Miracle-dz/UniFAR-FTUs huggingface dataset:
Disposition of cyclosporine in several animal species and man. I. Structural elucidation of its metabolites.

Nine ether-extractable metabolites of cyclosporine were isolated from urine of dog and man and from rat bile and feces and purified by preparative HPLC and TLC. Structural assignments were mainly based on spectroscopic data (1H NMR, 13C NMR, MS) and the results of the amino acid analysis after hydrolysis with hydrochloric acid. All the identified metabolites retained the intact cyclic oligopeptide structure of the parent drug. Structural modifications originated from enzymatic oxidation at specific sites of the peptide subunits. Transformation processes principally involved hydroxylation at the terminal carbon atom (eta-position) of the C9-amino acid 1 and the gamma-position of the N-methylleucines 4, 6, and 9, as well as N-demethylation of the N-methylleucine 4. Regioisomeric monohydroxylated cyclosporines (metabolites 1, and 17) and N-demethylcyclosporine (metabolite 21) were the primary metabolites resulting from hydroxylation of the C9-amino-acid 1 and the N-methylleucine 9, and from N-demethylation of the N-methylleucine 4. Dihydroxylated derivatives of cyclosporine (metabolites 8, 10, and 16) were generated by further oxidation of metabolite 1 on one of the other N-methylleucines (4 or 6) or on the C9-amino acid 1, or of metabolite 17 on the N-methylleucine 9. More extensive modifications were observed for metabolite 9, a dihydroxy-N-demethylcyclosporine, which could have been formed from the dihydroxy derivative 16 by N-demethylation or from the N-demethylcyclosporine 21 by dihydroxylation. Metabolite 18 differed from 17 (monohydroxycyclosporine) by the presence of a cyclic ether moiety, formally derived by intramolecular addition of the beta-hydroxyl group to the double bond of the C9-amino acid 1. (ABSTRACT TRUNCATED AT 250 WORDS)
[Subtotal colectomy with ceco-rectal anastomosis (Deloyers) for severe idiopathic constipation: an alternative to total colectomy reducing risks of digestive sequelae].

PURPOSE Functional results of total colectomy (TC) and ileorectal anastomosis for colonic inertia are often impaired by postoperative obstruction and diarrhea. In order to avoid these postoperative complications, we propose a subtotal colectomy (STC) preserving the ileo-caecal junction. METHODS Since 1989, 18 consecutive patients (17 F, 1 M; mean age: 54 years) with intractable constipation underwent TC (n = 6) or STC with caecorectal anastomosis (Deloyers Procedure) (n = 12). Mean preoperative bowel frequency was two movements every month. Colonic inertia was defined as diffuse marker delay during transit study without obstructed defecation on manometry or digitalised rectography. Rectocele (n = 10), rectal (n = 5) and genital prolapse (n = 6) were treated in the same operative time. RESULTS Postoperative course was uneventful after STC but bowel obstruction, requiring laparotomy, occurred in 3 patients (50%) after TC: enterolysis (n = 2), bowel resection (n = 2). Mean postoperative day stool frequency of TC (4.2 +/- 1.2) was higher than STC (1.2 +/- 0.1). Half of patients after TC needed anti-diarrheal treatment and diet, 33% had rectal evacuation difficulties despite liquid stools, 17% had episodic incontinence, 66% had persistent abdominal pain. Compared to TC, the functional results of STC were significantly better: regular normal transit return without diet or treatment in 75% of cases, 25% had rectal emptying difficulties easily treated by mild laxatives, only 17% had persistent abdominal pain. Postoperative obstruction, diarrhea or fecal incontinence never occurred after STC. CONCLUSION Compared to TC, STC with Deloyers procedure seems to reduce significantly the postoperative incidence of bowel obstruction, diarrhea and abdominal pain. Expected regular transit return after STC needs a careful selection of patients and simultaneous treatment of ano-rectal and pelvic floor abnormalities frequently associated with colonic inertia.
Relationships Between Explosive and Maximal Triple Extensor Muscle Performance and Vertical Jump Height

Abstract Chang, E, Norcross, MF, Johnson, ST, Kitagawa, T, and Hoffman, M. Relationships between explosive and maximal triple extensor muscle performance and vertical jump height. J Strength Cond Res 29(2): 545–551, 2015—The purpose of this study was to examine the relationships between maximum vertical jump height and (a) rate of torque development (RTD) calculated during 2 time intervals, 0–50 milliseconds (RTD50) and 0–200 milliseconds (RTD200) after torque onset and (b) peak torque (PT) for each of the triple extensor muscle groups. Thirty recreationally active individuals performed maximal isometric voluntary contractions (MVIC) of the hip, knee and ankle extensors, and a countermovement vertical jump. Rate of torque development was calculated from 0 to 50 (RTD50) and 0 to 200 (RTD200) milliseconds after the onset of joint torque. Peak torque was identified and defined as the maximum torque value during each MVIC trial. Greater vertical jump height was associated with greater knee and ankle extension RTD50, RTD200, and PT (p ⩽ 0.05). However, hip extension RTD50, RTD200, and PT were not significantly related to maximal vertical jump height (p > 0.05). The results indicate that 47.6 and 32.5% of the variability in vertical jump height was explained by knee and ankle extensor RTD50, respectively. Knee and ankle extensor RTD50 also seemed to be more closely related to vertical jump performance than RTD200 (knee extensor: 28.1% and ankle extensor: 28.1%) and PT (knee extensor: 31.4% and ankle extensor: 13.7%). Overall, these results suggest that training specifically targeted to improve knee and ankle extension RTD, especially during the early phases of muscle contraction, may be effective for increasing maximal vertical jump performance.
The dissolution of double Holliday junctions.

Double Holliday junctions (dHJS) are important intermediates of homologous recombination. The separate junctions can each be cleaved by DNA structure-selective endonucleases known as Holliday junction resolvases. Alternatively, double Holliday junctions can be processed by a reaction known as "double Holliday junction dissolution. " This reaction requires the cooperative action of a so-called "dissolvasome" comprising a Holliday junction branch migration enzyme (Sgs1/BLM RecQ helicase) and a type IA topoisomerase (Top3/TopoIIIα) in complex with its OB (oligonucleotide/oligosaccharide binding) fold containing accessory factor (Rmi1). This review details our current knowledge of the dissolution process and the players involved in catalyzing this mechanistically complex means of completing homologous recombination reactions.
Depressive Symptoms and Cigarette Smoking among Native Hawaiians

The present study estimated the prevalence of depressive symptoms and cigarette smoking and examined the relationship between depressive symptoms and cigarette smoking among native Hawaiians. Cross-sectional data from 524 rural, native Hawaiian from the Native Hawaiian Health Research Project are presented. Depressive symptoms were measured using the self-report Centre for Epidemiological Studies-Depression Scale. Information on smoking behavior and sociodemographic variables was collected. The prevalence of depressive symptoms was 15%, and significantly higher among participants with lower educational attainment. The prevalence of current smokers was 32%, and significantly higher among younger adults and participants with lower educational attainment. Regression analyses reported a significant relationship between CES-D scores and smoking status as well as between CES-D scores and number of cigarettes smoked daily. However, when education and age were included in the regression models, the relationships were attenuated. The findings and implications of this study are discussed.
Comparative evaluation of ankaferd blood stopper, ferric sulfate, and formocresol as pulpotomy agent in primary teeth: A clinical study

Aim: The aim of the study was to provide a comparative evaluation of the clinical and radiographic success of Ankaferd blood stopper (ABS), formocresol (FC), and ferric sulfate (FS) as pulpotomy agent in primary teeth. Settings and Design: This is a clinical study. Materials and Methods: A total of 45 primary mandibular molar teeth in 26 children aged 6–9 were selected for the study. Teeth were randomly divided into three groups according to the pulpotomy agents (ABS, FC, FS). Following treatment, for 24 months, teeth were clinically and radiographically evaluated once every 3 and 6 months respectively. Statistical Analysis Used: SPSS version 15 software was used in data analysis. Kaplan– Meier, Log Rank and Fisher's exact tests were used to analysis. Results: After follow-up periods ranging from 6 to 24 months (average 20.8±0.56), the clinical success rates for ABS, FC, and FS were 87%, 87%, and 100% respectively. The overall radiographic success was 87%, 80%, and 87%. When success rates of the ABS were compared with other agents, there were no significant differences between groups (P > 0.05). Conclusion: Similar success was achieved in the pulpotomy treatment of primary teeth that using ABS, FC, and FS. ABS would be considered a suitable agent for pulpotomy treatment and can be used as an alternative to other agents.
Stability analysis of set-point-related indirect iterative learning control with PI-type local controller

The set-point-related (SPR) indirect iterative learning control (ILC) is used to update the set-point for a local controller. Working as a supervision module for the local controller, SPR indirect ILC can improve the tracking performance of the closed-loop system along the batch direction. In the previous works, the local controller was assumed to be P-type for simplicity. In this work, a more general form for the local controller, the PI-type controller, was studied. Based on a 2-dimensional (2D) Roesser's system framework, a sufficient condition for asymptotical stability of multi-input multi-output linear batch processes under the SPR indirect ILC was derived in this paper. A numerical example was used to validate the proposed results.
Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in juvenile idiopathic arthritis patients

Objective To determine association of erythrocyte methotrexate polyglutamates (MTX-PG) with disease activity and adverse effects in a prospective juvenile idiopathic arthritis (JIA) cohort. Methods One hundred and thirteen JIA patients were followed from MTX start until 12 months. Erythrocyte MTX-PGs with 1–5 glutamate residues were measured at 3 months with tandem mass spectrometry. The outcomes were Juvenile Arthritis Disease Activity Score (JADAS)-27 and adverse effects. To determine associations of MTX-PGs with JADAS-27 at 3 months and during 1 year of MTX treatment, linear regression and linear mixed-model analyses were used. To determine associations of MTX-PGs with adverse effects during 1 year of MTX treatment, logistic regression was used. Analyses were corrected for JADAS-27 at baseline and co-medication. Results Median JADAS-27 decreased from 12.7 (IQR: 7.8–18.2) at baseline to 2.9 (IQR: 0.1–6.5) at 12 months. Higher concentrations of MTX-PG3 (β: −0.006, p=0.005), MTX-PG4 (β: −0.015, p=0.004), MTX-PG5 (β: −0.051, p=0.011) and MTX-PG3–5 (β: −0.004, p=0.003) were associated with lower disease activity at 3 months. Higher concentrations of MTX-PG3 (β: −0.005, p=0.028), MTX-PG4 (β: −0.014, p=0.014), MTX-PG5 (β: −0.049, p=0.023) and MTX-PG3–5 (β: −0.004, p=0.018) were associated with lower disease activity over 1 year. None of the MTX-PGs was associated with adverse effects. Conclusions In the first prospective study in JIA, long-chain MTX-PGs were associated with lower JADAS-27 at 3 months and during 1 year of MTX treatment. Erythrocyte MTX-PG could be a plausible candidate for therapeutic drug monitoring of MTX in JIA.
Interhemispheric Transfer of Stereognostic Information in Chronic Schizophrenics

Summary Ten chronic schizophrenic in-patients and ten matched normal controls were tested on a cross-hemispheric stereognostic task, using both meaningful objects and non-meaningful shapes of wood, under four different retention intervals. The main finding was that the schizophrenic group but not the control group displayed deficits in intermanual transfer of tactual material, as compared to the same task performed within hands. The implications of this result are discussed in relation to the possibility that some basic neurological disorder may accompany schizophrenia.
Different changes in expression and function of connexin 26 and connexin 32 during DNA synthesis and redifferentiation in primary rat hepatocytes using a DMSO culture system

In the present study, we determined in detail the changes of liver gap junctions, connexin 26 (Cx26), and connexin 32 (Cx32), during DNA synthesis and redifferentiation of hepatocytes in vitro. We used primary rat hepatocytes that expressed the liver gap junction proteins, which were cultured in the medium containing epidermal growth factor (EGF) with 2% dimethylsulfoxide (DMSO) and 10‐7 mol/L glucagon (a DMSO culture system), as we previously reported. In the present cultures, almost confluent hepatocytes cultured in the medium containing EGF with 2% DMSO and 10‐7 mol/L glucagon, underwent a nearly synchronous wave of DNA synthesis induced by the removal of 2% DMSO and 10‐7 mol/L glucagon, and the addition of 10 mmol/L nicotinamide, after which the DNA synthesis was completely re‐inhibited by the re‐addition of 2% DMSO and 10‐7 mol/L glucagon. During stimulation of DNA synthesis, both Cx26 and Cx32 messenger RNA (mRNAs) in hepatocytes transiently increased in the G1 phase and then markedly decreased before the onset of the S phase, while only Cx26 messenger RNA (mRNA) increased slightly in the S/M phase. Furthermore, before the onset of the S phase, a disappearance of both Cx26 and Cx32 immunoreactivities and gap junction plaques were observed. Gap junctional intercellular communication (GJIC), as measured by lucifer yellow, which indicated the function of Cx32, decreased markedly from before the onset of the S phase. GJIC measured by propidium iodide, which indicated the function of Cx26, decreased from before the onset of the S phase and then increased slightly in the S/M phase. During the re‐inhibition after the stimulation of DNA synthesis, Cx32 mRNA, but not Cx26 mRNA, rapidly returned to the pretreatment control level. Cx32 immunoreactivity and gap junction plaques also recovered. However, the recovery of GJIC measured by lucifer yellow was later than that of Cx32 expression. These results indicated the different changes of expression and function of Cx26 and Cx32 in the hepatocytes during stimulation and re‐inhibition of DNA synthesis. This culture system should be useful as a model in which to study liver gap junctions during hepatocyte growth and differentiation in vitro.
Consequences of early life stress on the expression of endocannabinoid-related genes in the rat brain

The endocannabinoid system is involved in several physiological and pathological states including anxiety, depression, addiction and other neuropsychiatric disorders. Evidence from human and rodent studies suggests that exposure to early life stress may increase the risk of psychopathology later in life. Indeed, maternal deprivation (MD) (24 h at postnatal day 9) in rats induces behavioural alterations associated with depressive-like and psychotic-like symptoms, as well as important changes in the endocannabinoid system. As most neuropsychiatric disorders first appear at adolescence, and show remarkable sexual dimorphisms in their prevalence and severity, in the present study, we analysed the gene expression of the main components of the brain cannabinoid system in adolescent (postnatal day 46) Wistar male and female rats reared under standard conditions or exposed to MD. For this, we analysed, by real-time quantitative PCR, the expression of genes encoding for CB1 and CB2 receptors, TRPV1 and GPR55 (Cnr1, Cnr2a, Cnr2b, Trpv1, and Gpr55), for the major enzymes of synthesis, N-acyl phosphatidyl-ethanolamine phospholipase D (NAPE-PLD) and diacylglycerol lipase (DAGL) (Nape-pld, Dagla and Daglb), and degradation, fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) (Faah, Magl and Cox-2), in specific brain regions, that is, the frontal cortex, ventral and dorsal striatum, dorsal hippocampus and amygdala. In males, MD increased the genetic expression of all the genes studied within the frontal cortex, whereas in females such an increase was observed only in the hippocampus. In conclusion, the endocannabinoid system is sensitive to early life stress at the gene expression level in a sex-dependent and region-dependent manner, and these changes are already evident in the adolescent brain.
Evaluation of high-resolution surface wind products at global and regional scales

High resolution surface wind fields covering the global ocean, estimated from remotely sensed wind data and ECMWF wind analyses, have been available since 2005 with a spatial resolution of 0.25° in longitude and latitude, and a temporal resolution of 6h. Their quality is investigated through various comparisons with surface wind vectors from 190 buoys moored in various oceanic basins, from research vessels and from QuikSCAT scatterometer data taken during 2005–2006. The NCEP/NCAR and NCDC blended wind products are also considered. The comparisons performed during January-December 2005 show that speeds and directions compare well to in-situ observations, including from moored buoys and ships, as well as to the remotely sensed data. The root-mean-squared differences of the wind speed and direction for the new blended wind data are lower than 2m/s and 30°, respectively. These values are similar to those estimated in the comparisons of hourly buoy measurements and QuikSCAT near real time retrievals. At global scale, it is found that the new products compare well with the wind speed and wind vector components observed by QuikSCAT. No significant dependencies on the QuikSCAT wind speed or on the oceanic region considered are evident.
Migration and the skill composition of the labour force: the impact of trade liberalization in LDCs.

"The purpose of this paper is to shed some light on the conditions under which trade liberalization in the developing countries is likely to cause an increase or a decrease in out-migration. We also examine the impact of trade liberalization on the skill composition of migration and of the labour force. For this purpose, we explicitly incorporate four additional features in the Heckscher-Ohlin model: heterogeneity of labour skills, international migration, migration costs, and constraints on financing migration. " (EXCERPT)
Heterogeneity of the rhamnomannans from one strain of the human pathogen Sporothrix schenckii determined by 13C nuclear magnetic resonance spectroscopy

The synthesis of different rhamnomannans in a strain of Sporothrix schenckii (1099.12) was shown by use of 13C nuclear magnetic resonance spectroscopy. Fractionation of a polysaccharide preparation from cells grown at 25 degrees C provided a neutral monorhamnosyl rhamnomannan and an acidic rhamnomannan containing 4-O-substituted glucuronic acid units and also (1 leads to 2)-linked dirhamnosyl side chains.
Left ventricular hypertrophy as a predictor of coronary heart disease mortality and the effect of hypertension.

BACKGROUND Although associations between hypertension, left ventricular hypertrophy (LVH), and coronary heart disease (CHD) have been described, it is less clear whether LVH is associated with increased rates of CHD in the absence of hypertension. METHODS We examined this association with Cox regression analyses of data from 7924 adults 25 to 74 years of age from the Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study (1976 to 1992). Covariates included age, race, sex, history of cardiovascular diseases and diabetes, cholesterol, body mass index, blood pressure, and smoking. RESULTS During 16.8 follow-up years, there were 462 (26%) deaths from CHD (ICD-9 410-414) and 667 (38%) deaths from diseases of the heart (ICD-9 390-398, 402, 404, 410-414, 415-417, 420-429). LVH prevalence was 13.3 per 1000 population. Hypertension prevalence was 29.1%. LVH prevalence was higher among hypertensive adults than among normotensive adults (29.9 vs 6.4 per 1000, P <.001). Persons with LVH were twice as likely to die of CHD (relative risk, 2.0; 95% confidence interval, 1.2, 3.5) and diseases of the heart (relative risk, 1.9; 95% confidence interval, 1.1, 3.0) after adjustment for hypertension and covariates. In age-adjusted predicted survival, probability plots for CHD, and diseases of the heart, normotensives with LVH had survival similar to hypertensive adults with LVH and lower survival than normotensive and hypertensive adults with no LVH. CONCLUSIONS Our results confirm previous findings that the presence of LVH is a strong predictor of future cardiovascular death. Although LVH appears to be rare among normotensives, clinicians should be aware that such individuals may have an increased risk for death similar to that of hypertensive adults with LVH.
An improved load-displacement prediction for a coned disc spring using the energy method

An improved computation of the load-displacement prediction for a coned disc spring is proposed. This work is an extension work of the previous proposed energy-based computation for coned disc springs. To show the validity of the improved method, the load-displacement results using the improved computation, the previous proposed method, and the finite element analyses are compared. In this work, the improved computation and the finite element analyses have accounted for the radial deflection of the disc spring in the form of energy method. This is different in the previous work where the radial deflection of the disc spring was ignored and the comparison to the finite element analyses without accounting the radial deflection is not practical. The present work makes the comparison to the finite element analyses to be more reasonable and more practical.