julilili42/papers huggingface dataset:
Elucidation of the genetic mechanisms contributing to moenomycin resistance in actinobacteria
2018-09-09

Aim. Moenomycins are phosphoglycolipid antibiotics produced almost exclusively by representatives of genus Streptomyces. These antibiotics directly inhibit peptidoglycan glycosyltransferases and are extremely active against cocci. Here we studied how antibiotic-producing actinobacteria protect themselves from toxic action of moenomycins. Methods. Microbiological and molecular genetic approaches were combined to reveal intrinsic levels and distribution of moenomycin resistance across actinobacteria genera, and to pinpoint genes contributing to moenomycin resistance in model strain Streptomyces coelicolor M145. Results. Out of 51 actinobacterial species (90 % of which Streptomyces) being tested, only Streptomyces albus J1074 turned out to be highly susceptible to moenomycin A, although resistant variants can be facilely raised. Several classes of mutations increased level of susceptibility of S. coelicolor to moenomycin, although in no case the latter was equal to what we observed in J1074 strain. Conclusions. Moenomycin resistance is widespread across actinobacteria, and it most likely is caused by a combination factors, such as richly decorated cell wall and organization of divisome apparatus. It is possible that moenomycin resistance mechanisms operating in actinobacteria and pathogenic cocci are different. Keywords: moenomycin, antibiotic resistance, peptidoglycan.
Assessment of mutation probabilities of KRAS G12 missense mutants and their long-timescale dynamics by atomistic molecular simulations and Markov state modeling
2018-09-10

A mutated KRAS protein is frequently observed in human cancers. Traditionally, the oncogenic properties of KRAS missense mutants at position 12 (G12X) have been considered as equal. Here, by assessing the probabilities of occurrence of all KRAS G12X mutations and KRAS dynamics we show that this assumption does not hold true. Instead, our findings revealed an outstanding mutational bias. We conducted a thorough mutational analysis of KRAS G12X mutations and assessed to what extent the observed mutation frequencies follow a random distribution. Unique tissue-specific frequencies are displayed with specific mutations, especially with G12R, which cannot be explained by random probabilities. To clarify the underlying causes for the nonrandom probabilities, we conducted extensive atomistic molecular dynamics simulations (170 μs) to study the differences of G12X mutations on a molecular level. The simulations revealed an allosteric hydrophobic signaling network in KRAS, and that protein dynamics is altered among the G12X mutants and as such differs from the wild-type and is mutation-specific. The shift in long-timescale conformational dynamics was confirmed with Markov state modeling. A G12X mutation was found to modify KRAS dynamics in an allosteric way, which is especially manifested in the switch regions that are responsible for the effector protein binding. The findings provide a basis to understand better the oncogenic properties of KRAS G12X mutants and the consequences of the observed nonrandom frequencies of specific G12X mutations.
Diagnostic accuracy of a new ex vivo confocal laser scanning microscope compared to H&E‐stained paraffin slides for micrographic surgery of basal cell carcinoma
2018-09-10

Abstract Background For safe excision of malignant skin tumours, complete negative surgical margins are mandatory. The gold standard for analysis is frozen sections or paraffin‐embedded haematoxylin and eosin (H&amp;E)‐stained slides. The production of H&amp;E‐stained slides is time‐consuming (&gt;20 h) while wounds remain unclosed. An upcoming method is confocal laser scanning microscopy (CLSM), a technique that scans unfixed fresh tissue rapidly. Objective Evaluation of the process to generate and analyse CLSM images and assessment of the accuracy to detect basal cell carcinoma (BCC) tissue. Methods Digital microscopic images were generated by the Histolog Scanner v1 from 544 fresh specimens of 148 BCC s that had been stained with a 0.01% proflavine solution. CLSM images were compared to the histological diagnoses of the corresponding H&amp;E‐stained slides. Results A total of 525 images could be analysed. The sensitivity was 73% (95% CI = [65.27%; 80.47%]), and the specificity was 96% (95% CI = [93.40%; 97.60%]). Detection of BCC s in punch biopsies was certainly detected (sensitivity of 100%). The median total time to generate and evaluate a CLSM image was 5.17 min (maximum 20.17 min and minimum 2.05 min). The greatest challenge was flattening the specimen to assure complete representation of the surgical margins. Conclusion Confocal laser scanning microscopy is a time‐saving and very effective alternative to classical paraffin‐embedded or frozen sections. Patient treatment could be improved due to shorter hospital stays or faster outpatient therapy due to reduced intervals between surgical stages. Diagnostic accuracy of the microscope used still must be improved.
Moderating effect of comorbid anxiety disorders on treatment outcome in a randomized controlled psychotherapy trial in early-onset persistently depressed outpatients
2018-09-10

Patients suffering from PDD comorbid with AD might experience greater benefit when they are treated with specific as opposed to unspecific therapy. Analyzing subgroups of patients with PDD seems worthwhile to improve treatment effectiveness even within disorder-specific treatment programms.
Intranasal oxytocin fails to acutely improve glucose metabolism in obese men
2018-09-10

The hypothalamic neuropeptide oxytocin not only modulates psychosocial function, but also contributes to metabolic regulation. We have recently shown that intranasal oxytocin acutely improves beta‐cell responsivity and glucose tolerance in normal‐weight men. In the present experiment, we investigated the acute glucoregulatory impact of oxytocin in obese men with impaired insulin sensitivity. Fifteen obese healthy men with an average body mass index of 35 kg/m 2 and an average body fat content of 33% received a single intranasal dose (24 IU) of oxytocin before undergoing an oral glucose tolerance test. Results were analysed according to the oral minimal model and compared with our findings in normal‐weight participants. In contrast to the results in normal‐weight subjects, oxytocin did not blunt postprandial glucose and insulin excursions in obese men, and moreover failed to enhance beta‐cell responsivity and glucose tolerance. These results indicate that pronounced obesity may be associated with a certain degree of resistance to the glucoregulatory impact of exogenous oxytocin, and underlines the need for further investigations into the potential of oxytocin to improve glucose homeostasis in the clinical context.
Tissue microarrays – translational biomarker research in the fast lane
2018-09-10

The tissue microarray (TMA) method allows high-throughput biomarker analysis of large cohorts of tissue samples. The method is used for diagnostic profiling, evaluation of predictive or prognostic ...
Scheler, Max (1874–1928)
2018-09-10

Scheler was a philosopher in the phenomenological school. His mother was Jewish; his father was Protestant. In high school he became a Catholic but abandoned formal religion in 1922. He studied with Wilhelm Dilthey, Georg Simmel, and Rudolf Eucken. His early research was on transcendental philosophy. From 1900 to 1906 he was an outside lecturer (Privatdozent) in Jena and here engaged the work of Edmund Husserl. He was later active in Munich and Gottingen and from 1917 to 1918 at the German Foreign Ministry in Geneva and The Hague. From 1919 onward he was the director of the Institute for Social Sciences in Cologne.
Marburg School
2018-09-10

The Marburg School is a term used to describe a group of Neo-Kantian philosophers at the University of Marburg in the second half of the 19th century and early part of the 20th century. The New Criticism, as neo-Kantianism was also called, was sceptical of 19th-century materialism and naturalism. Friedrich Albert Lange (1828–1875) called for a return to Kant and his distinction between aprioristic and empirical knowledge. The classical Kantian metaphysical realism (‘thing in itself’) was nevertheless rejected in the Kantian renaissance. The key figures of the new critical and transcendental idealism at its zenith were Hermann Cohen (1842–1918) and Paul Natorp (1854–1924).
Report on 1807.02697v2
2018-09-10

We present a functional renormalization group (fRG) study of the two dimensional Hubbard model, performed with an algorithmic implementation which lifts some of the common approximations made in fRG calculations.In particular, in our fRG flow; (i) we take explicitly into account the momentum and the frequency dependence of the vertex functions; (ii) we include the feedback effect of the self-energy; (iii) we implement the recently introduced multiloop extension which allows us to sum up all the diagrams of the parquet approximation with their exact weight.Due to its iterative structure based on successive one-loop computations, the loop convergence of the fRG results can be obtained with an affordable numerical effort.In particular, focusing on the analysis of the physical response functions, we show that the results become independent from the chosen cutoff scheme and from the way the fRG susceptibilities are computed, i.e., either through flowing couplings to external fields, or through a "post-processing" contraction of the interaction vertex at the end of the flow.The presented substantial refinement of fRG-based computation schemes paves a promising route towards future quantitative fRG analyses of more challenging systems and/or parameter regimes.
Weimar Republic
2018-09-10

The Weimar Republic (1918/1919–1933) is a term used to describe the German Reich (Deutsches Reich) after the end of World War I and after the dissolution of the German monarchy up to 1933 with the establishment of Nazi Germany. It refers first to the new federal state, constitutional government and parliamentary democracy that initially convened in Weimar. The term also refers to a cultural period of German history associated with the Golden Twenties, Expressionism and the rise of mass culture. It can be divided into three periods: 1919–1923, the founding of the Republic and internal struggle; 1924–1929, the phase of relative stability; and 1930–1933, the phase of economic and political crisis.
Monuments
2018-09-10

Abstract During the European Iron Age, human impact on the environment was considerable. Far from the impenetrable forests once envisaged, there had been extensive woodland clearance. A wide range of settlement types existed in intensively exploited landscapes. Sites and their hinterlands were often structured around older monuments, intentionally incorporated and integrated into local belief systems. Ancestral cemeteries, natural features, and places of resource procurement all acted as foci of collective identity, playing major roles in the mental construction of the landscape, intertwining sacred and profane. Structured settlement environs indicate an increasing importance of property rights and delimitation of social units. Social hierarchies were reproduced by architectural variability in settlements using monumental buildings as social markers, both in urban and rural contexts. The chapter also considers Iron Age exploitation of forests, which like other landscapes were heavily managed, their resources vital for constructing buildings, fortifications, and supplying the charcoal crucial for ironworking.
Spengler, Oswald (1880–1936)
2018-09-10

Oswald Spengler was a prominent historian in the Weimar Republic (1918–1933). From 1908 to 1911, he worked as a high school teacher in Hamburg. Thereafter he worked as an independent author in Munich. His The Decline of the West (Der Untergang des Abendlandes, 1918, 1922) provided an important impetus for cultural analysis in the 1920s and 1930s in Germany.
Niebuhr, Reinhold (1892–1971)
2018-09-10

Karl Paul Reinhold Niebuhr was an influential pastor and theologian in America. His thought initially centered on liberal pacifism, but it later turned to the program of the social gospel and, finally, to ‘Christian Realism’. Niebuhr’s father was a German immigrant Protestant pastor; his mother also came from an immigrant pastor’s family. Niebuhr completed his theological education at Eden Theological Seminary (Webster Groves, Missouri) and Yale Divinity School, and he was ordained in 1913.
Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 4‐year follow‐up and analysis of relative progression‐free survival from the randomized ELOQUENT‐2 trial
2018-09-11

Background The randomized phase 3 ELOQUENT‐2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab plus lenalidomide and dexamethasone (ELd) versus lenalidomide and dexamethasone (Ld) in relapsed/refractory multiple myeloma (RRMM), and to date, has the longest follow‐up of any monoclonal antibody in patients with RRMM. Methods In this extended 4‐year follow‐up of the ELOQUENT‐2 trial, the coprimary endpoints of progression‐free survival (PFS) and overall response rate as well as the secondary endpoint of overall survival were assessed. In the absence of head‐to‐head trials comparing Ld‐based triplet regimens to guide treatment selection, 4 randomized controlled trials—ELOQUENT‐2, ASPIRE, TOURMALINE‐MM1, and POLLUX—were indirectly compared to provide insight into the relative efficacy of these regimens in RRMM. Results Data at 4 years were consistent with 2‐ and 3‐year follow‐up data: ELd reduced the risk of disease progression/death by 29% versus Ld (hazard ratio, 0.71) while maintaining safety. The greatest PFS benefit among the assessed subgroups was observed in patients at the median time or further from diagnosis (≥3.5 years) with 1 prior line of therapy, who had a 44% reduction in the risk of progression/death, and in patients in the high‐risk category, who had a 36% reduction in favor of ELd. This regimen also showed a relative PFS benefit that was maintained beyond 50 months. Conclusions The sustained PFS benefit and long‐term safety of ELd at 4 years, similar to those observed at 2 and 3 years, support ELd as a valuable therapeutic option for the long‐term treatment of patients with RRMM.
Reovirus Neurotropism and Virulence Are Dictated by Sequences in the Head Domain of the Viral Attachment Protein
2018-09-11

Viral encephalitis is a serious and often life-threatening inflammation of the brain. Mammalian orthoreoviruses are promising oncolytic therapeutics for humans but establish virulent, serotype-dependent disease in the central nervous system (CNS) of many young mammals. Serotype 1 reoviruses infect ependymal cells and produce hydrocephalus, whereas serotype 3 reoviruses infect neurons and cause encephalitis. Reovirus neurotropism is hypothesized to be dictated by the filamentous σ1 viral attachment protein. However, it is not apparent how this protein mediates disease. We discovered that sequences forming the most virion-distal domain of T1 and T3 σ1 coordinate infection of either ependyma or neurons, respectively, leading to mutually exclusive patterns of tropism and disease in the CNS. These studies contribute new knowledge about how reoviruses target cells for infection in the brain and inform the rational design of improved oncolytic therapies to mitigate difficult-to-treat tumors of the CNS.
3D radiative transfer: Continuum and line scattering in non-spherical winds from OB stars
2018-09-11

\\nContext. State of the art quantitative spectroscopy utilizes synthetic spectra to extract information from observations. For hot, massive stars, these synthetic spectra are calculated by means of 1D, spherically symmetric, NLTE atmosphere and spectrum-synthesis codes. Certain stellar atmospheres, however, show strong deviations from spherical symmetry, and need to be treated in 3D.\\nAims. We present and test a newly developed 3D radiative transfer code, tailored to the solution of the radiation field in rapidly expanding stellar atmospheres. We apply our code to the continuum transfer in wind-ablation models, and to the UV resonance line formation in magnetic winds.\\nMethods. We have used a 3D finite-volume method for the solution of the time-independent equation of radiative transfer, to study continuum- and line-scattering problems, currently approximated by a two-level-atom. Convergence has been accelerated by coupling the formal solver to a non-local approximate Λ-iteration scheme. Particular emphasis has been put on careful tests, by comparing with alternative solutions for 1D, spherically symmetric model atmospheres. These tests allowed us to understand certain shortcomings of the methods, and to estimate limiting cases that can actually be calculated.\\nResults. The typical errors of the converged source functions, when compared to 1D solutions, are of the order of 10–20%, and rapidly increase for optically thick (τ ≳ 10) continua, mostly due to the order of accuracy of our solution scheme. In circumstellar discs, the radiation temperatures in the (optically thin) transition region from wind to disc are quite similar to corresponding values in the wind. For MHD simulations of dynamical magnetospheres, the line profiles, calculated with our new 3D code, agree well with previous solutions using a 3D-SEI method. When compared with profiles resulting from the so-called analytic dynamical magnetosphere (ADM) model, however, significant differences become apparent.\\nConclusions. Due to similar radiation temperatures in the wind and the transition region to the disc, the same line-strength distribution can be applied within radiation hydrodynamic calculations for optically thick circumstellar discs in “accreting high-mass stars”. To properly describe the UV line formation in dynamical magnetospheres, the ADM model needs to be further developed, at least in a large part of the outer wind.\\n
Seasonal variation of BMI at admission in German adolescents with anorexia nervosa
2018-09-11

Our findings are contrary to previous studies and question the thermoregulatory hypothesis, indicating that seasonality in AN is more complex and might be subject to other biological or psychological factors, for example physical activity or body dissatisfaction. Our results indicate only a small clinical relevance of seasonal associations of BMI-SDS merely at admission. Longitudinal studies investigating within-subject seasonal changes might be more promising to assess seasonality in AN and of higher clinical relevance.
Cortical circuit activity underlying sleep slow oscillations and spindles
2018-09-12

Significance Slow oscillations and spindles are hallmarks of the EEG during slow-wave sleep. They are thought to support memory consolidation, particularly in instances where the faster spindle nests into the “upstate” of a slow oscillation. Using two-photon and wide-field imaging, we recorded calcium transients from distinct populations of cortical excitatory and inhibitory neurons during sleep in mice. Compared with spindles or slow oscillations occurring in isolation, events where spindles nested in a slow oscillation upstate were indeed accompanied by a unique pattern of calcium activity where high pyramidal cell activity appears to concur with high perisomatic inhibition through parvalbumin-positive interneurons and with low dendritic inhibition through somatostatin-positive interneurons. These conditions might foster dendritic plasticity.
A Modified Case Definition to Facilitate Essential Hospital Care During Ebola Outbreaks
2018-09-12

During the late phase of the large West-African Ebola virus disease (EVD) outbreak, the majority of patients were cared for in designated treatment centers. However, the preexisting healthcare infrastructure was already overwhelmed by the outbreak. This had a huge impact on other, non-EVD-related diseases, causing an unprecedented increase in morbidity and mortality, which most likely exceeded the toll due to EVD directly. Consequently, a crucial question is how to provide appropriate healthcare and safeguard functionality of a healthcare system that also serves patients not suspected or diagnosed to have EVD. Here, we report on the Lion Heart Medical Center's experience in Sierra Leone and note that a case definition of Ebola that is broader than those commonly applied may be better suited when it is necessary to identify atypically presenting, pauci-symptomatic cases.
EU Citizenship, Duties and Social Rights
2018-09-12

Abstract EU migrant citizens are often considered as outsiders, who access social benefits and services without having fulfilled their duties in the country of destination. As a group, however, EU migrant citizens are net contributors to the public purse in key destination countries. The current debate on duties of citizens within (con)federal jurisdictions has been rehearsed in different contexts, such as the North German Federation or the US, and the arguments are no different. EU citizenship must become an unconditional fundamental status, if it is to be meaningful.
A calorimeter for the precise determination of the activity of the 144Ce-144Pr anti-neutrino source in the SOX experiment
2018-09-12

We describe the design and the performance of a high precision thermal calorimeter, whose purpose was the measurement of the total activity of the 144Ce-144Pr anti-neutrino source of the SOX (Short distance neutrino Oscillation with BoreXino) experiment. SOX aimed at the search for eV-scale sterile neutrinos by means of the Borexino detector at the Laboratori Nazionali del Gran Sasso in Italy and of a very powerful artificial anti-neutrino source located at 8.51 m from the detector center. In order to obtain the required sensitivity, the activity of the source (approximately 150 kCi) had to be known at 1% precision. In this work we report the design of the experimental apparatus and the results of calibration measurements performed with an electrical mockup of the source. We show that the calorimeter sensitivity exceeds design goals, reaching a precision of a few %.
Sensorimotor Oscillatory Phase–Power Interaction Gates Resting Human Corticospinal Output
2018-09-13

Abstract Oscillatory activity within sensorimotor networks is characterized by time-varying changes in phase and power. The influence of interactions between sensorimotor oscillatory phase and power on human motor function, like corticospinal output, is unknown. We addressed this gap in knowledge by delivering transcranial magnetic stimulation (TMS) to the human motor cortex during electroencephalography recordings in 20 healthy participants. Motor evoked potentials, a measure of corticospinal excitability, were categorized offline based on the mu (8–12 Hz) and beta (13–30 Hz) oscillatory phase and power at the time of TMS. Phase-dependency of corticospinal excitability was evaluated across a continuous range of power levels using trial-by-trial linear mixed-effects models. For mu, there was no effect of PHASE or POWER (P &gt; 0.51), but a significant PHASE × POWER interaction (P = 0.002). The direction of phase-dependency reversed with changing mu power levels: corticospinal output was higher during mu troughs versus peaks when mu power was high while the opposite was true when mu power was low. A similar PHASE × POWER interaction was not present for beta oscillations (P &gt; 0.11). We conclude that the interaction between sensorimotor oscillatory phase and power gates human corticospinal output to an extent unexplained by sensorimotor oscillatory phase or power alone.