Miracle-dz/UniFAR-FTUs huggingface dataset:
NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity

The SMC5/6 complex is the least understood of SMC complexes. In yeast, smc5/6 mutants phenocopy mutations in sgs1, the BLM ortholog that is deficient in Bloom's syndrome (BS). We here show that NSMCE2 (Mms21, in Saccharomyces cerevisiae), an essential SUMO ligase of the SMC5/6 complex, suppresses cancer and aging in mice. Surprisingly, a mutation that compromises NSMCE2‐dependent SUMOylation does not have a detectable impact on murine lifespan. In contrast, NSMCE2 deletion in adult mice leads to pathologies resembling those found in patients of BS. Moreover, and whereas NSMCE2 deletion does not have a detectable impact on DNA replication, NSMCE2‐deficient cells also present the cellular hallmarks of BS such as increased recombination rates and an accumulation of micronuclei. Despite the similarities, NSMCE2 and BLM foci do not colocalize and concomitant deletion of Blm and Nsmce2 in B lymphocytes further increases recombination rates and is synthetic lethal due to severe chromosome mis‐segregation. Our work reveals that SUMO‐ and BLM‐independent activities of NSMCE2 limit recombination and facilitate segregation; functions of the SMC5/6 complex that are necessary to prevent cancer and aging in mice.
Obesity and Endocrine Dysfunction in Mice with Deletions of both Neuropeptide Y and Galanin

ABSTRACT Neuropeptide Y (NPY) and galanin have both been implicated in the regulation of body weight, yet mice bearing deletions of either of these molecules have unremarkable metabolic phenotypes. To investigate whether galanin and NPY might compensate for one another, we produced mutants lacking both neuropeptides (GAL−/−/NPY−/−). We found that male GAL−/−/NPY−/− mice ate significantly more and were much heavier (30%) than wild-type (WT) controls. GAL−/−/NPY−/− mice responded to a high-fat diet by gaining more weight than WT mice gain, and they were unable to regulate their weight normally after a change in diet. GAL−/−/NPY−/− mice had elevated levels of leptin, insulin, and glucose, and they lost more weight than WT mice during chronic leptin treatment. Galanin mRNA was increased in the hypothalamus of NPY−/− mice, providing evidence of compensatory regulation in single mutants. The disruption of energy balance observed in GAL−/−/NPY−/− double knockouts is not found in the phenotype of single knockouts of either molecule. The unexpected obesity phenotype may result from the dysregulation of the leptin and insulin systems that normally keep body weight within the homeostatic range.
Inhibition of Calcineurin and Sarcolemmal Ca2+ Influx Protects Cardiac Morphology and Ventricular Function in Kv4.2N Transgenic Mice

Background—Cardiac-targeted expression of truncated Kv4.2 subunit (Kv4.2N) reduces transient outward current (Ito) density, prolongs action potentials (APs), and enhances contractility in 3- to 4-week-old transgenic mice. By 13 to 15 weeks of age, these mice develop severely impaired cardiac function and signs of heart failure. In this study, we examined whether augmented contractility in Kv4.2N mice results from elevations in intracellular calcium ([Ca2+]i) secondary to AP prolongation and investigated the putative roles of calcineurin activation in heart disease development of Kv4.2N mice. Methods and Results—At 3 to 4 weeks of age, L-type Ca2+ influx and peak [Ca2+]i were significantly elevated in Kv4.2N myocytes compared with control because of AP prolongation. Cardiac calcineurin activity was also significantly elevated in Kv4.2N mice by 5 weeks of age relative to controls and increased progressively as heart disease developed. This was associated with activation of protein kinase C (PKC)-&agr; and PKC-&thgr; but not PKC-&egr;, as well as increases in &bgr;-myosin heavy chain (&bgr;-MHC) and reductions in sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)-2a expression. Treatment with either cyclosporin A or verapamil prevented increases in heart weight to body weight ratios, interstitial fibrosis, impaired contractility, PKC activation, and changes in the expression patterns of &bgr;-MHC and SERCA2a. Conclusions—Our results demonstrate that AP prolongation caused by Ito reduction results in enhanced Ca2+ cycling and hypercontractility in mice and suggests that elevations in [Ca2+]i via ICa,L and activation of calcineurin play a central role in disease development after Ito reduction using the Kv4.2N construct.
High factor VIII levels contribute to the thrombotic risk in families with factor V Leiden

Factor V Leiden (FVL)‐carrying relatives of selected patients with venous thromboembolism (VTE) have much higher venous thrombotic risks than FVL‐carrying relatives of unselected consecutive patients with VTE. To find an explanation for this, we explored other risk factors of VTE, in particular the presence of high factor VIII levels, in a retrospective follow‐up study. We assessed levels of factor VIII, factor IX, fibrinogen, protein C, protein S, antithrombin, the presence of prothrombin 20210A, and the occurrence of VTE in 61 first‐degree relatives of 12 selected thrombophilic families harbouring FVL, and 183 first‐degree relatives of 47 unselected families of FVL carriers with a first VTE. In all families, FVL appeared to be an independent risk factor for VTE. Higher thrombosis incidence rates were found in carriers of both FVL and high factor VIII levels (≥ 150 IU/dl), while high levels of factor VIII appeared to be an independent thrombotic risk factor only in selected thrombophilic families. The fraction of individuals with more than one prothrombotic coagulation disorder was 10% higher in selected families. These results and the higher thrombotic risks we found in the thrombophilic families favour the hypothesis that other unknown co‐existing genetic defects contribute to thrombophilia.
Verification of streaming designs by combining symbolic simulation and equivalence checking

As design complexity grows, verification becomes a bottleneck in design development and implementation. This paper describes a novel approach for verifying reconfigurable streaming designs, based on symbolic simulation and equivalence checking. Compared with numerical simulation, symbolic simulation provides a more informative way of showing a design behaved as expected; equivalence checking enables automatic checking of equivalence of symbolic expressions. Our approach has been implemented for designs targeting Maxeler technologies, using an easy-to-use symbolic simulator and the Yices equivalence checker, together with other facilities such as an output combiner to support an automated verification flow. Several benchmarks including, including one-dimensional convolution and finite difference computation, are used to evaluate the proposed approach.
Geometry Super-Resolution by Example

The acquisition of high-resolution 3D models still requires delicate and time-consuming processes. In particular, each detail of the object should be scanned separately, although they may be similar. This can be simplified by copying a small set of details at different places of the model, synthesizing high geometric resolution from details exemplars, as introduced in this paper for three different contexts : when the detail exemplars are scanned separately at high resolution, when they are synthesized or edited from other models, or when they are obtained by accumulating repeated instances of the detail in the low-resolution scan. The main challenge here is to correctly register the high-resolution details with the low resolution model. To address this issue, this work proposes a careful resolution manipulation of 3D scans at each step of an automatic registration pipeline, combined with a robust selection of alignments. This results in a fully automatic process for geometry super-resolution by example. Experiments on synthetic and real data sets show applicability in different contexts, including resolution increase, noise removal by example and geometric texture insertion.
Reconstructing Generalized Logical Networks of Transcriptional Regulation in Mouse Brain from Temporal Gene Expression Data

Gene expression time course data can be used not only to detect differentially expressed genes but also to find temporal associations among genes. The problem of reconstructing generalized logical networks to account for temporal dependencies among genes and environmental stimuli from transcriptomic data is addressed. A network reconstruction algorithm was developed that uses statistical significance as a criterion for network selection to avoid false-positive interactions arising from pure chance. The multinomial hypothesis testing-based network reconstruction allows for explicit specification of the false-positive rate, unique from all extant network inference algorithms. The method is superior to dynamic Bayesian network modeling in a simulation study. Temporal gene expression data from the brains of alcohol-treated mice in an analysis of the molecular response to alcohol are used for modeling. Genes from major neuronal pathways are identified as putative components of the alcohol response mechanism. Nine of these genes have associations with alcohol reported in literature. Several other potentially relevant genes, compatible with independent results from literature mining, may play a role in the response to alcohol. Additional, previously unknown gene interactions were discovered that, subject to biological verification, may offer new clues in the search for the elusive molecular mechanisms of alcoholism.
Application of the operator splitting to the Maxwell equations with the source term

Motivated by numerical solution of the time-dependent Maxwell equations, we consider splitting methods for a linear system of differential equations $w'(t)=Aw(t)+f(t),$ $A\in\mathbb{R}^{n\times n}$ split into two subproblems $w_1'(t)=A_1w_1(t)+f_1(t)$ and $w_2'(t)=A_2w_2(t)+f_2(t),$ $A=A_1+A_2,$ $f=f_1+f_2. $ First, expressions for the leading term of the local error are derived for the Strang-Marchuk and the symmetrically weighted sequential splitting methods. The analysis, done in assumption that the subproblems are solved exactly, confirms the expected second order global accuracy of both schemes. Second, several relevant numerical tests are performed for the Maxwell equations discretized in space either by finite differences or by finite elements. An interesting case is the splitting into the subproblems $w_1'=Aw_1$ and $w_2'=f$ (with the split-off source term $f$). For the central finite difference staggered discretization, we consider second order splitting schemes and compare them to the classical Yee scheme on a test problem with loss and source terms. For the vector Nedelec finite element discretizations, we test the Gautschi-Krylov time integration scheme. Applied in combination with the split-off source term, it leads to splitting schemes that are exact per split step. Thus, the time integration error of the schemes consists solely of the splitting error.
Randomized Study Comparing Combined Pulmonary Vein–Left Atrial Junction Disconnection and Cavotricuspid Isthmus Ablation Versus Pulmonary Vein–Left Atrial Junction Disconnection Alone in Patients Presenting With Typical Atrial Flutter and Atrial Fibrillation

Background—Atrial flutter (AFL) and atrial fibrillation (AF) frequently coexist in the same patient. Recently it has been demonstrated that the triggers for both AF and AFL may originate in the pulmonary veins (PVs). We hypothesized that in patients with both AF and typical AFL, pulmonary vein–left atrial junction (PV-LAJ) disconnection may eliminate both arrhythmias. Methods and Results—Consecutive patients with documented symptomatic AF and typical AFL were randomly assigned to have PV-LAJ disconnection combined with cavotricuspid isthmus (CTI) ablation (group 1, n=49) or PV-LAJ disconnection alone (group 2, n=59). Within the first 8 weeks after ablation, 32 of the group 2 patients had typical AFL documented, whereas none was seen in group 1. Twenty of these 32 converted to sinus rhythm after initiating antiarrhythmic drugs (AADs). Twelve were cardioverted, and AADs were started. After 8 weeks, all AADS were stopped, and only 3 patients continued to have recurrent sustained typical AFL that was eliminated by CTI ablation. Beyond 8 weeks of follow-up, 7 patients in group 1 and 6 patients in group 2 (14% and 11%, respectively) continued to have AF. Ten of these 13 patients underwent a repeat PV-LAJ disconnection procedure and were cured. The remaining 3 remained in normal sinus rhythm while taking AADs. Conclusions—In patients with both AFL and AF, PV-LAJ disconnection alone may be sufficient to control both arrhythmias. CTI block reduced early postablation recurrence of arrhythmias, which in the majority of patients reflects a short-term clinical problem.
Distribution of DNA-condensing protein complexes in the adenovirus core

Genome packing in adenovirus has long evaded precise description, since the viral dsDNA molecule condensed by proteins (core) lacks icosahedral order characteristic of the virus protein coating (capsid). We show that useful insights regarding the organization of the core can be inferred from the analysis of spatial distributions of the DNA and condensing protein units (adenosomes). These were obtained from the inspection of cryo-electron tomography reconstructions of individual human adenovirus particles. Our analysis shows that the core lacks symmetry and strict order, yet the adenosome distribution is not entirely random. The features of the distribution can be explained by modeling the condensing proteins and the part of the genome in each adenosome as very soft spheres, interacting repulsively with each other and with the capsid, producing a minimum outward pressure of ∼0.06 atm. Although the condensing proteins are connected by DNA in disrupted virion cores, in our models a backbone of DNA linking the adenosomes is not required to explain the experimental results in the confined state. In conclusion, the interior of an adenovirus infectious particle is a strongly confined and dense phase of soft particles (adenosomes) without a strictly defined DNA backbone.
Security analysis of Bloom filter-based iris biometric template protection

This paper analyses the unlinkability and the irreversibility of the iris biometric template protection system based on Bloom filters introduced at ICB 2013. Hermans et al. presented at BIOSIG 2014 an attack on the unlinkability of these templates. In the worst case, their attack succeeds with probability at least 96%. But in their attack, they assume protected templates generated from the same iriscode. In this paper, we analyze unlinkability on protected templates generated with two different iriscodes coming from the same iris, and we moreover introduce irreversibility analysis that exploits non-uniformity of the data. Our experiments thus practically demonstrate new vulnerabilities of the scheme.
Is smoking during pregnancy a risk factor for psychopathology in young children? A methodological caveat and report on preschoolers.

OBJECTIVE While studies of the effects of prenatal smoking on child psychopathology have found positive relationships, most studies (1) failed to control for a range of correlates of maternal smoking that could affect children's behavior; (2) have been conducted with school-age rather than younger children, so it is not clear when such problems emerge; and (3) have not examined the effects on internalizing problems. METHOD This study examined the effects of prenatal smoke exposure on behaviors associated with externalizing and internalizing behavior problems and negative temperament in a diverse community sample of 679 4-year-olds. RESULTS After controlling for correlates that include socioeconomic status, life stress, family conflict, maternal depression, maternal scaffolding skills, mother-child attachment, child negative affect and effortful control, smoking during pregnancy was no longer associated with child behavior or emotional problems. CONCLUSIONS Future studies need to control for a wide range of covariates of maternal smoking.
BioFacets: Faceted Classification for Biological Information

Biologists are increasingly relying on online biological databases to conduct their research. Despite the availability of hundreds of such databases, only a handful of them are effectively deployed by the community. The main reason for this is the lack of metadata provided by the databases, such as, the types of data stored, its coverage, and its relationship with other databases. Nevertheless, each database has a potential for supporting existing research investigations. The opportunity to leverage the wealth of data available presents several challenges related to data integration and representation. In this paper, we present BioFacets, a new integration system for Web based biological databases. The main feature of this system is the proposal of a new faceted classification system that allows for dynamic categorization of biological result sets. Other features of the system include query optimization, cache management and support for a meta-search engine that allows the system to efficiently search across multiple online biological databases
A Generic, Homogenous Method for Measuring Kinase and Inhibitor Activity via Adenosine 5′-Diphosphate Accumulation

The authors describe an assay to measure the generation of adenosine 5′-diphosphate (ADP) resulting from phosphorylation of a substrate by a kinase. ADP accumulation is detected by conversion to a fluorescent signal via a coupled enzyme system. The technology has potential applications for the assessment of inhibitor potency and mode of action as well as kinetic analysis of enzyme activity. The assay has a wide dynamic range (0.25-75 μM) and has been validated with several kinases including the highly active cyclic adenosine monophosphate-dependent protein kinase (PKAα), casein kinase 1 (CK1), and the weakly active kinase Jun N-terminal kinase 2 (Jnk2α2). Kinase activity can be measured either in an end point or continuous mode. Assay performance in end point mode was compared with an adenosine 5′-triphosphate (ATP) depletion assay and in continuous mode with a pyruvate kinase/lactate dehydrogenase coupled assay. The ability to characterize kinase kinetics was demonstrated by deriving ATP/substrate affinity (Michaelis-Menten constant; Km) values for PKAα, CK1, and Jnk2α2. The assay readily measured activity with kinase reactions using protein substrates, indicating the suitability for use with large macromolecules. A wide range of inhibitor activities could be determined even in the presence of high ATP concentrations, making the assay highly suitable to characterize the mode of action of the inhibitor in question. Collectively, this assay provides a homogenous, generic method for a number of applications in kinase drug discovery.
Instance classification with prototype selection

We address the problem of instance classification: our goal is to annotate images with tags corresponding to objects classes which exhibit small intra-class variations such as logos, products or landmarks. We propose a novel algorithm for the selection of class-specific prototypes which are used in a voting-based classification scheme. We show significant improvements over two state-of-the-art methods, namely the Fisher vector and Hamming Embedding, on two challenging methods of logos and vehicles.
Nonvolatile SRAM based on Phase Change

We propose a novel architecture (phase change nonvolatile SRAM: PNSRAM) combining SRAM with PRAM. This architecture is possible solution to reduce the program cycle at the nonvolatile material to be divided a program sequence into volatile and nonvolatile. In this paper, we describe the PNSRAM architecture and a circuit simulation results of the volatile and nonvolatile operation
Choosing the right model: Conceptual modeling for simulation

In performing a simulation study the modeler needs to make decisions about what to include in the simulation model and what to exclude. The modeler is faced with the very difficult choice of determining what is the best model to develop. Make it too complex and it may not be possible to complete the model with the time and knowledge available. Make it too simple and the results may not be sufficiently accurate. The process of determining what to model is known as conceptual modeling. In this paper we explore conceptual modeling first with an illustrative example from a healthcare setting. Conceptual modeling, its artefacts and requirements are then defined. Finally, a framework for helping a modeler to determine the conceptual model is briefly outlined.
Integration of GPS and dead reckoning navigation system using moving horizon estimation

In this paper, we propose an integration of GPS and dead reckoning navigation system based on moving horizon estimation (MHE) in order to improve its performance. The basic idea of MHE is to minimize an estimation cost function defined on a sliding window composed of a finite number of time stages. From simulation results we have done an objective comparison which leads us to confirm that MHE method is more accuracy than Unscented Kalman Filter (UKF) and Extended Kalman filter (EKF).
Diffractive optics for laser welding and bonding

Standard laser welding practices are limited by the intensity profile of the beam and spot size. The introduction of Diffractive Optical Elements (DOE) to the welding process allows for new beam shapes that are better suited to the welding process. A particular problem in laser welding is the joining of dissimilar materials. Because these materials have different material properties including different melting temperatures, it is difficult to synchronize the welding process using a single spot. Additionally, significant thermal stresses are introduced by the welding process because of the keyhole weld shape formed by a gaussian beam. By using a power splitting DOE, two spots of unequal intensity distributions may be projected onto each side of the weld joint. This paper discusses the use of DOEs in laser welding and joining of dissimilar materials. Results are presented from the testing of several candidate aerospace materials.
Ordered Micro/Nanostructured Arrays Based on the Monolayer Colloidal Crystals†

Besides the traditional lithographical techniques to fabricate the ordered mciro/nanostructured arrays, the route of the monolayer colloidal crystal template is a recently promising, alternative process for the synthesis of the micro/nanostructures with different designed morphologies. By this strategy, two-dimensional ordered arrays, e.g., nanoparticle arrays, pore arrays, nanoring arrays, nanobowl arrays, hollow sphere arrays, etc., even one-dimensional nanostructures of ordered nanorod/nanopillar/nanowire arrays, etc., could be prepared. Recent progress in this area is reviewed, including synthesis strategies and morphology-dependent properties of the micro/nanostructured arrays such as optical properties, wettability, surface-enhanced Raman scattering, and photonic bandgap.