Miracle-dz/UniFAR-FTUs huggingface dataset:
Circulating adiponectin levels and cardiovascular risk factors in acromegalic patients.

OBJECTIVE Adiponectin (ApN) is an adipocytokine expressed in human adipose cells with anti-atherogenic and anti-inflammatory properties that plays a role in the pathophysiology of insulin resistance, metabolic syndrome and coronary artery disease. The aim of the study was to evaluate ApN secretion in patients with acromegaly, a chronic disease associated with insulin resistance and increased cardiovascular mortality, and to correlate ApN levels with hormonal, metabolic and cardiovascular parameters. DESIGN AND METHODS The study included 32 patients with active acromegaly (11 male and 21 female, aged 48+/-11 years, duration of disease: 8+/-6 years, GH: 9.2+/-9.8 microg/l, IGF-I: 80+/-33 nmol/l (means+/-s.d.)) and 38 control subjects sex- and body mass index (BMI)-matched. In all subjects, serum ApN, leptin and ghrelin levels, BMI, waist circumference, insulin resistance (assessed by homeostasis model assessment and the quantitative insulin check index), lipid profile and blood pressure values were evaluated. RESULTS Acromegalic patients and control subjects had similar ApN levels (9.4+/-3.5 vs 9.5+/-4.0 mg/l, NS), while when considering obese subjects acromegalic patients had ApN levels significantly higher than controls (10.2+/-4 vs 7.5+/-3 mg/l, P<0.05). No significant correlation between ApN and GH/IGF-I levels or duration of disease was found. ApN concentrations negatively correlated with BMI, waist circumference, glucose and diastolic blood pressure and positively with high-density lipoprotein cholesterol and ghrelin in controls, while all these correlations were lost in acromegalic patients. CONCLUSIONS We provide evidence that, although metabolic and cardiovascular abnormalities are present in most acromegalic patients, in these subjects ApN levels are not reduced and, contrary to what is found in BMI-matched controls, do not correlate with cardiovascular risk factors. These data support the view that atherosclerosis is not the main determinant of cardiovascular mortality in acromegaly and suggest a permissive action of GH and/or IGF-I excess on ApN secretion.
Socializing by Day May Affect Performance by Night: Vulnerability to Sleep Deprivation is Differentially Mediated by Social Exposure in Extraverts vs Introverts.

STUDY OBJECTIVES to examine the effects of socially enriched versus socially impoverished environments on performance and alertness decline during sleep deprivation in extraverts versus introverts. DESIGN participants (n = 29 men, n = 19 women) were assigned to socially enriched (n = 24; 13 introverts, 11 extraverts) or socially impoverished (n = 24; 12 introverts, 12 extraverts) conditions (activities matched) for 12 hours (1000-2200) on Day 1 followed by 22 hours of sleep deprivation (2200-2000; 36 h awake total), monitored by actigraphy. The median split of volunteers' Eysenck Extraversion scores was used for extravert/introvert categorization. The Psychomotor Vigilance Task (PVT), modified Maintenance of Wakefulness Test (MWT), and Stanford Sleepiness Scale (SSS) were administered every 2 hours throughout. PVT speed, transformed lapses, modified MWT sleep-onset latency, and SSS were analyzed using mixed-model analyses of variance, with covariates of age and total actigraphic activity during enrichment or impoverishment. SETTING residential sleep/performance testing facility. PARTICIPANTS forty-eight healthy adults (aged 18-39). INTERVENTIONS Twelve hours of socially enriched or isolated environments in extraverts and introverts prior to sleep deprivation. RESULTS Social experience interacted with personality type to affect alertness and vigilance. Social enrichment, as compared with social impoverishment, was associated with more PVT lapses at 04:00 overall. Similarly, following social enrichment, PVT speed was significantly slower among extraverts than among introverts during sleep deprivation, but no personality-group differences emerged following social impoverishment. MWT sleep latency and SSS subjective sleepiness did not show significant personality or social-condition effects during sleep deprivation. CONCLUSIONS the effect of social exposure on vulnerability or resiliency to sleep deprivation was modulated by introversion and extraversion. Extraverts exposed to social environments were more vulnerable to subsequent sleep deprivation than were introverts.
Dividend Announcement and Ex-Dividend Effects on Stock Return

We study the impact of dividend policy on the stock return by investigating reaction of the stock price on the dividend announcement date and the ex-dividend date. In order to achieve this goal, a sample comprising 1962 observations of dividend-related events from 432 listed companies in Vietnam during the period 2008 to 2015 is chosen to analyze and the event study methodology is used to estimate abnormal returns to the shares around the announcement date and the ex-dividend date. Our results clearly show that the effect of dividend announcement on the stock return is positive around the announcement date. In addition, the stock price moves up as long as the ex-dividend date approaches and then starts decreasing from this date onwards.
Effect of Drugs Used for Neuropathic Pain Management on Tetrodotoxin-resistant Na+ Currents in Rat Sensory Neurons

BackgroundTetrodotoxin-resistant Na+ channels play an important role in generation and conduction of nociceptive discharges in peripheral endings of small-diameter axons of the peripheral nervous system. Pathophysiologically, these channels may produce ectopic discharges in damaged nociceptive fibers, leading to neuropathic pain syndromes. Systemically applied Na+ channel–blocking drugs can alleviate pain, the mechanism of which is rather unresolved. The authors investigated the effects of some commonly used drugs, i.e., lidocaine, mexiletine, carbamazepine, amitriptyline, memantine, and gabapentin, on tetrodotoxin-resistant Na+ channels in rat dorsal root ganglia. MethodsTetrodotoxin-resistant Na+ currents were recorded in the whole-cell configuration of the patch-clamp method in enzymatically dissociated dorsal root ganglion neurons of adult rats. Half-maximal blocking concentrations were derived from concentration–inhibition curves at different holding potentials (−90, −70, and −60 mV). ResultsLidocaine, mexiletine, and amitriptyline reversibly blocked tetrodotoxin-resistant Na+ currents in a concentration- and use-dependent manner. Block by carbamazepine and memantine was not use-dependent at 2 Hz. Gabapentin had no effect at concentrations of up to 3 mm. Depolarizing the membrane potential from −90 mV to −60 mV reduced the available Na+ current only by 23% but increased the sensitivity of the channels to the use-dependent blockers approximately fivefold. The availability curve of the current was shifted by 5.3 mV to the left in 300 &mgr;m lidocaine. ConclusionsLess negative membrane potential and repetitive firing have little effect on tetrodotoxin-resistant Na+ current amplitude but increase their sensitivity to lidocaine, mexiletine, and amitriptyline so that concentrations after intravenous administration of these drugs can impair channel function. This may explain alleviation from pain by reducing firing frequency in ectopic sites without depressing central nervous or cardiac excitability.
Cranial performance in the Komodo dragon (Varanus komodoensis) as revealed by high‐resolution 3‐D finite element analysis

The Komodo dragon (Varanus komodoensis) displays a unique hold and pull‐feeding technique. Its delicate ‘space‐frame’ skull morphology differs greatly from that apparent in most living large prey specialists and is suggestive of a high degree of optimization, wherein use of materials is minimized. Here, using high‐resolution finite element modelling based on dissection and in vivo bite and pull data, we present results detailing the mechanical performance of the giant lizard's skull. Unlike most modern predators, V. komodoensis applies minimal input from the jaw muscles when butchering prey. Instead it uses series of actions controlled by postcranial muscles. A particularly interesting feature of the performance of the skull is that it reveals considerably lower overall stress when these additional extrinsic forces are added to those of the jaw adductors. This remarkable reduction in stress in response to additional force is facilitated by both internal and external bone anatomy. Functional correlations obtained from these analyses also provide a solid basis for the interpretation of feeding ecology in extinct species, including dinosaurs and sabre‐tooth cats, with which V. komodoensis shares various cranial and dental characteristics.
Protective Effect of Geranylgeranylacetone against Radiation-Induced Delayed Effects on Human Keratinocytes

Skin exposure to ionizing radiation affects the normal wound healing process. We investigated the beneficial effects of a pharmacological treatment with geranylgeranylacetone (GGA) on keratinocytes using in vitro scratch wound injury assay in nonirradiated and irradiated conditions. Irradiation affected the wound closure of keratinocytes 24 h after scratch injury, whereas re-epithelialization was markedly accelerated after GGA treatment when compared to nontreated keratinocytes. We demonstrated that GGA treatment increased migration of human epidermal keratinocytes and this migratory property was not related to RhoA signaling. Interestingly, Western blot analysis revealed that GGA treatment down-regulated caspase 3 active form expression and up-regulated the activated phenotype by inducing both keratin 6 (K6) expression and interleukin-1β (IL-1β) release without modification of the differentiate phenotype. Finally, the proteomic profiling was performed on keratinocytes, showing that global protein changes occurred after irradiation of keratinocytes treated or untreated with GGA.
Affinity and Cross-Reactivity Engineering of CTLA4-Ig To Modulate T Cell Costimulation

CTLA4-Ig is an Fc fusion protein containing the extracellular domain of CTLA-4, a receptor known to deliver a negative signal to T cells. CTLA4-Ig modulates T cell costimulatory signals by blocking the CD80 and CD86 ligands from binding to CD28, which delivers a positive T cell costimulatory signal. To engineer CTLA4-Ig variants with altered binding affinity to CD80 and CD86, we employed a high-throughput protein engineering method to map the ligand binding surface of CTLA-4. The resulting mutagenesis map identified positions critical for the recognition of each ligand on the three CDR-like loops of CTLA-4, consistent with the published site-directed mutagenesis and x-ray crystal structures of the CTLA-4/CD80 and CTLA-4/CD86 complexes. A number of single amino acid substitutions were identified that equally affected the binding affinity of CTLA4-Ig for both ligands as well as those that differentially affected binding. All of the high-affinity variants showed improved off-rates, with the best one being a 17.5-fold improved off-rate over parental CTLA4-Ig binding to CD86. Allostimulation of human CD4+ T cells showed that improvement of CD80 and CD86 binding activity augmented inhibition of naive and primed T cell activation. In general, increased affinity for CD86 resulted in more potent inhibition of T cell response than did increased affinity for CD80. Optimization of the affinity balance to CD80 and CD86 to particular disease settings may lead to development of a CTLA4-Ig molecule with improved efficacy and safety profiles.
Does finance accelerate or retard growth? : theory and evidence

Finance can be beneficial for growth, but it can also contribute to financial crises, which are often very damaging for growth. An extensive review of the literature suggests that financial development has a positive impact on economic growth at adequate levels of financial depth but that the effect vanishes, or even becomes negative, when finance becomes excessive. Excessive finance can incubate economic booms and asset price bubbles that end in financial crises, followed by low rates of economic growth for sustained periods. Too little finance is not desirable—but too much is not desirable either.
Environmental factors potentially associated with mumps transmission in Yeshivas during a mumps outbreak among highly vaccinated students: Brooklyn, New York, 2009–2010

During 2009–2010, a large US mumps outbreak occurred affecting two-dose vaccinated 9th–12th grade Orthodox Jewish boys attending all-male yeshivas (private, traditional Jewish schools). Our objective was to understand mumps transmission dynamics in this well-vaccinated population. We surveyed 9th-12th grade male yeshivas in Brooklyn, NY with reported mumps case-students between 9/1/2009 and 3/30/2010. We assessed vaccination coverage, yeshiva environmental factors (duration of school day, density, mixing, duration of contact), and whether environmental factors were associated with increased mumps attack rates. Ten yeshivas comprising 1769 9th–12th grade students and 264 self-reported mumps cases were included. The average yeshiva attack rate was 14.5% (median: 13.5%, range: 1–31%), despite two-dose measles-mumps-rubella vaccine coverage between 90–100%. School duration was 9–15.5 h/day; students averaged 7 h face-to-face/day with 1–4 study partners. Average daily mean density was 6.6 students per 100 square feet. The number of hours spent face-to-face with a study partner and the number of partners per day showed significant positive associations (p < 0.05) with classroom mumps attack rates in univariate analysis, but these associations did not persist in multivariate analysis. This outbreak was characterized by environmental factors unique to the yeshiva setting (e.g., densely populated environment, prolonged face-to-face contact, mixing among infected students). However, these features were present in all included yeshivas, limiting our ability to discriminate differences. Nonetheless, mumps transmission requires close contact, and these environmental factors may have overwhelmed vaccine-mediated protection increasing the likelihood of vaccine failure among yeshiva students.
The effect of carbon dioxide upon myocardial contractile performance, blood flow and oxygen consumption.

1. Mongrel dogs were anaesthetized with chloralose, paralysed, ventilated and vagotomized and given a beta‐blocking drug, sotalol, in sufficient doses to block the effects of 5 microgram of adrenaline. 2. Changes in inspired CO2 concentration were produced, causing increases of arterial PCO2 up to 120 mmHg. The effects on myocardial blood flow were measured with radioactive microspheres. Coronary sinus and arterial blood was sampled. 3. In the absence of beta‐blockade, an increase in arterial PCO2 produced variable effects. In some dogs coronary blood flow increased, while in others there was no change. There was a mean increase in coronary blood flow at arterial PCO2 values above 85 mmHg which was abolished by beta‐blockade. 4. In the presence of beta‐blockade, an increase of arterial PCO2 produced depression of left ventricular performance, i.e. a fall of maximum rate of rise of left ventricular pressure and a rise of left ventricular end‐diastolic pressure. 5. In the presence of beta‐blockade, there were no consistent changes in myocardial blood flow, left ventricular pressure or cardiac output. 6. In the absence of beta‐blockade, coronary arterial minus venous ocygen content was reduced by hypercapnia. In the presence of beta‐blockade, the changes were small and not statistically significant. The direct coronary vasodilator effect was therfore negligible. 7. It is concluded that the previously reported hypercapnic vasodilatation was mainly an effect of sympatho‐adrenergic stimulation by hypercapnia. 8. In the presence of beta‐blockade, coronary sinus PO2 increased markedly, with little change in coronary sinus oxygen content; this was consistent with a shift to the right of the oxy‐haemoglobin dissociation curve. Under circumstances of hypercapnia, a rise in coronary sinus (and presumably tissue) PO2 failed to produce vasoconstriction. 9. It is argued that the vasodilator effect of hydrogen ions and the vasoconstrictor effect of oxygen probably cancel one another when the arterial PCO2 is raised.
Increased number of substitutions in the D‐loop of mitochondrial DNA in the sudden infant death syndrome

The purpose of the present study was to investigate substitutions in the D‐loop of mitochondrial DNA (mtDNA) in sudden infant death syndrome (SIDS) and controls, since several observations indicate the involvement of mtDNA mutations in SIDS. These include elevated levels of vitreous humour hypoxanthine in SIDS victims, familial clustering without mendelian traits, and observations of increased sleepiness and a lower activity score in infants who later succumbed to SIDS. Eighty‐two cases of SIDS and 133 controls were investigated and the D‐loop sequences were recorded in the base‐pair range 16 055‐16 500 in the mtDNA sequence. The sequencing was carried out using the Applied Biosystems Sequenase dye terminator method and a ABD373A sequencer. The recorded D‐loop sequences were compared with the Cambridge sequence and differences were recorded as substitutions. The SIDS cases had a tendency towards a higher substitution rate in the D‐loop than the controls (p= 0:088). This observation makes it interesting to search for deleterious mutations in other locations in the mtDNA.
High-Intensity Interval Training Versus Moderate-Intensity Continuous Training in the Prevention/Management of Cardiovascular Disease

Moderate-intensity continuous training (MICT) has long been considered the most effective exercise treatment modality for the prevention and management of cardiovascular disease (CVD), but more recently high-intensity interval training (HIIT) has been viewed as a potential alternative to MICT in accruing such benefits. HIIT was initially found to induce significant improvements in numerous physiological and health-related indices, to a similar if not superior extent to MICT. Since then, many studies have attempted to explore the potential clinical utility of HIIT, relative to MICT, with respect to treating numerous cardiovascular conditions, such as coronary artery disease, heart failure, stroke, and hypertension. Despite this, however, the efficacy of HIIT in reversing the specific symptoms and risk factors of these cardiovascular pathologies is not well understood. HIIT is often perceived as very strenuous, which could render it unsafe for those at risk of or afflicted with CVD, but these issues are also yet to be reviewed. Furthermore, the optimal HIIT protocol for each of the CVD cohorts has not been established. Thus, the purpose of this review article is to (1) evaluate the efficacy of HIIT relative to MICT in the prevention and management of cardiovascular conditions, and (2) explore any potential safety issues surrounding the suitability and/or tolerability of HIIT for patients with CVD, and the potential optimal prescriptive variables of HIIT for application in the clinical environment.
The Role of Endometrial Selectins and Their Ligands on Bovine Conceptus Attachment to the Uterine Epithelium During Peri-Implantation Period1

ABSTRACT A successful pregnancy depends on the blastocyst's implantation to the maternal endometrium; however, the initial interaction between blastocyst and uterine epithelium has not been well characterized. The objectives of this study were to determine if selectins and their ligands were expressed in the bovine conceptus and/or uterus during the periattachment period and to study whether selectins were associated with conceptus attachment to the uterine epithelium. Through the RNA-sequence analysis of bovine conceptuses on Days 17, 20, and 22 (Day 0 = day of estrus), only the SELL ligand, podocalyxin (PODXL), and P-selectin (SELP) ligand, SELPLG, were found. Quantitative PCR analysis confirmed the presence of PODXL and SELPLG in these conceptuses and revealed that SELL, mRNA and protein, detected in the uterine epithelium but not in conceptuses increased during the periattachment period. In the cultured endometrial epithelial cells (EECs), SELL transcript was up-regulated when uterine flushings from Day 20 pregnant animals were placed onto these cells. SELL was also up-regulated when cultured EECs were treated with progesterone, EGF, or bFGF, but not with IFNT. In the coculture system with EECs and bovine trophoblast CT-1 cells, SELL expression in EECs was effectively reduced by its small interfering RNA; however, IFNT, a marker for CT-1 cell attachment to EECs, was not reduced, nor was a transcription factor of IFNT, CDX2. These observations suggest that the conceptus could attach to the uterine epithelium through the use of endometrial SELL and embryonic selectin ligands, possibly initiating the conceptus attachment process in the bovine species.
The Choice of Electoral Systems in Dictatorships

This paper develops a theory to account for the variation in electoral systems of dictatorships. We argue that resource-rich dictators who have capacity to induce compliance from ruling elites and citizens are incentivized to employ proportional representation systems to preserve their political dominance, while resource-poor dictators lacking this capacity tend to choose majoritarian systems to co-opt ruling elites in the legislature using seat advantages. Using newly collected cross-national data on electoral authoritarian regimes, we find strong empirical evidence supporting our theory. We also explicitly test the causal links with both additional statistical analyses and comparative case studies on Kazakhstan and Kyrgyzstan, finding that majoritarian systems bias seat distributions in favor of ruling politicians, foster a unified opposition, and lower voter turnout more than PR systems in electoral autocracies. Word Count: 11,966 words ∗Associate Professor of Political Science at Michigan State University. echang@msu.edu †Associate Professor of Political Science in the Graduate School of Information Sciences at Tohoku University. masaaki.higashijima. d8@tohoku.ac. jp
NG2 proteoglycan as a pericyte target for anticancer therapy by tumor vessel infarction with retargeted tissue factor

tTF-TAA and tTF-LTL are fusion proteins consisting of the extracellular domain of tissue factor (TF) and the peptides TAASGVRSMH and LTLRWVGLMS, respectively. These peptides represent ligands of NG2, a surface proteoglycan expressed on angiogenic pericytes and some tumor cells. Here we have expressed the model compound tTF-NGR, tTF-TAA, and tTF-LTL with different lengths in the TF domain in E. coli and used these fusion proteins for functional studies in anticancer therapy. We aimed to retarget TF to tumor vessels leading to tumor vessel infarction with two barriers of selectivity, a) the leaky endothelial lining in tumor vessels with the target NG2 being expressed on pericytes on the abluminal side of the endothelial cell barrier and b) the preferential expression of NG2 on angiogenic vessels such as in tumors. Chromatography-purified tTF-TAA showed identical Factor X (FX)-activating procoagulatory activity as the model compound tTF-NGR with Km values of approx. 0.15 nM in Michaelis-Menten kinetics. The procoagulatory activity of tTF-LTL varied with the chosen length of the TF part of the fusion protein. Flow cytometry revealed specific binding of tTF-TAA to NG2-expressing pericytes and tumor cells with low affinity and dissociation KD in the high nM range. In vivo and ex vivo fluorescence imaging of tumor xenograft-carrying animals and of the explanted tumors showed reduction of tumor blood flow upon tTF-TAA application. Therapeutic experiments showed a reproducible antitumor activity of tTF-TAA against NG2-expressing A549-tumor xenografts, however, with a rather small therapeutic window (active/toxic dose in mg/kg body weight).