Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Helicobacter pylori Seropositivity in Insulin Sensitivity, Beta Cell Function, and Abnormal Glucose Tolerance

Infection, for example, Helicobacter pylori (H. pylori), has been thought to play a role in the pathogenesis of type 2 diabetes mellitus (T2DM). Our aim was to determine the role of H. pylori infection in glucose metabolism in an American cohort. We examined data from 4,136 non-Hispanic white (NHW), non-Hispanic black (NHB), and Mexican Americans (MA) aged 18 and over from the NHANES 1999-2000 cohort. We calculated the odds ratios for states of glucose tolerance based on the H. pylori status. We calculated and compared homeostatic model assessment insulin resistance (HOMA-IR) and beta cell function (HOMA-B) in subjects without diabetes based on the H. pylori status. The results were adjusted for age, body mass index (BMI), poverty index, education, alcohol consumption, tobacco use, and physical activity. The H. pylori status was not a risk factor for abnormal glucose tolerance. After adjustment for age and BMI and also adjustment for all covariates, no difference was found in either HOMA-IR or HOMA-B in all ethnic and gender groups except for a marginally significant difference in HOMA-IR in NHB females. H. pylori infection was not a risk factor for abnormal glucose tolerance, nor plays a major role in insulin resistance or beta cell dysfunction.
Three‐dimensional tracking of axonal projections in the brain by magnetic resonance imaging

The relationship between brain structure and complex behavior is governed by large‐scale neurocognitive networks. The availability of a noninvasive technique that can visualize the neuronal projections connecting the functional centers should therefore provide new keys to the understanding of brain function. By using high‐resolution three‐dimensional diffusion magnetic resonance imaging and a newly designed tracking approach, we show that neuronal pathways in the rat brain can be probed in situ. The results are validated through comparison with known anatomical locations of such fibers. Ann Neurol 1999;45:265–269
Evidence for DNA Cleavage Caused Directly by a transfer RNA-Targeting Toxin

The killer yeast species Pichia acaciae produces a heteromeric killer protein, PaT, that causes DNA damage and arrests the cell cycle of sensitive Saccharomyces cerevisiae in the S phase. However, the mechanism by which DNA damage occurs remains elusive. A previous study has indicated that Orf2p, a subunit of PaT, specifically cleaves an anticodon loop of an S. cerevisiae transfer RNA (tRNAGln mcm5s2UUG). This finding raised a question about whether the DNA damage is a result of the tRNA cleavage or whether Orf2p directly associates with and cleaves the genomic DNA of sensitive yeast cells. We showed that Orf2p cleaves genomic DNA in addition to cleaving tRNA in vitro. This DNA cleavage requires the same Orf2p residue as that needed for tRNA cleavage, His299. The expression of Orf2p, in which His299 was substituted to alanine, abolished the cell cycle arrest of the host cell. Moreover, the translation impairment induced by tRNA cleavage enabled Orf2p to enter the nucleus, thereby inducing histone phosphorylation.
Genetic Diagnosis of Two Dopa-Responsive Dystonia Families by Exome Sequencing

Dopa-responsive dystonia, a rare disorder typically presenting in early childhood with lower limb dystonia and gait abnormality, responds well to levodopa. However, it is often misdiagnosed with the wide spectrum of phenotypes. By exome sequencing, we make a rapid genetic diagnosis for two atypical dopa-responsive dystonia pedigrees. One pedigree, presented with prominent parkinsonism, was misdiagnosed as Parkinson's disease until a known mutation in GCH1 (GTP cyclohydrolase 1) gene (NM_000161.2: c.631_632delAT, p.Met211ValfsX38) was found. The other pedigree was detected with a new compound heterozygous mutation in TH (tyrosine hydroxylase) gene [(NM_000360.3: c.911C>T, p.Ala304Val) and (NM_000360.3: c.1358G>A, p.Arg453His)], whose proband, a pregnant woman, required a rapid and less-biased genetic diagnosis. In conclusion, we demonstrated that exome sequencing could provide a precise and rapid genetic testing in the diagnosis of Mendelian diseases, especially for diseases with wide phenotypes.
Plasma extravasation induced by dietary supplemented histamine in histamine‐free mice

Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. To evaluate the role of histamine in skin allergic reaction, we used HDC gene knockout mice lacking histamine. No plasma extravasation reaction was observed in HDC(–/–) mice after passive cutaneous anaphylaxis (PCA) test. Compound 48/80, a mast cell granule depletor, produced plasma extravasation inHDC(+/+) mice but no extravasation in HDC(–/–) mice. Interestingly, orally administered histamine was distributed in the skin in HDC(–/–) mice and in these histamine‐supplemented mice the plasma extravasation reaction was observed after the injection of compound 48/80 and the PCA test. Cultured bone marrow‐derived mast cells of HDC(–/–) mice took up histamine from the histamine‐supplemented medium into the secretory granules. The absorbed histamine was released in response to the same antigen and antibody combination used as in PCA test. In contrast to the immediate‐type response, the delayed‐type hypersensitive response, observed as a thickening of the ear skin after trinitrochlorobenzene challenge (following sensitization), showed no differences between HDC(+/+) and HDC(–/–) mice. Therefore, among the allergic skin reactions, histamine is revealed to be an important mediator especially for the plasma extravasation in an immediate‐type allergy model.
Toward energy-efficient cloud computing: Prediction, consolidation, and overcommitment

Energy consumption has become a significant concern for cloud service providers due to financial as well as environmental factors. As a result, cloud service providers are seeking innovative ways that allow them to reduce the amount of energy that their data centers consume. They are calling for the development of new energy-efficient techniques that are suitable for their data centers. The services offered by the cloud computing paradigm have unique characteristics that distinguish them from traditional services, giving rise to new design challenges as well as opportunities when it comes to developing energy-aware resource allocation techniques for cloud computing data centers. In this article we highlight key resource allocation challenges, and present some potential solutions to reduce cloud data center energy consumption. Special focus is given to power management techniques that exploit the virtualization technology to save energy. Several experiments, based on real traces from a Google cluster, are also presented to support some of the claims we make in this article.
Long-Term (29 Years) Results of Reconstructive Surgery in Rheumatic Mitral Valve Insufficiency

Background—Results of conservative surgery are well established in degenerative mitral valve (MV) insufficiency. However, there are controversies in rheumatic disease. This study is the evaluation of one center for rheumatic MV insufficiency based on a functional approach. Methods and Results—From 1970 to 1994, 951 patients with rheumatic MV insufficiency were operated on with the reconstructive techniques elaborated by Alain Carpentier. Aortic valve diseases were excluded. Mean age was 25.8 years (4 to 75), and sinus rhythm was present in 63%. The functional classification used was type I, normal leaflet motion, 71 patients (7%); type II, prolapsed leaflet, 311 patients (33%); and type III, restricted leaflet motion, 345 patients (36%). The combined lesion of prolapse of the anterior leaflet and restriction of the posterior was present in 224 patients (24%). Surgical techniques used were implantation of a prosthetic ring in 95%, shortening of the chords and leaflet enlargement with autologous pericardium, and commissurotomy. Hospital mortality rate was 2%. The mean follow-up was 12 years (maximum, 29 years): 8618 patients per year. Actuarial survival was 89±19% at 10 years and 82±18% at 20 years. The rate of thromboembolic events was 0.4% patients per year (33 events), with 3 deaths. Freedom from reoperation was 82±19% at 10 years and 55±25% at 20 years. The main cause (83%) of reoperation was progressive fibrosis of the MV. The actuarial rate of reoperation was 2% patients per year and was correlated to the degree of preoperative fibrosis. Conclusions—Conservative surgery of rheumatic MV insufficiency has a low hospital mortality rate and an acceptable rate of reoperation. The results are excellent regarding the minimal risk of thromboembolic events.
Trimetazidine as cardioplegia addictive without pre-treatment does not improve myocardial protection: study in a swine working heart model.

OBJECTIVE The aim of this study is to verify in an isolated working heart swine model if the acute administration of trimetazidine to cardioplegia, without pre-treatment improves heart performance. METHODS Eighteen pairs of swine were used in this working heart model, divided into three groups (n = 6) that underwent regional and global ischemia. Each group was selected to a different treatment: St. Thomas cardioplegia (ST), St. Thomas enriched with trimetazidine (TMZ) and control group (Co). Data was collected during reperfusion period at 30, 60 and 90 minutes. Hemodynamic parameters such as elastance contractility index (Emax), preload recruitable stroke work relationship (PRSW) and heart "stiffness" (EDPVR) were measured. Other data included coronary flow, lactate, oxygen and glucose consumption. Results were statistically analyzed. RESULTS All contractility data were not significantly different among three groups. Lactate became constantly higher according to time uniformly in all three groups. Coronary flow, glucose consumption and oxygen consumption presented large variations during time periods but according to treatments showed no statistical differences in all three groups. Left ventricle final weight was significantly lower in trimetazidine group compared to both other groups. CONCLUSION Administration of trimetazidine enhanced cardioplegia, without pre-treatment, showed no hemodynamic or metabolic improvement in swine isolated working heart model.
Preterm Delivery Risk in Relation to Maternal Occupational and Leisure Time Physical Activity Among Thai Women.

BACKGROUND Little is known about the relationship between maternal occupational physical exertion and leisure time physical activity (LTPA) with preterm delivery (PTD) among Thai women, a population that differs in many respects from women in Western countries. OBJECTIVES To evaluate associations of maternal occupational physical exertion and LTPA with PTD in aggregate and in subgroups (i.e., spontaneous preterm labor, preterm premature rupture of membrane, medically indicated preterm delivery, moderate preterm delivery [gestational age 32-36 weeks], and very preterm delivery [<32 weeks]) among Thai women. METHODS This case-control study included 467 PTD cases and 467 term controls. Maternal occupational exertion during pregnancy, as well as habitual engagement in LTPA before and during pregnancy was assessed using a structured questionnaire administered after delivery. Logistic regression procedures were used to examine relationships between both occupational and leisure time physical activity and PTD. RESULTS After controlling for potential confounders, women who reported heavy physical occupational exertion during pregnancy, compared with other women, had a 2.42-fold increased risk of PTD overall [OR=2.42, 95% CI: 1.15, 5.09]. Very PTD [OR=4.57, 95% CI: 1.65, 12.64] and medically indicated PTD [OR=3.79, 95% CI: 1.54, 9.32] were particularly strongly associated with heavy occupational exertion. Maternal participation in LTPA before pregnancy was associated with a 24% reduction in PTD risk overall [OR=0.76, 95% CI: 0.57, 1.00], though no similar pattern in risk reduction was observed for LTPA performed during the first 6 months of pregnancy [OR=0.96, 95% CI: 0.68, 1.36]. CONCLUSION Consistent with some previous reports, we noted that heavy occupational physical exertion is associated with at least a doubling in PTD risk. Patterns of associations of PTD risk with LTPA were less well delineated in this Thai population.
Temperature-Dependent Conformational Changes in Herpes Simplex Virus ICP 4 That Affect Transcription Activation Peter Compel

The C-terminal 500 amino acids of herpes simplex virus type 1 ICP4 are required for full activator function and viral growth and are known to participate in interactions consistent with the role of ICP4 as an activator of transcription. Oligonucleotide mutagenesis was used to target stretches of amino acids that are conserved with the ICP4 analogs of other alphaherpesviruses and were also predicted to be exposed on the surface of the molecule. Seven mutants were isolated that possessed one to three amino acid changes to the residue alanine in four regions between residues 1000 and 1200. The mutants generated were analyzed first in transfection assays and subsequently after introduction into the viral genome. A number of phenotypes representing different degrees of functional impairment were observed. In transient assays conducted at 37°C, mutant M2 was indistinguishable from wild-type ICP4. Mutants M6 and M7 were marginally impaired. M3, M4, and M5 were more significantly impaired but still able to activate transcription, and M1 was completely impaired. In the context of the viral genome, M1, M3, and M7 were found to be temperature sensitive for growth. All three overproduced immediate-early (IE) proteins at the nonpermissive temperature (NPT). M3 and M7 produced early but not late proteins, and M1 produced neither early nor late proteins, at the NPT. The ICP4 proteins synthesized by all of the mutants tested were able to bind to specific ICP4 binding sites in electrophoretic mobility shift experiments. However, the DNA-protein complexes formed with the ICP4 from M1, M3, or M7 produced at the NPT possessed altered mobility. These complexes were not supershifted by a monoclonal antibody that recognizes an epitope in the C terminus; however, they were supershifted by a monoclonal antibody that recognizes the N terminus. The results suggest that the mutant forms of ICP4, while able to bind to DNA, are conformationally altered at the NPT, thus impairing the ability of the protein to activate transcription to different extents. The complete lack of ICP4 function characteristic of the M1 protein, and the inability of all the mutants to attenuate IE gene expression, suggest that the mutations additionally affect functions of the N terminus to different extents.
Herpes Simplex Virus Type 1 DNA Polymerase

Like true DNA replicases, herpes simplex virus type 1 DNA polymerase is equipped with a proofreading 3′-5′-exonuclease. In order to assess the functional significance of conserved residues in the putative exonuclease domain, we introduced point mutations as well as deletions within and near the conserved motifs' exonuclease (Exo) I, II, and III of the DNA polymerase gene from a phosphonoacetic acid-resistant derivative of herpes simplex virus-1 strain ANG. We examined the catalytic activities of the partially purified enzymes after overexpression by recombinant baculovirus. Mutations of the motifs' Exo I (D368A, E370A) and Exo III (Y577F, D581A) yielded enzymes without detectable and severely impaired 3′-5′-exonuclease activities, respectively. Except for the Exo I mutations, all other Exo mutations examined affected both exonuclease and polymerization activities. Mutant enzymes D368A, E370A, Y557S, and D581A showed a significant ability to extend mispaired primer termini. Mutation Y557S resulted in a strong reduction of the 3′-5′-exonuclease activity and in a polymerase activity that was hyperresistant to phosphonoacetic acid. The results of the mutational analysis provide evidence for a tight linkage of polymerase and 3′-5′-exonuclease activity in the herpesviral enzyme.
Cancer screening participation in schizophrenic outpatients and the influence of their functional disability on the screening rate: A cross‐sectional study in Japan

The influence of schizophrenic patients’ functional disability on cancer screening participation worldwide is unclear. There are few findings on the disparities in schizophrenic patients’ participation in cancer screening programs in Asia. The aim of this study was to investigate the screening rate and the associations between screening and symptom severity/functional disability in patients with schizophrenia.
Phenols in Leaves and Bark of Fagus sylvatica as Determinants of Insect Occurrences

Beech forests play an important role in temperate and north Mediterranean ecosystems in Greece since they occupy infertile montane soils. In the last glacial maximum, Fagus sylvatica (beech) was confined to Southern Europe where it was dominant and in the last thousand years has expanded its range to dominate central Europe. We sampled four different beech forest types. We found 298 insect species associated with beech trees and dead beech wood. While F. sylvatica and Quercus (oak) are confamilial, there are great differences in richness of the associated entomofauna. Insect species that inhabit beech forests are less than one fifth of those species living in oak dominated forests despite the fact that beech is the most abundant central and north European tree. There is a distinct paucity of monophagous species on beech trees and most insect species are shared between co-occurring deciduous tree species and beech. This lack of species is attributed to the vegetation history and secondary plant chemistry. Bark and leaf biophenols from beech indicate that differences in plant secondary metabolites may be responsible for the differences in the richness of entomofauna in communities dominated by beech and other deciduous trees.
Dual Gamma Rhythm Generators Control Interlaminar Synchrony in Auditory Cortex

Rhythmic activity in populations of cortical neurons accompanies, and may underlie, many aspects of primary sensory processing and short-term memory. Activity in the gamma band (30 Hz up to >100 Hz) is associated with such cognitive tasks and is thought to provide a substrate for temporal coupling of spatially separate regions of the brain. However, such coupling requires close matching of frequencies in co-active areas, and because the nominal gamma band is so spectrally broad, it may not constitute a single underlying process. Here we show that, for inhibition-based gamma rhythms in vitro in rat neocortical slices, mechanistically distinct local circuit generators exist in different laminae of rat primary auditory cortex. A persistent, 30–45 Hz, gap-junction-dependent gamma rhythm dominates rhythmic activity in supragranular layers 2/3, whereas a tonic depolarization-dependent, 50–80 Hz, pyramidal/interneuron gamma rhythm is expressed in granular layer 4 with strong glutamatergic excitation. As a consequence, altering the degree of excitation of the auditory cortex causes bifurcation in the gamma frequency spectrum and can effectively switch temporal control of layer 5 from supragranular to granular layers. Computational modeling predicts the pattern of interlaminar connections may help to stabilize this bifurcation. The data suggest that different strategies are used by primary auditory cortex to represent weak and strong inputs, with principal cell firing rate becoming increasingly important as excitation strength increases.
BMDFM: a hybrid dataflow runtime parallelization environment for shared memory multiprocessors

To complement existing compiler-optimization methods we propose a programming model and a runtime system called BMDFM (Binary Modular DataFlow Machine), a novel hybrid parallel environment for SMP (Shared Memory Symmetric Multiprocessors), that creates a data-dependence graph and exploits parallelism of user application programs at run time. This thesis describes the design and provides a detailed analysis of BMDFM, which uses a dataflow runtime engine instead of a plain fork-join runtime library, thus providing transparent dataflow semantics on the top virtual machine level. Our hybrid approach eliminates disadvantages of the parallelization at compile-time, the directive based paradigm and the dataflow computational model. BMDFM is portable and is already implemented on a set of available SMP platforms. The transparent dataflow paradigm does not require parallelization and synchronization directives. The BMDFM runtime system shields the end-users from these details.
A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non–Small Cell Lung Cancer Patients

Purpose: EGFR is a well-validated target for patients with non–small cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF conjugated to a carrier protein and Montanide ISA51 as adjuvant. The vaccine is intended to induce antibodies against self EGFs that block EGF–EGFR interaction. Experimental Design: To evaluate overall survival, safety, immunogenicity, and EGF concentration in serum after CIMAvax-EGF, a randomized phase III trial was done in patients with advanced NSCLC. Four to 6 weeks after first-line chemotherapy, 405 patients with stage IIIB/IV NSCLC were randomly assigned to a vaccine group, which received CIMAvax-EGF or a control group, treated with best supportive care. Results: Long-term vaccination was very safe. Most frequent adverse reactions were grade 1 or 2 injection-site pain, fever, vomiting, and headache. Vaccination induced anti-EGF antibodies and decreased serum EGF concentration. In the safety population, median survival time (MST) was 10.83 months in the vaccine arm versus 8.86 months in the control arm. These differences were not significant according the standard log rank (HR, 0.82; P = 0.100), but according a weighted log rank (P = 0.04) that was applied once the nonproportionality of the HR was verified. Survival benefit was significant (HR, 0.77; P = 0.036) in the per-protocol setting (patients receiving at least four vaccine doses): MST was 12.43 months for the vaccine arm versus 9.43 months for the control arm. MST was higher (14.66 months) for vaccinated patients with high EGF concentration at baseline. Conclusions: Switch maintenance with CIMAvax-EGF was well tolerated and significantly increased MST of patients that completed induction vaccination. Baseline EGF concentration predicted survival benefit. Clin Cancer Res; 22(15); 3782–90. ©2016 AACR.