Miracle-dz/UniFAR-FTUs huggingface dataset:
Kaffemik - a distributed JVM featuring a single address space

Java has rapidly gained a large user group and has become one of the most popular platforms for developing Internet applications, e.g., servlets. The Java VM is extensively used to execute servlets in web servers and Enterprise Java Beans in application servers. Due to Java’s platform independence, it has also gained large acceptance in the opensource community. This has lead to the development of a number of large server applications written entirely in Java, e.g., JigSaw, Jetty, JBoss, but also scientific applications a la Java Grande [1]. With the growing number of consumers using services deployed on these servers, there is a growing demand for scalable Java VMs to manage the increasing workload.
Potential of Tetracycline Resistance Proteins To Evolve Tigecycline Resistance

ABSTRACT Tigecycline is a glycylcycline antibiotic active against multidrug-resistant bacterial pathogens. The objectives of our study were to examine the potential of the Tet(A), Tet(K), Tet(M), and Tet(X) tetracycline resistance proteins to acquire mutations causing tigecycline resistance and to determine how this affects resistance to earlier classes of tetracyclines. Mutations in all four tet genes caused a significant increase in the tigecycline MIC in Escherichia coli, and strains expressing mutant Tet(A) and Tet(X) variants reached clinically relevant MICs (2 mg/liter and 3 mg/liter, respectively). Mutations predominantly accumulated in transmembrane domains of the efflux pumps, most likely increasing the accommodation of tigecycline as a substrate. All selected Tet(M) mutants contained at least one mutation in the functionally most important loop III of domain IV. Deletion of leucine 505 of this loop led to the highest increase of the tigecycline MIC (0.5 mg/liter) among Tet(M) mutants. It also caused collateral sensitivity to earlier classes of tetracyclines. A majority of the Tet(X) mutants showed increased activity against all three classes of tetracylines. All tested Tet proteins have the potential to acquire mutations leading to increased MICs of tigecycline. As tet genes are widely found in pathogenic bacteria and spread easily by horizontal gene transfer, resistance development by alteration of existing Tet proteins might compromise the future medical use of tigecycline. We predict that Tet(X) might become the most problematic future Tet determinant, since its weak intrinsic tigecycline activity can be mutationally improved to reach clinically relevant levels without collateral loss in activity to other tetracyclines.
Porcine leukocyte cellular subsets sensitive to African swine fever virus in vitro

African swine fever virus infected most, if not all, of the macrophages (monocytes) and ca. 4% of the polymorphonuclear leukocytes from porcine peripheral blood. B and T lymphocytes, either resting or stimulated with phytohemagglutinin, lipopolysaccharide, or pokeweed mitogen, were not susceptible to the virus. All of the mitogens used inhibited African swine fever multiplication in susceptible cells. The number of virus passages in vitro and the virulence degree of the virus did not affect the susceptibility of porcine B or T lymphocytes to African swine fever virus.
Altering a Histone H3K4 Methylation Pathway in Glomerular Podocytes Promotes a Chronic Disease Phenotype

Methylation of specific lysine residues in core histone proteins is essential for embryonic development and can impart active and inactive epigenetic marks on chromatin domains. The ubiquitous nuclear protein PTIP is encoded by the Paxip1 gene and is an essential component of a histone H3 lysine 4 (H3K4) methyltransferase complex conserved in metazoans. In order to determine if PTIP and its associated complexes are necessary for maintaining stable gene expression patterns in a terminally differentiated, non-dividing cell, we conditionally deleted PTIP in glomerular podocytes in mice. Renal development and function were not impaired in young mice. However, older animals progressively exhibited proteinuria and podocyte ultra structural defects similar to chronic glomerular disease. Loss of PTIP resulted in subtle changes in gene expression patterns prior to the onset of a renal disease phenotype. Chromatin immunoprecipitation showed a loss of PTIP binding and lower H3K4 methylation at the Ntrk3 (neurotrophic tyrosine kinase receptor, type 3) locus, whose expression was significantly reduced and whose function may be essential for podocyte foot process patterning. These data demonstrate that alterations or mutations in an epigenetic regulatory pathway can alter the phenotypes of differentiated cells and lead to a chronic disease state.
Low Hemoglobin A1c and Risk of All-Cause Mortality Among US Adults Without Diabetes

Background—Among individuals without diabetes, elevated hemoglobin A1c (HbA1c) has been associated with increased morbidity and mortality, but the literature is sparse regarding the prognostic importance of low HbA1c. Methods and Results—National Health and Nutrition Examination Survey III (NHANES III) participants, 20 years and older, were followed up to 12 years (median follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HbA1c levels and all-cause mortality for 14 099 participants without diabetes. There were 1825 deaths during the follow-up period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red blood cell volume, ferritin, and liver enzymes and the lowest levels of mean total cholesterol and diastolic blood pressure compared with their counterparts with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45 to 9.63) after adjustment for age, race-ethnicity, and sex. This association was attenuated but remained statistically significant after further multivariable adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI, 1.25 to 6.76). Conclusions—In this nationally representative cohort, low HbA1c was associated with increased all-cause mortality among US adults without diabetes. Additional research is needed to confirm these results and identify potential mechanisms that may be underlying this association.
Waiting time analysis of foreign currency exchange rates: Beyond the renewal-reward theorem

We evaluate the average waiting time between observing the price of financial markets and the next price change, especially in an on-line foreign exchange trading service for individual customers via the Internet. Basic technical idea of our present work is dependent on the so-called renewal-reward theorem. Assuming that stochastic processes of the market price changes could be regarded as a renewal process, we use the theorem to calculate the average waiting time of the process. In the conventional derivation of the theorem, it is apparently hard to evaluate the higher order moments of the waiting time. To overcome this type of difficulties, we attempt to derive the waiting time distribution Omega(s) directly for arbitrary time interval distribution (first passage time distribution) of the stochastic process PW(r) and observation time distribution PO (t) of customers. Our analysis enables us to evaluate not only the first moment (the average waiting time) but also any order of the higher moments of the waiting time. Moreover, in our formalism, it is possible to model the observation of the price on the internet by the customers in terms of the observation time distribution PW(t). We apply our analysis to the stochastic process of the on-line foreign exchange rate for individual customers from the Sony bank and compare the moments with the empirical data analysis
P‐value based analysis for shared controls design in genome‐wide association studies

An appealing genome‐wide association study design compares one large control group against several disease samples. A pioneering study by the Wellcome Trust Case Control Consortium that employed such a design has identified multiple susceptibility regions, many of which have been independently replicated. While reusing a control sample provides effective utilization of data, it also creates correlation between association statistics across diseases. An observation of a large association statistic for one of the diseases may greatly increase chances of observing a spuriously large association for a different disease. Accounting for the correlation is also particularly important when screening for SNPs that might be involved in a set of diseases with overlapping etiology. We describe methods that correct association statistics for dependency due to shared controls, and we describe ways to obtain a measure of overall evidence and to combine association signals across multiple diseases. The methods we describe require no access to individual subject data, instead, they efficiently utilize information contained in P‐values for association reported for individual diseases. P‐value based combined tests for association are flexible and essentially as powerful as the approach based on aggregating the individual subject data. Genet. Epidemiol. 34:725–738, 2010. © 2010 Wiley‐Liss, Inc.
Case Fatality Rate and Length of Hospital Stay among Patients with Typhoid Intestinal Perforation in Developing Countries: A Systematic Literature Review

Background Typhoid fever remains a major health problem in the developing world. Intestinal perforation is a lethal complication and continues to occur in impoverished areas despite advances in preventive and therapeutic strategies. Objectives To estimate the case fatality rate (CFR) and length of hospital stay among patients with typhoid intestinal perforation in developing countries. Data Sources Peer-reviewed publications listed in PubMed and Google Scholar. Study Eligibility The publications containing data on CFR or length of hospitalization for typhoid fever from low, lower middle and upper middle income countries based on World Bank classification. Limits are English language, human research and publication date from 1st January 1991 to 31st December 2011. Participants Subjects with reported typhoid intestinal perforation. Interventions None, standard practice as reported in the publication. Study Appraisal and Synthesis Methods Systematic literature review followed by meta-analysis after regional classification on primary data. Descriptive methods were applied on secondary data. Results From 42 published reports, a total of 4,626 hospitalized typhoid intestinal perforation cases and 706 deaths were recorded (CFR = 15·4%; 95% CI; 13·0%–17·8%) with a significant regional differences. The overall mean length of hospitalization for intestinal perforation from 23 studies was 18.4 days (N = 2,542; 95% CI; 15.6–21.1). Limitations Most typhoid intestinal perforation studies featured in this review were from a limited number of countries. Conclusions The CFR estimated in this review is a substantial reduction from the 39.6% reported from a literature review for years 1960 to 1990. Aggressive resuscitation, appropriate antimicrobial coverage, and prompt surgical intervention may have contributed to decrease mortality. Implications The quantification of intestinal perforation outcomes and its regional disparities as presented here is valuable in prioritizing and targeting typhoid-preventive interventions to the most affected areas.
Insights into erythromycin action from studies of its activity as inducer of resistance

Appreciation of the inducibility of erythromycin resistance began as an observation in the clinical bacteriology laboratory during susceptibility testing of erythromycin-resistant clinical isolates of Staphylococcus aureus. It was noted that inhibition zones surrounding spiramycin, lincomycin, and pristinamycin I (streptogramin B family) test disks placed close to an erythromycin test disk deviated from the expected circular shape and assumed a distorted ‘‘D’’ shape instead. Such observations suggested a possible antagonistic interaction between erythromycin, on the one hand, and spiramycin, lincomycin, or pristinamycin I, on the other (5, 7). The interaction turned out to be a functional rather than a physical antagonism, and out of these observations grew the notion of erythromycin-inducible resistance toward erythromycin, initially (41, 55), and then, more generally, toward all the macrolide, lincosamide, and streptogramin type B (MLS) antibiotics (57). Vazquez (50) and Vazquez and Monro (52) showed that antibiotics belonging to each subclass of the MLS antibiotics competed with chloramphenicol for uptake by intact cells. Competition for binding to purified 50S ribosome subunits was shown only for macrolides and lincosamides but not for streptogramin type B antibiotics. Collectively, these observations suggested that an alteration of 50S subunit function was involved in resistant cells. In a study of the time and concentration dependence of induction, Weisblum et al. (58) showed that (i) the optimal erythromycin concentration for induction was between 10 and 100 ng/ml, the threshold of its inhibitory action, (ii) at the optimal inducing concentration of erythromycin cells became phenotypically resistant within 40 min, and (iii) ribosomes from induced cells apparently bound labeled erythromycin and lincomycin with a reduced affinity. By mixing ribosome preparations from susceptible and resistant cells and noting no loss of expected antibiotic binding activity, it was possible to exclude the alteration of the antibiotic by modifying enzymes present as contaminants in the ribosome preparation. Consistent with this picture, Allen (1) showed that cell extracts of resistant S. aureus carried out erythromycin-resistant protein synthesis in vitro, suggesting that a component of the protein-synthesizing machinery had been altered. A posttranscriptional methylation of a single adenine residue in 23S rRNA, comprising the induced biochemical alteration (30, 31), was located at Escherichia coli coordinate 2058 (A-2058) (47), and translational attenuation (16, 24), the mechanism for its regulation, was proposed. As discussed below, this unusual mechanism of gene regulation requires no repressor proteins but, instead, is based on the conformational isomerization of the ermC message to a translationally active form. How might this be achieved?
Epidemiology of Major Depressive Disorder Disability in the US Military: FY 2007–2012

Abstract This study assesses the incidence of major depressive disorder (MDD) disability discharge and retirement in the Army, Navy, Marine Corps and Air Force and describes MDD comorbidity. Service members with a disability discharge for either MDD (n = 2,882) or any nonpsychiatric disability (n = 56,145), between fiscal years 2007 and 2012, were included in the study population. Those with MDD disability at first evaluation but not at last evaluation were excluded. The incidence of MDD disability discharge increased significantly in the Army and Air Force between fiscal years 2007 and 2012. MDD disability retirement significantly increased in the Army, Navy, and Air Force. Females, and those who experienced at least one deployment, had higher incidence rates of MDD disability discharge. All services included spinal diseases and posttraumatic stress disorder in their top five comorbid categories. Given the association between trauma and MDD, further research into the role of both combat exposure and injury on MDD is merited.
The cohesin acetyltransferase Eco1 coordinates rDNA replication and transcription

Eco1 is the acetyltransferase that establishes sister‐chromatid cohesion during DNA replication. A budding yeast strain with an eco1 mutation that genocopies Roberts syndrome has reduced ribosomal DNA (rDNA) transcription and a transcriptional signature of starvation. We show that deleting FOB1—a gene that encodes a replication fork‐blocking protein specific for the rDNA region—rescues rRNA production and partially rescues transcription genome‐wide. Further studies show that deletion of FOB1 corrects the genome‐wide replication defects, nucleolar structure, and rDNA segregation that occur in the eco1 mutant. Our study highlights that the presence of cohesin at the rDNA locus has a central role in controlling global DNA replication and gene expression.
Complex networks in brain electrical activity

This letter reports a method to extract a functional network of the human brain from electroencephalogram measurements. A network analysis was performed on the resultant network and the statistics of the cluster coefficient, node degree, path length, and physical distance of the links, were studied. Even given the low electrode count of the experimental data the method was able to extract networks with network parameters that clearly depend on the type of stimulus presented to the subject. This type of analysis opens a door to studying the cerebral networks underlying brain electrical activity, and links the fields of complex networks and cognitive neuroscience.
A microwave inverse scattering technique for image reconstruction based on a genetic algorithm

The problem of reconstructing locations, shapes, and dielectric permittivity distributions of two-dimensional dielectric objects from measurements of the scattered electric field is addressed. A numerical approach is proposed which is based on a multi-illumination multiview processing. In particular, the inverse problem is recast as a global nonlinear optimization problem, which is solved by a genetic algorithm. The final objective of the approach is the image reconstruction of highly contrasted bodies.
Penton-Dodecahedral Particles Trigger Opening of Intercellular Junctions and Facilitate Viral Spread during Adenovirus Serotype 3 Infection of Epithelial Cells

Human adenovirus serotypes Ad3, Ad7, Ad11, and Ad14 use the epithelial junction protein desmoglein 2 (DSG2) as a receptor for infection. During Ad infection, the fiber and penton base capsid proteins are produced in vast excess and form hetero-oligomers, called pentons. It has been shown for Ad3 that pentons self-assemble into penton-dodecahedra (PtDd). Our previous studies with recombinant purified Ad3 PtDd (produced in insect cells) showed that PtDd bind to DSG2 and trigger intracellular signaling resulting in the transient opening of junctions between epithelial cells. So far, a definitive proof for a function of Ad3 PtDd in the viral life cycle is elusive. Based on the recently published 3D structure of recombinant Ad3 PtDd, we generated a penton base mutant Ad3 vector (mu-Ad3GFP). mu-Ad3GFP is identical to its wild-type counterpart (wt-Ad3GFP) in the efficiency of progeny virus production; however, it is disabled in the production of PtDd. For infection studies we used polarized epithelial cancer cells or cell spheroids. We showed that in wt-Ad3GFP infected cultures, PtDd were released from cells before viral cytolysis and triggered the restructuring of epithelial junctions. This in turn facilitated lateral viral spread of de novo produced virions. These events were nearly absent in mu-Ad3GFP infected cultures. Our in vitro findings were consolidated in mice carrying xenograft tumors derived from human epithelial cancer cells. Furthermore, we provide first evidence that PtDd are also formed by another DSG2-interacting Ad serotype, the newly emerged, highly pathogenic Ad14 strain (Ad14p1). The central finding of this study is that a subgroup of Ads has evolved to generate PtDd as a strategy to achieve penetration into and dissemination in epithelial tissues. Our findings are relevant for basic and applied virology, specifically for cancer virotherapy.
Early assessment of brain maturation by MR imaging segmentation in neonates and premature infants.

PURPOSE We evaluated the impact of premature extrauterine life on brain maturation. PATIENTS AND METHODS Twelve neonates underwent MR imaging at 40 (39.64 +/- 0.98) weeks (full term). Fifteen premature infants underwent 2 MR imaging examinations, after birth (preterm at birth) and at 40 weeks (41.03 +/- 1.33) (preterm at term). A 3D MR imaging technique was used to measure brain volumes compared with intracranial volume: total brain volume, cortical gray matter, myelinated white matter, unmyelinated white matter, basal ganglia (BG), and CSF. RESULTS The average absolute volume of intracranial volume (269.8 mL +/- 36.5), total brain volume (246.5 +/- 32.3), cortical gray matter (85.53 mL +/- 22.23), unmyelinated white matter (142.4 mL +/-14.98), and myelinated white matter (6.099 mL +/-1.82) for preterm at birth was significantly lower compared with that for the preterm at term: the average global volume of intracranial volume (431.7 +/- 69.98), total brain volume (391 +/- 66,1), cortical gray matter (179 mL +/- 41.54), unmyelinated white matter (185.3 mL +/- 30.8), and myelinated white matter (10.66 mL +/- 3.05). It was also lower compared with that of full-term infants: intracranial volume (427.4 mL +/- 53.84), total brain volume (394 +/- 49.22), cortical gray matter (181.4 +/- 29.27), unmyelinated white matter (183.4 +/- 27.37), and myelinated white matter (10.72 +/- 4.63). The relative volume of cortical gray matter (30.62 +/- 5.13) and of unmyelinated white matter (53.15 +/- 4.8) for preterm at birth was significantly different compared with the relative volume of cortical gray matter (41.05 +/- 5.44) and of unmyelinated white matter (43.22 +/- 5.11) for the preterm at term. Premature infants had similar brain tissue volumes at 40 weeks to full-term infants. CONCLUSION MR segmentation techniques demonstrate that cortical neonatal maturation in moderately premature infants at term and term-born infants was similar.
Limited memory preconditioners for symmetric indefinite problems with application to structural mechanics

This paper presents a class of limited memory preconditioners (LMP) for solving linear systems of equations with symmetric indefinite matrices and multiple right‐hand sides. These preconditioners based on limited memory quasi‐Newton formulas require a small number k of linearly independent vectors and may be used to improve an existing first‐level preconditioner. The contributions of the paper are threefold. First, we derive a formula to characterize the spectrum of the preconditioned operator. A spectral analysis of the preconditioned matrix shows that the eigenvalues are all real and that the LMP class is able to cluster at least k eigenvalues at 1. Secondly, we show that the eigenvalues of the preconditioned matrix enjoy interlacing properties with respect to the eigenvalues of the original matrix provided that the k linearly independent vectors have been prior projected onto the invariant subspaces associated with the eigenvalues of the original matrix in the open right and left half‐plane, respectively. Third, we focus on theoretical properties of the Ritz‐LMP variant, where Ritz information is used to determine the k vectors. Finally, we illustrate the numerical behaviour of the Ritz limited memory preconditioners on realistic applications in structural mechanics that require the solution of sequences of large‐scale symmetric saddle‐point systems. Numerical experiments show the relevance of the proposed preconditioner leading to a significant decrease in terms of computational operations when solving such sequences of linear systems. A saving of up to 43% in terms of computational effort is obtained on one of these applications. Copyright © 2016 John Wiley & Sons, Ltd.