Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Neuronal Enhancers of the Proopiomelanocortin Gene by Transgenic Mouse Analysis and Phylogenetic Footprinting

ABSTRACT The proopiomelanocortin (POMC) gene is expressed in the pituitary and arcuate neurons of the hypothalamus. POMC arcuate neurons play a central role in the control of energy homeostasis, and rare loss-of-function mutations in POMC cause obesity. Moreover, POMC is the prime candidate gene within a highly significant quantitative trait locus on chromosome 2 associated with obesity traits in several human populations. Here, we identify two phylogenetically conserved neuronal POMC enhancers designated nPE1 (600 bp) and nPE2 (150 bp) located approximately 10 to 12 kb upstream of mammalian POMC transcriptional units. We show that mouse or human genomic regions containing these enhancers are able to direct reporter gene expression to POMC hypothalamic neurons, but not the pituitary of transgenic mice. Conversely, deletion of nPE1 and nPE2 in the context of the entire transcriptional unit of POMC abolishes transgene expression in the hypothalamus without affecting pituitary expression. Our results indicate that the nPEs are necessary and sufficient for hypothalamic POMC expression and that POMC expression in the brain and pituitary is controlled by independent sets of enhancers. Our study advances the understanding of the molecular nature of hypothalamic POMC neurons and will be useful to determine whether polymorphisms in POMC regulatory regions play a role in the predisposition to obesity.
Motoneuron pool excitability of hemiplegic patients: assessing recovery stages by using H-reflex and M response.

OBJECTIVES To compare the excitability of the motoneuron pools of both the spastic and the unimpaired sides of patients with hemiplegia with a new method by using H-reflexes and M responses. The method determines the ratio of the developmental slope of the H-reflex (Hslp) to the slope of the M response (Mslp). We also examined the relation between the Brunnstrom stages and the Hslp/Mslp. DESIGN Experiment. SETTING Electrophysiologic experimental laboratory in a Japanese medical school. PATIENTS Fifteen hemiplegic patients (9 men, 6 women; age range, 48-71yr; mean, 60yr) with spasticity caused by a stroke. INTERVENTIONS The subject was instructed to relax while seated in a reclining chair with his foot fixed on an immobile pedal. After the soleus H-reflex and M responses on one side were recorded, the same experimental procedures were carried out on the other side. MAIN OUTCOME MEASURES Hslp/Mslp Brunnstrom stages. RESULTS Hslp/Mslp had better predictive value than conventional indicators of motoneuron pool excitability. Hslp/Mslp appeared to be a better match for the bell-shaped pattern of the Brunnstrom stages. CONCLUSION Hslp/Mslp is the preferred index for evaluating the motoneuron pool excitability of the spastic side of hemiplegic patients.
Melengestrol acetate at greater doses than typically used for estrous synchrony in bovine females does not mimic endogenous progesterone in regulation of secretion of luteinizing hormone and 17 beta-estradiol.

Our working hypothesis was that doses of melengestrol acetate (MGA) greater than those typically administered in estrous synchrony regimens would regulate secretion of LH and 17 beta-estradiol (E2) as endogenous progesterone (P4) does during the midluteal phase of the estrous cycle. We also hypothesized that endogenous P4 from the CL would interact with MGA to further decrease the frequency of LH pulses and E2. Cows on Day 5 of their estrous cycle (Day 0 = estrus) were randomly assigned to an untreated control group (CONT, n = 5) or to one of six MGA treatment groups (n = 5 per group): 1) MGA administered orally each day via a gelatin capsule at a dose of 0.5 mg MGA/cow with the CL present (0.5CIL); 2) 0.5 mg MGA/cow daily in the absence of CL (0.5NO); 3) 1.0 mg MGA with CL present (1.0CL); 4) 1.0 mg MGA without CL (1.0NO); 5) 1.5 mg MGA with CL present (1.5CL); 6) 1.5 mg without CL (1.5NO). MGA was administered for 10 days (Day 5 = initiation of treatment). To regress CL, cows assigned to groups without CL received injections of prostaglandin F 2 alpha (PGF 2 alpha; 25 mg) on Days 6 and 7 of their estrous cycle. All cows were administered PGF2 alpha at the end of the 10-day treatment period. During the treatment period, daily blood samples were collected to determine concentrations of E2. Serial blood samples were collected at 15-min intervals for 24 h on Days 8, 11, and 14 to determine pattern of LH secretion. (ABSTRACT TRUNCATED AT 250 WORDS)
Population genetic and field‐ecological analyses return similar estimates of dispersal over space and time in an endangered amphibian

The explosive growth of empirical population genetics has seen a proliferation of analytical methods leading to a steady increase in our ability to accurately measure key population parameters, including genetic isolation, effective population size, and gene flow, in natural systems. Assuming they yield similar results, population genetic methods offer an attractive complement to, or replacement of, traditional field‐ecological studies. However, empirical assessments of the concordance between direct field‐ecological and indirect population genetic studies of the same populations are uncommon in the literature. In this study, we investigate genetic isolation, rates of dispersal, and population sizes for the endangered California tiger salamander, Ambystoma californiense, across multiple breeding seasons in an intact vernal pool network. We then compare our molecular results to a previously published study based on multiyear, mark–recapture data from the same breeding sites. We found that field and genetic estimates of population size were only weakly correlated, but dispersal rates were remarkably congruent across studies and methods. In fact, dispersal probability functions derived from genetic data and traditional field‐ecological data were a significant match, suggesting that either method can be used effectively to assess population connectivity. These results provide one of the first explicit tests of the correspondence between landscape genetic and field‐ecological approaches to measuring functional population connectivity and suggest that even single‐year genetic samples can return biologically meaningful estimates of natural dispersal and gene flow.
Differential Postnatal Expression of Neuronal Maturation Markers in the Dentate Gyrus of Mice and Rats

The dentate gyrus (DG) is a unique structure of the hippocampus that is distinguished by ongoing neurogenesis throughout the lifetime of an organism. The development of the DG, which begins during late gestation and continues during the postnatal period, comprises the structural formation of the DG as well as the establishment of the adult neurogenic niche in the subgranular zone (SGZ). We investigated the time course of postnatal maturation of the DG in male C57BL/6J mice and male Sprague-Dawley rats based on the distribution patterns of the immature neuronal marker doublecortin (DCX) and a marker for mature neurons, calbindin (CB). Our findings demonstrate that the postnatal DG is marked by a substantial maturation with a high number of DCX-positive granule cells (GCs) during the first two postnatal weeks followed by a progression toward more mature patterns and increasing numbers of CB-positive GCs within the subsequent 2 weeks. The most substantial shift in maturation of the GC population took place between P7 and P14 in both mice and rats, when young, immature DCX-positive GCs became confined to the innermost part of the GC layer (GCL), indicative of the formation of the SGZ. These results suggest that the first month of postnatal development represents an important transition phase during which DG neurogenesis and the maturation course of the GC population becomes analogous to the process of adult neurogenesis. Therefore, the postnatal DG could serve as an attractive model for studying a growing and functionally maturing neural network. Direct comparisons between mice and rats revealed that the transition from immature DCX-positive to mature CB-positive GCs occurs more rapidly in the rat by approximately 4–6 days. The remarkable species difference in the speed of maturation on the GC population level may have important implications for developmental and neurogenesis research in different rodent species and strains.
Cross‐border migration and initiation of others into drug injecting in Tijuana, Mexico

INTRODUCTION AND AIMS Efforts to prevent injection drug use (IDU) are increasingly focusing on the role that people who inject drugs (PWID) play in facilitating the entry of others into this behaviour. This is particularly relevant in settings experiencing high levels of IDU, such as Mexico's northern border region, where cross-border migration, particularly through forced deportation, has been found to increase a range of health and social harms related to injecting. DESIGN AND METHODS PWID enrolled in a prospective cohort study in Tijuana, Mexico, since 2011 were interviewed semi-annually, which solicited responses on their experiences initiating others into injecting. Univariate and multivariable logistic regression analyses were conducted at the Preventing Injection by Modifying Existing Responses (PRIMER) baseline, with the dependent variable defined as reporting ever initiating others into injection. The primary independent variable was lifetime deportation from the USA to Mexico. RESULTS Among 532 participants, 14% (n = 76) reported initiating others into injecting, the majority of participants reporting initiating acquaintances (74%, n = 56). In multivariable analyses, initiating others into injecting was independently associated with reporting living in the USA for 1-5 years [adjusted odds ratio (AOR) = 2.42; 95% confidence interval (CI) 1.22-4.79, P = 0.01], and methamphetamine and heroin injection combined (AOR = 3.67; 95% CI 1.11-12.17, P = 0.03). Deportation was not independently associated with initiating others into injecting. DISCUSSION AND CONCLUSIONS The impact of migration needs to be considered within binational programming seeking to prevent the expansion of epidemics of injecting and HIV transmission among mobile populations residing in the Mexico-USA border region.
Low precision arithmetic for deep learning

We simulate the training of a set of state of the art neural networks, the Maxout networks (Goodfellow et al., 2013a), on three benchmark datasets: the MNIST, CIFAR10 and SVHN, with three distinct arithmetics: floating point, fixed point and dynamic fixed point. For each of those datasets and for each of those arithmetics, we assess the impact of the precision of the computations on the final error of the training. We find that very low precision computation is sufficient not just for running trained networks but also for training them. For example, almost state-of-the-art results were obtained on most datasets with 10 bits for computing activations and gradients, and 12 bits for storing updated parameters.
Iodine in organic synthesis

Commercially available iodine has played an important role in organic synthesis. This review discusses the versatile uses of iodine in different chemical transformations. Reactions include esterification, cycloaddition reaction, allylation of aldehydes, acetalization of carbonyl compounds, acylation of alcohols, synthesis of cyclic ethers and aromatization of α,β-unsaturated ketones.
Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, developing over at least two months. Uncontrolled studies suggest that intravenous immunoglobulin (IVIg) helps. OBJECTIVES To review systematically the evidence from randomised controlled trials concerning the efficacy and safety of IVIg in CIDP. SEARCH STRATEGY We searched the Cochrane Neuromuscular Trials Register, MEDLINE, EMBASE and ISI from January 1985 to May 2008. SELECTION CRITERIA Randomised controlled studies testing any dose of IVIg versus placebo, plasma exchange or corticosteroids in definite or probable CIDP. DATA COLLECTION AND ANALYSIS Two authors reviewed literature searches to identify potentially relevant trials, scored their quality and extracted data independently. We contacted authors for additional information. MAIN RESULTS Seven randomised controlled trials were considered eligible including 287 participants. These trials were homogeneous and overall quality was high. Five studies on 235 participants compared IVIg against placebo. One trial with 20 participants compared IVIg with plasma exchange and one trial compared IVIg with prednisolone in 32 participants. A significantly higher proportion of participants improved in disability within one month after IVIg treatment as compared with placebo (relative risk 2.40, 95% confidence interval 1.72 to 3.36). Whether all these improvements are equally clinically relevant cannot be deduced from this analysis because each trial used different disability scales and definitions of significant improvement. In three trials including 84 participants the disability could be transformed to the modified Rankin score, on which significantly more patients improved one point after IVIg treatment compared to placebo (relative risk 2.40, 95% confidence interval 0.98 to 5.83). Only one study included in this review had a long-term follow-up. The results of this study suggest that intravenous immunoglobulin improves disability more than placebo over 24 and 48 weeks. The mean disability score revealed no significant difference between IVIg and plasma exchange at six weeks. There was no significant difference in improvement in disability on prednisolone compared with IVIg after two or six weeks. There were no statistically significant differences in frequencies of side effects between the three types of treatment. AUTHORS' CONCLUSIONS The evidence from randomised controlled trials shows that intravenous immunoglobulin improves disability for at least two to six weeks compared with placebo, with a number needed to treat of 3.00. During this period it has similar efficacy to plasma exchange and oral prednisolone. In one large trial, benefit of IVIg persisted for 24 and possibly 48 weeks.
Comparison of coherent and differential space-time block codes over spatially correlated channels

This paper compares the performance of coherent, differential and differential unitary space-time block codes operating over spatially correlated Rayleigh fading channels with up to four transmit antennas, ft is shown that, when operating over spatially correlated channels, the relative performance of all candidate codes is improved when the number of transmit antennas is kept low. Improved performance is also observed when differential STBC are used compared to coherent STBC.
Genomic aberrations and survival in chronic lymphocytic leukemia.

BACKGROUND Fluorescence in situ hybridization has improved the detection of genomic aberrations in chronic lymphocytic leukemia. We used this method to identify chromosomal abnormalities in patients with chronic lymphocytic leukemia and assessed their prognostic implications. METHODS Mononuclear cells from the blood of 325 patients with chronic lymphocytic leukemia were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 6q21, 11q22-23, 13q14, and 17p13; trisomy of bands 3q26, 8q24, and 12q13; and translocations involving band 14q32. Molecular cytogenetic data were correlated with clinical findings. RESULTS Chromosomal aberrations were detected in 268 of 325 cases (82 percent). The most frequent changes were a deletion in 13q (55 percent), a deletion in 11q (18 percent), trisomy of 12q (16 percent), a deletion in 17p (7 percent), and a deletion in 6q (7 percent). Five categories were defined with a statistical model: 17p deletion, 11q deletion, 12q trisomy, normal karyotype, and 13q deletion as the sole abnormality; the median survival times for patients in these groups were 32, 79, 114, 111, and 133 months, respectively. Patients in the 17p- and 11q-deletion groups had more advanced disease than those in the other three groups. Patients with 17p deletions had the shortest median treatment-free interval (9 months), and those with 13q deletions had the longest (92 months). In multivariate analysis, the presence or absence of a 17p deletion, the presence or absence of an 11q deletion, age, Binet stage, the serum lactate dehydrogenase level, and the white-cell count gave significant prognostic information. CONCLUSIONS Genomic aberrations in chronic lymphocytic leukemia are important independent predictors of disease progression and survival. These findings have implications for the design of risk-adapted treatment strategies.
Efectos dinámicos en puentes de ferrocarril

El comportamiento dinamico de los puentes constituye uno de los problemas clasicos de la Ingenieria Civil. Efectivamente, su origen se puede situar en el conocido accidente de Broughton en 1831, cuando un puente de hierro cedio al paso de una formacion militar. Desde entonces, han sido innumerables los trabajos a que el tema dio lugar, conducentes en su mayoria a la definicion de un coeficiente de mayoracion sobre las cargas estaticas. Uno de los organismos mas activos en este terreno ha sido la U.I. C. (Union Internationale des Chemins de Fer), a traves de la comision O.R. E. (Office de Recherches et d'Essais). Ya en la actualidad este organismo ha lanzado la Question D-160 referente al estudio de la flecha maxima admisible en relacion a la comodidad del pasajero. En una primera etapa se trataba de la obtencion de un programa de ordenador que contemplase el problema en su conjunto, lo cual permitiria posteriormente la realizacion de estudios parametricos y consecuentemente la eventual mejora de criterios de diseno. Se invito pues a una serie de centros de Investigacion Europeos, entre los cuales se encontraba el equipo de la catedra de Estructuras de la Escuela Tecnica Superior de Ingenieros Industriales. Este articulo pretende dar una vision general del programa realizado, asi como de algunos de los resultados obtenidos al pasar uno de los casos de prueba solicitados por la ORE, el puente de Platting, en la Republica Federal de Alemania.
Lipopolysaccharide Inhibits Long Term Potentiation in the Rat Dentate Gyrus by Activating Caspase-1*

Lipopolysaccharide, a component of the cell wall of Gram-negative bacteria, may be responsible for at least some of the pathophysiological sequelae of bacterial infections, probably by inducing an increase in interleukin-1β (IL-1β) concentration. We report that intraperitoneal injection of lipopolysaccharide increased hippocampal caspase-1 activity and IL-1β concentration; these changes were associated with increased activity of the stress-activated kinase c-Jun NH2-terminal kinase, decreased glutamate release, and impaired long term potentiation. The degenerative changes in hippocampus and entorhinal cortical neurones were consistent with apoptosis because translocation of cytochromec and poly(ADP-ribose) polymerase cleavage were increased. Inhibition of caspase-1 blocked these changes, suggesting that IL-1β mediated the lipopolysaccharide-induced changes.
Understanding dendritic cell immunotherapy in ovarian cancer

ABSTRACT Introduction: Approximately eighty percent of patients with ovarian cancer are diagnosed with advanced disease. Even with cutting edge surgical techniques and the best regimens of standard therapies most patients relapse and die of drug resistant disease within five years of diagnosis. Dendritic cell (DC) immunotherapy can induce anti-tumor T cell immunity in patients and holds great potential in the era of modern anti-cancer treatment. Areas Covered: This review outlines critical factors regulating the outcome of DC immunotherapy in ovarian cancer, summarizes the important findings in ovarian cancer DC clinical trials, and discusses new directions which may improve the effectiveness of DC immunotherapy. Expert Commentary: Administration of DC vaccines with other forms of immunotherapy may enhance the efficacy of these treatments, ultimately increasing cures for this disease.
VENOUS OXYGEN SATURATION AND LACTATE GRADIENT FROM SUPERIOR VENA CAVA TO PULMONARY ARTERY IN PATIENTS WITH SEPTIC SHOCK

Monitoring of central venous oxygen saturation (ScvO2) is considered comparable with mixed venous oxygen saturation (SvO2) in the initial resuscitation phase of septic shock. Our aim was to assess their agreement in septic shock in the intensive care unit setting and the effect of a potential difference in a computed parameter, namely, oxygen consumption (VO2). In addition, we sought for a central venous to pulmonary artery (PA) lactate gradient. We enrolled 37 patients with septic shock who were receiving noradrenaline infusions, and their attending physicians had placed a PA catheter for fluid management. Blood samples were drawn in succession from the superior vena cava, right atrium (RA), right ventricle, and PA. Hemodynamic and treatment parameters were monitored, and data were compared by correlation and Bland-Altman analysis. Mixed venous oxygen saturation was lower than ScvO2 (70.2% ± 11.4% vs. 78.6% ± 10.2%; P < 0.001), with a bias of −8.45% and 95% limits of agreement ranging from −20.23% to 3.33%. This difference correlated significantly to the noradrenaline infusion rate and the oxygen consumption and extraction ratio. These lower SvO2 values resulted in computed VO2v higher than the VO2cv (P < 0.001), with a bias of 104.97 mL min−1 and 95% limits of agreement from −4.12 to 214.07 mL min−1. Finally, lactate concentration was higher in the superior vena cava and RA than in the PA (2.42 ± 3.15 and 2.35 ± 3.16 vs. 2.17 ± 3.19 mM; P < 0.01 for both comparisons). Thus, our data suggest that ScvO2 and SvO2 are not equivalent in intensive care unit patients with septic shock. Additionally, the substitution of ScvO2 for SvO2 in the calculation of VO2 produces unacceptably large errors. Finally, the decrease in lactate between RA and PA may support the hypothesis that the mixing of RA and coronary sinus blood is at least partially responsible for the difference between ScvO2 and SvO2.
Physical game demands in elite rugby union: a global positioning system analysis and possible implications for rehabilitation.

STUDY DESIGN Descriptive. OBJECTIVES To evaluate the physical demands of an international Rugby Union-level game using a global positioning system (GPS). BACKGROUND Elite Rugby Union teams currently employ the latest technology to monitor and evaluate physical demands of training and games on their players. METHODS GPS data from 2 players, a back and a forward, were collected during an international Rugby Union game. Locomotion speed, total body load, and body load sustained in tackles and scrums were analyzed. RESULTS Players completed an average distance of 6715 m and spent the major portion of the game standing or walking, interspersed with medium- and high-intensity running activities. The back performed a higher number of high-intensity sprints and reached a greater maximal speed. Body load data revealed that high levels of gravitational force are sustained in tackling and scrum tasks. CONCLUSION The current study provides a detailed GPS analysis of the physical demands of international Rugby Union players. These data, when combined with game video footage, may assist sports medicine professionals in understanding the demands of the game and mechanism of injury, as well as improving injury rehabilitation.