Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct Interaction of the Cell Division Cycle 37 Homolog Inhibits Endothelial Nitric Oxide Synthase Activity

Endothelial NO synthase (eNOS) via the production of NO in the endothelium plays a key role in cardiovascular biology and is tightly regulated by co- and posttranslational mechanisms, phosphorylation, and protein–protein interactions. The cell division cycle 37 homolog (Cdc37) is a key heat shock protein 90 (Hsp90) cochaperone for protein kinase clients, and Akt/Hsp90 interaction is dependent on Cdc37. Because both Hsp90 and Akt are key eNOS regulatory proteins, we hypothesized that Cdc37 interacts with eNOS as part of the regulatory complex. In the present study, we demonstrate by coimmunoprecipitation and affinity purification in bovine aortic endothelial cells (BAECs) that Cdc37 is complexed with eNOS, Hsp90, and Akt. In addition, cell fractionation data indicate that Cdc37 is found in caveolae with eNOS. Further analysis by in vitro binding assays reveals a direct interaction between purified Cdc37 and eNOS. Incubation of purified Cdc37 with purified wild-type eNOS decreases eNOS activity in vitro. Overexpression of wild-type Cdc37 in BAECs inhibits eNOS activity and NO release, whereas overexpression of S13A-Cdc37 mutant in BAECs increases eNOS activity and NO release. Taken together, these data suggest that Cdc37 has a direct regulatory interaction with eNOS and may play an important role in mediating the eNOS protein complex formation as well as subsequent eNOS phosphorylation and activation.
Comparative Study of Extracellular Vesicles from the Urine of Healthy Individuals and Prostate Cancer Patients

Recent studies suggest that extracellular vesicles may be the key to timely diagnosis and monitoring of genito-urological malignancies. In this study we investigated the composition and content of extracellular vesicles found in the urine of healthy donors and prostate cancer patients. Urine of 14 PCa patients and 20 healthy volunteers was clarified by low-speed centrifugation and total extracellular vesicles fraction was obtain by high-speed centrifugation. The exosome-enriched fraction was obtained by filtration of total extracellular vesicles through a 0.1 μm pore filter. Transmission electron microscopy showed that cell-free urine in both groups contained vesicles from 20 to 230 nm. Immunogold staining after ultrafiltration demonstrated that 95% and 90% of extracellular vesicles in healthy individuals and cancer patients, respectively, were exosomes. Protein, DNA and RNA concentrations as well as size distribution of extracellular vesicles in both fractions were analyzed. Only 75% of the total protein content of extracellular vesicles was associated with exosomes which amounted to 90–95% of all vesicles. Median DNA concentrations in total extracellular vesicles and exosome-enriched fractions were 18 pg/ml and 2.6 pg/ml urine, correspondingly. Urine extracellular vesicles carried a population of RNA molecules 25 nt to 200 nt in concentration of no more than 290 pg/ml of urine. Additionally, concentrations of miR-19b, miR-25, miR-125b, and miR-205 were quantified by qRT-PCR. MiRNAs were shown to be differently distributed between different fractions of extracellular vesicles. Detection of miR-19b versus miR-16 in total vesicles and exosome-enriched fractions achieved 100%/93% and 95%/79% specificity/sensitivity in distinguishing cancer patients from healthy individuals, respectively, demonstrating the diagnostic value of urine extracellular vesicles.
Compressible Placing of Dummy Elements in Nano-Scale VLSI Layout

Multilevel discretization on quadtree base for dummy elements placing in nano-scale VLSI layout is proposed. The placing results are covered by simplest data type of GDSII and OASIS standard, which provides the data compression. The resulting placing of dummy elements is dense and uniform that improves the surface plain of dielectric.
Modeling gene-regulatory networks using evolutionary algorithms and distributed computing

Living organisms regulate the expression of genes using complex interactions of transcription factors, messenger RNA and active protein products. Due to their complexity, gene-regulatory networks are not fully understood, however, various modeling approaches can he used to gain insight into their function and operation. This paper describes an ongoing study to use evolutionary algorithms to create computational models of gene-regulatory networks based on observed microarray data. Because of the computational requirements of this approach (which requires the discovery of gene network topologies), it is critical that it is implemented on a computing platform capable of delivering significant compute power. We discuss how this can be achieved using distributed and grid computing technology. In particular we investigate how Condor and JavaSpaces technology is suited to the requirements of our modeling approach.
Muscle composition and its relation to sprint running in the lizard Dipsosaurus dorsalis.

Iguanid lizards exhibit considerable intraspecific variation in several aspects of their muscle composition. To determine the relationship of this variation to the variation in locomotor performance, running speeds of 20 male desert iguanas (Dipsosaurus dorsalis) of similar mass were measured from video recordings of animals as they sprinted down a 4.9-m runway maintained at 40 degrees C, the preferred body temperature of Dipsosaurus. Mean sprint speed ranged from 2.2 to 4.2 m/s. Selected muscles from these animals were then analyzed histochemically for fiber type size and composition, and the activities of citrate synthase, pyruvate kinase, and creatine kinase were measured. Muscle fiber cross-sectional areas were highly correlated within individuals, in three leg muscles and across all three fiber types, so that individuals could be characterized as possessing large or small fibers relative to the sample mean. Activities of all three enzymes also covaried within individuals so that individual lizards could be characterized as possessing high or low leg muscle catabolic capacity. There existed a significant and inverse relationship between fiber cross-sectional areas and muscle enzyme activities so that individuals with small muscle fibers tended to have higher catabolic capacities. Approximately 25-30% of the variation in mean sprint running speed could be predicted by variation in muscle fiber areas alone. The use of muscle fiber areas and snout vent length as independent variables in a multiple-regression equation explained approximately 50% of the sprint-running variation. (ABSTRACT TRUNCATED AT 250 WORDS)
Sensor Placement for Improved Robotic Navigation

Consider a set of fixed sensors used to estimate the state of a vehicle (e.g. position, orientation and velocity) while it attempts to follow a pre-planned trajectory. Since the sensor can only provide a measurement to the vehicle when it is within range, the deployment of the sensors will have a major impact on the ability of the vehicle to follow the trajectory. The problem addressed here is to optimally place the sensors in the environment such that the weighted function of the estimation error at each time-step is minimized. An optimization formulation is proposed that accounts for the uncertainty of the vehicle’s state in determining whether it can receive a measurement from a sensor. A confidence level is introduced as a tuning parameter that controls the conservativeness of the solution. Consequently, the resulting solution increases the likelihood of the vehicle successfully following its intended trajectory. Finally, due to the interdependence between the sensors’ positions, a novel incremental optimization algorithm is presented which significantly outperforms a standard nonlinear optimization procedure. Experimental and simulation results are shown which characterize the performance of the proposed algorithm.
HPV in oropharyngeal cancer: the basics to know in clinical practice

SUMMARY The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising in contrast to the decreasing incidence of carcinomas in other subsites of the head and neck, in spite of the reduced prevalence of smoking. Human papilloma virus (HPV) infection, and in particular type 16 (HPV-16), is now recognized as a significant player in the onset of HPV positive OPSCC, with different epidemiological, clinical, anatomical, radiological, behavioural, biological and prognostic characteristics from HPV negative OPSCC. Indeed, the only subsite in the head and neck with a demonstrated aetiological viral link is, at present, the oropharynx. These observations lead to questions regarding management choices for patients based on tumour HPV status with important consequences on treatment, and on the role of vaccines and targeted therapy over the upcoming years.
Lower‐Fluence, Higher‐Density versus Higher‐Fluence, Lower‐Density Treatment with a 10,600‐nm Carbon Dioxide Fractional Laser System: A Split‐Face, Evaluator‐Blinded Study

BACKGROUND Adequate laser settings in the treatment of scars using a carbon dioxide fractional laser system (CO2 FS) have not been established. OBJECTIVE To compare the efficacy and safety of low‐fluence, high‐density with high‐fluence, low‐density treatment with CO2 FS on acne scars and enlarged pores. METHODS Ten patients with mild to severe atrophic acne scars and enlarged pores were enrolled. Half of each subject's face was treated with a single session of CO2 FS with a fluence of 70 mJ and a density of 150 spots/cm2; the other half was treated with a fluence of 30 mJ and a density of 250 spots/cm2. RESULTS Follow‐up results 3 months after a single low‐fluence, high‐density treatment with CO2 FS showed that four of 10 participants had clinical improvement of 51% to 75% from baseline. After the high‐fluence, low‐density CO2 FS treatment, five of 10 patients demonstrated marked clinical improvements of more than 76%. CONCLUSION Higher‐energy, lower‐density laser settings seem to be more effective than lower‐energy, higher‐density settings for acne scars and enlarged pores, although our results do not constitute a conclusive comparison of the two different modes of CO2 FS. &NA; The authors have indicated no significant interest with commercial supporters.
Structural Identifiability of Systems Biology Models: A Critical Comparison of Methods

Analysing the properties of a biological system through in silico experimentation requires a satisfactory mathematical representation of the system including accurate values of the model parameters. Fortunately, modern experimental techniques allow obtaining time-series data of appropriate quality which may then be used to estimate unknown parameters. However, in many cases, a subset of those parameters may not be uniquely estimated, independently of the experimental data available or the numerical techniques used for estimation. This lack of identifiability is related to the structure of the model, i.e. the system dynamics plus the observation function. Despite the interest in knowing a priori whether there is any chance of uniquely estimating all model unknown parameters, the structural identifiability analysis for general non-linear dynamic models is still an open question. There is no method amenable to every model, thus at some point we have to face the selection of one of the possibilities. This work presents a critical comparison of the currently available techniques. To this end, we perform the structural identifiability analysis of a collection of biological models. The results reveal that the generating series approach, in combination with identifiability tableaus, offers the most advantageous compromise among range of applicability, computational complexity and information provided.
Down-regulation of miR-302b, an ESC-specific microRNA, in Gastric Adenocarcinoma

Objective: microRNAs (miRNAs) are a new class of non-coding RNAs involved in regulating various biological processes including proliferation, differentiation, and apoptosis, among others. Alterations in miRNA expression are reported in several human cancers, which suggests their potential roles in tumor initiation and progression. Members of the miR-302 cluster are highly expressed in embryonic stem cells (ESC), where they regulate cell self-renewal and pluripotency. Based on the cancer stem cell (CSC) hypothesis, mis-expression of such genes might contribute to tumorigenicity. This study aims to find a potential link between the expression level of human/homo sapiens miR-302b (has-miR- 302b) and tumor/grade state of gastric tissues. Materials and Methods: A matched based case-control study was conducted that included tumor and matched marginal non-tumor surgical specimens from 34 patients diagnosed with gastric adenocarcinoma. Randomly selected samples were obtained from the Iran National Tumor Bank. cDNA synthesis was carried out on total RNA, by using the miRCURY LNATM Universal RT microRNA PCR Kit. Real-time reverse transcriptionpolymerase chain reaction (RT-PCR) assays were performed with specific LNATM primers and SYBR Green master mix. The human embryonic carcinoma cell line, NTERA2 (NT2) and a human gastric adenocarcinoma cell line, AGS, were used to optimize the PCR reactions. A comparative evaluation of miR-302b expression in tumor and non-tumor gastric samples was performed by either paired t test or Wilcoxon non-parametric test. The ability of miR-302b to discriminate tumor from non-tumor gastric samples was evaluated using the area under the receiver operating characteristic (ROC) curve. Results: According to our data, miR-302b expression (normalized to that of the U6 snRNA housekeeping gene) in the pluripotent cell line NT2 was more than 500 times greater than that of the AGS cell line. The level of expression was even lower in tumor and non-tumor gastric tissue samples. The data further revealed a down-regulation of miR-302b in gastric tumor samples (p=0.001), particularly in high-grade adenocarcinoma (p=0.009). However, ROC analysis data demonstrated a low sensitivity and specificity of miR-302b expression to discriminate between the tumor and non-tumor state of the samples (AUC=0.63). Conclusion: Despite the upregulation of some hESC-specific genes in tumors, our data revealed a down-regulation of miR-302b in high-grade tumors. This data suggested a potential tumor-suppressor role for miR-302b in tumorigenesis of gastric tissue.
A Symptomatic De Novo Pheochromocytoma 23 Years after Liver Transplantation: A Case Report and Review of the Literature

We report a case of subacute onset of headaches and tremors with a newly discovered adrenal pheochromocytoma 23 years after an orthotopic liver transplantation and provide a review of the scarce literature regarding endocrine malignancies in liver transplant recipients. We describe the clinical presentation, diagnostic work-up, and management. This is the second case report in the literature of a de novo pheochromocytoma after solid organ transplantation. It shows that new-onset common symptoms in transplant recipients are always challenging and deserve a very thorough work-up until the cause of the symptoms is elucidated. A broad differential diagnosis should always be included in the study of any abnormalities in this patient population.
Filling Gaps in Biodiversity Knowledge for Macrofungi: Contributions and Assessment of an Herbarium Collection DNA Barcode Sequencing Project

Despite recent advances spearheaded by molecular approaches and novel technologies, species description and DNA sequence information are significantly lagging for fungi compared to many other groups of organisms. Large scale sequencing of vouchered herbarium material can aid in closing this gap. Here, we describe an effort to obtain broad ITS sequence coverage of the approximately 6000 macrofungal-species-rich herbarium of the Museum of Natural History in Venice, Italy. Our goals were to investigate issues related to large sequencing projects, develop heuristic methods for assessing the overall performance of such a project, and evaluate the prospects of such efforts to reduce the current gap in fungal biodiversity knowledge. The effort generated 1107 sequences submitted to GenBank, including 416 previously unrepresented taxa and 398 sequences exhibiting a best BLAST match to an unidentified environmental sequence. Specimen age and taxon affected sequencing success, and subsequent work on failed specimens showed that an ITS1 mini-barcode greatly increased sequencing success without greatly reducing the discriminating power of the barcode. Similarity comparisons and nonmetric multidimensional scaling ordinations based on pairwise distance matrices proved to be useful heuristic tools for validating the overall accuracy of specimen identifications, flagging potential misidentifications, and identifying taxa in need of additional species-level revision. Comparison of within- and among-species nucleotide variation showed a strong increase in species discriminating power at 1–2% dissimilarity, and identified potential barcoding issues (same sequence for different species and vice-versa). All sequences are linked to a vouchered specimen, and results from this study have already prompted revisions of species-sequence assignments in several taxa.
Fast Iterative Interpolated Beamforming for Accurate Single-Snapshot DOA Estimation

A single-snapshot fast computational Fourier-based direction-of-arrival (DOA) estimation method is introduced. This method applies the fast Fourier transform (FFT) to sensor data and performs effective cancellation of spectral leakage caused by sidelobe interactions, leading to unbiased DOA estimates of multiple sources. Successful elimination of spectral leakage is achieved by a sequential removal of strong sinc functions in the spatial frequency domain through an iterative interpolation process. The simulation results demonstrate superior performance of the proposed method over beamforming and other iterative FFT-based DOA estimation techniques as well as the high-resolution Root-MUSIC algorithm.
Communication Problems in Second Language Learning at Federal Government Secondary Schools

The study was designed to analyze the development of listening and speaking skills in English at secondary level. The purpose of the study was to examine factors because of which students of Federal Government schools Sihala sector (F.A) Islamabad are not proficient in listening and speaking skills in English language. The objectives of the study were: to analyze the present situation of development of listening and speaking skills at secondary level, to examine those factors because of which our students are not proficient in listening and speaking, to suggest recommendations for subsequent improvement. the research finding shows deficiency in specific syllabus and period allocation for the development of listening and speaking skills. The teacher should design activities, dialog, presentation and group discussion so that they can enhance the listening and speaking skills in students. Teachers should provide chances of free speech to student they should keep friendly environment in class so that the students may not feel hesitation and shyness in speaking English.
MoCog1: A computer simulation of recognition-primed human decision making

This report describes the successful results of the first stage of a research effort to develop a "sophisticated" computer model of human cognitive behavior. Most human decision-making is of the experience-based, relatively straight-forward, largely automatic, type of response to internal goals and drives, utilizing cues and opportunities perceived from the current environment. This report describes the development of the architecture and computer program associated with such "recognition-primed" decision-making. The resultant computer program was successfully utilized as a vehicle to simulate Dweck and Leggett's findings that relate how an individual's implicit theories orient them toward particular goals, with resultant cognitions, affects and behavior in response to their environment. The present work is an expanded version of NASA TM 102886 and is based on research reported while the author was an employee of NASA ARC.
The effect of sodium thiopental as a GABA mimetic drug in neonatal period on expression of GAD65 and GAD67 genes in hippocampus of newborn and adult male rats

Objective(s): Development of the nervous system in human and most animals is continued after the birth. Critical role of this period in generation and specialization of the neuronal circuits is confirmed in numerous studies. Any pharmacological intervention in this period may result in structural, functional or behavioral abnormalities. In this study, sodium thiopental a GABA mimetic drug was administrated to newborn rats and their GAD65 and GAD67 expression in hippocampus was evaluated before and after puberty. Materials and Methods: Newborn male Wistar rats were received sodium thiopental (35 mg/kg) daily for 11 days (from 4 to 14 days after birth). Expression of GAD65 and GAD67 in their hippocampus was compared with control groups in 15 and 45 days after birth with RT-qPCR method. Results: Significant down regulation of GAD65 and GAD67 gene expression was observed in treated rats compared with control group in 45 days after birth animals. But no significant difference was shown between experimental and control groups 15 days after birth animals. Conclusion: The effect of sodium thiopental on GAD65 and GAD67 expression only at adult rats showed a latent period of influence which can be attributed to dosage or intension of sodium thiopental neurotoxicity. Significant down regulation of GAD65 and GAD67 showed unwanted effect of sodium thiopental as GABA mimetic drug in critical period of development.
Prevalence, Clinical and Virologic Outcomes of Hepatitis B Virus Co-Infection in HIV-1 Positive Kenyan Women on Antiretroviral Therapy

Background Sub-Saharan Africa carries a high burden of co-infection with HIV-1 and hepatitis B virus (HBV). In this region, individuals with HIV-1/HBV co-infection on antiretroviral therapy (ART) frequently receive lamivudine as the only agent active against HBV, raising concerns for development of HBV resistance to lamivudine. We aimed to determine the prevalence, clinical, and virologic outcomes of chronic HBV infection, including HBV resistance to lamivudine, in a cohort of HIV-1 seropositive Kenyan women on long-term ART. Methods In this prospective cohort study, HIV-1 seropositive women initiated three-drug ART regimens that included lamivudine as the single drug active against HBV. Archived samples were tested for HBsAg, with further testing to determine HBeAg seroprevalence, HBV DNA suppression, and lamivudine resistance. We estimated the prevalence of chronic HBV and examined associations between HBV co-infection and clinical and virologic outcomes with chi-square tests, logistic regression, Kaplan-Meier and Cox regression. Results In a cohort of 159 women followed for a median of 3.4 years (interquartile range 1.4–4.5), 11 (6.9%; 95% CI 3.1–10.7) had chronic HBV infection. Of these, 9 (82%) achieved undetectable plasma HBV DNA levels. One woman developed lamivudine resistance, for an incidence of 3 per 100 person-years. The HBV co-infected women were at greater risk for abnormal ALT elevations compared to HIV-1 mono-infected women (HR 2.37; 95% CI 1.1–5.3). There were no differences between HBV-infected and uninfected women in mortality, CD4 count, or HIV-1 RNA suppression. Conclusion The prevalence of chronic HBV in this cohort was similar to recent studies from other African populations. Given our long-term follow-up, lamivudine resistance was lower than expected for HIV-1/HBV co-infected patients. Improved screening for HBV and extended follow-up of HIV-1/HBV co-infected individuals are needed to better understand the impact of different ART regimens on clinical outcomes in this population.