Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization and metabolic synthetic lethal testing in a new model of SDH-loss familial pheochromocytoma and paraganglioma

Succinate dehydrogenase (SDH)-loss pheochromocytoma and paraganglioma (PPGL) are tumors driven by metabolic derangement. SDH loss leads to accumulation of intracellular succinate, which competitively inhibits dioxygenase enzymes, causing activation of pseudohypoxic signaling and hypermethylation of histones and DNA. The mechanisms by which these alterations lead to tumorigenesis are unclear, however. In an effort to fundamentally understand how SDH loss reprograms cell biology, we developed an immortalized mouse embryonic fibroblast cell line with conditional disruption of Sdhc and characterize the kinetics of Sdhc gene rearrangement, SDHC protein loss, succinate accumulation, and the resultant hypoproliferative phenotype. We further perform global transcriptomic, epigenomic, and proteomic characterization of changes resulting from SDHC loss, identifying specific perturbations at each biological level. We compare the observed patterns of epigenomic derangement to another previously-described immortalized mouse chromaffin cell model of SDHB loss, and compare both models to human SDH-loss tumors. Finally, we perform analysis of SDHC synthetic lethality with lactate dehydrogenase A (LDHA) and pyruvate carboxylase (PCX), which are important for regeneration of NAD+ and aspartate biosynthesis, respectively. Our data show that SDH-loss cells are selectively vulnerable to LDH genetic knock-down or chemical inhibition, suggesting that LDH inhibition may be an effective therapeutic strategy for SDH-loss PPGL.
Skill Set Profile Clustering: The Empty K-Means Algorithm with Automatic Specification of Starting Cluster Centers

While students’ skill set profiles can be estimated with formal cognitive diagnosis models [8], their computational complexity makes simpler proxy skill estimates attractive [1, 4, 6]. These estimates can be clustered to generate groups of similar students. Often hierarchical agglomerative clustering or k-means clustering is utilized, requiring, for K skills, the specification of 2^K clusters. The number of skill set profiles/clusters can quickly become computationally intractable. Moreover, not all profiles may be present in the population. We present a flexible version of k-means that allows for empty clusters. We also specify a method to determine efficient starting centers based on the Q-matrix. Combining the two substantially improves the clustering results and allows for analysis of data sets previously thought impossible.
A brief survey of visual odometry for micro aerial vehicles

Recently, visual odometry (VO) has experienced a rapid growth, which makes it viable for a range of applications. This survey paper attempts to provide a timely and comprehensive review of this field, focusing specifically on micro aerial vehicles (MAVs), with monocular, stereo or RGB-D cameras onboard. In this survey, the milestones in the development of VO will be reviewed, followed by an illustration of its general workflow, the commonly used datasets. The survey is concluded by an overall discussion.
Chronic Postoperative Pain After Primary and Revision Total Knee Arthroplasty

Objectives:Clinical experience suggests that patients with osteoarthritis (OA) undergoing revision total knee arthroplasty (TKA) experience more chronic complications after surgery compared with patients receiving primary TKA. This study aimed to investigate the difference in pain, mobility, and quality of life (QoL) in patients after revision TKA compared with patients after primary TKA. Methods:A total of 99 OA patients after revision TKA surgery and 215 patients after primary TKA surgery were investigated in a cross-sectional study using: a pain description of current pain (non-existent, mild, moderate, severe, or unbearable), the pain intensity visual analogue scale, the Knee Society Score, and the Osteoarthritis Research Society International questionnaire. Results:Nineteen percent after primary TKA surgery and 47% after revision TKA surgery experienced severe to unbearable chronic postoperative pain. After revision TKA surgery patients reported higher pain intensities during rest (P=0.039), while walking (P=0.008), and on average over the last 24 hours (P=0.050) compared with the patients after primary TKA surgery. Patients after revision TKA surgery had reduced walking distance (P=0.001), increased use of walking aids (P=0.015), and showed an overall decreased QoL (P<0.001) compared with patients after primary TKA surgery. No significant improvement was found in walking distance (P=0.448) for patients before revision TKA surgery compared with after revision TKA surgery. Discussion:More than twice as many patients have pain after revision surgery compared with patients after primary TKA. Patients after revision TKA surgery have reduced function, poorer QoL, and higher pain intensity compared with patients after primary TKA surgery.
Measurement of chemically-available iron in foods by incubation with human gastric juice in vitro

1. The proportion of iron liberated from twenty foods was measured after incubation in vitro with human gastric juice. 2. Results with samples of gastric juice obtained from one subject on ten occasions and from sixteen subjects on a single occasion showed good agreement, the proportions of Fe liberated covering the entire range from zero for egg to 1.0 for wine. 3. Where there were small variations between the results obtained with different samples of gastric juice attempts were made to correlate these with peptic activity, various proteins and mucoproteins, pH and total and free acid; the only factors that varied with the proportions of Fe solubilized were the various measures of acidity. 4. The results correlated highly with those of Layrisse et al. (1969) for the in vivo absorption of Fe from similar foods, although the samples used were not the same. 5. The amounts of Fe solubilized when the foods were mixed with bran, oats or egg (known to reduce the in vivo absorption of Fe from foods) were less than calculated from the sum of each, with two exceptions. 6. The results obtained with human gastric juice differed from those obtained with in vitro methods prcviously reported, namely treatment with dilute hydrochloric acid and double incubation with pepsin plus HCI at pH 2.5 followed by adjustment to pH 7.5. 7. The amount of Fe solubilized from soya-bean flour by gastric juice was compared with that solubilized by pepsin plus HCI; both systems were shown to be pH dependent but the amount of Fe liberated with pepsin- HCI was much greater than that known to be absorbed by man in vivo. 8. It is suggested that incubation with human gastric juice may permit in vitro analyses of ‘chemically- available’ Fe in foods and thus be of value in food composition tables in terms of ‘Fe equivalents’ even though the amounts absorbed in vivo are subsequently influenced by other ingredients of the diet and by the Fe status of the individual.
SAS: Slot allocation scheme for the IEEE 802.15.4e LLDN mode

Wireless sensor networks are being widely used to support time-critical applications, even knowing that previous versions of the IEEE 802.15. 4 standard have a limited capacity to ensure a timely communication service. Its main limitation is the reduced number of available GTS slots. More recently, the IEEE 802.15. 4e LLDN mode has been released to address this issue. It provides static TDMA-based communication, with a larger number of available slots to support time-critical communication. However, it does not provide any guidelines on how to allocate slots, in order to guarantee the message real-time requirements. In this paper, we propose a methodology to allocate LLDN slots based on the traffic load imposed by the supported message streams. The proposed allocation scheme is able to handle message streams with periodicities that are not multiple of the beacon interval, and also to support static and dynamic prioritizing of message streams.
Investigation of 15q11-q13, 16p11.2 and 22q13 CNVs in Autism Spectrum Disorder Brazilian Individuals with and without Epilepsy

Copy number variations (CNVs) are an important cause of ASD and those located at 15q11-q13, 16p11.2 and 22q13 have been reported as the most frequent. These CNVs exhibit variable clinical expressivity and those at 15q11-q13 and 16p11.2 also show incomplete penetrance. In the present work, through multiplex ligation-dependent probe amplification (MLPA) analysis of 531 ethnically admixed ASD-affected Brazilian individuals, we found that the combined prevalence of the 15q11-q13, 16p11.2 and 22q13 CNVs is 2.1% (11/531). Parental origin could be determined in 8 of the affected individuals, and revealed that 4 of the CNVs represent de novo events. Based on CNV prediction analysis from genome-wide SNP arrays, the size of those CNVs ranged from 206 kb to 2.27 Mb and those at 15q11-q13 were limited to the 15q13.3 region. In addition, this analysis also revealed 6 additional CNVs in 5 out of 11 affected individuals. Finally, we observed that the combined prevalence of CNVs at 15q13.3 and 22q13 in ASD-affected individuals with epilepsy (6.4%) was higher than that in ASD-affected individuals without epilepsy (1.3%; p<0.014). Therefore, our data show that the prevalence of CNVs at 15q13.3, 16p11.2 and 22q13 in Brazilian ASD-affected individuals is comparable to that estimated for ASD-affected individuals of pure or predominant European ancestry. Also, it suggests that the likelihood of a greater number of positive MLPA results might be found for the 15q13.3 and 22q13 regions by prioritizing ASD-affected individuals with epilepsy.
Dynamic Partial Cooperative MIMO System for Delay-Sensitive Applications with Limited Backhaul Capacity

Considering backhaul consumption, it may not be the best choice to engage all the time in full cooperative MIMO for interference mitigation. In this paper, we propose a novel downlink partial cooperative MIMO (Pco-MIMO) physical layer (PHY) scheme, which allows flexible tradeoff between the partial data cooperation level and the backhaul consumption. Based on this Pco-MIMO scheme, we consider dynamic transmit power and rate allocation according to the imperfect channel state information at transmitters (CSIT) and the queue state information (QSI) to minimize the average delay cost subject to average backhaul consumption constraints and average power constraints. The delay-optimal control problem is formulated as an infinite horizon average cost constrained partially observed Markov decision process (CPOMDP). By exploiting the special structure in our problem, we derive an equivalent Bellman Equation to solve the CPOMDP. To reduce computational complexity and facilitate distributed implementation, we propose a distributed online learning algorithm to estimate the per-flow potential functions and Lagrange multipliers (LMs) and a distributed online stochastic partial gradient algorithm to obtain the power and rate control policy. We prove the convergence and asymptotic optimality of the proposed solution.
Application of Shape Similarity in Pose Selection and Virtual Screening in CSARdock2014 Exercise

To evaluate the applicability of shape similarity in docking-based pose selection and virtual screening, we participated in the CSARdock2014 benchmark exercise for identifying the correct docking pose of inhibitors targeting factor XA, spleen tyrosine kinase, and tRNA methyltransferase. This exercise provides a valuable opportunity for researchers to test their docking programs, methods, and protocols in a blind testing environment. In the CSARdock2014 benchmark exercise, we have implemented an approach that uses ligand 3D shape similarity to facilitate docking-based pose selection and virtual screening. We showed here that ligand 3D shape similarity between bound poses could be used to identify the native-like pose from an ensemble of docking-generated poses. Our method correctly identified the native pose as the top-ranking pose for 73% of test cases in a blind testing environment. Moreover, the pose selection results also revealed an excellent correlation between ligand 3D shape similarity scores and RMSD to X-ray crystal structure ligand. In the virtual screening exercise, the average RMSD for our pose prediction was found to be 1.02 Å, and it was one of the top performances achieved in CSARdock2014 benchmark exercise. Furthermore, the inclusion of shape similarity improved virtual screening performance of docking-based scoring and ranking. The coefficient of determination (r(2)) between experimental activities and docking scores for 276 spleen tyrosine kinase inhibitors was found to be 0.365 but reached 0.614 when the ligand 3D shape similarity was included.
Performance of Genotype Imputation for Low Frequency and Rare Variants from the 1000 Genomes

Genotype imputation is now routinely applied in genome-wide association studies (GWAS) and meta-analyses. However, most of the imputations have been run using HapMap samples as reference, imputation of low frequency and rare variants (minor allele frequency (MAF) < 5%) are not systemically assessed. With the emergence of next-generation sequencing, large reference panels (such as the 1000 Genomes panel) are available to facilitate imputation of these variants. Therefore, in order to estimate the performance of low frequency and rare variants imputation, we imputed 153 individuals, each of whom had 3 different genotype array data including 317k, 610k and 1 million SNPs, to three different reference panels: the 1000 Genomes pilot March 2010 release (1KGpilot), the 1000 Genomes interim August 2010 release (1KGinterim), and the 1000 Genomes phase1 November 2010 and May 2011 release (1KGphase1) by using IMPUTE version 2. The differences between these three releases of the 1000 Genomes data are the sample size, ancestry diversity, number of variants and their frequency spectrum. We found that both reference panel and GWAS chip density affect the imputation of low frequency and rare variants. 1KGphase1 outperformed the other 2 panels, at higher concordance rate, higher proportion of well-imputed variants (info>0.4) and higher mean info score in each MAF bin. Similarly, 1M chip array outperformed 610K and 317K. However for very rare variants (MAF≤0.3%), only 0–1% of the variants were well imputed. We conclude that the imputation of low frequency and rare variants improves with larger reference panels and higher density of genome-wide genotyping arrays. Yet, despite a large reference panel size and dense genotyping density, very rare variants remain difficult to impute.
Solvent Evaporation Technique of Microencapsulation: A Systemic Review

Solvent evaporation is one of the most widely employed and investigated technique in pharmaceutical industries and research area for microencapsulation process.Microspheres are particles coated with a continuous film of polymeric material, having a diameter in range of 1 to 1000 ? m and are widely used as drug carriers. This technique provides a controlled drug release, having various clinical benefits. While initial lab scale experiments are carried out in simple beaker, stirrer setups, clinical trials and market introduction needs more sophisticated technologies, permitting economic robust, well-controllable and aseptic production of microspheres. In this review article our aim is to review and compile recent research work on solvent evaporation technique while focusing on different methods of above said technique and various factors affecting microencapsulation prepared by solvent evaporation technique.
A less conservative consensus condition for multi-agent systems with double-integrator dynamics

How to improve consensus conditions for double-integrator multi-agent systems is investigated. First, a consensus algorithm is presented and the corresponding convergence condition is described. However, the given convergence condition is conservative such that consensus is still obtained when the parameters of the consensus algorithm violate the given convergence condition. Second, to cope with this issue, a less conservative convergence condition is proposed by using complex number and matrix properties. Finally, simulation results illustrate the effectiveness of the convergence condition through two examples.
Breakfast and exercise contingently affect postprandial metabolism and energy balance in physically active males

The present study examined the impact of breakfast and exercise on postprandial metabolism, appetite and macronutrient balance. A sample of twelve (blood variables n 11) physically active males completed four trials in a randomised, crossover design comprising a continued overnight fast followed by: (1) rest without breakfast (FR); (2) exercise without breakfast (FE); (3) breakfast consumption (1859 kJ) followed by rest (BR); (4) breakfast consumption followed by exercise (BE). Exercise was continuous, moderate-intensity running (expending approximately 2·9 MJ of energy). The equivalent time was spent sitting during resting trials. A test drink (1500 kJ) was ingested on all trials followed 90 min later by an ad libitum lunch. The difference between the BR and FR trials in blood glucose time-averaged AUC following test drink consumption approached significance (BR: 4·33 (sem 0·14) v. FR: 4·75 (sem 0·16) mmol/l; P= 0·08); but it was not different between FR and FE (FE: 4·77 (sem 0·14) mmol/l; P= 0·65); and was greater in BE (BE: 4·97 (sem 0·13) mmol/l) v. BR (P= 0·012). Appetite following the test drink was reduced in BR v. FR (P= 0·006) and in BE v. FE (P= 0·029). Following lunch, the most positive energy balance was observed in BR and least positive in FE. Regardless of breakfast, acute exercise produced a less positive energy balance following ad libitum lunch consumption. Energy and fat balance is further reduced with breakfast omission. Breakfast improved the overall appetite responses to foods consumed later in the day, but abrogated the appetite-suppressive effect of exercise.
Loss minimization of two stage solar powered speed sensorless vector controlled induction motor drive for water pumping

This paper deals with a two stage solar photovoltaic (SPV) fed speed sensorless vector controlled induction motor drive (IMD) for water pumping system which is superior to conventional controlled motor as it is cheaper and reliable. One common practice is to estimate the flux from the terminal voltages and currents. The performance of the drive depends on the accuracy of the flux estimator. Usually the efficiency of the induction motor drive (IMD) is high around the rated load and deteriorates at partial loading. However, the efficiency can be enhanced by operating the motor at optimum flux by controlling the flux component of current. In this paper, a minimization technique is proposed to minimize the total losses to operate the drive at maximum efficiency. A modified perturb and observe (P&O) algorithm is used to track maximum power from SPV array. The smooth starting of the motor is attained by vector control of an induction motor. The system performance is simulated in MATLAB/Simulink environment and the results are compared with the conventional vector controlled IMD.
Molecular Conformation and Structural Correlations of Liquid D-tert-Butanol at Room Temperature by Neutron Diffraction

Abstract An analysis of neutron diffraction data of liquid deuterated terr-butanol at room temperature to determine its molecular conformation is presented. Being a big molecule of 15 sites, the analysis is tricky and needs careful consideration. The resulting molecular parameters are compared with those obtained from other experimental data analysis and model calculations. The information about the intermolecular structural correlations, hydrogen-bonded molecular association in particular is also obtained from the diffraction data analysis. -PACS number: 61.25
Neurotoxic Concentration of Piperacillin during Continuous Infusion in Critically Ill Patients

ABSTRACT This retrospective cohort study included 53 patients admitted to the intensive care unit (ICU), with an average age of 69 years, without neurologic disorder before initiation of a continuous piperacillin infusion at the standard dose and who underwent piperacillin serum concentration monitoring. Among them, 23 developed a neurologic disorder for which the piperacillin causality was chronologically and semiologically suggestive. A concentration threshold of 157.2 mg/liter independently predicted neurotoxicity with 96.7% specificity and 52.2% sensitivity and may constitute a limitation when targeting less susceptible pathogens.
Pregnant women with substance use disorders: The intersection of history, ethics, and advocacy

ABSTRACT Pregnant women with substance use disorders face many obstacles, including obtaining evidence-based treatment and care. This article (1) briefly reviews the history of pregnant women in clinical trials and substance use disorders treatment research; (2) identifies current ethical issues facing researchers studying pregnant women with substance use disorders; (3) presents and describes an ethical framework to utilize; and (4) identifies future directions needed to develop appropriate research and treatment policies and practices. Current research is not providing enough information to clinicians, policy-makers, and the public about maternal and child health and substance use disorders, and the data will not be sufficient to offer maximum benefit until protocols are changed.
Epistasis and destabilizing mutations shape gene expression variability in humans via distinct modes of action

Increasing evidence shows that, like phenotypic mean, phenotypic variance is also genetically determined, but the underlying mechanisms of genetic control over the variance remain obscure. Here, we conducted variance-association mapping analyses to identify expression variability QTLs (evQTLs), i.e., genomic loci associated with gene expression variance, in humans. We discovered that common genetic variations may contribute to increasing gene expression variability via two distinct modes of action—epistasis and destabilization. Specifically, the epistasis model explains a quarter of the identified evQTLs, of which the formation is attributed to the presence of “third-party” eQTLs that influence the level of gene expression in a fraction, rather than the entire set, of sampled individuals. The destabilization model explains the other three-quarters of evQTLs, which tend to be associated with mutations that disrupt the stability of the transcription process of genes. To show the destabilizing effect, we measured discordant gene expression between monozygotic twins, and time-course stability of gene expression in single samples using repetitive qRT-PCR assays. The destabilizing evQTL SNPs were found to be associated with more pronounced expression discordance between twin pairs and less stable gene expression in single samples. Together, our results suggest that common SNPs may work interactively or independently to shape the variability of gene expression in humans. These findings contribute to the understanding of the mechanisms of genetic control over phenotypic variance and may have implications for the development of variability-centered analytic methods for quantitative trait mapping.