Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatic cytochromes P450: structural degrons and barcodes, posttranslational modifications and cellular adapters in the ERAD-endgame

Abstract The endoplasmic reticulum (ER)-anchored hepatic cytochromes P450 (P450s) are enzymes that metabolize endo- and xenobiotics i.e. drugs, carcinogens, toxins, natural and chemical products. These agents modulate liver P450 content through increased synthesis or reduction via inactivation and/or proteolytic degradation, resulting in clinically significant drug-drug interactions. P450 proteolytic degradation occurs via ER-associated degradation (ERAD) involving either of two distinct routes: Ubiquitin (Ub)-dependent 26S proteasomal degradation (ERAD/UPD) or autophagic lysosomal degradation (ERAD/ALD). CYP3A4, the major human liver/intestinal P450, and the fast-turnover CYP2E1 species are degraded via ERAD/UPD entailing multisite protein phosphorylation and subsequent ubiquitination by gp78 and CHIP E3 Ub-ligases. We are gaining insight into the nature of the structural determinants involved in CYP3A4 and CYP2E1 molecular recognition in ERAD/UPD [i.e. K48-linked polyUb chains and linear and/or “conformational” phosphodegrons consisting either of consecutive sequences on surface loops and/or disordered regions, or structurally-assembled surface clusters of negatively charged acidic (Asp/Glu) and phosphorylated (Ser/Thr) residues, within or vicinal to which, Lys-residues are targeted for ubiquitination]. Structural inspection of select human liver P450s reveals that such linear or conformational phosphodegrons may indeed be a common P450-ERAD/UPD feature. By contrast, although many P450s such as the slow-turnover CYP2E1 species and rat liver CYP2B1 and CYP2C11 are degraded via ERAD/ALD, little is known about the mechanism of their ALD-targeting. On the basis of our current knowledge of ALD-substrate targeting, we propose a tripartite conjunction of K63-linked Ub-chains, P450 structural “LIR” motifs and selective cellular “cargo receptors” as plausible P450-ALD determinants.
Elongator subunit 3 (ELP3) modifies ALS through tRNA modification

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal degenerative motor neuron disorder of which the progression is influenced by several disease-modifying factors. Here, we investigated ELP3, a subunit of the elongator complex that modifies tRNA wobble uridines, as one of such ALS disease modifiers. ELP3 attenuated the axonopathy of a mutant SOD1, as well as of a mutant C9orf72 ALS zebrafish model. Furthermore, the expression of ELP3 in the SOD1G93A mouse extended the survival and attenuated the denervation in this model. Depletion of ELP3 in vitro reduced the modified tRNA wobble uridine mcm5s2U and increased abundance of insoluble mutant SOD1, which was reverted by exogenous ELP3 expression. Interestingly, the expression of ELP3 in the motor cortex of ALS patients was reduced and correlated with mcm5s2U levels. Our results demonstrate that ELP3 is a modifier of ALS and suggest a link between tRNA modification and neurodegeneration.
Graphene Dirac point tuned by ferroelectric polarization field

Graphene has received numerous attention for future nanoelectronics and optoelectronics. The Dirac point is a key parameter of graphene that provides information about its carrier properties. There are lots of methods to tune the Dirac point of graphene, such as chemical doping, impurities, defects, and disorder. In this study, we report a different approach to tune the Dirac point of graphene using a ferroelectric polarization field. The Dirac point can be adjusted to near the ferroelectric coercive voltage regardless its original position. We have ensured this phenomenon by temperature-dependent experiments, and analyzed its mechanism with the theory of impurity correlation in graphene. Additionally, with the modulation of ferroelectric polymer, the current on/off ratio and mobility of graphene transistor both have been improved. This work provides an effective method to tune the Dirac point of graphene, which can be readily used to configure functional devices such as p–n junctions and inverters.
Stability of an Aqueous Extract of Larrea divaricata Cav. during a Simulated Digestion Process

Larrea divaricata Cav. (Zygophyllaceae) is a South American plant widely distributed in Argentina that is used in folk medicine to treat inflammatory diseases. The aqueous extract is known to have well‐documented biological activities such as antitumour, immunomodulatory, antimicrobial, antiinflammatory and antioxidant. However, its stability in gastrointestinal fluids is unknown. The latter is an important factor to assure the bioavailability of plant extracts intended to be administered via the oral route. The aim of this work was to study the stability of a lyophilized aqueous extract of L. divaricata compressed as a pill. To this end, the main polyphenol compound found in the extract, that is, the nordihydroguaiaretic acid, the total polyphenols and flavonoids content and the antioxidant activity such as diphenylpicrylhydrazyl scavenger activity and reducing power were assayed after subjecting the extract to different incubation times in simulated digestive fluids. The HPLC and spectroscopic methods were employed. Although the levels of polyphenols and flavonoids decreased upon incubation in gastric and intestinal fluids, the extract maintained its antioxidant activity related to the presence of nordihydroguaiaretic acid. These results are promising and encourage the potential use of the extract by the oral route as a supplement or phytomedicine with antioxidant activity. Copyright © 2017 John Wiley & Sons, Ltd.
Secure gateway defender- a network intrusion detection system

A secure defender strives to meet accuracy and active responses. Traditional approaches towards network security largely rely on the statistical and algorithm-based designs for detecting intrusion, but have largely left response up to the network operator. We will build a NIDS which will use Apriori algorithm. The basic idea of the algorithm is to find all frequency sets in first, the frequent item sets occur at least a predefined minimum support and confidence. The system permits an early classification of the data packets by making them pass through a central server where they are processed. This early classification improves the performance. This paper focuses on building a system for network administrators to securely manage the network along with providing systems for logging and intrusion detection.
Parametric fMRI of paced motor responses uncovers novel whole‐brain imaging biomarkers in spinocerebellar ataxia type 3

Machado‐Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole‐brain functional biomarkers, based on parametric performance‐level‐dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel‐based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio‐paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance‐level‐based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency‐dependent cortico/subcortical activation/deactivation patterns. Cerebellar/cortical rate‐dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger‐tapping task significantly often reached >80% sensitivity and specificity in single regions‐of‐interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and/or therapeutic targets in hereditary ataxia. Hum Brain Mapp 37:3656–3668, 2016. © 2016 Wiley Periodicals, Inc.
Assessing the Reliability and Use of the Expository Scoring Scheme as a Measure of Developmental Change in Monolingual English and Bilingual French/English Children.

Purpose The Expository Scoring Scheme (ESS) is designed to analyze the macrostructure of descriptions of a favorite game or sport. This pilot study examined inter- and intrarater reliability of the ESS and use of the scale to capture developmental change in elementary school children. Method Twenty-four children in 2 language groups (monolingual English and bilingual French/English) and 2 age groups (7-8 years, 11-12 years) participated (6 in each subgroup). Participants orally explained how to play their favorite game or sport in English. Expository discourse samples were rated for 10 macrostructure components using the ESS. Ratings were summed for a total score. Results Inter- and intrarater reliability was high for the total ESS score and for some but not all ESS components. In addition, the total score and ratings for many ESS components increased with age. Few differences were found in use of macrostructure components across language groups. Conclusions The ESS captures developmental change in the use of expository macrostructure in spoken discourse samples. It may be beneficial to take into account the lower reliability found for ratings of some ESS components in clinical practice. Due to the small sample size, these results should be considered preliminary and interpreted with caution.
The Relationship of Economic Factors and Stress among Employed, Married Women with Children

A convenience sample of 62 married women with children at home were measured on five economic variables and three stress-related variables: mother/marital role satisfaction, mother work role fulfillment and physical indicators of stress. The analysis reveals several significant relationships for the fulfillment and stress variables. Regression analysis also was used to model the relationship among economic and stress-related variables. The study suggests that financial health modules be integrated into stress management and other health enhancement programs for married, employed women.
Disentangling sex allocation in a viviparous reptile with temperature‐dependent sex determination: a multifactorial approach

Females are predicted to alter sex allocation when ecological, physiological and behavioural variables have different consequences on the fitness of male and female offspring. Traditionally, tests of sex allocation have examined single causative factors, often ignoring possible interactions between multiple factors. Here, we used a multifactorial approach to examine sex allocation in the viviparous skink, Niveoscincus ocellatus. We integrated a 16‐year observational field study with a manipulative laboratory experiment to explore whether the effects of the maternal thermal environment interact with the resources available to females for reproduction to affect sex allocation decisions. We found strong effects of temperature on sex allocation in the field, with females born in warm conditions and males in cold conditions; however, this was not replicated in the laboratory. In contrast, we found no effect of female resource availability on sex allocation, either independently, or in interaction with temperature. These results corresponded with an overall lack of an effect of resource availability on any of the life history traits that we predicted would mediate the benefits of differential sex allocation in this system, suggesting that selection for sex allocation in response to resource availability may be relatively weak. Combined, these results suggest that temperature may be the predominant factor driving sex allocation in this system.
Rheumatoid Arthritis and Coronary Artery Disease: Genetic Analyses Do Not Support a Causal Relation

Objective. Inflammatory diseases, specifically rheumatoid arthritis (RA), are assumed to increase the risk of coronary artery disease (CAD). More recently, multiple single-nucleotide polymorphisms (SNP) associated with RA risk were identified. If causal mechanisms affecting risks of RA and CAD are overlapping, risk alleles for RA might also increase the risk of CAD. Methods. Sixty-one SNP associating with RA in genome-wide significant analyses were tested for association with CAD in CARDIoGRAM (Coronary ARtery DIsease Genome wide Replication and Meta-analysis), a metaanalysis including genome-wide association data (22,233 CAD cases, 64,762 controls). In parallel, a set of SNP being associated with low-density lipoprotein cholesterol (LDL-C) was tested as a positive control. Results. Twenty-nine RA-associated SNP displayed a directionality-consistent association with CAD (OR range 1.002–1.073), whereas 32 RA-associated SNP were not associated with CAD (OR range 0.96–0.99 per RA risk-increasing allele). The proportion (48%) of directionality-consistent associated SNP equaled the proportion expected by chance (50%, p = 0.09). Of only 5 RA-associated SNP showing p values for CAD < 0.05, 4 loci (C5orf30, IL-6R, PTPN22, and RAD51B) showed directionality-consistent effects on CAD, and 1 (rs10774624, locus SH2B3) reached study-wide significance (p = 7.29E-06). By contrast, and as a proof of concept, 46 (74%) out of 62 LDL-C–associated SNP displayed a directionality-consistent association with CAD, a proportion that was significantly different from 50% (p = 5.9E-05). Conclusion. We found no evidence that RA-associated SNP as a group are associated with CAD. Even though we were not able to study potential effects of all genetic variants individually, shared nongenetic factors may more plausibly explain the observed coincidence of the 2 conditions.
Defeat and Entrapment in Bipolar Disorder: Exploring the Relationship with Suicidal Ideation from a Psychological Theoretical Perspective

Contemporary psychological theoretical models of suicide hypothesize that defeat and entrapment underlie the development of suicidal ideation. This hypothesis has never been tested in people who experience bipolar disorder. Regression analysis revealed that defeat and entrapment significantly predicted suicidal ideation at 4-month follow-up. The relationship between defeat and suicidal ideation was mediated by total entrapment and internal entrapment, but not external entrapment. Results suggest that perceived defeat and entrapment underlie the development of prospective suicidal ideation in bipolar disorder. Findings could potentially improve the assessment of suicide risk in people who experience bipolar disorder.
The Health Impact of Adult Cervical Deformity in Patients Presenting for Surgical Treatment: Comparison to United States Population Norms and Chronic Disease States Based on the EuroQuol‐5 Dimensions Questionnaire

BACKGROUND: Although adult cervical spine deformity (ACSD) is associated with pain and disability, its health impact has not been quantified in comparison to other chronic diseases. OBJECTIVE: To perform a comparative analysis of the health impact of symptomatic ACSD to US normative and chronic disease values using EQ‐5D (EuroQuol‐5 Dimensions questionnaire) scores. METHODS: ACSD patients presenting for surgical treatment were identified from a prospectively collected multicenter database. Baseline demographics and EQ‐5D scores were collected and compared with US normative and disease state values. RESULTS: Of 121 ACSD patients, 115 (95%) completed the EQ‐5D (60% women, mean age 61 years, previous spine surgery in 44%). Diagnoses included kyphosis with mid‐cervical (63.4%), cervico‐thoracic (23.5%), or thoracic (8.7%) apex and primary coronal deformity (4.3%). The mean ACSD EQ‐5D index was 0.511 (standard definition = 0.224), which is 34% below the bottom 25th percentile (0.780) for similar age‐ and gender‐matched US normative populations. Mean ACSD EQ‐5D index values were worse than the bottom 25th percentile for several other disease states, including chronic ischemic heart disease (0.708), malignant breast cancer (0.708), and malignant prostate cancer (0.708). ACSD mean index values were comparable to the bottom 25th percentile values for blindness/low vision (0.543), emphysema (0.508), renal failure (0.506), and stroke (0.463). EQ‐5D scores did not significantly differ based on cervical deformity type (P = .66). CONCLUSION: The health impact of symptomatic ACSD is substantial, with negative impact across all EQ‐5D domains. The mean ACSD EQ‐5D index was comparable to the bottom 25th percentile values for blindness/low vision, emphysema, renal failure, and stroke.
Integrating learning and reasoning services for explainable information fusion

—We present a distributed information fusion system able to integrate heterogeneous information processing services based on machine learning and reasoning approaches. We focus on higher (semantic) levels of information fusion, and highlight the requirement for the component services, and the system as a whole, to generate explanations of its outputs. Using a case study approach in the domain of traffic monitoring, we introduce component services based on (i) deep neural network approaches and (ii) heuristic-based reasoning. We examine methods for explanation generation in each case, including both transparency (e.g, saliency maps, reasoning traces) and post-hoc methods (e.g, explanation in terms of similar examples, identification of relevant semantic objects). We consider trade-offs in terms of the classification performance of the services and the kinds of available explanations, and show how service integration offers more robust performance and explainability.
Joint source power allocation and secure relay beamforming in non-orthogonal multiple access amplify-and-forward relay networks

In this paper, we investigate the joint power allocation and secure relay beamforming problem in a no-orthogonal multiple access (NOMA) amplify-and-forward relay network with two users. Our goal is to maximize the rate of the user who has better channel conditions, subject to total power constraints of the two users and a minimum signal-to-interference-ratio constraint of the user who has worse channel conditions. The formulated problem is non-convex and hard to tackle directly. To solve the problem, we firstly propose an algorithm which employing one-dimensional search to obtain the optimal solution. Since one-dimensional search may involve high computational complexity, we then propose to solve the problem with a sequential parametric convex approximation (SPCA) based iterative algorithm, which can achieve a locally optimal solution with low computational complexity. To further improve the network performance, we finally propose to solve the problem with a second-order cone programming (SOCP) based iterative algorithm. Simulation results demonstrate that the SOCP based iterative algorithm, which has lower computational complexity than one-dimensional iterative algorithm, has the performance close one-dimensional iterative algorithm. The SPCA based iterative algorithm has lowest computational complexity among proposed three methods, however, it's performance is worse.
An Exact Algorithm for Maximum Entropy Sampling

We study the experimental design problem of selecting a most informative subset, having prespecified size, from a set of correlated random variables. The problem arises in many applied domains, such as meteorology, environmental statistics, and statistical geology. In these applications, observations can be collected at different locations, and possibly, at different times. Information is measured by “entropy. ” In the Gaussian case, the problem is recast as that of maximizing the determinant of the covariance matrix of the chosen subset. We demonstrate that this problem is NP-hard. We establish an upper bound for the entropy, based on the eigenvalue interlacing property, and we incorporate this bound in a branch-and-bound algorithm for the exact solution of the problem. We present computational results for estimated covariance matrices that correspond to sets of environmental monitoring stations in the United States.
Infrastructure-based digital maps for connected autonomous vehicles

Abstract One major key to autonomous driving is reliable knowledge about the vehicle's surroundings. In complex situations like urban intersections, the vehicle's on-board sensors are often unable to detect and classify all features of the environment. Therefore, high-precision digital maps are widely used to provide the vehicle with additional information. In this article, we introduce a system which makes use of a mobile edge computing architecture (MEC) for computing digital maps on infrastructure-based, distributed computers. In cooperation with the mobile network operator Vodafone an LTE test field is implemented at the Aldenhoven Testing Center (ATC). The proving ground thus combines an urban crossing with the MEC capabilities of the LTE test field so that the developed methods can be tested in a realistic scenario. In the near future the LTE test field will be equipped with the new 5G mobile standard allowing for fast and reliable exchange of map and sensor data between vehicles and infrastructure.
RESONANCIA EN PLACAS DELGADAS

Dada la importancia del fenomeno de resonancia en diferentes aspectos de nuestra vida, se presenta un dispositivo de construccion sencilla para generar estados de resonancia en una placa metalica elastica, posibilitando diferentes niveles de analisis dependiendo de la preparacion de los alumnos.
Detection of three stable genetic clones of CTX-M-15-producing Klebsiella pneumoniae in the Barcelona metropolitan area, Spain.

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