Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways

Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process. We report the interaction of LRRK2 with the dishevelled family of phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways important for axon guidance, synapse formation and neuronal maintenance. Interestingly, DVLs can interact with and mediate the activation of small GTPases with structural similarity to the LRRK2 Roc domain. The LRRK2 Roc-COR domain and the DVL1 DEP domain were necessary and sufficient for LRRK2–DVL1 interaction. Co-expression of DVL1 increased LRRK2 steady-state protein levels, an effect that was dependent on the DEP domain. Strikingly, LRRK2–DVL1-3 interactions were disrupted by the familial PARK8 mutation Y1699C, whereas pathogenic mutations at residues R1441 and R1728 strengthened LRRK2–DVL1 interactions. Co-expression of DVL1 with LRRK2 in mammalian cells resulted in the redistribution of LRRK2 to typical cytoplasmic DVL1 aggregates in HEK293 and SH-SY5Y cells and co-localization in neurites and growth cones of differentiated dopaminergic SH-SY5Y cells. This is the first report of the modulation of a key LRRK2-accessory protein interaction by PARK8 Roc-COR domain mutations segregating with Parkinson's disease. Since the DVL1 DEP domain is known to be involved in the regulation of small GTPases, we propose that: (i) DVLs may influence LRRK2 GTPase activity, and (ii) Roc-COR domain mutations modulating LRRK2–DVL interactions indirectly influence kinase activity. Our findings also link LRRK2 to Wnt signalling pathways, suggesting novel pathogenic mechanisms and new targets for genetic analysis in Parkinson's disease.
Food Addiction in Gambling Disorder: Frequency and Clinical Outcomes

Background: The food addiction (FA) model is receiving increasing interest from the scientific community. Available empirical evidence suggests that this condition may play an important role in the development and course of physical and mental health conditions such as obesity, eating disorders, and other addictive behaviors. However, no epidemiological data exist on the comorbidity of FA and gambling disorder (GD), or on the phenotype for the co-occurrence of GD+FA. Objectives: To determine the frequency of the comorbid condition GD+FA, to assess whether this comorbidity features a unique clinical profile compared to GD without FA, and to generate predictive models for the presence of FA in a GD sample. Method: Data correspond to N = 458 treatment-seeking patients who met criteria for GD in a hospital unit specialized in behavioral addictions. Results: Point prevalence for FA diagnosis was 9.2%. A higher ratio of FA was found in women (30.5%) compared to men (6.0%). Lower FA prevalence was associated with older age. Patients with high FA scores were characterized by worse psychological state, and the risk of a FA diagnosis was increased in patients with high scores in the personality traits harm avoidance and self-transcendence, and low scores in cooperativeness (R2 = 0.18). Conclusion: The co-occurrence of FA in treatment-seeking GD patients is related to poorer emotional and psychological states. GD treatment interventions and related behavioral addictions should consider potential associations with problematic eating behavior and aim to include techniques that aid patients in better managing this behavior.
Voltage Sensorless Direct Model Predictive Control of 3L-NPC Back-to-Back Power Converter PMSG Wind Turbine Systems with Fast Dynamics

Full power rating three-level neutral-point clamped (3L-NPC) back-to-back power converters seem promising for wind turbine systems with high power. Direct Model Predictive Control (DMPC) is an attractive technique, in particular, for multi-level converters. Voltage sensorless control makes the voltage measurements obsolete. This work proposes and verifies an Initial Bias Compensation based Virtual Flux (IBC-VF) voltage sensorless DMPC scheme for 3L-NPC back-to-back power converter Permanentmagnet Synchronous Generator (PMSG) wind turbine systems. With the proposed VF estimation scheme, no grid side voltage measurement information is required; both generator and grid side controllers are realized using DMPC concepts incorporating both targeting and (nonlinear) constraint set into a single cost function with great flexibility. Compared to conventional filter based voltage sensorless control strategies, the proposed one shows fast dynamics and accurate estimation of the voltage (virtual flux), which leads to overshoot-free power/current and DC-link voltage control.
Transcriptional control of Pactolus: evidence of a negative control region and comparison with its evolutionary paralogue, CD18 (β2 integrin)

The mouse Pactolus and CD18 genes are highly conserved paralogues. The expression patterns of these genes are diverse in that most cells of hematopoietic lineage express CD18, but Pactolus is only expressed by maturing neutrophils. The minimal promoters of these two genes are homologous, including the conservation of two tandem PU.1‐binding sites upstream of the transcriptional start site. To define the means by which these two structurally similar but functionally distinct promoters operate, a series of reporter assays, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation analyses, were performed. Transfection of Pactolus constructs into mouse macrophages, which do not express Pactolus, defined a negative control element within the first 100 base pairs. The presence of this negative regulatory site, distinct from the PU.1‐binding site, was confirmed by EMSA oligonucleotide competition and gene reporter assays of Pactolus/CD18 chimeric constructs. Although PU.1 binding can be detected on Pactolus and CD18 minimal promoter segments with EMSA, only the CD18 promoter shows PU.1 binding in vivo, suggesting that the negative regulatory protein may block PU.1 from binding to the Pactolus promoter, thus inhibiting transcription of the gene. Sequence analysis of the negative control region in the Pactolus promoter suggested potential control by Snail and/or Smad families of transcription regulators. EMSA supershift analysis with antibodies against these proteins, using extracts from macrophages and mucosal mast cells, identified specific binding of Smuc to the promoter element, including a Smuc/PU.1/DNA trimeric complex. These data implicate Smuc as blocking Pactolus transcription in cells expressing PU.1 (and CD18) but not Pactolus.
Notice of Violation of IEEE Publication PrinciplesCTMIR: A Novel Correlated Topic Model for Image Retrieval

Representation of images by the Latent Dirichlet Allocation model combined with an appropriate similarity measure is suitable for performing large scale image retrieval in a real-world database. The LDA model, however, relies on the assumption that all topics are independent of each other something that is obviously not true in most cases. In this work we study a recently proposed model, the Correlated Topic Model (CTM) [1], in the context of large-scale image retrieval. This approach is able to explicitly model such correlations of topics. We experimentally evaluate the proposed retrieval approach on a real-world large-scale database consisting of more than 246,000 images and compare the performance to related approaches.
Static synchronous generators for distributed generation and renewable energy

In this paper, the idea of operating an inverter as a synchronous generator is developed after establishing a model for synchronous generators to cover all dynamics without any assumptions on the signals. The inverters which are operated in this way are called static synchronous generators (SSG). This means that the well-established theory/device for synchronous generators can still be used for inverters, which will dominate the power generation in the future because of the increasing share of distributed generation sources and renewable energy sources utilised. The power of an SSG can be regulated using the well-known frequency and voltage drooping mechanism. SSGs can also be easily operated in grid-connected mode or island mode. Simulation results are given to verify the idea.
The Relationship Between Aerobic and Anaerobic Performance in Recreational Runners

Research has indicated that combined aerobic and anaerobic training (concurrent training) may improve aerobic performance greater than aerobic training alone. The purpose of this investigation was to establish any associations between aerobic and anaerobic performance. Eleven participants (n = 11, age = 34.1 ± 13 years, VO2max = 58.4 ± 7.8) volunteered for this study. Participants were asked for endurance training experience (4.7 ± 3.7 years) and resistance training experience (4.1 ± 4.6 years). To meet training status, participants were to have a VO2max in the 80th percentile as per ACSM guidelines. The Bruce treadmill test was used to measure aerobic performance. In order to measure anaerobic performance, several tests were completed utilizing a force platform. A Pearson Product R Correlation Coefficient was calculated to determine correlations between variables. The results show significant correlation between VO2max and RFD (r = 0.68). Further analyses utilizing Cohen’s effect size indicated a strong association between VO2max and peak force, as well as running efficiency and peak power, relative peak power, and power endurance. These results indicate an existing possibility that anaerobic performance measures such as RFD may have a positive relationship with aerobic performance measures such as VO2max. Therefore, it may be beneficial to integrate specific training components which focus on improving RFD as a method of improving running performance.
Characteristics of Multimode Fibers at High Frequency Region using Rayleigh Distribution

1 Abstract – Multimode fiber (MF) has recently been considered as a high data rate medium for signals transmitted at its high frequency region. This high data rate transmission is made possible since there are many many passbands, which can be adopted as channels for sending many subcarrier signals. These passbands are located at different frequencies and vary from fiber to fiber. These different frequencies are determined from the delays of guided modes in the fiber. The passbands at high frequency region of multimode fiber are studied in this paper. Rayleigh distribution is used to statistically model the delays of guided modes. The characteristics in terms of the average magnitude response and the average bandwidth of these passbands are considered. It is found that the only factor that determines the average magnitude response of the passbands is the number of guided modes. Additionally, the average bandwidth of these passbands depends on the standard deviation of the delays.
Use of Single-Strand Conformation Polymorphism Analysis To Examine the Variability of the rpoSSequence in Environmental Isolates of Salmonellae

ABSTRACT The natural environment places its resident microflora under stress, which may often result in adaptation by the microflora in order to increase the probability of survival. One such mechanism that has been postulated involves rpoS, which encodes a sigma factor that is known to enhance survival upon exposure to stress. The present work aimed to examine the genetic variability of rpoS in a selection of Salmonella enterica subspecies environmental isolates with an automated single-strand conformation polymorphism analysis technique. The results indicated that sequence variation does occur and that these changes are mainly located in two areas: at the center and near the end of the coding region. The variability was generally at the single-base level, although one strain (S. arizonae) did demonstrate significant differences in nucleotide sequence.
Network modulation of a slow intrinsic oscillation of cat thalamocortical neurons implicated in sleep delta waves: cortically induced synchronization and brainstem cholinergic suppression

A slow (0.5–4 Hz) oscillation of thalamic neurons was recently described and attributed to the interplay of two intrinsic currents. In this study, we investigated the network modulation of this intrinsic thalamic oscillation within the frequency range of EEG sleep delta- waves. We performed intracellular and extracellular recordings of antidromically identified thalamocortical cells (n = 305) in sensory, motor, associational, and intralaminar nuclei of anesthetized cats. At the resting membrane potential, Vm (-60.3 +/- 0.4 mV, mean +/- SE), cortical stimulation induced spindle-like oscillations (7–14 Hz), whereas at Vm more negative than -65 mV the same stimuli triggered an oscillation within the EEG delta-frequency (0.5–4 Hz), consisting of low-threshold spikes (LTSs) followed by after hyperpolarizing potentials (AHPs). The LTS-AHP sequences outlasted cortical stimuli as a self-sustained rhythmicity at 1–2 Hz. Corticothalamic stimuli were able to transform subthreshold slow (0.5–4 Hz) oscillations, occurring spontaneously at Vm more negative than -65 mV, into rhythmic LTSs crowned by bursts of Na+ spikes that persisted for 10–20 sec after cessation of cortical volleys. Cortical volleys also revived a hyperpolarization-activated slow oscillation when it dampened after a few cycles. Auto- and crosscorrelograms of neuronal pairs revealed that unrelated cells became synchronized after a series of corticothalamic stimuli, with both neurons displaying rhythmic (1-2 Hz) bursts or spike trains. Since delta-thalamic oscillations, prevailing during late sleep stages, are triggered at more negative Vm than spindles characterizing the early sleep stage, we postulate a progressive hyperpolarization of thalamocortical neurons with the deepening of the behavioral state of EEG-synchronized sleep. In view of the evidence that cortical-elicited slow oscillations depend on synaptically induced hyperpolarization of thalamocortical cells, we propose that the potentiating influence of the corticothalamic input results from the engagement of two GABAergic thalamic cell classes, reticular and local-circuit neurons. The thalamocorticothalamic loop would transfer the spike bursts of thalamic oscillating cells to cortical targets, which in turn would reinforce the oscillation by direct pathways and/or indirect projections relayed by reticular and local-circuit thalamic cells. Stimulation of mesopontine cholinergic [peribrachial (PB) and laterodorsal tegmental (LDT)] nuclei in monoamine-depleted animals had an effect that was opposite to that exerted by corticothalamic volleys. PB/LDT stimulation reduced or suppressed the slow (1–4 Hz) oscillatory bursts of high- frequency spikes in thalamic cells. (ABSTRACT TRUNCATED AT 400 WORDS)
Basal insulin peglispro versus insulin glargine in insulin‐naïve type 2 diabetes: IMAGINE 2 randomized trial

To compare, in a double‐blind, randomized, multi‐national study, 52‐ or 78‐week treatment with basal insulin peglispro or insulin glargine, added to pre‐study oral antihyperglycaemic medications, in insulin‐naïve adults with type 2 diabetes.
Visual Discovery and Analysis

We have developed a flexible software environment called ADVIZOR for visual information discovery. ADVIZOR complements existing assumptive-based analyses by providing a discovery-based approach. ADVIZOR consists of five parts: a rich set of flexible visual components, strategies for arranging the components for particular analyses, an in-memory data pool, data manipulation components, and container applications. Working together, ADVIZOR's architecture provides a powerful production platform for creating innovative visual query and analysis applications.
Multifunction Sensors Using Coincidence Dark-Bright Soliton Pair in a MZI

A new system of multifunction sensors using dark and bright solitons in a Mach-Zehnder interferometer (MZI) is proposed. In this concept, the coincidence dark and bright soliton pair within the MZI can be arranged by using the phase controller, in which (|D)) and (|B)) states represent the orthogonal dark and bright solitons, respectively. We assume that both solitons are input into the MZI ports simultaneously (coincidently). The randomly input dark and bright soliton states into the MZI ports can perform the change in phase after propagating through a phase shifter/sensing unit, in which the phase change recovery using the phase related measurement device can be provided. By using the orthogonal soliton behaviors, a sensing application using a soliton(photon) pair can be formed. Moreover, the soliton power can be reduced to a single photon power (10-6 W), where finally the single photon sensor can be operated. The self calibration concept between signal and referencing arms of a MZI can also be established, which is discussed in details.
A Method for Constructing Large DNA Codesets

The word design problem is an important problem in DNA computing. The goal is to design a set of single-stranded DNA molecules that are structurefree and mutually non-crosshybridizing. We present an innovative method of constructing such large sets, so called codesets, whose degree of structurefreeness and non-crosshybridization is controlled by a given parameter. Using a well-known, simplified model of hybridization affinity, known as the h-distance model, our method produces sets larger than those produced under similar models, for example, a similar (slightly less realistic) model can construct 108 8-mers, while our construction produces 256 8-mers with the same constraints in terms of the strands’ mutual hybridization affinity and GC-content. We further provide a justification for the claimed large sizes of produced sets by estimating their relative sizes to those of theoretically maximal sets. The existence of such large sets of structure-free, non-crosshybridizing strands is necessary for largescale DNA computations and approaches. Current methods that employ more realistic estimates of DNA hybridization affinity have been unable to produce sets large enough to encode more than several thousands or even hundred parameters. It seems feasible to extend our methodology to include more realistic assumptions, such as making use of known thermodynamic parameters.
emphaSSL: Towards Emphasis as a Mechanism to Harden Networking Security in Android Apps

The use of secure HTTP calls is a first and critical step toward securing the Android application data when the app interacts with the Internet. However, one of the major causes for the unencrypted communication is app developer's errors or ignorance. Could the paradigm of literally repetitive and ineffective emphasis shift towards emphasis as a mechanism? This paper introduces emphaSSL, a simple, practical and readily-deployable way to harden networking security in Android applications. Our emphaSSL could guide app developer's security development decisions via real-time feedback, informative warnings and suggestions. At its core of emphaSSL, we use a set of rigorous security rules, which are obtained through an in-depth SSL/TLS security analysis based on security requirements engineering techniques. We implement emphaSSL via the PMD and evaluate it against 75 open- source Android applications. Our results show that emphaSSL is effective at detecting security violations in HTTPS calls with a very low false positive rate, around 2%. Furthermore, we identified 164 substantial SSL mistakes in these testing apps, 40% of which are potentially vulnerable to man-in-the-middle attacks. In each of these instances, the vulnerabilities could be quickly resolved with the assistance of our highlighting messages in emphaSSL. Upon notifying developers of our findings in their applications, we received positive responses and interest in this approach.
Assortativity in Chung Lu Random Graph Models

Due to the widespread interest in networks as a representation to investigate the properties of complex systems, there has been a great deal of interest in generative models of graph structure that can capture the properties of networks observed in the real world. Recent models have focused primarily on accurate characterization of sparse networks with skewed degree distributions, short path lengths, and local clustering. While assortativity---degree correlation among linked nodes---is used as a measure to both describe and evaluate connectivity patterns in networks, there has been little effort to explicitly incorporate patterns of assortativity into model representations. This is because many graph models are edge-based (modeling whether a link should be placed between a pair of nodes i and j) and assortativity is a second-order characteristic that depends on the global properties of the graph (i.e., the final degree of i and j). As such, it is difficult to incorporate direct optimization of assortativity into edge-based generative models. One exception is the BTER method [5], which generates graphs with positive assortativity (e.g., high degree nodes link to each other). However, BTER does not directly estimate assortativity and also is not applicable for networks with negative assortativity (e.g, high degree nodes link primarily to low degree nodes). In this work, we present a novel approach to directly model observed assortativity (both positive and negative) via accept-reject sampling. Our key observation is to use a coarse approximation of the observed joint degree distribution and modify the likelihood that two nodes i, j should link based on the output properties of the original model. We implement our approach as an augmentation of Chung-Lu models and refer to it as Binning Chung Lu (BCL). We apply our method to six network datasets and show that it captures assortativity significantly more accurately than other methods while maintaining other graph properties of the original CL models. Also, our BCL approach is efficient (linear in the number of observed edges), thus it scales easily to large networks.
The "Low-Country Advantage" for African-Americans in Georgia, 1880-1930

The "Low-Country Advantage" for African-Americans in Georgia, 1880-1930 Social historians interested in the slave South have made much of a set of social, economic, and cultural distinctions between the lowcountry coastal region and the interior sections of South Carolina and Georgia. The basis for these distinctions lies in the recognition that, although both areas featured the use of slaves in large-scale plantation agriculture, the slave-labor system on low-country plantations was organized very differently from that on plantations located within the interior. Specifically, the task system predominated in the long-staple cotton and rice plantations of coastal South Carolina and Georgia; the gang labor system was the norm on short-staple cotton plantations, as well as on tobacco, grain, and sugar plantations. Although the immediate consequences of these different labor systems on slaves' lives have been widely recognized, some historians have suggested that these differences also had more far-reaching repercussions that influenced the social and economic experiences of African-Americans long after emancipation. For example, the consensus is that, because of prior involvement and experiences with the task system of agricultural production, low-country blacks were able to acquire property earlier, had more economic opportunities, were more attached to the land, and were more effective in shaping their postbellum labor arrangements than their counterparts from gang-labor plantation systems.1