Miracle-dz/UniFAR-FTUs huggingface dataset:
Delayed Mitogen-Activated Protein Kinase/Extracellular Signal–Regulated Kinase Inhibition by Trametinib Attenuates Systemic Inflammatory Responses and Multiple Organ Injury in Murine Sepsis*

Objective:The mitogen-activated protein kinase/extracellular signal–regulated kinase signaling pathway is an essential component of innate immunity necessary for mediating proinflammatory responses in the setting of sepsis. We previously demonstrated that the mitogen-activated protein kinase 1/2 inhibitor trametinib prevents endotoxin-induced renal injury in mice. We therefore assessed efficacy of trametinib in a more clinically relevant experimental model of sepsis. Design:Controlled in vivo laboratory study. Setting:University animal research laboratory. Subjects:Male C57BL/6 mice. Interventions:Mice were subjected to cecal ligation and puncture to induce sepsis or underwent sham operation as controls. Six hours after cecal ligation and puncture, mice were randomized to four experimental groups as follows: 1) sham control; 2) sham control + trametinib (1 mg/kg, IP); 3) cecal ligation and puncture; and 4) cecal ligation and puncture + trametinib. All animals received buprenorphine (0.05 mg/kg, SC) and imipenem/cilastatin (14 mg/kg, SC) in 1.5 mL of warm saline (40 mL/kg) at the 6-hour time point. Mice were euthanized at 18 hours after induction of cecal ligation and puncture. Measurements and Main Results:Trametinib inhibition of mitogen-activated protein kinase/extracellular signal–regulated kinase signaling 6 hours after cecal ligation and puncture attenuated increases in circulating proinflammatory cytokines (tumor necrosis factor-&agr;, interleukin-1&bgr;, interleukin-6, and granulocyte macrophage colony-stimulating factor) and hypothermia at 18 hours. Trametinib also attenuated multiple organ injury as determined by serum creatinine, alanine aminotransferase, lactate dehydrogenase, and creatine kinase. At the organ level, trametinib completely restored peritubular capillary perfusion in the kidney. Restoration of microvascular perfusion was associated with reduced messenger RNA expression of well-characterized markers of proximal tubule injury. mitogen-activated protein kinase/extracellular signal–regulated kinase blockade attenuated cecal ligation and puncture-mediated up-regulation of cytokines (tumor necrosis factor-&agr;, interleukin-1&bgr;) and restored interleukin-6 to control levels in the renal cortex, indicating the protective effects on the proximal tubule occur primarily through modulation of the proinflammatory response in sepsis. Conclusions:These data reveal that the mitogen-activated protein kinase/extracellular signal–regulated kinase inhibitor trametinib attenuates systemic inflammation and multiple organ damage in a clinically relevant model of sepsis. Because trametinib has been safely used in humans, we propose that this drug might represent a translatable approach to limit organ injury in septic patients.
[Comparison of competence of olfactory globular nerve layer gliocytes, olfactory epithelial gliacytes and SC in repairing nerve defect].

OBJECTIVE To compare their competence of olfactory epithelial gliocytes, olfactory globular nerve layer (OGNL) gliocytes and SC in repair nerve defect of sciatic nerve, and select the best gliocytes for repair of peripheral nerve defect. METHODS Olfactory epithelial gliocytes, OGNL gliocytes and SC were extracted from 20 female Wistar rats aged 2-3 months and cultured in vitro for 2 weeks, then purified and condensed for transplantation. Eighty adult female Wistar rats were randomized into groups A, B, C and D (n = 20). The left sciatic nerves were excised 25 mm axons and retained epineurium lumen anastomosed to proximal ends. The culture mediums, SC, OGNL gliocytes, and olfactory epithelial gliocytes were transplanted into the epineurium lumen of groups A, B, C and D, respectively. Three months postoperatively, the injured sciatic nerve regeneration was evaluated by methods of macroscopic observation, photomicroscope, transmission electron microscope, retro-marked fluorescence transportation distance, the glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) were assayed by immunofluorescence, and the myelin basic protein (MBP) and neurofilament (NF) protein were assayed by ELISA. RESULTS The scores of ankle joint were (3.325 +/- 0.963), (4.200 +/- 1.005), (5.143 +/- 0.635) and (5.950 +/- 0.154) in groups A, B, C and D, respectively; showing statistically significant difference between groups (P < 0.05). The observations of gross, sections under microscope and transmission electron microscope showed the regeneration of defect nerve was best in group D, followed by group C, and group B was superior to group A. The transportation distance of retro-marked fluorescence was longest in group D, followed by group C, and group B was superior to group A. The concentrations of GFAP and NGF were largest in group D, followed by group C, and group B was superior to group A. The MBP concentrations were (9.817 +/- 3.267), (12.347 +/- 3.091), (14.937 +/- 2.075) and (22.757 +/- 0.871) ng/mL in groups A, B, C and D, respectively; showing statistically significant difference between other groups (P < 0.05) except between group A and group B (P > 0.05). And the NF concentrations were (13.869 +/- 5.677), (18.498 +/- 3.889), (23.443 +/- 2.260) and (27.610 +/- 1.125) ng/mL in groups A, B, C and D, respectively; showing statistically significant difference between groups (P < 0.05). CONCLUSION Olfactory epithelial gliocytes, OGNL gliocytes and SC transplantation could repair injured nerve. The competence of olfactory epitheliums is superior to the OGNL gliocytes and SC, and the OGNL gliocytes is better than SC.
Phenolic Content and Antioxidant Capacity of Pawpaw Fruit (Asimina triloba L.) at Different Ripening Stages

Pawpaw (Asimina triloba (L.) Dunal), a native species of the eastern United States, bears the largest edible fruit of all indigenous trees. Chemoprotective properties of fruits have been partly attributed to phenolics such as gallic acid and chlorogenic acid, and the phenolic content generally correlates with antioxidant capacity for various kinds of fruits. Despite many reports of commonly available fruits, little information is avail- able on phenolic content or antioxidant capacity for currently underused fruits. The objectives of this study were to determine the phenolic content (PC) and antioxidant capacity (AC) in fruit of two pawpaw cultivars at different stages of ripening. Sample extraction of pawpaw was achieved by adding acetone (2 mL/1g of sample) to the pulp of 'PA-Golden (#1)' and advanced selection 1-23, and then vortexing (30 s) and sonicating (15 min.) the sample and solvent before centrifuging it (15 min) twice at 2987 g. Folin- Ciocalteuassayandferric reducing/antioxidant powerassaywere usedfortheestimation of PC and AC, respectively. PC and AC tended to decrease with ripening of fruit. The highest AC was found in the semiripe 'PA-Golden (#1)' puree (22.06 mmol TE/g fresh weight), whereas the puree of ripe fruit contained the lowest AC (17.04 mmol TE/g fresh weight), about a 23% decrease. In contrast, the greatest PC and AC were observed in intermediate fruits for 1-23. A positive correlation was found between PC and ACof fruit of 'PA-Golden (#1)' (r = 0.62) and 1-23 (r = 0.82). These results suggest that phenolic components of pawpaw pulp have a major effect on AC, as reported for other fruits and vegetables. The relatively high AC found in pawpaw pulp may motivate more health- conscientious people to consume pawpaw fruit. The diversity in PC and AC between pawpaw cultivars emphasizes the need for additional screening to identify cultivars with high AC and health-promoting potential.
Hemostatic Alterations With Exercise Conditioning in NIDDM

Various parameters of coagulation and fibrinolysis were measured in 13 men (aged 54 ± 3 yr) with non-insulindependent diabetes mellitus (NIDDM) before and after 12-14 wk of exercise training. Subjects exercised for 30 min 3 times/wk at 70% of maximum O2 consumption (Vo2max). Training increased Vo2max by 12.5% but did not alter body weight, relative body fat, blood pressure, cholesterol, triglycerides, or high-density lipoprotein cholesterol. Slight downward trends were apparent for fasting glucose and insulin, but glycosylated hemoglobin was unchanged. There were no changes in coagulation parameters of plasminogen, hematocrit, or α2-antiplasmin. Plasma fibrinogen (303 ± 24.2 vs. 256 ± 12.3 mg/dl) and fibronectin (380 ± 41.9 vs. 301 ± 22.2 μg/ml) were significantly reduced (P < 0.02) by exercise conditioning. Three assays of fibrinolytic activity (tissue plasminogen activator, euglobulin lysis time, and an isotopic measure of fibrinolysis) confirmed that neither basal fibrinolysis nor the fibrinolytic responses to venous occlusion and maximal exercise were significantly altered. Exercise conditioning may have antithrombotic effects in NIDDM by reducing plasma fibrinogen and fibronectin. Although the significance of the fall in fibronectin awaits further studies, the reduction in plasma fibrinogen gives a rationale for the use of exercise training in men with NIDDM.
An overview of the UK Employment Appeal Tribunal decisions in sexual harassment cases 1995‐2005

Purpose – The purpose of this paper is to present research conducted with legal cases of sexual harassment (SH) in Great Britain over the past ten years. The paper contributes to the equal opportunities literature since it offers a rare interpretation of longitudinal case data with important implications for law, policy, social science and, indeed, for the management of equal opportunities within organizations. The paper approaches SH both as an evolving legal issue and as a type of organizational conflict, with particular power influences and effects.Design/methodology/approach – The population of individual case records with a SH component was accessed via the BALII database for the period 1995‐2005. These case records were content‐analyzed using a framework of variables developed for the study. Variables of interest initially were identified from a review of the social science, law and policy‐related literaturesFindings – The vast majority (96 per cent) of workers bringing appeals of SH were female. Th.
Photoperiod Modulates Fast Delayed Rectifier Potassium Currents in the Mammalian Circadian Clock

One feature of the mammalian circadian clock, situated in the suprachiasmatic nucleus (SCN), is its ability to measure day length and thereby contribute to the seasonal adaptation of physiology and behavior. The timing signal from the SCN, namely the 24 hr pattern of electrical activity, is adjusted according to the photoperiod being broader in long days and narrower in short days. Vasoactive intestinal peptide and gamma-aminobutyric acid play a crucial role in intercellular communication within the SCN and contribute to the seasonal changes in phase distribution. However, little is known about the underlying ionic mechanisms of synchronization. The present study was aimed to identify cellular mechanisms involved in seasonal encoding by the SCN. Mice were adapted to long-day (light–dark 16:8) and short-day (light–dark 8:16) photoperiods and membrane properties as well as K+ currents activity of SCN neurons were measured using patch-clamp recordings in acute slices. Remarkably, we found evidence for a photoperiodic effect on the fast delayed rectifier K+ current, that is, the circadian modulation of this ion channel’s activation reversed in long days resulting in 50% higher peak values during the night compared with the unaltered day values. Consistent with fast delayed rectifier enhancement, duration of action potentials during the night was shortened and afterhyperpolarization potentials increased in amplitude and duration. The slow delayed rectifier, transient K+ currents, and membrane excitability were not affected by photoperiod. We conclude that photoperiod can change intrinsic ion channel properties of the SCN neurons, which may influence cellular communication and contribute to photoperiodic phase adjustment.
Rejection sensitivity, loneliness, social anxiety, and social withdrawal in children.

REJECTION SENSITIVITY, LONELINESS, SOCIAL ANXIETY, AND SOCIAL WITHDRAWAL IN CHILDREN MAY 1999 CHERYL BONICA, B.S., UNION COLLEGE M.S., UNIVERSITY OF MASSACHUSETTS Directed by: Professor Sally I. Powers Some children experience angry expectations of rejection in reaction to ambiguously intentioned rejection feedback, whereas others experience anxious expectations of rejection. These children have been described as rejection sensitive (Downey, Lebolt, Rincon, & Freitas, 1998). Adopting a longitudinal design, rejection sensitivity, loneliness, social anxiety and social withdrawal in children were assessed at Time 1 and four months later, at Time 2. Data were from 171 urban, minority (primarily Hispanic and African American) sixth graders. Results indicated angry expectations of rejection predicted increases in feelings of loneliness over time. Whereas anxious expectations of rejection predicted increases in feelings of loneliness for girls, anxious expectations did not predict increases in feelings of loneliness for boys. Anxious expectations of rejection predicted increases in social anxiety and social withdrawal. Loneliness predicted increases in angry and anxious expectations of rejection. Results highlight the important role of rejection sensitivity in promoting internalizing difficulties.
Energy Efficiency and Process Variation Tolerance of 45 nm Bulk and High-k CMOS Devices

With transistor sizes being reduced to sub 45nm ranges, we have seen an improvement in speed, better performance, and deeper integration of digital circuits. However, there has been a corresponding increase in power consumption, along with greater energy dissipation. The reason is because of increased leakage current in the channel. A proposed solution is a shift towards high-k materials and metal gate from poly-silicon gate of yesteryear. Reduced feature sizes also suffer from greater parametric process variations during lithography and cause identical circuits to behave differently. With high-k technology overshadowing bulk technology ever since transistor sizes hit 45nm, a greater understanding of how the properties of high-k technology will affect digital devices especially their speed, power consumption, and energy dissipated upon voltage scaling is needed. Also, a better estimation of effects of parametric variations on circuits designed in high-k technology can provide valuable information which can be used to improve current designs.
A Closer Look at Gender and Strategy Use in L2 Reading

This study examines gender differences in cognitive and metacognitive strategy use in the context of an English as a foreign language reading comprehension test. Three hundred eighty-four Thai university students took a multiple-choice reading comprehension test, then completed a questionnaire on their strategy use. Gender differences were analyzed using multivariate analysis of variance. Males and females did not differ in their reading comprehension performance and their use of cognitive strategies. Unexpectedly, males reported significantly higher use of metacognitive strategies than females. Within the same achievement groups (highly successful, moderately successful, and unsuccessful), however, there were no gender differences in either reading performance or use of cognitive and metacognitive strategies. The article discusses the implications for future gender-based research.
A new—old algorithm for minimum‐cut and maximum‐flow in closure graphs

We present an algorithm for solving the minimum‐cut problem on closure graphs without maintaining flow values. The algorithm is based on an optimization algorithm for the open‐pit mining problem that was presented in 1964 (and published in 1965) by Lerchs and Grossmann. The Lerchs—Grossmann algorithm (LG algorithm) solves the maximum closure which is equivalent to the minimum‐cut problem. Yet, it appears substantially different from other algorithms known for solving the minimum‐cut problem and does not employ any concept of flow. Instead, it works with sets of nodes that have a natural interpretation in the context of maximum closure in that they have positive total weight and are closed with respect to some subgraph. We describe the LG algorithm and study its features and the new insights it reveals for the maximum‐closure problem and the maximum‐ flow problem. Specifically, we devise a linear time procedure that evaluates a feasible flow corresponding to any iteration of the algorithm. We show that while the LG algorithm is pseudopolynomial, our variant algorithms have complexity of O(mn log n), where n is the number of nodes and m is the number of arcs in the graph. Modifications of the algorithm allow for efficient sensitivity and parametric analysis also running in time O(mn log n). © 2001 John Wiley & Sons, Inc.
Parochial trust and cooperation across 17 societies

Significance In a study including 17 societies, we found that people are motivated to trust and cooperate more with their ingroup, than harm the outgroup. Reputation-based indirect reciprocity may offset this ingroup favoritism, because we found that reputational concern universally increases cooperation with both ingroup and outgroup members. We also found that people who are dispositionally cooperative are less parochial and more universal in their cooperation. In a time of increasing parochialism in both domestic and international relations, our findings affirm us of the danger of the strong human universal toward parochial altruism. Yet, our findings suggest that in all societies, there exist people whose cooperation transcends group boundaries and provides a solution to combating parochialism: reputation-based indirect reciprocity. International challenges such as climate change, poverty, and intergroup conflict require countries to cooperate to solve these complex problems. However, the political tide in many countries has shifted inward, with skepticism and reluctance to cooperate with other countries. Thus, cross-societal investigations are needed to test theory about trust and cooperation within and between groups. We conducted an experimental study in 17 countries designed to test several theories that explain why, who, and where people trust and cooperate more with ingroup members, compared with outgroup members. The experiment involved several interactions in the trust game, either as a trustor or trustee. We manipulated partner group membership in the trust game (ingroup, outgroup, or unknown) and if their reputation was at stake during the interaction. In addition to the standard finding that participants trust and cooperate more with ingroup than outgroup members, we obtained findings that reputational concerns play a decisive role for promoting trust and cooperation universally across societies. Furthermore, men discriminated more in favor of their ingroup than women. Individual differences in cooperative preferences, as measured by social value orientation, predicted cooperation with both ingroup and outgroup members. Finally, we did not find support for three theories about the cross-societal conditions that influence the degree of ingroup favoritism observed across societies (e.g., material security, religiosity, and pathogen stress). We discuss the implications for promoting cooperation within and between countries.
Suppression of Antiviral Silencing by Cucumber Mosaic Virus 2b Protein in Arabidopsis Is Associated with Drastically Reduced Accumulation of Three Classes of Viral Small Interfering RNAs[W][OA]

We investigated the genetic pathway in Arabidopsis thaliana targeted during infection by cucumber mosaic virus (CMV) 2b protein, known to suppress non-cell-autonomous transgene silencing and salicylic acid (SA)–mediated virus resistance. We show that 2b expressed from the CMV genome drastically reduced the accumulation of 21-, 22-, and 24-nucleotide classes of viral small interfering RNAs (siRNAs) produced by Dicer-like4 (DCL4), DCL2, and DCL3, respectively. The defect of a CMV 2b–deletion mutant (CMV-Δ2b) in plant infection was efficiently rescued in Arabidopsis mutants producing neither 21- nor 22-nucleotide viral siRNAs. Since genetic analysis further identifies a unique antiviral role for DCL3 upstream of DCL4, our data indicate that inhibition of the accumulation of distinct viral siRNAs plays a key role in 2b suppression of antiviral silencing. Strikingly, disease symptoms caused by CMV-Δ2b in Arabidopsis mutants defective in antiviral silencing were as severe as those caused by CMV, demonstrating an indirect role for the silencing suppressor activity in virus virulence. We found that production of CMV siRNAs without 2b interference depended largely on RNA-dependent RNA polymerase 1 (RDR1) inducible by SA. Given the known role of RDR6-dependent transgene siRNAs in non-cell-autonomous silencing, our results suggest a model in which 2b inhibits the production of RDR1-dependent viral siRNAs that confer SA-dependent virus resistance by directing non-cell-autonomous antiviral silencing.
Hitting the right target: taxonomic challenges for, and of, plant invasions

Taxonomic resources are essential for the effective management of invasive plants because biosecurity strategies, legislation dealing with invasive species, quarantine, weed surveillance and monitoring all depend on accurate and rapid identification of non-native taxa, and incorrect identifications can impede ecological studies. On the other hand, biological invasions have provided important tests of basic theories about species concepts. Modern taxonomy therefore needs to integrate both classical and new concepts and approaches to improve the accuracy of species identification and further refine taxonomic classification at the level of populations and genotypes in the field and laboratory.
An Exploration of L2 Teachers’ Use of Pedagogical Interventions Devised to Draw L2 Learners’ Attention to Form

This descriptive observational study aimed at exploring the form-focused instruction (FFI) interventions used by four French and four English as-a-second-language high school teachers to draw their students’ attention to form. With the help of an Intervention-on-Form(s)-Observation Scheme (IFOS) developed and tested for this purpose, each FFI intervention observed during 60 hours of video-recorded class time was coded according to its type (e.g., corrective feedback, explanation, enhancement, form-oriented exercises) and its related characteristics (e.g., linguistic focus, interactional pattern, source of the intervention). The results show that grammar-oriented interventions are rather frequent in these second-language classes and that some differences in preferences of intervention types exist in the two contexts. Although FFI interventions are more frequent in the English classes observed, the overall time spent on FFI is significantly higher in the French classes. The reasons for this as well as details regarding the characteristics of the interventions coded through the use of the IFOS will be discussed.