julilili42/papers huggingface dataset:
Perturbation of GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Induces Trans-regional Metaplasticity at the Medial Prefrontal Cortex
2017-10-23

GABAergic synapses in the basolateral amygdala (BLA) play an important role in fear memory generation. We have previously reported that reduction in GABAergic synapses innervating specifically at the axon initial segment (AIS) of principal neurons of BLA, by neurofascin (NF) knockdown, impairs fear extinction. BLA is bidirectionally connected with the medial prefrontal cortex (mPFC), which is a key region involved in extinction of acquired fear memory. Here, we showed that reducing AIS GABAergic synapses within the BLA leads to impairment of synaptic plasticity in the BLA-mPFC pathway, as well as in the ventral subiculum (vSub)-mPFC pathway, which is independent of BLA involvement. The results suggest that the alteration within the BLA subsequently resulted in a form of trans-regional metaplasticity in the mPFC. In support of that notion, we observed that NF knockdown induced a severe deficit in behavioral flexibility as measured by reversal learning. Interestingly, reversal learning similar to extinction learning is an mPFC-dependent behavior. In agreement with that, measurement of the immediate-early gene, c-Fos immunoreactivity after reversal learning was reduced in the mPFC and BLA, supporting further the notion that the BLA GABAergic manipulation resulted in trans-regional metaplastic alterations within the mPFC.
Offshoring Domestic Jobs
2017-10-23

We develop a two-country general equilibrium model, in which heterogeneous firms offshore routine tasks to a low-wage host country. In the presence of fixed costs for offshoring the most productive firms self-select into offshoring, which leads to a reallocation of domestic labor towards less productive uses if offshoring costs are high. As a consequence domestic welfare may fall. The reallocation effect is reversed and domestic welfare rises if offshoring costs are low. The aggregate income distribution, comprising wages and entrepreneurial incomes, becomes more unequal with offshoring.
Unemployment and the Welfare Effects of Trade Policy
2017-10-23

This chapter derives and compares the welfare effects of tariffs and import quotas in the presence of involuntary unemployment. The framework used is the standard model of a competitive small open economy with many goods and factors. Optimum levels of the respective trade policy instruments are derived, as well as welfare increasing reform strategies. In all cases, the labor intensity of the import competing sectors turns out to be a crucial variable for deriving the welfare effects.
Nanolevel Control of Gas Sensing Characteristics via p–n Heterojunction between Rh2O3 Clusters and WO3 Crystallites
2017-10-24

Today semiconducting metal oxide (SMOX) based gas sensors are used in a wide array of applications. Dopants, e.g., rhodium, are often used to change the sensor response of SMOXs. The adjustment of sensing characteristics with dopants is usually done empirically, and there is a knowledge gap surrounding how the presence of dopants alters the chemistry of sensing. Here using X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), dc resistance measurements, and operando diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, it was understood how surface loading with Rh2O3 changes sensing with WO3. As a result of uniform surface loading, reactions between the Rh2O3 clusters and the analyte gas dominate the reception. Changes in the p–n heterojunction between Rh2O3 and WO3 are responsible for the transduction. These results in combination with existing literature indicate that, through controlled surface doping, it is possible to intentionally tune the sensor characteristics of SMOXs.
Nurse‐driven analgesia and sedation in pediatric patients with univentricular hearts requiring extracorporeal life support after first‐stage palliation surgery: A pilot study
2017-10-24

Summary Background Few data are available regarding requirements of sedation and analgesia in children during extracorporeal life support. Aims The aim of this study was to evaluate if children with functionally univentricular hearts on extracorporeal life support after first‐stage palliation surgery have higher requirement of analgesics and sedatives compared with children without extracorporeal life support using a goal‐directed nurse‐driven analgesia and sedation protocol. Methods This prospective observational matched case‐control pilot study was conducted at a cardiac pediatric intensive care unit of a tertiary referral center. Seventeen patients with functionally univentricular hearts including hypoplastic left heart syndrome who were on extracorporeal life support after first‐stage palliation surgery were enrolled from July 2012 to January 2017. Seventeen matched patients served as controls. Doses of morphine, midazolam, clonidine, and muscle relaxants as well as sedation scores ( COMFORT behavior scale and the nurse interpretation of sedation scale) were assessed according to a nurse‐driven protocol every 8 hours up to 120 hours after first‐stage palliation surgery. Results Sedation scores were equal in the extracorporeal life support group and in the control group at most points in time. There was no significant difference in cumulative doses of morphine and midazolam. However, children of the extracorporeal life support group received higher doses of midazolam and morphine at some points in time. Conclusion A nurse‐driven protocol for analgesia and sedation of children with extracorporeal life support is feasible. Patients with extracorporeal life support do not need deeper sedation levels and have not higher cumulative sedation requirements than children without extracorporeal life support.
Prediction of HIV-1 sensitivity to broadly neutralizing antibodies shows a trend towards resistance over time
2017-10-24

Treatment with broadly neutralizing antibodies (bNAbs) has proven effective against HIV-1 infections in humanized mice, non-human primates, and humans. Due to the high mutation rate of HIV-1, resistance testing of the patient's viral strains to the bNAbs is still inevitable. So far, bNAb resistance can only be tested in expensive and time-consuming neutralization experiments. Here, we introduce well-performing computational models that predict the neutralization response of HIV-1 to bNAbs given only the envelope sequence of the virus. Using non-linear support vector machines based on a string kernel, the models learnt even the important binding sites of bNAbs with more complex epitopes, i.e., the CD4 binding site targeting bNAbs, proving thereby the biological relevance of the models. To increase the interpretability of the models, we additionally provide a new kind of motif logo for each query sequence, visualizing those residues of the test sequence that influenced the prediction outcome the most. Moreover, we predicted the neutralization sensitivity of around 34,000 HIV-1 samples from different time points to a broad range of bNAbs, enabling the first analysis of HIV resistance to bNAbs on a global scale. The analysis showed for many of the bNAbs a trend towards antibody resistance over time, which had previously only been discovered for a small non-representative subset of the global HIV-1 population.
Gain-of-functionHCN2variants in genetic epilepsy
2017-10-24

Genetic generalized epilepsy (GGE) is a common epilepsy syndrome that encompasses seizure disorders characterized by spike-and-wave discharges (SWDs). Pacemaker hyperpolarization-activated cyclic nucleotide-gated channels (HCN) are considered integral to SWD genesis, making them an ideal gene candidate for GGE. We identified HCN2 missense variants from a large cohort of 585 GGE patients, recruited by the Epilepsy Phenome-Genome Project (EPGP), and performed functional analysis using two-electrode voltage clamp recordings from Xenopus oocytes. The p.S632W variant was identified in a patient with idiopathic photosensitive occipital epilepsy and segregated in the family. This variant was also independently identified in an unrelated patient with childhood absence seizures from a European cohort of 238 familial GGE cases. The p.V246M variant was identified in a patient with photo-sensitive GGE and his father diagnosed with juvenile myoclonic epilepsy. Functional studies revealed that both p.S632W and p.V246M had an identical functional impact including a depolarizing shift in the voltage dependence of activation that is consistent with a gain-of-function. In contrast, no biophysical changes resulted from the introduction of common population variants, p.E280K and p.A705T, and the p.R756C variant from EPGP that did not segregate with disease. Our data suggest that HCN2 variants can confer susceptibility to GGE via a gain-of-function mechanism.
Early-Onset Myopathies: Clinical Findings, Prevalence of Subgroups and Diagnostic Approach in a Single Neuromuscular Referral Center in Germany
2017-10-24

Background: Early-onset myopathies are a heterogeneous group of neuromuscular diseases with broad clinical, genetic and histopathological overlap. The diagnostic approach has considerably changed since high throughput genetic methods (next generation sequencing, NGS) became available. Objective: We present diagnostic subgroups in a single neuromuscular referral center and describe an algorithm for the diagnostic work-up. Methods: The diagnostic approach of 98 index patients was retrospectively analysed. In 56 cases targeted sequencing of a known gene was performed, in 44 patients NGS was performed using large muscle specific panels, and in 12 individuals whole exome sequencing (WES) was undertaken. One patient was diagnosed via array CGH. Clinical features of all patients are provided. Results: The final diagnosis could be found in 63 out of 98 patients (64%) with molecular genetic analysis. In 55% targeted gene sequencing could establish the genetic diagnosis. However, this rate largely depended on the presence of distinct histological or clinical features. NGS (large myopathy-related panels and WES) revealed genetic diagnosis in 58.5% (52% and 67%, respectively). The genes detected by WES in our cohort of patients were all covered by the panels. Based on our findings we propose an algorithm for a practical diagnostic approach. Prevalences: MTM1- and LAMA2-patients are the two biggest subgroups, followed by SEPN1-, RYR1- and Collagen VI-related diseases. 31% of genetically confirmed cases represents a group with overlap between “congenital myopathies (CM)” and “congenital muscular dystrophies (CMD)”. In 36% of the patients a specific genetic diagnosis could not be assigned. Conclusions: A final diagnosis can be confirmed by high throughput genetic analysis in 58.5% of the cases, which is a higher rate than reported in the literature for muscle biopsy and should in many cases be considered as a first diagnostic tool. NGS cannot replace neuromuscular expertise and a close discussion with the geneticists on NGS is mandatory. Targeted candidate gene sequencing still plays a role in selected cases with highly suspicious clinical or histological features. There is a relevant clinical and genetic overlap between the entities CM and CMD.
Line-driven ablation of circumstellar discs – II. Analysing the role of multiple resonances
2017-10-24

We extend our previous study of radiative ablation of circumstellar discs by line-scattering of the star's radiation, accounting now for the effect of multiple line resonances off the stellar limb. For an analytic, three-dimensional model of the velocity structure of an equatorial Keplerian disc bounded at higher latitudes by a radially accelerating stellar wind outflow, we use root-finding methods to identify multiple resonances from a near-disc circumstellar location along starward rays both on and off the stellar core. Compared to our previous study that accounted only for the effect of on-core resonances in reducing the radiative driving through the scattering of radiation away from a near-disc circumstellar location, including off-limb resonances leads to additional radiative driving from scattering towards this location. Instead of the up to 50 per cent reduction in line-acceleration previously inferred from multiple resonance effects, we now find a more modest 15–20 per cent net reduction.
Dealing with Space and Place in Standard Survey Data
2017-10-24

Heterogeneity of local conditions and spatial dependencies are typical aspects of sociological phenomena. However, large-scale empirical data is often rather limited with regard to the spatial references that are (publicly) available to researchers. We describe several aspects of the problem and assess possibilities and potential errors associated with limited information. Our examples are returns to education and gender-based and migration-related wage gaps as popular research topics. We base our analyses upon widely used survey data from Germany, the GSOEP, which contains geographical information on various levels of aggregation. Our particular interest is in the decisions that have to be made with regard to problems of space and place in standard surveys, available options and consequences. We conclude with a number of practical suggestions for data users.
Analyzing Different Types of Moderated Method Effects in Confirmatory Factor Models for Structurally Different Methods
2017-10-24

An extension of two confirmatory factor models for multitrait-multimethod measurement designs with structurally different methods to the analysis of latent interaction effects is presented: the nonlinear latent difference (NL-LD) model and the nonlinear correlated trait–correlated method-minus-one (NL-CTC[M – 1]) model. Both models are compared with regard to (a) the psychometric definition of the latent variables, (b) the capabilities of explaining latent method effects, and (c) the analysis of latent interaction effects. Using the latent moderated structural equation approach, we show how moderated method effects can be examined in the NL-CTC(M – 1) model. This fine-grained analysis of method effects is not feasible using the classical NL-LD model. We propose an extended version of the NL-LD model, which recovers the results of the NL-CTC(M – 1) model. The different versions of the nonlinear multimethod models are illustrated using real data from a multirater study. Finally, the advantages and challenges of incorporating latent interaction effects in complex CFA–MTMM models are discussed.
Botulinumtoxin Improves both Generic and Disease-Specific Quality of Life in Cervical Dystonia
2017-10-24

Botulinumtoxin injection (BoNT) into affected muscles is effective to improve motor symptoms of cervical dystonia (CD) by reducing muscle contraction and involuntary dystonic movement and posturing. However, the understanding of the effect on health-related quality of life (HR-QoL) and patient referral under HR-QoL aspects is incomplete. In this open-label clinical prospective observational study, we characterized the outcomes in CD (<i>n</i> = 159) from botulinumtoxin on both generic HR-QoL (EuroQol; EQ-5D-5L) and disease-specific HR-QoL [craniocervical dystonia questionnaire (CDQ-24)]. Additionally, we characterized motor and non-motor signs of dystonia including motor symptom improvement, depressive symptoms, pain, and sleep quality. We assessed patients at the end of a regular 3-month period from last injection (Timepoint1) and 4 weeks after the re-injection of BoNT (Timepoint2). We aimed to define outcomes on both generic and disease-specific HR-QoL and to evaluate predictors of therapeutic outcome in terms of stepwise multiple regression models. Patients with CD showed a robust improvement of both generic and disease-specific HR-QoL. Furthermore, motor and non-motor signs improved. Multiple regression analyses revealed that EQ-5D-5L and "satisfaction with health" (Fragen zur Lebenszufriedenheit-G) at Timepoint1 predicted treatment response on generic HR-QoL outcome (<i>R</i><sup>2</sup> = 0.284; <i>P</i> = 0.019). Similarly, CDQ-24 and Beck's Depression inventory at Timepoint1 predicted the treatment response on disease-specific HR-QoL (<i>R</i><sup>2</sup> = 0.253; <i>P</i> = 0.026). Our study underscores both generic and disease-specific HR-QoL improvements in CD, and provides useful predictors on HR-QoL outcomes.
Can HCCH/HBNH Break B═N/C═C Bonds of Single-Wall BN/Carbon Nanotubes at Their Surface?
2017-10-24

The iminoborane (HBNH) molecule selectively breaks a B═N bond of smaller diameter single-wall BN nanotubes (BNNTs) and expands a ring at their surface, either at the edges or at the middle of the tube. Density functional theory is used to test whether its organic counterpart HCCH can do the same with BNNTs. HCCH–BNNT complexes are identified and transition states located for these combination reactions. Also explored are possible reactions of HBNH with single-wall carbon nanotubes (SWNTs) and HCCH with SWNTs. Data suggest that B═N (C═C) bond breaking, followed by ring expansion at the surface, may be possible. Although [2 + 2]cycloaddition reaction seems possible for HBNH–BNNTs, a high energy barrier hinders the process for other combinations of reactants. Introduction of substituents to HBNH/HCCH may allow a facile process. In most cases of HCCH–BNNTs, HBNH–SWNTs, and HCCH–SWNTs, transition states are identified and suggest an electron-rich reactant might lower barrier heights to form stable complexes. Reaction with HCCH or HBNH at the bay region of smaller diameter armchair tube is not favorable.
Retinal specializations to a micro-predatory and crypto-benthic life-style in the Mediterranean triplefin blennyTripterygion delaisi
2017-10-24

Abstract The environment and lifestyle of a species are known to exert selective pressure on the visual system, often demonstrating a tight link between visual morphology and ecology. Many studies have predicted the visual requirements of a species by examining the anatomical features of the eye. However, among the vast number of studies on visual specializations in aquatic animals, only a few have focused on small benthic fishes that occupy a heterogeneous and spatially complex visual environment. This study investigates the general retinal anatomy including the topography of both the photoreceptor and ganglion cell populations and estimates the spatial resolving power of the eye of the Mediterranean triplefin Tripterygion delaisi . Retinal wholemounts were prepared to systematically and quantitatively analyze photoreceptor and retinal ganglion cell densities using design-based stereology. To further examine the retinal structure, we also used magnetic resonance imaging and histological examination of retinal cross sections. Observations of the triplefin's eyes revealed them to be highly mobile, allowing them to view the surroundings without body movements. A rostral aphakic gap and the elliptical shape of the eye extend its visual field rostrally and allow for a rostro-caudal accommodatory axis, enabling this species to focus on prey at close range. Single and twin cones dominate the retina and are consistently arranged in one of two regular patterns, which may enhance motion detection and color vision. The retina features a prominent, dorso-temporal, convexiclivate fovea with an average density of 104,400 double and 30,800 single cones per mm 2 , and 81,000 retinal ganglion cells per mm 2 . Based on photoreceptor spacing, spatial resolving power was calculated to be between 6.7 and 9.0 cycles per degree. Location and resolving power of the fovea would benefit the detection and identification of small prey in the lower frontal region of the visual field.
Ilias and Odyssey: Two Epics, Two World Views
2017-10-24

The different world views of the authors of the Iliad and the Odyssey are illustrated by selection of verses used by both poets. The role of the gods in the Odyssey precludes the tragic conception of human life that is characteristic of the Iliad.
Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery
2017-10-25

In patients with drug-resistant focal epilepsy requiring surgery, hippocampal sclerosis was the most common histopathological diagnosis among adults, and focal cortical dysplasia was the most common diagnosis among children. Tumors were the second most common lesion in both groups. (Funded by the European Union and others.).
A Subpopulation of Stromal Cells Controls Cancer Cell Homing to the Bone Marrow
2017-10-25

Abstract Breast and prostate cancer cells home to the bone marrow, where they presumably hijack the hematopoietic stem cell niche. We characterize here the elusive premetastatic niche by examining the role of mesenchymal stromal cells (MSC) in cancer cell homing. Decreasing the number of MSC pharmacologically enhanced cancer cell homing to the bone marrow in mice. In contrast, increasing the number of these MSCs by various interventions including G-CSF administration diminished cancer cell homing. The MSC subpopulation that correlated best with cancer cells expressed stem, endothelial, and pericytic cell markers, suggesting these cells represent an undifferentiated component of the niche with vascular commitment. In humans, a MSC subpopulation carrying markers for endothelial and pericytic cells was lower in the presence of cytokeratin+ cells in bone marrow. Taken together, our data show that a subpopulation of MSC with both endothelial and pericytic cell surface markers suppresses the homing of cancer cells to the bone marrow. Similar to the presence of cytokeratin+ cells in the bone marrow, this MSC subpopulation could prove useful in determining the risk of metastatic disease, and its manipulation might offer a new possibility for diminishing bone metastasis formation. Significance: These findings establish an inverse relationship between a subpopulation of mesenchymal stromal cells and cancer cells in the bone marrow. Cancer Res; 78(1); 129–42. ©2017 AACR.
Click Chemistry: Novel Applications in Cell Biology and Drug Discovery
2017-10-25

A safe BET: Apart from target engagement, subcellular location and tissue distribution are critical parameters in drug discovery. A novel, generalizable approach has been reported that involves exploiting click chemistry to elucidate these parameters. By using clickable analogues of known Bromodomain and extraterminal domain (BET) inhibitors, various labels were introduced in situ and utilized to determine the biological fate of these probes.