julilili42/papers huggingface dataset:
Determination of skin penetration profiles by confocal Raman microspectroscopy: statistical evaluation of optimal microscope configuration
2016-08-11

The aim of the study was to statistically evaluate the optimal microscope configuration for confocal Raman microspectroscopic determination of the penetration of a pharmaceutical active into the skin (depth profiling). Pig ear skin and a hydrophilic formulation containing procaine HCl were used as a model system. Two configurations (40 × 0.6 NA objective and 25 μm pinhole or 100 × 1.25 NA oil immersion objective and 50 μm pinhole) that had been found to potentially give appropriate results were investigated. Measurements on cross sections of skin samples were used as a reference. Both microscope configurations were found to be appropriate for depth profiling. It was found that the use of a 100 × 1.25 NA oil immersion objective and 50 μm pinhole lead to higher variability of the results. The statistical approach was found to be highly valuable. This shows that both, metallurgic and immersion objective can be used for depth profiling. The statistical analysis can serve as an example on how to choose an appropriate microscope configuration for depth profiling of the skin. Copyright © 2016 John Wiley &amp; Sons, Ltd.
Catenin delta-1 (CTNND1) phosphorylation controls the mesenchymal to epithelial transition in astrocytic tumors
2016-08-11

Inactivating mutations of the TSC1/TSC2 complex (TSC1/2) cause tuberous sclerosis (TSC), a hereditary syndrome with neurological symptoms and benign hamartoma tumours in the brain. Since TSC effectors are largely unknown in the human brain, TSC patient cortical tubers were used to uncover hyperphosphorylation unique to TSC primary astrocytes, the cell type affected in the brain. We found abnormal hyperphosphorylation of catenin delta-1 S268, which was reversible by mTOR-specific inhibitors. In contrast, in three metastatic astrocytoma cell lines, S268 was under phosphorylated, suggesting S268 phosphorylation controls metastasis. TSC astrocytes appeared epithelial (i.e. tightly adherent, less motile, and epithelial (E)-cadherin positive), whereas wild-type astrocytes were mesenchymal (i.e. E-cadherin negative and highly motile). Despite their epithelial phenotype, TSC astrocytes outgrew contact inhibition, and monolayers sporadically generated tuberous foci, a phenotype blocked by the mTOR inhibitor, Torin1. Also, mTOR-regulated phosphokinase C epsilon (PKCe) activity induced phosphorylation of catenin delta-1 S268, which in turn mediated cell-cell adhesion in astrocytes. The mTOR-dependent, epithelial phenotype of TSC astrocytes suggests TSC1/2 and mTOR tune the phosphorylation level of catenin delta-1 by controlling PKCe activity, thereby regulating the mesenchymal-epithelial-transition (MET). Thus, some forms of TSC could be treated with PKCe inhibitors, while metastasis of astrocytomas might be blocked by PKCe stimulators.
Bootstrat: Population Informed Bootstrapping for Rare Variant Tests
2016-08-11

Abstract Recent advances in genotyping and sequencing technologies have made detecting rare variants in large cohorts possible. Various analytic methods for associating disease to rare variants have been proposed, including burden tests, C-alpha and SKAT. Most of these methods, however, assume that samples come from a homogeneous population, which is not realistic for analyses of large samples. Not correcting for population stratification causes inflated p -values and false-positive associations. Here we propose a population-informed bootstrap resampling method that controls for population stratification (Bootstrat) in rare variant tests. In essence, the Bootstrat procedure uses genetic distance to create a phenotype probability for each sample. We show that this empirical approach can effectively correct for population stratification while maintaining statistical power comparable to established methods of controlling for population stratification. The Bootstrat scheme can be easily applied to existing rare variant testing methods with reasonable computational complexity. Author Summary Recent technology advances have enabled large-scale analysis of rare variants, but properly testing rare variants remains a significant challenge as most rare variant testing methods assume a sample of homogenous ethnicity, an assumption often not true for large cohorts. Failure to account for this heterogeneity increases the type I error rate. Here we propose a bootstrap scheme applicable to most existing rare variant testing methods to control for population heterogeneity. This scheme uses a randomization layer to establish a null distribution of the test statistics while preserving the sample genetic relationships. The null distribution is then used to calculate an empirical p -value that accounts for population heterogeneity. We demonstrate how this scheme successfully controls the type I error rate without loss of statistical power.
Integrative synchronization mechanisms in connectionist cognitive neuroarchitectures
2016-08-11

Based on the mathematics of nonlinear Dynamical System Theory, neurocognition can be analyzed by convergent fluid and transient neurodynamics in abstract n-dimensional system phase spaces in the form of nonlinear vector fields, vector streams or vector flows (the so-called “vectorial form”). This processual or dynamical perspective on cognition, including the dynamical binding mechanisms in cognitive neuroarchitectures, has the advantage of a more accurately modeling of the transient cognitive processes. Thus, neurocognition can be considered as being organized by integrative synchronization mechanisms which best explain the liquid flow of neurocognitive information orchestrated in a network of positive and/or negative feedback loops in the subcortical and cortical areas. The human neurocognitive system can be regarded as a nonlinear, dynamical and open nonequilibrium system. This new fluid or liquid perspective in cognitive science and cognitive neuroscience can be regarded as a contribution towards bridging the gap between the discrete, abstract symbolic description of propositions in the mind, and their continuous, numerical implementation in self-organizing neural networks modelling the neural information processing in the human brain.
BDNFVal66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer’s disease
2016-08-12

SEE ROGAEVA AND SCHMITT-ULMS DOI101093/AWW201 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate amyloid-β-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer's disease. However, the effect of BDNF in autosomal dominant Alzheimer's disease is unknown. We aimed to determine the effect of BDNF Val66Met on cognitive function, hippocampal function, tau and amyloid-β in preclinical autosomal dominant Alzheimer's disease. We explored effects of apolipoprotein E (APOE) ε4 on these relationships. The Dominantly Inherited Alzheimer Network conducted clinical, neuropsychological, genetic, biomarker and neuroimaging measures at baseline in 131 mutation non-carriers and 143 preclinical autosomal dominant Alzheimer's disease mutation carriers on average 12 years before clinical symptom onset. BDNF genotype data were obtained for mutation carriers (95 Val<sub>66</sub> homozygotes, 48 Met<sub>66</sub> carriers). Among preclinical mutation carriers, Met<sub>66</sub> carriers had worse memory performance, lower hippocampal glucose metabolism and increased levels of cerebrospinal fluid tau and phosphorylated tau (p-tau) than Val<sub>66</sub> homozygotes. Cortical amyloid-β and cerebrospinal fluid amyloid-β<sub>42</sub> levels were significantly different from non-carriers but did not differ between preclinical mutation carrier Val<sub>66</sub> homozygotes and Met<sub>66</sub> carriers. There was an effect of APOE on amyloid-β levels, but not cognitive function, glucose metabolism or tau. As in sporadic Alzheimer's disease, the deleterious effects of amyloid-β on memory, hippocampal function, and tau in preclinical autosomal dominant Alzheimer's disease mutation carriers are greater in Met<sub>66</sub> carriers. To date, this is the only genetic factor found to moderate downstream effects of amyloid-β in autosomal dominant Alzheimer's disease.
Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity
2016-08-12

The cholinergic anti-inflammatory pathway reduces systemic tumor necrosis factor (TNF) via acetylcholine-producing memory T cells in the spleen. These choline acetyltransferase (ChAT)-expressing T cells are also found in the intestine, where their function is unclear. We aimed to characterize these cells in mouse and human intestine and delineate their function. We made use of the ChAT-enhanced green fluorescent protein (eGFP) reporter mice. CD4 Cre mice were crossed to ChAT fl/fl mice to achieve specific deletion of ChAT in CD4 + T cells. We observed that the majority of ChAT-expressing T cells in the human and mouse intestine have characteristics of Th17 cells and coexpress IL17A, IL22, and RORC. The generation of ChAT-expressing T cells was skewed by dendritic cells after activation of their adrenergic receptor β 2 . To evaluate ChAT T cell function, we generated CD4-specific ChAT-deficient mice. CD4ChAT −/− mice showed a reduced level of epithelial antimicrobial peptides lysozyme, defensin A, and ang4, which was associated with an enhanced bacterial diversity and richness in the small intestinal lumen in CD4ChAT −/− mice. We conclude that ChAT-expressing T cells in the gut are stimulated by adrenergic receptor activation on dendritic cells. ChAT-expressing T cells may function to mediate the host AMP secretion, microbial growth and expansion.
Astrophysical applications of the post-Tolman-Oppenheimer-Volkoff formalism
2016-08-12

The bulk properties of spherically symmetric stars in general relativity can\\nbe obtained by integrating the Tolman-Oppenheimer-Volkoff (TOV) equations. In\\nprevious work we developed a "post-TOV" formalism - inspired by parametrized\\npost-Newtonian theory - which allows us to classify in a parametrized,\\nphenomenological form all possible perturbative deviations from the structure\\nof compact stars in general relativity that may be induced by modified gravity\\nat second post-Newtonian order. In this paper we extend the formalism to deal\\nwith the stellar exterior, and we compute several potential astrophysical\\nobservables within the post-TOV formalism: the surface redshift , the\\napparent radius , the Eddington luminosity at infinity and the orbital frequencies. We show that, at leading order, all of\\nthese quantities depend on just two post-TOV parameters and , and\\nwe discuss the possibility to measure (or set upper bounds on) these\\nparameters.\\n
Metastasectomy for metastatic renal cell carcinoma in the era of modern systemic treatment: C‐reactive protein is an independent predictor of overall survival
2016-08-12

Objective To define the predictive capability of serum C‐reactive protein for a contemporary patient collective undergoing metastasectomy for metastatic renal cell carcinoma with access to modern targeted therapies. Methods A total of 88 patients treated with metastasectomy for metastatic renal cell carcinoma from 2003 to 2014 were evaluated for putative clinicopathological risk factors and survival. Kaplan–Meier analyses, univariate and multivariate testing were carried out. Receiver operating characteristic curve analysis was applied to evaluate available risk stratification instruments for patients undergoing metastasectomy. Results Median overall survival for the collective was 66.31 months (95% confidence interval 50.67–135.47; 5‐year overall survival 55%). The median preoperative C‐reactive protein level was 6.7 mg/L (range 0.1–161.7). A C‐reactive protein cut‐off value of 5 mg/dL was significantly discriminative of survival ( P = 0.029). Median survival in dependence of C‐reactive protein accounted for 50.67 months (range 33.86–63.05 months) in the C‐reactive protein &gt;5 mg/L group, and 135.47 months in the C‐reactive protein ≤5 mg/L group (range 66.31–135.47 months). C‐reactive protein elevation &gt;5 mg/L, anemia and surgical margin status were identified as significant predictors of overall survival in univariate analysis. In a multivariate model, resection margin status ( P = 0.015) and C‐reactive protein elevation ( P = 0.038) were confirmed as independent predictive variables. Conclusions Elevated C‐reactive protein &gt;5 mg/L was identified as an independent predictor of survival in a contemporary patient collective undergoing metastasectomy for metastatic renal cell carcinoma. Future analyses and risk stratification tools for patients undergoing metastasectomy for metastatic renal cell carcinoma should aim to evaluate and include C‐reactive protein. To overcome low patient numbers, multi‐institutional studies should be carried out.
Study of a new central compact object: The neutron star in the\\n supernova remnant G15.9+0.2
2016-08-12

\\n We present our study of the central point source CXOU J181852.0−150213 in the young Galactic supernova\\n remnant (SNR) G15.9+0.2 based on the recent ~90 ks Chandra observations. The point source\\n was discovered in 2005 in shorter Chandra observations and was\\n hypothesized to be a neutron star associated with the SNR. Our X-ray spectral analysis\\n strongly supports the hypothesis of a thermally emitting neutron star associated with\\n G15.9+0.2. We conclude that the object belongs to the class of young cooling\\n low-magnetized neutron stars referred to as central compact objects (CCOs). We modeled the\\n spectrum of the neutron star with a blackbody spectral function and with our hydrogen and\\n carbon neutron star atmosphere models, assuming that the radiation is uniformly emitted by\\n the entire stellar surface. Under this assumption, only the carbon atmosphere models yield\\n a distance that is compatible with a source located in the Galaxy. In this respect,\\n CXOU J181852.0−150213 is\\n similar to two other well-studied CCOs, the neutron stars in Cas A and in\\n HESS J1731−347, for which\\n carbon atmosphere models were used to reconcile their emission with the known or estimated\\n distances. \\n
Functional Role of γ-Crystallin N in the Auditory Hindbrain
2016-08-12

γ-crystallins are major components of the vertebrate lens but show expression in other tissues as well. Their extralenticular functions remain so far unclear. Here, we explored such roles in the rodent superior olivary complex in which previous analysis demonstrated developmentally regulated expression of Crygd, Cryge and Crygn. Immunohistochemistry with novel antibodies against Crygd/e and Crygn indicate that expression of Crygd/e was moderate and varied between the perinatal superior olivary complex of mice, rats, and gerbils. Crygn-immunoreactivity was more robust and consistently highest in the medial nucleus of the trapezoid body, but also present in other nuclei of the superior olivary complex. To analyze the function of Crygn in the auditory hindbrain, we used a Crygn allele with a floxed exon 2. Upon pairing with Egr2::Cre mice, exon 2, encoding the first two greek key motifs of Crygn, was deleted in the developing auditory hindbrain. Anatomical analysis of these mice revealed a 20% volume reduction in the medial nucleus of the trapezoid body and a 7% reduction in the lateral superior olive at postnatal day 25. This was due to cell loss between postnatal days 4 and 25, whereas cell size was unaffected. Auditory brainstem responses showed normal threshold but a significant increase in the amplitude of wave IV. Crygn is hence required for postmigratory survival and proper function of auditory hindbrain neurons. These results ascertain for the first time an essential extralenticular role for γ-crystallins in vivo.
Hyperbolicity of physical theories with application to general relativity
2016-08-12

We consider gauge theories from the free evolution point of view, in which\\ninitial data satisfying constraints of a theory are given. Because the\\nconstraints are compatible with the field equations they remain so. We study a\\nmodel constrained Hamiltonian theory and identify a particular structure in the\\nequations of motion which we call the standard gauge freedom. The pure gauge\\nsubsystem of this model theory is identified and the manner in which the gauge\\nvariables couple to the field equations is presented. We demonstrate that the\\nset of gauge choices that can be coupled to the field equations to obtain a,\\nproperly defined, wave-like formulation is exactly the set of wave-like pure\\ngauges. Consequently we analyze a parametrized family of formulations of\\ngeneral relativity. The generalization of the harmonic gauge formulation to a\\nfive parameter family of gauge conditions is obtained.\\n
Allergic Reaction to Polyether Ether Ketone Following Cross-Reactivity to Epoxy Resin
2016-08-13

Polyether ether ketone (PEEK) is a thermoplastic polymer frequently used in engineering but also in medical devices. Only 1 case of allergic reaction to PEEK used as an implanted medical device has been reported so far; however, the route of sensitization remained unclear. Here we report on a 62-year-old male patient with a preknown, severe type IV allergy to epoxy resin. He reported strong pain in his shoulder after implantation of a PEEK-containing device after a rotator cuff injury. For testing, the device was implanted in a small pouch subcutaneously on the abdomen. The patient reported massive pain starting 8 hours after the implantation, strictly limited to the procedural area and showing perifocal erythema. A possible explanation of the sensitization mode is the source material for PEEK and epoxy resin, as both are mainly based on bisphenols. An allergic reaction to PEEK with preknown epoxy resin sensitization has not been reported so far. As epoxy resins are a frequent cause of occupational contact dermatitis and PEEK is widely used for medical and nonmedical devices, we believe that this is of great clinical relevance.
DrosophilaKette coordinates myoblast junction dissolution and the ratio of Scar-to-WASp during myoblast fusion
2016-08-13

ABSTRACT The fusion of founder cells and fusion-competent myoblasts (FCMs) is crucial for muscle formation in Drosophila. Characteristic events of myoblast fusion include the recognition and adhesion of myoblasts, and the formation of branched F-actin by the Arp2/3 complex at the site of cell–cell contact. At the ultrastructural level, these events are reflected by the appearance of finger-like protrusions and electron-dense plaques that appear prior to fusion. Severe defects in myoblast fusion are caused by the loss of Kette (a homolog of Nap1 and Hem-2, also known as NCKAP1 and NCKAP1L, respectively), a member of the regulatory complex formed by Scar or WAVE proteins (represented by the single protein, Scar, in flies). kette mutants form finger-like protrusions, but the electron-dense plaques are extended. Here, we show that the electron-dense plaques in wild-type and kette mutant myoblasts resemble other electron-dense structures that are known to function as cellular junctions. Furthermore, analysis of double mutants and attempts to rescue the kette mutant phenotype with N-cadherin, wasp and genes of members of the regulatory Scar complex revealed that Kette has two functions during myoblast fusion. First, Kette controls the dissolution of electron-dense plaques. Second, Kette controls the ratio of the Arp2/3 activators Scar and WASp in FCMs.
Becoming the Phenomenon? An Alternative Approach to Reflexivity in Ethnography
2016-08-13

This article presents a praxeologically informed approach to “transgressing the researcher-subject” in ethnography. I unfurl a concept of “strong” reflexivity as developing a perspective of unfamiliarity toward one’s own practices and beliefs. By drawing on my study on practicing ballet, I illustrate how I dealt with my own bodily involvement as a professional dance student. Comparing my approach with evocative autoethnography, I not only emphasize that corporeal sensitivity and alertness are inherent to both styles of inquiry. Yet, I also point out their differences. Whereas evocative autoethnography takes subjectivity as a resource for insights, this approach uses it as an instrument for discovery.
A SOFTWARE PACKAGE FOR MORI DREAM SPACES
2016-08-14

Abstract. Mori dream spaces form a large example class of algebraic vari-eties, comprising the well known toric varieties. We provide a first software package for the explicit treatment of Mori dream spaces and present sample computations. 1.
Modelling accretion in transitional disks
2016-08-14

\\n Context. Transitional disks are protoplanetary disks around young stars that display inner holes in the dust distribution within a few au that are accompanied by some gas accretion onto the central star. These cavities could possibly be created by the presence of one or more massive planets that opened a large gap or even cleared the whole inner region.\\n Aims. If the gap is created by planets and gas is still present in it, then there should be a flow of gas past the planet into the inner region. It is our goal to study in detail the mass accretion rate into this planet-created gap in transitional disks and in particular the dependency on the planet’s mass and the thermodynamic properties of the disk.\\n Methods. We performed 2D hydrodynamical simulations using the grid-based <monospace>FARGO </monospace>code for disks with embedded planets. We added radiative cooling from the disk surfaces, radiative diffusion in the disk midplane, and stellar irradiation to the energy equation to have more realistic models.\\n Results. The mass flow rate into the gap region depends, for given disk thermodynamics, non-monotonically on the mass of the planet. Generally, more massive planets open wider and deeper gaps which would tend to reduce the mass accretion into the inner cavity. However, for larger mass planets the outer disk becomes eccentric and the mass flow rate is enhanced over the low mass cases. As a result, for the isothermal disks the mass flow is always comparable to the expected mass flow of unperturbed disks Ṁd, while for more realistic radiative disks the mass flow is very small for low mass planets (≤4 Mjup) and about 50% of Ṁd for larger planet masses. The critical planet mass that allows the disk to become eccentric is much larger for radiative disks than for purely isothermal cases.\\n Conclusions. Massive embedded planets can reduce the mass flow across the gap considerably, to values of about an order of magnitude smaller than the standard disk accretion rate, and can be responsible for opening large cavities. The remaining mass flow into the central cavity is in good agreement with the observations.\\n
ON CUBIC ELLIPTIC VARIETIES
2016-08-14

Abstract. Let pi: X → Pn−1 be an elliptic fibration obtained by resolving the indeterminacy of the projection of a cubic hypersurface Y of Pn+1 from a line L not contained in Y. We prove that the Mordell-Weil group of pi is finite if and only if the Cox ring of X is finitely generated. We also provide a presentation of the Cox ring of X when it is finitely generated.