julilili42/papers huggingface dataset:
Heterozygous carriage of the alpha1-antitrypsin Pi*Z variant increases the risk to develop liver cirrhosis
2018-08-01

Objective Homozygous alpha1-antitrypsin (AAT) deficiency increases the risk for developing cirrhosis, whereas the relevance of heterozygous carriage remains unclear. Hence, we evaluated the impact of the two most relevant AAT variants (‘Pi*Z’ and ‘Pi*S’), present in up to 10% of Caucasians, on subjects with non-alcoholic fatty liver disease (NAFLD) or alcohol misuse. Design We analysed multicentric case–control cohorts consisting of 1184 people with biopsy-proven NAFLD and of 2462 people with chronic alcohol misuse, both cohorts comprising cases with cirrhosis and controls without cirrhosis. Genotyping for the Pi*Z and Pi*S variants was performed. Results The Pi*Z variant presented in 13.8% of patients with cirrhotic NAFLD but only in 2.4% of counterparts without liver fibrosis (p&lt;0.0001). Accordingly, the Pi*Z variant increased the risk of NAFLD subjects to develop cirrhosis (adjusted OR=7.3 (95% CI 2.2 to 24.8)). Likewise, the Pi*Z variant presented in 6.2% of alcohol misusers with cirrhosis but only in 2.2% of alcohol misusers without significant liver injury (p&lt;0.0001). Correspondingly, alcohol misusers carrying the Pi*Z variant were prone to develop cirrhosis (adjusted OR=5.8 (95% CI 2.9 to 11.7)). In contrast, the Pi*S variant was not associated with NAFLD-related cirrhosis and only borderline with alcohol-related cirrhosis (adjusted OR=1.47 (95% CI 0.99 to 2.19)). Conclusion The Pi*Z variant is the hitherto strongest single nucleotide polymorphism-based risk factor for cirrhosis in NAFLD and alcohol misuse, whereas the Pi*S variant confers only a weak risk in alcohol misusers. As 2%–4% of Caucasians are Pi*Z carriers, this finding should be considered in genetic counselling of affected individuals.
Isotopic evidence for mobility at large-scale human aggregations in Copper Age Iberia: the mega-site of Marroquíes
2018-08-01

Settlements incorporating large-scale human aggregations are a well-documented but poorly understood phenomenon across late prehistoric Europe. The authors’ research examines the origins and trajectory of such aggregations through isotope analysis of human skeletal remains from the mega-site of Marroquíes in Jaén, Spain. The results indicate that eight per cent of 115 sampled individuals are of non-local origin. These individuals received mortuary treatments indistinguishable from those of locals, suggesting their incorporation into pre-existing social networks in both life and death. This research contributes to our understanding of the extent and patterning of human mobility, which underlies the emergence of late prehistoric mega-sites in Europe.
A Distributed Control Approach to Formation Balancing and Maneuvering of Multiple Multirotor UAVs
2018-08-01

In this paper, we propose and experimentally verify a distributed formation control algorithm for a group of multirotor unmanned aerial vehicles (UAVs). The algorithm brings the whole group of UAVs simultaneously to a prescribed submanifold that determines the formation shape in an asymptotically stable fashion in two- and three-dimensional environments. The complete distributed control framework is implemented with the combination of a fast model predictive control method executed at 50 Hz on low-power computers onboard multirotor UAVs and validated via a series of hardware-in-the-loop simulations and real-robot experiments. The experiments are configured to study the control performance in various formation cases of arbitrary time-varying (e.g., expanding, shrinking, or moving) shapes. In the actual experiments, up to four multirotors have been implemented to form arbitrary triangular, rectangular, and circular shapes drawn by the operator via a human-robot interaction device. We also carry out hardware-in-the-loop simulations using up to six onboard computers to achieve spherical formations and a formation moving through obstacles.
Individual Differences in the Competence for Physical-Activity-Related Affect Regulation Moderate the Activity–Affect Association in Real-Life Situations
2018-08-01

Physical activity (PA) is positively associated with affective well-being in adults. This study investigated the moderating role of the competence for PA-related affect regulation in the PA-affect association in real-life situations. A total of 37 women and 27 men completed an ecological momentary assessment study in which the authors used accelerometers to record PA and e-diaries to collect data on affective well-being on 4 study days. They applied multilevel analyses to estimate the within-person effects of PA on affective well-being and cross-level interactions between PA (within person) and PA-related affect regulation (between persons). Results revealed cross-level interaction effects between within-person PA variations and competence for PA-related affect regulation on the affect dimensions of calmness (p < .01) and valence (p = .04). Thus, the competence for PA-related affect regulation moderates the PA-affect association in real-life situations. Therefore, individual-based PA promotion should consider these individual differences to develop tailored interventions.
Coronary Computed Tomography Angiography–Specific Definitions of High-Risk Plaque Features Improve Detection of Acute Coronary Syndrome
2018-08-01

Background High-risk plaque (HRP) features as detected by coronary computed tomography angiography (CTA) predict acute coronary syndrome (ACS). We sought to determine whether coronary CTA-specific definitions of HRP improve discrimination of patients with ACS as compared with definitions from intravascular ultrasound (IVUS). Methods and Results In patients with suspected ACS, randomized to coronary CTA in the ROMICAT II (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography II) trial, we retrospectively performed semiautomated quantitative analysis of HRP (including remodeling index, plaque burden as derived by plaque area, low computed tomography attenuation plaque volume) and degree of luminal stenosis and analyzed the performance of traditional IVUS thresholds to detect ACS. Furthermore, we derived CTA-specific thresholds in patients with ACS to detect culprit lesions and applied those to all patients to calculate the discriminatory ability to detect ACS in comparison to IVUS thresholds. Of 472 patients, 255 patients (56±7.8 years; 63% men) had coronary plaque. In 32 patients (6.8%) with ACS, culprit plaques (n=35) differed from nonculprit plaques (n=172) with significantly greater values for all HRP features except minimal luminal area (significantly lower; all P &lt;0.01). IVUS definitions showed good performance while minimal luminal area (odds ratio: 6.82; P =0.014) and plaque burden (odds ratio: 5.71; P =0.008) were independently associated with ACS but not remodeling index (odds ratio: 0.78; P =0.673). Optimized CTA-specific thresholds for plaque burden (area under the curve: 0.832 versus 0.676) and degree of stenosis (area under the curve: 0.826 versus 0.721) showed significantly higher diagnostic performance for ACS as compared with IVUS-based thresholds (all P &lt;0.05) with borderline significance for minimal luminal area (area under the curve: 0.817 versus 0.742; P =0.066). Conclusions CTA-specific definitions of HRP features may improve the discrimination of patients with ACS as compared with IVUS-based definitions. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT01084239
HPCA confirmed as a genetic cause of DYT2‐like dystonia phenotype
2018-08-01

Abstract Background: HPCA (hippocalcin) is one of the underlying genetic causes of autosomal‐recessively inherited forms of dystonia. Here, we describe two consanguineous Turkish DYT‐HPCA families carrying the novel HPCA mutations. Methods: After detailed clinical and neurological examination, whole‐exome sequencing was performed. Results: Whole‐exome sequencing analysis revealed two homozygous novel truncating mutations (p.W103* and p.P10PfsTer80) in the HPCA gene in two unrelated Turkish dystonia families presenting with complex dystonia. Conclusions: After identification of HPCA as a genetic cause of DYT‐HPCA ‐like dystonia by Charlesworth et al, this is the second report in the scientific literature that describes dystonia families harboring HPCA mutations. Our findings confirm that HPCA leads to recessively inherited dystonia. © 2018 International Parkinson and Movement Disorder Society
Decentralized MPC based Obstacle Avoidance for Multi-Robot Target Tracking Scenarios
2018-08-01

In this work, we consider the problem of decentralized multi-robot target tracking and obstacle avoidance in dynamic environments. Each robot executes a local motion planning algorithm which is based on model predictive control (MPC). The planner is designed as a quadratic program, subject to constraints on robot dynamics and obstacle avoidance. Repulsive potential field functions are employed to avoid obstacles. The novelty of our approach lies in embedding these non-linear potential field functions as constraints within a convex optimization framework. Our method convexifies non-convex constraints and dependencies, by replacing them as pre-computed external input forces in robot dynamics. The proposed algorithm additionally incorporates different methods to avoid field local minima problems associated with using potential field functions in planning. The motion planner does not enforce predefined trajectories or any formation geometry on the robots and is a comprehensive solution for cooperative obstacle avoidance in the context of multi-robot target tracking. We perform simulation studies in different environmental scenarios to showcase the convergence and efficacy of the proposed algorithm. Video of simulation studies: \\url{https://youtu.be/umkdm82Tt0M}
Staphylococcus aureus counters phosphate limitation by scavenging wall teichoic acids from other staphylococci via the teichoicase GlpQ
2018-08-01

Staphylococcus aureus is part of the human nasal and skin microbiomes along with other bacterial commensals and opportunistic pathogens. Nutrients are scarce in these habitats, demanding effective nutrient acquisition and competition strategies. How S. aureus copes with phosphate limitation is still unknown. Wall teichoic acid (WTA), a polyol-phosphate polymer, could serve as a phosphate source, but whether S. aureus can utilize it during phosphate starvation remains unknown. S. aureus secretes a glycerophosphodiesterase, GlpQ, that cleaves a broad variety of glycerol-3-phosphate (GroP) headgroups of deacylated phospholipids, providing this bacterium with GroP as a carbon and phosphate source. Here we demonstrate that GlpQ can also use glycerophosphoglycerol derived from GroP WTA from coagulase-negative Staphylococcus lugdunensis, Staphylococcus capitis, and Staphylococcus epidermidis, which share the nasal and skin habitats with S. aureus. Therefore, S. aureus GlpQ is the first reported WTA-hydrolyzing enzyme, or teichoicase, from Staphylococcus. Activity assays revealed that unmodified WTA is the preferred GlpQ substrate, and the results from MS analysis suggested that GlpQ uses an exolytic cleavage mechanism. Importantly, GlpQ did not hydrolyze the ribitol-5-phosphate WTA polymers of S. aureus, underscoring its role in interspecies competition rather than in S. aureus cell wall homeostasis or WTA recycling. glpQ expression was strongly up-regulated under phosphate limitation, and GlpQ allowed S. aureus to grow in the presence of GroP WTA as the sole phosphate source. Our study reveals a novel and unprecedented strategy of S. aureus for acquiring phosphate from bacterial competitors under the phosphate-limiting conditions in the nasal or skin environments.
Learning from the past: A reverberation of past errors in the cerebellar climbing fiber signal
2018-08-01

The cerebellum allows us to rapidly adjust motor behavior to the needs of the situation. It is commonly assumed that cerebellum-based motor learning is guided by the difference between the desired and the actual behavior, i.e., by error information. Not only immediate but also future behavior will benefit from an error because it induces lasting changes of parallel fiber synapses on Purkinje cells (PCs), whose output mediates the behavioral adjustments. Olivary climbing fibers, likewise connecting with PCs, are thought to transport information on instant errors needed for the synaptic modification yet not to contribute to error memory. Here, we report work on monkeys tested in a saccadic learning paradigm that challenges this concept. We demonstrate not only a clear complex spikes (CS) signature of the error at the time of its occurrence but also a reverberation of this signature much later, before a new manifestation of the behavior, suitable to improve it.
Biochemical and kinetic properties of the complex Roco G-protein cycle
2018-08-01

Abstract Roco proteins have come into focus after mutations in the gene coding for the human Roco protein Leucine-rich repeat kinase 2 (LRRK2) were discovered to be one of the most common genetic causes of late onset Parkinson’s disease. Roco proteins are characterized by a Roc domain responsible for GTP binding and hydrolysis, followed by a COR dimerization device. The regulation and function of this RocCOR domain tandem is still not completely understood. To fully biochemically characterize Roco proteins, we performed a systematic survey of the kinetic properties of several Roco protein family members, including LRRK2. Together, our results show that Roco proteins have a unique G-protein cycle. Our results confirm that Roco proteins have a low nucleotide affinity in the micromolar range and thus do not strictly depend on G-nucleotide exchange factors. Measurement of multiple and single turnover reactions shows that neither P i nor GDP release are rate-limiting, while this is the case for the GAP-mediated GTPase reaction of some small G-proteins like Ras and for most other high affinity Ras-like proteins, respectively. The K M values of the reactions are in the range of the physiological GTP concentration, suggesting that LRRK2 functioning might be regulated by the cellular GTP level.
Attack Surface Modeling and Assessment for Penetration Testing of IoT System Designs
2018-08-01

Security by Design becomes a significant aspect for establishing the Internet-of-Things (IoT) paradigm. In this paper, we present an approach to utilize virtual prototypes (VP) at system level to enable security evaluation along the design process. The proposed VP-based penetration testing framework provides an approach for attack surface and attack behavior modeling. By utilizing a modular, reconfigurable system simulation, an attack scenario can be assessed with different system alternatives. As the VP simulates both hardware (HW) and software (SW) of a single IoT-device as well as the interconnections of different devices a comprehensive system analysis can be executed. Our framework is based on a model-driven approach, which underlines the achieved degree of automation and its potential for industrial application. A comprehensive system analysis tool is the enabler to apply penetration testing, for identifying weak points in the system design and implementation, from early stages in the design flow. The overall approach is demonstrated by an automotive use case derived from real-world security flaws.
Stress-induced body dissatisfaction in women with binge eating disorder.
2018-08-01

Stress is known to be a trigger for binge eating in individuals with binge eating disorder (BED). However, the influence of stressful situations on BED patients' body image is less understood. Our study objective was to gain insight into the effects of inducing psychosocial stress on body dissatisfaction in women with BED. Overweight women with BED (n = 29) and without an eating disorder (control group, CG; n = 38) underwent the Trier Social Stress Test for Groups (TSST-G stress) and a nonstressful control task (TSST-G no stress). Additionally, to test for the influence of body salience, participants were either exposed or not exposed to a mirror. Participants repeatedly rated their current body dissatisfaction and psychological distress. Simultaneously, biological stress reactivity was measured using salivary cortisol and alpha-amylase (sAA). Participants responded to TSST-G stress with significantly higher psychological and biological stress compared to the TSST-G control task. The psychological distress response was significantly greater in women with BED than the CG. As hypothesized, exposure to acute socioevaluative stress led to exacerbated body dissatisfaction in the BED group only. The findings of the present study suggest that acute socioevaluative stress may play an influential role in BED patients' body dissatisfaction. Body image programs might benefit from targeting stress management or coping skills in patients with BED. (PsycINFO Database Record
The prognostic and predictive value of IKZF1 and IKZF3 expression in T-cells in patients with multiple myeloma
2018-08-01

<b>Purpose</b>: While recent studies described the role of IKZF1/3 proteins in multiple myeloma (MM) cells, few have highlighted the significance of IKZF1/3 expression in T-cells. In this study we examine the prognostic and predictive value of IKZF1/3 expression in T-cells in patients with MM stage III. <b>Experimental design</b>: We analysed the IKZF1/3 expression levels in T-cells from 45 MM stage I (MMI) and 50 newly diagnosed MM stage III (MMIII) patients, according to Durie-Salmon staging system, by flow cytometry to examine their prognostic and predictive value. We also combined <i>in vivo</i> observations with <i>in vitro</i> assays to determine the effect of IKZF1/3 expression on the T-cell immunophenotype and anti-tumour T-cell response in 162 MMIII patients. <b>Results</b>: We found that high IKZF3, but not IKZF1, expression in T-cells correlates with superior overall survival in MMIII patients treated with immunomodulatory drugs (thalidomide, lenalidomide and pomalidomide). Moreover, we show that higher IKZF3 expression in T-cells inhibits myeloma-specific T-cell response <i>in vitro</i> and that the immunophenotype of patients with high IKZF3 expression shows features that are contrary to the changes induced by immunomodulatory drugs. Although we observed higher IKZF3 expression levels in T-cells from patients with MMIII compared to MMI, IKZF3 expression was unaffected by the tumour microenvironment. <b>Conclusion</b>: In conclusion, IKZF3 expression in T-cells is a predictive value for clinical outcome in MMIII patients treated with immunomodulatory drugs due to its profound modulation of T-cell functionality.
Unravelling the brain networks driving spike‐wave discharges in genetic generalized epilepsy—common patterns and individual differences
2018-08-01

Summary Objective Genetic generalized epilepsies ( GGEs ) are characterized by generalized spike‐wave discharges ( GSWD s) in electroencephalography ( EEG ) recordings without underlying structural brain lesions. The origin of the epileptic activity remains unclear, although several studies have reported involvement of thalamus and default mode network ( DMN ). The aim of the current study was to investigate the networks involved in the generation and temporal evolution of GSWD s to elucidate the origin and propagation of the underlying generalized epileptic activity. Methods We examined 12 patients with GGE and GSWD s using EEG – functional magnetic resonance imaging (fMRI) and identified involved brain areas on the basis of a classical general linear model ( GLM ) analysis. The activation time courses of these areas were further investigated to reveal their temporal sequence of activations and deactivations. Dynamic causal modeling ( DCM ) was used to determine the generator of GSWD s in GGE . Results We observed activity changes in the thalamus, DMN , dorsal attention network ( DAN ), salience network ( SN ), basal ganglia, dorsolateral prefrontal cortex, and motor cortex with supplementary motor area, however, with a certain heterogeneity between patients. Investigation of the temporal sequence of activity changes showed deactivations in the DMN and DAN and activations in the SN and thalamus preceding the onset of GSWDs on EEG by several seconds. DCM analysis indicated that the DMN gates GSWD s in GGE . Significance The observed interplay between DMN , DAN , SN , and thalamus may indicate a downregulation of consciousness. The DMN seems to play a leading role as a driving force behind these changes. Overall, however, there were also clear differences in activation patterns between patients, reflecting a certain heterogeneity in this cohort of GGE patients.
SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents
2018-08-01

Abstract We report the synthesis of SAHAquines and related primaquine (PQ) derivatives. SAHAquines are novel hybrid compounds that combine moieties of suberoylanilide hydroxamic acid (SAHA), an anticancer agent with weak antiplasmodial activity, and PQ, an antimalarial drug with low antiproliferative activity. The preparation of SAHAquines is simple, cheap, and high yielding. It includes the following steps: coupling reaction between primaquine and a dicarboxylic acid monoester, hydrolysis, a new coupling reaction with O ‐protected hydroxylamine, and deprotection. SAHAquines 5 a – d showed significant reduction in cell viability. Among the three human cancer cell lines (U2OS, HepG2, and MCF‐7), the most responsive were the MCF‐7 cells. The antibodies against acetylated histone H3K9/H3K14 in MCF‐7 cells revealed a significant enhancement following treatment with N ‐hydroxy‐ N ′‐{4‐[(6‐methoxyquinolin‐8‐yl)amino]pentyl}pentanediamide ( 5 b ). Ethyl (2 E )‐3‐({4‐[(6‐methoxyquinolin‐8‐yl)amino]pentyl}carbamoyl)prop‐2‐enoate ( 2 b ) and SAHAquines were the most active compounds against both the hepatic and erythrocytic stages of Plasmodium parasites, some of them at sub‐micromolar concentrations. The results of our research suggest that SAHAquines are promising leads for new anticancer and antimalarial agents.
Learning to Reproduce Visually Similar Movements by Minimizing Event-Based Prediction Error
2018-08-01

Prediction is believed to play an important role in the human brain. However, it is still unclear how predictions are used in the process of learning new movements. In this paper, we present a method to learn movements from visual prediction. The method consists of two phases: learning a visual prediction model for a given movement, then minimizing the visual prediction error. The visual prediction model is learned from a single demonstration of the movement where only visual input is sensed. Unlike previous work, we represent visual information with event streams as provided by a Dynamic Vision Sensor. This allows us to only process changes in the environment instead of complete snapshots using spiking neural networks. By minimizing the prediction error, movements visually similar to the demonstration are learned. We evaluate our method by learning simple movements from human demonstrations on different simulated robots. We show that the definition of the visual prediction error greatly impacts movements learned by our method.