Miracle-dz/UniFAR-FTUs huggingface dataset:
Link-based cluster ensembles for heterogeneous biological data analysis

Clinical data has been employed as the major factor for traditional cancer prognosis. However, this classic approach may be ineffective for analyzing morphologically indistinguishable tumor subtypes. As such, the microarray technology emerges as the promising alternative. Despite a large number of microarray studies, the actual clinical application of gene expression data analysis remains limited due to the complexity of generated data and the noise level. Recently, the integrative cluster analysis of both clinical and gene expression data has shown to be an effective alternative to overcome the above-mentioned problems. This paper presents a novel method for using cluster ensembles that is accurate for analyzing heterogeneous biological data. It overcomes the problem of selecting an appropriate clustering algorithm or parameter setting of any potential candidate, especially with a new set of data. The evaluation on real biological and benchmark datasets suggests that the quality of the proposed model is higher than many state-of-the-art cluster ensemble techniques and standard clustering algorithms. Also, its performance is robust to the parameter perturbation, thus providing a reliable and useful means for data analysts and bioinformaticians. Online supplementary is available at http://users.aber. ac.uk/nii07/bibm2010.
Myopia and polymorphisms in genes for matrix metalloproteinases.

PURPOSE To investigate the relation between myopia and variations in three genes coding for matrix metalloproteinases, enzymes that degrade matrix proteins and modulate scleral extensibility. METHODS Three hundred sixty-six men and women, from Sheffield, United Kingdom, were genotyped for the 1G/2G polymorphism in the MMP-1 gene, the 5A/6A polymorphism in the MMP-3 gene and the Arg-->Gln polymorphism in exon 6 of the MMP-9 gene and assessed for refractive error. RESULTS Risk of myopia was increased in people homozygous for the 5A allele of the MMP-3 gene (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-9.0) compared to those who were homozygous for the 6A allele, and in people homozygous for the Gln allele in exon 6 of the MMP-9 gene (OR, 2.8; 95% CI, 1.1-7.0) compared to those who were homozygous for the Arg allele. People who were homozygous for the 2G allele of the MMP-1 gene had an odds ratio for myopia of 2.3 (95% CI, 0.9-6.1), compared with those who were homozygous for the 1G allele, although this relation did not reach statistical significance. Risk of myopia increased progressively with the dose of these three alleles, showing a greater than 10-fold difference across the range. CONCLUSIONS The results suggest that common variations in three of the genes that control breakdown of matrix proteins in the sclera may contribute to the development of simple myopia.
High performance 300mm backside illumination technology for continuous pixel shrinkage

Backside Illumination (BSI) sensor with excellent optical performance has become the main-stream CMOS image sensor process. This work addressed the key factors and issues for 300mm BSI technology, including wafer distortion, silicon thickness variation, backside junction formation and dielectric film structure, thermal annealing and so on. It is demonstrated that with the optimized key process, a high performance 0.9um BSI pixel with low noise can be fabricated.
Comparison of definitions of metabolic syndrome in relation to risk for coronary artery disease and stroke.

OBJECTIVES To compare definitions of metabolic syndrome (MS) in relation to their association with coronary artery disease (CAD) and stroke. METHODS We performed a cross-sectional study in a primary care setting, involving 719 general practitioners and based on stratified distribution proportional to the population density. The first two adult patients scheduled for an appointment on a given day were invited to participate, irrespective of the reason for the consultation. A questionnaire was applied to record sociodemographic, clinical and laboratory data. A diagnosis of MS was defined according to NCEP-ATP III 2001, NCEP-ATP III 2004, IDF and AHA/NHLBI criteria. Multivariate logistic regression analysis was used to assess the risk of CAD and stroke according to gender, age, body mass index, waist circumference, HDL cholesterol, triglycerides, hypertension, diabetes and MS according to each definition. RESULTS The study included 16,856 individuals (age 58.1 +/- 15.1 years). The prevalence of MS adjusted for gender, age and region size according to the 2001 and 2004 NCEP-ATP III, IDF and AHA/NHLBI definitions was 28.4%, 32.8%, 65.5% and 69.4%, respectively. The degree of agreement according to k statistics was modest and only 60.3% simultaneously fulfilled the criteria of all definitions. Hypertension was the treatable risk factor most strongly associated with CAD and stroke. Only the IDF and AHA/NHLBI definitions of MS were independently associated with CAD (OR: 1.74 and 2.26, respectively). Regarding stroke, only the AHA/NHLBI criteria showed a statistically significant association (OR: 1.85). CONCLUSIONS MS as defined according to the AHA/NHLBI criteria appears to be the best predictor of CAD and stroke in the Portuguese population, and remains an independent risk factor for CAD and stroke after adjustment for its individual components.
Characterization of Japanese Polished Rice by Stable Hydrogen Isotope Analysis of Total Fatty Acids for Tracing Regional Origin

We determined the δD values of the total fatty acids of Japanese rice to test the hypothesis that there is a wide variation in the hydrogen isotopic composition (δD) of the total fatty acids of Japanese rice sourced from different growth areas in Japan and to distinguish the minor differences among these growth areas. The δD values showed a wide variation ranging from −216‰ (Hokkaido) to −183‰ (Okinawa), indicating a good correlation with the corresponding variations for ambient water ( r = 0.63) and mean temperature ( r = 0.84). These results suggest that the δD values for the total fatty acids can be representative of the growth environments in Japan.
Robustness, Evolvability, and the Logic of Genetic Regulation

In gene regulatory circuits, the expression of individual genes is commonly modulated by a set of regulating gene products, which bind to a gene's cis-regulatory region. This region encodes an input-output function, referred to as signal-integration logic, that maps a specific combination of regulatory signals (inputs) to a particular expression state (output) of a gene. The space of all possible signal-integration functions is vast and the mapping from input to output is many-to-one: For the same set of inputs, many functions (genotypes) yield the same expression output (phenotype). Here, we exhaustively enumerate the set of signal-integration functions that yield identical gene expression patterns within a computational model of gene regulatory circuits. Our goal is to characterize the relationship between robustness and evolvability in the signal-integration space of regulatory circuits, and to understand how these properties vary between the genotypic and phenotypic scales. Among other results, we find that the distributions of genotypic robustness are skewed, so that the majority of signal-integration functions are robust to perturbation. We show that the connected set of genotypes that make up a given phenotype are constrained to specific regions of the space of all possible signal-integration functions, but that as the distance between genotypes increases, so does their capacity for unique innovations. In addition, we find that robust phenotypes are (i) evolvable, (ii) easily identified by random mutation, and (iii) mutationally biased toward other robust phenotypes. We explore the implications of these latter observations for mutation-based evolution by conducting random walks between randomly chosen source and target phenotypes. We demonstrate that the time required to identify the target phenotype is independent of the properties of the source phenotype.
JARID1B is a histone H3 lysine 4 demethylase up-regulated in prostate cancer

Histone methylation is a dynamic process that participates in a diverse array of cellular processes and has been found to associate with cancer. Recently, several histone demethylases have been identified that catalyze the removal of methylation from histone H3 lysine residues. Through bioinformatic and biochemical analysis, we identified JARID1B as a H3K4 demethylase. Overexpression of JARID1B resulted in loss of tri-, di-, and monomethyl H3K4 but did not affect other histone lysine methylations. In vitro biochemical experiments demonstrated that JARID1B directly catalyzes the demethylation. The enzymatic activity requires the JmjC domain and uses Fe(II) and α-ketoglutarate as cofactors. Furthermore, we found that JARID1B is up-regulated in prostate cancer tissues, compared with benign prostate samples. We also demonstrated that JARID1B associates with androgen receptor and regulates its transcriptional activity. Thus, we identified JARID1B as a demethylase capable of removing three methyl groups from histone H3 lysine 4 and up-regulated in prostate cancer.
Frequent overcrowding in U.S. emergency departments.

OBJECTIVE To describe the definition, extent, and factors associated with overcrowding in emergency departments (EDs) in the United States as perceived by ED directors. METHODS Surveys were mailed to a random sample of EDs in all 50 states. Questions included ED census, frequency, impact, and determination of overcrowding. Respondents were asked to rank perceived causes using a five-point Likert scale. RESULTS Of 836 directors surveyed, 575 (69%) responded, and 525 (91%) reported overcrowding as a problem. Common definitions of overcrowding (>70%) included: patients in hallways, all ED beds occupied, full waiting rooms >6 hours/day, and acutely ill patients who wait >60 minutes to see a physician. Overcrowding situations were similar in academic EDs (94%) and private hospital EDs (91%). Emergency departments serving populations < or =250,000 had less severe overcrowding (87%) than EDs serving larger areas (96%). Overcrowding occurred most often several times per week (53%), but 39% of EDs reported daily overcrowding. On a 1-5 scale (+/-SD), causes of overcrowding included high patient acuity (4.3 +/- 0.9), hospital bed shortage (4.2 +/- 1.1), high ED patient volume (3.8 +/- 1.2), radiology and lab delays (3.3 +/- 1.2), and insufficient ED space (3.3 +/- 1.3). Thirty-three percent reported that a few patients had actual poor outcomes as a result of overcrowding. CONCLUSIONS Episodic, but frequent, overcrowding is a significant problem in academic, county, and private hospital EDs in urban and rural settings. Its causes are complex and multifactorial.
Development of effervescent tablets containing benznidazole complexed with cyclodextrin

Objectives Benznidazole (BNZ), the primary chemotherapy agent used to treat Chagas disease, has poor aqueous solubility, which results in low bioavailability. The purpose of this work was to develop stable effervescent tablets using an inclusion complex of BNZ with cyclodextrin (CD).
Proteinase Suppression by E-cadherin-mediated Cell-Cell Attachment in Premalignant Oral Keratinocytes*

The expression and activity of epithelial proteinases is under stringent control to prevent aberrant hydrolysis of structural proteins and disruption of tissue architecture. E-cadherin-dependent cell-cell adhesion is also important for maintenance of epithelial structural integrity, and loss of E-cadherin expression has been correlated with enhanced invasive potential in multiple tumor models. To address the hypothesis that there is a functional link between E-cadherin and proteinase expression, we have examined the role of E-cadherin in proteinase regulation. By using a calcium switch protocol to manipulate junction assembly, our data demonstrate that initiation of de novoE-cadherin-mediated adhesive contacts suppresses expression of both relative matrix metalloproteinase-9 levels and net urinary-type plasminogen activator activity. E-cadherin-mediated cell-cell adhesion increases both phosphatidylinositol 3′-kinase (PI3-kinase)-dependent AKT phosphorylation and epidermal growth factor receptor-dependent MAPK/ERK activation. Pharmacologic inhibition of the PI3-kinase pathway, but not the epidermal growth factor receptor/MAPK pathway, prevents E-cadherin-mediated suppression of proteinases and delays junction assembly. Moreover, inhibition of junction assembly with a function-blocking anti-E-cadherin antibody stimulates proteinase-dependent Matrigel invasion. As matrix metalloproteinase-9 and urinary-type plasminogen activator potentiate the invasive activity of oral squamous cell carcinoma, these data suggest E-cadherin-mediated signaling through PI3-kinase can regulate the invasive behavior of cells by modulating proteinase secretion.
Mediterranean Europe as an area of endemism for small mammals rather than a source for northwards postglacial colonization

There is a general perception that central and northern Europe were colonized by range expansion from Mediterranean refugia at the end of the last glaciation. Data from various species support this scenario, but we question its universality. Our mitochondrial DNA studies on three widespread species of small mammal suggest that colonization may have occurred from glacial refugia in central Europe–western Asia. The haplotypes on the Mediterranean peninsulae are distinctive from those found elsewhere. Rather than contributing to the postglacial colonization of Europe, Mediterranean populations of widespread small mammals may represent long–term isolates undergoing allopatric speciation. This could explain the high endemism of small mammals associated with the Mediterranean peninsulae.
Comparison of low-frequency electrical myostimulation and conventional aerobic exercise training in patients with chronic heart failure

Background Physical training is recommended as an efficient therapy in patients with chronic heart failure (CHF). Low-frequency electrical myostimulation (EMS) has recently been suggested as a good alternative to conventional aerobic training. The aim of this study was to compare the effects of EMS and conventional exercise training in patients with moderate to severe CHF. Methods Twenty-four patients with stable CHF (56.7±7.3 years, New York Heart Association grades II and III) underwent 5 weeks of exercise training, 5h a week, using EMS (n=12) or conventional (n=12) training programmes. At baseline and after the training period, patients performed a symptom-limited cardiopulmonary test, a 6-min and a 200-m walk exercises and an evaluation of maximal knee extensor strength. Results Oxygen uptake (VO2) and workload at the end of exercise (peak values) and at ventilatory threshold increased after EMS (P ≤ 0.05) and conventional exercise (P<0.05) training programmes. The slope of the relationship between VO2 and workload was reduced after EMS (P<0.05). The time to recover half of peak VO2 decreased irrespective of the training programme (P<0.001). EMS and conventional exercise training programmes also increased the maximal knee extensor strength (P<0.05), the distance walked in 6 min (P<0.01) and decreased the time elapsed to cover 200 m (P<0.05). These improvements were not statistically different between EMS and conventional exercise. Conclusion In patients with moderate to severe CHF, 5 weeks of EMS and conventional exercise training produce similar improvements to exercise capacity and muscle performance.
Determinants of high sensitivity troponin T concentration in chronic stable patients with heart failure: Ischemic heart failure versus non-ischemic dilated cardiomyopathy.

BACKGROUND Cardiac troponin T is a marker of myocardial injury, especially when measured by means of the high-sensitivity assay (hs-cTnT). The echocardiographic and clinical predictors of hs-cTnT may be different in ischemic heart failure (IHF) and non-ischemic dilated cardiomyopathy (DCM). METHODS Sixty consecutive patients (19 female, 41 male; mean age 56.3 ± 13.9 years) with stable congestive heart failure (33 patient with IHF and 27 patients with DCM), with New York Heart Association functional class I-II symptoms, and left ventricular ejection fraction < 40% were included. RESULTS In patients with IHF peak early mitral inflow velocity (E), E/peak early diastolic mitral annular tissue Doppler velocity (Em) lateral, peak systolic mitral annular tissue Doppler velocity (Sm) lateral and logBNP were univariate predictors of hs-cTnT above median. But only E/Em lateral was an independent predictor of hs-cTnT above median (p = 0.04, HR: 1.2,CI: 1-1.4). In patients with DCM; left atrial volume index, male sex, Sm lateral and global longitudinal strain (LV-GLS) were included in multivariate model and LV-GLS was detected to be an independent predictor for hs-cTnT above median (p < 0.05, HR: 0.7, CI: 0.4-1.0). CONCLUSIONS While LV-GLS is an independent predictor of hs-cTnT concentrations in patients with DCM, E/Em lateral predicted hs-TnT concentrations in patients with IHF.
Structural Insights into Substrate Binding by PvFKBP35, a Peptidylprolyl cis-trans Isomerase from the Human Malarial Parasite Plasmodium vivax

ABSTRACT The immunosuppressive drug FK506 binding proteins (FKBPs), an immunophilin family with the immunosuppressive drug FK506 binding property, exhibit peptidylprolyl cis-trans isomerase (PPIase) activity. While the cyclophilin-catalyzed peptidylprolyl isomerization of X-Pro peptide bonds has been extensively studied, the mechanism of the FKBP-mediated peptidylprolyl isomerization remains uncharacterized. Thus, to investigate the binding of FKBP with its substrate and the underlying catalytic mechanism of the FKBP-mediated proline isomerization, here we employed the FK506 binding domain (FKBD) of the human malarial parasite Plasmodium vivax FK506 binding protein 35 (PvFKBP35) and examined the details of the molecular interaction between the isomerase and a peptide substrate. The crystallographic structures of apo PvFKBD35 and its complex with the tetrapeptide substrate succinyl-Ala-Leu-Pro-Phe-p-nitroanilide (sALPFp) determined at 1.4 Å and 1.65 Å resolutions, respectively, showed that the substrate binds to PvFKBD35 in a cis conformation. Nuclear magnetic resonance (NMR) studies demonstrated the chemical shift perturbations of D55, H67, V73, and I74 residues upon the substrate binding. In addition, the X-ray crystal structure, along with the mutational studies, shows that Y100 is a key residue for the catalytic activity. Taken together, our results provide insights into the catalytic mechanism of PvFKBP35-mediated cis-trans isomerization of substrate and ultimately might aid designing substrate mimetic inhibitors targeting the malarial parasite FKBPs.
Optimal allocation of ad inventory in real-time bidding advertising markets

With the rapid development of big data analytics in online marketing, real-time bidding (RTB) has emerged as a promising business model in recent years and now becomes one of the major online advertising channels. Based on analysis of Web Cookies, RTB platforms are able to precisely identify the features and preferences of target audiences visiting publishers' websites, and forward the information to competing advertisers submitting bids for their best-matched audience in real-time ad auctions. As the supplier of ad impressions, publishers typically have multiple channels to sell their ad impressions (i.e., ad inventory), making their strategies for allocating ad inventory one of the most critical research problems. In this paper, we strive to study publishers' optimal strategy of allocating ad inventory across online channel of RTB-based auctions and offline channel prevailingly realized in the form of guaranteed contracts. Considering the ad reserve price as the control variable, we establish the optimization model. We also explicitly take the default penalty in offline channels into consideration, so as to balance the short-term online revenue and long-term offline revenue. In our work, we analyze altogether three kinds of strategies for publishers to allocate their ad inventory in pursuit of the optimal strategy, and validate our model and analysis via computational experiments. We find that there is no dominant strategy that can outperform others in all cases, and interestingly, publishers using the hybrid-channel strategy do not always gain more revenues than those using the single-channel strategy.
The stability of children's physical activity as measured by accelerometry and self-report.

The Computer Science Application (CSA) accelerometer uses integrated circuitry and memory to provide a continuous recording of minute-by-minute movement counts. It has been previously validated as an objective monitor of children's physical activity in field and laboratory settings. Our purpose was to derive accelerometry summary variables reflective of different physical activity intensity levels, evaluate the stability of these summary variables, and define the number of days needed to adequately measure usual physical activity. A secondary study purpose was to compare three self-report questionnaires to accelerometry. Thirty children (7-15 yr) wore accelerometers for 12 h.d-1 for 6 d. Daily summary variables of average movement count (total physical activity) and daily frequency of sedentary through vigorous activity were constructed. Intraclass correlation coefficients (R) and 95% confidence intervals (CI) were used to analyze the data. Accelerometry stability using 1 monitored day to represent usual physical activity was R = 0.42-0.47. When 6 d were used, stability increased to R = 0.81-0.84. Acceptable intraclass correlations and CI were achieved with 4 d of monitoring (R = 0.75-0.78, CI = 0.60-0.88). The self-report questionnaires were poorly to moderately correlated to accelerometry variables (r = -0.03-0.51). Data indicate that in field settings: 1) accelerometry can be used to assess the intensity of children's activity and 2) 4 or more days of activity monitoring are needed to achieve satisfactory reliability.
Effect of Free Fatty Acids on Insulin Receptor Binding and Tyrosine Kinase Activity in Hepatocytes Isolated From Lean and Obese Rats

We demonstrated previously that high physiological concentrations of free fatty acids (FFA) rapidly decrease insulin binding, degradation, and action in isolated rat hepatocytes. In this study, hepatocytes from lean and obese Sprague-Dawley rats (Alab, Stockholm) were preincubated with or without 0.4 mM oleic acid, and the effect on insulin binding and tyrosine kinase activity was measured. In the absence of exogenous FFA, insulin binding was reduced in hepatocytes from obese compared with lean rats (mean ± SE reduction 44 ±7%, n = 8, P < 0.01). Furthermore, the inhibitory effect of oleic acid added to hepatocytes from lean rats (n = 8; 40 ± 9%, P < 0.01) was not seen in cells from obese rats. Treating obese rats with Etomoxir, a carnitine palmitoyl transferase I inhibitor, increased insulin binding to isolated hepatocytes by 41 ± 13% (n = 5, P < 0.05). There was no difference in total binding to partially purified insulin receptors from solubilized hepatocytes from lean and obese rats, whether cells were or were not preincubated with oleic acid. Tyrosine kinase activity of partially purified receptors from basal or insulin-stimulated cells was not affected by either obesity, treatment with Etomoxir, or preincubating the cells with oleic acid. Thus, both obesity and elevated ambient FFA levels are associated with impaired insulin cell surface binding to isolated hepatocytes, possibly through an effect of lipid oxidation on the internalization/recycling of the insulin-receptor complex without any perturbation of the receptor tyrosine kinase activity. The data suggest that the reduced insulin binding to hepatocytes from obese rats is due to elevated ambient FFA levels.