Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of lactate consumption on exercise performance.

BACKGROUND Maintenance of plasma glucose is important in endurance performance. Gluconeogenesis or carbohydrate ingestion maintain glucose after hepatic glycogen depletion. Lactate may also serve as a gluconeogenic precursor as well as a blood buffer. METHODS To determine if an 8% carbohydrate (CHO) sports drink with and without a 2% lactate (L) solution increased endurance performance, peak power, and delayed blood acidosis, seven trained cyclists participated in a double-blind randomized study (6 males and 1 female) performed a bicycle test to determine max VO2max HR and the HR associated with the first respiratory exchange ratio (RER) value greater than 1.0 (target HR). Four bicycle rides to exhaustion, separated by one week, were done at a constant workload at a HR 10 beats below each subject's target HR. After a 12-hour fast, subjects received 100 g CHO 2-3 hrs before each test. Mean exercise heart rate was 86-87% max HR. During the final 30 s of each ride the Wingate power test was performed. Subjects consumed either (placebo, 2% L, 8% CHO or 8% CHO plus 2% L) every 20 min. Blood samples were collected before, every 30 min during and immediately following the test. RESULTS No significant differences were observed in total time (placebo: 95.3 +/- 25.8, 2% lactate: 95.7 +/- 30.0, 8% CHO: 105.2 +/- 37.2, 8% CHO + 2% lactate: 89.0 +/- 28.1 min) or peak power (placebo: 798.2 +/- 241.1, 2% L: 750.1 +/- 279.2, 8% CHO: 789.4 +/- 353.5, 8% CHO + 2% L: 716.3 +/- 331.3 Watts) among drinks. There were no differences in insulin, glucose, pH and HCO3- after the power tests among the drinks. CONCLUSION Exercise performance is unaffected by oral supplementation with lactate.
Stepwise Self-Titration of Oral Glucose-Lowering Medication Using a Mobile Telephone-Based Telehealth Platform in Type 2 Diabetes: A Feasibility Trial in Primary Care

Background: Telehealth-supported clinical interventions may improve diabetes self-management. We explored the feasibility of stepwise self-titration of oral glucose-lowering medication guided by a mobile telephone-based telehealth platform for improving glycemic control in type 2 diabetes. Methods: We recruited 14 type 2 diabetes patients to a one-year feasibility study with 1:1 randomization. Intervention group patients followed a stepwise treatment plan for titration of oral glucose-lowering medication with self-monitoring of glycemia using real-time graphical feedback on a mobile telephone and remote nurse monitoring using a Web-based tool. We carried out an interim analysis at 6 months. Results: We screened 3476 type 2 diabetes patients; 94% of the ineligible did not meet the eligibility criteria for hemoglobin A1c (HbA1c) or current treatment. Mean (standard deviation) patient age at baseline was 58 (11) years, HbA1c was 65 (12) mmol/mol (8.1% [1.1%]), body mass index was 32.9 (6.4) kg/m2, median [interquartile range (IQR)] diabetes duration was 2.6 (0.6 to 4.7) years, and 10 (71%) were men. The median (IQR) change in HbA1c from baseline to six months was −10 (−21 to 3) mmol/mol (−0.9% [-1.9% to 0%]) in the intervention group and −5 (−13 to 6) mmol/mol (−0.5% [-1.2% to 0.6%]) in the control group. Six out of seven intervention group patients and four out of seven control group patients changed their oral glucose-lowering medication (p = .24). Conclusions: Self-titration of oral glucose-lowering medication in type 2 diabetes with self-monitoring and remote monitoring of glycemia is feasible, and further studies using adapted recruitment strategies are required to evaluate whether it improves clinical outcomes.
Direct Activation of Genes Involved in Intracellular Iron Use by the Yeast Iron-Responsive Transcription Factor Aft2 without Its Paralog Aft1

ABSTRACT The yeast Saccharomyces cerevisiae contains a pair of paralogous iron-responsive transcription activators, Aft1 and Aft2. Aft1 activates the cell surface iron uptake systems in iron depletion, while the role of Aft2 remains poorly understood. This study compares the functions of Aft1 and Aft2 in regulating the transcription of genes involved in iron homeostasis, with reference to the presence/absence of the paralog. Cluster analysis of DNA microarray data identified the classes of genes regulated by Aft1 or Aft2, or both. Aft2 activates the transcription of genes involved in intracellular iron use in the absence of Aft1. Northern blot analyses, combined with chromatin immunoprecipitation experiments on selected genes from each class, demonstrated that Aft2 directly activates the genes SMF3 and MRS4 involved in mitochondrial and vacuolar iron homeostasis, while Aft1 does not. Computer analysis found different cis-regulatory elements for Aft1 and Aft2, and transcription analysis using variants of the FET3 promoter indicated that Aft1 is more specific for the canonical iron-responsive element TGCACCC than is Aft2. Finally, the absence of either Aft1 or Aft2 showed an iron-dependent increase in the amount of the remaining paralog. This may provide additional control of cellular iron homeostasis.
The Multifunctional RNA-Binding Protein La Is Required for Mouse Development and for the Establishment of EmbryonicStem Cells

ABSTRACT The La protein is a target of autoantibodies in patients suffering from Sjögren's syndrome, systemic lupus erythematosus, and neonatal lupus. Ubiquitous in eukaryotes, La functions as a RNA-binding protein that promotes the maturation of tRNA precursors and other nascent transcripts synthesized by RNA polymerase III as well as other noncoding RNAs. La also associates with a class of mRNAs that encode ribosome subunits and precursors to snoRNAs involved in ribosome biogenesis. Thus, it was surprising that La is dispensable in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, the organisms from which it has been characterized most extensively. To determine whether La is essential in mammals and if so, at which developmental stage it is required, mice were created with a disrupted La gene, and the offspring from La+/ −intercrosses were analyzed. La − / − offspring were detected at the expected frequency among blastocysts prior to implantation, whereas no nullizygotes were detected after implantation, indicating that La is required early in development. Blastocysts derived from La +/ − intercrosses yielded 38 La +/+ and La +/ − embryonic stem (ES) cell lines but no La − / − ES cell lines, suggesting that La contributes a critical function toward the establishment or survival of ES cells. Consistent with this, La − / − blastocyst outgrowths revealed loss of the inner cell mass (ICM). The results indicate that in contrast to the situation in yeasts, La is essential in mammals and is one of a limited number of genes required as early as the development of the ICM.
Long-term treatment-related morbidity in differentiated thyroid cancer: a systematic review of the literature

Background Differentiated thyroid cancer (DTC) occurs in relatively young patients and is associated with a good prognosis and long survival. The management of this disease involves thyroidectomy, radioiodine therapy, and long-term thyroid-stimulating hormone suppression therapy (THST). The long-term effects of the treatment and the interaction between subclinical hyperthyroidism and long-term hypoparathyroidism are poorly understood. This review sought to examine the available evidence. Methods A PubMed search was carried out using the search terms “Thyroid Neoplasms” AND (“Thyroxine” OR “Hypocalcemia” OR “Thyrotropin”). Original English language articles published in the last 30 years studying the morbidity from thyroid-stimulating hormone (TSH) suppression and hypoparathyroidism following a surgery for DTC were retrieved and reviewed by 2 authors. Results Of the 3,000 results, 66 papers including 4,517 patients were selected for the present study. Studies reported on a range of skeletal (included in 34 studies, 1,647 patients), cardiovascular (17 studies, 957 patients), psychological (10 studies, 663 patients), and other outcomes (10 studies, 1,348 patients). Nine of 26 studies on patients who underwent THST showed a reduction in bone density, and 13 of 23 studies showed an increase in bone turnover markers. Skeletal effects were more marked in postmenopausal women. There was no evidence of increased fracture risk, and only little data were available on hypoparathyroidism. Four of five studies showed an increased left ventricular mass index on echocardiography, and one study showed a higher prevalence of atrial fibrillation (AF). There was little difference in basic physiological parameters and limited literature regarding symptoms or significant events. Six studies showed associations between long-term TSH suppression and impaired quality of life. Impaired glucose metabolism and prothrombotic states were also found in DTC patients. Conclusion There is limited literature regarding long-term DTC treatment-related morbidity, particularly regarding the effects of long-term hypocalcemia. Most studies have focused on surrogate markers and not on clinical outcomes. A large prospective study on defined clinical outcomes would help characterize the morbidity of treatment and stimulate research on tailoring treatment strategies.
The WEST Project: Challenges of Diagnostic Integration

The W -for tungsten- environment in steady-state tokamak (WEST) project consists in transforming the French tokamak Tore Supra into an X-point divertor one and aims at testing the ITER technology of actively cooled high heat flux tungsten components during ITER-relevant long pulses. In addition to the integration in the vacuum vessel of a lower divertor and an upper one, this metamorphosis has a strong impact on diagnostics initially present in Tore Supra. Indeed, the introduction of a divertor in the upper part of the machine leads to block the lines of sight (LOS) of diagnostics previously installed in the upper ports. Therefore, new diagnostics playing a paramount role for the safe tokamak operation need to be implemented, such as an infrared (IR) thermography diagnostic for the protection of plasma-facing components (PFCs) and heating antennas, and a visible spectroscopy system for the protection of tungsten PFCs. Besides, several existing diagnostics need to be modified to adapt their LOS to the new divertor targets and plasma shape. This paper presents the main issues linked to the integration of diagnostics deriving from the WEST project. First, the changes involved by the upgrade on the set of diagnostics currently implemented in Tore Supra are described. Then, a particular focus is put on the integration of the two new optical systems, namely the IR system and the visible spectroscopy one. These two systems being located within the vacuum vessel, a special care must be paid to their design, to allow them to withstand their harsh environmental conditions. Other new or updated fundamental diagnostics are also briefly presented. Finally, the resulting new implementation of diagnostics envisaged to reach the scientific and technological goals of the WEST project is described.
Intraoperative Intracerebral MRI-Guided Navigation for Accurate Targeting in Nonhuman Primates

During in vivo intracerebral infusions, the ability to perform accurate targeting towards a 3D-specific point allows control of the anatomical variable and identification of the effects of variations in other factors. Intraoperative MRI navigation systems are currently being used in the clinic, yet their use in nonhuman primates and MRI monitoring of intracerebral infusions has not been reported. In this study rhesus monkeys were placed in a MRI-compatible stereotaxic frame. T1 MRIs in the three planes were obtained in a 3.0T GE scanner to identify the target and plan the trajectory to ventral postcommisural putamen. A craniotomy was performed under sterile surgical conditions at the trajectory entry point. A modified MRI-compatible trajectory guide base (Medtronic Inc.) was secured above the cranial opening and the alignment stem applied. Scans were taken to define the position of the alignment stem. When the projection of the catheter in the three planes matched the desired trajectory to the target, the base was locked in position. A catheter replaced the alignment stem and was slowly introduced to the final target structure. Additional scans were performed to confirm trajectory and during the infusion of a solution of gadoteridol (ProHance, Bracco Diagnostics; 2 mM/L) and bromophenol blue (0.16 mg/ml) in saline. Monitoring of the pressure in the infusion lines was performed using pressure monitoring and infusion pump controller system (Engineering Resources Group Inc.) in combination with a MRI-compatible infusion pump (Harvard). MRI during infusion confirmed successful targeting and matched postmortem visualization of bromophenol blue. Assessment of the accuracy of the targeting revealed an overall 3D mean ± SD distance error of 1.2 ± 0.6 mm and angular distance error of 0.9 ± 0.5 mm. Our results in nonhuman primates confirm the accuracy of intraoperative MRI intracerebral navigation combined with an adaptable, pivot point-based targeting system and validates its use for preclinical intracerebral procedures.
Maladaptive perfectionism's link to aggression and self-harm: Emotion regulation as a mechanism.

The negative affect that results from negative feedback is a substantial, proximal cause of aggression. People high in maladaptive perfectionism, the tendency to focus on the discrepancy between one's standards and performance, are characterized by an exaggerated negative affective response to negative feedback. This exacerbated affective response to failure may then dispose them to hurt others and themselves as aggression and self-harm are often perceived as a means to regulate negative affect. In Study 1, we demonstrated that maladaptive perfectionism was linked to greater aggressive behavior towards others after receiving negative feedback. Suggesting the presence of an emotion regulation strategy, this effect was mediated by the motivation to use aggression to improve mood. In Study 2, maladaptive perfectionism was linked to self-harm, an effect exacerbated by negative feedback and mediated by negative affect. These findings suggest that maladaptive perfectionists are at risk for greater harm towards others and the self because negative feedback has a stronger affective impact and harming others and the self is perceived a means to alleviate this aversive state. Aggr. Behav. 9999:XX-XX, 2014. © 2014 Wiley Periodicals, Inc.
Exploring the kinetic requirements for enhancement of protein folding rates in the GroEL cavity.

The chaperonin system, GroEL and GroES of Escherichia coli enable certain proteins to fold under conditions when spontaneous folding is prohibitively slow as to compete with other non-productive channels such as aggregation. We investigated the plausible mechanisms of GroEL-mediated folding using simple lattice models. In particular, we have investigated protein folding in a confined environment, such as those offered by the GroEL, to decipher whether rate and yield enhancement can occur when the substrate protein is allowed to fold within the cavity of the chaperonins. The GroEL cavity is modeled as a cubic box and a simple bead model is used to represent the substrate chain. We consider three distinct characteristic of the confining environment. First, the cavity is taken to be a passive Anfinsen cage in which the walls merely reduce the available conformation space. We find that at temperatures when the native conformation is stable, the folding rate is retarded in the Anfinsen cage. We then assumed that the interior of the wall is hydrophobic. In this case the folding times exhibit a complex behavior. When the strength of the interaction between the polypeptide chain and the cavity is too strong or too weak we find that the rates of folding are retarded compared to spontaneous folding. There is an optimum range of the interaction strength that enhances the rates. Thus, above this value there is an inverse correlation between the folding rates and the strength of the substrate-cavity interactions. The optimal hydrophobic walls essentially pull the kinetically trapped states which leads to a smoother the energy landscape. It is known that upon addition of ATP and GroES the interior cavity of GroEL offers a hydrophilic-like environment to the substrate protein. In order to mimic this within the context of the dynamic Anfinsen cage model, we allow for changes in the hydrophobicity of the walls of the cavity. The duration for which the walls remain hydrophobic during one cycle of ATP hydrolysis is allowed to vary. These calculations show that frequent cycling of the wall hydrophobicity can dramatically reduce the folding times and increase the yield as well under non-permissive conditions. Examination of the structures of the substrate proteins before and after the change in hydrophobicity indicates that there is global unfolding involved. In addition, it is found that a fraction of the molecules kinetically partition to the native state in accordabce with the iterative annealing mechanism. Thus, frequent "unfoldase" activity of chaperonins leading to global unfolding of the polypeptide chain results in enhancement of the folding rates and yield of the folded protein. We suggest that chaperonin efficiency can be greatly enhanced if the cycling time is reduced. The calculations are used to interpret a few experiments on chaperonin-mediated protein folding.
Performance analysis and comparisons of antenna and beam selection diversity

Smart antennas can greatly improve the performance of wireless communication systems by providing better link quality and immunity to interference. A simple smart antenna structure is fixed beamforming and beam selection. More complex structures require combining of the signals from multiple receivers. In this paper we compare the performance of beam and antenna selection and combining techniques. Our results are based on recently reported statistical and measurement based spatial channel models and in most cases include impact of co-channel interference. We derive the probability density function (pdf) of SINR in space- and frequency-selective multiple clustered Rayleigh fading channel with finite angle spread (AS). We also analyze the outage capacity and probability of beam selection in flat fading assuming both correlated and independent fading between the antennas. Our analysis also includes the impact of erroneous beam or antenna selection. Furthermore, theoretical bounds for a hybrid of beam/antenna selection and maximal ratio combining (MRC) are presented. We show that beam selection techniques can be very effective against both multipath fading and co-channel interference. We also show that simple fixed beamforming networks such as Butler matrices are nearly as effective as more complex fixed beamforming networks.
Approach to systematic analysis of serine/threonine phosphoproteome using Beta elimination and subsequent side effects: Intramolecular linkage and/or racemisation

Complete analysis of the phosphorylation of serine and threonine residues directly from biological extracts is still at an early stage and will remain a challenging goal for many years. Analysis of phosphorylated proteins and identification of the phosphorylated sites in a crude biological extract is a major topic in proteomics, since phosphorylation plays a dominant role in post‐translational protein modification. Beta elimination of the serine/threonine‐bound phosphate by alkali action generates (methyl)dehydroalanine. The reactivity of this group susceptible of nucleophilic attacks might be used as a tool for phosphoproteome analysis. Most of the known serine/threonine kinases recognize motifs in protein targets that are rich in lysine(s) and/or arginine(s). The (methyl)dehydroalanine resulting from beta elimination of the serine/threonine‐bound phosphate by alkali action is likely to react with the amino groups of these neighboring amino acids. Furthermore, the addition reaction of dehydroalanine‐peptides with a nucleophilic group more likely generates diastereoisomers derivatives. The internal cyclic bonds and/or the stereoisomer peptide derivatives thus generated confer resistance to trypsin cleavage and/or constitute stop signals for exopeptidases such as carboxypeptidase. This might form the basis of a method to facilitate the systematic identification of phosphorylated peptides. J. Cell. Biochem. 100: 875–882, 2007. © 2006 Wiley‐Liss, Inc.
The effect of carotid stenting on rheological parameters, free radical production and platelet aggregation.

INTRODUCTION Carotid artery stenting has become a possible treatment of significant carotid stenosis. The risk of stent occlusion and restenosis might be increased by abnormal rheological conditions amplified platelet aggregation and free radical production during the operation. AIMS The aim of our study was to assess the changes in hemorheological parameters, platelet aggregation, and catalase activity after endovascular treatment of carotid stenosis. METHODS 18 patients (11 men, ages 68 +/- 9 years and 7 women, ages 62 +/- 8 years) suffering from significant carotid stenosis and treated with carotid endovascular intervention were examined. Alteration in hemorheological parameters as well as epinephrine-, ADP-, and collagen-induced platelet aggregation were evaluated. Antioxidant reserve was characterized by the determination of catalase activity. The measurements were carried out directly before and after the procedure and 1, 2, 5 days and 1 month following the intervention. Preceding the operation the patients were administered a maximum dose (300 mg) of clopidogrel. RESULTS Hematocrit, plasma fibrinogen concentration (PFC) and whole blood-, and plasma viscosity values (WBV and PV) significantly decreased immediately after stenting (p<0.001). By the fifth day following the intervention the PFC, WBV, PV, red blood cell (RBC) aggregation and ADP-induced platelet aggregation significantly increased (p<0.0001) compared to values measured postprocedurally. At 1 month follow-up these parameters, except whole blood viscosity, decreased significantly compared to measurements made on the 5th day. On the other hand, catalase activity showed significant elevation by the end of the first month. CONCLUSION Hemorheological parameters and platelet aggregation showed specific changes following carotid stenting. Abnormal changes of the rheological conditions and increasing platelet activation are the most pronounced in the first week following stenting, which may lead to early stent occlusion. Oxidative stress production returned to baseline levels only by the end of the first month.