Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxidative stress and mitochondrial damage: importance in non-SOD1 ALS

It is well known that mitochondrial damage (MD) is both the major contributor to oxidative stress (OS) (the condition arising from unbalance between production and removal of reactive oxygen species) and one of the major consequences of OS, because of the high dependance of mitochondrial function on redox-sensitive targets such as intact membranes. Conditions in which neuronal cells are not able to cope with MD and OS seem to lead or contribute to several neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS), at least in the most studied superoxide dismutase 1 (SOD1)-linked genetic variant. As summarized in this review, new evidence indicates that MD and OS play a role also in non-SOD1 ALS and thus they may represent a target for therapy despite previous failures in clinical trials.
The Fluid Limit of an Overloaded Processor Sharing Queue

This paper primarily concerns strictly supercritical fluid models, which arise as functional law of large numbers approximations for overloaded processor sharing queues. Analogous results for critical fluid models associated with heavily loaded processor sharing queues are contained in Gromoll et al. (2002) and Puha and Williams (2004). An important distinction between critical and strictly supercritical fluid models is that the total mass for a solution that starts from zero grows with time for the latter, but it is identically equal to zero for the former. For strictly supercritical fluid models, this paper contains descriptions of each of the following: the distribution of the mass as it builds up from zero, the set of stationary solutions, and the limiting behavior of an arbitrary solution as time tends to infinity. In addition, a fluid limit result is proved that justifies strictly supercritical fluid models as first order approximations to overloaded processor sharing queues.
Quantitative measurements of autofluorescence with the scanning laser ophthalmoscope.

PURPOSE To evaluate the feasibility and reliability of a standardized approach for quantitative measurements of fundus autofluorescence (AF) in images obtained with a confocal scanning laser ophthalmoscope (cSLO). METHODS AF images (30°) were acquired in 34 normal subjects (age range, 20-55 years) with two different cSLOs (488-nm excitation) equipped with an internal fluorescent reference to account for variable laser power and detector sensitivity. The gray levels (GLs) of each image were calibrated to the reference, the zero GL, and the magnification, to give quantified autofluorescence (qAF). Images from subjects and fixed patterns were used to test detector linearity with respect to fluorescence intensity, the stability of qAF with change in detector gain, field uniformity, effect of refractive error, and repeatability. RESULTS qAF was independent of detector gain and laser power over clinically relevant ranges, provided that detector gain was adjusted to maintain exposures within the linear detection range (GL < 175). Field uniformity was better than 5% in a central 20°-diameter circle but decreased more peripherally. The theoretical inverse square magnification correction was experimentally verified. Photoreceptor bleaching for at least 20 seconds was performed. Repeatability (95% confidence interval) for same day and different-day retests of qAF was ±6% to ±14%. Agreement (95% confidence interval) between the two instruments was <11%. CONCLUSIONS Quantitative AF imaging appears feasible. It may enhance understanding of retinal degeneration, serve as a diagnostic aid and as a sensitive marker of disease progression, and provide a tool to monitor the effects of therapeutic interventions.
Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

ABSTRACT Maternal passive immunity typically plays a critical role in protecting infants from new infections; however, the specific contribution of neutralizing antibodies in limiting mother-to-child transmission of human immunodeficiency virus type 1 is unclear. By examining cloned envelope variants from 12 transmission pairs, we found that vertically transmitted variants were more resistant to neutralization by maternal plasma than were maternal viral variants near the time of transmission. The vertically transmitted envelope variants were poorly neutralized by monoclonal antibodies biz, 2G12, 2F5, and 4E10 individually or in combination. Despite the fact that the infant viruses were among the most neutralization resistant in the mother, they had relatively few glycosylation sites. Moreover, the transmitted variants elicited de novo neutralizing antibodies in the infants, indicating that they were not inherently difficult to neutralize. The neutralization resistance of vertically transmitted viruses is in contrast to the relative neutralization sensitivity of viruses sexually transmitted within discordant couples, suggesting that the antigenic properties of viruses that are favored for transmission may differ depending upon mode of transmission.
Indoor band pass frequency selective wall paper Equivalent Circuit & ways to enhance wireless signal

An objective of the work has been to create a band pass square mesh-patch array Frequency Selective Surface (FSS) wall paper. Modifying the indoor wireless physical propagation environment to increase the coverage of certain communication systems was investigated and demonstrated in this research. General analysis approach for rectangular waveguide with square section is presented. The FSS is analysed by Computer Simulation Technology (CST) Microwave Studio (MWS) and Equivalent Circuit (EC) modelling. Remcom ‘Wireless InSite’ is used to simulate indoor propagation and to predict the performance. The concept has been tested inside ‘Wireless InSite’ and compared with VisiWave site survey data. Significant improvements are shown using an FSS based surface.
GHSR DNA hypermethylation is a common epigenetic alteration of high diagnostic value in a broad spectrum of cancers

Identification of a single molecular trait that is determinant of common malignancies may serve as a powerful diagnostic supplement to cancer type-specific markers. Here, we report a DNA methylation mark that is characteristic of seven studied malignancies, namely cancers of lung, breast, prostate, pancreas, colorectum, glioblastoma and B cell chronic lymphocytic leukaemia (CLL) (n = 137). This mark was defined by substantial hypermethylation at the promoter and first exon of growth hormone secretagouge receptor (GHSR) through bisulfite pyrosequencing. The degree of aberrant methylation was capable of accurate discrimination between cancer and control samples. The highest sensitivity and specificity of cancer detection was achieved for cancers of pancreas, lung, breast and CLL yielding the area under the curve (AUC) values of 1.0000, 0.9952, 0.9800 and 0.9400, respectively. Narrowing to a single CpG site within the gene's promoter or four consecutive CpG units of the highest methylation levels within the first exon improved the detection power. GHSR hypermethylation was detected already at the early stage tumors. The accurate performance of this marker was further replicated in an independent set of pancreatic cancer and control samples (n = 78). These findings support the candidature of GHSR methylation as a highly accurate pan-cancer marker.
Cross-layer optimized routing for Bluetooth personal area network

In this paper, we present some observations and analysis on Bluetooth PAN's performance degradation in multi hop network based on our experiments. We highlight a situation in which control packets can be received properly but not data packets, as well as its effects on scatternet performance. Based on our analysis, we propose a cross-layer optimized routing protocol for Bluetooth (CORB), which outperforms AODV based routing protocols. CORB is a QoS-extended AODV routing protocol that is optimized for Bluetooth MAC. It has two unique characteristics. First, it uses a new load metric (LM) in QoS routing protocol instead of the number of hops as in conventional best effort routing. LM reflects nodes' link bandwidth with respect to Bluetooth nodes' role in the scatternet. This helps the CORB to bypass heavily the loaded nodes, and find routes with larger bandwidth. Second, LM and some MAC layer parameters are dynamically adjusted in response to the changes in radio conditions. These two characteristics of CORB contribute to its improved stability, and rapid response to changing radio conditions
SoxB1 transcription factors and Notch signaling use distinct mechanisms to regulate proneural gene function and neural progenitor differentiation

The preservation of a pool of neural precursors is a prerequisite for proper establishment and maintenance of a functional central nervous system (CNS). Both Notch signaling and SoxB1 transcription factors have been ascribed key roles during this process, but whether these factors use common or distinct mechanisms to control progenitor maintenance is unsettled. Here, we report that the capacity of Notch to maintain neural cells in an undifferentiated state requires the activity of SoxB1 proteins, whereas the mechanism by which SoxB1 block neurogenesis is independent of Notch signaling. A common feature of Notch signaling and SoxB1 proteins is their ability to inhibit the activity of proneural bHLH proteins. Notch represses the transcription of proneural bHLH genes, while SoxB1 proteins block their neurogenic capacity. Moreover, E-proteins act as functional partners of proneural proteins and the suppression of E-protein expression is an important mechanism by which Notch counteracts neurogenesis. Interestingly, in contrast to the Hes-dependent repression of proneural genes, suppression of E-protein occurs in a Hes-independent fashion. Together, these data reveal that Notch signaling and SoxB1 transcription factors use distinct regulatory mechanisms to control proneural protein function and to preserve neural cells as undifferentiated precursors.
Breathomics from exhaled volatile organic compounds in pediatric asthma

Asthma is the most common chronic disease in children, and is characterized by airway inflammation, bronchial hyperresponsiveness, and airflow obstruction. Asthma diagnosis, phenotyping, and monitoring are still challenging with currently available methods, such as spirometry, FENO or sputum analysis. The analysis of volatile organic compounds (VOCs) in exhaled breath could be an interesting non‐invasive approach, but has not yet reached clinical practice. This review describes the current status of breath analysis in the diagnosis and monitoring of pediatric asthma. Furthermore, features of an ideal breath test, different breath analysis techniques, and important methodological issues are discussed. Although only a (small) number of studies have been performed in pediatric asthma, of which the majority is focusing on asthma diagnosis, these studies show moderate to good prediction accuracy (80‐100%, with models including 6‐28 VOCs), thereby qualifying breathomics for future application. However, standardization of procedures, longitudinal studies, as well as external validation are needed in order to further develop breathomics into clinical tools. Such a non‐invasive tool may be the next step toward stratified and personalized medicine in pediatric respiratory disease.
“sparse” temporal sampling in auditory fMRI

The use of functional magnetic resonance imaging (fMRI) to explore central auditory function may be compromised by the intense bursts of stray acoustic noise produced by the scanner whenever the magnetic resonance signal is read out. We present results evaluating the use of one method to reduce the effect of the scanner noise: “sparse” temporal sampling. Using this technique, single volumes of brain images are acquired at the end of stimulus and baseline conditions. To optimize detection of the activation, images are taken near to the maxima and minima of the hemodynamic response during the experimental cycle. Thus, the effective auditory stimulus for the activation is not masked by the scanner noise.
The brain can mix different control strategies in a task-oriented and multi-referential manner: A simulation study

In everyday life the brain must adapt to variable situations that may require a mixture of approaches including anticipatory synergy formation, through an internal body schema, and different control strategies. Unstable tasks are particularly challenging because deteriorate the predictive power of internal models and further enhance the instability potential of delayed sensory feedback. We explore this issue by means of three simulation studies: A) The hybrid control of a double inverted pendulum model, B) The bimanual stabilization of a saddle-like instability, C) Whole-body focal-postural dynamics. The simulation results support the idea that the brain can mix different control strategies in a task-oriented and multi-referential manner.
ICA-based artifact removal diminishes scan site differences in multi-center resting-state fMRI

Resting-state fMRI (R-fMRI) has shown considerable promise in providing potential biomarkers for diagnosis, prognosis and drug response across a range of diseases. Incorporating R-fMRI into multi-center studies is becoming increasingly popular, imposing technical challenges on data acquisition and analysis, as fMRI data is particularly sensitive to structured noise resulting from hardware, software, and environmental differences. Here, we investigated whether a novel clean up tool for structured noise was capable of reducing center-related R-fMRI differences between healthy subjects. We analyzed three Tesla R-fMRI data from 72 subjects, half of whom were scanned with eyes closed in a Philips Achieva system in The Netherlands, and half of whom were scanned with eyes open in a Siemens Trio system in the UK. After pre-statistical processing and individual Independent Component Analysis (ICA), FMRIB's ICA-based X-noiseifier (FIX) was used to remove noise components from the data. GICA and dual regression were run and non-parametric statistics were used to compare spatial maps between groups before and after applying FIX. Large significant differences were found in all resting-state networks between study sites before using FIX, most of which were reduced to non-significant after applying FIX. The between-center difference in the medial/primary visual network, presumably reflecting a between-center difference in protocol, remained statistically significant. FIX helps facilitate multi-center R-fMRI research by diminishing structured noise from R-fMRI data. In doing so, it improves combination of existing data from different centers in new settings and comparison of rare diseases and risk genes for which adequate sample size remains a challenge.
Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion

The generation of invasiveness in transformed cells represents an essential step of tumor progression. We show here, first, that nontransformed Madin-Darby canine kidney (MDCK) epithelial cells acquire invasive properties when intercellular adhesion is specifically inhibited by the addition of antibodies against the cell adhesion molecule uvomorulin; the separated cells then invade collagen gels and embryonal heart tissue. Second, MDCK cells transformed with Harvey and Moloney sarcoma viruses are constitutively invasive, and they were found not to express uvomorulin at their cell surface. These data suggest that the loss of adhesive function of uvomorulin (which is identical to E-cadherin and homologous to L-CAM) is a critical step in the promotion of epithelial cells to a more malignant, i.e., invasive, phenotype. Similar modulation of intercellular adhesion might also occur during invasion of carcinoma cells in vivo.
Migration of Th1 Lymphocytes Is Regulated by CD152 (CTLA-4)-Mediated Signaling via PI3 Kinase-Dependent Akt Activation

Efficient adaptive immune responses require the localization of T lymphocytes in secondary lymphoid organs and inflamed tissues. To achieve correct localization of T lymphocytes, the migration of these cells is initiated and directed by adhesion molecules and chemokines. It has recently been shown that the inhibitory surface molecule CD152 (CTLA-4) initiates Th cell migration, but the molecular mechanism underlying this effect remains to be elucidated. Using CD4 T lymphocytes derived from OVA-specific TCR transgenic CD152-deficient and CD152-competent mice, we demonstrate that chemokine-triggered signal transduction is differentially regulated by CD152 via phosphoinositide 3-kinase (PI3K)-dependent activation of protein kinase B (PKB/Akt). In the presence of CD152 signaling, the chemoattractant CCL4 selectively induces the full activation of Akt via phosphorylation at threonine 308 and serine 473 in pro-inflammatory Th lymphocytes expressing the cognate chemokine receptor CCR5. Akt signals lead to cytoskeleton rearrangements, which are indispensable for migration. Therefore, this novel Akt-modulating function of CD152 signals affecting T cell migration demonstrates that boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response.
Inhaled inactivated-Mycobacterium phlei modulates γδT cell function and alleviates airway inflammation in a mouse model of asthma.

BACKGROUND Mycobacterium bovis Bacille Calmette-Guérin (BCG) and other mycobacterial infections suppress airway hyperresponsiveness and eosinophilic inflammation in asthma. γδT cells are important modulators of airway function and allergic inflammation. Vγ1+γδT cells increase eosinophilic airway inflammation and airway hyperresponsiveness, while Vγ4+γδT reduce airway hyperresponsiveness. The objective of this investigation was to determine the role of γδT cells and its subsets in the treatment of inhaled inactivated-Mycobacterium phlei for asthma. METHODS OVA-sensitised mice were treated with aerosol Mycobacterium phlei after OVA challenge. Pathological HE staining was performed to measure lung inflammation, flow cytometric analysis was used to assess the intracellular cytokines of each γδT cell, and quantitative real-time PCR was performed to assess Vγ1 mRNA and Vγ4 mRNA expression. RESULTS Airway inflammation was attenuated by treatment with inhaled inactivated-Mycobacterium phlei. IL-10+γδT cells, IFN-γ+γδT cells,Vγ4 mRNA expression were significantly increased. CONCLUSIONS Our results indicate that inhalation of Mycobacterium phlei can modulate γδT cell function, the proportion of different γδT cell subsets and reduce airway inflammation in asthmatic mice.
Catheter Ablation of Left Atrial Ganglionated Plexi for Atrial Fibrillation

Radiofrequency ablation of pulmonary vein ostia does not provide complete and long-term elimination of atrial fibrillation. Combining this procedure with local radiofrequency application on sites with strong vagal reflexes results in partial parasympathetic denervation and increases the antiarrhythmic effect. A novel catheter-ablation technique to modify ganglionated plexi in the left atrium was assessed in 58 patients (mean age, 52.1 ± 1.9 years, 67% male) with drug-refractory atrial fibrillation, which was chronic in 21 (36%; mean duration, 14.3 ± 2.9 months; range, 5–39 months). The mean left atrial volume was 93.1 ± 6.1 mL. The patients underwent ablation of 4 areas of ganglionated plexi in the left atrium, with no circumferential ablation of the pulmonary veins; atrial fibrillation ceased immediately in 94.1% of them. Transient vagal bradycardia was seen in 93% of patients. For 7.2 ± 0.4 months after the procedure, 86.2% of them were free from arrhythmias, and no antiarrhythmic drugs were administered. Ganglionated plexi ablation is an efficient treatment for atrial fibrillation.
How Good Is Crude MDL for Solving the Bias-Variance Dilemma? An Empirical Investigation Based on Bayesian Networks

The bias-variance dilemma is a well-known and important problem in Machine Learning. It basically relates the generalization capability (goodness of fit) of a learning method to its corresponding complexity. When we have enough data at hand, it is possible to use these data in such a way so as to minimize overfitting (the risk of selecting a complex model that generalizes poorly). Unfortunately, there are many situations where we simply do not have this required amount of data. Thus, we need to find methods capable of efficiently exploiting the available data while avoiding overfitting. Different metrics have been proposed to achieve this goal: the Minimum Description Length principle (MDL), Akaike’s Information Criterion (AIC) and Bayesian Information Criterion (BIC), among others. In this paper, we focus on crude MDL and empirically evaluate its performance in selecting models with a good balance between goodness of fit and complexity: the so-called bias-variance dilemma, decomposition or tradeoff. Although the graphical interaction between these dimensions (bias and variance) is ubiquitous in the Machine Learning literature, few works present experimental evidence to recover such interaction. In our experiments, we argue that the resulting graphs allow us to gain insights that are difficult to unveil otherwise: that crude MDL naturally selects balanced models in terms of bias-variance, which not necessarily need be the gold-standard ones. We carry out these experiments using a specific model: a Bayesian network. In spite of these motivating results, we also should not overlook three other components that may significantly affect the final model selection: the search procedure, the noise rate and the sample size.
Stabilization of Flicker-Like Effects in Image Sequences through Local Contrast Correction

In this paper, we address the problem of the restoration of image sequences which have been affected by local intensity modifications (local contrast changes). Such artifacts can be encountered particularly in biological or archive film sequences, and are usually due to inconsistent exposures or sparse time sampling. In order to reduce such local artifacts, we introduce a local stabilization operator, called LStab, which acts as a time filter on image patches and relies on a similarity measure which is robust to contrast changes. Thereby, this operator is able to take motion into account without relying on a sophisticated motion estimation procedure. The efficiency of the stabilization is shown on various sequences. The experimental results compare favorably with state-of-the-art approaches.
Multimodal Integration A Biological View

We present a novel methodology for building highly integrated multimodal systems. Our approach is motivated by neurological and behavioral theories of sensory perception in humans and animals. We argue that perceptual integration in multimodal systems needs to happen at all levels of the individual perceptual processes. Rather than treating each modality as a separately processed, increasingly abstracted pipeline – in which integration over abstract sensory representations occurs as the final step – we claim that integration and the sharing of perceptual information must also occur at the earliest stages of sensory processing. This paper presents our methodology for constructing multimodal systems and examines its theoretic motivation. We have followed this approach in creating the most recent version of a highly interactive environment called the Intelligent Room and we argue that doing so has provided the Intelligent Room with unique perceptual capabilities and gives insight into building similar complex multimodal systems.