Miracle-dz/UniFAR-FTUs huggingface dataset:
The Chaperone ClpX Stimulates Expression of Staphylococcus aureus Protein A by Rot Dependent and Independent Pathways

The Clp ATPases (Hsp100) constitute a family of closely related proteins that have protein reactivating and remodelling activities typical of molecular chaperones. In Staphylococcus aureus the ClpX chaperone is essential for virulence and for transcription of spa encoding Protein A. The present study was undertaken to elucidate the mechanism by which ClpX stimulates expression of Protein A. For this purpose, we prepared antibodies directed against Rot, an activator of spa transcription, and demonstrated that cells devoid of ClpX contain three-fold less Rot than wild-type cells. By varying Rot expression from an inducible promoter we showed that expression of Protein A requires a threshold level of Rot. In the absence of ClpX the Rot content is reduced below this threshold level, hence, explaining the substantially reduced Protein A expression in the clpX mutant. Experiments addressed at pinpointing the role of ClpX in Rot synthesis revealed that ClpX is required for translation of Rot. Interestingly, translation of the spa mRNA was, like the rot mRNA, enhanced by ClpX. These data demonstrate that ClpX performs dual roles in regulating Protein A expression, as ClpX stimulates transcription of spa by enhancing translation of Rot, and that ClpX additionally is required for full translation of the spa mRNA. The current findings emphasize that ClpX has a central role in fine-tuning virulence regulation in S. aureus.
Portfolio Rebalancing in General Equilibrium

Standard portfolio advice is that agents should hold a constant share of risky assets. All agents cannot, however, follow this advice because supply and demand of risky assets must be equal. To study equilibrium rebalancing, the paper develops an overlapping generations model in which agents differ both in age and risk tolerance. Equilibrium rebalancing is driven by a leverage effect that affects levered and unlevered agents in opposite directions, an aggregate risk tolerance effect which depends on the distribution of wealth, and an intertemporal hedging effect. Optimal equilibrium portfolio rebalancing departs significantly from the standard advice.
Both sides of human cerebellum involved in preparation and execution of sequential movements

Using an event-related fMRI procedure, we investigated the role of the human cerebellum in sequential finger movements. Subjects performed a delayed sequential finger movement task in which an instructive cue preceded the imperative signal by 16.5 s. Bilateral activation was observed in the cerebellum following both the cue and imperative signals. The activated regions overlapped within the cerebellum, extending across intermediate and lateral regions corresponding to lobules HV-HVII. In contrast, activation in primary motor cortex was primarily restricted to the execution phase and most prominent in the contralateral hemisphere. These results indicate that the cerebellum is bilaterally recruited for the preparation and execution of sequential movements.
Factors of Transferability for a Generic ConvNet Representation

Evidence is mounting that Convolutional Networks (ConvNets) are the most effective representation learning method for visual recognition tasks. In the common scenario, a ConvNet is trained on a large labeled dataset (source) and the feed-forward units activation of the trained network, at a certain layer of the network, is used as a generic representation of an input image for a task with relatively smaller training set (target). Recent studies have shown this form of representation transfer to be suitable for a wide range of target visual recognition tasks. This paper introduces and investigates several factors affecting the transferability of such representations. It includes parameters for training of the source ConvNet such as its architecture, distribution of the training data, etc. and also the parameters of feature extraction such as layer of the trained ConvNet, dimensionality reduction, etc. Then, by optimizing these factors, we show that significant improvements can be achieved on various (17) visual recognition tasks. We further show that these visual recognition tasks can be categorically ordered based on their similarity to the source task such that a correlation between the performance of tasks and their similarity to the source task w.r. t. the proposed factors is observed.
Analysis of a Non-Generational Mutationless Evolutionary Algorithm for Separable Fitness Functions

It is shown that the stochastic dynamics of non-generational evolutionary algorithms with binary tournament selection and gene pool recombination but without mutation is closely approximated by a stochastic process consisting of several de-coupled random walks, provided the fitness function is separable in a certain sense. This approach leads to a lower bound on the population size such that the evolutionary algorithm converges to a uniform population with globally optimal individuals for a given confidence level.
Adaptive Serious Game for Rehabilitation of Persons with Cognitive Disabilities

The task of generating personalized learning scenarios, in an automatic fashion, for learners is a complicated task. The difficulty is compounded when these scenarios are to be integrated within a serious game dedicated to people with disabilities. In this case, the specificities of the learner's preferences and competencies should also be taken into account in addition to the learning domain and the serious game specificities. Building on our previous work, we present in this paper the platform GOALS. This platform allows educational designers to generate learning scenarios for learners, manage learning domain and serious game knowledge, as well as, the learners' profiles. We also present two evaluations in the context of project CLES (Cognitive Linguistic Elements Stimulations). The objectives of these evaluations are to verify the functionality of GOALS, to verify the project CLES's knowledge and to study the impact of the generated scenarios on the learning of real-world learners.
The Dark Side of Forgiveness: The Tendency to Forgive Predicts Continued Psychological and Physical Aggression in Marriage

Despite a burgeoning literature that documents numerous positive implications of forgiveness, scholars know very little about the potential negative implications of forgiveness. In particular, the tendency to express forgiveness may lead offenders to feel free to offend again by removing unwanted consequences for their behavior (e.g., anger, criticism, rejection, loneliness) that would otherwise discourage reoffending. Consistent with this possibility, the current longitudinal study of newlywed couples revealed a positive association between spouses’ reports of their tendencies to express forgiveness to their partners and those partners’ reports of psychological and physical aggression. Specifically, although spouses who reported being relatively more forgiving experienced psychological and physical aggression that remained stable over the first 4 years of marriage, spouses who reported being relatively less forgiving experienced declines in both forms of aggression over time. These findings join just a few others in demonstrating that forgiveness is not a panacea.
Mirror descent learning in continuous games

Online Mirror Descent (OMD) is an important and widely used class of adaptive learning algorithms that enjoys good regret performance guarantees. It is therefore natural to study the evolution of the joint action in a multi-agent decision process (typically modeled as a repeated game) where every agent employs an OMD algorithm. This well-motivated question has received much attention in the literature that lies at the intersection between learning and games. However, much of the existing literature has been focused on the time average of the joint iterates. In this paper, we tackle a harder problem that is of practical utility, particularly in the online decision making setting: the convergence of the last iterate when all the agents make decisions according to OMD. We introduce an equilibrium stability notion called variational stability (VS) and show that in variationally stable games, the last iterate of OMD converges to the set of Nash equilibria. We also extend the OMD learning dynamics to a more general setting where the exact gradient is not available and show that the last iterate (now random) of OMD converges to the set of Nash equilibria almost surely.
Conditions for Unique Solutions in Stochastic Macroeconomic Models with Rational Expectations

This paper examines conditions for the uniqueness of an equilibrium price distribution in stochastic macroeconomic models with rational expectations. A model is developed in which many price distributions, each with a finite variance, satisfy the equilibrium requirements of rationality. Hence, the condition that the variance of the equilibrium price distribution be finite, or equivalently, that the conditionally expected price path be stable, does not guarantee uniqueness. In such cases it is shown that an arbitrary random quantity which is widely publicized can become a leading indicator of prices and, consequently, influence the behavior of actual prices. However, by extending the finite variance (stability) condition to a minimum variance condition, these nonuniqueness problems can be avoided. Such stability or minimum variance conditions suggest a kind of collective rationality which, although not unreasonable, has not yet been fully analyzed in rational expectations models.
Single-shot multi-slice T1 mapping at high spatial resolution – Inversion-recovery FLASH with radial undersampling and iterative reconstruction.

Purpose: To develop a method for T1 mapping at high spatial resolution and for multiple slices. Methods: The proposed method emerges as a single-shot inversion-recovery experiment which covers the entire spin- lattice relaxation process by serial acquisitions of highly undersampled radial FLASH images, either in single-slice or multi-slice mode. Serial image reconstructions are performed in time-reversed order and first involve regularized nonline- ar inversion (NLINV) to estimate optimum coil sensitivity profiles. Subsequently, the coil profiles are fixed for the calcu- lation of differently T1-weighted frames and the resulting linear inverse problem is solved by a conjugate gradient (CG) technique. T1 values are obtained by pixelwise fitting with a Deichmann correction modified for multi-slice applications. Results: T1 accuracy was validated for a reference phantom. For human brain, T1 maps were obtained at 0.5 mm resolu- tion for single-slice acquisitions and at 0.75 mm resolution for up to 5 simultaneous slices (5 mm thickness). Correspond- ing T1 maps of the liver were acquired at 1 mm and 1.5 mm resolution, respectively. All T1 values were in agreement with literature data. Conclusion: Inversion-recovery sequences with highly undersampled radial FLASH images and NLINV/CG reconstruc- tion allow for fast, robust and accurate T1 mapping at high spatial resolution and for multiple slices.
Calcium signals and calpain-dependent necrosis are essential for release of coxsackievirus B from polarized intestinal epithelial cells

In contrast to nonpolarized cells, coxsackievirus B (CVB)–infected polarized intestinal Caco-2 cells undergo necrotic cell death triggered by inositol 1,4,5-trisphosphate receptor–dependent calcium release. This CVB-induced necrosis depends on Ca2+-activated calpain-2, which is required for disruption of the apical tight junction complex.
Limiting amounts of budding yeast Rad53 S-phase checkpoint activity results in increased resistance to DNA alkylation damage

The Saccharomyces cerevisiae protein kinase Rad53 plays a key role in maintaining genomic integrity after DNA damage and is an essential component of the ‘intra-S-phase checkpoint’. In budding yeast, alkylating chemicals, such as methyl methanesulfonate (MMS), or depletion of nucleotides by hydroxyurea (HU) stall DNA replication forks and thus activate Rad53 during S-phase. This stabilizes stalled DNA replication forks and prevents the activation of later origins of DNA replication. Here, we report that a reduction in the level of Rad53 kinase causes cells to behave very differently in response to DNA alkylation or to nucleotide depletion. While cells lacking Rad53 are unable to activate the checkpoint response to HU or MMS, so that they rapidly lose viability, a reduction in Rad53 enhances cell survival only after DNA alkylation. This reduction in the level of Rad53 allows S-phase cells to maintain the stability of DNA replication forks upon MMS treatment, but does not prevent the collapse of forks in HU. Our results may have important implications for cancer therapies, as they suggest that partial impairment of the S-phase checkpoint Rad53/Chk2 kinase provides cells with a growth advantage in the presence of drugs that damage DNA.
Identifying Methamphetamine Exposure in Children

Objective: Methamphetamine (MAMP) use, distribution, and manufacture remain a serious public health and safety problem in the United States, and children environmentally exposed to MAMP face a myriad of developmental, social, and health risks, including severe abuse and neglect necessitating child protection involvement. It is recommended that drug-endangered children receive medical evaluation and care with documentation of overall physical and mental conditions and have urine drug testing. The primary aim of this study was to determine the best biological matrix to detect MAMP, amphetamine (AMP), methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), and 3,4-methylenedioxyethylamphetamine (MDEA) in environmentally exposed children. Methods: Ninety-one children, environmentally exposed to household MAMP intake, were medically evaluated at the Child and Adolescent Abuse Resource and Evaluation Diagnostic and Treatment Center at the University of California, Davis Children’s Hospital. MAMP, AMP, MDMA, MDA, and MDEA were quantified in urine and oral fluid (OF) by gas chromatography mass spectrometry and in hair by liquid chromatography tandem mass spectrometry. Results: Overall drug detection rates in OF, urine, and hair were 6.9%, 22.1%, and 77.8%, respectively. Seventy children (79%) tested positive for 1 or more drugs in 1 or more matrices. MAMP was the primary analyte detected in all 3 biological matrices. All positive OF (n = 5), and 18 of 19 positive urine specimens also had a positive hair test. Conclusions: Hair analysis offered a more sensitive tool for identifying MAMP, AMP, and MDMA environmental exposure in children than urine or OF testing. A negative urine or hair test does not exclude the possibility of drug exposure, but hair testing provided the greatest sensitivity for identifying drug-exposed children.
A posteriori evaluation of molecular divergence dates using empirical estimates of time-heterogeneous fossilization rates

The application of molecular clock concepts in phylogenetics permits estimating the divergence times of clades with an incomplete fossil record. However, the reliability of this approach is disputed, because the resulting estimates are often inconsistent with different sets of fossils and other parameters (clock models and prior settings) in the analyses. Here, we present the λ statistic, a likelihood approach for a posteriori evaluating the reliability of estimated divergence times. The λ statistic is based on empirically derived fossilization rates and evaluates the fit of estimated divergence times to the fossil record. We tested the performance of this measure with simulated data sets. Furthermore, we applied it to the estimated divergence times of (i) Clavigeritae beetles of the family Staphylinidae and (ii) all extant insect orders. The reanalyzed beetle data supports the originally published results, but shows that several fossil calibrations used do not increase the reliability of the divergence time estimates. Analyses of estimated inter-ordinal insect divergences indicate that uniform priors with soft bounds marginally outperform log-normal priors on node ages. Furthermore, a posteriori evaluation of the original published analysis indicates that several inter-ordinal divergence estimates might be too young. The λ statistic allows the comparative evaluation of any clade divergence estimate derived from different calibration approaches. Consequently, the application of different algorithms, software tools, and calibration schemes can be empirically assessed.
Finding Participants in a Chat: Authorship Attribution for Conversational Documents

In this work we study the problem of Authorship Attribution for a novel set of documents, namely online chats. Although the problem of Authorship Attribution has been extensively investigated for different document types, from books to letters and from emails to blog posts, to the best of our knowledge this is the first study of Authorship Attribution for conversational documents (IRC chat logs) using statistical models. We experimentally demonstrate the unsuitability of the classical statistical models for conversational documents and propose a novel approach which is able to achieve a high accuracy rate (up to 95%) for hundreds of authors.
Regulative patterning in limb bud transplants is induced by distalizing activity of apical ectodermal ridge signals on host limb cells

We have used the chick limb as a model to gain insight into the longstanding question of regulative vs. mosaic development. To test the influence of signals on limb proximodistal development, distal limb bud tips of several stages were grafted to regions of the embryo known to provide different signaling environments. Of interest, thin grafts (100‐micron thick) formed elements more proximal in character when grafted to the proximal limb region than when grafted to other regions. The extra elements were derived from host tissue, presumably distalized and recruited by the graft's apical ectodermal ridge signals. The results of classic and recent experiments have been reinterpreted in light of our conclusions. Developmental Dynamics 240:1203–1211, 2011. © 2011 Wiley‐Liss, Inc.
High risk of ‘de novo’ acute myeloid leukaemia in individuals with cytochrome P450 A1 (CYP1A1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) gene defects

To the Editor, The environmental exposure to benzene and tobacco’s polycyclic aromatic hydrocarbons (PAH) has been associated with an increased risk for acute myeloid leukaemia (AML). The ability to metabolise carcinogens varies among human beings and, therefore, healthy individuals may be at distinct risks of the disease. The cytochrome P450 (CYP) proteins are the first line of defence against toxic chemicals since participating in the activation of the agents in order to make their inactivation easier. PAH are activated by the CYP1A1 enzymes, coded by the CYP1A1 polymorphic gene, resulting in the formation of substances, which can act as carcinogens. The variant alleles of the CYP1A1 T6235C and A4889G polymorphism give rise to enzymes with increased activities in PAH activation (1). The variant CC and GG genotypes were found in 1–20% and 4–40% of healthy individuals of distinct ethnic populations, respectively, but their roles for the risk of AML are controversial (2–5). The NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme of the second line of defence against toxic chemicals, which detoxifies benzene-derived quinones. A polymorphism with a C fi T substitution at nucleotide 609 of the NQO1 gene was related to decreased activity of the coded enzyme (6). The variant TT genotype was found in 5–25% of different ethnic groups and seems to increase the AML risk (4, 7–11). The environmental diseases resulting from exposure to benzene and tobacco-related diseases were described as serious health problems in south-eastern Brazil. Thus, the identification of the genotypes of the CYP1A1 and the NQO1 polymorphisms in healthy and AML individuals from this region was considered necessary to test their influences, if any, on the risk for disease or on its clinical features in our population. Genomic DNA from peripheral blood of 133 consecutive de novo AML patients (70 males, 63 females; median age: 47 years, range: 11–89; 112 Caucasians, 17 Blacks, 4 no classified) and 133 controls (70 males, 63 females; median age: 53 years, range: 25–60; 116 Caucasians, 17 Blacks) was analysed by the polymerase chain reaction and the restriction fragment length polymorphism assays for identification of the CYP1A1 T6235C and A4889G (12), and the NQO1 C609T (9) genotypes. Both the patients and controls samples confirmed the Hardy-Weinberg expectations at the CYP1A1 T6235C (X = 2.20, P = 0.14; X = 0.82, P = 0.36) and A4889G (X = 2.54, P = 0.12; X = 0.89, P = 0.34) loci. Controls’ (X = 3.69, P = 0.08) but not patients’ samples (X = 6.52, P < 0.02) were in Hardy-Weinberg equilibrium at the NQO1 C609T locus. The frequency of the CYP1A1 6235TC+CC and NQO1 609CT+TT genotypes was higher in patients than in the controls. Carriers of the variant allele C of the CYP1A1 gene and the allele T of the NQO1 gene were under a 2.75-fold and a 1.92-fold increased risk of
Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients.

OBJECTIVE Fibromyalgia (FMS) is a chronic syndrome characterized by widespread pain, troubled sleep, disturbed mood, and fatigue. Several analgesic strategies have been evaluated but the results are moderate and inconsistent. Antidepressant agents are now considered the treatment of choice in most patients. It has been recently suggested that FMS may be associated with metabolic alterations including a deficit of carnitine. In this multicenter randomized clinical trial we evaluated the efficacy of acetyl L-carnitine (LAC) in patients with overt FMS. METHODS One hundred and two patients meeting the American College of Rheumatology criteria for FMS were randomized into the study. The treatment consisted of 2 capsules/day of 500 mg LAC or placebo plus one intramuscular (i.m.) injection of either 500 mg LAC or placebo for 2 weeks. During the following 8 weeks the patients took 3 capsules daily containing either 500 mg LAC or placebo. The patients were seen during treatment after 2 (visit 3), 6 (visit 4) and 10 weeks (visit 5). The patients were also visited 4 weeks after treatment discontinuation (follow-up visit). Outcome measures included the number of positive tender points, the sum of pain threshold (kg/cm2 or "total myalgic score"), the Short Form 36 (SF36), a 100 mm visual analog scale (VAS) for self-perceived stiffness, fatigue, tiredness on awakening, sleep, work status, depression, and muscular-skeletal pain, and the Hamilton depression scale. RESULTS The "total myalgic score" and the number of positive tender points declined significantly and equally in both groups until the 6th week of treatment. At the 10th week both parameters remained unchanged in the placebo group but they continued to improve in the LAC group with a statistically significant between-group difference. Most VAS scores significantly improved in both groups. A statistically significant between-group difference was observed for depression and musculo-skeletal pain. Significantly larger improvements in SF36 questionnaire were observed in LAC than in placebo group for most parameters. Treatment was well-tolerated. CONCLUSION Although this experience deserves further studies, these results indicate that LAC may be of benefit in patients with FMS, providing improvement in pain as well as the general and mental health of these patients.