Miracle-dz/UniFAR-FTUs huggingface dataset:
Brazilian Network for HIV Drug Resistance Surveillance (HIV-BResNet): a survey of chronically infected individuals

Objective: To study the prevalence of HIV drug resistance mutations and subtype distribution in a Brazilian drug-naive population. Asymptomatic, drug-naive HIV-1-infected individuals were targeted in 13 voluntary counseling and testing centers spread around the country. Methods: Plasma viral RNA was extracted from 535 HIV-1-positive subjects. Protease (PR) and reverse transcriptase (RT) genomic regions were sequenced for subtype determination and analysis of drug resistance mutations. Results: Eight samples (2.24 %) showed primary mutations related to protease inhibitor (PI) resistance, eight (2.36%) to nucleoside reverse transcriptase inhibitors (NRTI) and seven (2.06%) to non-nucleoside reverse transcriptase inhibitors (NNRTI). Accessory mutations were found in the PR gene at the following positions: L63P/V/T/A/I [153/345 (44.3%)], M36I/L [149/345 (43.2%)], L10I/F/V [82/345 (23.8%)], V77I [60/345 (17.4%)], A71V/T [11/345 (3.2%)], K20M/R [10/345 (2.9%)], and V82I [4/345 (1.2%)]. Mutations known to be associated with reduced sensitivity to NRTI or NNRTI (V118I, E44D, K219R, T69A, and V75L) were found in a low prevalence (0.6–2.4%). A high proportion of the isolates from subtype C was found in the southern states. Subtype F-related viruses were the main non-B variant in the rest of the country. Conclusions: Brazil has a low prevalence of drug-resistant strains circulating among recently diagnosed individuals. However, there was an increase in these rates compared with similar studies performed with samples collected in Brazil from 1996 to 1998. Continued surveys are required to detect trends in these rates, but routine genotypic testing in the drug-naive population prior to antiretroviral initiation is not required in Brazil.
Familial 16q24.3 microdeletion involving ANKRD11 causes a KBG‐like syndrome

Haploinsufficiency of ANKRD11 encoding ankyrin repeat domain‐containing protein 11 was recently reported as the cause of a syndrome due to microdeletion, characterized by intellectual disability with minor facial anomalies and short stature. Most recently, intragenic mutations of ANKRD11 were found in a cohort of patients with KBG syndrome. KBG is an autosomal dominant intellectual disability syndrome characterized by short stature, characteristic facial appearance, macrodontia, and skeletal anomalies. It remains unknown if deletion of the entire ANKRD11 causes KBG syndrome. We present a mother and child with a heterozygous 365 Kb deletion at 16q24.3 containing ANKRD11, ZNF778, and SPG7 genes. The child presented with developmental delay, facial anomalies, hand anomalies, and a congenital heart defect. The mother has short stature, facial anomalies, macrodontia, hand anomalies, and learning disability. Both individuals had many findings reported in KBG syndrome and the family met the suggested diagnostic criteria. However, typical macrodontia with fused incisors, costovertebral anomalies, and delayed bone age were not present. We conclude that microdeletions involving ANKRD11 result in a phenotype similar to that of KBG syndrome. © 2012 Wiley Periodicals, Inc.
Moment-SOS Approach to Interval Power Flow

Intermittent renewable sources and market-driven operation have brought many uncertainties into modern power systems. Power flow analysis tools are expected to be able to incorporate uncertainties into the solution process. Interval power flow (IPF) analysis which aims at obtaining the upper and lower bounds of power flow solutions under interval uncertainties, thereby emerges as a promising framework to meet such expectation. This paper describes a novel optimization-based method to obtain high-accuracy or even exact global solutions to IPF problems. At first, the IPF problems are formulated as polynomial optimization problems probably with rational objective functions. Then Lasserre's hierarchy, or moment-SOS approach, is introduced to relax the non-convex problems to convex semidefinite programming (SDP) problems. Correlative sparsity in the polynomial optimization problems is exploited to improve numerical tractability and efficiency. Finally, case studies on IEEE 6-bus, 9-bus and 14-bus systems demonstrate the second-order moment relaxation is capable of obtaining exact global interval solutions on small-scale systems, and numerical results on IEEE 57-bus, 118-bus and 300-bus systems show the proposed method can significantly improve the interval solutions compared with recent Linear Programming (LP) relaxation method on larger systems.
The Isolated N-terminal Domain of the Glucagon-like Peptide-1 (GLP-1) Receptor Binds Exendin Peptides with Much Higher Affinity than GLP-1*

Two fragments of the receptor for glucagon-like peptide-1 (GLP-1), each containing the N-terminal domain, were expressed and characterized in either bacterial or mammalian cells. The first fragment, rNT-TM1, included the N-terminal domain and first transmembrane helix and was stably expressed in the membrane of human embryonic kidney 293 cells. The second, 6H-rNT, consisted of only the N-terminal domain of the receptor fused with a polyhistidine tag at its N terminus. The latter fragment was expressed in Escherichia coli in the form of inclusion bodies from which the protein was subsequently purified and refolded in vitro. Although both receptor fragments displayed negligible 125I-labeled GLP-1(7–36)amide-specific binding, they both displayed high affinity for the radiolabeled peptide antagonist125I-exendin-4(9–39). Competition binding studies demonstrated that the N-terminal domain of the GLP-1 receptor maintains high affinity for the agonist exendin-4 as well as the antagonists exendin-4(3–39) and exendin-4(9–39) whereas, in contrast, GLP-1 affinity was greatly reduced. This study shows that although the exendin antagonists are not dependent upon the extracellular loops and transmembrane helices for maintaining their normal high affinity binding, the endogenous agonist GLP-1 requires regions outside of the N-terminal domain. Hence, distinct structural features in exendin-4, between residues 9 and 39, provide additional affinity for the N-terminal domain of the receptor. These data are consistent with a model for the binding of peptide ligands to the GLP-1 receptor in which the central and C-terminal regions of the peptides bind to the N terminus of the receptor, whereas the N-terminal residues of peptide agonists interact with the extracellular loops and transmembrane helices.
The effect of syringe size on the performance of an infusion pump

This study investigated the effect of using three different sized syringes on the accuracy of fluid delivery when using an infusion pump at low infusion rates (1 ml·h−1). The study also measured the influence of the syringe size on the time to occlusion alarm, and on the size of the subsequent bolus dose that might be infused after relief of the occlusion which triggered the alarm. The use of a larger size syringe was found not to affect the accuracy of infusate delivery, but delayed the time to occlusion alarm and increased the size of the postocclusion bolus dose.
Phylogeny and Polymorphism in the Long Control Region, E6, and L1 of Human Papillomavirus Types 53, 56, and 66 in Central Brazil

Introduction: Several studies related that different human papillomavirus (HPV) types and intratype variants can present different oncogenic potential. In opposite to HPVs 16 and 18 variants, information about variants of other carcinogenic HPV types is still scarce. The aim of this study was to investigate the genetic variability of HPVs 53, 56, and 66 from Central Brazil isolates. Methods: The long control region (LCR), E6, and L1 genomic regions were amplified and sequenced. We evaluate for nucleotide variations in relation to the reference sequence of each HPV type and also the conservation of physicochemical properties of the deduced amino acid substitutions. In silico analysis was performed to locate binding sites for transcriptional factors within the LCR. Moreover, we performed a phylogenetic analysis with the Central Brazilian and worldwide sequences available at genomic databases. Results: Gathering LCR, E6, and L1 genomic regions, the highest genetic variability was found among HPV-53 isolates with 52 nucleotide variations, followed by HPVs 56 and 66 with 24 and 16 nucleotide substitutions, respectively. The genetic analysis revealed 11 new molecular variants of all HPV types analyzed, totalizing 31 new nucleotide and 3 new amino acid variations. Eight nonconservative amino acid substitutions were detected, which may indicate a biological and pathogenic diversity among HPV types. Furthermore, 8 nucleotide substitutions were localized at putative binding sites for transcription factors in the LCR with a potential implication on viral oncogene expression. The HPVs 53, 56, and 66 phylogenetic analysis confirmed a dichotomic division only described to HPV subtypes and different from the patterns described for HPVs 16 and 18 variants. Conclusions: The high genetic variability observed emphasizes the importance of investigating polymorphisms in types other than HPVs 16 or 18 to better understand the molecular genomic profile of viral infection by different HPV types.
Plakophilins in Desmosomal Adhesion and Signaling

Abstract The regulation of adhesion and growth is important for epithelial function and dysfunction. β-catenin (armadillo in Drosophila) is the prototype of a multifunctional molecule that regulates cell adhesion via adherens junctions and cell signaling via LEF/TCF transcription factors. Desmosomal armadillo proteins comprise plakoglobin and the plakophilins 1, 2, and 3. These proteins are essential for building up the desmosome and linking the desmosomal cadherins to keratin filaments. High expression of plakophilins in desmosomes correlates with strong intercellular cohesion and is essential for tissue integrity under mechanical stress. However, like β-catenin, these proteins have diverse non-desmosomal functions, for example, in regulating actin organization, protein synthesis, and growth control. In line with these functions, their de-regulated expression with up- as well as down-regulation has been connected to cancer and metastasis. Now, recent evidence sheds light on the post-translational regulation and provides an explanation for how de-regulation of plakophilins can contribute to cancer.
In Vitro Relative Toxicity Screening of Combined Particulate and semivolatile Organic Fractions of Gasoline and Diesel Engine Emissions

Engine technology modifications designed to reduce engine emissions are likely to alter the physicochemical characteristics of the emissions. These changes may alter the biological effects of the emissions, but these effects cannot currently be predicted from the physical and chemical properties. Rapid in vitro toxicity screening techniques to compare the biological effects of emission samples would be useful as preliminary guides to assess the relative health impact of modified technology. Here, we demonstrate that selected responses of cultured human lung epithelial cells and rat alveolar macrophages can discriminate among combined particulate matter (PM) and semivolatile organic compound (SVOC) fractions of emissions collected from normal- and high-emitter, in-use gasoline and diesel vehicles. Macrophages were more susceptible to cytotoxicity than epithelial cells. Samples from gasoline vehicles (except a vehicle that produced visible white smoke) generally caused greater effects than the diesel engine samples. However, low concentrations of diesel emission samples were more potent stimulators of peroxide production than gasoline emission samples. The same rank order of potency applied to suppression of this response at high concentrations. A diesel PM fraction was much less toxic to both types of cells than the combined PM + SVOC fractions, consistent with a role for the SVOC fraction in cytotoxicity. However, the rank order of potency from the in vitro assays in general did not correspond with the previous rankings from in vivo comparisons of the same samples. Thus, while the in vitro assays may provide mechanistic in formation, revealing cel1 type–specific responses, they did not accurately reflect in vivo comparative toxicity in their current form.
Regulation and function of miRNA-21 in health and disease

The small regulatory RNA microRNA-21 (miR-21) plays a crucial role in a plethora of biological functions and diseases including development, cancer, cardiovascular diseases and inflammation. The gene coding for pri-miR-21 (primary transcript containing miR-21) is located within the intronic region of the TMEM49 gene. Despite pri-miR-21 and TMEM49 are overlapping genes in the same direction of transcription, pri-miR-21 is independently transcribed by its own promoter regions and terminated with its own poly(A) tail. After transcription, primiR- 21 is finally processed into mature miR-21. Expression of miR-21 has been found to be deregulated in almost all types of cancers and therefore was classified as an oncomiR. During recent years, additional roles of miR-21 in cardiovascular and pulmonary diseases, including cardiac and pulmonary fibrosis as well as myocardial infarction have been described. MiR-21 additionally regulates various immunological and developmental processes. Due to the critical functions of its target proteins in various signaling pathways, miR-21 has become an attractive target for genetic and pharmacological modulation in various disease conditions.
Versatility of the Posterior Auricular Flap in Partial Ear Reconstruction

Background: The posterior auricular flap alone has always been popular because of its prompt availability, its rich vascularity, and the ease of closing the donor-site defect primarily. Methods: Fifty-seven patients with partial ear defects covered with posterior auricular flaps during the period between 2002 and 2007 were reviewed. In the authors' series, posterior auricular flaps were harvested based on a simple random vascularization and tailored to reach almost any defect of the ear by a simplified and standardized approach. Results: The authors propose a simple nomenclature after grouping the flaps according to skin paddle type, pedicle type, pedicle base, flap transfer method, and flap movement; they present a standardized algorithm with which to choose the flap design for a given defect from this group. Conclusions: The authors contribute three new flap designs to enhance the versatility of the posterior auricular flap. These are the superiorly and inferiorly based twisted island flaps and the posterior auricular propeller flap.
Susceptibility to verotoxin as a function of the cell cycle

Infection with Verotoxin producing Escherichia coli (VTEC) has been implicated in hemolytic uremic syndrome, the leading cause of pediatric renal failure. Verotoxin (VT) binds to globotriaosylceramide (Galα1–4Galβ1–4GlcCer Gb3) in susceptible cells. Gb3 is required for cytotoxicity and toxin‐resistant cells deficient in Gb3 can be sensitized to VT cytotoxicity by incorporation of exogenous Gb3 into the cells. However, the absolute Gb3 content of cell lines does not necessarily correspond directly with the degree of sensitivity to VT. The present study demonstrates that susceptibility to VT is a function of cell growth and that stationary phase cells are resistant to VT. Using chemically synchronized Vero cells, we have also found a tenfold difference in susceptibility to VT during the cell cycle. Our experiments define a maximal sensitivity “window” of 1–2 hours from the G1/S boundary. This corresponds to increased VT binding without change in overall Gb3 content. Cell surface labelling indicated that cyclic turnover and exposure of Gb3 may be the critical parameter in determining VT sensitivity. Such changes during the cell cycle may also be of relevance in vivo in determining toxin pathology during VTEC infections and the physiology of plasma membrane Gb3.
The need for comprehensive educational osteoporosis prevention programs for young women: results from a second osteoporosis prevention survey.

OBJECTIVE To assess osteoporosis knowledge, beliefs, and preventive behaviors among young adult women and to identify sources that they would mostly likely utilize to learn more about the disease. METHODS Information was gathered through a cross-sectional survey of 321 women (mean age 21.6 years; 63.5% were white, 29.2% were black) enrolled in a required undergraduate health course at a southeastern state university. RESULTS Two hundred seventy-seven (86%) of the survey participants had heard about osteoporosis, but only 3.8% of respondents reported getting both adequate exercise and the recommended 1,200 mg of calcium per day. Respondents believed that they were unlikely to develop osteoporosis and that osteoporosis is less serious than other common causes of morbidity and mortality in women, such as heart disease and breast cancer (P < 0.0001). Brochures, magazines, and short counseling sessions were preferred information sources for learning about osteoporosis. CONCLUSIONS. The majority of young women studied are at risk for developing premature osteoporosis. They prefer brochures, magazines, and short counseling sessions during medical office visits to learn about osteoporosis.
Normal Development of the Muscular Region of the Interventricular Septum. II. The Importance of Myocardial Proliferation

In a first paper, we concluded that the muscular region of the interventricular septum is developed by the trabecular branches and showed evidence that the developing interventricular septum elongates in a direction opposite to that of atria. Nevertheless, to date the literature is lacking precise information on the importance of myocardial proliferation not only in this process but also in the morphogenesis of the ventricular cavities. The aim of this study was to determine the spatial and temporal distribution of high‐intensity foci of cycling myocytes in the ventricular region of the heart of chicken embryos during cardiac septation. Histological studies, detection of the proliferating cell nuclear antigen by light and confocal microscopy and flow cytometric analysis were carried out. The results corroborate that the developing interventricular septum grows in a direction opposite to that of atria. A remoulding mechanism that results in fenestrated trabecular sheets and trabecular branching is discussed. Our findings allowed us to summarize the normal morphogenesis of the muscular region of the interventricular septum in a way that is different from that suggested by other researchers.
Estimation of population coverage in the 1990 United States census based on demographic analysis.

"This article presents estimates of net coverage of the national population in the 1990 [U.S.] census, based on the method of demographic analysis. The general techniques of demographic analysis as an analytic tool for coverage measurement are discussed, including use of the demographic accounting equation, data components, and strengths and limitations of the method. Patterns of coverage displayed by the 1990 estimates are described, along with similarities or differences from comparable demographic estimates for previous censuses.A final section presents the results of the first statistical assessment of the uncertainty in the demographic coverage estimates for 1990. " Comments by Clifford C. Clogg and Christine L. Himes (pp. 1,072-4) and Jeffrey S. Passel (pp. 1,074-7) and a rejoinder by the authors (pp. 1,077-9) are included.
Regulation of Nuclear Positioning and Dynamics of the Silent Mating Type Loci by the Yeast Ku70/Ku80 Complex

ABSTRACT We have examined the hypothesis that the highly selective recombination of an active mating type locus (MAT) with either HMLα or HMRa is facilitated by the spatial positioning of relevant sequences within the budding yeast (Saccharomyces cerevisiae) nucleus. However, both position relative to the nuclear envelope (NE) and the subnuclear mobility of fluorescently tagged MAT, HML, or HMR loci are largely identical in haploid a and α cells. Irrespective of mating type, the expressed MAT locus is highly mobile within the nuclear lumen, while silent loci move less and are found preferentially near the NE. The perinuclear positions of HMR and HML are strongly compromised in strains lacking the Silent information regulator, Sir4. However, HMLα, unlike HMRa and most telomeres, shows increased NE association in a strain lacking yeast Ku70 (yKu70). Intriguingly, we find that the yKu complex is associated with HML and HMR sequences in a mating-type-specific manner. Its abundance decreases at the HMLα donor locus and increases transiently at MATa following DSB induction. Our data suggest that mating-type-specific binding of yKu to HMLα creates a local chromatin structure competent for recombination, which cooperates with the recombination enhancer to direct donor choice for gene conversion of the MATa locus.
Rethinking diabetes care in Canada

In a study published last year in Canadian Family Physician , Harris and associates[1][1] found evidence that many Canadians with diabetes are not being monitored appropriately: 16% had not had their glycosylated hemoglobin (A1C) level tested in the preceding year, 85% had not been assessed for
Measuring innovation around the world

Research on corporate innovation often focuses on firms with positive US patent activity and reported R&D, thereby excluding over 90% of the firms in Compustat. By exploiting data from 30 global patent offices, we investigate the nature of missing innovation data in the US and around the world. Our central research question is how studies of innovation, or those that rely on measures of innovation as a control variable, should assess firms without reported R&D or patent activity. Our preliminary analyses indicate systematic and predictable patterns across firms and countries for missing patents and R&D. We then compare the empirical efficacy of excluding firms without US patents or without reported R&D to simple replacement methods, and to various econometric solutions for missing innovation data. We show how excluding or deleting firms without US patents or reported R&D, even in studies of just US firms, provides biased coefficient estimates and standard errors. We also demonstrate how the biases from simply excluding the missing observations lead to specific distortions in tests related to corporate growth and country level innovation capacity. We then discuss best practices and provide specific guidelines in handling missing R&D and patent data.
XIAP downregulation accompanies mebendazole growth inhibition in melanoma xenografts

Mebendazole (MBZ) was identified as a promising therapeutic on the basis of its ability to induce apoptosis in melanoma cell lines through a B-cell lymphoma 2 (BCL2)-dependent mechanism. We now show that in a human xenograft melanoma model, oral MBZ is as effective as the current standard of care temozolomide in reducing tumor growth. Inhibition of melanoma growth in vivo is accompanied by phosphorylation of BCL2 and decreased levels of X-linked inhibitor of apoptosis (XIAP). Reduced expression of XIAP on treatment with MBZ is partially mediated by its proteasomal degradation. Furthermore, exposure of melanoma cells to MBZ promotes the interaction of SMAC/DIABLO with XIAP, thereby alleviating XIAP’s inhibition on apoptosis. XIAP expression on exposure to MBZ is indicative of sensitivity to MBZ as MBZ-resistant cells do not show reduced levels of XIAP after treatment. Resistance to MBZ can be reversed partially by siRNA knockdown of cellular levels of XIAP. Our data indicate that MBZ is a promising antimelanoma agent on the basis of its effects on key antiapoptotic proteins.