Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanisms of chiral discrimination by topoisomerase IV

Topoisomerase IV (Topo IV), an essential ATP-dependent bacterial type II topoisomerase, transports one segment of DNA through a transient double-strand break in a second segment of DNA. In vivo, Topo IV unlinks catenated chromosomes before cell division and relaxes positive supercoils generated during DNA replication. In vitro, Topo IV relaxes positive supercoils at least 20-fold faster than negative supercoils. The mechanisms underlying this chiral discrimination by Topo IV and other type II topoisomerases remain speculative. We used magnetic tweezers to measure the relaxation rates of single and multiple DNA crossings by Topo IV. These measurements allowed us to determine unambiguously the relative importance of DNA crossing geometry and enzymatic processivity in chiral discrimination by Topo IV. Our results indicate that Topo IV binds and passes DNA strands juxtaposed in a nearly perpendicular orientation and that relaxation of negative supercoiled DNA is perfectly distributive. Together, these results suggest that chiral discrimination arises primarily from dramatic differences in the processivity of relaxing positive and negative supercoiled DNA: Topo IV is highly processive on positively supercoiled DNA, whereas it is perfectly distributive on negatively supercoiled DNA. These results provide fresh insight into topoisomerase mechanisms and lead to a model that reconciles contradictory aspects of previous findings while providing a framework to interpret future results.
Characteristics of Chronic Pain and Its Impact on Quality of Life of Patients With HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)

ObjectivesWe describe the prevalence of chronic pain and their characteristics in 43 consecutive patients presenting with human T-lymphotropic virus Type I (HTLV-1) associated myelopathy (HAM) /tropical spastic paraparesis in Salvador, Brazil. MethodsIn this cross-sectional study, we included 43 consecutive patients with HAM/TSP from Sarah Salvador Unit of the Rehabilitation, in Bahia, Brazil. They were evaluated from September 2007 to July 2008. We used the following scales: Functional disability scales (EDSS, OSAME e HOFFER); visual analogue scale; Hospital Anxiety and Depression Scale; McGill Pain Questionnaire; DN4 Questionnaire and SF-36 Quality-of-Life Questionnaire. ResultsChronic pain was highly prevalent (38 patients---88.4%) in this population. We detected an inverse correlation between duration of the disease and the likelihood of patients to present with chronic pain (P<0.05). Individuals with greater neurologic deficits had much more neuropathic, whereas those with lower motor deficit had mainly the characteristics of nociceptive pain (P<0.05). A positive correlation was observed between the score of the dominant pain or the additional pain, and the number of pain descriptors (P<0.05 for both evaluations). The patients with chronic pain had worst Quality-of-Life scores (P<0.05). ConclusionChronic pain was significantly associated with a higher likelihood of signs/symptoms of anxiety and depression, reflecting a negative impact of pain on patients´ quality of life.
Risk of endometrial cancer following estrogen replacement with and without progestins.

BACKGROUND Unopposed estrogen replacement therapy (i.e., estrogen without progestins) increases the risk of endometrial cancer. In this study, we examined the endometrial cancer risk associated with combined estrogen-progestin regimens currently in use, since the safety profiles of these regimens have not been clearly defined. METHODS We conducted a nationwide population-based, case-control study in Sweden of postmenopausal women aged 50-74 years. We collected information on use of hormone replacement from 709 case patients with incident endometrial cancer and from 3368 control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) as estimates of relative risks. All individual comparisons were made with women who never used the respective hormone replacement regimens. RESULTS Treatment with estrogens alone was associated with a marked duration- and dose-dependent increase in the relative risk of endometrial cancer. Five or more years of treatment had an OR of 6.2 for estradiol (95% confidence interval [CI] = 3.1-12.6) and of 6.6 for conjugated estrogens (95% CI = 3.6-12.0). Following combined estrogen-progestin use, the association was considerably weaker than that for estrogen alone; the OR was 1.6 (95% CI = 1.1-2.4) after 5 or more years of use. This increase in risk was confined to women with cyclic use of progestins, i.e., fewer than 16 days per cycle (most commonly 10 days per cycle [OR = 2.9; 95% CI = 1.8-4.6 for 5 or more years of use]), whereas continuous progestin use along with estrogens was associated with a reduced risk (OR = 0.2; 95% CI = 0.1-0.8 for 5 or more years of use). CONCLUSION The risk of developing endometrial cancer is increased after long-term use of estrogens without progestins and with cyclically added progestins. Continuously added progestins may be needed to minimize the endometrial cancer risk associated with estrogen replacement therapy.
Cervical Medial Branch Blocks for Chronic Cervical Facet Joint Pain: A Randomized, Double-Blind, Controlled Trial With One-Year Follow-up

Study Design. A double-blind, randomized, controlled trial. Objective. To determine the clinical effectiveness of therapeutic local anesthetic cervical medial branch blocks with or without steroid in managing chronic neck pain of facet joint origin. Summary of Background Data. The prevalence of persistent neck pain, secondary to involvement of cervical facet or zygapophysial joints, has been described in controlled studies as varying from 39% to 67%. Intra-articular injections, medial branch nerve blocks, and neurolysis of medial branch nerves have been described in managing chronic neck pain of facet joint origin. Methods. A total of 120 patients were included, with 60 patients in each of the local anesthetic and steroid groups. All the patients met the diagnostic criteria of cervical facet joint pain by means of comparative, controlled diagnostic blocks, and the inclusion criteria. Group I consisted of medial branch blocks with bupivacaine. Group II consisted of cervical medial branch blocks with bupivacaine and steroid. Numerical pain scores, Neck Disability Index, opioid intake, and work status were evaluated at baseline, 3 months, 6 months, and 12 months. Results. Significant pain relief (≥50%) and functional status improvement was observed at 3 months, 6 months, and 12 months in over 83% of patients. The average number of treatments for 1 year was 3.5 ± 1.0 in the nonsteroid group and 3.4 ± 0.9 in the steroid group. Duration of average pain relief with each procedure was 14 ± 6.9 weeks in the nonsteroid group, and it was 16 ± 7.9 weeks in the steroid group. Significant relief and functional improvement was reported for 46 to 48 weeks in a year. Conclusion. Therapeutic cervical medial branch nerve blocks, with or without steroids, may provide effective management for chronic neck pain of facet joint origin.
Bone mineral density in middle-aged women with Turner's syndrome.

Bone mineral density (BMD), bone mineral content and body composition were determined in 47 middle-aged (mean age 47.9 +/- 1.1 years) women with Turner's syndrome. Bone mineral density was measured in the forearm, femoral neck and total body. The women investigated had a BMD lower than the normal mean. When expressed as Z scores (individual values compared to normal reference data matched for age, weight and sex), the median Z score of the total body was -1.23. When comparing women with the karyotype 45,X and mosaic women, the latter showed a higher BMD in all sites of measurement. Duration of hormonal replacement therapy (HRT) differed significantly between the mosaic and the 45,X women, with a longer duration in the mosaic group (20.7 +/- 2 vs 12.1 +/- 2.6 years; p < 0.01). The duration of HRT was found to be the more important factor to maintain bone mass, not the karyotype. Bone mineral density increased with years of HRT but not until after > 20 years of HRT could a significant difference be shown between the women with HRT < or = 20 years and those with HRT > 20 years. No correlation was found between BMD and body weight, body fat or percentage body fat. Whether the osteopenia found in women with Turner's syndrome is similar to that found postmenopausally or is a specific form related to the chromosome aberration remains to be investigated further. The present data support a relation to estrogen deficiency.
Short-term outcomes of Greenlight HPS laser photoselective vaporization prostatectomy (PVP) for benign prostatic hyperplasia (BPH).

PURPOSE We evaluated our initial experience with the GreenLight HPS laser, a technologically improved version of the potassium-titanyl-phosphate (KTP) laser for PVP. MATERIALS AND METHODS Transurethral PVP was performed using a GreenLight HPS side-firing laser system. Patients had American Urological Association Symptom Score (AUASS), Quality of Life (QoL) score, Sexual Health Inventory for Men (SHIM) score, serum prostate specific antigen (PSA), maximum flow rate (Qmax) and post void residual (PVR) determinations and volumetric prostate measurements with transrectal ultrasonography (TRUS). Laser and operative times and energy usage were recorded. AUASS, QoL, SHIM, Qmax and PVR were evaluated 1, 4, 12, 24, and 52 weeks post-surgery. Serum PSA and TRUS were obtained at 12 weeks and serum PSA was repeated at 52 weeks. RESULTS Seventy consecutive patients with a median age of 67 (45-86) years underwent GreenLight HPS laser PVP from July 2006 through March 2008. Median prostate volume was 61.6 (20.9-263.0) mL with a median PSA of 1.4 (0.1 -10.1) ng/mL. Mean laser and operative times and energy usage were 13 (3-34) minutes, 30 (6-100) minutes and 85 (11-235) kJ, respectively. All were outpatient procedures with 49 (70%) patients catheter-free at discharge. No urethral strictures or urinary incontinence were noted. Median AUASS decreased from 22 to 8, 6, 5, 5, and 4 (p<0.001) while the median Qmax increased from 9.4 to 20.4, 20.3, 21.2, 18.8, and 20.0 mL/s (p<0.001) during the follow-up period. CONCLUSIONS At one year, our experience suggests that GreenLight HPS laser PVP is safe and effective for treating lower urinary tract symptoms secondary to BPH.
Safeguards Against Opportunism in Freelance Contracting on the Internet

Based on a large sample of 5,756 Russian‐speaking freelancers from an international online labour market, this study provides rare quantitative evidence of the external labour market where freelancers act under constant threat of client‐side opportunism. We explore how the formalization of agreements, social embeddedness and mode of communication are associated with the incidence of opportunism and further possibilities of resolving problems caused by agreement violations. Social ties and face‐to‐face contact appear to be better safeguards against opportunism in freelance contracting, which is largely informal. The study has important implications for the debates about non‐standard work, online labour markets and job quality in the new economy.
Proverbs of Nonprofit Financial Management

Whereas the field of public administration has benefited from periods of critical reflection and reform aimed at reexamining the field’s traditional management paradigms, the related field of nonprofit management has generally lacked such an analogously explicit and sustained research program to reevaluate its own conventional wisdoms. Meanwhile, accumulated findings from the last several decades of nonprofit management research have problematized many traditional assumptions and practices in nonprofit management, specifically regarding the soundness of nomothetic management theory, the unintended negative consequences of certain management norms, and underlying assumptions about the nature and purpose of nonprofit management. This article critically reexamines four well-known “proverbs” of nonprofit financial management—minimize overhead, diversify revenues, be lean, and avoid debt—to demonstrate the need for a critical and reflective research program that takes stock and reconsiders the field’s foundational principles and assumptions. Implications are derived for scholars and practitioners, as well as for information intermediaries that evaluate nonprofits based on financial information.
Is There Smart Money? How Information in the Commodity Futures Market Is Priced into the Cross Section of Stock Returns with Delay

Abstract We document a new empirical phenomenon in which the aggregate positions of money managers, who are sophisticated speculators in the commodity futures market, as disclosed by the Disaggregated Commitments of Traders reports, can predict the cross section of commodity producers’ stock returns in the subsequent week. We employ a number of cross-sectional methods, including calendar-time regression analysis, single-sort, double-sort, and Fama–MacBeth regressions, to confirm the predictability results. The results are more pronounced in firms with higher information asymmetry. We thus add more empirical evidence to the literature on costly information processing, which leads to gradual information diffusion across asset markets.
Guidance values for surface monitoring of antineoplastic drugs in German pharmacies.

OBJECTIVES Antineoplastic drugs are widely used in anticancer therapy due to their cytotoxic activity but many of them are classified as carcinogenic, mutagenic, or teratogenic to humans. In order to evaluate personal exposure, surface monitoring has been successfully applied for several years. In this study, we present a statistical description of our data set from 102 German pharmacies and propose 'threshold guidance values (TGVs)' to facilitate interpretation of monitoring results. METHODS Our database included 1008 results for platinum (PT) and 1237 for 5-fluorouracil (FU) collected in 102 pharmacies in Germany. Wipe sampling on site was performed with one validated procedure. PT concentrations were measured by voltammetry and FU by gas chromatography/mass spectrometry. Data were stratified into 10 locations and statistically evaluated. RESULTS Contamination was detected on all surfaces in the pharmacies with high levels on storage shelves and floors. The median values for the different locations ranged from 0.20 to 1.70 pg cm(-2) (mean: 0.57 pg cm(-2)) for PT and from 2.50 to 10.00 pg cm(-2) (mean: 5.34 pg cm(-2)) for FU. The mean 75th percentiles were 3.92 pg cm(-2) (PT) and 28.90 pg cm(-2) (FU). The TGV 1 value was set at the median value and results below demonstrate good working practices. Contaminations above the TGV 2, which was assigned at the 75th percentile, show a clear need for optimizing the handling procedures. CONCLUSIONS The introduction of TGVs helps to reduce occupational exposure and allows pharmacy personnel to benchmark their own contamination levels. This provides a basis for improvement in occupational safety precautions and for regular contamination controls.
Economic freedom and veto players jointly affect entrepreneurship

Purpose The purpose of this paper is to explore how the strength of political veto players affects the long-run credibility of economic institutions and how they jointly affect entrepreneurial activity. Design/methodology/approach The authors employ an annual panel covering 30 OECD countries from 1993 to 2011. Findings An error correction model identifies a positive and significant short-run effect on self-employment from large government spending at low levels of veto player strength. A static model conversely indicates that smaller government spending is positively associated with entrepreneurship at lower levels of veto player strength in the long run. Originality/value The authors are the first to explore the interaction of economic and political institutions in the development of entrepreneurship.
EXTREME DRAG FORCES AND THE SURVIVAL OF WIND- AND WATER-SWEPT ORGANISMS

A stationary organism exposed to steady turbulent flow is subjected to a drag force that fluctuates about a mean, and when the drag on the organism is characterized, it is traditionally this mean force that is cited. Important information is lost, however, when the fluctuations in drag are ignored. This is particularly true when extreme drag forces are relevant; for instance, when predicting the survival of benthic animals on wave-swept shores and in torrential streams, or of plants in windblown terrestrial habitats. This study reports on the probability distribution of drag fluctuations for five objects: a flat plate, large and small cylinders, a sphere and a limpet shell. Distributions vary substantially among different objects exposed to the same mainstream flow; the sphere and limpet exhibit larger fluctuations than the plate and cylinders. The distribution of extremes in drag is used to predict the likelihood that an organism will be dislodged. For organisms in which the applied fluid-dynamic stress is near the mean breaking stress (e.g. some corals, trees and mussels), calculations made using the extreme drag can yield a probability of dislodgment substantially higher than that calculated using the average.
Biopolymeric Modification of Superoxide Dismutase (mPEG-SOD) to Prevent Muscular Ischemia-Reperfusion Damage

The efficacy of preventing ischemia-reperfusion damage by employing native or modified (mPEG-SOD) superoxide dismutase in an experimental animal model of acute ischemia of the left hindlimb was tested. Four hours and thirty minutes complete warm ischemia was induced in the left hindlimb of 43 Wistar rats, by clamping the femoral artery and monitoring its efficacy with Laser Doppler flowmetry. After ten days, a significative difference (p=0.004) of the survival leg rate was found in the group treated with mPEG-SOD (86.6%) compared with the control group (30%). Histomorphological and ultrastructural analysis were performed at different time intervals confirming what the clinical course had already pointed out. These results show that SOD in its modified form, despite the lower dosage, can provide good protection against ischemia/reperfusion injury of muscles.
Superoxide Dismutase-Dependent, Catalase-Sensitive Peroxides in Human Endothelial Cells Infected by Rickettsia rickettsii

ABSTRACT The generation and intracellular accumulation of reactive oxygen species have been shown to be associated with the infection of human umbilical vein endothelial cells (HUVEC) by Rickettsia rickettsii. In response to the oxidant superoxide, the activity of the enzyme superoxide dismutase (SOD) increases following infection by this obligate intracellular bacterium. Other oxidants which are capable of oxidizing the fluorescent probe 2′,7′-dichlorofluorescin (DCFH) also accumulate intracellularly within infected cells. In the study reported here, we show that (i) an inhibitor of SOD, diethyldithiocarbamic acid, reduces the observed rise in SOD activity in infected cells by 40 to 60% and at the same time reduces the degree of intracellular oxidation of DCFH; (ii) catalase-sensitive peroxides can be detected in supernatants of R. rickettsii-infected cells shortly after rickettsial exposure; and (iii) fluorescence-activated cell sorter analysis demonstrates significant intracellular oxidant activity in infected cells within 5 h after exposure to R. rickettsii. The results of these experiments indicate that hydrogen peroxide is a major oxidant associated with infection of HUVEC by R. rickettsii and that intracellular oxidant activity sensitive to SOD inhibition is detectable early and prior to significant rickettsial multiplication and much earlier than the ultrastructural manifestations of cell injury seen by electron microscopy.
A STUDY OF FACTORS THAT INFLUENCE THE SEVERITY OF NEONATAL NARCOTIC WITHDRAWAL

A prospective study of 198 infants of drug dependent mothers included: (1) history of maternal drue habit, (2) measurement in infant's urine of total morphine & qualitative detection of other drugs by gas chromatograph, (3) evaluation of severity of neonatal withdrawal by a scoring system & (4) study of the effect of a modified environment (quiet, warm, dimly lit & frequent feeding) on withdrawal.RESULTS: (1) history is unreliable in assessing maternal drug habit. Mean morphine levels of 1.02 & 0.99mg% were found in the urine of infants whose mothers claim non-usage of heroin for 1-3 months before delivery, respectively. (2) severity of neonatal withdrawal did not correlate with infant's urine morphine level range 0-9.4 mg%, P<0.35), but correlated significantly to maternal methadone dose (P<0.005). None to mild withdrawl was seen in mean maternal methadone dose of 21.9 mg/day vs. 31 mg/day in moderate to severe withdrawl. The duration of methadone intake did not correlate with severity of withdrawl. (3) in order of decreasing frequency the S & S of withdrawal were: fist-sucking, irritability, tremors, sneezing, shrill cry, hypertonia, stuffy nose, sweating, diarrhea, vomiting and yawning. Convulsion was not noted. No death occurred. Mean birthweight = 2885 ± 454 g & gest. age = 39 ± 1.1 wks. (> 10th percentile). Mean weight loss = 160.5 g (4)the control (C) & experimental (E) groups for modified environment study were matched for weight, sex, gest. age and maternal methadone dose. The incidence of mild withdrawal was 68% (C) vs. 71% (E); of moderate withdrawal, 27% (C) vs. 26% (E): of severe withdrawal, 5% (C) vs. 3% (E). The difference between the 2 groups was not significant. (5) the qualitative detection of other drugs in the infant's urine will be presented.
Signaling through murine CD38 is impaired in antigen receptor‐unresponsive B cells

CD38 is a 42‐kDa membrane associated enzyme which converts NAD into cyclic ADP‐ribose (cADPR), a Ca2+‐mobilizing second messenger, and ADP‐ribose (ADPR). Agonistic antibodies to murine CD38 deliver a potent growth co‐stimulus to mature splenic B lymphocytes. In this report we demonstrate a striking relationship between CD38‐mediated mitogenesis and the ability of surface IgM to promote B cell proliferation. Tolerized B lymphocytes obtained from a double‐transgenic mouse model of B cell tolerance do not proliferate in response to antigen stimulation through the Ig receptor or to agonistic anti‐CD38 antibodies. Similarly, B‐1 cells isolated from the peritoneal cavity of normal mice, and splenic B cells isolated from newborn mice were also unresponsive to both anti‐IgM and anti‐CD38 stimulation. All of these CD38‐unresponsive B cells expressed normal levels of cell surface CD38 and responded to numerous other stimuli. CD38 immunoprecipitated from these B cell populations was normal in size and effectively hydrolyzed NAD, suggesting that the defect in CD38 signaling likely occurs downstream of CD38 itself. Signaling through CD38 and IgM does not always have identical effects on B cells since anti‐CD38 cannot deliver inhibitory growth or differentiation signals to normal B cells or immature B cell lines. Nevertheless, the correlative data with these multiple B cell models of unresponsiveness suggests that the signaling pathway utilized by CD38 and IgM intersect, possibly sharing at least one of the crucial components of the Ig receptor signaling cascade.