Miracle-dz/UniFAR-FTUs huggingface dataset:
Smooth muscle cell responsiveness to nitrovasodilators in hypertensive and normotensive rats.

Endothelium-derived relaxing factor and exogenous nitrovasodilators are thought to produce smooth muscle relaxation by activation of soluble guanylate cyclase. To investigate whether diminished cyclic GMP (cGMP) accumulation underlies the differences in vascular reactivity to nitrovasodilators between Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR), we determined cGMP formation in aortic smooth muscle cells from the two strains. Both cultured cells and aortic rings from 12- to 14-week-old SHR accumulated greater amounts of cGMP on stimulation with exogenous nitrovasodilators (ie, sodium nitroprusside) than those from WKY rats, whereas there was no difference observed in cells from prehypertensive animals (5- to 6-week old) between the two strains. Responsiveness of smooth muscle cells to endothelium-derived relaxing factor was investigated in cocultures of bovine aortic endothelial cells (BAE) and smooth muscle cells from SHR and WKY rats. cGMP accumulation elicited by endothelium-derived relaxing factor released either basally or in response to bradykinin and the calcium ionophore A23187 was greater in smooth muscle from 12- to 14-week-old SHR than from age-matched WKY rats (80 +/- 17 versus 11 +/- 2 for basal; 152 +/- 12 versus 80 +/- 26 for A23187; 163 +/- 21 versus 40 +/- 12 pmol/mg protein per 15 minutes for bradykinin) in SHR/BAE and WKY/BAE cocultures, respectively. Northern blot analysis of steady-state messenger RNA levels for the beta 1 subunit of soluble guanylate cyclase revealed higher levels of the message in SHR. (ABSTRACT TRUNCATED AT 250 WORDS)
Transcription profiling of eleven cytochrome P450s potentially involved in xenobiotic metabolism in the mosquito Aedes aegypti

Transcription profiles of 11 Aedes aegypti P450 genes from CYP6 and CYP9 subfamilies potentially involved in xenobiotic metabolism were investigated. Many genes were preferentially transcribed in tissues classically involved in xenobiotic metabolism including midgut and Malpighian tubules. Life‐stage transcription profiling revealed important variations amongst larvae, pupae, and adult males and females. Exposure of mosquito larvae to sub‐lethal doses of three xenobiotics induced the transcription of several genes with an induction peak after 48 to 72 h exposure. Several CYP genes were also induced by oxidative stress and one gene strongly responded to 20‐hydroxyecdysone. Overall, this study revealed that these P450s show different transcription profiles according to xenobiotic exposures, life stages or sex. Their putative chemoprotective functions are discussed.
Chondroprotective Potential of Fruit Extracts of Phyllanthus emblica in Osteoarthritis

There is a need for effective nutraceuticals for osteoarthritis care. The fruit of Phyllanthus emblica is used as a powerful rejuvenator in Ayurvedic medicine. This study measured the chondroprotective potential of P. emblica (‘Amalaki’) fruits in vitro. We used aqueous extracts of unprocessed P. emblica fruit powder (powder A), and the powder obtained after hot water extraction and drying of powder A (powder B). Chondroprotection was measured in three different assay systems. First, we tested the effects of both fruit powders on the activities of the enzymes hyaluronidase and collagenase type 2. Second, an in vitro model of cartilage degradation was set-up with explant cultures of articular knee cartilage from osteoarthritis patients. Cartilage damage was assayed by measuring glycosaminoglycan release from explants treated with/without P. emblica fruit powders. Aqueous extracts of both fruit powders significantly inhibited the activities of hyaluronidase and collagenase type 2 in vitro. Third, in the explant model of cartilage matrix damage, extracts of glucosamine sulphate and powder B (0.05 mg/ml) exhibited statistically significant, long-term chondroprotective activity in cartilage explants from 50% of the patients tested. This result is important since glucosamine sulphate is the leading nutraceutical for osteoarthritis. Powder A induced a statistically significant, short-term chondroprotective activity in cartilage explants from all of the patients tested. This is the first study to identify and quantitate new chondroprotective activities of P. emblica fruits. These data provide pilot pre-clinical evidence for the use of P. emblica fruits as a chondroprotective agent in osteoarthritis therapy.
Genetics of infantile seizures with paroxysmal dyskinesia: the infantile convulsions and choreoathetosis (ICCA) and ICCA-related syndromes

The relationship between paroxysmal movement disorders (PD: paroxysmal dyskinesia) and epilepsy continues to present a challenging problem. Attacks of PD and epileptic seizures have several characteristics in common: both are paroxysmal in nature with a tendency to spontaneous remission, and a subset of PD responds well to anticonvulsants. In 1997, description of the ICCA (infantile convulsions and choreoathetosis) syndrome and linkage to chromosome 16p12-q12 provided the first genetic evidence for common mechanisms shared by benign infantile seizures and PD. The chromosome 16 ICCA locus is by far the most frequently involved in such associations as well as in pure forms of benign infantile seizures. The ICCA region at the pericentromeric area of chromosome 16 shows complicated genomic architecture and the ICCA gene still remains unknown. Genetic studies focusing on PD with or without epilepsy have led to the identification of other genes linked to chromosomes 2q35 and 10q22. Alterations of ion channel and ion pump subunits could provide a simple, albeit probably non-unique, explanation for the pathophysiology of the link between epilepsy and PD. The aim of this review is to update genetic aspects of infantile epileptic seizures and PD and their association in the context of ICCA and ICCA related syndromes.
Windowing techniques for ICI mitigation in multicarrier systems

In multicarrier systems, the time variation of the multipath channel generates intercarrier interference (ICI). In this paper, we investigate ICI mitigation techniques that rely on a band approximation of the minimum mean-squared error (MMSE) block linear equalizer (BLE). We show that windowing is an effective method to reduce the ICI at the output of the BLE. We also point up that receiver windowing is more convenient than transmitter windowing. Finally, we show that the windowed MMSE-BLE outperforms an improved MMSE-BLE that takes into account the covariance of the ICI neglected in the band approximation.
The impact of mergers on relaxed x-ray clusters II: effects on global X-ray and Sunyaev-Zel'dovich properties and their scaling relations

We use the suite of simulations presented by Poole et al. to examine global X-ray and Sunyaev-Zel'dovich (SZ) observables for systems of merging relaxed X-ray clusters. The time evolution of our merging systems' X-ray luminosities, temperatures, total mass measures, SZ central Compton parameters and integrated SZ fluxes are presented and the resulting impact on their scaling relations examined. In all cases, and for all parameters, we observe a common time evolution: two rapid transient increases during first and second pericentric passage, with interceding values near or below their initial levels. This is in good qualitative agreement with previous idealized merger simulations, although we find several important differences related to the inclusion of radiative cooling in our simulations. These trends translate into a generic evolution in the scaling-relation planes as well: a rapid transient roughly along the mass scaling relations, a subsequent slow drift across the scatter until virialization, followed by a slow evolution along and up the mass scaling relations as cooling recovers in the cluster cores. However, this drift is not sufficient to account for the observed scatter in the scaling relations. We also study the effects of mergers on several theoretical temperature measures of the intracluster medium: emission-weighted measures (T ew ), the spectroscopic-like measure (T si ) proposed by Mazzotta et al. and plasma model fits to the integrated spectrum of the system (T spec ). We find that T S1 tracks T spec for the entire duration of our mergers, illustrating that it remains a good tool for observational comparison even for highly disturbed systems. Furthermore, the transient temperature increases produced during first and second pericentric passage are 15-40 per cent larger for T ew than for T S1 or T spec . This suggests that the effects of transient temperature increases on σ8 and ΩM derived by Randall et al. are over estimated. Lastly, we examine the X-ray SZ proxy proposed by Kravtsov, Vikhlinin & Nagai (2006) and find that the tight mass scaling relation they predict remains secure through the entire duration of a merger event, independent of projection effects.
In Vitro Assessment of Metabolic Drug-Drug Interaction Potential of Apixaban through Cytochrome P450 Phenotyping, Inhibition, and Induction Studies

Apixaban is an oral, direct, and highly selective factor Xa inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases. The metabolic drug-drug interaction potential of apixaban was evaluated in vitro. The compound did not show cytochrome P450 inhibition (IC50 values >20 μM) in incubations of human liver microsomes with the probe substrates of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5. Apixaban did not show any effect at concentrations up to 20 μM on enzyme activities or mRNA levels of selected P450 enzymes (CYP1A2, 2B6, and 3A4/5) that are sensitive to induction in incubations with primary human hepatocytes. Apixaban showed a slow metabolic turnover in incubations of human liver microsomes with formation of O-demethylation (M2) and hydroxylation products (M4 and M7) as prominent in vitro metabolites. Experiments with human cDNA-expressed P450 enzymes and P450 chemical inhibitors and correlation with P450 activities in individual human liver microsomes demonstrated that the oxidative metabolism of apixaban for formation of all metabolites was predominantly catalyzed by CYP3A4/5 with a minor contribution of CYP1A2 and CYP2J2 for formation of M2. The contribution of CYP2C8, 2C9, and 2C19 to metabolism of apixaban was less significant. In addition, a human absorption, distribution, metabolism, and excretion study showed that more than half of the dose was excreted as unchanged parent (fm CYP <0.5), thus significantly reducing the overall metabolic drug-drug interaction potential of apixaban. Together with a low clinical efficacious concentration and multiple clearance pathways, these results demonstrate that the metabolic drug-drug interaction potential between apixaban and coadministered drugs is low.
Extremal problems on triangle areas in two and three dimensions

The study of extremal problems on triangle areas was initiated in a series of papers by Erdös and Purdy in the early 1970s. Here we present new results on such problems, concerning the number of triangles of the same area that are spanned by finite point sets in the plane and in 3-space, and the number of distinct areas determined by the triangles. In the plane, our main result is an <i>O</i>(<i>n</i><sup>44/19</sup>) = <i>O</i>(<i>n</i><sup>2.3158</sup>) upper bound on the number of unit-area triangles spanned by n points, which is the first improvement of the classical bound of <i>O</i>(<i>n</i><sup>7/3</sup>) from 1992. We also make progress in a number of important special cases: We show: (i) For points in convex position, there exist <i>n</i>-element point sets that span Ω(<i>n</i> log <i>n</i>) triangles of unit area. (ii) The number of triangles of minimum (nonzero) area determined by n points is at most 2/3(<i>n</i><sup>2</sup> -- <i>n</i>); there exist <i>n</i>-element point sets (for arbitrarily large <i>n</i>) that span (6/π<sup>2</sup> -- <i>o</i>(1))<i>n</i><sup>2</sup> minimum-area triangles. (iii) The number of acute triangles of minimum area determined by n points is <i>O</i>(<i>n</i>); this is asymptotically tight. (iv) For n points in convex position, the number of triangles of minimum area is <i>O</i>(<i>n</i>); this is asymptotically tight. (v) If no three points are allowed to be collinear, there are n-element point sets that span (<i>n</i> log <i>n</i>) minimum-area triangles (in contrast to (ii), where collinearities are allowed and a quadratic lower bound holds). In 3-space we prove an <i>O</i>(<i>n</i><sup>17/7</sup>β(<i>n</i>)) = <i>O</i>(<i>n</i><sup>2.4286</sup>) upper bound on the number of unit-area triangles spanned by n points, where β(<i>n</i>) is an extremely slowly growing function related to the inverse Ackermann function. The best previous bound, <i>O</i>(<i>n</i><sup>8/3</sup>), is another classical result of Erdös and Purdy from 1971. We further show, for point sets in3-space: (i) The number of minimum nonzero area triangles is at most <i>n</i><sup>2</sup> + <i>O</i>(<i>n</i>), and this is worst-case optimal, up to a constant factor. (ii) There are n-element point sets that span (<i>n</i><sup>4/3</sup>) triangles of maximum area, all incident to a common point. In any <i>n</i>-element point set, the maximum number of maximum-area triangles incident to a common point is <i>O</i>(<i>n</i><sup>4/3+ε</sup>), for any ε > 0. (iii) Every set of <i>n</i> points, not all on a line, determines at least (<i>n</i><sup>2/3</sup>/β(<i>n</i>)) triangles of distinct areas, which share a common side.
Elevated systemic levels of endothelin-1 and blood pressure correlate with blunted constrictor responses and downregulation of endothelin(A), but not endothelin(B), receptors in an animal model of hypertension.

Hypertension is a major risk factor in the development of cardiovascular disease. Adenovirus gene transfer of endothelin-1 (Ad.CMV.ET-1) in rats produced significant (5-fold) increases in plasma ET-1 and systemic blood pressure (46%) 4 days after viral administration, compared with beta-galactosidase (Ad.CMV.beta-gal) injected as control. The density (B(max)) of the ET receptor ET(A) measured in aortas was reduced significantly by more than 50% to 17+/-2 fmol.mg(-1) of protein for the Ad.CMV. ET-1 group compared with 39+/-6 fmol x mg(-1) of protein for the control. There was no change in the density of the smaller population of the ET(B) sub-type. In agreement, the ratio of ET(A) mRNA to cyclophilin mRNA (a housekeeping gene) measured by Northern analysis was reduced in Ad.CMV. ET-1 rats compared with controls. The ratio of mRNA encoding the ET(B) sub-type did not change. ET-1 vasoconstriction was significantly reduced (P<0.05) in aortas from Ad.CMV. ET-1-treated rats [pD(2)=8.67+/-0.14 (where pD(2) is -log(10)EC(50)); n=11] versus the control (pD(2)=9.11+/-0.06; n=14) but there was no significant difference in the potency of two other vasoconstrictors tested (noradrenaline and Arg-vasopressin), indicating this was a specific effect on ET receptors. There was no change in the affinity of ET-1 binding to either receptor sub-type in the experimental group compared with the control, demonstrating that the attenuation in the constrictor response is the result of the reduced density of receptors rather than a change in affinity. The results show that ET(A) (but not ET(B)) receptors are modulated in this experimental model of hypertension and provide further evidence for selective blockade of the ET(A) receptor as a therapeutic strategy.
Self-Compassion as a Mediator of Maladaptive Perfectionism and Depressive Symptoms in College Students

ABSTRACT The purpose of the study was to examine the relationships among maladaptive perfectionism, self-compassion, and depressive symptoms in college students. It was hypothesized that self-compassion would mediate the relationship between maladaptive perfectionism and depressive symptoms, with maladaptive perfectionism related to lower levels of self-compassion, and lower levels of self-compassion related to greater endorsement of depressive symptoms. Results supported partial mediation, indicating that self-compassion partially accounts for the relationship between maladaptive perfectionism and depressive symptoms. Implications for practice and research are discussed.
Protective Effects of Resveratrol against Chronic Immobilization Stress on Testis

Objective. The aim of this study was to investigate protective effects of resveratrol, a strong antioxidant, against possible negative effects of chronic immobilization stress on testes of male rats histochemically, immunohistochemically, ultrastructurally, and biochemically. Material and Methods. Male Wistar rats were divided into 4 groups (n = 7). Group I, control group (C), was not exposed to stress. Group II, stress group (S), was exposed to chronic immobilization stress. In Group III, low dose resveratrol + stress group (LRS), rats were given 10 mg/kg/day resveratrol just before the stress application. In Group IV, high dose resveratrol + stress group (HRS), rats were given 20 mg/kg/day resveratrol just before the stress application. For chronic immobilization stress application animals were put in the plastic tubes (6 cm in diameter, 15 cm in length) during 32 days for 6 hours. All animals were sacrificed 18 hours after the last stress application. Results. Histochemical and ultrastructural investigations showed that in stress group there was germ cell deprivation in seminiferous tubules and increase of connective tissue on interstitial area. No significant changes were seen in low and high dose resveratrol groups. After immunohistochemical investigations, TUNEL (+) and Active Caspase-3 (+) cells were increased in seminiferous tubules of stress group compared with those control group, but they were decreased in low and high dose resveratrol groups. According to biochemically results, MDA, GSH, and testosterone levels in stress group showed no significant difference when compared with those of the other groups. Conclusion. The chronic immobilization stress increases oxidative stress and apoptosis and causes histological tissue damages; resveratrol can minimize the histological damage in testes significantly.
Stability Analysis of Time-Delay Fuzzy Systems Using Fuzzy Lyapunov Method

This study presents an H-infinite controller design for time-delay Takagi-Sugeno (T-S) fuzzy systems based on the fuzzy Lyapunov method, which is defined in terms of fuzzy blending quadratic Lyapunov functions. The delay-dependent robust stability criterion is derived in terms of the fuzzy Lyapunov method to guarantee the stability of time-delay T-S fuzzy systems subjected to disturbances. Based on the delay-dependent condition and parallel distributed compensation (PDC) scheme, the controller design problem is transformed into solving linear matrix inequalities (LMI).
Active surveillance compared with initial treatment for men with low-risk prostate cancer: a decision analysis.

CONTEXT In the United States, 192,000 men were diagnosed as having prostate cancer in 2009, the majority with low-risk, clinically localized disease. Treatment of these cancers is associated with substantial morbidity. Active surveillance is an alternative to initial treatment, but long-term outcomes and effect on quality of life have not been well characterized. OBJECTIVE To examine the quality-of-life benefits and risks of active surveillance compared with initial treatment for men with low-risk, clinically localized prostate cancer. DESIGN AND SETTING Decision analysis using a simulation model was performed: men were treated at diagnosis with brachytherapy, intensity-modulated radiation therapy (IMRT), or radical prostatectomy or followed up by active surveillance (a strategy of close monitoring of newly diagnosed patients with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies, with treatment at disease progression or patient choice). Probabilities and utilities were derived from previous studies and literature review. In the base case, the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was assumed to be 0.83. Men incurred short- and long-term adverse effects of treatment. PATIENTS Hypothetical cohorts of 65-year-old men newly diagnosed as having clinically localized, low-risk prostate cancer (prostate-specific antigen level <10 ng/mL, stage ≤T2a disease, and Gleason score ≤6). MAIN OUTCOME MEASURE Quality-adjusted life expectancy (QALE). RESULTS Active surveillance was associated with the greatest QALE (11.07 quality-adjusted life-years [QALYs]), followed by brachytherapy (10.57 QALYs), IMRT (10.51 QALYs), and radical prostatectomy (10.23 QALYs). Active surveillance remained associated with the highest QALE even if the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was as low as 0.6. However, the QALE gains and the optimal strategy were highly dependent on individual preferences for living under active surveillance and for having been treated. CONCLUSIONS Under a wide range of assumptions, for a 65-year-old man, active surveillance is a reasonable approach to low-risk prostate cancer based on QALE compared with initial treatment. However, individual preferences play a central role in the decision whether to treat or to pursue active surveillance.
The Impact of Disability Compensation on Long-term Treatment Outcomes of Patients With Sciatica Due to a Lumbar Disc Herniation

Study Design. Prospective, observational study. Objective. To compare long-term disability and health-related quality of life outcomes of individuals receiving or not receiving workers’ compensation at baseline evaluation. Summary of Background Data. Disability compensation has long been associated with poor clinical outcomes. However, most studies have assessed outcomes over short time periods using unvalidated measures without controlling for potential confounders. Method. Patients with sciatica due to a herniated lumbar disc were treated by physicians in community based orthopedic, neurosurgical, and occupational medicine practices throughout Maine. Outcomes assessed included disability compensation and work status, and health-related quality of life, controlling for initial treatment received and factors predicting initial workers’ compensation status. Results. Among 440 eligible patients, 172 (86%) receiving workers’ compensation and 222 (92%) not receiving workers’ compensation at baseline evaluation completed at least one follow-up between 5 and 10 years (80% completed 10-year). Baseline demographics, past back history, imaging findings, symptoms, functional status, and expectations significantly differed according to the patient’s baseline workers’ compensation status. After 5−10 years, most patients, regardless of baseline workers’ compensation status (yes or no), were not receiving disability compensation (83% vs. 96%, respectively) and were employed (78% for both groups). However, workers’ compensation patients were significantly more likely to be receiving disability compensation and had worse symptoms, functional status, and satisfaction outcomes. Outcome differences diminished in magnitude after controlling for baseline differences among patients receiving workers’ compensation or not but continued to favor those not initially receiving workers’ compensation. Initial treatment received, either surgical or nonsurgical, did not influence these findings. Conclusions. Long-term employment and disability outcomes were favorable for most patients with a discherniation, regardless of initial workers’ compensation status. However, individuals initially receiving workers’ compensation had worse disability and quality of life outcomes compared to individuals not receiving workers’ compensation. Despite these differences, long-term work outcomes were similarly favorable.