Miracle-dz/UniFAR-FTUs huggingface dataset:
The cardiac renin-angiotensin system. An appraisal of present experimental and clinical evidence.

D uring the past two decades we have witnessed our view of the renin-angiotensin system expand in a major way. Although originally perceived as a classical humoral system in which biologically active molecules are secreted from a dedicated gland to reach their target tissues via the bloodstream, a number of observations have indicated that local renin-angiotensin systems, complete with respect to all the components of the enzymatic pathway, may reside within individual organs or tissues. The existence of these so-called tissue reninangiotensin systems, still conjectural at the beginning of the 1980s, has become much more firmly established during the past decade.1'2 We owe this, in large part, to the advent of molecular biological methods that, for the first time, allowed unequivocal confirmation of local synthesis of the elements comprising the renin-angiotensin system's catalytic cascade in a number of extrarenal tissues. In parallel, observations based primarily on the use of drugs interfering with the renin-angiotensin system have stimulated interest in the pathophysiological importance of local renin-angiotensin systems. This article will examine the evidence for, and the potential physiological and pathophysiological importance of, such a local reninangiotensin system in the heart. The remarkable effectiveness of converting enzyme inhibition in heart failure, which has brought major progress in the therapy of this common and lethal affliction, and the mounting evidence for additional cardioprotective effects of these drugs have sparked particular interest in a cardiac tissue renin-angiotensin system and its role in normal and diseased states. This year marks the fiftieth anniversary of the first demonstration of a direct interaction between the renin-angiotensin system and the heart3; since then,
ENDOTOXIN AND INTERFERON-&ggr; INHIBIT TRANSLATION IN SKELETAL MUSCLE CELLS BY STIMULATING NITRIC OXIDE SYNTHASE ACTIVITY

The purpose of the present study was to test the hypothesis that endogenous NO negatively affects translation in skeletal muscle cells after exposure to a combination of endotoxin (LPS) and interferon-&ggr; (IFN-&ggr;). Individually, LPS and IFN-&ggr; did not alter protein synthesis, but in combination, they inhibited protein synthesis by 80% in C2C12 myotubes. The combination of LPS and IFN-&ggr; dramatically downregulated the autophosphorylation of the mammalian target of rapamycin and its substrates S6K1 and 4EBP-1. The phosphorylation of ribosomal protein S6 was decreased, whereas phosphorylation of elongation factor 2 and raptor was enhanced, consistent with defects in both translation initiation and elongation. Reduced S6 phosphorylation occurred 8 to 18 h after LPS/IFN-&ggr; and coincided with a prolonged upregulation of NOS2 messenger RNA and protein. NOS2 protein expression and the LPS/IFN-&ggr;−induced fall in phosphorylated S6 were prevented by the proteasome inhibitor MG-132. The general NOS inhibitor, L-NAME, and the specific NOS2 inhibitor, 1400W, also prevented the LPS/IFN-&ggr;-induced decrease in protein synthesis and restored translational signaling. LPS/IFN-&ggr; downregulated the phosphorylation of multiple Akt substrates, including the proline-rich Akt substrate 40, while enhancing the phosphorylation of raptor on a 5&vprime;-AMP-activated kinase (AMPK)-regulated site. The negative effects of LPS/IFN-&ggr; were blunted by the AMPK inhibitor compound C. The data suggest that, in combination, LPS and IFN-&ggr; induce a prolonged expression of NOS2 and excessive production of NO that reciprocally alter Akt and AMPK activity and consequently downregulate translation via reduced mammalian target of rapamycin signaling.
The New Toad in Town: Distribution of the Asian Toad, Duttaphrynus Melanostictus, in the Toamasina Area of Eastern Madagascar

In March 2014, the Asian toad Duttaphrynus melanostictus was reported from Madagascar's second largest city and main port Toamasina, raising immediate concerns about the invasive nature of the newly introduced toad and its environmental impact should it spread throughout the island. As part of a study on the feasibility of eradication, we conducted 516 interviews and 120 visual encounter surveys between April and November 2014. We found the toad to be widespread to the south and west of city center and estimate its minimum range to include an area of at least 108 km2. Social surveys indicate that the toad may have already been present for some years and potentially introduced prior to 2010, with the site of its introduction likely south of Toamasina near National Route 2 and the Ambatovy Plant. We discuss limitations of our survey methodology, proposed improvements for future work, and the implications of our results on eradication and control measures.
Mental health impairment associated with eating-disorder features in a community sample of women

Background and Aims: Impairment in mental health associated with eating-disorder features was examined in a large, general population sample of women aged 18 to 42 years. Method: Participants (n = 5255) completed self-report measures of eating-disordered behaviour, mental health functioning, height and weight and socio-demographic information. Results: The most common eating-disorder features were extreme concerns about weight or shape (14.6%), subjective overeating (12.7%), objective overeating (10.6%) and extreme concerns about dietary intake (10.4%). In multivariable analysis, in which mental health functioning was regressed on eating-disorder features, while also controlling for age and body weight, objective overeating (β = −0.07), subjective overeating (β = −0.07), extreme dietary restriction (β = −0.06) and extreme concerns about eating (β = −0.04) showed small, but statistically significant associations with mental health impairment, whereas extreme weight or shape concerns showed a very strong association (β = −0.24). Conclusions: From a clinical perspective, the findings are consistent with the importance attached to the “over-evaluation” of weight or shape as a core component of eating-disorder psychopathology. From a public health perspective, the findings indicate the need to conceive of body dissatisfaction as a target for health promotion in its own right.
The association of concurrent vitamin D and sex hormone deficiency with bone loss and fracture risk in older men: The osteoporotic fractures in men (MrOS) study

Low 25‐hydroxyvitamin D (VitD), low sex hormones (SH), and high sex hormone binding globulin (SHBG) levels are common in older men. We tested the hypothesis that combinations of low VitD, low SH, and high SHBG would have a synergistic effect on bone mineral density (BMD), bone loss, and fracture risk in older men. Participants were a random subsample of 1468 men (mean age 74 years) from the Osteoporotic Fractures in Men Study (MrOS) plus 278 MrOS men with incident nonspine fractures studied in a case‐cohort design. “Abnormal” was defined as lowest quartile for VitD (<20 ng/mL), bioavailable testosterone (BioT, <163 ng/dL), and bioavailable estradiol (BioE, <11 pg/mL); and highest quartile for SHBG (>59 nM). Overall, 10% had isolated VitD deficiency; 40% had only low SH or high SHBG; 15% had both SH/SHBG and VitD abnormality; and 35% had no abnormality. Compared to men with all normal levels, those with both SH/SHBG and VitD abnormality tended to be older, more obese, and to report less physical activity. Isolated VitD deficiency, and low BioT with or without low VitD, was not significantly related to skeletal measures. The combination of VitD deficiency with low BioE and/or high SHBG was associated with significantly lower baseline BMD and higher annualized rates of hip bone loss than SH abnormalities alone or no abnormality. Compared to men with all normal levels, the multivariate‐adjusted hazard ratio (95% confidence interval [CI]) for incident nonspine fracture during 4.6‐year median follow‐up was 1.2 (0.8–1.8) for low VitD alone; 1.3 (0.9–1.9) for low BioE and/or high SHBG alone; and 1.6 (1.1–2.5) for low BioE/high SHBG plus low VitD. In summary, adverse skeletal effects of low sex steroid levels were more pronounced in older men with low VitD levels. The presence of low VitD in the presence of low BioE/high SHBG may contribute substantially to poor skeletal health. © 2012 American Society for Bone and Mineral Research.
A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group.

BACKGROUND Valproate is approved for use primarily in patients with absence seizures, but the drug has a broad spectrum of activity against seizures of all types. Partial or secondarily generalized tonic-clonic seizures are often difficult to control adequately with standard treatment, usually carbamazepine or phenytoin. METHODS We conducted a multicenter, double-blind trial that compared valproate with carbamazepine in the treatment of 480 adults with complex partial seizures (206 patients) or secondarily generalized tonic-clonic seizures (274 patients). The patients were randomly assigned to treatment with carbamazepine or divalproex sodium (valproate) at doses adjusted to achieve blood levels in the middle of the therapeutic range. Patients were followed for one to five years or until seizures became uncontrollable, treatment had unacceptable adverse effects, or both these events occurred. RESULTS For the control of secondarily generalized tonic-clonic seizures, carbamazepine and valproate were comparably effective (in 136 patients and 138 patients, respectively). For complex partial seizures, four of five outcome measures favored carbamazepine (100 patients) over valproate (106 patients): the total number of seizures (2.7 vs. 7.6, P = 0.05), the number of seizures per month (0.9 vs. 2.2, P = 0.01), the time to the first seizure (P less than 0.02), and the seizure-rating score (P = 0.04). Carbamazepine was also superior according to a composite score that combined scores for the control of seizures and for adverse effects (P less than 0.001). Valproate was associated more frequently than carbamazepine with a weight gain of more than 5.5 kg (12 lb) (20 percent vs. 8 percent, P less than 0.001), with hair loss or change in texture (12 percent vs. 6 percent, P = 0.02), and with tremor (45 percent vs. 22 percent, P less than 0.001). Rash was more often associated with carbamazepine (11 percent vs. 1 percent, P less than 0.001). CONCLUSIONS Valproate is as effective as carbamazepine for the treatment of generalized tonic-clonic seizures, but carbamazepine provides better control of complex partial seizures and has fewer long-term adverse effects.
New therapeutic strategies for the treatment and prevention of head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy that is now the sixth most common neoplasm in the world today. Approximately 50,000 cases in the United States and more than 500,000 cases worldwide will be diagnosed in 2000 [1]. Despite numerous advances in treatment utilising the most recent protocols for surgery, radiation and chemotherapy, the long-term survival has remained at less than 50% over the past 40 years [2]. This poor long-term survival is due to a number of variables including delayed diagnosis as well as the frequent development of multiple primary tumours. Therefore, in addition to early detection, continued emphasis must be placed on preventing the development of new primaries as well as establishing more effective treatments for individuals who present with advanced disease. This review will summarise some of the recent advances in the realms of chemotherapy and radiation therapy. In addition, it will discuss the present status of chemoprevention in HNSCC. Finally, we will discuss the rationale for the use of anti-angiogenic agents as one possible means of developing new chemopreventive protocols that result in reduced toxicity while maintaining similar clinical efficacies.
Otimizaçao de Métodos Analíticos Usando Metodologia de Superfícies De Resposta - Parte I: Variáveis de Processo

O presente artigo aborda a aplicacao de metodologia de superficies de resposta (MSR) na otimizacao de variaveis para o desenvolvimento de metodos analiticos. Alguns principios basicos desse metodo multivariado sao apresentados e as caracteristicas dos principais planejamentos experimentais sao discutidas. Exemplos de aplicacoes da MSR na otimizacao de metodos analiticos sao tambem apresentados para ilustrar as potencialidades dessas ferramentas quimiometricas.
Detection of fault-prone program modules in a very large telecommunications system

Telecommunications software is known for its high reliability. Society has become so accustomed to reliable telecommunications, that failures can cause major disruptions. This is an experience report on application of discriminant analysis based on 20 static software product metrics, to identify fault prone modules in a large telecommunications system, so that reliability may be improved. We analyzed a sample of 2000 modules representing about 1.3 million lines of code, drawn from a much larger system. Sample modules were randomly divided into a fit data set and a test data set. We simulated utilization of the fitted model with the test data set. We found that identifying new modules and changed modules mere significant components of the discriminant model, and improved its performance. The results demonstrate that data on module reuse is a valuable input to quality models and that discriminant analysis can be a useful tool in early identification of fault prone software modules in large telecommunications systems. Model results could be used to identify those modules that would probably benefit from extra attention, and thus, reduce the risk of unexpected problems with those modules.
Identification of Cytokinin-Responsive Genes Using Microarray Meta-Analysis and RNA-Seq in Arabidopsis1[C][W][OA]

Meta-analysis of cytokinin-regulated gene expression across multiple transcriptome studies identifies the transcriptional changes occurring in response to cytokinin. Cytokinins are N6-substituted adenine derivatives that play diverse roles in plant growth and development. We sought to define a robust set of genes regulated by cytokinin as well as to query the response of genes not represented on microarrays. To this end, we performed a meta-analysis of microarray data from a variety of cytokinin-treated samples and used RNA-seq to examine cytokinin-regulated gene expression in Arabidopsis (Arabidopsis thaliana). Microarray meta-analysis using 13 microarray experiments combined with empirically defined filtering criteria identified a set of 226 genes differentially regulated by cytokinin, a subset of which has previously been validated by other methods. RNA-seq validated about 73% of the up-regulated genes identified by this meta-analysis. In silico promoter analysis indicated an overrepresentation of type-B Arabidopsis response regulator binding elements, consistent with the role of type-B Arabidopsis response regulators as primary mediators of cytokinin-responsive gene expression. RNA-seq analysis identified 73 cytokinin-regulated genes that were not represented on the ATH1 microarray. Representative genes were verified using quantitative reverse transcription-polymerase chain reaction and NanoString analysis. Analysis of the genes identified reveals a substantial effect of cytokinin on genes encoding proteins involved in secondary metabolism, particularly those acting in flavonoid and phenylpropanoid biosynthesis, as well as in the regulation of redox state of the cell, particularly a set of glutaredoxin genes. Novel splicing events were found in members of some gene families that are known to play a role in cytokinin signaling or metabolism. The genes identified in this analysis represent a robust set of cytokinin-responsive genes that are useful in the analysis of cytokinin function in plants.
Immune-adherence test for syphilis; comparison with TPI and VDRL slide tests.

A REACTION between human erythrocytes and treponemes sensitized by antibody from syphilitic serum was first described by R. A. Nelson, Jr. (1, 2). In a later report (3) it was stated that "The specificity of this reaction for antibody in syphilis serum was established by examination of three hundred eighty-five (385) human sera. " This report also stated that the results of this test, referred to as the immune-adherence phenomenon or reaction, "corresponded with the clinical diagnosis of syphilis and with the results of the TPI test [Treponema pallidunm immobilization] in all except five (5) instances. " Since the immune-adherence reaction is technically a much simpler procedure than the TPI test and therefore would be a desirable substi-
2 Crosstalk Coregulation Mechanisms of G Protein-Coupled Receptors and Receptor Tyrosine Kinases

G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) are transmembrane receptors that initiate intracellular signaling cascades in response to a diverse array of ligands. Recent studies have shown that signal transduction initiated by GPCRs and RTKs is not organized in distinct signaling cassettes where receptor activation leads to cell division and gene transcription in a linear manner. In fact, signal integration and diversification arises from a complex network involving crosscommunication between separate signaling units. Several different styles of crosstalk between GPCRand RTKinitiated pathways exist, with GPCRs or components of GPCR-induced pathways being either upstream or downstream of RTKs. Activation of GPCRs sometimes results in a phenomenon known as “transactivation” of RTKs, which leads to the recruitment of scaffold proteins, such as Shc, Grb2, and Sos in addition to mitogen-activated protein kinase activation. In other cases, RTKs use different components of GPCR-mediated signaling, such as β-arrestin, G protein-receptor kinases, and regulator of G protein signaling to integrate signaling pathways. This chapter outlines some of the more common mechanisms used by both GPCRs and RTKs to initiate intracellular crosstalk, thereby creating a complex signaling network that is important to normal development.
Fetal ethanol exposure during pregnancy – how big is the problem and how do we fix it?

In this issue of Acta Paediatrica, Taisto Sarkola and collaborators describe and discuss risk markers of child maltreatment in connection with parental alcohol/substance abuse in Finland. They identify an array of factors associated with increased risk of out-of-home custody care of the child. One inescapable impression of their study is that the severity of the parental addiction, together with the accompanying social consequences of the addiction, distinctly determines the risk for out-of-home care of the child. The question why and when children have to be removed from their alcohol-abusing parent(s) has thus been clearly answered by the Finnish authors with respect to paternal/environmental factors. To fully comprehend the situation in the families with parental alcohol/substance abuse we also need to know the influence of the compromised intrauterine development on the children, i.e. extent of ethanol-induced developmental damage and its consequences. In other words, we may inquire how much does the occurrence and severity of FAS (Fetal Alcohol Syndrome) or FASD (Fetal Alcohol Spectrum Disorder) in the child affect the life of that child, as well as the whole family? What is the importance of FAS/FASD? This is the problem. We need to understand the nature and magnitude of the FAS/FASD influence on the child and its environment. We therefore need knowledge of the FAS/FASD psychological and biological effects on the child, and we need knowledge of the actual occurrence of FAS/FASD in the community, now and in the future.
Ability of Deutan Color Defectives to Perform Simulated Air Traffic Control Tasks

ABSTRACT Air traffic controllers perform a variety of tasks which require them to identify, discriminate, and name colors. Qualification standards for this occupation require applicants and incumbents to have normal color vision. The validity of this standard has been questioned and is currently under review. In this study, 22 deutans and 78 normals were tested on a set of tasks which simulated critical tasks performed daily by air traffic controllers. The four tasks included discriminating red from black pencil marks on flight progress strips, color‐naming of 1° and 0.1° discs, and identification of colored line segments embedded in a multicolored background. Deutans classified as mild were found to perform all tasks as well as normals. Moderate deutans performed only the large disc color‐naming task as well as normals, whereas severe deutans performed none of the tasks as well as normals. Different methods for scoring the color vision tests were explored to determine their value as predictors of task performance. The D‐15 relative error score was found to be the single best predictor of performance on the tasks (r‐square = 0.602). It is concluded that mild deutan color defectives have adequate color vision for safe performance of several critical air traffic control tasks. Moderate and severe deutans do not. In addition, the results of several methods for scoring color vision tests can be used to predict group, but not individual, performance with high reliability.
Discriminability measures for predicting readability

Several discriminability measures were correlated with reading sped over a range of screen backgrounds. Reading speed was measured using a search task in which observers tried to find one of three works in a short paragraph of black text. There were four background patterns combined with three colors at two intensities. The text contrast had a small positive correlation with speed. Background RMS contrast showed a stronger, negative correlation. Text energy in the spatial frequency bands corresponding to lines and letters also showed strong relationships. A general procedure for constructing a masking index from an image discrimination model is described and used to generate two examples indices: a global masking index, based on a single filter model combining text contrast and background RMS contrast, and a spatial-frequency-selective masking index. These indices did not lead to better correlations than those of the RMS measures alone, but they should lead to better correlations when there are larger variations in text contrast and masking patterns.