Miracle-dz/UniFAR-FTUs huggingface dataset:
Partitioning the Synaptic Landscape: Distinct Microdomains for Spontaneous and Spike-Triggered Neurotransmission

Spontaneous and evoked release of glutamate activates distinct NMDA receptor pools. For over 50 years, it has been recognized that two distinct modes of neurotransmission are operative at synapses: the release of neurotransmitter triggered by the invasion of action potentials into presynaptic terminals and spontaneous neurotransmitter release that occurs independently of action potentials. In the past, spontaneous neurotransmitter release has been dismissed as mere synaptic noise, but recent studies have suggested that spontaneous release has important functional roles at synapses. New evidence indicates that spontaneous release and action potential–evoked release preferentially activate distinct subsets of postsynaptic receptors, suggesting that synapses use physically segregated pathways to decode spontaneous and evoked neurotransmission.
Theodor Eimer and orthogenesis: evolution by 'definitely directed variation'.

Apres un apercu biographique de T. E. , etude du role de la variation (travaux de H. W. Bates, K. von Nageli), presentation de l'orthogenese et critique de A. Weismann. Les reactions en Angleterre et aux Etats-Unis (E. Cope, V. L. Kellogg, J. T. Cunningham, C. O. Whitman).
Plasma membrane Na(+)-H+ antiporter and H(+)-ATPase in the medullary thick ascending limb of rat kidney.

To characterize H+ transport mechanisms in a fresh suspension of rat medullary thick ascending limb (MTAL) tubules, we have monitored intracellular pH (pHi) with use of the fluorescent probe 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein. First, a Na(+)-H+ antiporter was identified in bicarbonate-free N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered media at 25 degrees C. pHi recovery of Na-depleted acidified cells was dependent on extracellular sodium concentration, which was inhibited by amiloride in a manner consistent with simple competitive interaction with one external transport site (amiloride Ki = 1.5-2.1 x 10(-5) M); Na-induced pHi recovery of acidified cells was electroneutral since it was not affected by 5 or 100 mM extracellular potassium in the presence or absence of valinomycin. Second, at 37 degrees C, pHi recovery after acute intracellular acidification caused by 40 mM acetate addition to cell suspension was inhibited 36% by 200-400 nM bafilomycin A1, a macrolide antibiotic that specifically inhibits vacuolar-type H(+)-ATPase at submicromolar concentrations. In addition, amiloride-insensitive pHi recovery was inhibited by bafilomycin A1, 10(-3) M N-ethylmaleimide, and 10(-4) M preactivated omeprazole but not by 10(-5) M vanadate, 10(-4) M SCH 28080, or removal of extracellular potassium. Also, metabolic inhibition by absence of substrate, 10(-4) M KCN, or 5 x 10(-4) M iodoacetic acid inhibited amiloride-insensitive pHi recovery. The inhibitory effects of absence of metabolic substrate and iodoacetic acid were removed by reexposure to glucose and L-leucine and by exogenous ATP, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
IL-4/STAT6 immune axis regulates peripheral nutrient metabolism and insulin sensitivity

Immune cells take residence in metabolic tissues, providing a framework for direct regulation of nutrient metabolism. Despite conservation of this anatomic relationship through evolution, the signals and mechanisms by which the immune system regulates nutrient homeostasis and insulin action remain poorly understood. Here, we demonstrate that the IL-4/STAT6 immune axis, a key pathway in helminth immunity and allergies, controls peripheral nutrient metabolism and insulin sensitivity. Disruption of signal transducer and activator of transcription 6 (STAT6) decreases insulin action and enhances a peroxisome proliferator-activated receptor α (PPARα) driven program of oxidative metabolism. Conversely, activation of STAT6 by IL-4 improves insulin action by inhibiting the PPARα-regulated program of nutrient catabolism and attenuating adipose tissue inflammation. These findings have thus identified an unexpected molecular link between the immune system and macronutrient metabolism, suggesting perhaps the coevolution of these pathways occurred to ensure access to glucose during times of helminth infection.
What Have We Learned?

In this chapter, the editors of the issue summarize the responses of four theorists—Patton, Scriven, House, and Boruch—to the Women Affirming Motherhood request for evaluation proposals. They highlight the similarities and differences and identify four major themes across responses: stakeholder engagement, use, collective impact, and methods.
Effects of the NFL's Amendments to the Free Kick Rule on Injuries during the 2010 and 2011 Seasons

Recognizing the chronic health effects associated with playing football, the National Football League (NFL) has enacted policies and rules aimed at improving player health and safety. Prior to the 2011 season, amendments to the Free Kick rule were implemented, whereby the restraining line was moved from the 30- to the 35-yard line and all kicking team players other than the kicker were required to line up no more than 5 yards behind their restraining line. The objective of this analysis was to evaluate the effects of these rule changes on injury rates. Data for injuries occurring on special teams plays during the 2010 and 2011 NFL seasons were obtained from publically available NFL gamebooks and injury reports. Injury rates for kickoff plays across seasons were statistically compared using incidence rate ratios (RR) and 95% confidence intervals. To evaluate whether injury rate changes could be attributable to the rule amendments, comparisons were made with punt injury rates (presumably unaffected by the Free Kick rule changes) and distributions of potential confounders were assessed across seasons. Incidence of injuries occurring on kickoff plays fell from 2010 to 2011 (RR: 0.45, 95% CI: 0.28–0.73), although on kickoff plays where the ball was returned, this decrease became non-significant (RR: 0.67, 95% CI: 0.41–1.08). While the incidence of head injuries decreased by approximately 3-fold during kickoff plays, this change was not statistically significant (RR: 0.33, 95% CI: 0.09–1.21). No difference was observed in injury incidence during punts between the two seasons, and the distribution of confounding factors was largely uniform across seasons. The observed decrease in injuries occurring during kickoffs was likely directly attributable to the Free Kick rule amendments, principally from the increased frequency of touchbacks. The absence of a significant change in head injuries during kickoffs was unexpected, but may be attributable to small sample size. Despite the injury rate reductions, the rule changes likely had little effect on player safety during active gameplay.
Canine Myocardial Reperfusion Injury: Protection by a Free Radical Scavenger, N‐2‐Mcrcaptopropionyl Glycine

Summary: Oxygen-derived free radicals and their metabolites may contribute to the extension of irreversible cellular injury, which occurs on reperfusion of the previously ischemic myocardium. Therefore, therapy directed against the toxic effects of reactive oxygen species may provide protection to the ischemic myocardium, which undergoes subsequent reperfusion. We evaluated the effectiveness of N-2-mercaptopropionyl glycine (MPG), a free radical scavenger, to limit the extent of irreversible injury resulting from 90 min of ischemia followed by 6 h of reperfusion in a canine model of myocardial infarction. In three groups of dogs, MPG (20 mg/kg) was administered as a constant infusion into the left atrium. Group I received MPG for 2 h, starting 15 min before occlusion of the left circumflex coronary artery and ending 15 min after reperfusion. Group II received MPG for 1 h, starting 15 min before reperfusion. Group III received MPG for 1 h beginning 45 min after reperfusion. Each group was compared with its respective saline control group. Infarct size was reduced by 35% in Group I (32.2 ± 5.1% vs. 47.7 ± 3.4% of the area at risk, p < 0.05) and Group II (31.4 ± 3.6% vs. 47.5 ± 5.1% of the area at risk, p < 0.025) in comparison with the saline treated control animals. In contrast, in Group III infarct size did not differ significantly from the saline-treated control group (45.9 ± 3.3% vs. 47.7 ± 3.5% of the area at risk). The percent of left ventricle at risk did not differ among the groups. The beneficial effects of MPG could not be explained on the basis of hemodynamic differences. In addition, MPG did not influence regional myocardial blood flow. In vitro studies indicated that MPG effectively scavanges O2- generated by the hypoxanthine-xanthine oxidase reaction, as well as by PMA-activated polymorphonuclear leukocytes. Based on these observations, we propose that MPG exerts its beneficial effects by protecting against free radical-mediated damage during the early phase of reperfusion.
Awareness of Necessity to Call 9-1-1 for Stroke Symptoms, Upstate New York

Introduction Stroke is the third leading cause of death and a leading cause of disability in New York State. A New York study determined that only 19.9% of patients arrived at a designated stroke center within 3 hours of symptom onset. Yet, receiving treatment within 90 minutes of stroke symptom onset is optimal for improved outcomes. Delay in recognition of stroke symptoms and their severity contributes to treatment delay. Methods A random-digit–dialed, list-assisted telephone survey about stroke knowledge was administered to 1789 adults aged 30 years or older in upstate New York in 2006. Bivariate and regression analysis were used to examine factors associated with intent to call 9-1-1 for symptoms of stroke. Results The largest proportion of respondents (72.4%; 95% confidence interval [CI], 69.9%–74.8%) reported they would call 9-1-1 if they noticed they or someone else had difficulty speaking, and the fewest (33.3%; 95% CI, 30.7%–36.0%) respondents reported they would call 9-1-1 for trouble seeing or double vision. Multivariate analysis found that those who had a history of delay in getting medical care in the past 6 months had decreased odds of intending to call 9-1-1 for stroke symptoms (difficulty speaking: adjusted odds ratio [AOR], 0.76; 95% CI, 0.58–1.00; trouble seeing: AOR, 0.69; 95% CI, 0.53–0.91; facial droop: AOR, 0.85; 95% CI, 0.65–1.11; arm weakness: AOR, 0.80; 95% CI, 0.63–1.03). Age, education, and history of a stroke or heart event were not consistently associated with intent to call 9-1-1. Conclusion Survey respondents do not interpret some stroke symptoms as urgent enough to activate the emergency medical system. History of delaying care is a behavioral pattern that influenced intent to call 9-1-1.
Benzoxazinoid Metabolites Regulate Innate Immunity against Aphids and Fungi in Maize1[W][OA]

Benzoxazinoids (BXs), such as 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA), are secondary metabolites in grasses. The first step in BX biosynthesis converts indole-3-glycerol phosphate into indole. In maize (Zea mays), this reaction is catalyzed by either BENZOXAZINELESS1 (BX1) or INDOLE GLYCEROL PHOSPHATE LYASE (IGL). The Bx1 gene is under developmental control and is mainly responsible for BX production, whereas the Igl gene is inducible by stress signals, such as wounding, herbivory, or jasmonates. To determine the role of BXs in defense against aphids and fungi, we compared basal resistance between Bx1 wild-type and bx1 mutant lines in the igl mutant background, thereby preventing BX production from IGL. Compared to Bx1 wild-type plants, BX-deficient bx1 mutant plants allowed better development of the cereal aphid Rhopalosiphum padi, and were affected in penetration resistance against the fungus Setosphaeria turtica. At stages preceding major tissue disruption, R. padi and S. turtica elicited increased accumulation of DIMBOA-glucoside, DIMBOA, and 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one-glucoside (HDMBOA-glc), which was most pronounced in apoplastic leaf extracts. Treatment with the defense elicitor chitosan similarly enhanced apoplastic accumulation of DIMBOA and HDMBOA-glc, but repressed transcription of genes controlling BX biosynthesis downstream of BX1. This repression was also obtained after treatment with the BX precursor indole and DIMBOA, but not with HDMBOA-glc. Furthermore, BX-deficient bx1 mutant lines deposited less chitosan-induced callose than Bx1 wild-type lines, whereas apoplast infiltration with DIMBOA, but not HDMBOA-glc, mimicked chitosan-induced callose. Hence, DIMBOA functions as a defense regulatory signal in maize innate immunity, which acts in addition to its well-characterized activity as a biocidal defense metabolite.
Reagentless biosensor based on layer-by-layer assembly of functional multiwall carbon nanotubes and enzyme-mediator biocomposite

A simple and controllable layer-by-layer (LBL) assembly method was proposed for the construction of reagentless biosensors based on electrostatic interaction between functional multiwall carbon nanotubes (MWNTs) and enzyme-mediator biocomposites. The carboxylated MWNTs were wrapped with polycations poly(allylamine hydrochloride) (PAH) and the resulting PAH-MWNTs were well dispersed and positively charged. As a water-soluble dye methylene blue (MB) could mix well with horseradish peroxidase (HRP) to form a biocompatible and negativelycharged HRP-MB biocomposite. A (PAH-MWNTs/HRP-MB)n bionanomultilayer was then prepared by electrostatic LBL assembly of PAH-MWNTs and HRP-MB on a polyelectrolyte precursor film-modified Au electrode. Due to the excellent biocompatibility of HRP-MB biocomposite and the uniform LBL assembly, the immobilized HRP could retain its natural bioactivity and MB could efficiently shuttle electrons between HRP and the electrode. The incorporation of MWNTs in the bionanomultilayer enhanced the surface coverage concentration of the electroactive enzyme and increased the catalytic current response of the electrode. The proposed biosensor displayed a fast response (2 s) to hydrogen peroxide with a low detection limit of 2.0×10−7 mol/L (S/N=3). This work provided a versatile platform in the further development of reagentless biosensors.
Multiple Effects of Codon Usage Optimization on Expression and Immunogenicity of DNA Candidate Vaccines Encoding the Human Immunodeficiency Virus Type 1 Gag Protein

ABSTRACT We have analyzed the influence of codon usage modifications on the expression levels and immunogenicity of DNA vaccines, encoding the human immunodeficiency virus type 1 (HIV-1) group-specific antigen (Gag). In the presence of Rev, an expression vector containing the wild-type (wt) gag gene flanked by essentialcis-acting sites such as the 5′-untranslated region and 3′-Rev response element supported substantial Gag protein expression and secretion in human H1299 and monkey COS-7 cells. However, only weak Gag production was observed from the murine muscle cell line C2C12. In contrast, optimization of the Gag coding sequence to that of highly expressed mammalian genes (syngag) resulted in an obvious increase in the G+C content and a Rev-independent expression and secretion of Gag in all tested mammalian cell lines, including murine C2C12 muscle cells. Mice immunized intramuscularly with thesyngag plasmid showed Th1-driven humoral and cellular responses that were substantially higher than those obtained after injection of the Rev-dependent wild-type (wt) gag vector system. In contrast, intradermal immunization of both wtgag and syngag vector systems with the particle gun induced a Th2-biased antibody response and no cytotoxic T lymphocytes. Deletion analysis demonstrated that the CpG motifs generated within syngag by codon optimization do not contribute significantly to the high immunogenicity of thesyngag plasmid. Moreover, low doses of coadministered stimulatory phosphorothioate oligodeoxynucleotides (ODNs) had only a weak effect on antibody production, whereas at higher doses immunostimulatory and nonstimulatory ODNs showed a dose-dependent suppression of humoral responses. These results suggest that increased Gag expression, rather than modulation of CpG-driven vector immunity, is responsible for the enhanced immunogenicity of thesyngag DNA vaccine.
Multichannel Parallel Polymer Waveguide With Circular W-Shaped Index Profile Cores

We fabricate a parallel optical waveguide whose cores are composed of perdeuterated acrylate polymer. We experimentally demonstrate that this waveguide has lower loss by one order of magnitude compared to an acrylate-based waveguide at 850-nm wavelength. The eye diagram measured after a 12.5-Gb/s 15-m transmission shows that this waveguide has sufficiently high bandwidth. In addition, we verify a strong crosstalk reduction due to the specific (W-shaped) refractive index profile in the waveguide.
Green shipping oriented berth allocation based on decentralized decision-making

In contrast to the existing literature on berth allocation problem (BAP) considering fuel consumption and emissions in the terminal-centralized decision environment, the coordinated BAP in a decentralized decision environment is proposed. The port and shipping lines are regarded as rational and autonomous agents, which is more reasonable and practical. Moreover, the study of discrete BAP is extended to the case of two adjacent ports in the same region. In the solution based on combinatorial auction, the port agent solves the BAP, and the vessel agent optimizes its sailing speed and arrival time. An extensive numerical experiment conducted and the results show that the proposed strategy can significantly reduce the total waiting time, the fuel consumption and mitigate the vessel emissions without severely compromising the service level of the ports, which can provide theoretical support for energy saving and emission reduction of ports from the operational perspective.
Geriatric Trauma Patients at a Suburban Level-I Trauma Center in Japan

Abstract Background: Despite the increases in the aged population in Japan, there are little data on geriatric patients with traumatic injuries. A prospective clinical study was carried out to evaluate the use of the emergency medical services (emergency medical services) system, mechanisms of injury, and prehospital assessment and triage of elderly victims of trauma. Patients and Methods: From July 1996 through June 1997, a group of geriatric trauma (Group G, n = 22) and a control group of younger trauma patients (n = 173) were compared with respect to transfer method to an Emergency Center (direct or indirect), Revised Trauma Scores on the scene of the accident (revised trauma score-l) and on admission to the Emergency Center (revised trauma score-2), and outcome (survival). Results: The mean values for revised trauma score-l in the Control Group (Group C) were not different from those in Group G, but revised trauma score-2 of the indirect-transfer patients (indirectly transported patients) in Group G were significantly lower than were those for Group C. Group G mortality rates were significantly higher than were the control rates (p = 0.0001). The mortality rate of the indirectly transported patients subgroup was significantly lower than that of the direct transfer subgroup (directly transported patients) (30/68 vs. 5/70, p<0.0001) in the Group C, but mortality rate of the indirectly transported patients subgroup exceeded that of the directly transported patients subgroup of Group G (8/14 vs. 5/8). Conclusion: The data suggest that in geriatric-age patients, direct transfer patients have a lower mortality rate than do indirect transfer patients when controlled for injury severity score. Therefore, it seems that a different set of triage criteria should be developed and implemented for geriatric-age victims with trauma-induced injuries and that those who meet these more stringent criteria should be transferred directly to a Trauma Center.
Gα12/13-mediated Production of Reactive Oxygen Species Is Critical for Angiotensin Receptor-induced NFAT Activation in Cardiac Fibroblasts*

Angiotensin II (Ang II) activates multiple signaling pathways leading to hyperplasia of cardiac fibroblasts. Reactive oxygen species (ROS) produced by Ang II stimulation are assumed to play pivotal roles in this process. Here, we show that ROS mediate Ang II-induced activation of nuclear factor of activated T cells (NFAT) in rat cardiac fibroblasts. Ang II-induced NFAT activation was suppressed by diphenyleneiodonium (an NADPH oxidase inhibitor), dominant negative (DN)-Rac, DN-p47phox, and an inhibitor of Gα12/13 (Gα12/13-specific regulator of G protein signaling domain of p115RhoGEF, p115-regulator of G protein signaling (RGS)). Stimulation of Ang II receptor increased the intracellular ROS level in a Rac- and p47phox-dependent manner. Because p115-RGS suppressed Ang II-induced Rac activation, Ang II receptor-coupled Gα12/13 mediated NFAT activation through ROS production by Rac activation. Ang II-induced nuclear translocation of the green fluorescent protein (GFP)-tagged amino-terminal region of NFAT4 (GFP-NFAT4) was suppressed by p115-RGS or BAPTA but not by diphenyleneiodonium. The expression of constitutively active (CA)-Gα12/13, CA-G translocation α13, or CA-Rac increased the nuclear of GFP-NFAT4. These results suggest that NFAT activity is regulated by both Ca2+-dependent and ROS-dependent pathways. Furthermore, activation of c-Jun NH2-terminal kinase (JNK) induced by Ang II stimulation is required for NFAT activation because Ang II-induced NFAT activation was inhibited by SP600125, a selective JNK inhibitor. These results indicate that Ang II stimulates the nuclear translocation and activation of NFAT by integrated pathways including the activation of Gα12/13, Rac, NADPH oxidase, and JNK and that Gα12/13-mediated ROS production is essential for NFAT transcriptional activation.
The changing epidemiology of Ross River virus disease in South Australia

OBJECTIVE To investigate changes in epidemiology and symptoms of Ross River virus (RRV) disease in South Australia. DESIGN Longitudinal questionnaire-based survey of notified cases from one to 36 months after infection. SUBJECTS All patients with recent serologically confirmed RRV infection notified to the Communicable Disease Control Unit, South Australian Health Commission, between 1 October 1992 and 30 June 1993. OUTCOME MEASURES Sociodemographic data, source of infection, symptoms and ability to carry out daily activities (at onset of illness and at time of questionnaire, up to 36 months after infection), symptom duration, economic impact of the illness, cases recovery time, factors predictive of delayed recovery. RESULTS Information was obtained on the acute illness from 698 of the 821 subjects and at 15 months after infection from 436. At 15 months, 51% of respondents still had joint pain and 45% had persistent tiredness and lethargy. Other common symptoms included myalgia (34%), lymphadenopathy (25%), headache (23%) and depression (22%). These symptoms were still common 30 months after infection. Increasing age was the only statistically significant predictor of delayed recovery. Infections were acquired across the State, away from previously recognised RRV-endemic areas. CONCLUSIONS For many people, RRV disease is debilitating, with long term symptoms similar to those of chronic fatigue syndrome. The geographic range of the infection has expanded in SA.