Miracle-dz/UniFAR-FTUs huggingface dataset:
Preimplantation Embryo Development in the Mouse Requires the Latency of TRP53 Expression, Which Is Induced by a Ligand-Activated PI3 Kinase/AKT/MDM2-Mediated Signaling Pathway1 (Reprinted with Correction)

Abstract A universal response to cellular stress is the expression of transformation-related protein 53 (TRP53). This transcription factor reduces cell proliferation and/or survival and is classed as a tumour suppressor protein. Several stresses (including culture) cause increased TRP53 expression in blastocysts and their reduced long-term developmental potential. This study shows that culture from the zygote stage (but not the 2-cell stage) reduced the development of C57BL6 inbred (but not hybrid) strain mouse embryos. Reduced viability was TRP53 dependent, being partially reversed by a TRP53 inhibitor (Pifithrin-alpha). However, the presence of culture did not cause an increase in Trp53 mRNA levels (levels were reduced following culture, P < 0.001). Transformed mouse 3T3 cell double minute 2 (MDM2) causes the ubiquitination and degradation of TRP53. MDM2 activation is accompanied by phosphorylation of Ser-166, and this is commonly catalyzed by the phosphatidylinositol-3 kinase and RAC-alpha serine/threonine-protein kinase (AKT) signaling pathway. Paf is an autocrine embryotrophin that activates the phosphatidylinositol-3 kinase/AKT pathway. High levels of TRP53 expression occurred following the culture of zygotes lacking the Paf receptor (Ptafr−/−) and following inhibition of phosphatidylinositol-3 kinase or AKT. Inhibition of MDM2 caused a Trp53-dependent reduction in zygote development. Inbred strain embryos cultured from the zygote stage expressed less phosphorylated MDM2 than similar embryos collected from the uterus. The addition of Paf to the media caused increased phosphorylation of MDM2, and this was blocked by inhibitors of phosphatidylinositol-3 kinase and AKT. The study identifies trophic ligand signaling via the activation of phosphatidylinositol-3 kinase and AKT as a mechanism resulting in the activation of MDM2.
Endotoxin Shock‐Associated Hypothermia

In sum, our results indicate that LPS shock-associated hypothermia involves the following major mechanisms: 1) a decrease in the threshold Tb for activation of cold thermogenesis; 2) the resultant widening of the interthreshold zone; and 3) cold-seeking behavior. We speculate that, in severe systemic inflammation, this hypothermia constitutes an adaptive response.
Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure.

PURPOSE Azacitidine (AZA) is the current standard of care for high-risk (ie, International Prognostic Scoring System high or intermediate 2) myelodysplastic syndrome (MDS), but most patients will experience primary or secondary treatment failure. The outcome of these patients has not yet been described. PATIENTS AND METHODS Overall, 435 patients with high-risk MDS and former refractory anemia with excess blasts in transformation (RAEB-T) were evaluated for outcome after AZA failure. The cohort of patients included four data sets (ie, AZA001, J9950, and J0443 trials and the French compassionate use program). RESULTS The median follow-up after AZA failure was 15 months. The median overall survival was 5.6 months, and the 2-year survival probability was 15%. Increasing age, male sex, high-risk cytogenetics, higher bone marrow blast count, and the absence of prior hematologic response to AZA were associated with significantly worse survival in multivariate analysis. Data on treatment administered after AZA failure were available for 270 patients. Allogeneic stem-cell transplantation and investigational agents were associated with a better outcome when compared with conventional clinical care. CONCLUSION Outcome after AZA failure is poor. Our results should serve as a basis for designing second-line clinical trials in this population.
Coreference resolution between sources of opinions in Spanish texts

This paper presents a system that identifies coreferent elements in Spanish texts, with the purpose of contributing to an opinion extraction project. In particular, the system looks for the actual source when it is not identified in the opinion and solves coreferences between opinion sources in digital media texts in Spanish. The developed system takes as input texts where the opinions have already been identified, and uses syntactic and semantic information to identify the relationships between the different entities, in order to create coreference chains between the sources of the opinions in the text. The algorithm uses a score method to select the correct antecedent between the candidates. It achieved a precision of 82.8% and a recall of 85.6%.
Thirty years of European research on international trade in food and agricultural products

This survey focuses on the economic studies of international trade in agricultural and food products that has been an expanding area of specialisation in the agricultural economics profession in Europe since 1984. The contributions of agricultural economists have been particularly significant in Europe by assessing (i) the compatibility of agricultural policies with the multilateral trade rules and (ii) the macroeconomic impacts of agricultural trade agreements on Northern agricultures and on market access of developed and developing countries. Recent developments have shifted the focus of the international trade from countries and food industries towards food firms and products. The future research agenda will be driven by the needs of policy makers to find solutions to new and pressing issues and in particular growing societal concerns over the environmental, public health, diet composition, animal welfare and climate impacts of food production, and re-emerging food security concerns for developing countries.
A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis

TRPV4 ion channel mediates vascular mechanosensitivity and vasodilation. Here, we sought to explore whether non-mechanical activation of TRPV4 could limit vascular inflammation and atherosclerosis. We found that GSK1016790A, a potent and specific small-molecule agonist of TRPV4, induces the phosphorylation and activation of eNOS partially through the AMPK pathway. Moreover, GSK1016790A inhibited TNF-α-induced monocyte adhesion to human endothelial cells. Mice given GSK1016790A showed increased phosphorylation of eNOS and AMPK in the aorta and decreased leukocyte adhesion to TNF-α-inflamed endothelium. Importantly, oral administration of GSK1016790A reduced atherosclerotic plaque formation in ApoE deficient mice fed a Western-type diet. Together, the present study suggests that pharmacological activation of TRPV4 may serve as a potential therapeutic approach to treat atherosclerosis.
Comparative phylogeography among hydrothermal vent species along the East Pacific Rise reveals vicariant processes and population expansion in the South

The use of sequence polymorphism from individual mitochondrial genes to infer past demography has recently proved controversial because of the recurrence of selective sweeps acting over genes and the need for unlinked multilocus data sets. However, comparative analyses using several species for one gene and/or multiple genes for one species can serve as a test for potential selective effects and clarify our understanding of historical demographic effects. This study compares nucleotide polymorphisms in mitochondrial cytochrome oxidase I across seven deep‐sea hydrothermal vent species that live along the volcanically active East Pacific Rise. Approximate Bayesian Computation (ABC) method, developed to trace shared vicariant events across species pairs, indicates the occurrence of two across species divergence times, and suggests that the present geographical patterns of genetic differentiation may be explained by two periods of significant population isolation. The oldest period dates back 11.6 Ma and is associated with the vent limpet Lepetodrilus elevatus, while the most recent period of isolation is 1.3 Ma, which apparently affected all species examined and coincides with a transition zone across the equator. Moreover, significant negative Tajima’s D and star‐like networks were observed for all southern lineages, suggesting that these lineages experienced a concomitant demographic and geographical expansion about 100 000–300 000 generations ago. This expansion may have initiated from a wave of range expansions during the secondary colonization of new sites along the Southern East Pacific Rise (founder effects below the equator) or recurrent bottleneck events because of the increase of eruptive phases associated with the higher spreading rates of the ridge in this region.
Availability evaluation of Multi-Terminal DC networks with DC circuit breakers

This paper evaluates the availability of three conceptual offshore Multi-Terminal HVDC (MTDC) grids with DC circuit breakers (DC-CBs). MTDC grids can simultaneously support integration of offshore wind power plants, cross-border trade of electricity and electrification of oil&gas installations. A Reliability, Availability and Maintainability (RAM) approach has been used to analyse the systems. Discrete-event simulations are performed using Monte-Carlo techniques for random sampling. With DC-CBs, DC faults can be isolated, hence avoiding complete shutdown of the entire MTDC grid. The results show that local converter faults are the most dominant source of unavailability and that DC-CBs will only marginally increase the availability of power at the offshore nodes. On the other hand, DC-CBs will significantly increase the reliability of power. Assessing the consequences of power outages to the affected nodes and to the onshore AC power systems is therefore of utmost importance to quantify the benefit of DC-CBs.
The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome

Abstract A numeric scoring system for the assessment of hypoxic ischaemic encephalopathy during the neonatal period was tested. The value of the score in predicting neurodevelopmental outcome at 1 y of age was assessed. Forty‐five infants who developed hypoxic ischaemic encephalopathy after birth were studied prospectively. In addition to the hypoxic ischaemic encephalopathy score all but two infants had at least one cranial ultrasound examination. Thirty‐five infants were evaluated at 12 months of age by full neurological examination and the Griffiths Scales of Mental Development. Five infants were assessed at an earlier stage, four who died before 6 months of age and one infant who was hospitalized at the time of the 12 month assessment. Twenty‐three (58%) of the infants were normal and 17 (42%) were abnormal, 16 with cerebral palsy and one with developmental delay. The hypoxic ischaemic encephalopathy score was highly predictive for outcome. The best correlation with outcome was the peak score; a peak score of 15 or higher had a positive predictive value of 92% and a negative predictive value of 82% for abnormal outcome, with a sensitivity and specificity of 71% and 96%, respectively. For the clinician working in areas where sophisticated technology is unavailable this scoring system will be useful for assessment of infants with hypoxic ischaemic encephalopathy and for prognosis of neurodevelopmental outcome.
Tax Policy and the Economy, Volume 29

The papers in Volume 29 of Tax Policy and the Economy illustrate the depth and breadth of the taxation-related research by NBER research associates, both in terms of methodological approach and in terms of topics. In the first paper, former NBER President Martin Feldstein estimates how much revenue the federal government could raise by limiting tax expenditures in various ways, such as capping deductions and exclusions. The second paper, by George Bulman and Caroline Hoxby, makes use of a substantial expansion in the availability of education tax credits in 2009 to study whether tax credits have a significant causal effect on college attendance and related outcomes. In the third paper, Casey Mulligan discusses how the Affordable Care Act (ACA) introduces or expands taxes on income and on full-time employment. In the fourth paper, Bradley Heim, Ithai Lurie, and Kosali Simon focus on the “young adult” provision of the ACA that allows young adults to be covered by their parents’ insurance policies. They find no meaningful effects of this provision on labor market outcomes. The fifth paper, by Louis Kaplow, identifies some of the key conceptual challenges to analyzing social insurance policies, such as Social Security, in a context where shortsighted individuals fail to save adequately for their retirement.
Increased Immunogenicity of a DNA-Launched Venezuelan Equine Encephalitis Virus-Based Replicon DNA Vaccine

ABSTRACT A novel genetic vaccine that is based on a Venezuelan equine encephalitis virus (VEE) replicon launched from plasmid DNA is described. The plasmid encodes a VEE replicon under the transcriptional control of the cytomegalovirus immediate-early promoter (VEE DNA). The VEE DNA consistently expressed 3- to 15-fold more green fluorescent protein in vitro than did a conventional DNA vaccine. Furthermore, transfection with the DNA-launched VEE replicon induced apoptosis and type I interferon production. Inoculation of mice with VEE DNA encoding human immunodeficiency virus type 1 gp160 significantly increased humoral responses by several orders of magnitude compared to an equal dose of a conventional DNA vaccine. These increases were also observed at 10- and 100-fold-lower doses of the VEE DNA. Cellular immune responses measured by gamma interferon and interleukin 2 enzyme-linked immunospot assay were significantly higher in mice immunized with the VEE DNA at decreased doses. The immune responses induced by the VEE DNA-encoded antigen, however, were independent of an intact type I interferon signaling pathway. Moreover, the DNA-launched VEE replicon induced an efficient prime to a VEE replicon particle (VRP) boost, increasing humoral and cellular immunity by at least 1 order of magnitude compared to VEE DNA only. Importantly, immunization with VEE DNA, as opposed to VRP, did not induce any anti-VRP neutralizing antibodies. Increased potency of DNA vaccines and reduced vector immunity may ultimately have an impact on the design of vaccination strategies in humans.
Quantitative analysis of foot-and-mouth disease virus RNA loads in bovine tissues: implications for the site of viral persistence.

To understand better the pathogenesis of foot-and-mouth disease (FMD), the levels of viral RNA in various bovine tissues during the acute and persistent stages of FMD virus (FMDV) infection were investigated by using quantitative RT-PCR. The viral RNA levels in the tissues examined had peaked by day 1 post-infection (p.i.) and were markedly different among the tissues examined. The epithelium collected from sites of lesion development, i.e. the interdigital area and coronary band on the feet, and the tongue, contained the highest level of viral RNA, indicating the predominant tissue sites of viral infection and amplification during the acute stage of infection. Clearance of viral RNA from most of the tissues occurred relatively rapidly and the rate of clearance was largely independent of the level of viral RNA. The viral RNA load in most of the tissues declined slower than in serum, in which viral clearance is rapid. Beyond 28 days p.i. , a proportion of pharyngeal region tissues (soft palate, pharynx, tonsil and mandibular lymph node) from infected animals still contained a detectable level of viral RNA, while viral RNA in non-pharyngeal region tissues was generally only detectable for variable periods ranging from 4 to 14 days p.i. The presence of viral RNA in dorsal soft palate tissue had a good correlation with the presence of infectious virus in oesophageal-pharyngeal fluid (OP-fluid) samples, a finding indicative of the specific tissue sites of FMDV persistence.
Design and implementation of light load energy saving current-limiting circuit

This article presents a current-limiting protection circuit, which is being used in the design of USB power management chip. Compared with the traditional current-limiting protection circuit, its advantage lies in using a constant current source to replace the traditional series sampling resistor to reduce the power consumption generated by the drive circuit. What's more, on the purpose of energy conservation, it increases the voltage feedback control signal to change the current mirror ratio for reducing the power consumption of the chip itself under the condition of light load. The principle of this current limiting circuit is analyzed theoretically in this article. Meanwhile, the theory is verified by CMOS0.35um process simulation.
Different forms of Go alpha mRNA arise by alternative splicing of transcripts from a single gene on human chromosome 16

Go alpha, (gene symbol GNA01), a member of the signal-transducing guanine nucleotide-binding (G) protein family, has been implicated in ion channel regulation. Some tissues contain multiple Go alpha mRNAs of different sizes that differ in the 3' untranslated regions (UTRs). Using sequence-specific 48-base oligonucleotides, two complementary to the different 3' UTRs and one complementary to the coding region, we investigated the origin of the multiple Go alpha transcripts, the organization of the Go alpha gene, the interspecies conservation of 3' UTRs, and the chromosomal localization of Go alpha. Oligonucleotides labeled to high specific activity by using terminal deoxynucleotidyltransferase each hybridized with a single band of restriction enzyme-digested mouse and human DNAs. In three of four digests of human DNA, the two probes specific for the different 3' UTRs hybridized with the same restriction fragment. Thus, these nucleotide sequences are in close proximity in the human genome. The order of the UTRs in the bovine, human, and mouse genomes was confirmed directly by polymerase chain reaction (PCR) amplification and sequencing. Hybridization of bovine oligonucleotide sequence with mouse and human genomic DNA indicated a high degree of interspecies sequence conservation: conservation was confirmed by PCR amplification and sequencing. Bands detected by both UTR probes, as well as the predominant bands detected by a bovine Go alpha cDNA, segregated with human chromosome 16 on Southern blot analysis of human-mouse somatic cell hybrids. We conclude that Go alpha mRNAs with different 3' UTRs arise by alternative splicing of transcripts from a single gene. The UTRs, which exhibit a high degree of interspecies conservation, may play a role in regulation of Go alpha expression during differentiation or in specific tissues. The use of oligonucleotide probes of the type described here represents a new strategy, potentially widely applicable for mapping and elucidating structural features of genes.
Cardiorespiratory fitness, BMI, and risk of hypertension: the HYPGENE study.

INTRODUCTION Cardiorespiratory fitness and regular physical activity are inversely associated with the risk of hypertension, and exercise training has been shown to lower elevated blood pressure (BP). Genetic factors contribute significantly to the interindividual differences in endurance training-induced changes in BP. However, similar data on the genotype-by-fitness interactions on the risk of hypertension are scarce. METHODS In 2000, we started a systematic collection of blood samples from all consenting subjects of the Aerobics Center Longitudinal Study (ACLS) with a goal to generate a resource for studies addressing genotype-by-fitness interaction effects on various health-related end points. Here, we introduce the rationale and design of the first study based on the ACLS genetics resource focusing on hypertension as the health outcome (HYPGENE study), and we report the associations of cardiorespiratory fitness and body mass index (BMI) with the risk of hypertension. All HYPGENE subjects (N = 1234) were healthy and normotensive at their first clinic visit. Cases (N = 629) developed hypertension during the follow-up period (mean 8.7 yr), whereas controls (N = 605) remained normotensive (mean follow-up 10.1 yr). RESULTS Cardiorespiratory fitness was the strongest predictor of the hypertension risk, with each maximal metabolic equivalent unit being associated with a 19% lower risk (95% confidence interval [95% CI], 12-24%). Each baseline BMI unit was associated with a 9% higher hypertension risk (95% CI, 4-13%). However, the association of BMI was greatly attenuated (odds ratio 1.04 [95% CI, 0.99-1.09]) when fitness also was included in the model. CONCLUSIONS The HYPGENE study will provide an excellent resource to address hypotheses regarding the genetic basis of hypertension while taking cardiorespiratory fitness level into account.
Polyurethane-covered metal stent for management of distal malignant biliary obstruction.

BACKGROUND The efficacy of polyurethane-covered metal expandable stents for treatment of neoplastic distal biliary obstruction was analyzed. METHODS Twenty-one patients with unresectable malignant tumors involving the mid to distal bile duct who were seen with obstructive jaundice were consecutively enrolled. Eighteen patients underwent endoscopic implantation of a polyurethane-covered metal stent and 3 patients underwent transhepatic insertion because of duodenal obstruction. The stent patency, complications, and patient survival were analyzed. RESULTS Effective biliary decompression was achieved in all patients. Adverse events were minor: mild pancreatitis (1) and cholecystitis (2) occurred within 7 days of stent insertion. Mean survival and stent patency were 233 days and 206 days, respectively. Stent occlusion occurred in 3 patients (14%) after a mean of 188 days. Tumor ingrowth through the stent mesh was not observed. However, 2 stents were occluded by tumor overgrowth and 1 by compacted alimentary debris. CONCLUSIONS A polyurethane membrane may prevent tumor ingrowth and reduce the occlusion rate for expandable metal stents implanted in patients with malignant obstruction of the distal bile duct.
Role of the Cytoskeleton in Mediating cAMP-dependent Protein Kinase Inhibition of the Epithelial Na+/H+ Exchanger NHE3*

The Na+/H+exchanger NHE3 isoform mediates the entry of Na+ into epithelial cells of the kidney and gastrointestinal tract. Hormones and pharmacological agents that activate cAMP-dependent protein kinase A (PKA) are potent inhibitors of native and ectopically expressed NHE3 in epithelial and Chinese hamster ovary AP-1 cells, respectively. Previous studies have shown that acute inhibition is coupled to direct phosphorylation of the exchanger, but this only partly accounts for the observed effects. In this report, we show that inhibition of NHE3 activity by forskolin, an activator of adenylate cyclase, occurs without changes in surface expression of the exchanger but is associated with altered cytoskeletal structure. This effect resembles that obtained with cytochalasin D or latrunculin B, actin disrupting agents that also inhibit NHE3. Such similarities prompted us to further investigate the relationship between PKA-induced inhibition of the exchanger and changes in the actin cytoskeleton. Inhibition of NHE3 by cytochalasin D does not require PKA, because the inhibitory effect is preserved in a mutant NHE3 that is not phosphorylated by PKA and in cells pretreated with the PKA inhibitor H89. In contrast, involvement of actin in the effect of cAMP on the exchanger is supported by the following observations: (i) jasplakinolide, an F-actin stabilizer, prevents the inhibition caused by forskolin, and (ii) constitutively active forms of RhoA and Rho kinase interfere with actin disruption by forskolin and also decrease inhibition of the transporter. These results suggest that reorganization of the cytoskeleton by PKA is involved in mediating inhibition of NHE3.