julilili42/papers huggingface dataset:
Testing the Kerr hypothesis using x-ray reflection spectroscopy with NuSTAR data of Cygnus X-1 in the soft state
2019-06-11

We continue exploring the constraining capabilities of x-ray reflection spectroscopy to test the Kerr-nature of astrophysical black holes, and we present the results of our analysis of two NuSTAR observations of Cygnus X-1 in the soft state. We find that the final measurement can strongly depend on the assumption of the intensity profile. We conclude that Cygnus X-1 is not suitable for tests of general relativity using x-ray reflection spectroscopy, and we discuss the desired properties of a source to be a good candidate for our studies.
The Glycosylation Site of Myelin Oligodendrocyte Glycoprotein Affects Autoantibody Recognition in a Large Proportion of Patients
2019-06-11

Autoantibodies to myelin oligodendrocytes glycoprotein (MOG) are found in a fraction of patients with inflammatory demyelination and are detected with MOG-transfected cells. While the prototype anti-MOG mAb 8-18C5 and polyclonal anti-MOG responses from different mouse strains largely recognize the FG loop of MOG, the human anti-MOG response is more heterogeneous and human MOG-Abs recognizing different epitopes were found to be pathogenic. The aim of this study was to get further insight into details of antigen-recognition by human MOG-Abs focusing on the impact of glycosylation. MOG has one known N-glycosylation site at N31 located in the BC loop linking two beta-sheets. We compared the reactivity to wild type MOG with that toward two different mutants in which the neutral asparagine of N31 was mutated to negatively charged aspartate or to the neutral alanine. We found that around 60% of all patients (16/27) showed an altered reactivity to one or both of the mutations. We noted seven different patterns of recognition of the two glycosylation-deficient mutants by different patients. The introduced negative charge at N31 enhanced recognition in some, but reduced recognition in other patients. In 7/27 patients the neutral glycosylation-deficient mutant was recognized stronger. The folding of the extracellular domain of MOG with the formation of beta-sheets did not depend on its glycosylation as seen by circular dichroism. We determined the glycan structure of MOG produced in HEK cells by mass spectrometry. The most abundant glycoforms of MOG expressed in HEK cells are diantennary, contain a core fucose, an antennary fucose, and are decorated with α2,6 linked Neu5Ac, while details of the glycoforms of MOG in myelin remain to be identified. Together, we (1) increase the knowledge about heterogeneity of human autoantibodies to MOG, (2) show that the BC loop affects recognition in about 60% of the patients, (3) report that all patients recognized the unglycosylated protein backbone, while (4) in about 20% of the patients the attached sugar reduces autoantibody binding presumably via steric hindrance. Thus, a neutral glycosylation-deficient mutant of MOG might enhance the sensitivity to identify MOG-Abs.
MRPC3b mass production for CBM-TOF and eTOF at STAR
2019-06-11

The Compressed Baryonic Matter (CBM) spectrometer aims to study strongly interacting matter under extreme conditions. The key element providing hadron identification at incident energies between 2 and 11 AGeV in heavy-ion collisions at the SIS100 accelerator is a Time-of-Flight (TOF) wall covering the polar angular range from -- and full azimuth. CBM is expected to be operational in the year 2024 at the Facility for Anti-proton and Ion Research (FAIR) in Darmstadt, Germany. The existing conceptual design foresees a 120 m^2 TOF-wall composed of Multi-gap Resistive Plate Chambers (MRPC) which is subdivided into a high rate region, a middle rate region and a low rate region. The MRPC3b Multistrip-MRPCs, foreseen to be integrated in the low rate region, have to cope with charged particle fluxes up to 1 kHz/cm2 and therefore will be constructed with thin float glass (0.28 mm thickness) as resistive electrode material. In the scope of the FAIR phase 0 program it is planned to install about 36 \\% of the MRPC3b counters in the east endcap region of the STAR experiment at BNL as an upgrade for the Beam Energy Scan campaign (BESII) in 2019/2020.
Alkaline Earth Cluster Compounds AE[W6I14] and the Solvate [Ca(C2H6SO)6][W6I14]
2019-06-11

Alkaline earth tungsten iodide clusters AE [W 6 I 14 ] with AE = Mg, Ca, Sr, Ba and the solvated compound [Ca(C 2 H 6 SO) 6 ][W 6 I 14 ] were prepared and structurally characterized. A new synthesis was employed, starting from W 6 I 22 , which is an exceptional compound among binary tungsten iodides because it is soluble in common polar organic solvents. As evidence for the wide range of the applicability of W 6 I 22 , we report the synthesis of the new AE [W 6 I 14 ] compounds in comparison to a solid‐state reaction departing from W 3 I 12 .
β-Actin mRNA interactome mapping by proximity biotinylation
2019-06-12

The molecular function and fate of mRNAs are controlled by RNA-binding proteins (RBPs). Identification of the interacting proteome of a specific mRNA in vivo remains very challenging, however. Based on the widely used technique of RNA tagging with MS2 aptamers for RNA visualization, we developed a RNA proximity biotinylation (RNA-BioID) technique by tethering biotin ligase (BirA*) via MS2 coat protein at the 3′ UTR of endogenous MS2-tagged β-actin mRNA in mouse embryonic fibroblasts. We demonstrate the dynamics of the β-actin mRNA interactome by characterizing its changes on serum-induced localization of the mRNA. Apart from the previously known interactors, we identified more than 60 additional β-actin–associated RBPs by RNA-BioID. Among these, the KH domain-containing protein FUBP3/MARTA2 has been shown to be required for β-actin mRNA localization. We found that FUBP3 binds to the 3′ UTR of β-actin mRNA and is essential for β-actin mRNA localization, but does not interact with the characterized β-actin zipcode element. RNA-BioID provides a tool for identifying new mRNA interactors and studying the dynamic view of the interacting proteome of endogenous mRNAs in space and time.
The Influence of Blood Contamination on Cerebrospinal Fluid Diagnostics
2019-06-12

<b>Background:</b> Blood contamination due to traumatic lumbar puncture presents a diagnostic pitfall in cerebrospinal fluid (CSF) analysis. It is controversially discussed if phagocytosis of erythrocytes which can be found in the CSF after subarachnoid hemorrhage can also develop <i>in vitro</i> in the presence of artificial blood contamination. Furthermore, there is no consensus about the acceptable amount of artificial blood contamination on CSF protein results. <b>Methods:</b> Two measurement series were performed in order to investigate the role of artificial blood contamination on the possible development of erythrophages and siderophages in the CSF: (1) blood contamination was simulated <i>in vitro</i> by adding blood into the CSF. (2) CSF was investigated when blood contamination occurred during a traumatic lumbar puncture. In both types of experiments, CSF including blood was incubated for 24 h and for 72 h at room temperature or at 4°C. In the third measurement series, the effects of artificial blood contamination on CSF protein results were investigated. Blood contamination was simulated <i>in vitro</i> by adding different amounts of blood ending up with five different samples containing erythrocyte counts of 2,500, 5,000, 7,500, 10,000, and 20,000 per μl CSF. <b>Results:</b> Cytological examination revealed no evidence of erythrophages or siderophages <i>in vitro</i>. In contrast, already a low blood contamination (2,500 erythrocytes/μl CSF) led to false pathological results of total protein and albumin. Along with increasing amounts of blood, the frequency of false pathological protein results increased. A blood contamination of 5,000 erythrocytes/μl CSF resulted in a false positive intrathecal IgM production in nearly every fifth patient. In contrast, blood contamination with 5,000 erythrocytes/μl CSF was the acceptable amount of blood which did not lead to a false positive intrathecal synthesis of IgG and IgA. <b>Conclusion:</b> Erythrophages and siderophages do not develop <i>in vitro</i>. An extensive diagnostic work up for the source of blood in the CSF should be performed when erythrophages or siderophages are found in the CSF. The contamination of CSF with increasing volume of blood resulted in falsely elevated CSF protein concentrations. Hence, the amount of blood contamination has to be taken into consideration when interpreting CSF protein measurement results.
Dementia with lewy bodies: GBA1 mutations are associated with cerebrospinal fluid alpha‐synuclein profile
2019-06-12

Abstract Background Patients with dementia with Lewy bodies reveal a variable pathology including alpha‐synuclein, amyloid‐beta, and Tau. Mutations in GBA1 are specifically associated with synucleinopathies. PD patients with GBA1 mutations show reduced CSF levels of total alpha‐synuclein. Objective Whether GBA1 mutations are associated with a CSF alpha‐synuclein profile in dementia with Lewy bodies. Methods Screening of the GBA1 gene and single‐nucleotide polymorphisms in SNCA rs356220, APOE rs429358, and MAPT rs1052587 as well as CSF levels of total alpha‐synuclein, amyloid‐beta 1‐42 , total‐Tau, phospho‐Tau, and neurofilament light chain were assessed in 100 dementia with Lewy bodies and 39 controls cross‐sectionally. Results Severity of GBA1 mutations was associated with a younger age at onset and higher prevalence of rapid eye movement sleep behavior disorder. CSF levels of total alpha‐synuclein were lowest in DLB GBA_pathogenic compared to DLB GBA_mild and DLB GBA_wildtype . Conclusion Similar to PD, pathogenic GBA1 mutations seem to be associated with CSF alpha‐synuclein profiles in dementia with Lewy bodies. That might be useful for patient stratification for specific alpha‐synuclein–lowering compounds. © 2019 International Parkinson and Movement Disorder Society
Gelatin-Collagen Nonwoven Scaffold Provides an Alternative to Suprathel for Treatment of Superficial Skin Defects
2019-06-12

ABSTRACT OBJECTIVE: To evaluate the effect of a new biologic gelatin-collagen nonwoven scaffold compared with a more common synthetic wound dressing on the healing of superficial wounds. METHODS: Three superficial wounds with a depth of 0.5 mm and a length of 2.4 cm were created on the flanks of six minipigs using a skin dermatome. One wound on each pig was treated with the new nonwoven scaffold, one with the more common synthetic wound dressing, and one functioned as an untreated control wound. All three wounds were then covered with a semipermeable, sterile, transparent film. RESULTS: After 7 days, complete wound closure of all wounds could be detected; epidermal thickness and the number of epidermal cells of all treated wounds were significantly increased compared with the control wounds. The nonwoven dressing showed slightly better results compared with the more common dressing. CONCLUSIONS: The nonwoven scaffold is an interesting and competitive material for promoting epidermal wound healing. Because it is a biologic dressing, it degenerates completely and does not have to be removed from the wound. Further research should be conducted to compare this new dressing with other currently available wound treatments.
The continuous downgrading of malnutrition in the German DRG system: possible effects on the treatment of patients at risk for malnutrition
2019-06-12

It has been internationally recognized that malnutrition is an independent risk factor for patients' clinical outcome. A new mandatory fixed price payment system based on diagnosis-related groups (G-DRG) went into effect in 2004. The aim of our study was to demonstrate the importance of carefully coding the secondary diagnosis of "malnutrition" in the G-DRG system and to highlight how the economic relevance of malnutrition in the G-DRG system has changed from 2014 to 2016. 1372 inpatients at the Berufsgenossenschaftliche Unfallklinik (Trauma Center) in Tübingen were screened for the risk of malnutrition using Nutritional Risk Screening (NRS-2002). Patient data were compared with the NRS values collected during the study and a case simulation was carried out separately for each year. We used the codes E44.0 for NRS = 3 and E43.0 for NRS &gt; 3. The ICD codes were entered as an additional secondary diagnosis in the internal hospital accounting system DIACOS to determine possible changes in the effective weight. In 2014 the highest additional revenue by far was calculated by coding malnutrition. For the 638 patients enrolled in the study in 2014, we were able to calculate an average additional revenue per patient coded with malnourishment of €107. In 2016, we were unable to calculate any additional revenue for the 149 patients enrolled. Although it is well known that malnutrition is an independent risk factor for poor patient outcomes, nationwide screening for a risk of malnutrition when patients are admitted to a hospital is still not required. For this reason, malnutrition in German hospitals continues to be insufficiently documented. Due to the continuous downgrading of diagnosis-related severity (CCL) of malnutrition in the G-DRG system in trauma surgery patients, it is no longer possible to refinance the costs incurred by malnourished patients through the conscientious coding of malnutrition. We assume that the indirect positive effects of nutritional interventions will have to be taken into account more in the costing calculations and possibly lead to indirect cost compensation.
Systems Biology Graphical Notation: Process Description language Level 1 Version 2.0
2019-06-13

Abstract The Systems Biology Graphical Notation (SBGN) is an international community effort that aims to standardise the visualisation of pathways and networks for readers with diverse scientific backgrounds as well as to support an efficient and accurate exchange of biological knowledge between disparate research communities, industry, and other players in systems biology. SBGN comprises the three languages Entity Relationship, Activity Flow, and Process Description (PD) to cover biological and biochemical systems at distinct levels of detail. PD is closest to metabolic and regulatory pathways found in biological literature and textbooks. Its well-defined semantics offer a superior precision in expressing biological knowledge. PD represents mechanistic and temporal dependencies of biological interactions and transformations as a graph. Its different types of nodes include entity pools (e.g. metabolites, proteins, genes and complexes) and processes (e.g. reactions, associations and influences). The edges describe relationships between the nodes (e.g. consumption, production, stimulation and inhibition). This document details Level 1 Version 2.0 of the PD specification, including several improvements, in particular: 1) the addition of the equivalence operator, subunit, and annotation glyphs, 2) modification to the usage of submaps, and 3) updates to clarify the use of various glyphs (i.e. multimer, empty set, and state variable).
Kistamicin biosynthesis reveals the biosynthetic requirements for production of highly crosslinked glycopeptide antibiotics
2019-06-13

Abstract Kistamicin is a divergent member of the glycopeptide antibiotics, a structurally complex class of important, clinically relevant antibiotics often used as the last resort against resistant bacteria. The extensively crosslinked structure of these antibiotics that is essential for their activity makes their chemical synthesis highly challenging and limits their production to bacterial fermentation. Kistamicin contains three crosslinks, including an unusual 15-membered A- O -B ring, despite the presence of only two Cytochrome P450 Oxy enzymes thought to catalyse formation of such crosslinks within the biosynthetic gene cluster. In this study, we characterise the kistamicin cyclisation pathway, showing that the two Oxy enzymes are responsible for these crosslinks within kistamicin and that they function through interactions with the X-domain, unique to glycopeptide antibiotic biosynthesis. We also show that the kistamicin OxyC enzyme is a promiscuous biocatalyst, able to install multiple crosslinks into peptides containing phenolic amino acids.
Approximate Bayesian Inference for a Mechanistic Model of Vesicle Release at a Ribbon Synapse
2019-06-13

Abstract The inherent noise of neural systems makes it difficult to construct models which accurately capture experimental measurements of their activity. While much research has been done on how to efficiently model neural activity with descriptive models such as linear-nonlinear-models (LN), Bayesian inference for mechanistic models has received considerably less attention. One reason for this is that these models typically lead to intractable likelihoods and thus make parameter inference difficult. Here, we develop an approximate Bayesian inference scheme for a fully stochastic, biophysically inspired model of glutamate release at the ribbon synapse, a highly specialized synapse found in different sensory systems. The model translates known structural features of the ribbon synapse into a set of stochastically coupled equations. We approximate the posterior distributions by updating a parametric prior distribution via Bayesian updating rules and show that model parameters can be efficiently estimated for synthetic and experimental data from in vivo two-photon experiments in the zebrafish retina. Also, we find that the model captures complex properties of the synaptic release such as the temporal precision and outperforms a standard GLM. Our framework provides a viable path forward for linking mechanistic models of neural activity to measured data.
Novel Ideas in Nonleptonic Decays of Double Heavy Baryons
2019-06-13

The recent discovery of double charm baryon states by the LHCb Collaborarion and their high precision mass determination calls for a comprehensive analysis of the nonleptonic decays of double and single heavy baryons. Nonleptonic baryon decays play an important role in particle phenomenology since they allow for studying the interplay of long and short distance dynamics of the Standard Model (SM). Furthermore, they allow one to search for New Physics effects beyond the SM. We review recent progress in experimental and theoretical studies of the nonleptonic decays of heavy baryons with a focus on double charm baryon states and their decays. In particular, we discuss new ideas proposed by the present authors to calculate the W-exchange matrix elements of the nonleptonic decays of double heavy baryons. An important ingredient in our approach is the compositeness condition of Salam and Weinberg, and an effective implementation of infrared confinement both of which allow one to describe the nonperturbative structure of baryons composed of light and heavy quarks. Furthermore, we discuss an ab initio calculational method for the treatment of the so-called W-exchange diagrams generated by W ± boson exchange between quarks. We found that the W ± -exchange contributions are not suppressed in comparison with the tree-level (factorizing) diagrams and must be taken into account in the evaluation of matrix elements. Moreover, there are decay processes such as the doubly Cabibbo-suppressed decay Ξ c + → p φ recently observed by the LHCb Collaboration, which is contributed to only by one single W-exchange diagram.
Day-Ahead Optimization of Production Schedules for Saving Electrical Energy Costs
2019-06-13

The integration of weather-dependent renewable energy sources leads to an increased volatility of electrical energy supply. As a result, considerable intra-day price spreads can be observed at the spot markets for electrical energy. To benefit from variable energy prices, enterprises can use price forecasts for cost-optimized load scheduling. Thereby energy costs can be reduced by shifting energy-intensive processes to times with lower energy prices.
Phonetic effects of morphology and context: Modeling the duration of word-final S in English with naïve discriminative learning
2019-06-14

Recent research on the acoustic realization of affixes has revealed differences between phonologically homophonous affixes, e.g. the different kinds of final [s] and [z] in English (Plag, Homann &amp; Kunter 2017, Zimmermann 2016a). Such results are unexpected and unaccounted for in widely accepted post-Bloomfieldian item-and-arrangement models (Hockett 1954), which separate lexical and post-lexical phonology, and in models which interpret phonetic effects as consequences of different prosodic structure. This paper demonstrates that the differences in duration of English final S as a function of the morphological function it expresses (non-morphemic, plural, third person singular, genitive, genitive plural, cliticized has , and cliticized is ) can be approximated by considering the support for these morphological functions from the words’ sublexical and collocational properties. We estimated this support using naïve discriminative learning and replicated previous results for English vowels (Tucker, Sims &amp; Baayen 2019), indicating that segment duration is lengthened under higher functional certainty but shortened under functional uncertainty. We discuss the implications of these results, obtained with a wide learning network that eschews representations for morphemes and exponents, for models in theoretical morphology as well as for models of lexical processing.
Regulation of fibroblast growth factor 23 (FGF23) in health and disease
2019-06-14

Fibroblast growth factor 23 ( FGF 23) is mainly produced in the bone and, upon secretion, forms a complex with a FGF receptor and coreceptor αKlotho. FGF 23 can exert several endocrine functions, such as inhibiting renal phosphate reabsorption and 1,25‐dihydroxyvitamin D3 production. Moreover, it has paracrine activities on several cell types, including neutrophils and hepatocytes. Klotho and Fgf23 deficiencies result in pathologies otherwise encountered in age‐associated diseases, mainly as a result of hyperphosphataemia‐dependent calcification. FGF 23 levels are also perturbed in the plasma of patients with several disorders, including kidney or cardiovascular diseases. Here, we review mechanisms controlling FGF 23 production and discuss how FGF 23 regulation is perturbed in disease.
The cGMP Pathway and Inherited Photoreceptor Degeneration: Targets, Compounds, and Biomarkers
2019-06-14

Photoreceptor physiology and pathophysiology is intricately linked to guanosine-3’,5’-cyclic monophosphate (cGMP)-signaling. Here, we discuss the importance of cGMP-signaling for the pathogenesis of hereditary retinal degeneration. Excessive accumulation of cGMP in photoreceptors is a common denominator in cell death caused by a variety of different gene mutations. The cGMP-dependent cell death pathway may be targeted for the treatment of inherited photoreceptor degeneration, using specifically designed and formulated inhibitory cGMP analogues. Moreover, cGMP-signaling and its down-stream targets may be exploited for the development of novel biomarkers that could facilitate monitoring of disease progression and reveal the response to treatment in future clinical trials. We then briefly present the importance of appropriate formulations for delivery to the retina, both for drug and biomarker applications. Finally, the review touches on important aspects of future clinical translation, highlighting the need for interdisciplinary cooperation of researchers from a diverse range of fields.