Miracle-dz/UniFAR-FTUs huggingface dataset:
Fragile Histidine Triad Expression in Oral Squamous Cell Carcinoma and Precursor Lesions

Pupose: Fragile histidine triad (FHIT) expression in precursor oral lesions (POL) and oral squamous cell carcinomas (OSCC) was studied with regard to (a) the frequency of loss of FHIT expression, (b) whether loss of FHIT expression correlates with degree of dysplasia in POLs, (c) whether FHIT loss predicts high-risk POLs that are more likely to transform, and (d) whether FHIT loss in OSCCs correlates with survival. Experimental Design: Ninety-four POLs and 86 OSCCs were immunostained for FHIT. Survival analysis was done for cases with validated clinical outcomes. Results: By optimizing the immunostaining protocol, we found that FHIT is expressed in a distinctive strong nuclear and weak cytoplasmic pattern in oral tissues. Loss of FHIT expression was found in 42 of 94 (45%) POLs and in 66 of 86 (77%) OSCCs. We observed a statistically significant positive correlation between frequency of FHIT loss and increasing grade of dysplasia (χ2 = 13.8; degrees of freedom = 4; P = 0.008). Loss of FHIT expression in POLs that progressed to malignancy was more frequent than in those that did not [17 of 25 (68%) versus 12 of 29 (41.4%), respectively]. This difference was statistically significant (χ2 = 3.8; degrees of freedom = 1; P = 0.046). In OSCCs, loss of FHIT staining indicated a worse prognosis (survival rate, 36.2%) than when positive FHIT staining was observed (survival rate, 50%), but the difference was not statistically significant (P = 0.546, Kaplan-Meier, log-rank). Conclusions: FHIT seems to localize to both nuclear and cytoplasmic domains. FHIT inactivation occurs early in oral carcinogenesis and may be useful molecular marker for progressive dysplastic oral lesions.
CORONARY ARTERY DISEASE Association of levels of lipoprotein Lp ( a ) , plasma lipids , and other lipoproteins with coronary artery disease documented by angiography

Association of levels of lipoprotein Lp(a), plasma lipids, and other lipoproteins with coronary artery disease documented by angiography ABSTRACT In a study of 307 white patients who underwent coronary angiography, the relationship of coronary artery disease (CAD) to plasma levels of lipoprotein Lp(a) and other lipid-lipoprotein variables was examined. Lp(a) resembles low-density lipoprotein (LDL) in several ways, but can be distinguished and quantified by electroimmunoassay. CAD was rated as present or absent and was also represented by a quantitative lesion score derived from estimates of stenosis in four major coronary vessels. Coronary lesion scores significantly correlated with Lp(a), total cholesterol, triglycerides, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol levels by univariate statistical analysis. By multivariate analysis levels of Lp(a) were associated significantly and independently with the presence of CAD (p < .02), and tended to correlate with lesion scores (p .06). Among subgroups Lp(a) level was associated with CAD in women of all ages and in men 55 years old or younger. An apparent threshold for coronary risk occurred at Lp(a) lipoprotein mass concentrations of 30 to 40 mg/dl, corresponding to Lp(a) cholesterol concentrations of approximately 10 to 13 mg/dl. Plasma Lp(a) in white patients appears to be a major coronary risk factor with an importance approaching that of the level of LDL or HDL cholesterol. THE ASSOCIATION between coronary artery disease and a plasma lipoprotein migrating on agarose gel or cellulose acetate electrophoresis as a distinct pre-beta, band was reported independently in 1972-1973 from several laboratories. '-3 The activity of the pre-beta, lipoprotein4 was soon discovered to be identical to Lp(a) plasma antigenic activity, discovered by Berg in 1963,5 and results of qualitative assays for Lp(a) likewise were associated with various manifestations of coronary artery disease.4 6 7 Studies using quantitative assays of plasma Lp(a) have tended to confirm an association with coronary artery disease, but thus far statistically significant associations have been reported from these studies only in the context of retrospective subgroup analysis8' 9 or dichotomization of Lp(a) levels above and below an arbitrary value. '0 Furthermore, the relative strength and independence of Lp(a) as an atherosclerotic risk factor have not been tested in direct comparison with other, better known risk factors. Lipoprotein Lp(a) is a cholesterol-rich lipoprotein that generally makes up less than 15% of the total plasma cholesterol. On ultracentrifugation it is recovered mostly within the high-density lipoprotein (HDL) range. 1 1 Apolipoprotein B and apolipoprotein [a], …
Bayesian Analysis of a Markov Switching Stochastic Volatility Model

This article analyzes a Markov switching stochastic volatility (MSSV) model to accommodate the shift in the mean of log-volatility. Since it is difficult to estimate the parameters in this model based on the maximum likelihood method, a Bayesian Markov-chain Monte Carlo (MCMC) approach is adopted. A particle filter for the MSSV model, which is used for model comparison and diagnostics, is constructed. The estimation result, based on weekly returns of the TOPIX, confirms the finding by previous researchers that the estimate of the persistence parameter drops and the estimate of the error variance rises in the volatility equation of the MSSV model compared to those of the standard SV model. The model comparison provides evidence that the MSSV model is favored over the standard SV model. It is also found that the MSSV model passes the diagnostic tests based on the statistics obtained from the particle filter while the SV model does not.
Penalty approach for a constrained optimization to solve on-line the inverse kinematic problem of redundant manipulators

In this paper, a penalty approach which deals with a constrained optimization to solve the inverse kinematic of redundant robot manipulators is considered. An optimization procedure using neural networks is formulated, it produces on-line position and velocity trajectories in joint space from position and orientation trajectories in Cartesian space. This new method offers substantially better accuracy and guarantees a good minimization of a performance function subject to joint limitations while achieving the end-effector task.
Molecular characterization of an atypical inv dup del 8q. Proposal of a mechanism of formation

Molecular Characterization of an Atypical Inv Dup Del 8q. Proposal of a Mechanism of Formation Laura Rodrı́guez,* Juli an Nevado, Elena Vallespin, Marı́a Palomares, Luz Golmayo, Marı́a Clara Bonaglia, Alicia Delicado, and Elena Abarca AbaCid-Gen etica, Grupo Hospital de Madrid, Madrid, Spain INGEMM (Instituto de Gen etica M edica y Molecular), IDIPAZ, Hospital Universitario de La Paz, Madrid, Spain CIBERER (ISCIII), Madrid, Spain Servicio de Endocrinolog ıa, Pedi atrica del Grupo Hospital de Madrid, Madrid, Spain Laboratorio di Citogenetica, Scientific Institute E. Medea, Bosisio Parini, LC, Italy
SUMOylation of Paraflagellar Rod Protein, PFR1, and Its Stage-Specific Localization in Trypanosoma cruzi

Background The flagellate protozoan parasite, Trypanosoma cruzi, is a causative agent of Chagas disease that is transmitted by reduviid bugs to humans. The parasite exists in multiple morphological forms in both vector and host, and cell differentiation in T. cruzi is tightly associated with stage-specific protein synthesis and degradation. However, the specific molecular mechanisms responsible for this coordinated cell differentiation are unclear. Methodology/Principal Findings The SUMO conjugation system plays an important role in specific protein expression. In T. cruzi, a subset of SUMOlylated protein candidates and the nuclear localization of SUMO have been shown. Here, we examined the biological roles of SUMO in T. cruzi. Site-directed mutagenesis analysis of SUMO consensus motifs within T. cruzi SUMO using a bacterial SUMOylation system revealed that T. cruzi SUMO can polymerize. Indirect fluorescence analysis using T. cruzi SUMO-specific antibody showed the extra-nuclear localization of SUMO on the flagellum of epimastigote and metacyclic and bloodstream trypomastigote stages. In the short-flagellate intracellular amastigote, an extra-nuclear distribution of SUMO is associated with basement of the flagellum and becomes distributed along the flagellum as amastigote transforms into trypomastigote. We examined the flagellar target protein of SUMO and show that a paraflagellar rod protein, PFR1, is SUMOylated. Conclusions These findings indicate that SUMOylation is associated with flagellar homeostasis throughout the parasite life cycle, which may play an important role in differentiation of T. cruzi.
Sexual selection in Japanese macaques II: female mate choice and male–male competition

Mating and reproductive outcomes are the product of the potentially conficting strategies of breeding males and females. In a captive group of Japanese macaques, Macaca fuscata fuscatabehavioural, endocrine and genetic data were combined to assess the independent effects of male-male competition and female mate choice on mating and reproductive success. Males were ranked by social dominance and by their attractivity to females. Computer simulation and logistic regression analyses showed that male attractivity had a stronger effect than male dominance on both mating and reproductive outcome. Although male dominance and attractivity both significantly predicted mating success during fertile periods, only male attractivity significantly predicted actual male reproductive success. These results provide evidence that female mate choice can be a stronger determinant of mating and reproductive outcome in this species when male and female strategies are in conflict. The lack of a consistent correlation between male dominance rank and reproductive success in this species may be accounted for in part by female mate choice of socially subordinate males. Sires who were observed to mate with the mother during her fertile period were more likely to be socially dominant than sires who were not observed to do so. This observation suggests the existence of alternative mating strategies by subordinate males, which may also contribute to the lack of a consistent correlation between male dominance rank and reproductive success in this species.1997The Association for the Study of Animal Behaviour
Serotonin and nitric oxide interaction in the control of bioluminescence in northern krill, Meganyctiphanes norvegica (M. Sars)

SUMMARY The role of nitric oxide (NO) in the control of bioluminescence (light production) in the crustacean Meganyctiphanes norvegica (krill) was investigated using pharmacological and immunohistochemical methods. All nitrergic drugs tested failed to induce bioluminescence per se but modulated light production stimulated by 5-hydroxytryptamine (5-HT). NO donors [sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP)] injected in live specimens significantly reduced light production stimulated by 5-HT, whereas inhibition of the enzyme NO synthase (NOS) with l-NAME (NG-nitro-l-arginine methyl ester) resulted in an enhancement of the 5-HT response. The effects of NO do not seem to be mediated via production of cGMP as injections of a cGMP analogue (8-Bromoguanosine 3′,5′-cyclic monophosphate) gave inconclusive effects on the 5-HT-stimulated light response. Inhibition of cGMP production with ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) did not affect the light response. Moreover, a few individuals showed a considerably higher response to 5-HT in April and June compared with specimens collected in the autumn and winter. Furthermore, both NOS-like and 5-HT-like materials were detected by immunohistochemistry inside the light organs. NOS-like immunoreactivity was primarily observed in structures associated with vessels inside the light organs, whereas 5-HT-like material was abundant in nerve fibres throughout the whole light organ. The results suggest that NO has a modulatory role at several levels in the control of light production in M. norvegica and that NO and 5-HT interact in this regulation.
Pharmacokinetics of intravenously administered liposomal all-trans-retinoic acid (ATRA) and orally administered ATRA in healthy volunteers.

PURPOSE To determine single-and multiple-dose pharmacokinetics of liposomal-all- trans -retinoic acid (Atragen) following intravenous and oral ATRA (Vesanoid) administration in healthy volunteers. METHODS This was a randomized, prospective, open-label, parallel pharmacokinetic study in which 29 subjects were given 90 mg/m (2) i.v. liposomal (L)-ATRA (16 subjects) every other day or 45 mg/m (2) oral ATRA (13 subjects) daily over 15 days. Pharmacokinetic parameters were assessed on days 1, 9, and 15. RESULTS Twenty-two subjects (11 in each group) completed the study and were evaluated. Area under the plasma concentration-time curve [AUC(0, infinity)] and maximum plasma concentration (C(max) ) of ATRA did not decrease during the 15 days of L-ATRA treatment. However, the oral ATRA regimen resulted in a significant decrease in the AUC(0, infinity) and C(max) of 45.3% and 31.8%, respectively, on day 9 as compared with that to day 1 (p< 0.05). In addition, the mean AUC(0, infinity) was 13- and 22-fold greater for L-ATRA than for oral ATRA on days 1 and 9, respectively. Despite the significantly higher plasma concentrations after L-ATRA treatment, the side effects of each formulation were similar, except for dermal exfoliation, which was seen in 31% of the subjects after L-ATRA dosing, and abnormal liver function tests that were seen in 23% of the subjects after oral ATRA administration. CONCLUSIONS These findings suggest that i.v. administration of L-ATRA maintains higher and stable plasma ATRA concentrations than oral ATRA in healthy subjects after repetitive administration. L-ATRA with a favorable pharmacokinetic profile may have potential advantages over oral ATRA and may be more efficacious in the treatment of acute promyelocytic leukemia or other retinoid-responsive cancers.
Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision

The set of guidelines for good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents, which was developed following an international consensus conference in Copenhagen, has been revised and updated following the second consensus conference in Stockholm in 2005. It is hoped that these guidelines will continue to help researchers in the field and assist the pharmaceutical industry and equipment manufacturers in enhancing the standards of the studies they sponsor.
Mechanism underlying bupivacaine inhibition of G protein-gated inwardly rectifying K+ channels

Local anesthetics, commonly used for treating cardiac arrhythmias, pain, and seizures, are best known for their inhibitory effects on voltage-gated Na+ channels. Cardiovascular and central nervous system toxicity are unwanted side-effects from local anesthetics that cannot be attributed to the inhibition of only Na+ channels. Here, we report that extracellular application of the membrane-permeant local anesthetic bupivacaine selectively inhibited G protein-gated inwardly rectifying K+ channels (GIRK:Kir3) but not other families of inwardly rectifying K+ channels (ROMK:Kir1 and IRK:Kir2). Bupivacaine inhibited GIRK channels within seconds of application, regardless of whether channels were activated through the muscarinic receptor or directly via coexpressed G protein Gβγ subunits. Bupivacaine also inhibited alcohol-induced GIRK currents in the absence of functional pertussis toxin-sensitive G proteins. The mutated GIRK1 and GIRK2 (GIRK1/2) channels containing the high-affinity phosphatidylinositol 4,5-bisphosphate (PIP2) domain from IRK1, on the other hand, showed dramatically less inhibition with bupivacaine. Surprisingly, GIRK1/2 channels with high affinity for PIP2 were inhibited by ethanol, like IRK1 channels. We propose that membrane-permeant local anesthetics inhibit GIRK channels by antagonizing the interaction of PIP2 with the channel, which is essential for Gβγ and ethanol activation of GIRK channels.
Sympathetic Activity in Major Depressive Disorder: Identifying Those at Increased Cardiac Risk?

Background Evidence exists linking major depressive disorder (MDD) with clinical cardiovascular events. The importance of the sympathetic nervous system in the generation of cardiac risk in other contexts is established. Objective To examine the importance of the sympathetic nervous system in the generation of cardiac risk in patients with major depressive disorder (MDD). Methods Studies were performed in 39 patients meeting the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria for MDD and in 76 healthy subjects. Treatment for patients consisted of selective serotonin reuptake inhibition (SSRI) for 12 weeks. Whole body and cardiac sympathetic activity were examined using noradrenaline isotope dilution methodology and sympathetic nerve recording techniques. Measurement of the extraction of infused tritiated noradrenaline by the heart, and estimation of cardiac dihydroxyphenylglycol production provided direct quantification of neuronal noradrenaline reuptake. Results Sympathetic activity, particularly in the heart and for the whole body, in patients with MDD followed a bimodal distribution. Elevated values were observed in patients with co-morbid panic disorder (P = 0.006). Consistent with a defect in noradrenaline reuptake, the cardiac extraction of tritiated noradrenaline (0.80 ± 0.01 versus 0.56 ± 0.04%, P < 0.001) and cardiac dihydroxyphenylglycol overflow (109 ± 8 versus 73 ± 11, P = 0.01) were reduced in patients with MDD. SSRI therapy abolished the excessive sympathetic activation, with whole body noradrenaline spillover falling from 518 ± 83 to 290 ± 41 ng/min (P = 0.008). Conclusions We have identified a subset of patients with MDD in whom sympathetic nervous activity is extraordinarily high, including in the sympathetic outflow to the heart. Treatment with an SSRI may reduce sympathetic activity in a manner likely to reduce cardiac risk.
Experimentally-induced and real-world acute anxiety have no effect on goal-directed behaviour

Compulsivity is associated with failures in goal-directed control, an important cognitive faculty that protects against developing habits. But might this effect be explained by co-occurring anxiety? Previous studies have found goal-directed deficits in other anxiety disorders, and to some extent when healthy individuals are stressed, suggesting this is plausible. We carried out a causal test of this hypothesis in two experiments (between-subject N=88; within-subject N=50) that used the inhalation of hypercapnic gas (7.5% CO2) to induce an acute state of anxiety in healthy volunteers. In both experiments, we successfully induced anxiety, assessed physiologically and psychologically, but this did not affect goal-directed performance. In a third experiment (N=1413), we used a correlational design to test if real-life anxiety-provoking events (panic attacks, stressful events) impair goal-directed control. While small effects were observed, none survived controlling for individual differences in compulsivity. These data suggest that anxiety has no meaningful impact on goal-directed control.
Burdens among caregivers of older adults with advanced cancer and risk factors.

UNLABELLED Family caregivers of older cancer patients face many challenges in managing illness. The burden impacts physical, emotional, spiritual, and social health. The objective of this study was to identify burden among caregivers of older patients with advanced cancer, and associated factors. MATERIALS AND METHODS Caregivers of older cancer patients were randomly interviewed from March-September 2012. Information on baseline characteristics and caregiver burden using the Zarit Burden Inventory (ZBI) was collected. Descriptive statistics were used to analyze baseline data, with univariate and multiple linear regression to analyze factors associated with higher burden. RESULTS One hundred and fifty participants were assessed. The mean ZBI was 19.2 ± 12.9 (95%CI, 17.1, 21.2). Two-thirds of caregivers reported no burden (63%) and the main impact variable on ZBI was guilt. High burdens were associated with single caregiver, relationship with the patient as siblings, presence of migraines, and cancer types of the patients. CONCLUSIONS Caregiver burden of Thai cancer patients is low. This unexpected small number could be the result of the socio-cultural viewpoint. Assessment of caregivers and focusing on related factors should be incorporated into treatment plans.
Social Media and the Decision to Participate in Political Protest: Observations From Tahrir Square

Based on a survey of participants in Egypt’s Tahrir Square protests, we demonstrate that social media in general, and Facebook in particular, provided new sources of information the regime could not easily control and were crucial in shaping how citizens made individual decisions about participating in protests, the logistics of protest, and the likelihood of success. We demonstrate that people learned about the protests primarily through interpersonal communication using Facebook, phone contact, or face-to-face conversation. Controlling for other factors, social media use greatly increased the odds that a respondent attended protests on the first day. Half of those surveyed produced and disseminated visuals from the demonstrations, mainly through Facebook.
The Effects of Age and Gender on Gingival Tissue and Peripheral Blood T-Lymphocyte Subsets: A Study in Mice

The aim of this study is to investigate the effects of age and gender on relative number of CD4+ and CD8+ T lymphocyte and CD4+/CD8+ ratios in gingival tissue and peripheral blood of periodontally healthy BALB/c mice with flow cytometric analysis. The study was carried out on periodontally healthy 60 BALB/c mice. They were separated into five groups according to the life expectancy: Group I (newborn, 1–10 days old), Group II (age at weaning, 21–28 days old), Group III (age of sexual maturity, puberty, 7–8 weeks old), Group IV (adult, 8 months old), and Group V (the aged, 14 and over). Males and females were equally represented in each group. CD4+ and CD8+ T lymphocytes and CD4+/CD8+ ratio values in gingival tissue and peripheral blood were determined using flow cytometry in the biopsy samples. The relative number of CD8+ T lymphocyte in gingival tissue was higher in puberty (p < 0.05) and the aged (p < 0.05), with more significantly difference in males (p < 0.05). The CD4+/CD8+ ratios in gingival tissue were lower in puberty group and the-aged groups compared to the other groups (p < 0.05). The peripheral blood CD4+/CD8+ ratio increased in puberty and the aged groups. These differences were more significant in females than in males (p < 0.05). There were considerable negative correlations between CD4+/CD8+ T lymphocyte ratio in gingival tissue and CD4+/CD8+ T lymphocyte ratio in peripheral blood in puberty (r = 0.647, p < 0.01) and the aged ( r = 0.599, p < 0.05). In conclusion, our data suggest that CD4+/CD8+ T lymphocyte ratios in peripheral blood increase periodontally healthy mice in puberty and the old groups, while CD4+/CD8+ T lymphocyte ratios in gingival tissue decrease in the same groups. The relative number of CD8+ T lymphocytes increases in gingival tissue in puberty and the old groups when it decreases in peripheral blood. Results from this study indicated that periodontally healthy BALB/c mice may represent important information to determine the character of an immune response in the course of a lifetime.