julilili42/papers huggingface dataset:
Pentapeptide‐rich peptidoglycan at the Bacillus subtilis cell‐division site
2017-01-24

Summary Peptidoglycan (PG), the major component of the bacterial cell wall, is one large macromolecule. To allow for the different curvatures of PG at cell poles and division sites, there must be local differences in PG architecture and eventually also chemistry. Here we report such local differences in the Gram‐positive rod‐shaped model organism Bacillus subtilis . Single‐cell analysis after antibiotic treatment and labeling of the cell wall with a fluorescent analogue of vancomycin or the fluorescent D‐amino acid analogue (FDAA) HCC‐amino‐D‐alanine revealed that PG at the septum contains muropeptides with unprocessed stem peptides (pentapeptides). Whereas these pentapeptides are normally shortened after incorporation into PG, this activity is reduced at division sites indicating either a lower local degree of PG crosslinking or a difference in PG composition, which could be a topological marker for other proteins. The pentapeptides remain partially unprocessed after division when they form the new pole of a cell. The accumulation of unprocessed PG at the division site is not caused by the activity of the cell division specific penicillin‐binding protein 2B. To our knowledge, this is the first indication of local differences in the chemical composition of PG in Gram‐positive bacteria.
Probing the possibility of hotspots on the central neutron star in HESS J1731−347
2017-01-24

\\n The X-ray spectra of the neutron stars located in the centers of supernova remnants Cas A and HESS J1731−347 are well fit with carbon atmosphere models. These fits yield plausible neutron star sizes for the known or estimated distances to these supernova remnants. The evidence in favor of the presence of a pure carbon envelope at the neutron star surface is rather indirect and is based on the assumption that the emission is generated uniformly by the entire stellar surface. Although this assumption is supported by the absence of pulsations, the observational upper limit on the pulsed fraction is not very stringent. In an attempt to quantify this evidence, we investigate the possibility that the observed spectrum of the neutron star in HESS J1731−347 is a combination of the spectra produced in a hydrogen atmosphere of the hotspots and of the cooler remaining part of the neutron star surface. The lack of pulsations in this case has to be explained either by a sufficiently small angle between the neutron star spin axis and the line of sight, or by a sufficiently small angular distance between the hotspots and the neutron star rotation poles. As the observed flux from a non-uniformly emitting neutron star depends on the angular distribution of the radiation emerging from the atmosphere, we have computed two new grids of pure carbon and pure hydrogen atmosphere model spectra accounting for Compton scattering. Using new hydrogen models, we have evaluated the probability of a geometry that leads to a pulsed fraction below the observed upper limit to be about 8.2%. Such a geometry thus seems to be rather improbable but cannot be excluded at this stage. \\n
Kinetics of copper growth on graphene revealed by time-resolved small-angle x-ray scattering
2017-01-24

Metal growth on graphene has many applications. Transition metals are known to favor three-dimensional (3D) cluster growth on graphene. Copper is of particular interest for cost-effective surface-supported catalysis applications and as a contact material in electronics. This paper presents an in situ real-time study of Cu growth kinetics on graphene covering all stages preceding formation of a continuous film performed by laboratory-based grazing-incidence small-angle x-ray scattering (GISAXS) technique. In particular, nucleation and 3D cluster growth, coalescence, and percolation stages were identified. The cluster nucleation saturates after reaching a density of at monolayer thickness. A Kratky plot and a paracrystal model with cumulative structural disorder were necessary to evaluate properly cluster growth and coalescence, respectively. The power law scaling constants and of the temporal evolution of Cu cluster size suggest the growth of isolated clusters and dynamic cluster coalescence keeping the cluster shape, respectively. Coalescence and percolation thresholds occur at Cu thicknesses of and , respectively. This paper demonstrates the potential of laboratory-based in situ GISAXS as a vital diagnostic tool for tailoring a large variety of Cu nanostructures on graphene based on an in situ Cu growth monitoring which is applicable in a broad range of deposition times.
Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways
2017-01-25

Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson's disease. Genome-wide screens in yeast identified 332 genes that impact α-syn toxicity. To "humanize" this molecular network, we developed a computational method, TransposeNet. This integrates a Steiner prize-collecting approach with homology assignment through sequence, structure, and interaction topology. TransposeNet linked α-syn to multiple parkinsonism genes and druggable targets through perturbed protein trafficking and ER quality control as well as mRNA metabolism and translation. A calcium signaling hub linked these processes to perturbed mitochondrial quality control and function, metal ion transport, transcriptional regulation, and signal transduction. Parkinsonism gene interaction profiles spatially opposed in the network (ATP13A2/PARK9 and VPS35/PARK17) were highly distinct, and network relationships for specific genes (LRRK2/PARK8, ATXN2, and EIF4G1/PARK18) were confirmed in patient induced pluripotent stem cell (iPSC)-derived neurons. This cross-species platform connected diverse neurodegenerative genes to proteinopathy through specific mechanisms and may facilitate patient stratification for targeted therapy.
The Bruton tyrosine kinase inhibitor ibrutinib abrogates triggering receptor on myeloid cells 1-mediated neutrophil activation
2017-01-25

Recurrent infections are common complications in patients with non-Hodgkin lymphomas, for example, chronic lymphocytic leukemia (CLL). The secondary immune defect as the underlying cause of frequent infections is in part due to hypoimmunoglobulinemia or diminished T- and B-cell responses suppressing
Diagnostic Performance of Tuberculosis-Specific IgG Antibody Profiles in Patients with Presumptive Tuberculosis from Two Continents
2017-01-25

Although M. tuberculosis antigens were recognized by the IgG response during tuberculosis, no single antigen or multiantigen set performance approached WHO TPP criteria for clinical utility among HIV-uninfected adults with presumed tuberculosis in high-volume, urban settings in tuberculosis-endemic countries.
Relativistic effects and three-nucleon forces in nuclear matter and nuclei
2017-01-25

We review a large body of predictions obtained within the framework of relativistic meson theory together with the Dirac–Brueckner–Hartree–Fock approach to nuclear matter and finite nuclei. The success of this method has been largely related to its ability to take into account important three-body effects. Therefore, the overarching theme of this paper is the interpretation of the so-called “Dirac effects” as an effective three-nucleon force. We address the equation of state (EoS) of isospin symmetric and asymmetric nucleonic matter and related issues, ranging from proton and neutron density distributions to momentum distributions and short-range correlations. A central part of the discussion is devoted to the optical model potential for nucleon–nucleus scattering. We also take the opportunity to explore similarities and differences with predictions based on the increasingly popular chiral effective field theory.
Therapeutic Drug Monitoring of Everolimus: Comparability of Concentrations Determined by 2 Immunoassays and a Liquid Chromatography Tandem Mass Spectrometry Method
2017-01-25

Background: Therapeutic drug monitoring is recommended to guide therapy with the immunosuppressant everolimus (EVL) in solid organ transplantation to prevent rejections and to limit toxicity. For therapeutic drug monitoring, predose EVL concentrations are measured in whole blood mainly by liquid chromatography tandem mass spectrometry (LC-MS/MS). In addition, 2 immunoassays [Quantitative Microsphere System (QMS) EVL and Elecsys EVL] are commercially available. The aim of this study was to evaluate the comparability of EVL results determined with the 2 immunoassays and a validated LC-MS/MS test using samples from kidney, liver, and heart transplant (KT, LT, and HT, respectively) recipients. Methods: Analysis of predose samples from KT ( n = 56), LT ( n = 60), and HT ( n = 59) recipients, obtained at variable time points after transplantation, was performed by LC-MS/MS and with the 2 immunoassays. The QMS EVL assay was applied on Dimension Xpand Plus and the Elecsys EVL assay on cobas e 411 analyzer. Results were compared by the Spearman's rank correlation coefficient, unbiased Passing and Bablok linear regression test, and Bland–Altman plot. Results: Results generated with both immunoassays correlated well with those of LC-MS/MS. An overestimation of EVL concentrations by the Elecsys EVL compared with LC-MS/MS was observed (mean bias: 34.2%). Using the QMS EVL, a small but significant negative deviation (mean bias: −8.0%) was found. Looking at KT, HT, and LT samples separately, the bias to LC-MS/MS seen with the Elecsys EVL was similar. With the QMS EVL, the best agreement was observed with the KT samples followed by LT and HT. Conclusions: Results generated by the 3 methods are not consistent regarding their diagnostic value. Both laboratories and manufacturers should take care to inform their costumers about the between-method differences to avoid misinterpretation of the results in clinical practice.
Popper's Notion of Duality and His Theory of Negations
2017-01-25

Karl Popper developed a theory of deductive logic in the late 1940s. In his approach, logic is a metalinguistic theory of deducibility relations that are based on certain purely structural rules. Logical constants are then characterized in terms of deducibility relations. Characterizations of this kind are also called inferential definitions by Popper. In this paper, we expound his theory and elaborate some of his ideas and results that in some cases were only sketched by him. Our focus is on Popper's notion of duality, his theory of modalities, and his treatment of different kinds of negation. This allows us to show how his works on logic anticipate some later developments and discussions in philosophical logic, pertaining to trivializing (-like) connectives, the duality of logical constants, dual-intuitionistic logic, the (non-)conservativeness of language extensions, the existence of a bi-intuitionistic logic, the non-logicality of minimal negation, and to the problem of logicality in general.
Repeated electromagnetic induction measurements for mapping soil moisture at the field scale: validation with data from a wireless soil moisture monitoring network
2017-01-26

Abstract. Electromagnetic induction (EMI) measurements are widely used for soil mapping, as they allow fast and relatively low-cost surveys of soil apparent electrical conductivity (ECa). Although the use of non-invasive EMI for imaging spatial soil properties is very attractive, the dependence of ECa on several factors challenges any interpretation with respect to individual soil properties or states such as soil moisture (θ). The major aim of this study was to further investigate the potential of repeated EMI measurements to map θ, with particular focus on the temporal variability of the spatial patterns of ECa and θ. To this end, we compared repeated EMI measurements with high-resolution θ data from a wireless soil moisture and soil temperature monitoring network for an extensively managed hillslope area for which soil properties and θ dynamics are known. For the investigated site, (i) ECa showed small temporal variations whereas θ varied from very dry to almost saturation, (ii) temporal changes of the spatial pattern of ECa differed from those of the spatial pattern of θ, and (iii) the ECa–θ relationship varied with time. Results suggest that (i) depending upon site characteristics, stable soil properties can be the major control of ECa measured with EMI, and (ii) for soils with low clay content, the influence of θ on ECa may be confounded by changes of the electrical conductivity of the soil solution. Further, this study discusses the complex interplay between factors controlling ECa and θ, and the use of EMI-based ECa data with respect to hydrological applications.
DOP083 Recombinant subcutaneous human beta-Defensin 2 (hBD2) ameliorates experimental colitis in different in vivo models
2017-01-26

&lt;b&gt;Background:&lt;/b&gt; In recent years, the significance of antimicrobial peptides for the maintenance of epithelial barriers has been recognized and various diseases have been associated with compromised antimicrobial barrier function. Of note, colonic Crohn's disease has been related to an attenuated induction of human beta defensin 2 (hBD2) in the colon. In addition to their antimicrobial activity, defensins also have important immune-modulatory functions. Here, we screened hBD2 for potency and toxicity and produced this peptide using a microbial expression system. Furthermore, we tested its preclinical efficacy using different &lt;it&gt;in vivo&lt;/it&gt; models of colitis. &lt;b&gt;Methods:&lt;/b&gt; We established a cellular expression-system, Saccharomyces cerevisiae, to produce sufficient amounts of hBD2 for &lt;it&gt;in vivo&lt;/it&gt; screening and determined its antimicrobial activity &lt;it&gt;in vitro&lt;/it&gt;. Next, we tested hBD2 for cytotoxicity in human PBMCs and in murine fibroblasts and assessed its anti-inflammatory properties in human PBMCs stimulated with LPS. Finally, we tested hBD2 in different mouse models of colitis using subcutaneous (s.c.) application. We used DSS (dextran sulfate sodium, n=10), TNBS (Trinitrobenzenesulfonic acid, n=15) and T-cell transfer from wild-type into SCID mice to induce colitis (n=11). To test the protective effect of hBD2, animals were treated once a day by s.c. injection of a dose range of 0.1–3 mg/kg. &lt;b&gt;Results:&lt;/b&gt; We obtained a yield of &gt;400 mg/L of hBD2 on a 10 L scale. HBD2 showed antimicrobial activity in radial diffusion assays while we did not find any cytotoxic effect against human PBMCs and murine fibroblasts. Treatment of LPS-activated human PBMCs with hBD2 decreased the release of pro-inflammatory TNFalpha, IL-1β and IL-23 while upregulating anti-inflammatory IL-10 and IL-24. In all colitis models tested s. c. application of hBD2 led to a remarkable improvement of disease at an optimal dose of 0.1 mg/kg (DSS and TNBS) and 1 mg/kg (transfer) on par with anti-TNFalpha (DSS), prednisolone (TNBS) and dexamethasone (transfer), respectively. In the DSS model hBD2 ameliorated loss of body weight (p&lt;0.05), improved the disease activity index (p&lt;0.001) as well as the histological score (p&lt;0.001), significantly. In the TNBS model the histological score was significantly improved by hBD2 treatment (p&lt;0.001) while in the T-cell-transfer model hBD2 again improved the disease activity index. &lt;b&gt;Conclusions:&lt;/b&gt; We were able to produce and purify hBD2 in relevant amounts. Since hBD2 showed no cytotoxicity, strong anti-inflammatory properties and protected mice from colitis our data provided evidence that hBD2 could be used as potential therapeutic agent in the treatment of inflammatory bowel diseases.
P171 Reliable assessment of ultrasound parameters during transabdominal ultrasonography in inflammatory bowel disease
2017-01-26

&lt;b&gt;Background:&lt;/b&gt; The inflammatory activity of chronic inflammatory bowel disease (IBD) may effectively be controlled by means of intestinal ultrasound (IUS). Although IUS is considered to be safe and inexpensive, it is criticised for being dependent on the examiner. The aim of this study was to evaluate whether ultrasound parameters are interpreted in the same way by examiners with experience in this diagnostic procedure. &lt;b&gt;Methods:&lt;/b&gt; 40 participants (38 IBD specialists, including 27 gastroenterologists with professional experience between &lt;5 years and &gt;10 years) from nationwide IBD centres were included. Using a standardised questionnaire, the participants assessed 20 ultrasound images and videos of IBD patients. In addition, all study participants independently performed “simulator” investigations of 3 IBD-specific pathologica (Schallware simulator, Germany). Overall, the participants all received the same questions for the exact assessment of US image recordings. The questions related to both the assessment of the technical image quality, the methodology of imaging and the evaluation of specific parameters such as bowel wall thickness, vascularisation, etc. were used as reference results for the consensus of a group of experts (n=3). The parameters were evaluated according to the correspondence between the cases and the conformity of the participants. Mann-Whitney U test and Kappa coefficient were used for the statistical evaluation. &lt;b&gt;Results:&lt;/b&gt; The inter-observer variability, as measured by the kappa coefficient, determined moderate agreement between 0.36 to 0.59 with regard to all parameters assessed by the participants. The evaluation of the specific IBD activity parameters revealed a good match with an average of 60.9%. The relevant parameters for an IBD assessment (bowel wall thickness, etc.) were recognised by all participants. The heterogeneity of agreement with regard to interpretation of the findings ranged between 88.5% (item “extraintestinal air”) and 35.6% (item “unevenly altered bowel wall stratification”). Subgroup analyses using the Man-Whitney U test showed that examiners with greater experience reached a higher degree of consensus. &lt;b&gt;Conclusions:&lt;/b&gt; The examiners were able to equally interpret images derived during intestinal ultrasound. In particular, examiners were able to reliably interpret ultrasound parameters relevant for the assessment of IBD activity and complications. The reliability of the assessment increased with the experience of the examiner. Further studies with a larger number of participants to evaluate the reliability of assessment would be meaningful
P563 Psychotherapy experience and demand for it and their association in inflammatory bowel disease – results from an internet-based survey
2017-01-26

&lt;b&gt;Background:&lt;/b&gt; Quality of life is often negatively affected in patients with inflammatory bowel diseases (IBD) (Crohn's Disease, CD; ulcerative colitis, UC) associated with depression and anxiety. The clinical need as well as the efficacy of psychotherapeutic interventions in IBD patients is a matter of constant debate. However, the perspective of IBD patients has largely been ignored in this debate. &lt;b&gt;Methods:&lt;/b&gt; Psychometric tests namely the Short-Form IBD Questionnaire (SIBDQ) for quality-of-life assessment, the ADAP test measuring demand for psychological therapy and the Fear-of-Progression Questionnaire Short Form (FoP-Q-SF) as well as disease related questions, e.g. experience with psychotherapy were web-based positioned and advertised by the DCCV (“Deutsche Crohn und Colitis Vereinigung”), the biggest IBD patient organization in Germany. Data were analyzed by a stepwise forward regression model using SPSS Version 19. Statistical significance was set at &lt;0.05. &lt;b&gt;Results:&lt;/b&gt; A total of n=631 patients responded. Data from n=578 (356 CD, 219 UC, 3 unclear) were complete and used for the analysis. 90% of the respondents show an at least slightly diminished quality of life (SIBDQ&lt;60) and 60% had significant fear of disease progression (FoP-Q-SF &gt;36). 55% had a demand for psychotherapy (ADAPT &gt;60). More than half of all IBD patients (n=296) had previous experiences with psychotherapy, while the remaining had not (n=282). This distribution clearly determined the factor “demand for psychotherapy” (chi-square = 23.7, p&lt;0.001). Regression model analysis revealed that psychotherapy demand was dependent on previous experience (p&lt;0.001), fear of progression (p&lt;0.001), quality of life (p=0.001), smoking (p=0.003) and previous surgery (p=0.005) with the total model explaining 29.7% of the variance. The total explained variance of this model was higher in UC alone (37.6%) than in CD alone (25.4%). Other models showed similarly high explanation using fear of progression (49.7%) or quality-of-life (48.5%) as dependent variable. &lt;b&gt;Conclusions:&lt;/b&gt; A high number of patients showed a diminished quality of life as well as a high demand for psychotherapy. Demand for psychotherapy as additional therapy in IBD depends on previous experience with psychotherapy, fear for disease progression but also other disease characteristics. To improve the quality of life of IBD patients, physicians should be aware of the enormous need of IBD patients for additional therapeutic interventions as shown in our cohort. Psychometric tests, as used in our study, could help to identify patients with a need for psychotherapy in the daily routine, to deliver the best possible combined treatment options for IBD patients.