Miracle-dz/UniFAR-FTUs huggingface dataset:
Promoters controlling expression of the alternative nitrogenase and the molybdenum uptake system in Rhodobacter capsulatus are activated by NtrC, independent of sigma54, and repressed by molybdenum

The alternative nitrogenase of Rhodobacter capsulatus is expressed only under conditions of nitrogen and molybdenum depletion. The analysis of anfA-lacZ fusions demonstrated that this dual control occurred at the level of transcription of anfA, which encodes a transcriptional activator specific for the alternative nitrogenase. The anfA promoter was found to be activated under nitrogen-limiting conditions by NtrC in a sigma54-independent manner. In addition, anfA transcription was repressed by traces of molybdenum. This molybdenum-dependent repression of anfA was released in R. capsulatus mutants carrying either lesions in the high-affinity molybdenum uptake system (modABCD) or a double deletion of mopA and mopB, two genes encoding molybdenum-pterin-binding proteins. The expression of the molybdenum transport system itself was shown to be negatively regulated by molybdenum and, unexpectedly, to be also regulated by NtrC. This finding is in line with the presence of two tandemly arranged DNA motifs located in front of the R. capsulatus mopA-modABCD operon, which are homologous to R. capsulatus NtrC binding sites. Mapping of the transcriptional initiation sites of mopA and anfA revealed promoter sequences exhibiting significant homology to each other but no homology to known prokaryotic promoters. In addition, a conserved DNA sequence of dyad symmetry overlapping the transcriptional initiation sites of mopA and anfA was found. Deletions within this element resulted in molybdenum-independent expression of anfA, indicating that this DNA sequence may be the target of MopA/MopB-mediated repression.
gamma-H2AX foci formation in peripheral blood lymphocytes of tumor patients after local radiotherapy to different sites of the body: Dependence on the dose-distribution, irradiated site and time from start of treatment

Purpose: To evaluate the relationship between an estimated integral total body radiation dose delivered and phosphorylated histone H2AX protein (γ-H2AX) foci formation in peripheral blood lymphocytes of cancer patients. Material and methods: γ-H2AX formation was quantified as the mean number of foci per lymphocyte (NmeanH2AX) and the percentage of lymphocytes with ≥n foci. The integrated total body radiation dose was estimated from the dose volume histogram of patient's body corrected for the proportion of the body scanned by computed tomography for 3D treatment planning. Results: There was a strong linear correlation between the mean number of γ-H2AX foci per lymphocyte in the peripheral blood sample and integrated total body radiation dose (r = 0.83, p < 0.0001). The slope of the relationship was dependent on the site of body irradiated. In comparison to chest irradiation with a slope of 8.7 ± 0.8 foci Gy−1, the slopes for brain, upper leg and pelvic sites were significantly shallower by −4.7, −4.3, and −3.8 Gy−1, respectively (p < 0.0001), while the slope for upper abdomen irradiation was significantly larger by 9.1 ± 2.6 Gy−1 (p = 0.0007). There was a slight time effect since the start of radiotherapy on the slopes of the in vivo dose responses leading to shallower slopes (−1.5 ± 0.7 Gy−1, p = 0.03) later (≥10 day) during radiotherapy. After in vitro irradiation, lymphocytes showed 10.41 ± 0.12 foci per Gy with no evidence of inter-individual heterogeneity. Conclusions: γ-H2AX measurements in peripheral lymphocytes after local radiotherapy allow the estimation of the applied integral body dose. The site and time dependence have to be considered.
Long-term outcome of critically ill elderly patients requiring intensive care.

OBJECTIVE To evaluate the long-term mortality and morbidity of critically ill elderly patients requiring intensive care. DESIGN Prospective comparison of outcome of critically ill patients aged 75 years and older with patients aged 65 to 74 years. PATIENTS Critically ill patients aged 65 years and older who required intensive care and who were recruited during a 3-month period. MAIN OUTCOME MEASURES Duration of hospitalization, hospital charges, procedures used in the intensive care unit, mortality in the hospital and during the follow-up period, and quality of life of survivors during the follow-up period. RESULTS Ninety-seven patients were included in the study; 54 were 75 years or older and 43 were aged 65 to 74 years. No significant difference was noted between the two groups for length of stay in the hospital, hospital charges, or mortality at 1 year. Severity of illness, as assessed by Acute Physiology and Chronic Health Evaluation score at the time of intensive care unit admission, was a better predictor of survival than age. Quality of life, as assessed by activities of daily living, perceived quality of life, and Center for Epidemiologic Studies-Depression score, were not significantly different in either group at 1, 6, and 12 months after discharge from the hospital. Most patients in both groups described their quality of life as adequate and were willing to receive intensive care again, if necessary. CONCLUSION Age alone is not an adequate predictor of long-term survival and quality of life in critically ill elderly patients.
Investigations on genotoxic effects of groundwater from the Mitterndorfer Senke and from the vicinity of Wiener Neustadt.

INTRODUCTION This report describes the first study on genotoxic effects of Austrian ground- and drinking waters. Samples from the Mitterndorfer Senke (MS) and the vicinity of Wiener Neustadt were tested over a three years period. The MS is the largest aquifer in Austria. Due to deposition of industrial and community wastes, chemicals have polluted the groundwater in this area. Aim of the present study was to elucidate if consumption of these waters might pose a carcinogenic risk to humans. METHODS 43 Water samples were tested in a test battery which consisted of bacterial gene mutation assays (Salmonella strains TA100 and TA98), micronucleus (MN) assays with cultures of primary rat hepatocytes and plant bioassays (MN tests with Tradescantia and Vicia faba). For the bacterial assays, the water samples were extracted with XAD resins. RESULTS In total, 27.9% of the samples caused positive effects; 8 samples were active in Salmonella microsome assays, Strain TA100 was particularly sensitive upon addition of metabolic activation mix (6 positive samples). Four samples were positive exclusively in MN assays with cultures of primary rat hepatocytes; one sample gave positive results in all three bioassays. Finished waters from waterworks were consistently devoid of mutagenic activity under all experimental conditions. DISCUSSION Overall, only a small fraction of the groundwaters caused mutagenic effects and in all cases the activities were moderate. Comparison of the results of the present study with data obtained in other investigations under similar experimental conditions shows that the genotoxicity of groundwaters of the MS area are lower than the effects caused by ground- and drinking waters from other countries. The fact that no genotoxic activity was detected in any of the finished drinking waters can be taken as an indication that consumption of these waters does not pose a health hazard arising from contamination with genotoxic carcinogens to humans.
Characterization of 5,7‐Dichlorokynurenate‐Insensitive d‐[3H]Serine Binding to Synaptosomal Fraction Isolated from Rat Brain Tissues

Abstract: To explore target sites for endogenous d‐serine that are different from the glycine site of the N‐methyl‐d‐aspartate (NMDA) type glutamate receptor, we have studied the binding of d‐[3H]serine to the synaptosomal P2 fraction prepared from the rat brain and peripheral tissues in the presence of an excess concentration (100 µM) of the glycine site antagonist 5,7‐dichlorokynurenate (DCK). Nonspecific binding was defined in the presence of 1 mM unlabeled d‐serine. Association, dissociation, and saturation experiments indicated that d‐[3H]serine bound rapidly and reversibly to a single population of recognition sites in the cerebellar P2 fraction in the presence of DCK, with a KD of 614 nM and a Bmax of 2.07 pmol/mg of protein. d‐Serine, l‐serine, and glycine produced a total inhibition of the specific DCK‐insensitive d‐[3H]serine binding to the cerebellum with similar Ki values. Strychnine and 7‐chlorokynurenate failed to inhibit the binding at 10 µM. The profiles of displacement of the DCK‐insensitive d‐[3H]serine binding by various amino acids and glutamate and glycine receptor‐related compounds differ from those of any other defined recognition sites. DCK‐insensitive d‐[3H]serine binding was at high levels in the cerebral cortex and cerebellum but very low in the kidney and liver. The present findings indicate that the DCK‐insensitive d‐[3H]serine binding site could be a novel candidate for a target for endogenous d‐serine in mammalian brains.
No Strings Attached: The Behavioral Effects of U.S. Unconditional Cash Transfer Programs

The universal basic income has become a widely discussed measure in policy circles around the world. In this review, we cover the evidence relevant to its potential impact in the US, and in developed countries more generally. Many studies find no statistically significant effect of an unconditional cash transfer on the probability of working. In the studies that do find an effect on labor supply, the effect is small: a 10% income increase induced by an unconditional cash transfer decreases labor supply by about 1%. The evidence shows that an unconditional cash transfer can improve health and educational outcomes, and decrease criminality and drug & alcohol use, especially among the most disadvantaged youths.
The Pharmacokinetics and Hemodynamic Effects of Intravenous and Intramuscular Dexmedetomidine Hydrochloride in Adult Human Volunteers

Background:Dexmedetomidine is an α2 agonist with potential utility in clinical anesthesia for both its sedative and sympatholytic properties. Methods:The pharmacokinetics and hemodynamic changes that occurred in ten healthy male volunteers were determined after administration of dexmedetomidine 2 µg/kg by intravenous or intramuscular route in separate study sessions. Results:The intramuscular absorption profile of dexmedetomidine, as determined by deconvolution of the observed concentrations against the unit disposition function derived from the intravenous data, was biphasic. The percentage bioavailability of dexmedetomidine administered intramuscularly compared with the same dose administered intravenously was 73 ± 11% (mean ± SD). After Intramuscular administration, the mean time to peak concentration was 12 min (range 2-60 min) and the mean peak concentration was 0.81 ± 0.27 ng/ml. After intravenous administration of dexmedetomidine, there were biphasic changes in blood pressure. During the 5-min intravenous infusion of 2 μg/kg dexmedetomidine, the mean arterial pressure (MAP) increased by 22% and heart rate (HR) declined by 27% from baseline values. Over the 4 h after the infusion, MAP declined by 20% from baseline and HR rose to 5% below baseline values. The hemodynamic profile did not show acute alterations after intramuscular administration. During the 4 h after intramuscular administration, MAP declined by 20% and HR declined by 10% Conclusions:The intramuscular administration of dexmedetomidine avoids the acute hemodynamic changes seen with intravenous administration, but results in similar hemodynamic alterations within 4 h.
Decline in VO2max with aging in master athletes and sedentary men.

Fifteen well-trained master endurance athletes [62.0 +/- 2.3 (SE) yr] and 14 sedentary control subjects (61.4 +/- 1.4 yr) were reevaluated after an average follow-up period of approximately 8 yr to obtain information regarding the effects of physical activity on the age-related decline in maximal O2 uptake capacity (VO2max). The master athletes had been training for 10.2 +/- 2.9 yr before initial testing and continued to train during the follow-up period. The sedentary subjects' VO2max declined by an average of 3.3 ml.kg-1.min-1 (33.9 +/- 1.7 vs. 30.6 +/- 1.6, P less than 0.001) over the course of the study, a decline of 12% per decade. In these subjects maximal heart rate declined 8 beats/min (171 vs. 163) and maximal O2 pulse decreased from 0.20 to 0.18 ml.kg-1.beat (P less than 0.05). The master athletes' VO2 max decreased by an average of 2.2 ml.kg-1.min-1 (54.0 +/- 1.7 vs. 51.8 +/- 1.8, P less than 0.05), a 5.5% decline per decade. The master athletes' maximal heart rate was unchanged (171 +/- 3 beats/min) and their maximal O2 pulse decreased from 0.32 to 0.30 ml.kg-1.beat (P less than 0.05). These findings provide evidence that the age-related decrease in VO2max of master athletes who continue to engage in regular vigorous endurance exercise training is approximately one-half the rate of decline seen in age-matched sedentary subjects. Furthermore our results suggest that endurance exercise training may reduce the rate of decline in maximal heart rate that typically occurs as an individual ages.
IMPACT OF NEONATAL HYPOTHYROIDISM ON LEYDIG CELL NUMBER, PLASMA, AND TESTICULAR INTERSTITIAL FLUID SEX STEROIDS CONCENTRATION

We have previously demonstrated that neonatal and transient neonatal hypothyroidism modulates Leydig, Sertoli, and germ cell numbers, sex steroids and androgen binding protein concentration. The present study was undertaken to study the effect of neonatal onset hypothyroidism on Leydig and peritubular myoid cell numbers, plasma and testicular interstitial fluid (TIF) sex steroid concentration at different age groups of Wistar rats. Hypothyroidism was induced by giving 0.05% methimazole (MMI) to lactating mothers or directly to the male pups from day 1 postpartum through days 10, 15, 30, 40 and 60 postpartum. To confirm hypothyroidism, plasma thyroid hormones and TSH were assayed. Plasma and TIF testosterone, progesterone, dihydrotestosterone (DHT) and estradiol were assayed by radioimmunoassay. Leydig cell number in hypothyroid rats were less than the age-matched controls. The diameter of Leydig cells in hypothyroid rats was smaller than the controls but 10 days old hypothyroids alone had larger than control rats. A significant decrease of peritubular myoid cell number was observed in 30, 40 and 60 days hypothyroid rats and increased in 10 and 15 days hypothyroidism. Hypothyroid rats had elevated level of plasma LH and decreased GH (except day 10 postpartum). Plasma PRL level was increased in 10 and 15 days hypothyroid rats and an opposite effect was observed in 40 and 60 days hypothyroidism. Plasma testosterone, DHT and estradiol were decreased in all hypothyroid rats. However, plasma progesterone level in hypothyroid rats was significantly higher at days 10, 30, and 40 postpartum and an opposite effect was seen in 15 and 60 days experimental groups. TIF testosterone and progesterone titre showed a consistent decrease in hypothyroid rats irrespective of the duration. In hypothyroid rats, TIF DHT levels decreased significantly in days 10, 40 and 60 postpartum. However, it increased in days 15 and 30 postpartum. Except at day 10 postpartum, the level of TIF estradiol in hypothyroid rats was significantly less than their age matched controls. Our data clearly indicate that neonatal onset hypothyroidism adversely affect Leydig cell proliferation along with impaired steroidogenesis.
Long‐term evolution of the acute tubular necrosis (ATN) induced by glycerol: role of myofibroblasts and macrophages

Late structural changes such as interstitial fibrosis in the renal cortex and tubular atrophy have been detected after severe acute tubular necrosis (ATN). The aim of this study was to investigate the expression of fibronectin, α‐smooth muscle actin and macrophages during the evolution of the ATN induced by glycerol and their relationship with the late structural changes observed in the kidneys of these animals. Forty‐nine male Wistar rats were injected with a 50% glycerol solution, 8 mL/kg (4 mL/kg applied i.m. to each hind leg) and 14 with 0.15 m NaCl solution. Before glycerol injection on day 1, water was removed for 17 h. Blood and urine samples were collected 1 day after the injection to quantify sodium and creatinine. The animals were killed 5, 30 and 60 days after the injections and the kidneys removed for histological and immunohistochemical studies. The results of the histological and immunohistochemical studies were scored according to the extent of lesion or staining in the cortical tubulointerstitium, respectively. The percentage of tubulointerstitial lesions was determined by morphometry. Glycerol‐injected rats presented a transitory increase in plasma creatinine levels and in fractional sodium excretion. The immunohistochemical studies showed increased fibronectin, α‐smooth muscle actin (α‐SM‐actin), TGF‐β and ED‐1 (macrophages) staining in the renal cortex from rats killed 5, 30 and 60 days after glycerol injection (P < 0.05) compared to control. The animals killed on day 30 and 60 also presented chronic lesions (fibrosis, tubular dilatation and atrophy) in the renal cortex, despite the recovery of renal function. Macrophages, TGF‐β and myofibroblasts may have contributed to the development of renal fibrosis in these rats.
New Perspectives in Internal Audit Research: A Structured Literature Review

This structured literature review adopts a multimethod and multitheoretical approach to identify current knowledge about internal audit as well as related knowledge gaps. To that end, it provides an overview of post‐Sarbanes‐Oxley Act literature, organizing it under three themes: the multiple roles of internal audit, internal audit quality (IAQ), and the practice of internal audit. Despite the volume of literature published during the period covered by this review (2005 to mid‐2017), the first two themes are still in development, while the third is emergent. We suggest research avenues to fill the following main gaps: (i) Given differing opinions about the expected or actual roles of internal audit, prior literature infers that the internal audit function has become the “jack of all trades” of governance, but does not clearly capture its actual roles. (ii) The viewpoint of external auditors has dominated IAQ research, leading to a misunderstanding of how actors with greater stakes in the practice of internal audit conceptualize and evaluate IAQ. (iii) Knowledge of the actual practice of internal audit and its accountability and ethical issues is fragmentary, therefore the literature's current picture of internal audit is far from comprehensive. Resume Nouvelles perspectives de recherche en audit interne : Une recension des ecrits structuree L'analyse documentaire structuree a laquelle procedent les auteurs fait appel a une demarche multimethode et multitheorie pour definir les connaissances actuelles au sujet de l'audit interne ainsi que les lacunes du savoir a ce chapitre. A cet egard, cet exercice donne un apercu de la documentation posterieure a la SOX, en l'organisant selon trois themes : les roles multiples de l'audit interne, la qualite de l'audit interne et l'exercice de l'audit interne. Malgre le volume de la documentation publiee au cours de la periode sur laquelle porte cette analyse (de 2005 jusqu'au milieu de 2017), les deux premiers themes sont toujours en developpement, alors que le troisieme est emergent. Les auteurs proposent des pistes de recherche afin de combler les principales lacunes qui suivent. 1) Compte tenu des divergences d'opinion quant aux roles attendus ou reels de l'audit interne, les ecrits laissent supposer jusqu’a maintenant que la fonction d'audit interne est desormais le « factotum » de la gouvernance, sans toutefois en saisir clairement les roles reels. 2) Le point de vue des auditeurs externes a domine la recherche sur la qualite de l'audit interne, ce qui a mene a une meprise quant a la facon dont les acteurs pour lesquels les enjeux de l'exercice de l'audit interne sont plus importants conceptualisent et evaluent la qualite de l'audit interne. 3) La connaissance de l'exercice reel de l'audit interne et de l'obligation de rendre compte ainsi que des questions ethiques qui y sont associees est fragmentaire, si bien que le portrait actuel de la documentation est loin d’etre complet.
Tenderness classification of beef: I. Evaluation of beef longissimus shear force at 1 or 2 days postmortem as a predictor of aged beef tenderness.

The present experiments were conducted to evaluate the use of longissimus shear force at 1 or 2 d postmortem as a predictor of beef longissimus shear force at 14 d postmortem. Experiments 1 (n = 400) and 2 (n = 554) included carcasses slaughtered and processed under laboratory and commercial conditions, respectively. A carcass was classified as "tender," "intermediate," or "tough" if its longissimus shear value at 1 or 2 d postmortem was < 6 kg, 6 to 9 kg, or > 9 kg, respectively. For Exp. 1 and 2, large (P < .001) differences existed between each successive tenderness class in mean shear force at 14 d postmortem. Moreover, frequency analysis indicated that tenderness classification accurately (84.8 and 94.8% for Exp. 1 and 2, respectively) predicted whether the sample would have a "low" (< 6 kg) Warner-Bratzler shear (WBS) value at 14 d postmortem. All (100%) of the carcasses in the "tender" class had "low" WBS values at 14 d postmortem, most (81 and 85% for Exp. 1 and 2, respectively) of the carcasses in the "intermediate" class had "low" WBS values at 14 d postmortem, and most (74 and 67% for Exp. 1 and 2, respectively) of the carcasses in the "tough" class did not have "low" WBS values at 14 d postmortem. Although shear force at 2 d postmortem was only moderately correlated (r = .68) with shear force at 14 d postmortem, 68% of the carcasses sampled in Exp. 2 could be guaranteed tender with 100% accuracy based on shear force at 2 d postmortem. Thus, cooked beef longissimus shear force can be measured at 1 or 2 d postmortem and used to predict longissimus tenderness after cooler aging (14 d postmortem) with a relatively high degree of accuracy.
Increased Ig‐null B lymphocytes in the peripheral blood of pediatric solid organ transplant recipients with elevated Epstein‐Barr viral loads

Abstract: In this study, the characteristics of Ig‐null B cells in high viral load carriers were examined by four‐color flow cytometry. The frequency of Ig‐null B cells in patients with high, low or undetectable virus loads was found that while patients with a high load had more Ig‐null cells, these cells were also present in the low and undetectable load groups. As Ig‐null cells from patients with no viral load were EBV‐negative, EBV infection was not absolutely required for the generation or survival of Ig‐null cells. Ig‐null cells were CD19+, sIg‐, CD5−, CD10−, CD27−, CD23−, CD38−, and CD69− with variable surface expression of CD20 and CD40. Ig‐null cells did not have a proliferating cell phenotype (Ki67‐) and a high proportion were HLA class I‐ and class II‐. Virus copy number in CD19+ Ig‐null cell populations may be much higher than in CD19+ Ig+ cell populations. EBV infected Ig‐null cells were common in blood specimens from pediatric solid organ transplant recipients and infected Ig‐null cells may pose potential problems for immunotherapies that target infected B cells directly.