Miracle-dz/UniFAR-FTUs huggingface dataset:
Tissue levels, source, and regulation of 3'-AMP: an intracellular inhibitor of adenylyl cyclases.

Tissue levels of 3'-AMP were measured in several rat tissues and the sensitivities of the respective adenylyl cyclases were compared with respect to "P" site-mediated inhibition by 3'-AMP2'-deoxy-3'AMP (2'd3'-AMP), and 2',5'-dideoxyadenosine. IC50 values for these P site inhibitors of adenylyl cyclases varied widely among tissues, e.g., with skeletal muscle being least sensitive to 3'-AMP (IC50 greater than 170 microM) and brain being most sensitive (IC50 approximately 10 microM). These differences were noted when activation was with Mn2+ but diminished with Mn2+ plus forskolin and conceivably may reflect the distribution of different isozymes of adenylyl cyclase. 3'-AMP levels also varied significantly among rat tissues, with spleen having the highest levels (approximately 280 nmol/g), kidney, liver, heart, and brain having decreasing 3'-AMP content, and skeletal muscle levels being immeasureably low (less than 0.1 nmol/g). When rats were made diabetic with streptozotocin, the 3'-AMP content of livers increased from approximately 47 nmol/g in control animals to approximately 84 nmol/g, a change largely reversed by maintenance of diabetic animals with insulin. The data suggest that tissue 3'-AMP levels may be regulated and in certain tissues may be sufficient to inhibit adenylyl cyclase in vivo. Three potential sources of 3'-AMP and 2'd3'-AMP, the most potent naturally occurring P site inhibitors of adenylyl cyclase, were examined. No evidence was found for the formation of either nucleotide from the respective cyclic nucleotide by a unique cyclic nucleotide phosphodiesterase or from the respective nucleoside by a hypothetical adenosine 3'-kinase and ATP. Substantial 3'-AMP and 2'd3-AMP were formed by spleen and liver homogenates from the respective oligonucleotides (RNA, mRNA, and DNA) in a time- and protein-dependent manner. The data imply the existence of enzymes in these tissues to catalyze the formation of 3'-AMP and 2'd3'-AMP from nucleic acids and suggest that these activities may account for the formation of P site agonists under in vivo conditions. The data suggest that these P site inhibitors are a potential link between fluctuations in nucleic acid metabolism and altered sensitivity of membrane-bound adenylyl cyclase to stimulatory signals.
Pharmacogenetic Analysis of Pediatric Patients with Acute Lymphoblastic Leukemia: A Possible Association between Survival Rate and ITPA Polymorphism

Genetic polymorphisms are important factors in the effects and toxicity of chemotherapeutics. To analyze the pharmacogenetic and ethnic differences in chemotherapeutics, major genes implicated in the treatment of acute lymphoblastic leukemia (ALL) were analyzed. Eighteen loci of 16 genes in 100 patients with ALL were analyzed. The distribution of variant alleles were CYP3A4*1B (0%), CYP3A5*3 (0%), GSTM1 (21%), GSTP1 (21%), GSTT1 (16%), MDR1 exon 21 (77%), MDR1 exon 26 (61%), MTHFR 677 (63%), MTHFR 1298 (29%), NR3C1 1088 (0%), RFC1 80 (68%), TPMT combined genotype (7%), VDR intron 8 (11%), VDR FokI (83%), TYMS enhancer repeat (22%) and ITPA 94 (30%). The frequencies of single nucleotide polymorphisms (SNPs) of 10 loci were statistically different from those in Western Caucasians. Dose percents (actual/planned dose) or toxicity of mercaptopurine and methotrexate were not related to any SNPs. Event free survival (EFS) rate was lower in ITPA variants, and ITPA 94 AC/AA variant genotypes were the only independent risk factor for lower EFS in multivariate analysis, which was a different pharmacogenetic implication from Western studies. This study is the first pharmacogenetic study in Korean pediatric ALL. Our result suggests that there are other possible pharmacogenetic factors besides TPMT or ITPA polymorphisms which influence the metabolism of mercaptopurine in Asian populations.
[Lipid peroxides concentration in women with intrauterine growth restriction].

OBJECTIVES Intrauterine growth restriction is connected to high free radicals activity. One of the indices of lipid cell membrane destruction in free radical processes are lipid peroxides. DESIGN The aim of the study was to find correlation between lipid peroxides products concentration in healthy women and intrauterine growth restriction. MATERIAL AND METHODS The study was done in Medical University in Lodz in 1999-2002. The study group consist of women with IUGR, the controls of healthy pregnant women. The lipid peroxides were measured by colometric method, using Bioxytech kit for lipid peroxides. RESULTS In IUGR group concentration of lipid peroxides was 42.17 +/- 11.77 mumol/l. In controls 53.754 +/- 14.07 mumol/l. We found significant difference between two groups and the increase of lipid peroxides in IUGR group. CONCLUSIONS In women with IUGR the processes of lipid peroxidation increased.
The Influence of Reduced Susceptibility to Fluoroquinolones in Salmonella enterica Serovar Typhi on the Clinical Response to Ofloxacin Therapy

Background Infection with Salmonella enterica serovar Typhi (S. Typhi) with reduced susceptibility to fluoroquinolones has been associated with fluoroquinolone treatment failure. We studied the relationship between ofloxacin treatment response and the ofloxacin minimum inhibitory concentration (MIC) of the infecting isolate. Individual patient data from seven randomised controlled trials of antimicrobial treatment in enteric fever conducted in Vietnam in which ofloxacin was used in at least one of the treatment arms was studied. Data from 540 patients randomised to ofloxacin treatment was analysed to identify an MIC of the infecting organism associated with treatment failure. Principal Findings The proportion of patients failing ofloxacin treatment was significantly higher in patients infected with S. Typhi isolates with an MIC≥0.25 µg/mL compared with those infections with an MIC of ≤0.125 µg/mL (p<0.001). Treatment success was 96% when the ofloxacin MIC was ≤0.125 µg/mL, 73% when the MIC was between 0.25 and 0.50 µg/mL and 53% when the MIC was 1.00 µg/mL. This was despite a longer duration of treatment at a higher dosage in patients infected with isolates with an MIC≥0.25 µg/mL compared with those infections with an MIC of ≤0.125 µg/mL. Significance There is a clear relationship between ofloxacin susceptibility and clinical outcome in ofloxacin treated patients with enteric fever. An ofloxacin MIC of ≥0.25 µg/mL, or the presence of nalidixic acid resistance, can be used to define S. Typhi infections in which the response to ofloxacin may be impaired.
Pathologic Findings in Equine Muscle (Excluding Polysaccharide Storage): A Necropsy Study

Gross and histopathologic evaluation of skeletal muscle was performed in 229 equids (217 horses, 8 ponies, 3 donkeys, and 1 mule) 1 year of age or older undergoing postmortem examination at Oregon State University in a 2.5-year period. Animals were evaluated for grossly evident muscle lesions, and muscle samples were fixed in formalin, processed routinely, and stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) for glycogen. Muscle lesions were detected in 149 animals (65%). Chronic myopathic change (excessive fiber size variation and internal nuclei) was evaluated in horses without polysaccharide storage myopathy and was the most common finding (36 animals; 15.7%). Chronic myopathic change was more common in older animals. Generalized muscle atrophy was present in 30 animals (13.1%). Myonecrosis was attributed to endotoxic injury (11 animals; 4.8%), bone fracture (8 animals; 3.5%), bacterial infection (5 animals; 2.2%), muscle rupture (3 animals; 1.3%), selenium deficiency (2 animals; 0.9%), and exertional rhabdomyolysis (1 horse; 0.4%); cause was not determined in 9 animals (3.9%). Intramyofiber protozoa were detected in 19 horses and ponies (8.3%). Denervation atrophy was detected in 14 animals (6.1%). Neoplasia involving muscle occurred in 3 animals (1.3%), injection site reactions were detected in 4 animals (1.7%), and focal lymphocytic infiltrates were found in 6 animals (2.6%). Other findings were ring fibers (2 horses; 0.9%), fiber splitting (2 horses; 0.9%), and fat infiltration (1 horse; 0.4%). Skeletal muscle lesions are common in equids examined at postmortem. Transverse sections stained with HE and PAS are invaluable when evaluating equine muscle.
Spatial and Temporal Misperceptions in Amblyopic Vision

The aim of this study was to investigate the spatial and temporal distortions that occur in strabismic and anisometropic amblyopic vision. Twelve subjects with strabismic (n = 4), anisometropic (n = 4), mixed amblyopia (n = 3) and bilateral refractive amblyopia (n = 1) were asked to describe and sketch their subjective percept of different geometrical patterns, as seen with their amblyopic eye. Based on their descriptions, computer-animated patterns were generated, which were then validated by the subjects. Both spatial distortions and temporal instability were perceived mainly by strabismic and strabismic-anisometropic amblyopes. Temporal instability occurred mainly at high spatial frequencies. Our data suggest that strabismus, in addition to amblyopia, is needed to elicit significant spatial and temporal distortions. The occurrence of these distortions may be related to the early history of each subject.
No overall progression and occasional repair of erosions despite persistent inflammation in adalimumab-treated rheumatoid arthritis patients: results from a longitudinal comparative MRI, ultrasonography, CT and radiography study

Aim To monitor joint inflammation and destruction in rheumatoid arthritis (RA) patients receiving adalimumab/methotrexate combination therapy using MRI and ultrasonography. To assess the predictive value of MRI and ultrasonography for erosive progression on CT and compare MRI/ultrasonography/radiography for erosion detection/monitoring. Methods Fifty-two erosive biological-naive RA patients were followed with repeated MRI/ultrasonography/radiography (0/6/12 months) and clinical/biochemical assessments during adalimumab/methotrexate combination therapy. Results No overall erosion progression or repair was observed at 6 or 12 months (Wilcoxon; p>0.05), but erosion progressors and regressors were observed using the smallest detectable change cut-off. Scores of MRI synovitis, grey-scale synovitis (GSS) and power Doppler ultrasonography decreased after 6 and 12 months (p<0.05), as did DAS28, HAQ and tender and swollen joint counts (p<0.001). Patients with progression on CT had higher baseline MRI bone oedema scores. The RR for CT progression in bones with versus without baseline MRI bone oedema was 3.8 (95% CI 1.5 to 9.3) and time-integrated MRI bone oedema, power Doppler and GSS scores were higher in bones/joints with CT progression (Mann–Whitney; p<0.05). With CT as the reference method, sensitivities/specificities for erosion in metacarpophalangeal joints were 68%/92%, 44%/95% and 26%/98% for MRI, ultrasonography and radiography, respectively. Median intraobserver correlation coefficient was 0.95 (range 0.44–0.99). Conclusion During adalimumab/methotrexate combination therapy, no overall erosive progression or repair occurred, whereas repair of individual erosions was documented on MRI, and MRI and ultrasonography synovitis decreased. Inflammation on MRI and ultrasonography, especially MRI bone oedema, was predictive for erosive progression on CT, at bone/joint level and MRI bone oedema also at patient level.
Plantar sensory vibration thresholds are not influenced by body position

Abstract Monitoring skin sensitivity is studied to clarify its relationship on balance. Measuring skin sensitivity is performed when subjects are sitting or lying, whereas balance tests are measured during standing. However, afferent signal processing and subsequent efferent responses can be altered by different body positions. Therefore, this study investigated whether vibration perception thresholds (VPTs) are influenced by body positions. Sixty-six healthy subjects (41♀; 25♂) participated in this study. Five measurements of VPTs were performed at each of the three analyzed anatomical locations (heel, first metatarsal head, hallux) of the right plantar foot under two randomized conditions: during sitting and standing. The contact force applied to the probe was measured and controlled within the five trials. Contact forces between the probe and the foot were higher during standing. However, no differences in VPTs were found between conditions. This indicates that VPTs are not different during standing compared to sitting, contrary to our expectations. We conclude that higher forces did not induce increased receptor activity. Since no differences were found between thresholds, future clinical studies can implement plantar VPT tests during sitting in association with balance tests during standing.
Predictors of burnout and self -efficacy among special education teachers

Abstract Burnout and decreased levels of self-efficacy are contributors to the high attrition rate and increasing demand for highly qualified special educators nationwide. This study investigated factors that impact special education teacher burnout and self-efficacy. The results indicated that teacher stressors, emotional demands, quality of leadership, and quantitative demands were the best set of predictors of emotional exhaustion in special educators. Secondly, it was found that quantitative demands, quality of leadership, administrative support and coworker support were the best set of predictors of personal accomplishment. Finally, learning disability, school level, number of meetings with an administrator, emotional demands, role conflict, and quality of leadership were the best set of predictors of self-efficacy among special educators. Keywords: special education, burnout, self-efficacy, attrition, teacher retention
Silencing of the Mouse H-rev107 Gene Encoding a Class II Tumor Suppressor by CpG Methylation*

H-rev107 is a tumor suppressor originally isolated in revertants of H-ras-transformed cell lines. The gene is ubiquitously expressed in normal tissues but down-regulated in primary carcinomas or in many cell lines derived from tumors, including WEHI 7.1 lymphoma cells. Here, we show that unlike inH-rev107-expressing cells or tissues the 5′-end ofH-rev107 containing a CpG-rich region of 421 bp is highly methylated in WEHI 7.1 lymphoma cells, correlating with silencing of this gene. Repression of H-rev107 transcription in these cells could be relieved by chemically induced hypomethylation with 5-aza-dC. In addition, upon in vitro methylation, expression of the luciferase reporter gene driven by theH-rev107 promoter decreased by 80% in WEHI 7.1 and 293 cells. Furthermore, co-transfection of the methyl-CpG binding proteins, MeCP2 and MBD2, inhibited H-rev107 promoter activity up to 70% in SL2 cells when the promoter was methylated. By chromatin immunoprecipitation assays, we observed in vivo binding of MeCP2 and MBD2 to the 5′-end of H-rev107 in WEHI 7.1 cells, which was reduced to undetectable levels upon 5-aza-dC treatment, concluding that MeCP2 and MBD2 might be involved in silencing the methylated H-rev107 gene in lymphoma cells and probably certain tumors.
Adversarial Training and Robustness for Multiple Perturbations

Defenses against adversarial examples, such as adversarial training, are typically tailored to a single perturbation type (e.g., small $\ell_\infty$-noise). For other perturbations, these defenses offer no guarantees and, at times, even increase the model's vulnerability. Our aim is to understand the reasons underlying this robustness trade-off, and to train models that are simultaneously robust to multiple perturbation types. We prove that a trade-off in robustness to different types of $\ell_p$-bounded and spatial perturbations must exist in a natural and simple statistical setting. We corroborate our formal analysis by demonstrating similar robustness trade-offs on MNIST and CIFAR10. Building upon new multi-perturbation adversarial training schemes, and a novel efficient attack for finding $\ell_1$-bounded adversarial examples, we show that no model trained against multiple attacks achieves robustness competitive with that of models trained on each attack individually. In particular, we uncover a pernicious gradient-masking phenomenon on MNIST, which causes adversarial training with first-order $\ell_\infty, \ell_1$ and $\ell_2$ adversaries to achieve merely $50\%$ accuracy. Our results question the viability and computational scalability of extending adversarial robustness, and adversarial training, to multiple perturbation types.
Institutional Repository Prevalence of eating disorders amongst dancers : a systemic review and meta-analysis

Eating disorders in dancers are thought to be common, but the exact rates remain to be clarified. The aim of this study is to systematically compile and analyse the rates of eating disorders in dancers. A literature search, appraisal and meta-analysis were conducted. Thirty-three relevant studies were published between 1966 and 2013 with sufficient data for extraction. Primary data were extracted as raw numbers or confidence intervals. Risk ratios and 95% confidence intervals were calculated for controlled studies. The overall prevalence of eating disorders was 12.0% (16.4% for ballet dancers), 2.0% (4% for ballet dancers) for anorexia, 4.4% (2% for ballet dancers) for bulimia, and 9.5% (14.9% for ballet dancers) for EDNOS. The dancer group had higher mean scores on the EAT-26 and the EDI subscales. Dancers had a higher risk of suffering from eating disorders in general, anorexia nervosa, and EDNOS, but no higher risk of suffering from bulimia nervosa. The study concluded that as dancers had a three times higher risk of suffering from eating disorders, particularly anorexia nervosa and EDNOS, specifically designed services for this population should be considered.
Econometric Modelling of Time Series with Outlying Observations

Economies are buffeted by natural shocks, wars, policy changes, and other unanticipated events. Observed data can be subject to substantial revisions. Consequently, a correct theory can manifest serious mis-specification if just fitted to data ignoring its time-series characteristics. Modelling U.S. expenditure on food, the simplest theory implementation fails to describe the evidence. Embedding that theory in a general framework with dynamics, outliers and structural breaks and using impulse-indicator saturation, the selected model performs well, despite commencing with more variables than observations (see Doornik, 2009b), producing useful robust forecasts. Although this illustration involves a simple theory, the implications are generic and apply to sophisticated theories.
The Hypotriglyceridemic Effect of Fish Oil in Adult‐Onset Diabetes without Adverse Glucose Control a

Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat, high complex carbohydrate diet. Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation; plasma total and HDL cholesterol concentrations did not change. The LDL cholesterol level was significantly increased with fish oil supplementation, suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and/or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease. The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients.
Hypersensitivity of pulmonary chemosensitive neurons induced by activation of protease‐activated receptor‐2 in rats

This study was carried out to determine the effect of protease‐activated receptor‐2 (PAR2) activation on the pulmonary chemoreflex responses and on the sensitivity of isolated rat vagal pulmonary chemosensitive neurons. In anaesthetized, spontaneously breathing rats, intratracheal instillation of trypsin (0.8 mg ml−1, 0.1 ml), an endogenous agonist of PAR2, significantly amplified the capsaicin‐induced pulmonary chemoreflex responses. The enhanced responses were completely abolished by perineural capsaicin treatment of both cervical vagi, suggesting the involvement of pulmonary C‐fibre afferents. In patch‐clamp recording experiments, pretreatment with trypsin (0.1 μm, 2 min) potentiated the capsaicin‐induced whole‐cell inward current in isolated pulmonary sensory neurons. The potentiating effect of trypsin was mimicked by PAR2‐activating peptide (PAR2‐AP) in a concentration‐dependent manner. PAR2‐AP pretreatment (100 μm, 2 min) also markedly enhanced the acid‐evoked inward currents in these sensory neurons. Furthermore, the sensitizing effect of PAR2 was completely abolished by pretreatment with either U73122 (1 μm, 4 min), a phospholipase C inhibitor, or chelerythrine (10 μm, 4 min), a protein kinase C (PKC) inhibitor. In summary, our results have demonstrated that activation of PAR2 upregulates the pulmonary chemoreflex sensitivity in vivo and the excitability of isolated pulmonary chemosensitive neurons in vitro, and this effect of PAR2 activation was mediated through the PKC‐dependent transduction pathway. These results further suggest that the hypersensitivity of these neurons may play a part in the development of airway hyper‐responsiveness resulting from PAR2 activation.
Characterization and modeling of CMOS on-chip coupled interconnects

In this paper, an S-parameter measurement based modeling methodology is proposed for characterization of coupled interconnects on silicon substrate. First, a set of single transmission lines in ground-signal-ground configuration is measured and modeled as multiple Gamma-sections. A pair of coupled lines is then modeled as two single lines interconnected by coupling capacitance, mutual inductance and mutual resistance. Asymptotic techniques and closed-form analytical expressions are used to determine the initial guesses for optimization of the model parameters of single and coupled lines. It is found that in extending the single line model to the coupled lines, only a couple of model parameters need to change due to the proximity effect. Further, the time-domain crosstalk is measured for Cu/oxide and Cu/Ultra low-kappa interconnects and analyzed using the proposed model. Good agreement is found between the simulated and measured results in both the frequency and the time domains for different lengths, widths and spacing (for coupled-lines) confirming the accuracy of the modeling methodology. The compact modeling approach presented here facilitates accurate characterization and modeling of coupled interconnects based on measured S-parameters data.