Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial DNA defects in caused by functional interactions between DNA polymerase gamma mutations associated with disease in human

The yeast mitochondrial DNA (mtDNA) replicase Mip1 has been used as a model to generate five mutations equivalent to POLG mutations associated with a broad spectrum of diseases in human. All mip1 mutations, alone or in combination in cis or in trans, increase mtDNA instability as measured by petite frequency and Ery R mutant accumulation. This phenotype is associated with decreased Mip1 levels in mitochondrial extracts and/or decreased polymerase activity. We have demonstrated that (1) in the mip1 G651S (hG848S) mutant the high mtDNA instability and increased frequency of point Ery R mutations is associated with low Mip1 levels and polymerase activity; (2) in the mip1 A692T-E900G (hA889T-hE1143G) mutant, A692T is the major contributor to mtDNA instability by decreasing polymerase activity, and E900G acts synergistically by decreasing Mip1 levels; (3) in the mip1 H734Y /mip1 G807R (hH932Y/hG1051R) mutant, H734Y is the most deleterious mutation and acts synergistically with G807R as a result of its dominant character; (4) the mip1 E900G (h1143G) mutation is not neutral but results in a temperature-sensitive phenotype associated with decreased Mip1 levels, a property explaining its synergistic effect with mutations impairing the polymerase activity. Thus, the human E1143G mutation is not a true polymorphism. plasmid was taken as the negative control. The gap-filling activity assay was carried out in a reaction mixture containing 20 mM Tris-HCl pH 8.0, 5 mM dithiothreitol, 50 mM MgCl 2 , 25 m M each dATP, dCTP, dGTP, 6 m M [ 3 H]-dTTP, 150 m g/ml calf thymus activated DNA and the mitochondrial extract. Samples were taken after 6 min of incubation at 30°C. The activity was expressed in nmol dTTP incorporated into trichloroacetic precipitable material per h and per mg protein present in the extract or was reported to an arbitrary amount of Mip1 (100 for the wild-type).
Clinical diagnosis of fissure caries with conventional and laser-induced fluorescence techniques

We studied the in vivo validity of dentinal fissure caries diagnosis by visual examination, bitewing radiography, and use of a laser-induced fluorescence device (DIAGNOdent). A total of 144 and second molars with macroscopically intact occlusal surfaces in 41 Chinese young adults were examined visually, by bitewing radiography, and by DIAGNOdent. Visual examination after pit and fissure opening was used as the reference standard. The sensitivity and specificity of detecting caries that had extended into the dentin were, respectively, 0.89 and 0.44 by visual detection of opacity or discoloration after air drying, 0.13 and 1.00 by bitewing radiography to detect radiolucency extending into the dentin, and 0.70 and 0.84 by DIAGNOdent testing with a cut-off score of 40. Caries detection by a combination of visual examination and DIAGNOdent had a sensitivity of 0.67 and specificity of 0.94. Receiver operating characteristic analysis showed that this combined approach was superior to the other methods.
Pb 2+ inhibition of sympathetic α 7 -nAChR-mediated nitrergic neurogenic dilation in porcine basilar arteries

Chronic exposure to inorganic lead (Pb 2+ ) has been shown to facilitate peripheral vasoconstriction causing hypertension. Effect of lead on cerebral vascular function has not been reported. We have suggested in isolated porcine cerebral arteries that α 7 nicotinic acetylcholine receptor ( α 7 -nAChRs) on perivascular sympathetic nerves mediate calcium influx in these neurons resulting in release of norepinephrine. The released norepinephrine then acts on presynaptic β 2 -adrenoceptors located on the neighboring nitrergic nerve terminals, causing NO release and vasodilation. Since Pb 2+ has been shown to inhibit α 7 -nAChR-mediated responses in the central nervous system, effects of Pb 2+ on α 7 -nAChR-mediated nitrergic neurogenic dilation in isolated porcine basilar arteries and calcium influx in cultured superior cervical ganglion (SCG) cells of the pig were examined using in vitro tissue bath and confocal microscopic techniques. The results indicated that Pb 2+ (but not Cd 2+ , Zn 2+ , or Al 3+ ) in a concentration dependent manner blocked relaxation of endothelium-denuded basilar arterial rings induced by nicotine (100 µ M) and choline (1mM) without affecting relaxation induced by sodium nitroprusside or isoproterenol. Furthermore, significant calcium influx in cultured SCG cells induced by choline and nicotine was attenuated specifically by Pb 2+ with IC 50 values comparable to those from tissue bath study. These results provide evidence supporting that lead is a likely antagonist for α 7 -nAChRs that are found on postganglionic sympathetic adrenergic nerve terminals of SCG origin. Furthermore, these results indicate that lead can attenuate dilation of cerebral arteries by blocking sympathetic nerve-mediated release of NO from the perivascular nitrergic nerves. drug bath. Results were expressed as means ± S.E. M. Statistical analysis was evaluated by Analysis of Variance (ANOVA) and Student’s t-test for paired or unpaired samples as appropriate. The P < 0.05 level of probability was accepted as significant. In summary, the present studies demonstrate that α 7 -nAChRs located on cerebral postganglionic sympathetic neurons are specifically blocked by lead, resulting in inhibition of neuronal calcium influx and diminished nicotine- and choline-induced sympathetic dependent nitrergic dilation in isolated porcine basilar arteries. Since choline is an endogenous agonist and lead a likely antagonist for α 7 -nAChRs, the present finding provides further evidence supporting the presence of functional α 7 -nAChRs on the sympathetic neurons of SCG origin. This result also reveals that lead can cause “vasoconstriction” such as in the cerebral circulation by blocking α 7 -nAChR-mediated neurogenic nitrergic vasodilation. Results of the present study also point out that the exact systemic hemodynamic effects of chronic lead exposure will not be clarified until the subtypes of nicotinic receptors found on sympathetic nerves in peripheral vascular beds are fully determined.
Experience with Forecasting Univariate Time Series and the Combination of Forecasts

A number of procedures for forecasting a time series from its own current and past values are surveyed. Forecasting performances of three methodsBox-Jenkins, Holt-Winters and stepwise autoregression-are compared over a large sample of economic time series. The possibility of combining individual forecasts in the production of an overall forecast is explored, and we present empirical results which indicate that such a procedure can frequently be profitable.
Thermo-economics analysis of a cane bio-refinery

ABSTRACT A cane bio-refinery consists of the following components: sugar mill, distillery, refinery and cogeneration power plant. The latter supplies electricity and process heat needed by the other components of the bio-refinery. Although process heat and electricity have the same units of energy, they are of different quality levels. Appropriate attention can be directed to those components causing major exergy loss. Furthermore, a device/system can be exergy efficient but may not be cost-effective. Thus, the financial implications need also to be assessed. The performance of an existing cane bio-refinery was assessed on the basis of thermo-economics analysis. It was found that the addition of an evaporator of the falling film thin type in the sugar mill would not only reduce the exergy loss but would also generate more revenues. A better-informed decision could be made for the optimisation of a bio-refinery.
CMAR_A_217264 7647..7655

1Department of Hematology, Zhongnan Hospital of Wuhan University, Wuchang, Wuhan, Hubei 430071, People’s Republic of China; 2Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan 430071, People’s Republic of China; 3Karnali Academy of Health Sciences, Jumla, Nepal; 4Zhongnan Hospital of Wuhan University, Hope School of Nursing, Wuhan, Hubei, People’s Republic of China; 5Department of Pathology, Patan Hospital, Patan Academy of Health Sciences, Kathmandu, Nepal; 6Department of Clinical Laboratory Science, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China Purpose: Tumor infiltrating lymphocytes (TILs) have been extensively described in anti-
COMPARATIVE EVALUATION OF CELLULAR AND HUMORAL IMMUNITY PARAMETERS IN RADIOGRAPHERS AND NON RADIOGRAPHERS

It has been suggested that prolonged exposure to ionizing radiation may induce immune alteration which may facilitate the development of cancer. However, over the past decades some scientists have reported that low-dose of ionizing radiation is not only a harmless agent but often is benefical. The aim of this study was to evaluate the effects of occupational exposure to low levels of ionizing radiation on immune system. The studied population consisted of 48 healthy radiographers exposed to annual dose of x-rays below the maximum permissible occupational limit(MPOL 50 mSv/year) and 18 healthy unexposed individuals similar in age, gender and job grade. Total number of WBC, lymphocytes, lymphocyte subsets(CD19, CD3, CD4, CD8, CD16-56) HLA-DR, CD4/CD8 ratio, platelet and concentration of IgG, IgM, IgA, C3, C4 were measured. The investigation was carried out by flow cytometry for lymphocyte subsets and immunoturbidimetry for immunoglubolin and complements. Although the number of CD8 and CD4/CD8 ratio decreased and increased respectively with increase in age, no influence of the radiation on the immunological parameters in peripheral blood was found. This study showed that ionizing radiation received by radiographers (at least in very low-dose range) does not affect the immune system.
An Instantaneous Event-Triggered Hz–Watt Control for Microgrids

This paper proposes a distributed control scheme to compensate for droop-induced frequency deviations in autonomous microgrids. In this scheme, no extra direct frequency control and proportional-integral compensation are employed to remove the frequency deviations; that is, the deviations are compensated instantaneously. To reduce the communication burden, the scheme is then equipped with a need-based (event-triggered) data exchange strategy. An event-triggering mechanism is introduced, which highly reduces the amount of communications in both transient and steady-state stages and ensures that the intervals between consecutive communication instants are positive (i.e., the system is Zeno-free). Stability and equilibrium analyses of the resultant system considering the whole system dynamics are provided, as well. Effectiveness of the proposed controller for different cases is verified by simulating a microgrid in MATLAB/SimPowerSystems software environment.
Selective role of SULT2A1 in the N-sulfoconjugation of quinolone drugs in human

N-Sulfoconjugation is a common metabolic pathway of amine compounds in vivo. In the present study, we have investigated the N-sulfation of quinolones and other amine drugs (ciprofloxacin, moxifloxacin, garenoxacin, desipramine and metoclopramide) to assess the contribution of specific human cytosolic sulfotransferases (SULTs) to the reactions using purified recombinant enzymes and human liver cytosols (HLCs). Among the enzymes examined, human (h) SULT2A1 exhibited N-sulfoconjugation activities toward all drugs tested, whereas the other five different forms (hSULT1A1, hSULT1A3, hSULT1B1, hSULT1C2 and hSULT1E1) showed no detectable activities except hSULT1A1 for garenoxacin sulfation. The N-sulfoconjugating activity of hSULT2A1 was highest toward moxifloxacin (6.3 ± 0.1 nmol/min/mg protein) at the substrate concentration of 100 µM. Kinetic analyses demonstrated that HLC-mediated N-sulfations were monophasic for all the substrates examined with apparent K m values comparable to those mediated by hSULT2A1. The K m values for N-sulfation mediated by hSULT2A1 were as follows: 1.08 ± 0.03 mM for ciprofloxacin, 0.53 ± 0.01 mM for moxifloxacin, 0.19 ± 0.01 mM for garenoxacin, 0.054 ± 0.001 mM for desipramine, and 2.32 ± 0.12 mM for metoclopramide. The sulfating activities of HLCs toward the amines were well correlated with those for O-sulfation of dehydroepiandrosterone, a hSULT2A1 probe substrate. Taken together, the present results unequivocally demonstrate that hSULT2A1 is responsible for the N-sulfation of quinolones and possibly other therapeutic drugs in human. 1 5 mM 2 , 1 bovine µM [ 35 S]PAPS to 5 µg/ml of His 6 -SULT protein or mg/ml of HLC, and various concentrations of substrates in the final volume of 10 µl. The reaction was initiated by addition of [ 35 S]PAPS and terminated by addition of 5 µl of ice-cold acetonitrile after incubation at 37°C for 7 min (for DHEA) or 20 min (for others). Portions (10 µl) of the reaction mixture were spotted on a thin layer plate (thin layer chromatography aluminum plate silica gel 60 F 254 , 250 µm; The metabolites of ciprofloxacin, moxifloxacin, garenoxacin and metoclopramide were developed with a solvent system of n- butanol:acetic acid:water (4:1:2), and those of DHEA and desipramine were developed with chloroform:methanol:water:28% ammonia aqueous (60:35:7.5:0.5). The radioactive spots were analyzed with FLA-3000 image analyzer (FujiFilm, Analyses to determine apparent kinetic parameters were performed with various substrate concentrations ranging 0.05 - 5 µM for DHEA, 50 µM - 3 mM for ciprofloxacin and moxifloxacin, 10 µM - 1.5 mM for garenoxacin, 1 µM - 1 mM for desipramine, and 100 µM - 10 mM for metoclopramide. for
Gender differences and occupational factors in the risk of obesity in the Italian working population.

Background Obesity is a multifactorial condition and a major risk factor associated with several non- communicable diseases, as cardiovascular diseases, and with a higher risk of premature death and disability. Sex-specific factors play a key role and must be taken into consideration in studying occupational factors associated to the risk of obesity. The aim of this study was to investigate gender differences in Body Mass Index in a large cohort representative of Italian workers and, correlating this index with several demographic and occupational variables to verify differences due to the gender and work in the risk of obesity. Methods We utilized data from INSuLa, a cross-sectional nationally representative survey of the Italian workers population conducted in 2013 by the Italian Workers’ Compensation Authority to investigate the health and safety at work. Analysis were run on a large sample of 8,000 Italian workers, aged from 16 to 64 years, representative of the Italian working population. Logistic regression models were carried out to assess gender differences in the association between occupational characteristics and Body Mass Index. We adjusted for age, education, variables related to health protection at work and chronic conditions and diseases. Results Findings showed several differences among males and females in the Body Mass Index due to exposure to several occupational factors, as occupational sector. Among the others, female shift workers were 1.32 times (95% CI = 1.11-1.57) more likely to be overweight or obese compared to normal workers, this association is maintained when controlling for confounders. A significant increase of 1.5-1.6 times in the likelihood of overweight or obesity was observed among women who worked 1-2 night shifts per week. Conclusions Gender-specific differences in studying occupational factors associated to the risk of obesity are useful in the view of characterizing the risk of obesity and contributing to the identification of workplace-targeted intervention strategies.
The estimated life expectancy in a community cohort of Parkinson’s disease patients with and without dementia, compared to the United Kingdom population.

Objective: To compare survival, life expectancies (LE), and the anticipated age at the time of death (AAD), in a community-based cohort of Parkinson’s disease (PD) patients with and without significant cognitive impairment, with an age sex matched population of England and Wales. Methods : The age and sex specific standardised mortality ratios (SMR) were calculated and stratified by dementia status. The LE and AAD estimations were calculated from the SMR’s of the 2003 United Kingdom population, using a modified Gompertz function. Results: In total, 166 PD patients participated in the investigation, of which 91 died by the four-year follow-up. The overall SMR was 2.09 (95% CI 1.68, 2.57). Demented patients had significantly higher SMR’s than non-demented patients (SMR3.10, 95% CI 2.39-3.96 vs. SMR 1.15, 95% CI 0.75 – 1.69 p< 0.001. In our cohort, the LE in younger onset demented patients (55-74 years) was much lower than in non-demented patients (7.5; SD 3 vs. 12.4; SD 7). Likewise, the estimated AAD in younger onset patients with dementia was also much lower (demented 72.4; SD 4 vs. not demented 77.8; SD 7). In older onset patients with dementia (< 75 years), the differences in LE (demented 2.1; SD 1 vs. not demented 4.7; SD 4), and AAD were less apparent (demented 89.5; SD 6 vs. not demented 92.2; SD 6). Conclusion: The survival, LE and AAD in patients with PD is much lower compared with the general population, apart from those patients who do not develop dementia, who appear to have near normal population mortality rates. However, dementia and younger onset of PD appear to be important determinants of survival, LE and AAD. with an age sex matched population of England and Wales. We also investigated the associations with prevalent and incident dementia in the cohort of patients, controlling for disease specific and non-motor variables. We also calculated life expectancies (LE; anticipated mean remaining time to live) based on standard mortality rates (SMR), to compare the LE and the anticipated age at the time of death (AAD) of the PD patients by age group, gender, and the presence or absence of dementia, compared to the general population of England and Wales
(2020). Screening for high hip fracture risk does not impact on falls risk: a post hoc analysis from the SCOOP study. Osteoporosis

(246 of 250 words allowed) Purpose: To investigate whether effectiveness of an osteoporosis screening programme to reduce hip fractures was mediated by modification of falls risk in the screening arm. Methods: The SCOOP study recruited 12,483 women aged 70-85 years, individually randomised to a control (n=6,250) or screening (n=6,233) arm; in the latter, osteoporosis treatment was recommended to women at high risk of hip fracture, while the control arm received usual care. Falls were captured by self-reported questionnaire. We determined the influence of baseline risk factors on future falls, and then examined for differences in falls risk between the randomisation groups, particularly in those at high fracture risk. Result: Women sustaining one or more falls were slightly older at baseline than those remaining falls free during follow up (mean difference 0.70 years, 95%CI 0.55-0.85, p<0.001). A higher FRAX 10-year probability of hip fracture was associated with increased likelihood of falling, with fall risk increasing by 1-2% for every 1% increase in hip fracture probability. However, falls risk factors were well balanced between the study arms and, importantly, there was no evidence of a difference in falls occurrence. In particular, there was no evidence of interaction (p=0.18) between baseline FRAX hip fracture probabilities and falls risk in the two arms, consistent with no impact of screening on falls in women informed to be at high risk of hip fracture. Conclusion: Effectiveness of screening for high FRAX hip fracture probability to reduce hip fracture risk was not mediated by a reduction in falls.
Salsolinol stimulates dopamine neurons in slices of posterior VTA indirectly by activating μ -opioid receptors

Previous studies in vivo have shown that salsolinol, the condensation product of acetaldehyde and dopamine has properties that may contribute to alcohol abuse. Although opioid receptors, especially the µ-opioid receptors (MORs), may be involved, the cellular mechanisms mediating the effects of salsolinol have not been fully explored. In the current study, we used whole-cell patch-clamp recordings to examine the effects of salsolinol on dopamine neurons of the ventral tegmental area (VTA) in acute brain slices from Sprague-Dawley rats. Salsolinol (0.01-1 μ M) dose-dependently and reversibly increased the ongoing firing of dopamine neurons; this effect was blocked by naltrexone, an antagonist of MORs, and by gabazine, an antagonist of GABA A receptors. We further showed that salsolinol reduced the frequency without altering the amplitude of spontaneous GABA A receptor-mediated IPSCs in dopamine neurons. The salsolinol-induced reduction was blocked by both naltrexone and DAMGO, an agonist of MORs. Thus, salsolinol excites VTA-dopamine neurons indirectly by activating MORs, which inhibit GABA neurons in the VTA. This form of disinhibition appears to be a novel mechanism underlying the effects of salsolinol. cellular mechanism underlying salsolinol’s reinforcing property.
Identification of various allosteric interaction sites on M 1 muscarinic receptor using [125I]MT7ox toxin.

A monoiodinated MT7ox toxin was synthesized and its affinity constants for free or NMS-occupied hM 1 receptor were measured directly by equilibrium and kinetic binding experiments. Identical values were obtained with the two types of assay methods, 14 pM and 0.9 nM in free or NMS-liganded receptor states, respectively, highlighting a strong negative cooperativity between this allosteric toxin and NMS. Identical results were obtained with indirect binding experiments with [3H]NMS using the ternary complex model, clearly demonstrating the reciprocal nature of this cooperativity. Furthermore, the effects of various orthosteric and allosteric agents on the dissociation kinetic of [125I]MT7ox were measured and show that, with the exception of the MT1 toxin, all the ligands studied (NMS, atropine, gallamine, brucine, tacrine, staurosporine and KT5720) interact allosterically with MT7 toxin. Equilibrium binding experiments with [125I]MT7ox and [3H]NMS were conducted to reveal the effects of these ligands on the free receptor and affinity constants (pKx values) were calculated using the allosteric ternary complex model. Our results suggest that MT7 toxin interacts with hM 1 receptor at a specific allosteric site which may partially overlap those previously identified for “classical” or “atypical” allosteric agents and highlight the potential of this new allosteric tracer in studying allosterism at muscarinic receptors. [3H]NMS by increasing concentrations of orthosteric ligands and MT1 toxin. Curve fitting was based on a nonlinear regression analysis using the Hill equation. The results are expressed as the ratio of the specific [125I]MT7ox binding measured with (B) or without (Bo) the different toxins. Data are mean values ±SEM of at least three inhibition experiments.