Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicting treatment effects using biomarker data in a meta‐analysis of clinical trials

A biomarker (S) measured after randomization in a clinical trial can often provide information about the true endpoint (T) and hence the effect of treatment (Z). It can usually be measured earlier and more easily than T and as such may be useful to shorten the trial length. A potential use of S is to completely replace T as a surrogate endpoint to evaluate whether the treatment is effective. Another potential use of S is to serve as an auxiliary variable to help provide information and improve the inference on the treatment effect prediction when T is not completely observed. The objective of this report is to focus on its role as an auxiliary variable and to identify situations when S can be useful to increase efficiency in predicting the treatment effect in a new trial in a multiple‐trial setting. Both S and T are continuous. We find that higher efficiency gain is associated with higher trial‐level correlation but not individual‐level correlation when only S, but not T is measured in a new trial; but, the amount of information recovery from S is usually negligible. However, when T is partially observed in the new trial and the individual‐level correlation is relatively high, there is substantial efficiency gain by using S. For design purposes, our results suggest that it is often important to collect markers that have high adjusted individual‐level correlation with T and at least a small amount of data on T. The results are illustrated using simulations and an example from a glaucoma clinical trial. Copyright © 2010 John Wiley & Sons, Ltd.
Power-efficient flexible processor architecture for embedded applications

In the design of embedded systems, a processor architecture is a tradeoff between energy consumption, area, speed, design time, and flexibility to cope with future design changes. New versions in a product generation may require small design changes in any part of the design. We propose a novel processor architecture concept, which provides the flexibility needed in practice at a reduced power and performance cost compared to a fully programmable processor. The crucial element is a novel protocol combining an efficient, customized component with a flexible processor into a hybrid architecture.
The myth of testing construct validity using factor analysis or correlations with normal or mixed clinical populations: Lessons from memory assessment

Abstract For nearly a century, the primary method employed by psychologists to define and test the validity of constructs evaluated by assessment instruments has been shared-variance techniques such as intervariable correlations or factor analysis with large normative or mixed clinical samples. To illustrate the shortcomings of this approach, we conducted (1) correlational analyses of immediate- and delayed-memory measures separately in normal participants and in homogeneous samples of patients with either Alzheimer's disease or Huntington's disease; and (2) factor analysis of immediate and delayed-recall and recognition measures in a large, homogeneous sample of patients with Alzheimer's disease. The findings revealed that cognitive measures that share variance in the intact brain—thereby giving the facade of assessing a unitary construct—can dissociate and contribute to unique variance in the damaged brain, but only if the pathology occurs in brain regions known to disrupt vital cognitive processes tapped by those measures. The results illustrate that shared-variance procedures applied to normal or mixed clinical populations can mask some of the most vital cognitive constructs, such as the classic distinction between short- and long-term memory. Implications of these findings for research and clinical practice are discussed. (JINS, 2003, 9, 936–946.)
The -Helical to -Strand Transition in the Amino-terminal Fragment of the Amyloid -Peptide Modulates Amyloid Formation *

Amyloid-β peptide (Aβ) consists of a hydrophobic C-terminal domain (residues 29-42) that adopts β-strand conformation and an N-terminal domain (amino acids 10-24) whose sequence permits the existence of a dynamic equilibrium between an α-helix and a β-strand. In this paper we analyzed the effect of the alternate N-terminal conformations on amyloid fibril formation through the study of the analogous Aβ peptides containing single amino acidic substitutions. The single mutation of valine 18 to alanine induces a significant increment of the α-helical content of Aβ, determined by Fourier transform infrared spectroscopy and circular dichroism and dramatically diminishes fibrillogenesis, measured by turbidity, thioflavine T binding, Congo red staining, and electron microscopic examination. In hereditary Dutch cerebral hemorrhage with amyloidosis (a variant of Alzheimer's disease), the substitution of glutamine for glutamic acid at position 22 decreased the propensity of the Aβ N-terminal domain to adopt an α-helical structure, with a concomitant increase in amyloid formation. We propose that Aβ exists in an equilibrium between two species: one “able” and another “unable” to form amyloid, depending on the secondary structure adopted by the N-terminal domain. Thus, manipulation of the Aβ secondary structure with therapeutical compounds that promote the α-helical conformation may provides a tool to control the amyloid deposition observed in Alzheimer's disease patients.
Glutamine deprivation facilitates tumour necrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate

Background and aims: Factors that induce luminal bacteria to cross the intestinal epithelium following injury remain poorly defined. The aim of this study was to investigate the interaction between glutamine metabolism, energy supply, and inflammatory mediators in determining the translocation of non-pathogenic bacteria across cultured enterocytes. Methods: The effect of tumour necrosis factor α (TNF-α) on translocation of Escherichia coli C25 across Caco-2 epithelial monolayers was studied in the presence of products and inhibitors of glutamine metabolism. Simultaneous measurements of transepithelial electrical resistance (TEER) and flux of lucifer yellow were used to assess effects on the paracellular pathway. Lactate dehydrogenase release was used to monitor enterocyte integrity. Imaging of monolayers in these experimental conditions was undertaken with transmission electron microscopy. Results: Exposure to basolateral TNF-α (20 ng/ml) for six hours induced translocation of E coli across Caco-2 but only if accompanied by simultaneous glutamine depletion (p<0.01). Translocation was inhibited by addition of glutamine for two hours (p<0.01) but not by an isonitrogenous mixture of non-glutamine containing amino acids. Inhibition of glutamine conversion to α-ketoglutarate, but not blockade of glutathione or polyamine synthesis, also induced translocation in the presence of TNF-α. Manipulations that induced bacterial translocation were associated with a marked reduction in enterocyte ATP levels. No effect of these treatments on paracellular permeability or lactate dehydrogenase release was observed. Conditions in which translocation occurred were associated with the presence of bacteria within enterocyte vacuoles but not the paracellular space. Conclusions: In inflammatory conditions, the availability of glutamine as an enterocyte fuel substrate is essential for the preservation of a functional barrier to microorganisms. In conditions of acute glutamine depletion, cytokine mediated bacterial translocation appears to be primarily a transcellular process.
Modeling of Standing Column Wells in Ground Source Heat Pump Systems

In recent years, ground source heat pump systems have become increasingly popular for use in residential and commercial buildings. These systems include several different variations, all of which reject heat and/or extract heat from the sub-surface environment: • Ground-coupled heat pump (GCHP) systems (Closed-loop) • Surface water heat pump (SWHP) systems • Groundwater heat pump (GWHP) systems: -Standing column well (SCW) systems, which utilize a single well for both extraction and injection of groundwater. -Open loop groundwater systems with separate extraction and injection wells or single extraction well.
International Journal of Health Geographics Open Access the Population Health Approach: Health Gis as a Bridge from Theory to Practice Community Health Planningneeds Assessmentpublic Health Informaticsmedical Geographygeographic Information Systems

Background: The Population Health Approach, proposed by Health Canada, is the articulation of a long advocated model of human health. This approach strives to ensure that the health system is appropriately oriented to improve health status by applying evidence based practices across the continuum from health determinants to service interventions. Although conceptually appealing, it has been difficult to implement widely in the existing program-based health care system. The Population Health Surveillance Unit (PHSU) of the Vancouver Island Health Authority (VIHA) has developed a health geographical information system (HGIS), where GIS is used as both platform for information integration and as an analytical tool supporting comprehensive data analysis. With the assistance of the HGIS, the theory of the population health approach can be transformed into a practical, stepwise process supporting health services and program planning.
Diversity of Group B Streptococcus Serotypes Causing Urinary Tract Infection in Adults

ABSTRACT Serotypes of group B streptococcus (GBS) that cause urinary tract infection (UTI) are poorly characterized. We conducted a prospective study of GBS UTI in adults to define the clinical and microbiological characteristics of these infections, including which serotypes cause disease. Patients who had GBS cultured from urine over a 1-year period were grouped according to symptoms, bacteriuria, and urinalysis. Demographic data were obtained by reviewing medical records. Isolates were serotyped by latex agglutination and multiplex PCR-reverse line blotting (mPCR/RLB). Antibiotic susceptibilities were determined by disc diffusion. GBS was cultured from 387/34,367 consecutive urine samples (1.1%): 62 patients had bacteriuria of >107 CFU/liter and at least one UTI symptom; of these patients, 31 had urinary leukocyte esterase and pyuria (others not tested), 50 (81%) had symptoms consistent with cystitis, and 12 (19%) had symptoms of pyelonephritis. Compared with controls (who had GBS isolated without symptoms), a prior history of UTI was an independent risk factor for disease. Increased age was also significantly associated with acute infection. Serotyping results were consistent between latex agglutination and mPCR/RLB for 331/387 (85.5%) isolates; 22 (5.7%) and 7 (1.8%) isolates were nontypeable with antisera and by mPCR/RLB, respectively; and 45/56 (80.4%) isolates with discrepant results were typed by mPCR/RLB as belonging to serotype V. Serotypes V, Ia, and III caused the most UTIs; serotypes II, Ib, and IV were less common. Nontypeable GBS was not associated with UTI. Erythromycin (39.5%) and clindamycin (26.4%) resistance was common. We conclude that a more diverse spectrum of GBS serotypes causes UTI than previously recognized, with the exception of nontypeable GBS.
Delineation of prevalence and risk factors for early coronary artery disease by electron beam computed tomography in young adults with type 1 diabetes.

OBJECTIVE Type 1 diabetes increases the risk for coronary artery disease (CAD), but limited information is available regarding the early natural history of this process. Electron beam tomography (EBT) can measure coronary artery calcification (CAC), an early marker for CAD. This study was designed to assess the prevalence and risk factors for CAC in young adults with established type 1 diabetes. RESEARCH DESIGN AND METHODS A total of 101 subjects aged 17-28 years with type 1 diabetes of over 5 years' duration and no history of heart disease underwent cardiac EBT with calcium scoring. Medical histories were obtained and physical examinations were conducted to document the presence of cardiac risk factors as well as evidence of microvasculopathy and diabetic arthropathy. Laboratory evaluation included measurement of fasting lipoproteins, homocysteine concentration, lipoprotein(a) [Lp(a)], urinary microalbumin, and HbA(1c). Contingency table analysis was used to assess bivariate relationships. Logistic regression was employed to construct a parsimonious model of independent risk factors. RESULTS Eleven subjects (10.9%) had CAC. Smokers were nearly five times more likely than nonsmokers to have CAC (P = 0.03). In addition, each 0.36-mm/l increment of Lp(a) was associated with a 10% increased risk for CAC (P = 0.05) after controlling for potentially confounding factors. There was no association of other CAD or diabetes risk factors studied with CAC. CONCLUSIONS The prevalence of early CAD as evidenced by CAC in young adults with type 1 diabetes is significant. Smoking and Lp(a) levels independently predict the presence of CAC. Additional study is necessary to delineate the natural history of CAC and the role of risk factor modification to prevent progression of CAD in this high-risk population.
Towards designing robust QCA architectures in the presence of sneak noise paths

Quantum-dot cellular automata (QCA) are attracting a lot of attention due to their extremely small feature sizes and ultra low power consumption. Several designs using QCA technology have been proposed. However, we have found that not all of the designs function properly. Further, no general design guidelines have been proposed so far. A straightforward extension of a simple functional design pattern may fail. This makes designing large scale circuits using QCA technology an extremely time-consuming process. We show several critical vulnerabilities in the structures of primitive QCA gates and QCA interconnects, and propose a disciplinary guideline to prevent any additional plausible, but malfunctioning, QCA designs.
Characterisation of Age-Dependent Beta Cell Dynamics in the Male db/db Mice

Aim To characterise changes in pancreatic beta cell mass during the development of diabetes in untreated male C57BLKS/J db/db mice. Methods Blood samples were collected from a total of 72 untreated male db/db mice aged 5, 6, 8, 10, 12, 14, 18, 24 and 34 weeks, for measurement of terminal blood glucose, HbA1c, plasma insulin, and C-peptide. Pancreata were removed for quantification of beta cell mass, islet numbers as well as proliferation and apoptosis by immunohistochemistry and stereology. Results Total pancreatic beta cell mass increased significantly from 2.1 ± 0.3 mg in mice aged 5 weeks to a peak value of 4.84 ± 0.26 mg (P < 0.05) in 12-week-old mice, then gradually decreased to 3.27 ± 0.44 mg in mice aged 34 weeks. Analysis of islets in the 5-, 10-, and 24-week age groups showed increased beta cell proliferation in the 10-week-old animals whereas a low proliferation is seen in older animals. The expansion in beta cell mass was driven by an increase in mean islet mass as the total number of islets was unchanged in the three groups. Conclusions/Interpretation The age-dependent beta cell dynamics in male db/db mice has been described from 5-34 weeks of age and at the same time alterations in insulin/glucose homeostasis were assessed. High beta cell proliferation and increased beta cell mass occur in young animals followed by a gradual decline characterised by a low beta cell proliferation in older animals. The expansion of beta cell mass was caused by an increase in mean islet mass and not islet number.
Identification by high-throughput imaging of the histone methyltransferase EHMT2 as an epigenetic regulator of VEGFA alternative splicing

Recent evidence points to a role of chromatin in regulation of alternative pre-mRNA splicing (AS). In order to identify novel chromatin regulators of AS, we screened an RNAi library of chromatin proteins using a cell-based high-throughput in vivo assay. We identified a set of chromatin proteins that regulate AS. Using simultaneous genome-wide expression and AS analysis, we demonstrate distinct and non-overlapping functions of these chromatin modifiers on transcription and AS. Detailed mechanistic characterization of one dual function chromatin modifier, the H3K9 methyltransferase EHMT2 (G9a), identified VEGFA as a major chromatin-mediated AS target. Silencing of EHMT2, or its heterodimer partner EHMT1, affects AS by promoting exclusion of VEGFA exon 6a, but does not alter total VEGFA mRNA levels. The epigenetic regulatory mechanism of AS by EHMT2 involves an adaptor system consisting of the chromatin modulator HP1γ, which binds methylated H3K9 and recruits splicing regulator SRSF1. The epigenetic regulation of VEGFA is physiologically relevant since EHMT2 is transcriptionally induced in response to hypoxia and triggers concomitant changes in AS of VEGFA. These results characterize a novel epigenetic regulatory mechanism of AS and they demonstrate separate roles of epigenetic modifiers in transcription and alternative splicing.
An overview of recent health care support systems for eEmergency and mHealth applications

Advances in mobile communications and medical technologies facilitate the development of emerging mobile systems and applications for healthcare. The objective of this paper is to provide an overview and the current status of mobile health care systems (mHealth) and their applications for Emergency healthcare support (eEmergency). Our paper reports on journal papers that use wireless, emergency telemedicine systems that appeared since 2000. The majority of the applications are focused on the transmission of crucial biosignals (mainly ECG) for the support of heart-related healthcare. A limited number of new studies were focused on supporting emergency healthcare for trauma by facilitating both 2D image or video transmission (eg: ultrasound). Alternatively, new studies have focused on integrated systems for specialized emergency scenaria such as stroke. This paper is an extension of work previously published by our group [1].
Phospholipids undergo hop diffusion in compartmentalized cell membrane

The diffusion rate of lipids in the cell membrane is reduced by a factor of 5–100 from that in artificial bilayers. This slowing mechanism has puzzled cell biologists for the last 25 yr. Here we address this issue by studying the movement of unsaturated phospholipids in rat kidney fibroblasts at the single molecule level at the temporal resolution of 25 μs. The cell membrane was found to be compartmentalized: phospholipids are confined within 230-nm-diameter (φ) compartments for 11 ms on average before hopping to adjacent compartments. These 230-nm compartments exist within greater 750-nm-φ compartments where these phospholipids are confined for 0.33 s on average. The diffusion rate within 230-nm compartments is 5.4 μm2/s, which is nearly as fast as that in large unilamellar vesicles, indicating that the diffusion in the cell membrane is reduced not because diffusion per se is slow, but because the cell membrane is compartmentalized with regard to lateral diffusion of phospholipids. Such compartmentalization depends on the actin-based membrane skeleton, but not on the extracellular matrix, extracellular domains of membrane proteins, or cholesterol-enriched rafts. We propose that various transmembrane proteins anchored to the actin-based membrane skeleton meshwork act as rows of pickets that temporarily confine phospholipids.
Sensitive Enzyme-Linked Immunosorbent Assay for Detection of Antibodies Against Typhus Rickettsiae, Rickettsia prowazekii and Rickettsia typhi

An enzyme-linked immunosorbent assay (ELISA) has been developed for the titration of rickettsial antibodies in human and animal sera. Two preparations of soluble typhus-group antigens were obtained from Rickettsia typhi and Rickettsia prowazekii by ether extraction: a standard antigen from infected yolk sacs (YS antigen) and one free of yolk sac contaminants from Renografin-purified rickettsiae (PR antigen). Rabbit, mouse, and guinea pig sera were obtained by immunization with viable purified R. typhi or R. prowazekii. Human sera were obtained from individuals who had recovered from laboratory infections with either typhus rickettsia months or years previously. Goat-derived anti-immunoglobulins were conjugated to alkaline phosphatase with glutaraldehyde. Although the PR and YS antigens gave equivalent antibody titers in the complement fixation test, the PR antigen was clearly superior in the ELISA. With this antigen, the titration curves of all antisera were linear over a wider range of serum concentrations and the titers were higher than with the YS antigen. With YS and PR antigens, ELISA titers were higher than those obtained by complement fixation by one and two orders of magnitude, respectively. In human sera, immunoglobulin G and immunoglobulin M antibodies were demonstrated by their respective anti-immunoglobulins and by differential susceptibility to ethanethiol. ELISA titers showed some type specificity, whereas none was observed in complement fixation tests. The ELISA is highly sensitive, reproducible, and easily adaptable to the various requirements of clinical and research laboratories.
Replacement and Structure of S-Boxes in Rijndael

This paper describes the designation and structure of S-boxes which are the fundament of the Rijndael algorithm and finds the optimization of them using four kinds of testing methods. Firstly, it constructs different S-boxes by Matlab using 30 irreducible polynomials the maximum power of which is eight in a finite field. Through taking their performance analysis, we find that they have the similar performances in differential testing and linear or correlation testing. But in avalanche testing and Boolean expressions testing, the S-boxes which are constructed by No. 9 and No. 18 irreducible polynomial are optimal structure respectively.