Miracle-dz/UniFAR-FTUs huggingface dataset:
The 220-kDa Rim Protein of Retinal Rod Outer Segments Is a Member of the ABC Transporter Superfamily*

Outer segments of mammalian rod photoreceptor cells contain an abundantly expressed membrane protein that migrates with an apparent molecular mass of 220 kDa by SDS-gel electrophoresis. We have purified the bovine protein by immunoaffinity chromatography, determined its primary structure by cDNA cloning and direct peptide sequence analysis, and mapped its distribution in photoreceptors by immunocytochemical and biochemical methods. The full-length cDNA encodes a 2280-amino acid protein (calculated molecular mass of 257 kDa) consisting of two structurally related, tandem arranged halves. Each half consists of a hydrophobic domain containing six putative transmembrane segments followed by an ATP-binding cassette. A data base homology search showed that the rod outer segment 220-kDa protein is 40-50% identical in amino acid sequence to the ABC1 and ABC2 proteins cloned from a mouse macrophage cell line. Photoaffinity labeling with 8-azido-ATP and nucleotide inhibition studies confirmed that both ATP and GTP bind to this protein with similar affinities. Concanavalin A labeling and endoglycosidase H digestion indicated that the rod outer segment protein contains at least one carbohydrate chain. Immunocytochemical and biochemical studies have revealed that the 220-kDa glycoprotein is distributed along the rim region and incisures of rod outer segment disc membranes. From these studies we conclude that the 220-kDa glycoprotein of bovine rod outer segment disc membranes or Rim ABC protein is a new member of the superfamily of ABC transporters and is the mammalian homolog of the frog photoreceptor rim protein.
Socioeconomic and geographical variation in general practitioner consultations for allergic rhinitis in England, 2003–2014: an observational study

Objective Allergic rhinitis (AR) is a global health problem, potentially impacting individuals’ sleep, work and social life. We aimed to use a surveillance network of general practitioners (GPs) to describe the epidemiology of AR consultations in England. Setting A large GP surveillance network covering approximately 53% of the English population. Methods GP consultations for AR across England between 30 December 2002 and 31 December 2014 were analysed. Using more granular data available between 2 April 2012 and 31 December 2014 rates and rate ratios (RR) of AR were further analysed in different age groups, gender, rural-urban classification and index of multiple deprivation score quintile of location of GP. Results The mean weekly rate for AR consultations was 19.8 consultations per 100 000 GP registered patients (range 1.13–207), with a regular peak occurring during June (weeks 24–26), and a smaller peak during April. Between 1 April 2012 and 31 December 2014, the highest mean daily rates of consultations per 1 00 000 were: in age group 5–14 years (rate=8.02, RR 6.65, 95% CI 6.38 to 6.93); females (rate=4.57, RR 1.12 95% CI 1.12 to 1.13); persons registered at a GP in the most socioeconomically deprived quintile local authority (rate=5.69, RR 1.48, 95% CI 1.47 to 1.49) or in an urban area with major conurbation (rate=5.91, RR 1.78, 95% CI 1.69 to 1.87). Conclusions AR rates were higher in those aged 5–14 years, females and in urban and socioeconomically deprived areas. This needs to be viewed in the context of this study’s limitations but should be considered in health promotion and service planning.
The Range Alignment Algorithm for High-Resolution Range Profile Based on Image Segmentation

Aiming at the problem of the difficulty in the range alignment of HRRP because of more than one target in the window of radar image, this paper propose a alignment method for multiple targets in the target group by using an image segmentation method. First, we accumulate the HRRP of the target, and get the HRRP process diagram. By calculating the correlation coefficient between each frame of HRRP and the reference HRRP, the unaligned HRRP sequence is aligned roughly in frequency domain. After rough alignment, the image segmentation method is used to segment the range image of each target. In the end, the envelope alignment for the HRRP of each target is finished using FFT cross-correlation method. The algorithm is simple and fast, and can achieve a better alignment effect on multi object tracking. The effectiveness of the proposed method is verified by the analysis of the simulation data.
Reduction of neonatal mortality after multiple doses of bovine surfactant in low birth weight neonates with respiratory distress syndrome.

To determine if outcomes of low birth weight neonates with respiratory distress syndrome can be improved by the administration of multiple doses of bovine surfactant, we conducted two identical multicenter, controlled trials, and the results were combined for analysis. Seven hundred and ninety-eight neonates weighing 600 to 1750 g at birth who had developed respiratory distress syndrome within 6 hours of birth were assigned randomly to receive either 100 mg of phospholipid/kg of Survanta, a modified bovine surfactant (n = 402), or a sham dosing procedure (n = 396). Neonates whose respiratory distress persisted could be given up to three more doses, with all doses to be given in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Fewer Survanta-treated neonates died of any cause (18.4% vs 27.3%, P = .002), died of respiratory distress syndrome (9.0% vs 20.3%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (51.2% vs 64.6%, P less than .001). Neonates who received Survanta also had greater improvement in their oxygenation and ventilatory status from baseline to 72 hours than did control neonates. Survanta-treated neonates were at lowered risk for developing pulmonary interstitial emphysema (18.6% vs 39.3%, P less than .001) and other pulmonary air leaks (11.5% vs 25.9%, P less than .001). We conclude that multiple doses of Survanta given after diagnosis of respiratory distress syndrome reduce mortality and morbidity.
Transitions in Early Embryonic Atrioventricular Valvular Function Correspond With Changes in Cushion Biomechanics That Are Predictable by Tissue Composition

Endocardial cushions are critical to maintain unidirectional blood flow under constantly increasing hemodynamic forces, but the interrelationship between endocardial cushion structure and the mechanics of atrioventricular junction function is poorly understood. Atrioventricular (AV) canal motions and blood velocities of embryonic chicks at Hamburger and Hamilton (HH) stages 17, 21, and 25 were quantified using ultrasonography. Similar to the embryonic zebrafish heart, the HH17 AV segment functions like a suction pump, with the cushions expanding in a wave during peak myocardial contraction and becoming undetectable during the relaxation phase. By HH25, the AV canal contributes almost nothing to the piston-like propulsion of blood, but the cushions function as stoppers apposing blood flow with near constant thickness. Using a custom built mesomechanical testing system, we quantified the nonlinear pseudoelastic biomechanics of developing AV cushions, and found that both AV cushions increased in effective modulus between HH17 and HH25. Enzymatic digestion of major structural constituent collagens or glycosaminoglycans resulted in distinctly different stress-strain curves suggestive of their individual contributions. Mixture theory using histologically determined volume fractions of cells, collagen, and glycosaminoglycans showed good prediction of cushion material properties regardless of stage and cushion position. These results have important implications in valvular development, as biomechanics may play a larger role in stimulating valvulogenic events than previously thought.
X-ray microscopy.

The subject of X-ray microscopy (high-resolution X-ray imaging of general nonperiodic structures), an area in which much progress has been made in recent years, is reviewed. The main techniques are briefly described. Achievable performance levels, which for many years were highly speculative, can now be understood with fair accuracy in terms of basic X-ray and specimen properties, and techniques have progressed to the point where actual results are nearing those levels. In terms of specimen size and imaging resolution, X-ray microscopies lie between electron and light microscopy, and are thus suited to imaging extremely large and complex structures; in addition, they demand little or no specimen preparation, and can be used to observe local composition and chemical state as well as structure. Thus X-rays, which have played the leading role in imaging crystallizable materials, may also prove to be highly valuable in the imaging of very large non-crystalline structures. Throughout the treatment, attention is paid to the relationships connecting the subject with X-ray crystallography.
Submitted to the Annals of Probability THE KLS ISOPERIMETRIC CONJECTURE FOR GENERALIZED ORLICZ BALLS By

What is the optimal way to cut a convex bounded domain K in Euclidean space (R, |·|) into two halves of equal volume, so that the interface between the two halves has least surface area? A conjecture of Kannan, Lovász and Simonovits asserts that, if one does not mind gaining a universal numerical factor (independent of n) in the surface area, one might as well dissect K using a hyperplane. This conjectured essential equivalence between the former non-linear isoperimetric inequality and its latter linear relaxation, has been shown over the last two decades to be of fundamental importance to the understanding of volume-concentration and spectral properties of convex domains. In this work, we address the conjecture for the subclass of generalized Orlicz balls
G-Protein-Coupled Receptor 30 Mediates Rapid Neuroprotective Effects of Estrogen via Depression of NR2B-Containing NMDA Receptors

17-β-Estradiol (E2) is a steroid hormone involved in neuroprotection against excitotoxicity and other forms of brain injury. Through genomic and nongenomic mechanisms, E2 modulates neuronal excitability and signal transmission by regulating NMDA and non-NMDA receptors. However, the mechanisms and identity of the receptors involved remain unclear, even though studies have suggested that estrogen G-protein-coupled receptor 30 (GPR30) is linked to protection against ischemic injury. In the culture cortical neurons, treatment with E2 and the GPR30 agonist G1 for 45 min attenuated the excitotoxicity induced by NMDA exposure. The acute neuroprotection mediated by GPR30 is dependent on G-protein-coupled signals and ERK1/2 activation, but independent on transcription or translation. Knockdown of GPR30 using short hairpin RNAs (shRNAs) significantly reduced the E2-induced rapid neuroprotection. Patch-clamp recordings revealed that GPR30 activation depressed exogenous NMDA-elicited currents. Short-term GPR30 activation did not affect the expression of either NR2A- or NR2B-containing NMDARs; however, it depressed NR2B subunit phosphorylation at Ser-1303 by inhibiting the dephosphorylation of death-associated protein kinase 1 (DAPK1). DAPK1 knockdown using shRNAs significantly blocked NR2B subunit phosphorylation at Ser-1303 and abolished the GPR30-mediated depression of exogenous NMDA-elicited currents. Lateral ventricle injection of the GPR30 agonist G1 (0.2 μg) provided significant neuroprotection in the ovariectomized female mice subjected to middle cerebral artery occlusion. These findings provide direct evidence that fast neuroprotection by estradiol is partially mediated by GPR30 and the subsequent downregulation of NR2B-containing NMDARs. The modulation of DAPK1 activity by GPR30 may be an important mediator of estradiol-dependent neuroprotection.
A systematic review of the worldwide prevalence and incidence of Parkinson's disease.

BACKGROUND A number of epidemiologic studies of Parkinson 's disease (PD) have been conducted worldwide over the years. Although every study reported the rise in prevalence and incidence rate of PD with the increasing age, the overall estimates were different across countries. The variation in reported data may partly be contributed by case ascertainment, case finding method, data collection, and most importantly different population structures. OBJECTIVE Systematically review prevalence and incidence of PD and find the causes of variation in the results. MATERIAL AND METHOD A literature search was conducted on Medline and EMBASE for studies worldwide investigating the prevalence and incidence of PD and included all adults, English and publication between 1965 and January 2010. The primary search of both databases yielded 5,330 results. After screening topics and abstracts, 168 relevant abstracts were tagged and saved for more thorough perusal. Ultimately, 40 papers were selected for review after applying the pre-specified inclusion criteria RESULTS The worldwide prevalence of PD varies widely. One reason for the variation in prevalence estimates could be due to the differences in survival across countries. The use of epidemiological studies using medical records could be another reason for the variation in disease frequency. CONCLUSION PD is common in the elderly. A number of descriptive epidemiologic studies have been conducted worldwide. Comparing the incidence and prevalence of Parkinson's disease is difficult.
Viral gene inhibition of class I major histocompatibility antigen expression: not a general mechanism governing the tumorigenicity of adenovirus type 2-, adenovirus type 12-, and simian virus 40-transformed Syrian hamster cells

The association between the level of class I major histocompatibility (MHC) antigen expression and the tumorigenic phenotype was determined for cells from a series of 15 lines of adenovirus type 2 (Ad2)-, Ad12-, and simian virus 40 (SV40)-transformed hamster cells and 16 lines of cells established from hamster tumors induced by SV40 mutants. These cells range from nontumorigenic to highly tumorigenic in both syngeneic and allogeneic adult hamsters. The Ad2-transformed cells--cells that were nontumorigenic in syngeneic adult hamsters--expressed either high levels or low levels of class I MHC antigens. The SV40-transformed cells--cells transformed in vitro that produced tumors with equal efficiency in both syngeneic and allogeneic adult hamsters--or cells derived from SV40-induced tumors expressed very high levels of class I MHC antigens. The Ad12-transformed cells uniformly expressed low levels of class I MHC antigens; these cells produced tumors 200- to 1,000-fold less efficiently in allogeneic adult hamsters than in syngeneic adult hamsters and produced tumors with about the same efficiency in immunoimmature newborns and immunocompetent syngeneic adult hamsters. We conclude that the expression of either high levels or low levels of class I MHC antigens is, at most, a minor factor in the differences observed among these adenovirus- and SV40-transformed cells in their tumor-inducing capacity in naive, immunocompetent hamsters.
DIFFERENT BASIC DOSIMETRIC QUANTITIES FOR THE CHARACTERIZATION OF EXPOSURE TO LOW-FREQUENCY ELECTRIC AND MAGNETIC FIELDS AND THE IMPLICATION FOR PRACTICAL EXPOSURE CONDITIONS AND GUIDELINES

In this paper, the different quantities for characterizing human exposure at extremely low frequencies (ELF) up to 100 kHz are described. It is explained how the incident field is disturbed by the human body and how the in-situ fields and current densities are created in the body. Incident electric and magnetic fields are treated separately. Incident field characteristics such as homogeneity, time dependence, and polarization and body characteristics such as dimensions, shape, and position will influence the induced quantities. The use of in situ fields or of induced current densities to set the basic restrictions is discussed. The methods for deriving the reference levels from the basic restrictions in the international standards such as ICNIRP and IEEE guidelines are mentioned. Elliptical human models have been typically used in the past. In recent years, high-resolution anatomical models have become available. In this case maximum induced field levels or current densities can be determined for each organ. The validity of using elliptical or high-resolution anatomical models to derive reference levels is discussed. Special attention is paid to non-uniform (such as domestic exposure) or partial exposure of the human body.
Mitochondrial respiratory chain dysfunction in muscle from patients with amyotrophic lateral sclerosis.

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a major cause of neurological disability and its pathogenesis remains elusive despite a multitude of studies. Although defects of the mitochondrial respiratory chain have been described in several ALS patients, their pathogenic significance is unclear. OBJECTIVE To review systematically the muscle biopsy specimens from patients with typical sporadic ALS to search for possible mitochondrial oxidative impairment. DESIGN Retrospective histochemical, biochemical, and molecular studies of muscle specimens. SETTING Tertiary care university. Subjects Fifty patients with typical sporadic ALS (mean age, 55 years). Main Outcome Measure Number of patients showing a clear muscle mitochondrial dysfunction assessed through histochemical and biochemical muscle analysis. RESULTS Histochemical data showed cytochrome c oxidase (COX)-negative fibers in 46% patients. Based on COX histochemical activity, patients fell into 4 groups: 27 had normal COX activity; and 8 had mild (2-4 COX-negative fibers of 100 fibers), 8 had moderate (5-10 COX-negative fibers of 100), and 7 had severe (>10 COX-negative fibers of 100) COX deficiency. Spectrophotometric measurement of respiratory chain activities showed that 3 patients with severe histochemical COX deficiency also showed combined enzyme defects. In 1 patient, COX deficiency worsened in a second biopsy taken 9 months after the first. Among the patients with severe COX deficiency, one had a new mutation in the SOD1 gene, another a mutation in the TARDBP gene, and a third patient with biochemically confirmed COX deficiency had multiple mitochondrial DNA deletions detectable by Southern blot analysis. CONCLUSIONS Our data confirm that the histochemical finding of COX-negative fibers is common in skeletal muscle from patients with sporadic ALS. We did not find a correlation between severity of the oxidative defect and age of the patients or duration of the disease. However, the only patient who underwent a second muscle biopsy did show a correlation between severity of symptoms and worsening of the respiratory chain defect. In 7 patients, the oxidative defect was severe enough to support the hypothesis that mitochondrial dysfunction must play a role in the pathogenesis of the disease.
Chemically Assisted Phytoextraction: A Review of Potential Soil Amendments for Increasing Plant Uptake of Heavy Metals

The contamination of soils by trace metals has been an unfortunate sideeffect of industrialization. Some of these contaminants can interfere with vulnerable enduses of soil, such as agriculture or nature, already at relatively low levels of contamination. Reversely, conventional civil–technical soil-remediation techniques are too expensive to remediate extended areas of moderately contaminated soil. Phytoextraction has been proposed as a more economic complementary approach to deal with this specific niche of soil contamination. However, phytoextraction has been shown to be a slow-working process due to the low amounts of metals that can be annually removed from the soil under normal agronomic conditions. Therefore, extensive research has been conducted on process optimization by means of chemically improving plant availability and the uptake of heavy metals. A wide range of potential amendments has been proposed in the literature, with considerable attention being spent on aminopolycarboxylic acids such as ethylenediaminetetraacetic acid (EDTA). However, these compounds have received increasing criticism due to their environmental persistence and associated risks for leaching. This review presents an overview of potential soil amendments that can be employed for enhancing metal uptake by phytoextraction crops, with a distinct focus on more degradable alternatives to persistent compounds such as EDTA.
Leptin promotes KATP channel trafficking by AMPK signaling in pancreatic β-cells

Leptin is a pivotal regulator of energy and glucose homeostasis, and defects in leptin signaling result in obesity and diabetes. The ATP-sensitive potassium (KATP) channels couple glucose metabolism to insulin secretion in pancreatic β-cells. In this study, we provide evidence that leptin modulates pancreatic β-cell functions by promoting KATP channel translocation to the plasma membrane via AMP-activated protein kinase (AMPK) signaling. KATP channels were localized mostly to intracellular compartments of pancreatic β-cells in the fed state and translocated to the plasma membrane in the fasted state. This process was defective in leptin-deficient ob/ob mice, but restored by leptin treatment. We discovered that the molecular mechanism of leptin-induced AMPK activation involves canonical transient receptor potential 4 and calcium/calmodulin-dependent protein kinase kinase β. AMPK activation was dependent on both leptin and glucose concentrations, so at optimal concentrations of leptin, AMPK was activated sufficiently to induce KATP channel trafficking and hyperpolarization of pancreatic β-cells in a physiological range of fasting glucose levels. There was a close correlation between phospho-AMPK levels and β-cell membrane potentials, suggesting that AMPK-dependent KATP channel trafficking is a key mechanism for regulating β-cell membrane potentials. Our results present a signaling pathway whereby leptin regulates glucose homeostasis by modulating β-cell excitability.
SRRM4 Expression and the Loss of REST Activity May Promote the Emergence of the Neuroendocrine Phenotype in Castration-Resistant Prostate Cancer

Purpose: The neuroendocrine phenotype is associated with the development of metastatic castration-resistant prostate cancer (CRPC). Our objective was to characterize the molecular features of the neuroendocrine phenotype in CRPC. Experimental Design: Expression of chromogranin A (CHGA), synaptophysin (SYP), androgen receptor (AR), and prostate-specific antigen (PSA) was analyzed by IHC in 155 CRPC metastases from 50 patients and in 24 LuCaP prostate cancer patient-derived xenografts (PDX). Seventy-one of 155 metastases and the 24 LuCaP xenograft lines were analyzed by whole-genome microarrays. REST splicing was verified by PCR. Results: Coexpression of CHGA and SYP in >30% of cells was observed in 22 of 155 metastases (9 patients); 11 of the 22 metastases were AR+/PSA+ (6 patients), 11/22 were AR–/PSA– (4 patients), and 4/24 LuCaP PDXs were AR−/PSA−. By IHC, of the 71 metastases analyzed by whole-genome microarrays, 5 metastases were CHGA+/SYP+/AR−, and 5 were CHGA+/SYP+/AR+. Only CHGA+/SYP+ metastases had a neuroendocrine transcript signature. The neuronal transcriptional regulator SRRM4 transcript was associated with the neuroendocrine signature in CHGA+/SYP+ metastases and all CHGA+/SYP+ LuCaP xenografts. In addition, expression of SRRM4 in LuCaP neuroendocrine xenografts correlated with a splice variant of REST that lacks the transcriptional repressor domain. Conclusions: (i) Metastatic neuroendocrine status can be heterogeneous in the same patient, (ii) the CRPC neuroendocrine molecular phenotype can be defined by CHGA+/SYP+ dual positivity, (iii) the neuroendocrine phenotype is not necessarily associated with the loss of AR activity, and (iv) the splicing of REST by SRRM4 could promote the neuroendocrine phenotype in CRPC. Clin Cancer Res; 21(20); 4698–708. ©2015 AACR.