Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional Regulation of Human 11β-Hydroxylase (hCYP11B1).

Steroid 11β-hydroxylase is a mitochondrial enzyme that catalyzes the conversion of deoxycortisol to cortisol. The gene encoding human 11β-hydroxylase (hCYP11B1) is expressed in the adrenal cortex under the control of circulating levels of ACTH. The current study was undertaken to define the cis-regulatory elements and transacting factors that regulate hCYP11B1 transcription. The hCYP11B1 5′-flanking DNA was studied using transient transfection of luciferase reporter constructs in NCI-H295R human adrenocortical cells. A cAMP analogue ((Bu)2cAMP) increased expression of a construct containing −1102 bp of hCYP11B1 5′-flanking DNA (pB1–1102). An element at position −71/−64 (TGACGTGA, previously termed Ad1) resembling a consensus cAMP response element (CRE) was required for maximal induction by cAMP. The Ad1 element bound several transcriptional factors in electrophoretic mobility shift assays, including CRE-binding protein, activating transcription factor-1 (ATF-1), and ATF-2, but only the ATF-2 complex migra.
Onychomatricoma: epidemiological and clinical findings in a large series of 30 cases

DEAR EDITOR, Onychomatricoma (OM), first described by Baran and Kint, is considered a rare benign tumour of the nail matrix with no more than 80 cases reported in the literature. The fingernails of white adult patients are most commonly affected. Reported clinical features include localized or diffuse thickening of the nail plate, transverse overcurvature, xanthonychia, multiple splinter haemorrhages, which often affect the proximal nail plate, and the presence of holes in the distal margin of the nail plate. When the proximal nail fold is reflected and the nail plate is avulsed, OM appears as a villous matrix tumour with projections that penetrate along the length of the thickened nail plate. Differential diagnoses include fibrokeratoma of the nail matrix, onychomycosis, squamous cell carcinoma, Bowen disease, viral warts, nail fibroma and longitudinal melanonychia. Diagnosis can be confirmed with nail clipping and imaging methods including ultrasound, magnetic resonance imaging and confocal microscopy. Histological examination reveals distinctive features that confirm the diagnosis. The aim of this study is to collect epidemiological and clinical data of a large series of patients with OM and to compare the findings with previous studies. The medical records and clinical pictures of 30 patients with OM, diagnosed from 2005 to 2012 by five dermatologists with a special interest in nail disorders, were retrospectively collected and evaluated for epidemiological data and clinical features. All lesions had been surgically removed and the diagnosis was confirmed by pathology. For each case, all clinical manifestations described in previous studies were scored as present or absent. Statistical analysis by simple percentage was performed for age, sex, skin photo type, digit and duration. The clinical features (Figs 1 and 2) and demographic data of the 30 patients identified in this study are summarized below. The relative and absolute frequencies of clinical features are reported in Table 1. Nineteen tumours (64%) occurred in the fingers (seven in the thumb, three in the second finger, seven in the third finger, two in the fifth finger). Overall, 12 tumours occurred in the dominant hand and 18 in the nondominant hand. Eleven tumours involved the toenails (37%); seven in the big toenail, two in the second toe and two in the third toe. The observed clinical features (Table 1) were as follows: increased nail thickness (25 of 30 cases; 83%), splinter haemorrhages (24 of 30 cases; 80%) with proximal splinters in four cases and both proximal and distal splinters in another four cases (information about splinter localization was not available for two cases), longitudinal xanthonychia (22 of 30
Periodic Solutions and KAM Tori in a Triaxial Potential

The existence and stability of periodic solutions for an autonomous Hamiltonian system in 1:1:1 resonance depending on two real parameters $\alpha$ and $\beta$ is established using reduction and averaging theories. The different types of periodic solutions as well as their bifurcation curves are characterized in terms of the parameters. The linear stability of each periodic solution, together with the determination of KAM 3-tori encasing some of the linearly stable periodic solutions, is proved.
Characterization of a Low Affinity Binding Protein for Growth Hormone in Rat Serum1.

GH forms a high Mr complex in rat serum distinct from that with GH-binding protein (GHBP). The present study investigates the nature of this complex. When subjected to AcA44 filtration chromatography, 125I-labeled human GH (hGH) in rat serum eluted in four peaks. Peak 1 eluted at the void volume, whereas peaks 2, 3, and 4 corresponded to the GHBP complex, free hGH, and iodide, respectively. Stripping of GHBP in serum by immunoaffinity chromatography depleted peak 2 but did not affect peak 1. Peak 1 accounted for 11.4 ± 1.2% of the total radioactivity (mean± sem; n = 6) in stripped serum. Addition of unlabeled hGH (0.9–9 μm) demonstrated the binding of[ 125I]hGH to be specific, with Scatchard analysis revealing an affinity of 0.88 ± 0.03 × 105 m−1 (n = 3) and a capacity of 2.46± 0.14 μm. Sepharose CL-6B filtration chromatography showed the complex to be 260 kDa in size. The distribution of GH binding to GHBP and this high Mr serum factor was investigated by incubating [125I]hGH in sera containing a low (5 .
Effects of Long-term Infusion of Prostacyclin (Epoprostenol) on Echocardiographic Measures of Right Ventricular Structure and Function in Primary Pulmonary Hypertension

Background Right heart failure is an important cause of morbidity and mortality in primary pulmonary hypertension. In a recent prospective, randomized study of severely symptomatic patients, treatment with prostacyclin (epoprostenol) produced improvements in hemodynamics, quality of life, and survival. This article describes the echocardiographic characteristics of participants in this trial; the relationships of echocardiographic variables to hemodynamic parameters, exercise capacity, and quality of life; and the echocardiographic changes associated with prostacyclin therapy. Methods and Results The 81 patients enrolled in this multicenter trial were randomized to treatment with a long-term infusion of prostacyclin in addition to conventional therapy (n=41) or conventional therapy alone (n=40) for 12 weeks. Echocardiograms and assessments of hemodynamics, exercise capacity, and quality of life were performed before and after the treatment phase. On baseline evaluation, patients had marked right ventricul.
Protection against Diabetes-Induced Nephropathy in Growth Hormone Receptor/Binding Protein Gene-Disrupted Mice1.

To further investigate the role of GH in diabetic nephropathy, experimental diabetes was induced with streptozotocin (STZ) in mice in which the GH receptor/binding protein gene was disrupted. Body weight, blood glucose, and renal histology and morphometry were studied 10 weeks after diabetes induction in wild-type (+/+) mice and in mice heterozygous (+/−) and homozygous (−/−) for the disruption. Equivalent levels of hyperglycemia developed in all diabetic groups. Normal weight gain was absent in +/+ and +/− diabetic groups, and− /− diabetics lost weight during the study. Diabetic +/+ and +/− groups both showed evidence of glomerulosclerosis, increases in glomerular volume, and increases in the ratio of mesangial area to total glomerular area, whereas diabetic −/− mice showed none of these pathological changes. These results extend our previous findings of protection against diabetes-associated kidney damage in transgenic mice expressing a GH antagonist. Taken together, the results argue for an important r.
Scattering and Field Enhancement of a Perfect Conducting Narrow Slit

This paper is concerned with the scattering and field enhancement of a narrow slit perforated in a slab of perfect conductor. We demonstrate that the enhancement of the electromagnetic field for such a configuration can be induced by either Fabry--Perot type scattering resonances or a certain nonresonant effect in the quasi-static regime. We derive the asymptotic expansions of Fabry--Perot type resonances and quantitatively analyze the field enhancement at the resonant frequencies, for which both the enhancement order and the shapes of resonant modes are precisely characterized. The field enhancement at nonresonant frequencies in the quasi-static regime is also investigated. It is shown that the fast transition of the magnetic field in the slit induces strong electric field enhancement.
Impairment of Cardiac Function and Bioenergetics in Adult Transgenic Mice Overexpressing the Bovine Growth Hormone Gene.

Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy status in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged matched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each group were examined with 31P magnetic resonance spectroscopy to determine the cardiac energy status. Transgenic mice had a significantly higher body weight (BW), 53.2+/-2.4 vs. 34.6+/-3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6+/-1.6 vs. 2.7+/-0.2 mg/g, P < 0.01. Several indexes of systolic function were depressed in transgenic animals compared with controls mice such as shortening fraction 25+/-3.0% vs. 39.9+/-3.1%; ejection fraction, 57+/-9 vs. 77+/-5; mean velocity of circumferential shortening, 4.5+/-0.8 vs. 7.0+/-1.1 circ/sec, p < 0.01. Creatine phosphate-to-ATP ratio was significantly lower in bGH overexpressing mice (1.3+/-0.08 vs. 2.1+/-0.23 in controls, P < 0.05). Ultrastructural examination of the hearts from transgenic mice revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deteriorating effects of long exposure to high level of GH on heart function.
Analytical Validation of a Continuum Model for the Evolution of a Crystal Surface in Multiple Space Dimensions

In this paper we are concerned with the existence of a weak solution to the initial boundary value problem for the equation $\frac{\partial u}{\partial t} = \Delta\mbox{$left(\Delta u\right)^-3 $}$. This problem arises in the mathematical modeling of the evolution of a crystal surface. Existence of a weak solution $u$ with $\Delta u\geq 0$ is obtained via a suitable substitution. Our investigations reveal the close connection between this problem and the equation $\partial_t\rho+\rho^2\Delta^2\rho^3=0$, another crystal surface model first proposed by H. Al Hajj Shehadeh, R. V. Kohn, and J. Weare [Phys. D, 240 (2011), pp. 1771--1784].
Structure Preserving Model Reduction of Parametric Hamiltonian Systems

While reduced-order models (ROMs) have been popular for efficiently solving large systems of differential equations, the stability of reduced models over long-time integration presents challenges. We present a greedy approach for a ROM generation of parametric Hamiltonian systems that captures the symplectic structure of Hamiltonian systems to ensure stability of the reduced model. Through the greedy selection of basis vectors, two new vectors are added at each iteration to the linear vector space to increase the accuracy of the reduced basis. We use the error in the Hamiltonian due to model reduction as an error indicator to search the parameter space and identify the next best basis vectors. Under natural assumptions on the set of all solutions of the Hamiltonian system under variation of the parameters, we show that the greedy algorithm converges at an exponential rate. Moreover, we demonstrate that combining the greedy basis with the discrete empirical interpolation method also preserves the symplecti.
Stimulation of Intracellular Free Calcium in GH3 Cells byγ 3-Melanocyte-Stimulating Hormone. Involvement of a Novel Melanocortin Receptor?

The melanocortin (MC) γ3MSH is a peptide that can be generated from the N-terminal domain of POMC and is believed to signal through the MC3 receptor. We recently showed that it induces a sustained rise in intracellular free calcium levels ([Ca2+]i) in a subpopulation of pituitary cells, particularly in the lactosomatotroph lineage. In the present study we report that γ3MSH and some analogs increase [Ca2+]i in the GH- and PRL-secreting GH3 cell line and evaluate on the basis of pharmacological experiments and gene expression studies which MC receptor may be involved. A dose as low as 1 pm γ3MSH induced an oscillating[ Ca2+]i increase in a significant percentage of GH3 cells. Increasing the dose recruited an increasing number of responding cells; a maximum was reached at 0.1 nm. γ2MSH,α MSH, and NDP-αMSH displayed a similar effect. SHU9119, an MC3 and MC4 receptor antagonist, and an MC5 receptor agonist, did not affect the number of cells showing a [Ca2+]i rise in response to γ3MSH. SHU9119 had also no effe.
Large Scale Graph Mining and Inference for Malware Detection

We present Polonium, a novel Symantec technology that detects malware through large-scale graph inference. Based on the scalable Belief Propagation algorithm, Polonium infers every file’s reputation, flagging files with low reputation as malware. We evaluated Polonium with a billion-node graph constructed from the largest file submissions dataset ever published (60 terabytes). Polonium attained a high true positive rate of 87% in detecting malware; in the field, Polonium lifted the detection rate of existing methods by 10 absolute percentage points. We detail Polonium’s design and implementation features instrumental to its success. Polonium has served 120 million people and helped answer more than one trillion queries for file reputation.
Improvements and Generalizations of Stochastic Knapsack and Multi-Armed Bandit Approximation Algorithms: Extended Abstract

The multi-armed bandit (MAB) problem features the classical tradeoff between exploration and exploitation. The input specifies several stochastic arms which evolve with each pull, and the goal is to maximize the expected reward after a fixed budget of pulls. The celebrated work of Gittins et al., surveyed in [8], presumes a condition on the arms called the martingale assumption. In [9], A. Gupta et al. obtained an LP-based 1 48 -approximation for the problem with the martingale assumption removed. We improve the algorithm to a 4 27 -approximation, with simpler analysis. Our algorithm also generalizes to the case of MAB superprocesses with (stochastic) multi-period actions. This generalization captures the framework introduced by Guha and Munagala in [11], and yields new results for their budgeted learning problems. Also, we obtain a ( 1 2 − e)-approximation for the variant of MAB where preemption (playing an arm, switching to another arm, then coming back to the first arm) is not allowed. This contains the stochastic knapsack problem of Dean, Goemans, and Vondrak in [6] with correlated rewards, where we are given a knapsack of fixed size, and a set of jobs each with a joint distribution for its size and reward. The actual size and reward of a job can only be discovered in real-time as it is being scheduled, and the objective is to maximize expected reward before the knapsack size is exhausted. Our ( 1 2 − e)-approximation improves the 1 16 and 1 8 approximations in [9] for correlated stochastic knapsack with cancellation and no cancellation, respectively, providing to our knowledge the first tight algorithm for these problems that matches the integrality gap of 2. We sample probabilities from an exponential-sized dynamic programming solution, whose existence is guaranteed by an LP projection argument. We hope this technique can also be applied to other dynamic programming problems which can be projected down onto a small LP.
Testosterone Effect on Insulin Content, Messenger Ribonucleic Acid Levels, Promoter Activity, and Secretion in the Rat.

Coexistence of hyperinsulinemia and hyperandrogenism in women has been frequently described. Most of the studies addressing this issue have focused on the mechanisms by which insulin produces hyperandrogenism. In the present study, we analyzed the effects of testosterone in vivo and in vitro upon insulin gene expression and release in the rat. Our studies demonstrate that testosterone increases insulin messenger RNA (mRNA) levels in vitro as well as in vivo. In both prepuberal and intact adult rats, serum testosterone concentrations were positively correlated with insulin mRNA levels and insulin concentration in serum. Testosterone deprivation after gonadectomy decreased both insulin gene expression and serum insulin concentration. Insulin mRNA levels were partially restored after 3 days of testosterone administration and serum insulin was 80% and 27% above baseline values at 5 and 7 days posttreatment. Primary cultured pancreatic islets treated with the sexual steroid increased about 80% insulin mRNA, as well as protein, and release. In transfected islets, testosterone increased the activity of the -410 bp rat insulin promoter I by 154%. These data demonstrate that testosterone has a direct effect upon pancreatic islet function by favoring insulin gene expression and release.
Psychological and social characteristics of attenders for breast screening

Abstract Demographic characteristics, health behaviour and knowledge of breast cancer were assessed in 183 women from a regional breast screening unit and compared with those of 182 women from a breast clinic and 41 control subjects. A questionnaire yielded information on (i) demographic characteristics and cancer-related behaviours including breast self-examination (BSE), use of screening and promptness of presentation of breast symptoms in the clinic group, (ii) the extent and effects of knowledge about breast cancer and (iii) the role of Health Belief Model dimensions. Results showed the screening unit attenders to be significantly older and to be significantly more likely to be from higher social classes. Differences between the groups in health beliefs and knowledge did not remain once the effects of age and social class were partialled out. While attitudes towards BSE and its practice related to health beliefs. only a minority of the women indicated that they practised BSE with any regularity. The r.
An independent evaluation of a home safety equipment scheme in a high-risk community: views and safety practices of families

Unintentional injury is a major public health issue across the world. The home is the most common location for unintentional injuries for young children, with children living in socio-economically deprived circumstances most at risk of injury. The provision of home safety education, with or without the provision of free or low-cost safety equipment, has been shown to improve home safety practices undertaken by parents. An evaluation was undertaken of a home safety equipment running in north-east England. A randomly selected sample of families participating in the scheme was sent a questionnaire and data were sought on home safety practices, possession and use of home safety equipment and satisfaction with the equipment scheme. The majority of families (87.9%) reported never drinking hot drinks while holding a child and 96.2% reported almost always keeping medicines locked away. Many families (88.3%) reported that they never leave their children in the bath alone. Of families with children under one year, only just over a third (37.4%) said they never use a baby walker. Satisfaction with the scheme was generally very high. While the prevalence of many safety practices was reportedly high in families, this survey found deficiencies particularly in use of baby walkers and storage of cleaning products. Surveys identifying prevalence data on parental safety practices are essential for evaluating and informing future interventions.
Novel Expression and Functional Role of Ghrelin in Rat Testis.

Ghrelin, the endogenous ligand for the GH-secretagogue receptor (GHS-R), is a recently cloned peptide, primarily expressed in the stomach and hypothalamus, that acts at central levels to elicit GH release and, notably, to regulate food intake. However, the possibility of additional, as yet unknown, peripheral effects of ghrelin cannot be ruled out. In the present communication, we provide evidence for the novel expression of ghrelin and its functional receptor in rat testis. Testicular ghrelin gene expression was demonstrated throughout postnatal development, and ghrelin protein was detected in Leydig cells from adult testis specimens. Accordingly, ghrelin mRNA signal became undetectable in rat testis following selective Leydig cell elimination. In addition, testicular expression of the gene encoding the cognate ghrelin receptor was observed from the infantile period to adulthood, with the GHS-R mRNA being persistently expressed after selective withdrawal of mature Leydig cells. From a functional standpoint, ghrelin, in a dose-dependent manner, induced an average 30% inhibition of human CG- and cAMP-stimulated T secretion in vitro. This inhibitory effect was associated with significant decreases in human CG-stimulated expression levels of the mRNAs encoding steroid acute regulatory protein, and P450 cholesterol side-chain cleavage, 3beta-hydroxy steroid dehydrogenase, and 17beta-hydroxy steroid dehydrogenase type III enzymes. Overall, our data are the first to provide evidence for a possible direct action of ghrelin in the control of testicular function. Furthermore, the present results underscore an unexpected role of ghrelin as signal with ability to potentially modulate not only growth and body weight homeostasis but also reproductive function, a phenomenon also demonstrated recently for the adipocyte-derived hormone, leptin.
Minireview: GnRH and GnRH Receptor Genes in the Human Genome.

Four different GnRHs and one GnRH receptor are reported to be expressed in various mammals, whereas 13 GnRHs and numerous GnRH receptors have been identified in various nonmammalian vertebrates. The nucleotide sequencing of the human genome provided the opportunity to determine which of these peptides and receptors might be expressed in primates. Of the four GnRHs reportedly expressed in mammals, only GnRH I (mammalian GnRH) and GnRH II (chicken GnRH II) genes were identified in the human genome. Three GnRH receptor or receptor-like genes were identified: 1) the well-established GnRH I receptor gene located on chromosome 4; 2) an apparent GnRH II receptor gene located on chromosome 1, and; 3) a sterile GnRH II receptor-like homolog gene on chromosome 14. A cDNA cloned from monkey RNA that was 96% identical with the putative human GnRH receptor type II gene encoded a 379-amino acid G protein-coupled/7-transmembrane receptor having a C-terminal cytoplasmic tail. The experimentally expressed GnRH II receptor was functional with and specific for GnRH II, and, unlike the GnRH I receptor, desensitized to continuous GnRH treatment. GnRH II receptor mRNA is expressed ubiquitously in human tissues. Significant questions remain about the potential functions of the primate GnRH II receptor such as regulation of gonadotropin secretion, female sexual behavior, and tumor cell growth; also, about whether it is expressed as a full-length, functional gene transcript in humans.