Miracle-dz/UniFAR-FTUs huggingface dataset:
Human NDR Kinases Control G1/S Cell Cycle Transition by Directly Regulating p21 Stability

ABSTRACT The G1 phase of the cell cycle is an important integrator of internal and external cues, allowing a cell to decide whether to proliferate, differentiate, or die. Multiple protein kinases, among them the cyclin-dependent kinases (Cdks), control G1-phase progression and S-phase entry. With the regulation of apoptosis, centrosome duplication, and mitotic chromosome alignment downstream of the HIPPO pathway components MST1 and MST2, mammalian NDR kinases have been implicated to function in cell cycle-dependent processes. Although they are well characterized in terms of biochemical regulation and upstream signaling pathways, signaling mechanisms downstream of mammalian NDR kinases remain largely unknown. We identify here a role for human NDR in regulating the G1/S transition. In G1 phase, NDR kinases are activated by a third MST kinase (MST3). Significantly, interfering with NDR and MST3 kinase expression results in G1 arrest and subsequent proliferation defects. Furthermore, we describe the first downstream signaling mechanisms by which NDR kinases regulate cell cycle progression. Our findings suggest that NDR kinases control protein stability of the cyclin-Cdk inhibitor protein p21 by direct phosphorylation. These findings establish a novel MST3-NDR-p21 axis as an important regulator of G1/S progression of mammalian cells.
Distribution of fluorescent microspheres in vascular space and parenchymal organs of intact nude rats

Purpose: To assess kinetics of elimination of different sized microspheres (MS) from the blood pool and tendency of their distribution in parenchymal organs of intact nude rats. Materials and methods: A mixture of 1 μm and 3 μm MS in phosphate-buffered saline was injected intravenously into eight rats under intraperitoneal anaesthesia. Blood samples were collected before, just after and in 2, 5 and 10 min after MS injection. Dynamics of MS elimination from blood pool was evaluated with flow cytometry. After euthanasia, histological sections were prepared and distributions of MS through the liver, spleen, kidney and lung were analysed with fluorescence microscopy and flow cytometry. Results: The number of microspheres registered in the intravascular space showed a marked exponential decrease over time independent of MS size. Different amounts and proportions of 1 μm and 3 μm MS were revealed in lung, liver, spleen and kidneys of the rats. Most of 1 μm MS were localised in liver and spleen. In contrast, 3 μm MS were detected predominantly in lung. Conclusion: 1 μm and 3 μm MS may be assumed as free circulating particles only for a short period of time after injection. Their elimination kinetics seems to be tightly linked to specific tissue properties such a pulmonary vasoconstriction and phagocytosis.
CYP19A1 Genetic Variation in Relation to Prostate Cancer Risk and Circulating Sex Hormone Concentrations in Men from the Breast and Prostate Cancer Cohort Consortium

Sex hormones, particularly the androgens, are important for the growth of the prostate gland and have been implicated in prostate cancer carcinogenesis, yet the determinants of endogenous steroid hormone levels remain poorly understood. Twin studies suggest a heritable component for circulating concentrations of sex hormones, although epidemiologic evidence linking steroid hormone gene variants to prostate cancer is limited. Here we report on findings from a comprehensive study of genetic variation at the CYP19A1 locus in relation to prostate cancer risk and to circulating steroid hormone concentrations in men by the Breast and Prostate Cancer Cohort Consortium (BPC3), a large collaborative prospective study. The BPC3 systematically characterized variation in CYP19A1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNP) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,166 prostate cancer cases and 9,079 study-, age-, and ethnicity-matched controls. CYP19A1 htSNPs, two common missense variants and common haplotypes were not significantly associated with risk of prostate cancer. However, several htSNPs in linkage disequilibrium blocks 3 and 4 were significantly associated with a 5% to 10% difference in estradiol concentrations in men [association per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 1 × 10-5], and with inverse, although less marked changes, in free testosterone concentrations. These results suggest that although germline variation in CYP19A1 characterized by the htSNPs produces measurable differences in sex hormone concentrations in men, they do not substantially influence risk of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2734–44)
Towards Indonesian speech-emotion automatic recognition (I-SpEAR)

Even though speech-emotion recognition (SER) has been receiving much attention as research topic, there are still some disputes about which vocal features can identify certain emotion. Emotion expression is also known to be differed according to the cultural backgrounds that make it important to study SER specific to the culture where the language belongs to. Furthermore, only a few studies addresses the SER in Indonesian which what this study attempts to explore. In this study, we extract simple features from 3420 voice data gathered from 38 participants. The features are compared by means of linear mixed effect model which shows that people who are in emotional and non-emotional state can be differentiated by their speech duration. Using SVM and speech duration as input feature, we achieve 76.84% average accuracy in classifying emotional and non-emotional speech.
Evaluation of Carotid Atherosclerosis from the Perspective of Blood Flow Reflection

Detection and prevention of atherosclerosis at an early stage is important for its prevention. The aim of this study was to propose a valid and highly reliable index for the evaluation of carotid atherosclerosis or carotid function. Images of carotid Doppler wave profiles were processed using an image processing software, and the relative fluctuation in blood flow was calculated from the luminance in one cardiac cycle. Frequency analysis was performed and up to 10 time components of basic frequency (f1) were indicated. The evaluation functionαwas estimated by calculating the ratio of the sum of components f3–f10 against the f1 + f2 components. Blood pressure of the finger was continuously measured using Finapress during passive postural change from the supine to the standing position, the baroreceptor function was evaluated by the frequency method, and the plaque score was measured by ultrasound tomography. The influence of factors such as arterial compliance, blood vessel resistance, and heart rate on this index was studied using electric circuit model simulation. The subjects were 33 patients (18 men, 15 women) who had various types of atherosclerotic disease and hypertension. The average age was 67.3 + 12.2 years. The results showed that index α had a strong negative correlation with age and plaque score, and a weak positive correlation with baroreceptor function. Simulation results supported the clinical result. We proposed a new index to evaluate carotid atherosclerosis without blood pressure measurement using the carotid Doppler method. It is a potential index for detecting atherosclerosis of local arteries such as the carotid.
Efficient Pass-Transistor-Logic Synthesis for Sequential Circuits

An efficient logic synthesis based on pass-transistor logic (PTL) is developed which can generate both combinational and sequential circuits. Instead of using traditional CMOS cell library which usually contains hundred of different types of cells, the proposed PTL synthesizer uses only three types of cells: 2-to-1 multiplexer (MUX), inverter, and D flip-flop (DFF). The PTL synthesizer first employs Synopsys design compiler (DC) to perform preliminary logic translation and minimization for the input HDL descriptions. Then, the PTL-based logic mapping performs area reduction and automatic driving strength selection considering user's area and/or speed requirements. The area reduction process eliminates redundant inverters during PTL logic mapping. The driving strength selection is to determine the best choice of the driving strength for each PTL cell without sacrificing the speed performance. Post-layout simulation shows that the synthesizer generates results with better area, speed and power performance compared with those with Artisan standard cell library which is popularly used in current cell-based design flow
Factors associated with sexual dysfunction; a population based study in Iranian reproductive age women.

BACKGROUND Sexual function results from complex interactions of neurovascular and endocrine factors. The prevalence of sexual dysfunction varies in different countries. This study aimed to determine the prevalence of sexual dysfunction and the related factors among reproductive age women in Iran. METHODS A community-based cross-sectional descriptive study was carried out on 784 married women living in urban areas of 4 provinces of Iran. Participants were recruited using a stratified, multistage probability cluster sampling method. Female sexual function was assessed using the Female sexual function index questionnaire. Data was analyzed using Spearman and logistic regression tests. RESULTS The results demonstrated 27.3% prevalence of sexual dysfunction including 0.8% severe, 20.3% moderate, and 6.3% mild sexual dysfunction. Among women with sexual dysfunction, the frequency of desire, arousal, lubrication, and orgasmic disorders were 35.6%, 39.9%, 18.9%, and 27.3%, respectively. Dyspareunia was reported by 56.1% of women. Among the participants, 15.2% were unsatisfied with their sexual life. There was a statistically significant relationship between sexual dysfunction and duration of married life, perceived attraction of spouse, overall satisfaction with routine life and the women's ability to express their sexual desires. CONCLUSION Sexual dysfunction is prevalent among Iranian women. A comprehensive service including counseling programs for sexual dysfunction at primary health care is highly recommended.
Bronchiolitis in infants

Bronchiolitis is a common cause of wheezing among infants. Respiratory syncytial virus (RSV) is the most common infectious agent to cause bronchiolitis, and RSV infection accounts for more than 125,000 hospitalizations per year in the United States. Beyond supportive measures, the care of infants with bronchiolitis remains controversial. Practitioners continue to treat infants with a variety of pharmacologic agents, despite limited evidence of their efficacy. Investigators continue to search for the safest and most cost-effective methods to treat infants with bronchiolitis, not only to overcome obstructive symptoms during the acute illness, but also to prevent recurrent symptoms of airway obstruction that occur in some children for years after their initial episode of bronchiolitis. Improved understanding of the pathogenesis of RSV infection and of virus-host interactions may one day lead to the development of agents that alter the initial inflammatory response and strategies that help prevent recurrent episodes of wheezing and the development of asthma after acute bronchiolitis.
Enhanced Resistance of Gastric Mucosa to Damaging Agents in the Rat Stomach Adapted to Helicobacter pylori Lipopolysaccharide

Background and Aim: Lipopolysaccharide (LPS) has been proposed to act as one of numerous virulence factors in the Helicobacter pylori (HP)-infected stomach. However, little is known as to whether the gastric mucosa can withstand the repeated LPS insult, and how the possible adaptation to this endotoxin influences the damage induced by strong irritants. We determined the effect of a single or repeated parenteral administration of LPS obtained from HP on acute gastric lesions induced by intragastric application of 100% ethanol (1.5 ml) and by water immersion and restraint stress (WRS). Methods: The area of the gastric lesions was measured by planimetry, mucosal gastric blood flow (GBF) was determined by H2 gas clearance, and gastric luminal content was collected for the determination of luminal NO2–/NO3– levels by the Griess reaction. Biopsy samples were taken for the measurement of prostaglandin (PG) E2 by radioimmunoassay and mucosal expression of constitutive and inducible nitric oxide synthase (cNOS and iNOS), constitutive (COX-1) and inducible cyclooxygenase (COX-2), heat shock protein 70 (HSP 70) mRNA and protein were analyzed by RT-PCR and Western blot. Results:HP LPS (1 mg/kg i.p.) injected once or 5 times produced negligible macroscopic injury and failed to influence GBF significantly compared to the injuries recorded in vehicle-controlled rats. Single and repeated (5 times) administration of HP LPS significantly reduced ethanol- and WRS-induced lesions, these protective effects were accompanied by a rise in GBF and excessive luminal release of NO. The suppression of NOS activity by L-NAME (20 mg/kg i.p.), a nonspecific NOS inhibitor, or L- (30 mg/kg i.g.), a specific iNOS inhibitor, and of COX-2 activity by NS-398 reversed the protective and hyperemic effects of single or repeated LPS administrations against ethanol and WRS damage and the accompanying rise in NO and PGE2 production. These effects of L-NAME were significantly antagonized by the addition of L-arginine, a substrate for NO synthesis. The signals for cNOS, COX-1 and HSP 70 mRNA were detected by RT-PCR in the vehicle-treated gastric mucosa, whereas gene and protein expression of iNOS, COX-2 and HSP 70 mRNA were significantly increased only in rats treated with 1 or 5 applications of HP LPS. Conclusions: Repeated injections of HP LPS enhance gastric mucosal resistance to the mucosal damage induced by ethanol and WRS via a mechanism involving mucosal overexpression of iNOS, COX-2 and HSP 70 with subsequent excessive production of NO and PGE2.
Association of hypertension and sleep-disordered breathing.

BACKGROUND To our knowledge, the association between sleep-disordered breathing (SDB) and hypertension has not been evaluated in subjects from the general population with a wide age range while adjusting for the possible confounding factors of age, body mass index, sex, menopause and use of hormone replacement therapy, race, alcohol use, and smoking. METHODS In the first phase of this study, we interviewed 4364 men and 12,219 women, aged 20 to 100 years. In the second phase of this study, 741 men and 1000 women, previously interviewed, were selected based on the presence of risk factors for SDB (snoring, daytime sleepiness, obesity, hypertension, and, for women, menopause). Each subject selected for the second phase of the study provided a comprehensive history, underwent a physical examination, and was evaluated for 1 night in the sleep laboratory. In terms of severity of SDB, 4 groups were identified: moderate or severe (obstructive apnea/hypopnea index > or =15.0), mild (snoring and an obstructive apnea/hypopnea index of 0.1-14.9), snoring, and no SDB, the control group. RESULTS Sleep-disordered breathing was independently associated with hypertension when potential confounders were controlled for in the logistic regression analysis. The strength of this association decreased with age and was proportional to the severity of SDB. In the best-fitted model, neither sex nor menopause changed the relationship between hypertension and SDB. CONCLUSIONS In the results of this study, SDB, even snoring, was independently associated with hypertension in both men and women. This relationship was strongest in young subjects, especially those of normal weight, a finding that is consistent with previous findings that SDB is more severe in young individuals.
[Analysis of complications and prognosis for different types of stroke patients registered between 1993 and 2000 in Aichi Prefecture].

PURPOSE This study was designed to analyze complications and prognosis for different types of stroke patients registered in Aichi Prefecture between 1993 and 2000. METHODS A total of 23,979 out of 27,304 registered patients in the Aichi stroke patient registration program with 4 type of strokes (cerebral thrombosis (CRT), cerebral embolism (CRE), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH)) were analyzed for complications and prognosis (survival, disability, dementia), with reference to gender, age-groups, and types of stroke. RESULTS A total of 13,365 (55.7%) male (65.5 +/- 12.2 yr: Mean +/- SD) and 10,614 (44.3%) female (69.7 +/- 13.3 yr) patients were registered. As the type of stroke, CRT comprised the highest percentage, both in males (49.5%) and females (41.1%), followed by ICH (males: 30.4%, females: 29.8%). The percentage of SAH in females (17.3%) was found to be about twice as high as that in males (8.3%). Analyses of complications revealed hypertension to be the greatest risk factor in both sexes (about 50%), followed by history of stroke (males: 20.1%, females: 16.2%). Male patients had a significantly higher overall survival rate (84.7%) than females (81.0%) (P <0.001). SAH was associated with the lowest survival rate in both sexes (about 60%), with statistical significance (P<0.001). Development of disability or/and dementia as sequela of stroke was higher in females (disability: 54.5%, dementia: 21.1%) than in males (44.2%, 15.1%, respectively) (P< 0.001). Logistic regression analyses revealed that the factors most contributing to death were advanced age, a history of stroke, heart disease, and renal insufficiency. For the development of disability and dementia, being femal, of advanced age, with a history of stroke, heart disease, and renal insufficiency were important. Abnormal lipid metabolism appeared to be a protection factor regarding prognosis (survival, disability, dementia). CONCLUSIONS This study demonstrated that hypertension is the most frequently reported complication for all types of stroke except CRE, and logistic regression analyses revealed that the factor contributing most to prognosis (survival, disability, dementia) was a history of stroke. The results suggested the importance of: i) removing hypertansion as the most significant risk factor, as well as diabetes and heart disease in order to prevent strokes; and ii) preventing re-attack(s) of stroke in order to improve the prognosis.
Earliest time to onset of action leading to successful intercourse with vardenafil determined in an at-home setting: a randomized, double-blind, placebo-controlled trial.

INTRODUCTION Vardenafil, a potent and selective oral PDE5 inhibitor, is efficacious and generally well-tolerated in men with erectile dysfunction (ED). Of considerable interest to patients and physicians is an understanding of the time required after dosing to attain penile erection sufficient for successful sexual intercourse. AIM To determine the earliest time to onset of action of vardenafil 10 and 20 mg leading to successful intercourse compared to placebo in men with ED. METHODS A prospective, randomized, double-blind, parallel-group, at-home study of 732 men with ED (mean age 55.5 years) was conducted at 64 sites in North America and Europe. Following a 4-week run-in period, patients were randomized to either vardenafil 10 (N = 237) or 20 mg (N = 248) or placebo (N = 247) to be taken on demand over 4 weeks. Using a stopwatch, patients recorded the elapsed time from dosing to attainment of an erection perceived to be adequate for penetration that led to intercourse completion. Earliest time of onset was defined as the fastest time among the first four doses for each patient. Time points from 25 to 5 minutes were tested for significance (alpha = 0.025) using a backward stepping procedure. RESULTS Mean baseline erectile function domain score (13.4) indicated moderate ED. Within 25 minutes after dosing, 50%/53% of men on vardenafil 10/20 mg had at least one erection in the first four doses perceived to be sufficient for penetration with subsequent intercourse completion compared to 26% on placebo (P < 0.0001). A statistically superior response to vardenafil vs. placebo was observed in these responders at all times >or= 10 and >or= 11 minutes (P < 0.025) in the 10 and 20 mg groups, respectively. In a retrospective analysis using time intervals of <or= 15, <or= 20, <or= 25 and <or= 30 minutes between dosing and erection adequate for penetration, 75-77% of these intercourse attempts were successful (SEP3 positive) by patients receiving vardenafil 10/20 mg, compared to 45-47% of attempts by those who received placebo. Vardenafil 10/20 mg was generally well-tolerated with headache (7%/12% vs. 1%) and flushing (6%/9% vs. < 1%) reported more frequently than with placebo. No patient discontinued vardenafil therapy due to adverse events. CONCLUSION In this large, at-home study, the onset of action of vardenafil with subsequent intercourse completion was recognized as early as 10 minutes after dosing.
In vitro comparison of A-56619, A-56620, amifloxacin, ciprofloxacin, enoxacin, norfloxacin, and ofloxacin against methicillin-resistant Staphylococcus aureus

Seven quinolone antibiotics were tested against 115 isolates of methicillin-resistant Staphylococcus aureus. The MICs for 90% of the strains tested were 0.5 microgram/ml for A-56619, A-56620, ciprofloxacin, and ofloxacin; 2.0 micrograms/ml for amifloxacin and enoxacin; and 4.0 micrograms/ml for norfloxacin. Killing kinetic studies showed a similar killing rate for all seven antibiotics.
Nanomechanics of Cells and Biomaterials Studied by Atomic Force Microscopy

The behavior and mechanical properties of cells are strongly dependent on the biochemical and biomechanical properties of their microenvironment. Thus, understanding the mechanical properties of cells, extracellular matrices, and biomaterials is key to understanding cell function and to develop new materials with tailored mechanical properties for tissue engineering and regenerative medicine applications. Atomic force microscopy (AFM) has emerged as an indispensable technique for measuring the mechanical properties of biomaterials and cells with high spatial resolution and force sensitivity within physiologically relevant environments and timescales in the kPa to GPa elastic modulus range. The growing interest in this field of bionanomechanics has been accompanied by an expanding array of models to describe the complexity of indentation of hierarchical biological samples. Furthermore, the integration of AFM with optical microscopy techniques has further opened the door to a wide range of mechanotransduction studies. In recent years, new multidimensional and multiharmonic AFM approaches for mapping mechanical properties have been developed, which allow the rapid determination of, for example, cell elasticity. This Progress Report provides an introduction and practical guide to making AFM‐based nanomechanical measurements of cells and surfaces for tissue engineering applications.