Miracle-dz/UniFAR-FTUs huggingface dataset:
Site‐directed mutagenesis of the ATM promoter: Consequences for response to proliferation and ionizing radiation

Although ATM, the protein defective in ataxia‐telangiectasia (A‐T), is activated primarily by radiation, there is also evidence that expression of the protein can be regulated by both radiation and growth factors. Computer analysis of the ATM promoter proximal 700‐bp sequence reveals a number of potentially important cis‐regulatory sequences. Using nucleotide substitutions to delete putative functional elements in the promoter of ATM, we examined the importance of some of these sites for both the basal and the radiation‐induced activity of the promoter. In lymphoblastoid cells, most of the mutations in transcription factor consensus sequences [Sp1(1), Sp1(2), Cre, Ets, Xre, γIre(2), a modified AP1 site (Fse), and GCF] reduced basal activity to various extents, whereas others [γIre(1), NF1, Myb] left basal activity unaffected. In human skin fibroblasts, results were generally the same, but the basal activity varied up to 8‐fold in these and other cell lines. Radiation activated the promoter approximately 2.5‐fold in serum‐starved lymphoblastoid cells, reaching a maximum by 3 hr, and all mutated elements equally blocked this activation. Reduction in Sp1 and AP1 DNA binding activity by serum starvation was rapidly reversed by exposure of cells to radiation. This reduction was not evident in A‐T cells, and the response to radiation was less marked. Data provided for interaction between ATM and Sp1 by protein binding and co‐immunoprecipitation could explain the altered regulation of Sp1 in A‐T cells. The data described here provide additional evidence that basal and radiation‐induced regulation of the ATM promoter is under multifactorial control. © 2003 Wiley‐Liss, Inc.
A randomly assigned double‐blind cross‐over study examining the relative anti‐parkinsonian tremor effects of pramipexole and pergolide

This study examined the relative anti‐Parkinson's disease (PD) tremor potencies of pergolide and pramipexole in people with PD, using a 3‐month double‐blind cross‐over design. Patients were randomly assigned to receive either pergolide and then pramipexole (n = 9) or vice versa (n = 8). The dose of the respective dopamine agonist was increased according to a titration schedule up to a maximum 1.5 mg t.d. s. , with cross‐over at 10 weeks. Assessments were performed at baseline, 4, 8 and 12 weeks. The primary outcome measures were the differences in the clinical (rest and postural) tremor scores on pergolide versus pramipexole. Seventeen PD patients (11 females and six males) with a mean age 68.4 years (range: 55–84 years) and a mean disease duration of 3.9 years (range: 2 months to 13 years) participated in the study. Twelve of the patients were taking other anti‐parkinsonian medications. Two patients dropped out of the study whilst on pergolide. Fifteen of 16 patients were able to cross‐over from one dopamine agonist to the other, without major retitration. There were no significant differences between the effects of the two drugs on the primary outcome measures, suggesting that the anti‐PD tremor efficacies of dopaminergic medications are not dependent on differential affinities for dopamine receptor types.
Cerebrospinal Fluid Markers of Alzheimer's Disease Pathology and Microglial Activation are Associated with Altered White Matter Microstructure in Asymptomatic Adults at Risk for Alzheimer's Disease.

BACKGROUND The immune response in Alzheimer's disease (AD) involves activation of microglia which may remove amyloid-β (Aβ). However, overproduction of inflammatory compounds may exacerbate neural damage in AD. AD pathology accumulates years before diagnosis, yet the extent to which neuroinflammation is involved in the earliest disease stages is unknown. OBJECTIVE To determine whether neuroinflammation exacerbates neural damage in preclinical AD. METHODS We utilized cerebrospinal fluid (CSF) and magnetic resonance imaging collected in 192 asymptomatic late-middle-aged adults (mean age = 60.98 years). Neuroinflammatory markers chitinase-3-like protein 1 (YKL-40) and monocyte chemoattractant protein-1 (MCP-1) in CSF were utilized as markers of neuroinflammation. Neural cell damage was assessed using CSF neurofilament light chain protein (NFL), CSF total tau (T-Tau), and neural microstructure assessed with diffusion tensor imaging (DTI). With regard to AD pathology, CSF Aβ42 and tau phosphorylated at threonine 181 (P-Tau181) were used as markers of amyloid and tau pathology, respectively. We hypothesized that higher YKL-40 and MCP-1 in the presence of AD pathology would be associated with higher NFL, T-Tau, and altered microstructure on DTI. RESULTS Neuroinflammation was associated with markers of neural damage. Higher CSF YKL-40 was associated with both higher CSF NFL and T-Tau. Inflammation interacted with AD pathology, such that greater MCP-1 and lower Aβ42 was associated with altered microstructure in bilateral frontal and right temporal lobe and that greater MCP-1 and greater P-Tau181 was associated with altered microstructure in precuneus. CONCLUSION Inflammation may play a role in neural damage in preclinical AD.
Environmental correlates of geographic divergence in a phenotypic trait: A case study using bat echolocation

Abstract Divergence in phenotypic traits may arise from the interaction of different evolutionary forces, including different kinds of selection (e.g., ecological), genetic drift, and phenotypic plasticity. Sensory systems play an important role in survival and reproduction, and divergent selection on such systems may result in lineage diversification. Such diversification could be largely influenced by selection in different environments as a result of isolation by environment (IbE). We investigated this process using geographic variation in the resting echolocation frequency of the horseshoe bat species, Rhinolophus damarensis, as a test case. Bats were sampled along a latitudinal gradient ranging from 16°S to 32°S in the arid western half of southern Africa. We measured body size and peak resting frequencies (RF) from handheld individual bats. Three hypotheses for the divergence in RF were tested: (1) James’ Rule, (2) IbE, and (3) genetic drift through isolation by distance (IbD) to isolate the effects of body size, local climatic conditions, and geographic distance, respectively, on the resting frequency of R. damarensis. Our results did not support genetic drift because there was no correlation between RF variation and geographic distance. Our results also did not support James' Rule because there was no significant relationship between (1) geographic distances and RF, (2) body size and RF, or (3) body size and climatic variables. Instead, we found support for IbE in the form of a correlation between RF and both region and annual mean temperature, suggesting that RF variation may be the result of environmental discontinuities. The environmental discontinuities coincided with previously reported genetic divergence. Climatic gradients in conjunction with environmental discontinuities could lead to local adaptation in sensory signals and directed dispersal such that gene flow is restricted, allowing lineages to diverge. However, our study cannot exclude the role of processes like phenotypic plasticity in phenotypic variation.
Constrained Nonlinear Finite-Time Control Allocation

This paper proposed an optimal control allocation method for a general class of overactuated nonlinear systems with internal dynamics. Dynamic inversion technique is used for the commanded subsystem to track a stable model reference control law. The corresponding control allocation law has to guarantee the stability of the internal dynamics and satisfy control constraints. The proposed method is based on a Lyapunov design approach with finite-time convergence to optimality. The derived control allocation is in the form of a dynamic update law, which, together with the stable model reference control law, guarantees the stability of the closed-loop nonlinear system.
Guided tissue regeneration in jawbone defects prior to implant placement.

The principle of guided tissue regeneration has been successfully applied for the regeneration of bone in various jaw defects in human. The purpose of this study was to assess the bone volume regenerated using nonresorbable membrane barriers. Nineteen patients with jaw bone defects of various sizes and configurations were included in the study. Combined split-thickness/full-thickness mucosal flaps were elevated in the area of missing bone. The size of the defects was assessed by measuring the distance from a reference line between 2 adjacent teeth (cementoenamel junctions) to the alveolar crest (a) every 2 or 3 mm. In addition, the crestal width was measured. Consequently, the surface of the triangle formed by a and the width of the crest as well as the volume between all triangles were calculated geometrically. Following the placement of Gore-Tex augmentation material as a barrier, the distance (b) to the top of the membrane from the reference line was assessed, and the maximum possible volume for bone regeneration based on (a-b) and the width of the crest was calculated. At the time of membrane removal (3-8 months later), the same measurements were performed and the percentages of regenerated bone in relation to the possible volume for regeneration determined. In 6 patients in whom the membranes had to be removed early due to an increased risk for infection between 3 and 5 months, bone regeneration varied between 0 and 60%. In 13 patients in whom membranes were left for 6-8 months, regenerated bone filled 90-100% of the possible volume. (ABSTRACT TRUNCATED AT 250 WORDS)
Self-Care Behaviors among Patients with Heart Failure in Iran.

INTRODUCTION Recovery from heart failure and dealing with its effects is significantly influenced by patient's self-care. In order to maximize the effects of behavioral interventions and for educational planning, it is essential to know how much experience and information do patients with heart failure have about their disease and self-care behaviors. The present study aimed to identify self-care behaviors in patients with heart failure. METHODS Eighty heart failure patients hospitalized in Shahid Madani Training Center in Tabriz, Iran, participated in this study. Data collection was done through Self-Care of Heart Failure Index (SCHFI) that contained 22 questions in three sections including self-care behaviors, self-care management and confidence in performing self-care behaviors. RESULTS The patient's self-care behaviors in three behavioral sub categories of maintaining, managing and confidence were low. The most repeated self-care behavior in the participating patients was taking medication and visiting the doctor. CONCLUSION The results of the study showed low levels of self-care behaviors in patients with heart failure, which notes the need for patient empowerment. It is necessary to develop appropriate strategies in this regard by the authorities.
Inflammatory Mediators for the Diagnosis and Treatment of Sepsis in Early Infancy

Interleukin-6 (IL-6), interleukin-8 (IL-8), and procalcitonin (PCT) are important parameters in the diagnosis of sepsis and for differentiating between viral and bacterial infection in children. We compared the value of IL-6, IL-8, and PCT with C-reactive protein (CRP) in the diagnosis and treatment of late-onset sepsis among infants admitted to the neonatal intensive care unit (group I) and febrile infants admitted to general hospitals from home (group II). Group I was divided into subgroups Ia, positive blood culture (all Gram-positive cocci); Ib, negative blood culture; and Ic, controls. Group II was divided into subgroups IIa, systemic enterovirus infection, and IIb, no enterovirus infection. Enterovirus was identified by real-time (RT) polymerase chain reaction (PCR) and/or by culture in blood and cerebrospinal fluid (CSF). The positive predictive values of IL-6, IL-8, and PCT (78%, 72%, and 83%, respectively) were better than that of CRP (63%) in the diagnosis of neonatal sepsis. After 48 h of antibiotic treatment, IL-6 and IL-8 levels significantly decreased and PCT stabilized in clinically recovered patients, suggesting that these markers may be useful in distinguishing patients in which antibiotic treatment may be discontinued. Among infants of subgroup IIa, 80%–90% had normal values of IL-6, IL-8, and PCT, whereas CRP was increased in 40%. In conclusion, IL-6, IL-8, and PCT are better parameters than CRP in the diagnosis and follow-up of neonatal sepsis due to coagulase-negative staphylococci (CoNS) and in the exclusion of bacterial infection among those with enteroviral infection among febrile infants presenting from home.
Nonprofit Governance in the United States: Findings on Performance and Accountability from the First National Representative Study

Nonprofit boards are increasingly a focus of those interested in greater accountability and transparency, including policymakers, media, and the public. To help inform current policy debates and initiatives to strengthen nonprofit governance, in 2005 the Urban Institute conducted the first ever national representative survey of nonprofit governance, with over 5,100 participants. This report presents survey findings, discussing: relationships between public policy and governance, factors that promote or impede boards' performance of basic stewardship responsibilities, board composition and factors associated with board diversity, and recruitment processes, including the difficulty experienced by many nonprofits in finding members.
Echinocandins in the management of invasive fungal infections, Part 2.

PURPOSE The chemistry, pharmacology, spectrum of activity, resistance, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, drug interactions, dosage and administration, cost, and place in therapy of echinocandins are reviewed. SUMMARY Three echinocandins are currently available: caspofungin, micafungin, and anidulafungin. The principal mechanism of action of the echinocandins is the noncompetitive inhibition of beta-(1,3)-D-glucan synthase, an essential component of the cell wall of many fungi that is not present in mammalian cells. Echinocandins exhibit fungicidal activity against Candida species, including triazole-resistant isolates, and fungistatic activity against Aspergillus species. While fungistatic against mold, echinocandins may hold promise for the treatment of these pathogens when given in combination with amphotericin B or broad-spectrum triazoles, such as voriconazole. To date, resistance to echinocandins has been reported in only two patients. Echinocandins exhibit concentration-dependent activity against Candida species. In clinical trials, caspofungin has demonstrated efficacy in treating candidemia, esophageal candidiasis, and febrile neutropenia. Micafungin has demonstrated efficacy as antifungal prophylaxis in hematopoietic stem cell transplant recipients and in the treatment of esophageal candidiasis. Anidulafungin received approved labeling from the Food and Drug Administration in February 2006. Clinical efficacy data will be forthcoming. CONCLUSION Echinocandins are fungicidal against yeast and fungistatic against mold. Their limited toxicity profile and minimal drug-drug interactions make them an attractive new option for the treatment of invasive fungal infections. Their cost may limit their use as initial therapy for patients with fungemia in medical centers or intensive care units with a high rate of triazoleresistant Candida infections.
Risk factors for hospitalization and death from diarrhea in a public pediatric hospital in Rio de Janeiro, Brazil.

OBJECTIVE This study was carried out in a public pediatric hospital located in the city of Rio de Janeiro, Brazil, with the aim of identifying risk factors for hospitalization and/or death due to diarrhea in children. MATERIAL AND METHODS The study included 406 children under three years of age who were seen or admitted for diarrhea from January 1987 to February 1988. The main variable of interest was the outcome of clinical evaluation and subsequent hospitalization, which was classified as follows: 1) outpatient treatment; 2) hospitalization and survival; and 3) death during hospitalization. The chi-square test was used to identify variables (p = < 0.05) that were significantly related to the treatment outcome. RESULTS The group was composed by 60.6% males and 39.4% females. A proportion of 26.8% of children was under two months of age, 24.9% was 3-5 months old, 25.9% was 6-11 months old, and 22.4% was 12 months or older. The variables most significantly related to the risk of hospitalization from diarrhea were age, current nutritional status (weight-for-age percentile), and concomitant illness. Variables most significantly associated with risk of death from diarrhea were low birth weight and past hospitalization. CONCLUSIONS Use of this study's results by health services could make a substantial contribution to reducing children's hospitalization and death due to diarrhea in the city of Rio de Janeiro.
Pregnancy and Lupus Nephritis

Family planning and pregnancy are important and usually problematic issues for a young woman with lupus nephritis. Moderate renal insufficiency and previous use of alkylating cytotoxic drugs are associated with decreased fertility. Oral contraceptives containing synthetic estrogens are contraindicated in women with active lupus nephritis, uncontrolled hypertension, history of thromboembolic diseases or high levels of antiphospholipid antibodies. Mild flares of systemic lupus erythematosus (SLE) are common during pregnancy, severe renal flares and permanent impairment of renal function are uncommon. The outlook of pregnancy for women with lupus nephritis is usually favourable if the disease (both renal and nonrenal) has been quiescent for at least 6 months before pregnancy, and if, at conception, serum creatinine is less than 140 µmol/l, proteinuria less than 3 g/24 h and blood pressure controlled. The risk of fetal loss is, however, at least 2? 3 times higher than in the normal population and pre-eclampsia, prematurity and fetal growth retardation frequently complicate these pregnancies. Especially poor fetal outcome is associated with antiphospholipid antibodies. Pregnancies in women with lupus nephritis require intense fetal and maternal surveillance.
Clinical significance of V617F mutation of the JAK2 gene in patients with chronic myeloproliferative disorders

Abstract Objective: To determine the prevalence of JAK2 V617F mutation and its clinical correlation in patients with chronic myeloproliferative disorders (CMD): polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). Materials and methods: Detection of JAK2 V617F mutation by allele specific-PCR. Results: One hundred and three patients with CMD were included in the study. JAK2 V617F distribution was PV 40/45 (89%), ET 30/43 (69%), and IMF 7/15 (47%). In PV and ET patients only, 18 had thrombosis at diagnosis and 12 during follow-up (these were microvascular: 11, venous: 7 and arterial: 12); of these 28/70 (40%) were JAK2pos versus 2/18 (11%) JAK2neg; P=0·02. In a median of 4 years, two patients with PV JAK2pos evolved to myelofibrosis and one patient with PV presented in leukemic transformation (JAK2pos before and after transformation); six patients died: four patients with IMF and two patients with PV. Conclusions: We found an association between JAK2 V617F and thrombotic events in patients with PV and ET.
Ouabain at Nanomolar Concentration Promotes Synthesis and Release of Angiotensin II from the Endothelium of the Tail Vascular Bed of Spontaneously Hypertensive Rats

The effects of 1 nM ouabain (OUA) on the contractile actions of phenylephrine (PHE, 0.001–100 μg) and functional activity of the sodium pump (NKA) in isolated-perfused tail vascular beds from WKY and SHR were investigated. In preparations from SHR, perfusion with OUA in the presence of endothelium (E+) increased the sensitivity (pED50) of PHE (before: 2.14 ± 0.06 versus after: 2.47 ± 0.07; P < 0.05) without altering the maximal response (Emax). After endothelial damage, OUA reduced the Emax of PHE in SHR (before: 350 ± 29 versus after: 293 ± 25 mm Hg; P < 0.05). In SHR/E+, pretreatment with losartan (10 μM) or enalaprilat (1 μM) prevented the increased sensitivity to PHE induced by OUA. OUA increased NKA activity in SHR/E+ (before: 45 ± 6 versus after: 58 ± 5%, P < 0.05). Losartan (10 mg/Kg, i.v.) also abolished the increment in systolic and diastolic blood pressure induced by OUA (0.18 μg/Kg, i.v.) in anesthetized SHR. OUA did not alter the actions of PHE in either anesthetized WKY rats or vascular preparations. Results suggest that 1 nM OUA increased the vascular reactivity to PHE only in SHR/E+. This effect is mediated by OUA-induced activation of endothelial angiotensin converting enzyme that promotes the local formation of angiotensin II, which sensitizes the vascular smooth muscle to the actions of PHE.
Asymptotic Capacity Analysis of Large-Scale MIMO AF Relay Networks in a Composite Fading Environment

Large-scale multiple-input-multiple-output (MIMO) networks, together with relay technology, have received considerable attention due to their remarkable capacity potential. Nevertheless, the majority of recent research studies on the asymptotic capacity of large-scale MIMO amplify-and-forward (AF) relay networks are limited to a fundamental assumption of smallscale fading, where the effect of large-scale fading, including shadow fading and path loss, is ignored. Motivated by this observation, in this paper, we present an extended model for the asymptotic capacity analysis in a composite fading environment, where Rayleigh fading, shadow fading, and path loss effect are incorporated altogether. Moreover, a realistic relay distribution is considered for real-world application of our capacity analysis. The proposed model consists of one source and one destination that are both equipped with M antennas, which communicate through K relays, each having N antennas. We first employ random matrix theory to derive the empirical cumulative distribution of the channel covariance matrix and analyze the asymptotic capacity per source-destination antenna pair as both M and NK tend to infinity, but their ratio remains as a constant. We then consider the asymptotic capacity under two asymptotic cases for a finite and an infinite number of relays, respectively. It is shown through both theoretical analysis and Monte Carlo simulations that increasing the shadowing standard deviation can improve asymptotic capacity, whereas increasing the path loss exponent would lead to a capacity reduction. Our simulation results also reveal the effects of the relay distribution, as well as the source and relay transmission powers, on the asymptotic capacity.