Miracle-dz/UniFAR-FTUs huggingface dataset:
Contrasting effects of intracellular redox couples on the regulation of maxi‐K channels in isolated myocytes from rabbit pulmonary artery.

1. The effects of intracellular redox couples were investigated on the activation by voltage, Ca2+ and NS 1619 of maxi‐K channels in enzymatically isolated smooth muscle cells from large pulmonary arteries of rabbits. 2. In inside‐out membrane patches, maxi‐K channels were characterized by a single‐channel conductance of 266 pS in symmetrical 140 mM KCl solutions. The relationship between the open‐state probability (Po) and the membrane potential could be fitted to the Boltzmann equation. The activating action of intracellular Ca2+ was reversible, concentration dependent, and was manifested as the reduction in the voltage necessary to half‐activate the channel (V1/2) with no change in the slope factor. NS 1619 also predisposed the maxi‐K channel to open at more hyperpolarized membrane potentials. 3. The oxidizing agent 5,5'‐dithio‐bis(2‐nitrobenzoic acid) (DTNB, 1 mM) activated maxi‐K channels by inducing a negative shift of the activity‐voltage curve, while the reducing agent 2‐hydroxy‐1‐ethanethiol (beta‐mercaptoethanol) (BME, 1 mM) had no effect. DTNB increased the efficacy of Ca2+ in activating maxi‐K channels. The action of DTNB was not reversible upon wash‐out, but could be counteracted by BME. 4. Maxi‐K channel activity was unaffected by other oxidizing agents, such as NAD (2 mM) and glutathione disulphide (GSSG, 5 mM), or by their reduced forms (NADH and GSH). Mg‐ATP (0.1 and 1 mM) increased the channel activity in a dose‐dependent manner, while guanine nucleotides (100 microM GTP gamma S, 500 microM GDP and 200 microM GDP beta S) had no effect. 5. Our data suggest that a change in the intracellular redox state, which would be expected during acute hypoxia, does not alter the activity of maxi‐K channels of large pulmonary artery smooth muscle cells. The sulfhydryl‐specific redox reagents (DTNB and BME) must act through another regulatory mechanism.
The Inflation-Growth Relationship in SSA Inflation-Targeting Countries

Abstract This paper investigates the relationship between inflation and economic growth for South Africa and Ghana using quarterly empirical data collected from 2001 to 2016 applied to the quantile regression method. For our full sample estimates we find that inflation is positively related with growth in Ghana at high inflation levels whilst inflation in South Africa exerts its least adverse effects at high inflation levels. However, when particularly focusing on the post-crisis period, we find inflation exerts negative effects at all levels of inflation for both countries with inflation having its least adverse effects at high levels for Ghana and at moderate levels for South Arica. Based on these findings bear important implications for inflation targeting frameworks adopted by Central Banks in both countries.
Heat‐ and anesthesia‐induced malignant hyperthermia in an RyR1 knock‐in mouse

Malignant hyperthermia (MH) is a life‐threatening disorder characterized by skeletal muscle rigidity and elevated body temperature in response to halogenated anesthetics such as isoflurane or halothane. Mutation of tyrosine 522 of RyR1 (the predominant skeletal muscle calcium release channel) to serine has been associated with human malignant hyperthermia. In the present study, mice created harboring this mutation were found to represent the first murine model of human malignant hyperthermia. Mice homozygous for the Y522S mutation exhibit skeletal defects and die during embryonic development or soon after birth. Heterozygous mice, which correspond to the human occurrence of this mutation, are MH susceptible, experiencing whole body contractions and elevated core temperatures in response to isoflurane exposure or heat stress. Skeletal muscles from heterozygous mice exhibit increased susceptibility to caffeine‐ and heat‐induced contractures in vitro. In addition, the heterozygous expression of the mutation results in enhanced RyR1 sensitivity to activation by temperature, caffeine, and voltage but not uncompensated sarcoplasmic reticulum calcium leak or store depletion. We conclude that the heterozygous expression of the Y522S mutation confers susceptibility to both heat‐ and anesthetic‐induced MH responses.
Evaluating Changes in Ocular Redness Using a Novel Automated Method

Purpose To evaluate interobserver concordance in measured ocular redness among a group of raters using an objective computer-assisted method (ocular redness index [ORI]) and a group of clinicians using an ordinal comparative scale. Methods We conducted a prospective study to evaluate ocular redness in clinical photographs of 12 patients undergoing pterygium surgery. Photographs were acquired preoperatively, and at 1 week and 1 month postoperatively. One group of clinicians graded conjunctival redness in the photographs using an image-based comparative scale. A second group applied the ORI to measure redness in the same photographs. We evaluated redness change between time points, level of agreement among raters, and assessed redness score differences among observers within each group. Results Interobserver agreement using the image-based redness scale was 0.458 (P < 0.001). Interobserver agreement with the ORI was 0.997 (P < 0.001). We observed statistically significant differences among clinicians' measurements obtained with the image-based redness scale (P < 0.001). There were no significant differences among measurements obtained with the ORI (P = 0.27). We observed a significant change in redness between baseline and follow-up visits with all scoring methods. Detailed analysis of redness change was performed only in the ORI group due to availability of continuous scores. Conclusion Our findings suggest that the ORI scores provide higher consistency among raters than ordinal scales, and can discriminate redness changes that clinical observers often can miss. Translational Relevance The ORI may be a reliable alternative to measure ocular redness objectively in the clinic and in clinical trials.
Inhibition of FGF/FGFR autocrine signaling in mesothelioma with the FGF ligand trap, FP-1039/GSK3052230

Fibroblast growth factor (FGF) ligand-dependent signaling has a fundamental role in cancer development and tumor maintenance. GSK3052230 (also known as FP-1039) is a soluble decoy receptor that sequesters FGFs and inhibits FGFR signaling. Herein, the efficacy of this molecule was tested in models of mesothelioma, a tumor type shown to express high levels of FGF2 and FGFR1. GSK3052230 demonstrated antiproliferative activity across a panel of mesothelioma cell lines and inhibited growth of tumor xenografts in mice. High expression of FGF2 and FGFR1 correlated well with response to FGF pathway inhibition. GSK3052230 inhibited MAPK signaling as evidenced by decreased phospho-ERK and phospho-S6 levels in vitro and in vivo. Additionally, dose-dependent and statistically-significant reductions in tumor vessel density were observed in GSK3052230-treated tumors compared to vehicle-treated tumors. These data support the role of GSK3052230 in effectively targeting FGF-FGFR autocrine signaling in mesothelioma, demonstrate its impact on tumor growth and angiogenesis, and provide a rationale for the current clinical evaluation of this molecule in mesothelioma patients.
Pneumocystis carinii Pneumonia: Differences in Lung Parasite Number and Inflammation in Patients with and without AIDS

Pneumocystis carinii pneumonia has emerged as a significant cause of morbidity and mortality in immunocompromised patients with and without AIDS. To determine differences in P. carinii pneumonia in patients with and without AIDS, the P. carinii parasite numbers, lung inflammatory cell populations, gas exchange, and survival were assessed in a series of 75 consecutive patients with P. carinii pneumonia. Bronchoalveolar lavage was used to quantify the parasite and inflammatory cell numbers in these patients. The data from this study indicate: (1) patients with P. carinii pneumonia and AIDS have significantly greater numbers of P. carinii per ml of lavage compared to other immunocompromised patients with P. carinii pneumonia (p < 0.0001); (2) patients with P. carinii pneumonia and AIDS also have significantly fewer neutrophils recovered in the lavage compared to other immunocompromised patients with P. carinii pneumonia (p = 0.0001); (3) patients with AIDS and P. carinii pneumonia have higher arterial oxygen.
Efficacy and safety of amphotericin B colloidal dispersion compared with those of amphotericin B deoxycholate suspension for treatment of disseminated murine cryptococcosis

The efficacy and safety of amphotericin B colloidal dispersion (ABCD) were compared with those of amphotericin B deoxycholate suspension (ABDS) (Fungizone) in a murine model of disseminated cryptococcosis. Mice were treated intravenously with either ABDS at 0.2, 0.8, or 3.2 mg/kg of body weight per dose or ABCD at 0.8, 3.2, 6.4, 12.8, or 19.2 mg/kg dose three times per week for 2 weeks. Excluding mice treated with ABDS at 3.2 mg/kg, which was acutely lethal in 100% of mice, and ABCD at 19.2 mg/kg, which also resulted in two early deaths, the survival of ABCD- and ABDS-treated groups was prolonged over survival of controls (P < or = 0.05). Survival of ABCD (3.2 mg/kg)-treated mice was improved over that of ABDS (0.2 mg/kg)-treated mice (P < 0.05); however, comparisons of mice given all other dosages of ABCD with mice given sublethal dosages of ABDS did not demonstrate differences in survival. Comparative fungal burdens in organs showed a decrease in liver (P < 0.05) and spleen (P < 0.05) burdens for ABCD with the 19.2-mg/kg therapy versus those with ABDS with the 0.8-mg/kg therapy and liver burdens for ABCD with the 12.8-mg/kg therapy versus ABDS with the 0.8-mg/kg therapy (P < 0.05). There was no difference in organ burdens between therapy with ABCD at 0.8 mg/kg and ABDS at 0.8 mg/kg. These data show that the efficacy of ABCD is equal to that of ABDS on a milligram-per-kilogram basis for murine disseminated cryptococcosis. Because of its decreased toxicity, greater efficacy with ABCD could be achieved through doses fourfold higher than the 100% lethal dose for ABDS. Thus, ABCD shows promise as an effective but less toxic alternative to ABDS for the treatment of disseminated cryptococcosis.
Intraplastidial trafficking of a phage-type RNA polymerase is mediated by a thylakoid RING-H2 protein

The plastid genome of dicotyledonous plants is transcribed by three different RNA polymerases; an eubacterial-type enzyme, PEP; and two phage-type enzymes, RPOTp and RPOTmp. RPOTp plays an important role in chloroplast transcription, biogenesis, and mesophyll cell proliferation. RPOTmp fulfills a specific function in the transcription of the rrn operon in proplasts/amyloplasts during seed imbibition/germination and a more general function in chloroplasts during later developmental stages. In chloroplasts, RPOTmp is tightly associated with thylakoid membranes indicating that functional switching of RPOTmp is connected to thylakoid association. By using the yeast two-hybrid system, we have identified two proteins that interact with RPOTmp. The two proteins are very similar, both characterized by three N-terminal transmembrane domains and a C-terminal RING domain. We show that at least one of these proteins is an intrinsic thylakoid membrane protein that fixes RPOTmp on the stromal side of the thylakoid membrane, probably via the RING domain. A model is presented in which light by triggering the synthesis of the RING protein determines membrane association and functional switching of RPOTmp.
Live birth after transfer of a tripronuclear embryo: An intracytoplasmic sperm injection as a combination of microarray and time-lapse technology

Although around 1-4% of human zygotes have been found to be tripronuclear, there is little information about the subsequent development and chromosomal composition of embryos that derive from these zygotes. Herein, we report a pregnancy and subsequent delivery of a healthy newborn after the transfer of a blastocyst that developed from a tripronuclear zygote that had a euploid microarray result.
How well do you know your spectators? A study on spectator segmentation based on preference analysis and willingness to pay for tickets

ABSTRACT Research question: Do club managers know enough about their spectators? Fan protests against increasing ticket prices in European sports show the ongoing disconnect between fans and clubs. The purpose of this article is to examine sport event spectators’ preferences for tickets and their willingness to pay (WTP) considering innovative ticket features. This research contributes to existing research on spectator segmentation and ticket pricing. Research methods: This study is the first in sport management literature to apply choice-based conjoint analysis in combination with latent classes. We conduct online surveys of two German basketball clubs and collect data on more than 750 spectators. Results and findings: Benefit segmentation analyses of both spectator groups lead to four spectator segments each, which differ depending on preferences for opposing teams, seat categories, and WTP. The results show that the prevailing assumption of homogeneous spectator preferences in sport management research leads to estimation bias. Implications: Spectator preferences are heterogeneous. Therefore, club managers need to know and understand their spectators to better adjust ticket options. Furthermore, the results provide theoretical contributions for spectator segmentation and ticket pricing literature.
Increased T-helper interferon-gamma-secreting cells in obese children.

OBJECTIVE Leptin, an adipocyte-secreted hormone, has emerged as a potential candidate for the link between obesity and the proinflammatory state. Specifically, leptin modulates T-helper (Th) cells toward a Th1 phenotype, with the secretion of proinflammatory cytokines. The aim of this study was to evaluate the Th1/Th2 balance in obese children and its relation with hormonal and metabolic features. STUDY DESIGN In 50 obese children and 20 control children, we measured the CD4-positive Th cells that secrete interferon (IFN)-gamma or interleukin (IL)-2 (taken as an index of Th1 cells), and IL-4 (taken as an index of Th2 cells) as well as serum glucose, insulin, insulin resistance (IR) index (as homeostasis model assessment model (HOMA)), lipid profile, aminotransferases, leptin and ghrelin. Obese children also underwent dual energy X-ray absorptiometry scan measurements, and liver ultrasound scanning. RESULTS Geometric mean percentages of IL-2- and IL-4-CD4 secreting cells in obese children were not significantly different from those found in control children. However, the geometric mean percentage of CD4-positive T cells secreting IFN-gamma was significantly higher in the obese than in the control (P < 0.0001, t-test) group. Within the entire group of study children, the percentage of IFN-gamma-positive cells was positively associated with leptin (P = 0.002), insulin (P < 0.00 005), and HOMA-IR values (P < 0.00 005). However, when these associations were restricted to the group of obese subjects, insulin and HOMA-IR values, but not leptin, retained statistical significance. Yet, in the obese group, the percentage of IFN-gamma-positive cells was associated with nonalcoholic steatohepatitis (NASH) (P = 0.001), but not with body mass index-standard deviation score and total body fat mass. CONCLUSIONS In obese children, a shift to Th1-cytokine profile dominated by the production of IFN-gamma is related to insulin resistance as well as to NASH independently of anthropometric features and other metabolic characteristics. The prevalent Th1 pattern of secreted cytokines may be regarded as a mechanism contributing to inflammation in obesity.
Characterizing Periodic Messaging Interventions Across Health Behaviors and Media: Systematic Review

Background Periodic prompts serve as tools for health behavior interventions to encourage and maintain behavior changes. Past literature reviews have examined periodic messages targeting specific behaviors (smoking, physical activity, diet, etc) or media (telephone, email, face-to-face, newsletter, etc) and have found them to be effective in impacting health behavior in the short term. Objective Our goal was to review the literature related to periodic messaging and prompts in order to explore typical characteristics, assess the role of prompt timing, identify common theoretical models used, and identify characteristics associated with the effectiveness of periodic prompts. Methods Electronic searches of PubMed, PsycINFO, CINAHL, and Web of Science were conducted in October 2012 and May 2013. Database search terms included variant terms for periods, prompts, interventions, media, and health behaviors. Results Forty-two of the 55 included research articles found that prompts resulted in significant positive behavioral outcomes for participants. Prompts were delivered via text messages, email, mailed communications, and in a few instances via phone. Generally, the provision of feedback and specific strategies to accomplish behavior change appears to be important for the success of periodic prompts. Rationale for prompt timing was rarely provided, although some studies did organize message content around days of the week or times perceived to be high risk for particular behaviors. Smoking cessation interventions tended to be organized around quit date. Among studies using theoretical models to inform their interventions, the transtheoretical model was most common. Conclusions Periodic messaging interventions yield positive results for short-term health behavior changes. Interventions including feedback and prompts that included strategies were more likely to report significantly positive outcomes. Work remains to better understand elements that make periodic prompts successful and whether they are effective in producing long-term outcomes.
A novel radiation protection drape reduces radiation exposure during fluoroscopy guided electrophysiology procedures.

OBJECTIVE The purpose of this study was to evaluate a novel disposable lead-free radiation protection drape for decreasing radiation scatter during electrophysiology procedures. BACKGROUND In recent years, there has been an exponential increase in the number of electrophysiology (EP) procedures exposing patients, operators and laboratory staff to higher radiation doses. METHODS The RADPAD was positioned slightly lateral to the incision site for pectoral device implants and superior to the femoral vein during electrophysiology studies. Each patient served as their own control and dosimetric measurements were obtained at the examiner's elbow and hand. Radiation badge readings for the operator were obtained three months prior to RADPAD use and three months after introduction. RESULTS Radiation dosimetry was obtained in twenty patients: 7 electrophysiology studies, 6 pacemakers, 5 catheter ablations, and 2 implantable cardioverter-defibrillators. Eleven women and nine men with a mean age of 63 +/- 4 years had an average fluoroscopy time of 2.5 +/- 0.42 minutes per case. Mean dosimetric measurements at the hand were reduced from 141.38 +/- 24.67 to 48.63 +/- 9.02 milliroentgen (mR) per hour using the protective drape (63% reduction; p < 0.0001). Measurements at the elbow were reduced from 78.78 +/- 7.95 mR per hour to 34.50 +/- 4.18 mR per hour using the drape (55% reduction; p < 0.0001). Badge readings for three months prior to drape introduction averaged 2.45 mR per procedure versus 1.54 mR per procedure for 3 months post-initiation (37% reduction). CONCLUSION The use of a novel radiation protection surgical drape can significantly reduce scatter radiation exposure to staff and operators during a variety of EP procedures.
VPS26A–SNX27 Interaction-Dependent mGluR5 Recycling in Dorsal Horn Neurons Mediates Neuropathic Pain in Rats

Retromer, which crucially contributes to endosomal sorting machinery through the retrieval and recycling of signaling receptors away from degradation, has been identified as a critical element for glutamatergic-receptor-dependent neural plasticity at excitatory synapses. We observed it accompanied by behavioral allodynia; neuropathic injury time-dependently enhanced VPS26A and SNX27 expression; VPS26A–SNX27 coprecipitation; and VPS26A-positive, SNX27-positive, and VPS26A–SNX27 double-labeled immunoreactivity in the dorsal horn of Sprague Dawley rats that were all sufficiently ameliorated through the focal knock-down of spinal VPS26A expression. Although the knock-down of spinal SNX27 expression exhibited similar effects, spinal nerve ligation (SNL)-enhanced VPS26A expression remained unaffected. Moreover, SNL also increased membrane-bound and total mGluR5 abundance, VPS26A-bound SNX27 and mGluR5 and mGluR5-bound VPS26A and SNX27 coprecipitation, and mGluR5-positive and VPS26A/SNX27/mGluR5 triple-labeled immunoreactivity in the dorsal horn, and these effects were all attenuated through the focal knock-down of spinal VPS26A and SNX27 expression. Although administration with MPEP adequately ameliorated SNL-associated allodynia, mGluR5 expression, and membrane insertion, SNL-enhanced VPS26A and SNX27 expression were unaffected. Together, these results suggested a role of spinal VPS26A–SNX27-dependent mGluR5 recycling in the development of neuropathic pain. This is the first study that links retromer-associated sorting machinery with the spinal plasticity underlying pain hypersensitivity and proposes the possible pathophysiological relevance of endocytic recycling in pain pathophysiology through the modification of glutamatergic mGluR5 recycling. SIGNIFICANCE STATEMENT VPS26A–SNX27-dependent mGluR5 recycling plays a role in the development of neuropathic pain. The regulation of the VPS26A–SNX27 interaction that modifies mGluR5 trafficking and expression in the dorsal horn provides a novel therapeutic strategy for pain relief.
Improved CMA-ES with Memory based Directed Individual Generation for Real Parameter Optimization

Covariance Matrix Adaptation and Evolution Strategy (CMA-ES) is an efficient method of optimization that iteratively generates new individuals around an ever-adaptive recombination point. Although it ensures speed and high rate of exploitation, CMA-ES suffers a major drawback as the scheme of generating new members scattered around an influential mean may often lead to members drawn to local minima. The result is that while precision of better solutions increases, the ability to reform is lost. In this paper we incorporate a directional feature to the generation wise perturbation of individuals in standard version of CMA-ES that utilizes potentially useful information from previous generation to retain the influence of old recombination point. Coupled with a modified population size we attempt to form an algorithm that amalgamates the effectiveness of CMA-ES along with the ability to explore. The performance is tested on IEEE CEC (Congress on Evolutionary Computation) 2013 Special Session on Real-Parameter Optimization in 10, 30 and 50 dimensions. The results obtained clearly indicates that the proposed algorithm addressed as CMA-ES with Memory based Directed Individual Generation (CMA-ES-DIG) is able to perform excessively well on majority of the test cases in a statistically meaningful way.