Miracle-dz/UniFAR-FTUs huggingface dataset:
Progesterone and allopregnanolone enhance the miniature synaptic release of glycine in the rat hypoglossal nucleus

It is well known that progesterone is synthesised and metabolised within the nervous system, and that one of its metabolites, allopregnanolone, potentiates the activity of GABA receptor anionic channels and modulates GABAergic neurotransmission. Progesterone is now under clinical trial for its neuroprotective properties, but its possible effects on neurotransmission have not yet been fully explored. The present study investigated acute effects of progesterone on the other major type of synaptic inhibition, glycinergic neurotransmission. Spontaneous glycinergic miniature currents were recorded in hypoglossal motoneurons, using the whole‐cell patch‐clamp technique in rat brainstem slices. A 20‐min superfusion with progesterone (1 μm) triggered an increase in the frequency of glycinergic miniatures, whereas no effect of progesterone was observed after block with finasteride (5 μm) of 5α ‐reductase, the first enzymatic step leading from progesterone to allopregnanolone. The effect of progesterone could be mimicked by superfusion with allopregnanolone (0.3 μm), whereas no effect was induced by epiallopregnanolone. Thus, progesterone can increase the synaptic miniature release of glycine and this effect appears to be indirect, resulting from its metabolism into 5α‐reduced derivatives, in particular into allopregnanolone. A low concentration of an exogenous GABAA agonist can also increase the frequency of inhibitory miniature currents in hypoglossal motoneurons. Thus, the effects of progesterone and allopregnanolone on glycine release can be at least partly explained by the potentiation of the activity of depolarizing presynaptic GABA receptor channels. The increase in the tonic synaptic release of a major inhibitory neurotransmitter should reduce the excitability of the neurons and contribute to their protection against excitotoxicity.
Monte-Carlo model development for evaluation of current clinical target volume definition for heterogeneous and hypoxic glioblastoma

Clinical target volume (CTV) determination may be complex and subjective. In this work a microscopic-scale tumour model was developed to evaluate current CTV practices in glioblastoma multiforme (GBM) external radiotherapy. Previously, a Geant4 cell-based dosimetry model was developed to calculate the dose deposited in individual GBM cells. Microscopic extension probability (MEP) models were then developed using Matlab-2012a. The results of the cell-based dosimetry model and MEP models were combined to calculate survival fractions (SF) for CTV margins of 2.0 and 2.5 cm. In the current work, oxygenation and heterogeneous radiosensitivity profiles were incorporated into the GBM model. The genetic heterogeneity was modelled using a range of α/β values (linear-quadratic model parameters) associated with different GBM cell lines. These values were distributed among the cells randomly, taken from a Gaussian-weighted sample of α/β values. Cellular oxygen pressure was distributed randomly taken from a sample weighted to profiles obtained from literature. Three types of GBM models were analysed: homogeneous-normoxic, heterogeneous-normoxic, and heterogeneous-hypoxic. The SF in different regions of the tumour model and the effect of the CTV margin extension from 2.0–2.5 cm on SFs were investigated for three MEP models. The SF within the beam was increased by up to three and two orders of magnitude following incorporation of heterogeneous radiosensitivities and hypoxia, respectively, in the GBM model. However, the total SF was shown to be overdominated by the presence of tumour cells in the penumbra region and to a lesser extent by genetic heterogeneity and hypoxia. CTV extension by 0.5 cm reduced the SF by a maximum of 78.6 ± 3.3%, 78.5 ± 3.3%, and 77.7 ± 3.1% for homogeneous and heterogeneous-normoxic, and heterogeneous hypoxic GBMs, respectively. Monte-Carlo model was developed to quantitatively evaluate SF for genetically heterogeneous and hypoxic GBM with two CTV margins and three MEP distributions. The results suggest that photon therapy may not provide cure for hypoxic and genetically heterogeneous GBM. However, the extension of the CTV margin by 0.5 cm could be beneficial to delay the recurrence time for this tumour type due to significant increase in tumour cell irradiation.
CT Screening for lung cancer: diagnoses resulting from the New York Early Lung Cancer Action Project.

PURPOSE To evaluate prospectively the diagnostic performance of the New York Early Lung Cancer Action Project (NY-ELCAP) regimen in the diagnosis of early lung cancer at baseline and annual repeat computed tomographic (CT) screenings. MATERIALS AND METHODS Informed consent and institutional review board approval were obtained for this HIPAA-compliant study of baseline and annual repeat low-dose CT screening performed with a common regimen in asymptomatic individuals at 12 institutions in New York State. All 6295 participants were aged 60 years or older, had smoked for at least 10 pack-years, had no prior cancer, had not undergone chest CT in the previous 3 years, and were medically fit to undergo thoracic surgery. Median age was 66 years, and median smoking history was 40 pack-years. The proportion (and 95% exact confidence intervals [CIs]) of subjects with a positive result, as determined by using nodule size; the diagnoses of lung cancer resulting from subsequent work-up; and the distribution by cancer stage and cell type were determined. When relevant, 95% CIs for the proportions were calculated. RESULTS Initial CT imaging led to recommendations for further work-up in 14.4% (95% CI: 13.5%, 15.3%) of the 6295 baseline screenings and 6.0% (95% CI: 5.1%, 6.6%) of the 6014 annual repeat screenings. Of 101 patients in whom the diagnosis of lung cancer resulted from baseline screening and three in whom a diagnosis of lung cancer was prompted by symptoms prior to the first scheduled repeat screening, 95 (91.3%) had no clinical evidence of metastases. Of the 20 patients in whom the diagnosis of lung cancer resulted from annual repeat screening, 17 (85%) showed no evidence of metastases. Of the 134 recommended biopsies, 125 (93.3%) resulted in diagnosis of lung cancer or another malignancy, while none of the 24 biopsies performed outside of the recommendation of the regimen resulted in diagnosis of lung cancer. CONCLUSION The NY-ELCAP regimen of screening revealed that annual CT screening for lung cancer resulted in identification of a high proportion of patients with early-stage disease.
Treatment of hepatitis C virus recurrence after transplantation with sofosbuvir/ledipasvir: The role of ribavirin

Hepatitis C virus (HCV) recurrence after liver transplantation (LT) used to be a serious problem in the era of interferon‐based treatment. Since the introduction of modern directly acting antivirals, treatment has become easier and shorter. According to published data, in the natural course of hepatitis C infection the duration of antiviral treatment with sofosbuvir (SOF) and ledipasvir (LDV) may be shortened to 12 instead of 24 weeks, using ribavirin (RBV) in addition. Furthermore, the question of whether or not RBV is really necessary, in a 12‐week SOF/LDV treatment in the post‐transplant setting, is still unanswered.
Analysis of Factors Triggering Distress Migration in Bundelkhand Region of Central In

Bundelkhand region of central India, a major drought affected area of the country is associated to high level of rural to urban migration. The present study was conducted to analyze the socio-economic characteristics of the migrants and to examine the key factors triggering migration decision of agriculture practicing households. The region was facing drought for the fourth consecutive period which had left the population, mainly dependent on agricultural income, out of option than migration. The analysis of socio-economic profile of migrants showed that majority of the migrants were between the age group of 20-39 (70.1%) and the education level was secondary (54.8%). The population of female migrants was comparatively low, as many of them followed their family to the migrating place after marriage. Majority of the migrants (81.73%) were engaged in unskilled manual labour activities like construction works in destination cities. The various factors identified triggering migration decision were associated to livelihood security, climatic, agricultural, institutional and socio-cultural factors.
Catenins, Wnt signaling and cancer.

Recent studies indicate that plakoglobin may have a similar function to that of beta-catenin within the Wnt signaling pathway. beta-catenin is known to be an oncogene in many forms of human cancer, following acquisition of stabilizing mutations in amino terminal sequences. Kolligs(1) and coworkers show, however, that unlike beta-catenin, plakoglobin induces neoplastic transformation of rat epithelial cells in the absence of such stabilizing mutations. Cellular transformation by plakoglobin also appears to be distinct from that of beta-catenin in that it requires activation of the proto-oncogene c-myc. Surprisingly, c-myc is activated more efficiently by plakoglobin than beta-catenin, despite its previous identification as a target of Tcf/beta-catenin. (2) In contrast, a synthetic Tcf reporter gene is activated to a much greater extent by beta-catenin than plakoglobin. Plakoglobin and beta-catenin may therefore have different roles in Wnt signaling and cancer, which reflect their differential effects on target gene activity.
Financial instability and the macroeconomy: measurement, interdependency and the role of monetary policy

The recent crisis brought to the fore the issue of systemic risk, an issue still not sufficiently well understood. The Great Recession put this deficit to the spotlight such that researchers and policy authorities all around the world stepped up efforts to increase our theoretical and empirical understanding of how systemic risk evolves, how it affects the real economy (and vice versa), and which policy tools may address systemic risk both ex ante (crisis prevention) and ex post (crisis management). The three papers of this dissertation shall help closing some of the related knowledge gaps. Chapter 2 tackles systemic risk from a measurement perspective. It presents a financial stress index called the Composite Indicator of Systemic Stress, CISS, with systemic stress understood as materialised systemic risk. Its distinctive design highlights the systemic dimension of financial stress by applying time-varying correlation weights to the aggregation of individual indicators into the composite indicator. I furthermore estimate a threshold VAR model to identify a level of financial stress at which it depresses the real economy and thus becomes fully systemic. Chapter 3 puts the CISS into a broader macro-model perspective to investigate the interrelationships between financial stress, the real economy and monetary policy. Standard and non-standard monetary policy is measured by a short-term interest rate and the growth rate of the ECB balance sheet, respectively. The CISS turns out to be a major and robust driver behind the dynamics of almost all model variables. Chapter 4 adopts a similar VAR setup but allows for independent regime switches in coefficients and error variances, respectively. The CISS impacts particularly strongly on economic activity in the systemic crisis regime that combines the highest shock variances with a stronger transmission of financial shocks to the real economy.
Ultrahigh Porosity in Metal-Organic Frameworks

Network Approaches to Highly Porous Materials Metal-organic frameworks (MOFs), in which inorganic centers are bridged by organic linkers, can achieve very high porosity for gas absorption. However, as the materials develop larger void spaces, there is also more room for growing interpenetrating networks—filling the open spaces not with gas molecules but with more MOFs. Furukawa et al. (p. 424, published online 1 July) describe the synthesis of a MOF in which zinc centers are bridged with long, highly conjugated organic linkers, but in which the overall symmetry of the networks created prevents formation of interpenetrating networks. Extremely high surface areas and storage capacities for hydrogen, carbon dioxide, and methane were observed. The large surface areas of these materials would correspond to that of dispersed nanocubes just 3 to 6 nanometers wide. Crystalline solids with extended non-interpenetrating three-dimensional crystal structures were synthesized that support well-defined pores with internal diameters of up to 48 angstroms. The Zn4O(CO2)6 unit was joined with either one or two kinds of organic link, 4,4′,4″-[benzene-1,3,5-triyl-tris(ethyne-2,1-diyl)]tribenzoate (BTE), 4,4′,44″-[benzene-1,3,5-triyl-tris(benzene-4,1-diyl)]tribenzoate (BBC), 4,4′,44″-benzene-1,3,5-triyl-tribenzoate (BTB)/2,6-naphthalenedicarboxylate (NDC), and BTE/biphenyl-4,4′-dicarboxylate (BPDC), to give four metal-organic frameworks (MOFs), MOF-180, -200, -205, and -210, respectively. Members of this series of MOFs show exceptional porosities and gas (hydrogen, methane, and carbon dioxide) uptake capacities. For example, MOF-210 has Brunauer-Emmett-Teller and Langmuir surface areas of 6240 and 10,400 square meters per gram, respectively, and a total carbon dioxide storage capacity of 2870 milligrams per gram. The volume-specific internal surface area of MOF-210 (2060 square meters per cubic centimeter) is equivalent to the outer surface of nanoparticles (3-nanometer cubes) and near the ultimate adsorption limit for solid materials.
Genome-Wide Analyses on Loss of Heterozygosity in Head and Neck Squamous Cell Carcinomas

Head and neck squamous cell carcinoma (HNSCC) is a frequent malignancy with a poor survival rate. Identifying the tumor suppressor gene (TSG) loci by genomic studies is an important step to uncover the molecular mechanisms involved in HNSCC pathogenesis. We therefore performed comprehensive analyses on loss of heterozygosity (LOH) using a genome-wide panel of 191 microsatellite markers in 22 HNSCC samples. We found 53 markers with significantly high LOH (>30%) on 21 chromosomal arms; the highest values of those were observed on 3p, 9p, 13q, 15q, and 17p, corresponding to D3S2432 (67%), D9S921-D9S925 (67%) and GATA62F03 (86%), D13S1493 (60%), D15S211 (62%), and D17S1353 (88%), respectively. Fifteen hot spots of LOH were defined in 13 chromosomal arms: 2q22-23, 4p15.2, 4q24-25, 5q31, 8p23, 9p23-24, 9q31.3, 9q34.2, 10q21, 11q21-22.3, 14q11-13, 14q22.3, 17p13, 18q11, and 19q12 as loci reported previously in HNSCCs. Furthermore, we identified five novel hot spots of LOH on three chromosomal arms in HNSCC at 2q33 (D2S1384), 2q37 (D2S125), 8q12-13 (D8S1136), 8q24 (D8S1128), and 15q21 (D15S211). In conclusion, our comprehensive allelotype analyses have unveiled and confirmed a total of 20 possible TSG loci that could be involved in the development of HNSCC. These results provide useful clues for identification of putative TSGs involved in HNSCC by fine mapping of the suspected regions and subsequent analysis for functional genes.
Clinical and nonclinical predictors of the cost of coronary bypass surgery: potential effects on health care delivery and reimbursement.

BACKGROUND Health care providers are being pressured to lower the cost of care. Because of the inherent cost variability in providing health care, as reimbursement falls, providers may not be able to cover all costs. Understanding the underlying causes of this wide variability is important in determining optimum pricing. Prior studies on the cost of coronary bypass surgery have determined which clinical variables affect cost, yet none have studied nonclinical variables that can influence the cost of coronary bypass surgery. METHODS In a cohort of 882 consecutive patients with treatment classified in the diagnosis-related group (DRG) 107, we examined 55 clinical and nonclinical variables obtained from our prospective database. For explanatory purposes, we used multiple linear regression to determine the variables that were predictive of direct cost and the magnitude of contribution of each variable. RESULTS Eleven clinical and 4 nonclinical variables were predictive of direct cost. Nonclinical variables added significant cost-predictive information beyond that of the traditional clinical variables, and their magnitude of effect was equal to or greater than the traditional clinical variables. CONCLUSIONS Nonclinical patient characteristics add important predictive information concerning the cost of coronary bypass surgery to traditional clinical variables. These data will be important in developing contracting strategies, in the evaluation of individual physician performance, and in modifying national methods of reimbursement.
Phenomenology, genetics, and CNS network abnormalities in laryngeal dystonia: A 30‐year experience

Laryngeal dystonia (LD) is a functionally specific disorder of the afferent–efferent motor coordination system producing action‐induced muscle contraction with a varied phenomenology. This report of long‐term studies aims to review and better define the phenomenology and central nervous system abnormalities of this disorder and improve diagnosis and treatment.
Construction of an anatomically accurate geometric model of the forearm and hand musculo-skeletal system

An anatomically accurate model of the forearm and hand musculo-skeletal system using finite element geometries is presented. Anatomical data has been digitized from the male Visible Human dataset to create meshes which accurately approximate each bone and muscle volume. Each muscle's anatomical structure has been accounted for via the topology of the initial mesh generation. Cylindrical muscles have been modeled using collapsed bicubic-linear elements, while more complex muscle topologies have required tricubic elements. Bifurcating muscle meshes combine 1D elements for the tendons and 3D elements for the adjoining muscle. The fitting process of each mesh to its dataset was carried out using a least-squares algorithm, to minimize the distances between the mesh and the data points. Sobelov smoothing constraints have been implemented to account for sparse and scattered data. The fitted forearm muscles contain 1085 nodes, 797 elements, and an average RMS error of 1.8207 mm; while the fitted hand muscles use 509 nodes, 274 elements, and an average RMS error of 1.1136 mm. Applications of the model as a framework for visualization of anatomical data relevant for biomedical and medical education are discussed. With mesh customization and further functional modeling this provides the basis for surgical training and functional development.
Calsarcin-3, a Novel Skeletal Muscle-specific Member of the Calsarcin Family, Interacts with Multiple Z-disc Proteins*

The Z-disc is a highly specialized multiprotein complex of striated muscles that serves as the interface of the sarcomere and the cytoskeleton. In addition to its role in muscle contraction, its juxtaposition to the plasma membrane suggests additional functions of the Z-disc in sensing and transmitting external and internal signals. Recently, we described two novel striated muscle-specific proteins, calsarcin-1 and calsarcin-2, that bind α-actinin on the Z-disc and serve as intracellular binding proteins for calcineurin, a calcium/calmodulin-dependent phosphatase shown to be integral in cardiac hypertrophy as well as skeletal muscle differentiation and fiber-type specification. Here, we describe an additional member of the calsarcin family, calsarcin-3, which is expressed specifically in skeletal muscle and is enriched in fast-twitch muscle fibers. Like calsarcin-1 and calsarcin-2, calsarcin-3 interacts with calcineurin, and the Z-disc proteins α-actinin, γ-filamin, and telethonin. In addition, we show that calsarcins interact with the PDZ-LIM domain protein ZASP/Cypher/Oracle, which also localizes to the Z-disc. Calsarcins represent a novel family of sarcomeric proteins that serve as focal points for the interactions of an array of proteins involved in Z-disc structure and signal transduction in striated muscle.
TGF-beta expression in renal transplant biopsies: a comparative study between cyclosporin-A and tacrolimus.

BACKGROUND Chronic rejection is a major cause of graft dysfunction after kidney transplantation. This fibroproliferative disease may be promoted by overproduction of transforming growth factor beta (TGF-beta). Previous studies have suggested that CsA might increase production of this growth factor. The current study was designed to measure the expression of TGF-beta(b) in renal transplant biopsy specimens from patients undergoing immunosuppressive therapy with either CsA or tacrolimus (FK506). METHOD Paraffin-embedded renal biopsy specimens were sectioned, dewaxed, and incubated with primary antibody against TGF-beta(b)1 latency-associated protein and active TGF-beta(b1). After washing, the sections were treated with secondary antibody conjugated with FITC. In each case, the sections were assessed by semi-quantitative scanning laser confocal microscopic method. RESULTS There was no significant difference in latent TGF-beta(b) expression between biopsy specimens from patients receiving CsA and patients receiving FK506. However, biopsy specimens from patients receiving CsA expressed significantly more active TGF-beta(b1) than biopsy specimens from patients receiving FK506 (P<0.0001, Mann-Whitney test). DISCUSSION The increased level of active TGF-beta1 expression in renal biopsy specimens of patients receiving CsA may indicate a mechanism of chronic rejection. However, these biopsies were performed to assess deranged renal function; therefore, the specimens may reflect events rather than differences in medication.
Power Quality Improvement from Grid Connected Renewable Energy Sources At Distribution Level Using Fuzzy Logic Controller.

Harmonic pollution of the power supply system has risen significantly in recent years due primarily to an increase of non-linear loads connected to the utility through residential, commercial and industrial customers. Power supply voltages become distorted due to the high level of undesired harmonic current drawn from the utility. Additionally, drops in fundamental voltage are caused by the interaction between the reactive current and network impedances. Renewable energy resources (RES) are being increasingly connected in distribution systems utilizing power electronic converters. This paper presents a novel control strategy for achieving maximum benefits from these grid-interfacing inverters using the closed loop fuzzy logic control, when installed in 3-phase 4-wire distribution systems. The inverter is controlled to perform as a multi-function device by incorporating active power filter functionality. The inverter can thus be utilized as: power converter to inject power generated from RES to the grid, and 1) shunt APF to compensate current unbalance, load current harmonics, load reactive power demand and load neutral current. All of these functions may be accomplished either individually or simultaneously. This new control concept is demonstrated with extensive MATLAB/Simulink . Finally the proposed scheme is implemented using conventional DC link controller and intelligence controller. Index Terms: Point of Common Coupling (PCC), power quality, Photo Voltaic (PV) System, Fuzzy Logic Controller (FLC).