Miracle-dz/UniFAR-FTUs huggingface dataset:
Aerobic interval training compensates age related decline in cardiac function

Objectives. To study the effect of aerobic interval training (AIT) on myocardial function in sedentary seniors compared to master athletes (MA) and young controls. Design. Sixteen seniors (72± 1 years, 10 men) performed AIT (4 × 4 minutes) at ∼90% of maximal heart rate three times per week for 12 weeks. Results were compared with 11 male MA (74± 2 years) and 10 young males (23±2 years). Results. Seniors had an impaired diastolic function compared to the young at rest. AIT improved resting diastolic parameters, increased E/A ratio (44%, p <0.01), early diastolic tissue Doppler velocity (e′) (11%, p <0.05) and e′ during exercise (11%, p <0.01), shortened isovolumic relaxation rate (IVRT) (13%, p <0.01). Left ventricle (LV) systolic function (S′) was unaffected at rest, whereas S′ during stress echo increased by 29% (p <0.01). Right ventricle (RV) S′ and RV fractional area change (RFAC) increased (9%, p <0.01, 12%, p =0.01, respectively), but not RV e′. MA had the highest end-diastolic volume, stroke volume, diastolic reserve and RV S′. Conclusion. AIT partly reversed the impaired age related diastolic function in healthy seniors at rest, improved LV diastolic and systolic function during exercise as well as RV S′ at rest.
Cyclin D1 Regulates Cellular Migration through the Inhibition of Thrombospondin 1 and ROCK Signaling

ABSTRACT Cyclin D1 is overexpressed in human tumors, correlating with cellular metastasis, and is induced by activating Rho GTPases. Herein, cyclin D1-deficient mouse embryo fibroblasts (MEFs) exhibited increased adhesion and decreased motility compared with wild-type MEFs. Retroviral transduction of cyclin D1 reversed these phenotypes. Mutational analysis of cyclin D1 demonstrated that its effects on cellular adhesion and migration were independent of the pRb and p160 coactivator binding domains. Genomewide expression arrays identified a subset of genes regulated by cyclin D1, including Rho-activated kinase II (ROCKII) and thrombospondin 1 (TSP-1). cyclin D1−/− cells showed increased Rho GTP and ROCKII activity and signaling, with increased phosphorylation of LIM kinase, cofilin (Ser3), and myosin light chain 2 (Thr18/Ser19). Cyclin D1 repressed ROCKII and TSP-1 expression, and the migratory defect of cyclin D1−/− cells was reversed by ROCK inhibition or TSP-1 immunoneutralizing antibodies. cyclin E knockin to the cyclin D1−/− MEFs rescued the DNA synthesis defect of cyclin D1−/− MEFs but did not rescue either the migration defect or the abundance of ROCKII. Cyclin D1 promotes cellular motility through inhibiting ROCK signaling and repressing the metastasis suppressor TSP-1.
Novel epitopes identified by anti-PrP monoclonal antibodies produced following immunization of Prnp0/0 Balb/cJ mice with purified scrapie prions.

Prions, or infectious proteins, cause a class of uniformly fatal neurodegenerative diseases. Prions are composed solely of an aberrantly folded isoform (PrP(Sc)) of a normal cellular protein (PrP(C)). Shared sequence identity of PrP(Sc) with PrP(C) has limited the detection sensitivity of immunochemical assays, as antibodies specific for the disease-causing PrP(Sc) isoform have not been developed. Here we report the generation of three new monoclonal antibodies (MAbs) to PrP, which were isolated following immunization of Prnp(0/0) Balb/cJ mice with highly purified PrP(Sc) isolated from brain lipid rafts. Epitope mapping using synthetic PrP peptides revealed that the three MAbs bind different epitopes of PrP. The DRM1-31 MAb has a conformational epitope at the proposed binding site for the putative prion conversion co-factor "protein X. " The DRM1-60 MAb binds a single linear epitope localized to the β2-α2 loop region of PrP, whereas DRM2-118 binds an epitope that includes sequences within the octarepeat region and near the site of N-terminal truncation of PrP(Sc) by proteinase K. Our novel anti-PrP MAbs with defined PrP epitopes may be useful in deciphering the conformational conversion of PrP(C) into PrP(Sc).
Sista: a Metacircular Architecture for Runtime Optimisation Persistence. (Sista: une architecture meta-circulaire pour la persistance d'optimisations à la volée)

Most high-level programming languages run on top of a virtual machine (VM) to abstract away from the underlying hardware. To reach high-performance, the VM typically relies on an optimising just-in-time compiler (JIT), which speculates on the program behavior based on its first runs to generate at runtime efficient machine code and speed-up the program execution. As multiple runs are required to speculate correctly on the program behavior, such a VM requires a certain amount of time at start-up to reach peak performance. The optimising JIT itself is usually compiled ahead-of-time to executable code as part of the VM. The dissertation proposes Sista, an architecture for an optimising JIT, in which the optimised state of the VM can be persisted across multiple VM start-ups and the optimising JIT is running in the same runtime than the program executed. To do so, the optimising JIT is split in two parts. One part is high-level: it performs optimisations specific to the programming language run by the VM and is written in a metacircular style. Staying away from low-level details, this part can be read, edited and debugged while the program is running using the standard tool set of the programming language executed by the VM. The second part is low-level: it performs machine specific optimisations and is compiled ahead-of-time to executable code as part of the VM. The two parts of the JIT use a well-defined intermediate representation to share the code to optimise. This representation is machine-independent and can be persisted across multiple VM start-ups, allowing the VM to reach peak performance very quickly. To validate the architecture, the dissertation includes the description of an implementation on top of Pharo Smalltalk and its VM. The implementation is able to run a large set of benchmarks, from large application benchmarks provided by industrial users to micro-benchmarks used to measure the performance of specific code patterns. The optimising JIT is implemented according to the architecture proposed and shows significant speed-up (up to 5x) over the current production VM. In addition, large benchmarks show that peak performance can be reached almost immediately after VM start-up if the VM can reuse the optimised state persisted from another run.
Predicting and preventing measles epidemics in New Zealand: application of a mathematical model

A mathematical model of the dynamics of measles in New Zealand was developed in 1996. The model successfully predicted an epidemic in 1997 and was instrumental in the decision to carry out an intensive MMR (measles–mumps–rubella) immunization campaign in that year. While the epidemic began some months earlier than anticipated, it was rapidly brought under control, and its impact on the population was much reduced. In order to prevent the occurrence of further epidemics in New Zealand, an extended version of the model has since been developed and applied to the critical question of the optimal timing of MMR immunization.
Functional Assays of Oxidative Stress Using Genetically Engineered Escherichia coli Strains

Oxidative stress may be induced in bacteria by exogenous biocidal agents and is involved in endogenous metabolism. The oxyR operon is a main sensor of oxidative stress and oxyR‐deficient bacteria show enhanced sensitivity to oxidative stress and increased accumulation of intracellular reactive oxygen species (ROS). Flow cytometric functional assays in bacteria are limited by the impaired penetration of vital dyes trough the cell wall. Escherichia coli B WP2 strains possess an altered cell‐wall lipopolysaccharide that leads to increased membrane permeability. Flow cytometric analysis of WP2 strains is a convenient alternative for cytometric assays of bacterial function. This unit presents protocols for flow cytometric studies of intracellular oxidative stress in two E. coli B WP2 strains, wild‐type or deficient in the oxyR function, using ROS‐sensitive fluorogenic substrates. Support Protocols describe preparation of phage C21 stock for bacterial verification, verification of the WP2 phenotype, and verification of the deficiency in oxyR function.
Inhalation of the Phosphodiesterase-3 Inhibitor Milrinone Attenuates Pulmonary Hypertension in a Rat Model of Congestive Heart Failure

Background:Most patients with congestive heart failure (CHF) develop pulmonary venous hypertension, but right ventricular afterload is frequently further elevated by increased pulmonary vascular resistance. To investigate whether inhalation of a vasodilatory phosphodiesterase-3 inhibitor may reverse this potentially detrimental process, the authors studied the effects of inhaled or intravenous milrinone on pulmonary and systemic hemodynamics in a rat model of CHF. Methods:In male Sprague-Dawley rats, CHF was induced by supracoronary aortic banding, whereas sham-operated rats served as controls. Milrinone was administered as an intravenous infusion (0.2–1 &mgr;g · kg body weight−1 · min−1) or by inhalation (0.2–5 mg/ml), and effects on pulmonary and systemic hemodynamics and lung water content were measured. Results:In CHF rats, intravenous infusion of milrinone reduced both pulmonary and systemic arterial blood pressure. In contrast, inhalation of milrinone predominantly dilated pulmonary blood vessels, resulting in a reduced pulmonary-to-systemic vascular resistance ratio. Repeated milrinone inhalations in 20-min intervals caused a stable reduction of pulmonary artery pressure. No hemodynamic effects were detected when 0.9% NaCl was administered instead of milrinone or when milrinone was inhaled in sham-operated rats. No indications of potentially adverse effects of milrinone inhalation in CHF, such as left ventricular volume overload, were detected. Moreover, lung edema was significantly reduced by repeated milrinone inhalation. Conclusion:If these results can be confirmed in humans, inhalation of nebulized milrinone may present a novel, effective, safe, and pulmonary selective strategy for the treatment of pulmonary venous hypertension in CHF.
Prey or predator? Body size of an approaching animal affects decisions to attack or escape

An animal must assess an approaching heterospecific to determine whether it is prey or predator. Because prey tend to be smaller than their predators, foraging responses decrease and escape responses are predicted to increase over a range of approacher size. Sufficiently, small approachers may be readily identified as prey and large ones as predators. However, more time and closer approach may be required to assess approachers of intermediate size, leading to predictions that predator/prey evaluations may differ among individuals, that attacks on the approacher begin from shorter distances than for smaller approachers and that escape begins at shorter distance than for larger approachers. In a field experiment, we dragged tethered model orthopterans of 3 sizes toward 2 lizard species that differ in body size. As model size increased, lizards were more likely to flee and had longer flight initiation distance. As model size decreased, lizards were more likely to advance toward and bite models and began advances from longer distances. At the intermediate model size, some individuals fled and others attacked intermediate models. Sceloporus jarrovii, the larger species, was more likely to attack and less likely to flee than S. virgatus at intermediate model size. The prediction of optimal escape theory that flight initiation distance increases with predator size due to greater risk was verified. Our evidence indicates that as approacher size increases, successive transitions occur between rapid assessment of the approacher as prey, uncertainty requiring closer inspection, and rapid identification of a potential predator. Copyright 2010, Oxford University Press.
Family and School Influences on Youths' Behavioral and Academic Outcomes: Cross-Level Interactions between Parental Monitoring and Character Development Curriculum

ABSTRACT The authors examined the joint (interactive) roles of the Second Step curriculum (a validated social-emotional learning and bullying prevention program; Committee for Children, Seattle, WA) and parenting practices on students' behavioral and academic outcomes in Grades 5–8. Participants were 763 parents and their children from 22 schools (8 control and 14 treatment). A 2-level random coefficient model was conducted to assess the effect of parental monitoring on school outcomes, as well as the interaction between character development curriculum and parental monitoring. Results indicated that parental monitoring was a significant predictor of school behaviors and school grades. Furthermore, the Second Step curriculum moderated the relationship between parental monitoring and problem behaviors, prosocial behaviors, and grades at school. Specifically, in schools without the Second Step curriculum parental monitoring predicted higher school grades but had no impact on students' school behaviors. By contrast, in schools with the Second Step curriculum, parental monitoring predicted fewer problem behaviors as well as more prosocial behaviors. The study results highlight the joint influences of the family and the school in children's behavioral and academic trajectories. Results have implications for education and intervention, including improving the school climate, student behaviors, and learning or achievement.
Preparation and mechanical properties of edible rapeseed protein films.

UNLABELLED Edible films were manufactured from rapeseed oil extraction residues. To prepare rapeseed protein (RP) films, various concentrations of plasticizers and emulsifiers were incorporated into the preparation of a film-forming solution. The optimal conditions for the preparation of the RP film were 2% sorbitol/0.5% sucrose as plasticizer and 1.5% polysorbate 20 as an emulsifier. In addition, RP blend films were prepared. Gelidium corneum or gelatin was added to improve the physical properties of the RP film, and the highest tensile strength value of the films was 53.45 MPa for the 3% RP/4% gelatin film. Our results suggest that the RP-gelatin blend film is suitable for applications in food packaging. PRACTICAL APPLICATION Edible RP films prepared in the present investigation can be applied in food packaging.
Aroclor 1254 causes atrophy of exocrine pancreas in mice and the mechanism involved

Polychlorinated biphenyls (PCBs) are a class of organic pollutants that have been linked to pancreatic disease. However, their role in affecting the exocrine function of pancreas and the underlying mechanism remains elusive. In the present study, male C57 mice were treated with Aroclor 1254, a commercially available PCBs mixture, at a dosage of 0.5, 5, 50, or 500 μg kg−1 every 3 days by oral gavage. Decrease in pancreas/soma index and acinar atrophy were observed in the mice after exposure for 50 days. Aroclor 1254 exposure significantly decreased the PCNA‐positive cells in the pancreatic acini in a dose‐dependent manner. In addition, western blot analysis showed that PCNA expression was decreased in pancreas in the presence of Aroclor 1254, which suggests that Aroclor 1254 suppresses cell proliferation. TUNEL‐positive apoptotic cells as well as the expression of Bcl2, BclXL, BAX, and Bad of exocrine pancreas did not show significant changes in the treated mice, indicating that Aroclor 1254 has no effect on apoptosis. We also found that phosphorylation of ERK1/2, P90RSK1 and Bad was increased in the treated groups; this compensatory activation of phosphorylation in ERK1/2‐P90RSK1‐Bad signaling cascade could protect cell from apoptosis to maintain the cell numbers and function of exocrine pancreas. Moreover, we found that the expression of Kras and TNFα was increased in the pancreas, indicating that Aroclor 1254 exposure could result in increased risk of inflammation and carcinoma. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 671–678, 2016.
Lysophosphatidic acid regulates the proliferation and migration of olfactory ensheathing cells in vitro

Olfactory ensheathing cells (OECs) are a unique type of macroglia with axonal growth‐promoting properties. However, our understanding of the factors that regulate OECs is at early stages. Lysophosphatidic acid (LPA) is a lipid that influences diverse functions in the nervous system. Recent studies suggest that glial cells, including astrocytes and Schwann cells, are important targets of LPA. However, the influences of LPA on OECs are not known. To address if LPA can influence OECs, we examined effects of LPA on the proliferation and migration of OECs and intracellular effector events. Initially, we observed that OECs expressed the genes for LPA1, LPA2, and LPA3 receptors. When OECs were treated with LPA, we observed stimulated proliferation and migration of OECs. Treatment of OECs with LPA also induced actin cytoskeleton reorganization and focal adhesion assembly. These effects of LPA were blocked by treatment with C3 exoenzyme or Y‐27632, which inhibit Rho‐GTPase and Rho‐associated kinase, respectively. Effects of LPA on OEC proliferation were blocked by the MEK inhibitors PD098059 and U0126 and by the phosphotidylinositol 3‐kinase (PI 3‐K) inhibitors LY0294002 and wortmannin. These results show that LPA acts via Rho‐GTPase, MAPK, and PI 3‐K signaling cascades to influence OEC proliferation, migration, and cytoskeleton assembly. © 2003 Wiley‐Liss, Inc.
Assessment of Atrial Fibrillation Organization During Internal Electrical Cardioversion Using Sample Entropy

Predicting non-invasively the effectiveness of a shock on Internal Electrical Cardio version (IECV) is clinically relevant to enhance step-up voltage protocols in the treatment of Persistent Atrial Fibrillation (PAF). The present study assess the ability of a non-linear index, such as sample entropy (SampEn), to follow-up noninvasively AF organization under successive attempts of IECV and to predict the effectiveness of every single shock. Results showed a SampEn significant difference just after the first attempt in successful vs. unsuccessful patients (0.0398 Â± 0.0139) vs. (0.0608 Â± 0.0221) p = 0.0094, indicating that probably first shock plays the most important role in the procedure.
Evaluation of the HPV ISH Assay in Cervical Cancer

Background : Human papillomavirus (HPV) infection can be detected by in situ hybridization (ISH), in which a punctate signal pattern indicates integrated HPV DNA and a diffuse pattern denotes the presence of episomal viral DNA. This study was conducted to evaluate the usefulness of an HPV ISH assay for invasive cervical cancer. Methods : The HPV ISH assay for high-risk HPV and immunohistochemical staining for p16INK4a , p53, bcl-2, and Ki-67 were performed in a tissue microarray of 279 cervical cancers. Results : High-risk HPV ISH was positive in 194 (69.5%) of the samples. Punctate, diffuse, and mixed signal patterns were observed in 157 (56.3%), one (0.4%), and 36 cases (12.9%), respectively. Positive results in high-risk HPV ISH were associated with p16 and bcl-2 expression (p = 0.01 and p < 0.01, respectively). According to a Cox regression analysis, HPV infection and its surrogate immunohistochemical markers such as p16, bcl-2, and Ki-67 were not independent prognostic factors, but stage and grade were independent prognostic factors. Conclusions : Our results confirm that an HPV ISH assay is reasonably sensitive for HPV infection and that it might be useful to identify integrated HPV DNA in formalin-fixed and paraffin-embedded specimens. Further study encompassing HPV type, E2/E6 ratio, and therapeutic modality is necessary to understand the clinical meaning of HPV status in cervical cancer.
Rapid Virological Diagnosis of Central Nervous System Infections by Use of a Multiplex Reverse Transcription-PCR DNA Microarray

ABSTRACT Viruses are the main etiological cause of central nervous system (CNS) infections. A rapid molecular diagnosis is recommended to improve the therapeutic management of patients. The aim of this study was to evaluate the performances of a DNA microarray, the Clart Entherpex kit (Genomica, Coslada, Spain), allowing the rapid and simultaneous detection of 9 DNA and RNA neurotropic viruses: herpes simplex virus 1 (HSV-1), HSV-2, varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), HHV-7, HHV-8, and the human enteroviruses (HEVs). This evaluation was performed with 28 samples from the European proficiency panels (Quality Control for Molecular Diagnostics [QCMD]; Glasgow, Scotland) and then with 78 cerebrospinal fluid (CSF) specimens. The majority of the QCMD results obtained by the DNA microarray were similar to those recorded by the overall QCMD participants. The main discrepant results were observed for low concentrations of HSV-2 and HEVs. From the clinical samples, the kit detected 27 of the 28 herpesvirus CNS infections and all of the 30 HEV-positive CSF samples. No false-positive result was observed among the 20 virus-negative CSF samples. The clinical sensitivity, specificity, and negative and positive predictive values of the assay were 98.3, 100, 95.2, and 100%, respectively, when the results were compared to those of commercially available PCR assays. Interestingly, HHV-7 was detected in 11 (37%) of the 30 HEV-positive CSF samples from children suffering from aseptic meningitis causing significantly longer lengths of stay at the hospital than infection with HEVs alone (2.4 versus 1.4 days; P = 0.038). In conclusion, this preliminary study showed that this DNA microarray could be a valuable molecular diagnostic tool for single and mixed DNA and RNA virus infections of the CNS.
Induction of resistance with heat-killed compact-type strains of Staphylococcus aureus against challenge with the diffuse variant of the Smith strain of Staphylococcus aureus

Active immunization of mice with high doses of heat-killed and autoclaved vaccine of unencapsulated strains of Staphylococcus aureus, which was grown in brain heart infusion media, protected against challenge with the Smith diffuse strain of Staphylococcus aureus. These organisms were capable of absorbing the protective antibody in rabbit hyperimmune sera prepared with the Smith diffuse strain. Also, mice treated with rabbit hyperimmune sera prepared with these strains (four out of six strains) protected against challenge with the Smith diffuse strain. Protective activities of these rabbit hyperimmune sera were assumed to be essentially identical to the protective antibody induced by the Smith diffuse strain.