by anoxygenic photoautotrophic Fe(II)-oxidizing microorganisms which are widespread in photic habitats and use electrons from Fe(II) to fix CO2. Here, we used the photoautotrophic Fe(II)-oxidizer Rhodopseudomonas palustris TIE-1 to demonstrate that Fe(II) complexation by OM significantly accelerated the rates of Fe(II) oxidation by strain TIE-1 compared to the oxidation of nonorganically bound, free Fe(II), although a fraction of the Fe(II) present as Fe(II)–OM complexes seemed to resist microbial oxidation. Analysis of Fe–OM aggregate sizes showed that the remaining, nonoxidized Fe(II) and almost all of the Fe(III) in the Fe(II)–humic and Fe(II)–fulvic acid oxidation products were in the form of colloids (3–200 nm). In summary, this study shows that Fe(II)–OM complexes can be oxidized microbially in the photic zone, and the complexation of Fe(II) by OM controls the kinetics and extent of Fe(II) oxidation.
The Modulatory Effect of Gender and Cytomegalovirus-Seropositivity on Circulating Inflammatory Factors and Cognitive Performance in Elderly Individuals
2019-02-25

Aging is characterized by a chronic increase in the systemic levels of inflammatory cytokines even in ostensibly healthy individuals. The drivers of age-related increase in systemic inflammation are unclear but one potential contributor may be a persistent infection with Cytomegalovirus (CMV). In this study, we characterized the inflammatory status of 161 older participants recruited to undergo a six-month training intervention. We investigated the influence of gender and CMV-seropositivity on the main inflammatory and anti-inflammatory circulating biomarkers, such as cytokines, receptor antagonist, soluble receptor, immune cells, and relevant metabolic markers. We found that both gender and CMV-seropositivity modulate circulating peripheral biomarkers, and that CMV-infection modifies associations among the latter. Moreover, we observed an interaction between CMV-serostatus and gender associations with cognitive abilities: gender differences in fluid intelligence (Gf) and working memory (WM) were noted only in CMV-negative individuals. Finally, we found that in the CMV-seronegative participants Gf, episodic memory (EM), and WM correlated negatively with pro-inflammatory tumor necrosis factor (TNF); and EM correlated positively with anti-inflammatory interleukin (IL)-10. In CMV-seropositive individuals EM and Gf correlated negatively with pro-inflammatory IL-6, while EM, Gf, and WM correlated negatively with anti-inflammatory IL-1RA. We conclude that both CMV-serostatus and gender may modulate neuroimmune factors, cognitive performance and the relationship between the two domains and should therefore be considered in comparative and interventional studies with elderly people.
On the benefits of ‘doing science’: Does integrative writing about scientific controversies foster epistemic beliefs?
2019-02-25

We examine the effects of writing tasks on epistemic change in the context of an intervention which aims at modifying psychology students' epistemic beliefs (beliefs about the nature of knowledge and knowing). The intervention uses a multiple-texts approach. Participants first read multiple texts containing controversial evidence from 18 fictional studies on gender stereotyping. After reading, they are asked to write a balanced scientific essay explicitly focusing on the conditions under which boys respectively girls are discriminated against. We expected (1) that an intervention combining reading and writing has positive effects on epistemic beliefs, (2) that the beneficial effects of writing are reduced when the task instructions require writing a general overview or a one-sided argumentative text instead of a balanced essay, and (3) that reading and writing both uniquely contribute to epistemic change. Moreover, (4) we examined the effects of reading and writing on different levels of epistemic beliefs (topic-specific vs. domain-specific). Hypotheses were largely supported using data from two experimental and one correlational study (Study 1: N = 86; Study 2: N = 153; Study 3: N = 93). Implications of the results for research and practice are discussed.
Cytochrome P450 CYP2B6*6 distribution among Congolese individuals with HIV, Tuberculosis and Malaria infection
2019-02-25

This study contributes to increasing understanding on population pharmacogenetics and may help policy makers regulate treatment guidelines in the Congolese population with a high burden of HIV, Malaria and TB.
Glycolipid composition of the heterocyst envelope of Anabaena sp. PCC 7120 is crucial for diazotrophic growth and relies on the UDP‐galactose 4‐epimerase HgdA
2019-02-25

Abstract The nitrogenase complex in the heterocysts of the filamentous freshwater cyanobacterium Anabaena sp. PCC 7120 fixes atmospheric nitrogen to allow diazotrophic growth. The heterocyst cell envelope protects the nitrogenase from oxygen and consists of a polysaccharide and a glycolipid layer that are formed by a complex process involving the recruitment of different proteins. Here, we studied the function of the putative nucleoside‐diphosphate‐sugar epimerase HgdA, which along with HgdB and HgdC is essential for deposition of the glycolipid layer and growth without a combined nitrogen source. Using site‐directed mutagenesis and single homologous recombination approach, we performed a thoroughly functional characterization of HgdA and confirmed that the glycolipid layer of the hgdA mutant heterocyst is aberrant as shown by transmission electron microscopy and chemical analysis. The hgdA gene was expressed during late stages of the heterocyst differentiation. GFP‐tagged HgdA protein localized inside the heterocysts. The purified HgdA protein had UDP‐galactose 4‐epimerase activity in vitro. This enzyme could be responsible for synthesis of heterocyst‐specific glycolipid precursors, which could be transported over the cell wall by the ABC transporter components HgdB/HgdC.
Modeling Multiple Item Context Effects With Generalized Linear Mixed Models
2019-02-25

Item context effects refer to the impact of features of a test on an examinee's item responses. These effects cannot be explained by the abilities measured by the test. Investigations typically focus on only a single type of item context effects, such as item position effects, or mode effects, thereby ignoring the fact that different item context effects might operate simultaneously. In this study, two different types of context effects were modeled simultaneously drawing on data from an item calibration study of a multidimensional computerized test (<i>N</i> = 1,632) assessing student competencies in mathematics, science, and reading. We present a generalized linear mixed model (GLMM) parameterization of the multidimensional Rasch model including <i>item position effects</i> (distinguishing between <i>within-block position effects</i> and <i>block position effects</i>), <i>domain order effects</i>, and the interactions between them. Results show that both types of context effects played a role, and that the moderating effect of domain orders was very strong. The findings have direct consequences for planning and applying mixed domain assessment designs.
Disembedded Markets
2019-02-25

This book offers a sociological analysis of globalised capitalist markets, advancing the notion of 'disembedded markets' to challenge the idea of 'social embeddedness' common in economic sociology. Avoiding an exclusive focus on institutions, networks and trust relationships surrounding markets, the author concentrates on private property as the key institution of markets, in order to emphasise the historical origins of modern capitalism the free market narrative, and develop a socio-historical analysis of the disembedding process together with an account of the built-in contradictions and limits of market universalisation. Through an analysis of their encompassing character, this volume demonstrates that disembedded markets do not fit standard theoretical accounts of sociality – a problem taken up not only by Karl Marx, but also by Friedrich August von Hayek and Niklas Luhmann – and questions the attempts of the emerging approach of 'economic theology' to draw parallels between the practices that arise from disembedded markets and from forms of religious experience and ritual. A rigorous examination of the phenomenon of disembedded markets and the claims to which they give rise concerning the equivalences between religion and capitalism, this book will appeal to scholars of sociology and economics with interests in capitalism, social theory, and global markets.
Task-evoked activity quenches neural correlations and variability across cortical areas
2019-02-25

Abstract Many large-scale functional connectivity studies have emphasized the importance of communication through increased inter-region correlations during task states. In contrast, local circuit studies have demonstrated that task states primarily reduce correlations among pairs of neurons, likely enhancing their information coding by suppressing shared spontaneous activity. Here we sought to adjudicate between these conflicting perspectives, assessing whether co-active brain regions during task states tend to increase or decrease their correlations. We found that variability and correlations primarily decrease across a variety of cortical regions in two highly distinct data sets: non-human primate spiking data and human functional magnetic resonance imaging data. Moreover, this observed variability and correlation reduction was accompanied by an overall increase in dimensionality (reflecting less information redundancy) during task states, suggesting that decreased correlations increased information coding capacity. We further found in both spiking and neural mass computational models that task-evoked activity increased the stability around a stable attractor, globally quenching neural variability and correlations. Together, our results provide an integrative mechanistic account that encompasses measures of large-scale neural activity, variability, and correlations during resting and task states.
Impurity Analysis and Microstructure Along the Climatic Transition From MIS 6 Into 5e in the EDML Ice Core Using Cryo-Raman Microscopy
2019-02-26

Impurities in polar ice cores have been studied so far mainly for the purpose of reconstructions of past atmospheric aerosol concentrations. However, impurities also critically influence physical properties of the ice matrix itself. To improve the data basis regarding the in-situ form of incorporation and spatial distribution of impurities in ice we used micro-cryo-Raman spectroscopy to identify the location, phase and composition of micrometer-sized inclusions in natural ice samples around the transition from marine isotope stage (MIS) 6 into 5e in the EDML ice core. The combination of Raman results with ice-microsctructure measurements and complementary impurity data provided by the standard analytical methods (IC, CFA, and DEP) allows for a more interdisciplinary approach interconnecting ice core chemistry and ice core physics. While the interglacial samples were dominated by sulfate salts—mainly gypsum, sodium sulfate (possibly thenardite) and iron–potassium sulfate (likely jarosite)—the glacial ice contained high numbers of mineral dust particles—in particular quartz, mica, feldspar, anatase, hematite and carbonaceous particles (black carbon). We cannot confirm cumulation of impurities in the grain boundary network as reported by other studies, neither micro-particles being dragged by migrating grain boundaries nor in form of liquid veins in triple junctions. We argue that mixing of impurities on millimeter scale and chemical reactions are facilitated by the deforming ice matrix. We review possible effects of impurities on physical properties of ice, however the ultimate identification of the deformation agent and the mechanism behind remains challenging.
A classical density functional from machine learning and a convolutional neural network
2019-02-26

We use machine learning methods to approximate a classical density functional. The functional ‘learns’ by comparing the density profile it generates with that of simulations. As a study case, we choose the model problem of a Lennard–Jones fluid in one dimension where there is no exact solution available. After separating the excess free energy functional into a “repulsive” and an “attractive” part, machine learning finds a functional for the attractive part in weighted–density form. The predictions of density profile at a hard wall shows good agreement when subject to thermodynamic conditions beyond those in the training set. This also holds for the equation of state if this is evaluated near the training temperature. We discuss the applicability to problems in higher dimensions.
Low-budget 3D-printed equipment for continuous flow reactions
2019-02-26

This article describes the development and manufacturing of lab equipment, which is needed for the use in flow chemistry. We developed a rack of four syringe pumps controlled by one Arduino computer, which can be manufactured with a commonly available 3D printer and readily available parts. Also, we printed various flow reactor cells, which are fully customizable for each individual reaction. With this equipment we performed some multistep glycosylation reactions, where multiple 3D-printed flow reactors were used in series.
Latent TB Infection (LTBI) – Mycobacterium tuberculosis pathogenesis and the dynamics of the granuloma battleground
2019-02-26

Latent tuberculosis infection (LTBI) is established in over 90% of persons infected with Mycobacterium tuberculosis (Mtb), from whom new active TB cases will arise. Understanding the spatio-temporal dynamics of host immune responses in LTBI granulomas is essential to designing effective post-exposure therapies that inhibit progression to TB. Information arising from cancer studies and other modalities - where local chronic inflammation leads to immunopathology - can help provide insights into the biological pathways at play in LTBI granulomas. Translational studies using patient material as well as LTBI+ donor-derived tissue samples are instrumental in understanding the various components of granuloma dynamics, immunological landscapes therein and how this could help to identify therapeutic targets. Deep sequencing technologies may aid to decipher the genetic changes in lung granuloma and blood samples from LTBI+ individuals associated with progression to active TB disease. This may lead to advancement of development of targeted Host-Directed Therapies (HDTs) and their evaluation as adjunct TB therapies for improving treatment outcomes for LTBI and pulmonary TB.
Inhibition of NK Reactivity Against Solid Tumors by Platelet-Derived RANKL
2019-02-26

NK cells play an important role in tumor immunosurveillance. Their reactivity is governed by various activating and inhibitory surface receptors, which include several members of the TNF/TNF receptor family. For more than 50 years, it has been recognized that tumor immunosurveillance and in particular NK cell antitumor reactivity is largely influenced by platelets, but the underlying mechanisms remain to be fully elucidated. Here we report that upon activation, which reportedly occurs following interaction with cancer cells, platelets upregulate the TNF family member RANKL. Comparative analysis of the expression of RANK among different NK cell subsets and RANKL on platelets in cancer patients and healthy volunteers revealed a distinct malignant phenotype, and platelet-derived RANKL was found to inhibit the activity of normal NK cells against cancer cells. Notably, NK cell antitumor reactivity could be partially restored by application of denosumab, a RANKL-neutralizing antibody approved for treatment of benign and malignant osteolysis. Together, our data not only unravel a novel mechanism of tumor immune evasion mediated by platelets, but they also provide a functional explanation for the clinical observation that denosumab, beyond protecting from bone loss, may prolong disease-free survival in patients with solid tumors.
Timing Modulates the Effect of Sleep Loss on Glucose Homeostasis
2019-02-26

Although sleep deprivation acutely reduced insulin sensitivity irrespective of its nocturnal timing, sleep loss in the early morning compromised α-cell and hypothalamic-pituitary-adrenal axis activity to a greater extent than sleep loss in the first half of the night. This pattern suggests that the timing of sleep restriction can partly potentiate its deleterious metabolic effects.
Singularity-free black holes in conformal gravity: New observational constraints
2019-02-26

We consider the family of singularity-free rotating black hole solutions in\\nEinstein's conformal gravity found in Bambi, Modesto &amp; Rachwal (2017) and we\\nconstrain the value of the conformal parameter from the analysis of a 30 ks\\nNuSTAR observation of the stellar-mass black hole in GS 1354-645 during its\\noutburst in 2015. Our new constraint is much stronger than that found in\\nprevious work. Here we obtain (99% confidence level, statistical\\nuncertainty only).\\n
Photon-antibunching in the fluorescence of statistical ensembles of emitters at an optical nanofiber-tip
2019-02-26

This proposal investigates the photon-statistics of light emitted by a\\nstatistical ensemble of cold atoms excited by the near-field of an optical\\nnanofiber tip. Dipole-dipole interactions of atoms at such short distance from\\neach other suppress the simultaneous emission of more than one photon and lead\\nto antibunching of photons. We consider a mean atom number on the order of one\\nand deal with a poissonian mixture of one and two atoms including dipole-dipole\\ninteractions and collective decay. Time tracks of the atomic states are\\nsimulated in quantum Monte Carlo simulations from which the -photon\\nautocorrelation function is derived. The general results can be applied to any\\nstatistical ensemble of emitters that are interacting by dipole-dipole\\ninteractions.\\n