Miracle-dz/UniFAR-FTUs huggingface dataset:
Projected Changes in Climate Extremes over the Northeastern United States

AbstractProjections of historical and future changes in climate extremes are examined by applying the bias-correction spatial disaggregation (BCSD) statistical downscaling method to five general circulation models (GCMs) from phase 5 of the Coupled Model Intercomparison Project (CMIP5). For this analysis, 11 extreme temperature and precipitation indices that are relevant across multiple disciplines (e.g., agriculture and conservation) are chosen. Over the historical period, the simulated means, variances, and cumulative distribution functions (CDFs) of each of the 11 indices are first compared with observations, and the performance of the downscaling method is quantitatively evaluated. For the future period, the ensemble average of the five GCM simulations points to more warm extremes, fewer cold extremes, and more precipitation extremes with greater intensities under all three scenarios. The changes are larger under higher emissions scenarios. The inter-GCM uncertainties and changes in probability distri.
Deep inelastic scattering from gauge string duality in the soft wall model

Deep inelastic structure functions have been calculated by Polchinski and Strassler in gauge/string duality introducing a hard infrared (IR) cut off in AdS space. Here we investigate this problem using a soft IR cut off that leads to linear Regge trajectories for mesons. We calculate the structure functions for scalar particles in the large x regime where supergravity approximation holds and the small x regime where massive string states contribute. We also propose a hybrid model to calculate structure functions for fermions in the supergravity approximation. In the deep inelastic limit our results are in agreement with those obtained using a hard cut off.
Hormonal control of apoptotic cell death in the testis: gonadotropins and androgens as testicular cell survival factors.

Although the requirement for pituitary gonadotropins during testicular cell differentiation is well documented, the possible role of FSH and LH in regulating testicular cell survival has not been studied. Using a quantitative autoradiographic method for the detection of internucleosomal DNA fragmentation, a hallmark feature of apoptosis, the hormonal control of apoptotic cell death was studied in testicular cells collected from immature rats after hypophysectomy. After surgery, animals were treated with daily injections of 20 IU long-acting FSH agonist (FSH-CTP) or 50 IU human CG (hCG) for 2 days. Hypophysectomy decreased testis weight by 25%, but treatment with FSH-CTP or hCG prevented the effect of hypophysectomy. Testes of intact animals contained predominantly high-mol wt DNA, whereas hypophysectomy increased DNA cleavage into low-mol wt (< 15 kilobases) ladders characteristics of apoptosis. In contrast, treatment with FSH-CTP or hCG inhibited hypophysectomy-induced apoptotic DNA cleavage by 84% and 51%, respectively. Hypophysectomy-induced DNA fragmentation was found in both interstitial cells and seminiferous tubules. Similar to whole testis, treatment with FSH-CTP suppressed hypophysectomy-induced apoptosis by over 90% in seminiferous tubules and interstitial cells. In contrast, hCG treatment was less effective in preventing hypophysectomy-induced DNA cleavage (46% suppression in tubules and 77% suppression in interstitial cells). Furthermore, testosterone replacement also suppressed hypophysectomy-induced DNA fragmentation by 75% in the whole testis tissue, 64% in tubules, and 55% in interstitial cells. To further study the role of gonadotropins, intact animals were treated with a potent GnRH antagonist (Azaline B, 10 microgram/day) to decrease serum gonadotropin levels. (ABSTRACT TRUNCATED AT 250 WORDS)
Using Brain Imaging to Unravel the Mysteries of Stuttering

Editor’s note: After many decades of attributing stuttering to causes ranging from childhood trauma to overly anxious personalities, scientists have used neuroimaging techniques to uncover measurable differences in the brain activity of people who stutter versus fluent speakers. But while researchers have made great strides in understanding stuttering in adults, the neural basis of stuttering in children largely remains a mystery. We do not yet know why up to 80 percent of children who stutter recover without intervention, nor do we know how to distinguish those who will recover without intervention from those who will not. However, recent findings support the idea that early intervention can alter or normalize brain function before stuttering-induced changes become hardwired.
La construcción y el peso del discurso racial en México. El caso de los jóvenes estudiantes en la ciudad de León, Guanajuato

espanolEl articulo trata de responder las siguientes preguntas: ? cual es el peso de las categorias raciales en las relaciones cotidianas de la poblacion joven leonesa? , y ? cual es el tipo de racismo que opera en regiones mestizas, con escasa poblacion indigena? Desde una perspectiva sociologica, distinguiendo conceptualmente racialismo, racializacion y racismo, y a partir de encuestas sobre representaciones sociales y practicas de discriminacion racial, realizadas en preparatorias del municipio de Leon, Guanajuato, el estudio demuestra la presencia de un doble discurso: el de la igualdad y el de la otrificacion, ademas de un predominio del lenguaje racializador que media las relaciones y las representaciones sociales de los jovenes. En este contexto el racismo opera de forma sutil; se hace explicito cuando una posible relacion de proximidad proyecta la ruptura de la distincion social. EnglishThis article attempts to respond to the following questions: 1) What is the weight of racial categories in day-to-day relations of young people in Leon? and, 2) What kind of racism exists in mestizo areas with little indigenous population? The study is done from a sociological point of view, conceptually distinguishing between racialism, racialization, and racism, and is based on surveys on racially discriminatory social representations and practices carried out in high schools in the municipality of Leon, Guanajuato. The results show the presence of a dual discourse: equality versus othering. It also uncovers the predominance of racializing language that ties together young people’s relations and social representations. In this context, racism is subtle; it becomes explicit when a possible close relationship projects a break in the social distinction.
Establishing the Research Agenda for Increasing the Representation of Women in Engineering and Computing

While there is an extensive body of research on gender equity in engineering and computing, there have been few efforts to glean insight from a dialog among experts. To encourage collaboration and to develop a shared vision of the future research agenda, a 2 day workshop of 50 scholars who work on the topic of gender in engineering and computing was held at a rural conference center. The structure of the conference and the location allowed for time to reflect, dialog, and to craft an innovative research agenda aimed at increasing the representation of women in engineering and computing. This paper has been written by the conference organizers and details the ideas and recommendations from the scholars. The result is an innovative, collaborative approach to future research that focuses on identifying effective interventions. The new approach includes the creation of partnerships with stakeholders including businesses, government agencies, non-profits and academic institutions to allow a broader voice in setting research priorities. Researchers recommend incorporating multiple disciplines and methodologies, while expanding the use of data analytics, merging and mining existing databases and creating new datasets. The future research agenda is detailed and includes studies focused on socio-cultural interventions particularly on career choice, within undergraduate and graduate programs, and for women in professional careers. The outcome is a vision for future research that can be shared with researchers, practitioners and other stakeholders that will lead to gender equity in the engineering and computing professions.
Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease

Post-mitotic neurons are typically terminally differentiated and in a quiescent status. However, in Alzheimer disease (AD), many neurons display ectopic re-expression of cell cycle-related proteins. Cyclin-dependent kinase 11 (CDK11) mRNA produces a 110-kDa protein (CDK11p110) throughout the cell cycle, a 58-kDa protein (CDK11p58) that is specifically translated from an internal ribosome entry site and expressed only in the G2/M phase of the cell cycle, and a 46-kDa protein (CDK11p46) that is considered to be apoptosis specific. CDK11 is required for sister chromatid cohesion and the completion of mitosis. In this study, we found that the expression patterns of CDK11 vary such that cytoplasmic CDK11 is increased in AD cellular processes, compared to a pronounced nuclear expression pattern in most controls. We also investigated the effect of amyloid precursor protein (APP) on CDK11 expression in vitro by using M17 cells overexpressing wild-type APP and APP Swedish mutant phenotype and found increased CDK11 expression compared to empty vector. In addition, amyloid-β25–35 resulted in increased CDK11 in M17 cells. These data suggest that CDK11 may play a vital role in cell cycle re-entry in AD neurons in an APP-dependent manner, thus presenting an intriguing novel function of the APP signaling pathway in AD.
A bacterial genome in flux: the twelve linear and nine circular extrachromosomal DNAs in an infectious isolate of the Lyme disease spirochete Borrelia burgdorferi

We have determined that Borrelia burgdorferi strain B31 MI carries 21 extrachromosomal DNA elements, the largest number known for any bacterium. Among these are 12 linear and nine circular plasmids, whose sequences total 610 694 bp. We report here the nucleotide sequence of three linear and seven circular plasmids (comprising 290 546 bp) in this infectious isolate. This completes the genome sequencing project for this organism; its genome size is 1 521 419 bp (plus about 2000 bp of undetermined telomeric sequences). Analysis of the sequence implies that there has been extensive and sometimes rather recent DNA rearrangement among a number of the linear plasmids. Many of these events appear to have been mediated by recombinational processes that formed duplications. These many regions of similarity are reflected in the fact that most plasmid genes are members of one of the genome's 161 paralogous gene families; 107 of these gene families, which vary in size from two to 41 members, contain at least one plasmid gene. These rearrangements appear to have contributed to a surprisingly large number of apparently non‐functional pseudogenes, a very unusual feature for a prokaryotic genome. The presence of these damaged genes suggests that some of the plasmids may be in a period of rapid evolution. The sequence predicts 535 plasmid genes ≥300 bp in length that may be intact and 167 apparently mutationally damaged and/or unexpressed genes (pseudogenes). The large majority, over 90%, of genes on these plasmids have no convincing similarity to genes outside Borrelia, suggesting that they perform specialized functions.
Transfusion in critically ill children: an ongoing dilemma

Transfusion of blood products is a cornerstone in managing many critically ill children. Major improvements in blood product safety have not diminished the need for caution in transfusion practice. In this review, we aim to discuss the interplay between benefits and potential adverse effects of transfusion in critically ill children by including 65 papers, which were evaluated based on previously agreed selection criteria. Current practice on transfusing critically ill children is mainly founded on the basis of adult studies, common practices with cut‐off values, and expert opinions, rather than evidence‐based medicine. Paediatric patients have explicit physiological challenges and requirements to be addressed. Critically ill children often suffer from anaemia, have substantial iatrogenic blood loss with subsequent transfusions, and are at a higher risk of complications, often due to human errors. Transfusion in children is associated with increased morbidity. A restrictive transfusion strategy is not associated with increased morbidity. Thus, transfusion in paediatrics should be considered a high‐risk treatment and requires individual clinical assessment. Current level of evidence support the notion that in most stable cases, despite high severity of illness (cyanotic children and neonates excluded), a restrictive haemoglobin threshold of 70 g/l (4.3 mmol/l) is no more harmful than to transfuse at a liberal trigger, e.g. haemoglobin 95 g/l (5.9 mmol/l). Thus, balanced against potential benefits and often its necessity, a restrictive approach may be appropriate due to the associated risks of transfusion.
Phospholipase D2 functions as a downstream signaling molecule of MAP kinase pathway in L1‐stimulated neurite outgrowth of cerebellar granule neurons

Stimulation of the neuronal cell adhesion molecule L1 in cerebellar granule neurons (CGNs) enhances neurite outgrowth and this response is inhibited by the primary alcohol ethanol. Because primary alcohols suppress the formation of the signaling lipid phosphatidic acid (PA) by phospholipase D (PLD), this observation prompted us to investigate whether PLD plays a role in the L1‐mediated neurite outgrowth in CGNs. In the cerebellum of postnatal day 8 mice, PLD2 protein was abundantly expressed, while PLD1 expression was not detected. The L1‐stimulated neurite outgrowth was inhibited by primary alcohols and by overexpression of lipase‐deficient PLD2. Increases in cellular PA levels by direct PA application or overexpression of wild‐type PLD2 mimicked the L1‐dependent stimulation of neurite outgrowth. Furthermore, it was found that L1 stimulation in CGNs increased PLD activity concomitantly with phosphorylation of extracellular signal‐regulated kinase (ERK), both of which were inhibited by the MAP kinase‐ERK kinase (MEK) inhibitor. These results provide evidence that PLD2 functions as a downstream signaling molecule of ERK to mediate the L1‐dependent neurite outgrowth of CGNs, a mechanism that may be related to alcohol‐related neurodevelopmental disorders.
Phagocytic activity of neutrophils in chronic obstructive pulmonary disease

1. Shanmugam L, Johnson P, Ravinder S, Padmavathi R, Rajagopalan B, Kindo A. Assessment of phagocytic activity of neutrophils in chronic obstructive pulmonary disease. Lung India 2015;32:437. 2. Zhang P, Nelson S, Summer WR, Spitzer JA. Acute ethanol intoxication suppresses the pulmonary inflammatory response in rats challenged with intrapulmonary endotoxin. Alcohol Clin Exp Res 1997;21:773‐8. 3. Güntsch A, Erler M, Preshaw PM, Sigusch BW, Klinger G, Glockmann E. Effect of smoking on crevicular polymorphonuclear neutrophil function in periodontally healthy subjects. J Periodontal Res 2006;41:184‐8. 4. Walton GM, Purvis T, Chadwick C, Stockley RA, Sapey E. S46 phagocytosis by blood neutrophils is not attenuated in patients with chronic obstructive pulmonary disease. Thorax 2014;69 Suppl 2:A26‐7. Sir,
Distribution of enrofloxacin in intestinal tissue and contents of healthy pigs after oral and intramuscular administrations.

The concentration of enrofloxacin in plasma, intestinal tissue, lymph nodes and intestinal contents was investigated in healthy pigs after oral (p.o.) and intramuscular (i.m.) administration of a single dose of 2.5 mg/kg bw. Tissue and content samples were collected from jejunum, ileum, caecum and colon from pigs killed at 2, 3 and 6 h after dosing. Intramuscular administration resulted in significantly higher concentrations in plasma, intestinal tissue and lymph nodes at 2 h but not at 3 or 6 h compared with p.o. administration. The absorption and distribution phase was longer after oral administration, and maximum concentrations in tissue and plasma were determined later than after i.m. administration. No difference between route of administration was observed in the intestinal content. Enrofloxacin concentrations in faeces during a 5-day dosing regimen with i.m. and p.o. administration were determined by both HPLC and bio-assay. Higher concentrations were found after i.m. administration during the first day, but the difference was not significant after 2 days. The biologically active concentrations determined by bio-assay constituted 48-75% of the total concentrations determined by HPLC. On the basis of these results it was concluded that in order to ensure an immediate high concentration of enrofloxacin, and thereby avoid an initial selection for resistant mutants, the intramuscular route seems to be preferable to the oral route.
Beyond fatigue: Assessing variables associated with sleep problems and use of sleep medications in multiple sclerosis

Background: Recent research indicates that sleep disturbances are common in persons with multiple sclerosis (MS), though research to date has primarily focused on the relationship between fatigue and sleep. In order to improve treatment of sleep disorders in MS, a better understanding of other factors that contribute to MS sleep disturbance and use of sleep medications in this population is needed. Methods: Individuals with MS (N = 473) involved in an ongoing self-report survey study were asked to report on use of over-the-counter and prescription sleep medications. Participants completed the Medical Outcomes Study Sleep (MOSS) scale and other common self-report symptom measures. Multiple regression was used to evaluate factors associated with sleep problems and descriptive statistics were generated to examine use of sleep medications. Results: The mean score on the MOSS scale was 35.9 (standard deviation, 20.2) and 46.8% of the sample had moderate or severe sleep problems. The majority of participants did not use over-the-counter (78%) or prescription (70%) sleep medications. In a regression model variables statistically significantly associated with sleep problems included depression, nighttime leg cramps, younger age, pain, female sex, fatigue, shorter duration of MS, and nocturia. The model explained 45% of the variance in sleep problems. Of the variance explained, depression accounted for the majority of variance in sleep problems (33%), with other variables explaining significantly less variance. Conclusions: Regression results indicate that fatigue may play a minor role in sleep disturbance in MS and that clinicians should consider the interrelationship between depression and sleep problems when treating either symptom in this population. More research is needed to explore the possibility of under-treatment of sleep disorders in MS and examine the potential effectiveness of nonpharmaceutical treatment options.
Identification of Novel Genes Selectively Expressed in the Follicle-Associated Epithelium from the Meta-Analysis of Transcriptomics Data from Multiple Mouse Cell and Tissue Populations

The follicle-associated epithelium (FAE) overlying the Peyer's patches and the microfold cells (M cells) within it are important sites of antigen transcytosis across the intestinal epithelium. Using a meta-analysis approach, we identified a transcriptional signature that distinguished the FAE from a large collection of mouse cells and tissues. A co-expressed cluster of 21 FAE-specific genes was identified, and the analysis of the transcription factor binding site motifs in their promoter regions indicated that these genes shared an underlying transcriptional programme. This cluster contained known FAE- (Anxa10, Ccl20, Psg18 and Ubd) and M-cell-specific (Gp2) genes, suggesting that the others were novel FAE-specific genes. Some of these novel candidate genes were expressed highly by the FAE and M cells (Calcb, Ces3b, Clca2 and Gjb2), and others only by the FAE (Ascl2, Cftr, Fgf15, Gpr133, Kcna1, Kcnj15, Mycl1, Pgap1 and Rps6kl). We also identified a subset of novel FAE-related genes that were induced in the intestinal epithelium after receptor activator of nuclear factor (NF)-κB ligand stimulation. These included Mfge8 which was specific to FAE enterocytes. This study provides new insight into the FAE transcriptome. Further characterization of the candidate genes identified here will aid the identification of novel regulators of cell function in the FAE.
Stability of Latanoprost in Generic Formulations Using Controlled Degradation and Patient Usage Simulation Studies

Abstract Purpose: To evaluate the stability of latanoprost in generic formulations by using controlled degradation and patient usage simulation studies Methods: Standard latanoprost was subjected to controlled degradation studies. Latanoprost content was assessed by using MRM, and generated Degradation Products (DP) were analysed by using the Information Dependent Acquisition (IDA) protocol of positive ESI-LC-MS/MS. Latanoprost content and formation of DP were assessed in generic formulations and were compared with Xalatan® in a controlled patient usage simulation studies. The last few drops of latanoprost, present in containers used by patients were also evaluated. Results: Extreme pH conditions, oxidation, light and heat were found to be the significant factors for high degree of latanoprost degradation. Systematic analysis of 7 selected generics revealed that the latanoprost content varied from 90–330%. Concentration of the latanoprost in Xalatan was found to be 97% of the label claim. Degradation studies showed the formation of 3 novel and 3 already known impurities. Upon simulated patient usage, 2 of the generic formulations showed significant degradation of latanoprost. Generic formulations having thermally sealed gas tight packing showed good stability during patient usage. Overage of latanoprost was observed in generics with other than thermal sealing. Latanoprost bottles used by patients showed concentrations ranging from 20 to 250% of label claim (144% median). Conclusion: This study revealed the presence of overage of latanoprost in some generic formulations and formation of degradation products. Packaging with gas tight containers may be one of the important factors for latanoprost stability, along with its storage at low temperature during patient usage.
Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that serves as a model for the human disease multiple sclerosis. We evaluated rolipram, a type IV phosphodiesterase inhibitor, for its efficacy in preventing EAE in the common marmoset Callithrix jacchus. In a blinded experimental design, clinical signs of EAE developed within 17 days of immunization with human white matter in two placebo-treated animals but in none of three monkeys that received rolipram (10 mg/kg s.c. every other day) beginning 1 week after immunization. In controls, signs of EAE were associated with development of cerebrospinal fluid pleocytosis and cerebral MRI abnormalities. In the treatment group, there was sustained protection from clinical EAE, transient cerebrospinal fluid pleocytosis in only one of three animals, no MRI abnormality, and marked reduction in histopathologic findings. Rolipram-treated and control animals equally developed circulating antibodies to myelin basic protein. Thus, inhibition of type IV phosphodiesterase, initiated after sensitization to central nervous system antigens, protected against autoimmune demyelinating disease.