Miracle-dz/UniFAR-FTUs huggingface dataset:
Arf6 and Phosphoinositol-4-Phosphate-5-Kinase Activities Permit Bypass of the Rac1 Requirement for β1 Integrin–mediated Bacterial Uptake

Efficient entry of the bacterium Yersinia pseudotuberculosis into mammalian cells requires the binding of the bacterial invasin protein to β1 integrin receptors and the activation of the small GTPase Rac1. We report here that this Rac1-dependent pathway involves recruitment of phosphoinositol-4-phosphate-5-kinase (PIP5K) to form phosphoinositol-4,5-bisphosphate (PIP2) at the phagocytic cup. Reducing the concentration of PIP2 in the target cell by using a membrane-targeted PIP2-specific phosphatase lowered bacterial uptake proportionately. PIP2 formation is regulated by Arf6. An Arf6 derivative defective for nucleotide binding (Arf6N122I) interfered with uptake and decreased the level of PIP2 around extracellular bacteria bound to host cells. This reduction in PIP2 occurred in spite of fact that PIP5K appeared to be recruited efficiently to the site of bacterial binding, indicating a role for Arf6 in activation of the kinase. The elimination of the Rac1-GTP–bound form from the cell by the introduction of the Y. pseudotuberculosis YopE RhoGAP protein could be bypassed by the overproduction of either PIP5K or Arf6, although the degree of bypass was greater for Arf6 transfectants. These results indicate that both Arf6 and PIP5K are involved in integrin-dependent uptake, and that Arf6 participates in both activation of PIP5K as well as in other events associated with bacterial uptake.
Optimising the widths of radial basis functions

In the context of regression analysis with penalised linear models (such as RBF networks) certain model selection criteria can be differentiated to yield a re-estimation formula for the regularisation parameter such that an initial guess can be iteratively improved until a local minimum of the criterion is reached. In this paper we discuss some enhancements of this general approach including improved computational efficiency, detection of the global minimum and simultaneous optimisation of the basis function widths. The benefits of these improvements are demonstrated on a practical problem.
Toll-like Receptor

Toll like receptor (TLR), one of the key functions of innate immune system, can recognize not only exogenous pathogen-associated molecular patterns, namely PAMPs, but also endogenous molecules created upon tissue injury, sterile inflammation and degeneration. Endogenous TLR ligands are called as damage-associated molecular patters (DAMPs), including endogenous molecules released by activated and necrotic cells, and extracellular matrix molecules. DAMPs are also known as alarmins. TLR research has brought about new insights in the rheumatic diseases. Previous reports suggest that TLRs and the signal pathways intensively contribute to the pathogenesis of rheumatoid arthritis (RA) and other arthritic conditions with interaction of various TLR ligands. Accumulated knowledge of TLR system is summarized to overlook TLRs and the signaling pathway in arthritis conditions, with special reference to RA. [J Clin Exp Hematopathol 51(2) : 77-92, 2011]
Extending the Knowledge Compilation Map: Closure Principles

We extend the knowledge compilation map introduced by Darwiche and Marquis with new propositional fragments obtained by applying closure principles to several fragments studied so far. We investigate two closure principles: disjunction and implicit forgetting (i.e., existential quantification). Each introduced fragment is evaluated w.r. t. several criteria, including the complexity of basic queries and transformations, and its spatial efficiency is also analyzed.
Randomized 4‐Week Exercise Program in Patients With Impaired Left Ventricular Function

BackgroundThis study was designed to determine the controlled effects of a short-term exercise rehabilitation program on patients with moderate-to-severe left ventricular dysfunction after a recent myocardial infarction. Methods and ResultsThirty-nine male patients 51 + 8 years old with a large anterior myocardial infarction less than 10 weeks old were recruited for the study. The patients were randomly assigned to either one of two training or control groups on the basis of their resting ejection fraction: training, less than 30%; control, less than 30%; training, 31–50%1; or control, 31–50%. Patients were evaluated for filling pressures, radionuclide ventriculography, heart volume, echocardiography, and work capacity. Patients who underwent training participated in an intensive 4-week in-hospital exercise program, whereas the control patients were restricted to a minimal activity program. Results indicated that there were no significant improvements in resting, submaximal, and maximal hemodynamic measurements as a result of the program. Mean work capacity and peak oxygen consumption improved significantly in the less-than-30% training group but was accompanied by a significant increase in mean pulmonary wedge pressure. Resting ejection fraction improved markedly in both less-than-30Q% training and control patients, but ejection fraction measures were not associated with work capacity. Training did not cause further deterioration in ventricular function. ConclusionsIt was concluded that in the present study, exercise training had little or no effect on hemodynamic measurements and that the training effects achieved in patients with left ventricular dysfunction are most likely due to corrected impaired vasodilation, not necessarily to cardiac function. The importance ofusing a control group in this type of study and the wide intefindividual variations in training responses are emphasized.
Simulating ultrasound fields for 2D phased-array probes design optimization

Nowadays, ultrasound diagnostic imaging is one of the non-invasive techniques mostly used in the clinical practice. Recent advances in this field have brought to the development of small and portable systems. New bidimensional probes consisting of 2D phased arrays, allow to obtain real-time 3D representations of moving organs and blood vessels anatomy. Being the complexity of such 4D ultrasound imaging systems significantly increased, new challenges concerning electronics integration arise for designers. In this paper a software simulator is described, which has been developed in order to model ultrasound wave generation, pressure field distribution and echoes reception, with the aim to become a useful tool for optimizing the probe design. The paper mainly focuses on linear ultrasound field modeling; preliminary results on non-linear interactions with contrast agents are also here introduced.
Frontiers in Aging Neuroscience Aging Neuroscience Review Article

plays major roles in learning and memory processes; in humans the size of the hippocampus decreases during aging and more so in Alzheimer's disease (Jack et al., 2005; Driscoll et al., 2009). The layered structural organization of the neurons and their synaptic connections permits reproducible electrophysiological measurements of synaptic transmission and long-term changes in synaptic strength. Moreover, the functional status of the hippocampus in cognition can be evaluated using well-characterized behavioral tests such as the water maze and novel object recognition tasks (Heldt et al., 2007). Studies using animal models are essential for understanding the impact of dietary energy intake on the brain at the molecular and cellular levels and, importantly, data obtained from animal experiments directs the design of clinical studies in humans. This article focuses mainly on fi ndings from animal studies which have elucidated the effects of dietary energy restriction and excess on cognitive function in the absence of disease, and in experimental models of diabetes, Alzheimer's disease, stroke and epilepsy. The collective literature on this topic leaves the reader with several take home messages including: (1) excessive energy intake and obesity adversely affect cognitive function; (2) diabetes also adversely affects cognitive function; (3) a sedentary lifestyle exacerbates the adverse effects of overeating and diabetes on cognitive function; (4) excessive energy intake renders neurons vulnerable to aging and neurodegenerative disorders including Alzheimer's disease; (5) dietary energy restriction can enhance neural plasticity and cogni-tive function, and may protect against neurodegenerative disorders and improve the recovery from brain injuries. (6) excessive energy intake can impair, whereas energy restriction can enhance, adaptive cellular stress response pathways that protect neurons against aging,
EXISTENCE AND UNIQUENESS OF SOLUTIONS TO FIRST-ORDER SYSTEMS OF NONLINEAR IMPULSIVE BOUNDARY-VALUE PROBLEMS WITH SUB-, SUPER-LINEAR OR LINEAR GROWTH

In this work we present some new results concerning the existence and uniqueness of solutions to an impulsive first-order, nonlinear ordinary dif- ferential equation with "non-periodic" boundary conditions. These boundary conditions include, as a special case, so-called "anti-periodic" boundary condi- tions. Our methods to prove the existence and uniqueness of solutions involve new dierential inequalities, the classical fixed-point theorem of Schaefer, and the Nonlinear Alternative. Our new results apply to systems of impulsive dif- ferential equations where the right-hand side of the equation may grow linearly, or sub- or super-linearly in its second argument.
A Risk Tertiles Model for Predicting Mortality in Patients With Acute Respiratory Distress Syndrome: Age, Plateau Pressure, and PaO2/FIO2 at ARDS Onset Can Predict Mortality

BACKGROUND: Predicting mortality has become a necessary step for selecting patients for clinical trials and defining outcomes. We examined whether stratification by tertiles of respiratory and ventilatory variables at the onset of acute respiratory distress syndrome (ARDS) identifies patients with different risks of death in the intensive care unit. METHODS: We performed a secondary analysis of data from 220 patients included in 2 multicenter prospective independent trials of ARDS patients mechanically ventilated with a lung-protective strategy. Using demographic, pulmonary, and ventilation data collected at ARDS onset, we derived and validated a simple prediction model based on a population-based stratification of variable values into low, middle, and high tertiles. The derivation cohort included 170 patients (all from one trial) and the validation cohort included 50 patients (all from a second trial). RESULTS: Tertile distribution for age, plateau airway pressure (Pplat), and PaO2/FIO2 at ARDS onset identified subgroups with different mortalities, particularly for the highest-risk tertiles: age (> 62 years), Pplat (> 29 cm H2O), and PaO2/FIO2 (< 112 mm Hg). Risk was defined by the number of coexisting high-risk tertiles: patients with no high-risk tertiles had a mortality of 12%, whereas patients with 3 high-risk tertiles had 90% mortality (P < .001). CONCLUSIONS: A prediction model based on tertiles of patient age, Pplat, and PaO2/FIO2 at the time the patient meets ARDS criteria identifies patients with the lowest and highest risk of intensive care unit death.
Shift Design with Answer Set Programming

Answer Set Programming (ASP) is a powerful declarative programming paradigm that has been successfully applied to many different domains. Recently, ASP has also proved successful for hard optimization problems like course timetabling. In this paper, we approach another important task, namely, the shift design problem, aiming at an alignment of a minimum number of shifts in order to meet required numbers of employees (which typically vary for different time periods) in such a way that over- and understaffing is minimized. We provide an ASP encoding of the shift design problem, which, to the best of our knowledge, has not been addressed by ASP yet.
Quantize and Conquer: A Dimensionality-Recursive Solution to Clustering, Vector Quantization, and Image Retrieval

Inspired by the close relation between nearest neighbor search and clustering in high-dimensional spaces as well as the success of one helping to solve the other, we introduce a new paradigm where both problems are solved simultaneously. Our solution is recursive, not in the size of input data but in the number of dimensions. One result is a clustering algorithm that is tuned to small codebooks but does not need all data in memory at the same time and is practically constant in the data size. As a by-product, a tree structure performs either exact or approximate quantization on trained centroids, the latter being not very precise but extremely fast. A lesser contribution is a new indexing scheme for image retrieval that exploits multiple small codebooks to provide an arbitrarily fine partition of the descriptor space. Large scale experiments on public datasets exhibit state of the art performance and remarkable generalization.
Implication of DNA Demethylation and Bivalent Histone Modification for Selective Gene Regulation in Mouse Primordial Germ Cells

Primordial germ cells (PGCs) sequentially induce specific genes required for their development. We focused on epigenetic changes that regulate PGC-specific gene expression. mil-1, Blimp1, and Stella are preferentially expressed in PGCs, and their expression is upregulated during PGC differentiation. Here, we first determined DNA methylation status of mil-1, Blimp1, and Stella regulatory regions in epiblast and in PGCs, and found that they were hypomethylated in differentiating PGCs after E9.0, in which those genes were highly expressed. We used siRNA to inhibit a maintenance DNA methyltransferase, Dnmt1, in embryonic stem (ES) cells and found that the flanking regions of all three genes became hypomethylated and that expression of each gene increased 1.5- to 3-fold. In addition, we also found 1.5- to 5-fold increase of the PGC genes in the PGCLCs (PGC-like cells) induced form ES cells by knockdown of Dnmt1. We also obtained evidence showing that methylation of the regulatory region of mil-1 resulted in 2.5-fold decrease in expression in a reporter assay. Together, these results suggested that DNA demethylation does not play a major role on initial activation of the PGC genes in the nascent PGCs but contributed to enhancement of their expression in PGCs after E9.0. However, we also found that repression of representative somatic genes, Hoxa1 and Hoxb1, and a tissue-specific gene, Gfap, in PGCs was not dependent on DNA methylation; their flanking regions were hypomethylated, but their expression was not observed in PGCs at E13.5. Their promoter regions showed the bivalent histone modification in PGCs, that may be involved in repression of their expression. Our results indicated that epigenetic status of PGC genes and of somatic genes in PGCs were distinct, and suggested contribution of epigenetic mechanisms in regulation of the expression of a specific gene set in PGCs.
A ranking of diffusion MRI compartment models with in vivo human brain data

Diffusion magnetic resonance imaging (MRI) microstructure imaging provides a unique noninvasive probe into tissue microstructure. The technique relies on biophysically motivated mathematical models, relating microscopic tissue features to the magnetic resonance (MR) signal. This work aims to determine which compartment models of diffusion MRI are best at describing measurements from in vivo human brain white matter.
The role of cell-mediated cytotoxicity in acute GVHD after MHC-matched allogeneic bone marrow transplantation in mice

The role of cell-mediated cytotoxicity in the complex pathophysiology of graft-versus-host disease (GVHD) has remained poorly defined for several decades. We transplanted T cells from Fas-ligand (FasL)- defective and perforin-deficient mutant donor mice into lethally irradiated MHC-matched allogeneic recipient mice to characterize the role of cell-mediated cytotoxicity in GVHD. Although recipients of allogeneic FasL-defective donor T cells underwent severe GVHD- associated cachexia, they exhibited only minimal signs of hepatic and cutaneous GVHD pathology. Recipients of perforin-deficient allogeneic donor T cells developed signs of acute GVHD, but the time of onset was significantly delayed. These findings demonstrate that Fas-mediated anti-recipient cytotoxicity may be critical for the development of hepatic and cutaneous GVHD, but is not required for GVHD-associated cachexia. In addition, perforin-mediated anti-recipient cytotoxicity appears to play an important role in the kinetics of GVHD pathophysiology, but is not required for GVHD-associated tissue damage.
Neural Organization of the Median Ocellus of the Dragonfly

Two types of presumed synaptic contacts have been recognized by electron microscopy in the synaptic plexus of the median ocellus of the dragonfly. The first type is characterized by an electron-opaque, button-like organelle in the presynaptic cytoplasm, surrounded by a cluster of synaptic vesicles. Two postsynaptic elements are associated with these junctions, which we have termed button synapses. The second synaptic type is characterized by a dense cluster of synaptic vesicles adjacent to the presumed presynaptic membrane. One postsynaptic element is observed at these junctions. The overwhelming majority of synapses seen in the plexus are button synapses. They are found most commonly in the receptor cell axons where they synaptically contact ocellar nerve dendrites and adjacent receptor cell axons. Button synapses are also seen in the ocellar nerve dendrites where they appear to make synapses back onto receptor axon terminals as well as onto adjacent ocellar nerve dendrites. Reciprocal and serial synaptic arrangements between receptor cell axon terminals, and between receptor cell axon terminals and ocellar nerve dendrites are occasionally seen. It is suggested that the lateral and feedback synapses in the median ocellus of the dragonfly play a role in enhancing transients in the postsynaptic responses.
In Vitro Activities of Piperacillin against β-Lactamase-Negative Ampicillin-Resistant Haemophilus influenzae

ABSTRACT The in vitro activities of piperacillin (PIP) against β-lactamase-negative ampicillin (AMP)-resistant (BLNAR) Haemophilus influenzae were compared with those of cefotaxime (CTX) and ceftriaxone (CRO), and the potency of PIP as therapy for meningitis caused by BLNAR is also discussed. PIP showed good activity (MIC at which 90% of strains are inhibited, 0.25 μg/ml) against 69 BLNAR strains, and its activity was comparable to that of CRO and superior to that of CTX. No significant correlation was observed between the MICs of PIP and CTX or CRO or AMP, whereas a high correlation was observed between the MICs of CTX and CRO. In the killing study, PIP showed potent bactericidal activity compared with those of CTX and CRO. By microscopic examination, PIP caused the formation of a spindle and short filamentous cells with bulges and induced cell lysis in BLNAR strains, while treatment with CTX and CRO resulted in the formation of large, spherical cells without any obvious lysis. The affinity of Bocillin FL, a fluorescent penicillin used for determination of the 50% inhibitory concentration (IC50s) for penicillin-binding proteins (PBPs), to PBPs 3a and 3b of BLNAR strains was drastically decreased compared with that to an AMP-susceptible strain (ATCC 33391). In the case of the BLNAR strains, the IC50s for PBPs 1a, 1b, and 2 were similar to those for the PBPs of ATCC 33391. Since the affinity of binding to PBPs 3a and 3b of the BLNAR strains decreased drastically, the second targets among the PBPs were PBP 2 for PIP, PBP1 (1a and 1b) for CTX and CRO. In conclusion, PIP showed excellent activities against BLNAR strains in a manner different from those of cephem antibiotics, suggesting that it could be a candidate therapeutic agent for the treatment of meningitis caused by BLNAR strains.
Inter Individual Variations of the Fish Skin Microbiota: Host Genetics Basis of Mutualism?

The commensal microbiota of fish skin is suspected to provide a protection against opportunist infections. The skin of fish harbors a complex and diverse microbiota that closely interacts with the surrounding water microbial communities. Up to now there is no clear evidence as to whether the host regulates the recruitment of environmental bacteria to build a specific skin microbiota. To address this question, we detected Quantitative Trait Loci (QTL) associated with the abundance of specific skin microbiota bacterial strains in brook charr (Salvelinus fontinalis), combining 16S RNA tagged-amplicon 454 pyrosequencing with genetic linkage analysis. Skin microbiota analysis revealed high inter-individual variation among 86 F2 fish progeny based upon the relative abundance of bacterial operational taxonomic units (OTUs). Out of those OTUs, the pathogenic strain Flavobacterium psychrophilum and the non-pathogenic strain Methylobacterium rhodesianum explained the majority of inter-individual distances. Furthermore, a strong negative correlation was found between Flavobacterium and Methylobacterium, suggesting a mutually competitive relationship. Finally, after considering a total of 266 markers, genetic linkage analysis highlighted three major QTL associated with the abundance of Lysobacter, Rheinheimera and Methylobacterium. All these three genera are known for their beneficial antibacterial activity. Overall, our results provide evidence that host genotype may regulate the abundance of specific genera among their surface microbiota. They also indicate that Lysobacter, Rheinheimera and Methylobacterium are potentially important genera in providing protection against pathogens.
Continuous Subcutaneous Insulin Infusion in Children and Adolescents with Diabetes Mellitus: Decreased HbA1c with Low Risk of Hypoglycemia

AIM To evaluate blood glucose and HbA1c levels, insulin dosage, hypoglycemia rate and body mass index (BMI) at baseline, and at 3 and 6 months after initiation of continuous subcutaneous insulin infusion (CSII) in children and youth with type 1 diabetes mellitus (DM). METHODS A 6-month trial of pump therapy was carried out in 40 patients with type 1 DM and one with cystic fibrosis (CF) induced DM (25 males), aged 4-25 years (mean 13.5 +/- 4.2 [SD]; 4-8 years, n = 6; 8-10 years, n = 8; 10-12 years, n = 4; 12-15 years, n = 11; >15 years, n = 12). RESULTS HbA1c was significantly reduced from 9.5 +/- 1.7% to 8.6 +/- 1.2% at 3 months (p < 0.03), and at 6 months 8.8 +/- 1.5% (p < 0.05). The mean daily values of blood glucose, as well as individual mean values of blood glucose at fasting and before lunch, also exhibited a significant reduction (p < 0.05) at 3 and 6 months. There was a significant reduction in the number of hypoglycemic events (level of plasma glucose <3.3 mmol/l, calculated as number of events per patient/30 days) at 3 months (6.5 +/- 5.5 vs 2.8 +/- 3.3; p = 0.02) and at 6 months (6.5 +/- 5.5 vs 3.5 +/- 3.0; p = 0.04). The insulin requirement dropped by 27.2% (1.03 +/- 0.30 U/kg/day before starting CSII; 0.75 +/- 020 U/kg/day on insulin pump therapy onset; 0.76 +/- 0.18 U/kg/day at 3 months; 0.75 +/- 0.21 U/kg/day at 6 months). During the follow-up 0.10 events of diabetic ketoacidosis/patient/year were recorded. The patients exhibited no increase in BMI during the 6 months of follow-up. CONCLUSION CSII was safe and effective in improving short- and medium-term metabolic control in young adults, adolescents and younger children with DM.