Miracle-dz/UniFAR-FTUs huggingface dataset:
Individualized Mutation Detection in Circulating Tumor DNA for Monitoring Colorectal Tumor Burden Using a Cancer-Associated Gene Sequencing Panel

Background Circulating tumor DNA (ctDNA) carries information on tumor burden. However, the mutation spectrum is different among tumors. This study was designed to examine the utility of ctDNA for monitoring tumor burden based on an individual mutation profile. Methodology DNA was extracted from a total of 176 samples, including pre- and post-operational plasma, primary tumors, and peripheral blood mononuclear cells (PBMC), from 44 individuals with colorectal tumor who underwent curative resection of colorectal tumors, as well as nine healthy individuals. Using a panel of 50 cancer-associated genes, tumor-unique mutations were identified by comparing the single nucleotide variants (SNVs) from tumors and PBMCs with an Ion PGM sequencer. A group of the tumor-unique mutations from individual tumors were designated as individual marker mutations (MMs) to trace tumor burden by ctDNA using droplet digital PCR (ddPCR). From these experiments, three major objectives were assessed: (a) Tumor-unique mutations; (b) mutation spectrum of a tumor; and (c) changes in allele frequency of the MMs in ctDNA after curative resection of the tumor. Results A total of 128 gene point mutations were identified in 27 colorectal tumors. Twenty-six genes were mutated in at least 1 sample, while 14 genes were found to be mutated in only 1 sample, respectively. An average of 2.7 genes were mutated per tumor. Subsequently, 24 MMs were selected from SNVs for tumor burden monitoring. Among the MMs found by ddPCR with > 0.1% variant allele frequency in plasma DNA, 100% (8 out of 8) exhibited a decrease in post-operation ctDNA, whereas none of the 16 MMs found by ddPCR with < 0.1% variant allele frequency in plasma DNA showed a decrease. Conclusions This panel of 50 cancer-associated genes appeared to be sufficient to identify individual, tumor-unique, mutated ctDNA markers in cancer patients. The MMs showed the clinical utility in monitoring curatively-treated colorectal tumor burden if the allele frequency of MMs in plasma DNA is above 0.1%.
An insight into the active site of a type I DNA topoisomerase from the kinetoplastid protozoan Leishmania donovani.

DNA topoisomerases are ubiquitous enzymes that govern the topological interconversions of DNA thereby playing a key role in many aspects of nucleic acid metabolism. Recently determined crystal structures of topoisomerase fragments, representing nearly all the known subclasses, have been solved. The type IB enzymes are structurally distinct from other known topoisomerases but are similar to a class of enzymes referred to as tyrosine recombinases. A putative topoisomerase I open reading frame from the kinetoplastid Leishmania donovani was reported which shared a substantial degree of homology with type IB topoisomerases but having a variable C-terminus. Here we present a molecular model of the above parasite gene product, using the human topoisomerase I crystal structure in complex with a 22 bp oligonucleotide as a template. Our studies indicate that the overall structure of the parasite protein is similar to the human enzyme; however, major differences occur in the C-terminal loop, which harbors a serine in place of the usual catalytic tyrosine. Most other structural themes common to type IB topoisomerases, including secondary structural folds, hinged clamps that open and close to bind DNA, nucleophilic attack on the scissile DNA strand and formation of a ternary complex with the topoisomerase I inhibitor camptothecin could be visualized in our homology model. The validity of serine acting as the nucleophile in the case of the parasite protein model was corroborated with our biochemical mapping of the active site with topoisomerase I enzyme purified from L.donovani promastigotes.
Speech Polarity Detection Using Hilbert Phase Information

The objective of the present work is to propose a method to automatically detect polarity of the speech signals by estimating instants of significant excitation of the vocaltract and the cosine phase of the analytic signal representation. The phase changes in the analytic signal around the Hilbert envelope (HE) peaks are found to vary according to the polarity of the given speech signal. The relevant HE peaks for the Hilbert phase analysis are selected by estimating the instants of significant excitation in speech. The speech polarity identification rate obtained for the proposed method is almost equal to the state of the art residual skewness method for speech polarity detection. The proposed method also provides the same results for the polarity detection in electro-glottogram signals. Finally, the robustness of the proposed method is confirmed from the reduced detection error rates obtained in noisy environments with various signal to noise ratios (SNRs). The MATLAB codes used for implementing the proposed method are available for download from the following link: this http URL
Atheism in Higher Education: A Phenomenological Study of Identity in the Workplace

Abstract Institutions of higher education are perceived to be welcoming to individuals from a variety of backgrounds, including race, ethnicity, sexual orientation, and religion. Is this true for those who identify as atheist as well? This phenomenological study explored how the atheist identity manifests for those who are employed as professional staff in higher education. The participants were employed at public, Midwestern universities in rural communities. Participants who identified with this particular religious minority reported that they were compelled to remain closeted for fear of stigmatization and the risk of discrimination as staff of educational institutions made up of highly Christian communities. The implication for practice is the need to include atheism as a form of religious diversity in order to reduce stigma associated with this identity.
Analysis and Synthesis of Facial Image Sequences Using Physical and Anatomical Models

An approach to the analysis of dynamic facial images for the purposes of estimating and resynthesizing dynamic facial expressions is presented. The approach exploits a sophisticated generative model of the human face originally developed for realistic facial animation. The face model which may be simulated and rendered at interactive rates on a graphics workstation, incorporates a physics-based synthetic facial tissue and a set of anatomically motivated facial muscle actuators. The estimation of dynamical facial muscle contractions from video sequences of expressive human faces is considered. An estimation technique that uses deformable contour models (snakes) to track the nonrigid motions of facial features in video images is developed. The technique estimates muscle actuator controls with sufficient accuracy to permit the face model to resynthesize transient expressions. >
Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

Background Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS) and steatohepatitis (NASH) cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients. Materials and Methods We used a gas chromatography-quadruple time-of-flight-mass spectrometry analysis to quantify alpha-ketoglutarate in serum from normal-weight subjects (n = 30) and morbidly obese women (n = 97) with or without NAFLD. Results We found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, there was no difference between SS and NASH. Moreover, we observed that circulating levels of alpha-ketoglutarate were associated with glucose metabolism parameters, lipid profile, hepatic enzymes and steatosis degree. In addition, diagnostic performance of alpha-ketoglutarate has been analyzed in NAFLD patients. The AUROC curves from patients with liver steatosis exhibited an acceptable clinical utility. Finally, we showed that the combination of biomarkers (AST, ALT and alpha-ketoglutarate) had the highest accuracy in diagnosing liver steatosis. Conclusion These findings suggest that alpha-ketoglutarate can determine the presence of non-alcoholic fatty liver in morbidly obese patients but it is not valid a biomarker for NASH.
Shift from Extracellular Signal-Regulated Kinase to AKT/cAMP Response Element-Binding Protein Pathway Increases Survival-Motor-Neuron Expression in Spinal-Muscular-Atrophy-Like Mice and Patient Cells

Spinal muscular atrophy (SMA), a recessive neurodegenerative disease, is characterized by the selective loss of spinal motor neurons. No available therapy exists for SMA, which represents one of the leading genetic causes of death in childhood. SMA is caused by a mutation of the survival-of-motor-neuron 1 (SMN1) gene, leading to a quantitative defect in the survival-motor-neuron (SMN) protein expression. All patients retain one or more copies of the SMN2 gene, which modulates the disease severity by producing a small amount of stable SMN protein. We reported recently that NMDA receptor activation, directly in the spinal cord, significantly enhanced the transcription rate of the SMN2 genes in a mouse model of very severe SMA (referred as type 1) by a mechanism that involved AKT/CREB pathway activation. Here, we provide the first compelling evidence for a competition between the MEK/ERK/Elk-1 and the phosphatidylinositol 3-kinase/AKT/CREB signaling pathways for SMN2 gene regulation in the spinal cord of type 1 SMA-like mice. The inhibition of the MEK/ERK/Elk-1 pathway promotes the AKT/CREB pathway activation, leading to (1) an enhanced SMN expression in the spinal cord of SMA-like mice and in human SMA myotubes and (2) a 2.8-fold lifespan extension in SMA-like mice. Furthermore, we identified a crosstalk between ERK and AKT signaling pathways that involves the calcium-dependent modulation of CaMKII activity. Together, all these data open new perspectives to the therapeutic strategy for SMA patients.
Information Flow in Animal-Robot Interactions

The nonverbal transmission of information between social animals is a primary driving force behind their actions and, therefore, an important quantity to measure in animal behavior studies. Despite its key role in social behavior, the flow of information has only been inferred by correlating the actions of individuals with a simplifying assumption of linearity. In this paper, we leverage information-theoretic tools to relax this assumption. To demonstrate the feasibility of our approach, we focus on a robotics-based experimental paradigm, which affords consistent and controllable delivery of visual stimuli to zebrafish. Specifically, we use a robotic arm to maneuver a life-sized replica of a zebrafish in a predetermined trajectory as it interacts with a focal subject in a test tank. We track the fish and the replica through time and use the resulting trajectory data to measure the transfer entropy between the replica and the focal subject, which, in turn, is used to quantify one-directional information flow from the robot to the fish. In agreement with our expectations, we find that the information flow from the replica to the zebrafish is significantly more than the other way around. Notably, such information is specifically related to the response of the fish to the replica, whereby we observe that the information flow is reduced significantly if the motion of the replica is randomly delayed in a surrogate dataset. In addition, comparison with a control experiment, where the replica is replaced by a conspecific, shows that the information flow toward the focal fish is significantly more for a robotic than a live stimulus. These findings support the reliability of using transfer entropy as a measure of information flow, while providing indirect evidence for the efficacy of a robotics-based platform in animal behavioral studies.
U.S. speed limit sign detection and recognition from image sequences

In this paper, we present a novel visual speed limit signs detection and recognition system for American signs. Firstly, rectangle detector is used to search rectangle candidate. Secondly, the Improved Stroke Width Transform (ISWT) is introduced to seek stroke width inside each rectangle candidate. Thirdly, the modified Connected-Component labeling is used to group these pixels into digit candidates. Fourthly, a method is presented for segmenting the digit candidates in order to make every digit candidate contains only single digit. Finally, every segmented digit candidate is recognized respectively based on the Support Vector Machine using Majority Voting strategy (MV). We call the SVM using the MV strategy MV-SVM. And, all the recognized digits are verified whether combination of them is speed limit or not according to rule set. The presented system is tested in different conditions, including sunny, cloudy, rainy weather and night, and the experimental results demonstrate that it is much efficient for detecting and recognizing rectangular speed limit signs.
MANAGEMENT OF CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION

The incidence of cardiogenic shock in community studies has not decreased significantly over time. Despite decreasing mortality rates associated with increasing utilisation of revascularisation, shock remains the leading cause of death for patients hospitalised with acute myocardial infarction (MI). Although shock often develops early after MI onset, it is typically not diagnosed on hospital presentation. Failure to recognise early haemodynamic compromise and the increased early use of hypotension inducing treatments may explain this observation. Recently, a randomised trial has demonstrated that early revascularisation reduces six and 12 month mortality.1,2 The current American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend the adoption of an early revascularisation strategy for patients < 75 years of age with cardiogenic shock.3 In this article, we review the incidence, aetiology, prevention, and recognition of shock, as well as its management. The extent of myocardial salvage from reperfusion treatment decreases exponentially with time to re-establishing coronary flow. Unfortunately, there has been little progress in reducing time to hospital presentation over the past decade,4 and this perhaps accounts for the stagnant incidence of cardiogenic shock in community studies (7.1%). 5 Cardiogenic shock also complicates non-ST elevation acute coronary syndromes. The incidence of shock in the PURSUIT trial was 2.9% (1995–97),6 similar to the 2.5% incidence reported in the non-ST elevation arm of the GUSTO II-B trial (1994–95). 7 A number of strategies that centre on reducing the time to effective treatment may help decrease the incidence of shock. These include public education to decrease the time to hospital presentation, triage and early transfer of high risk patients to selected centres, and early primary percutaneous coronary intervention (PCI) or rescue PCI for failed thrombolysis in high risk patients. The onset of cardiogenic shock in a patient following ST elevation MI heralds a dismal …
Surveillance and outbreak reports Déjà vu : Ralstonia mannitolilytica infection associated with a humidifying respiratory therapy device , Israel , June to July 2011

C Block (colinb@ekmd.huji.ac.il)1, Z Ergaz-Shaltiel2, L Valinsky3, V Temper1, C Hidalgo-Grass1, N Minster1, C Weissman4, S Benenson1, J Jaffe3, A E Moses1, B Bar-Oz2 1. Department of Clinical Microbiology and Infectious Diseases, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel 2. Department of Neonatal Medicine, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel 3. Laboratory of Molecular Biology, Israel Ministry of Health, Jerusalem, Israel 4. Department of Anaesthesiology, Hadassah-Hebrew University Medical Centre, Jerusalem, Israel
Communication coping strategies of victims of crime

This study offers an analysis of the reflections of victims of crime about the strategies they used to cope with their experiences. Interviews with seventeen victims of crime were conducted and analyzed qualitatively. Six major themes were discovered based on the analysis including the victim recalling having had an initial instinct or gut reaction about their perpetrator, a change in their attitudes, beliefs and behaviors as a result of the crime, the desire for monetary reimbursement for the crime, the desire to restore emotional balance, advocating the importance of victims’ rights, and finally the consideration of a risk-benefit ratio when disclosing to others.
A representative particle approach to coagulation and fragmentation of dust aggregates and fluid droplets

Context. There is increasing need for good algorithms for modeling the aggregation and fragmentation of solid particles (dust grains, dust aggregates, boulders) in various astrophysical settings, including protoplanetary disks, planetary- and sub-stellar atmospheres and dense molecular cloud cores. Here we describe a new algorithm that combines advantages of various standard methods into one. Aims. The aim is to develop a method that 1) can solve for aggregation and fragmentation; 2) can easily include the effect and evolution of grain properties such as compactness, composition, etc.; and 3) can be built as a coagulation/fragmentation module into a hydrodynamics simulation where it 3a) allows for non-“thermalized” non-local motions of particles (e.g. movement of particles in turbulent flows with stopping time larger than eddy turn-over time) and 3b) focuses computational effort there where most of the mass is. Methods. We develop a Monte-Carlo method in which we follow the “life” of a limited number of representative particles. Each of these particles is associated with a certain fraction of the total dust mass and thereby represents a large number of true particles which all are assumed to have the same properties as their representative particle. Under the assumption that the total number of true particles vastly exceeds the number of representative particles, the chance of a representative particle colliding with another representative particle is negligibly small, and we therefore ignore this possibility. This now makes it possible to employ a statistical approach to the evolution of the representative particles, which is the core of our Monte Carlo method. Results. The method reproduces the known analytic solutions of simplified coagulation kernels, and compares well to numerical results for Brownian motion using other methods. For reasonably well-behaved kernels it produces good results even for moderate number of swarms.
Dissimilarity in Graph-Based Semi-Supervised Classification

Label dissimilarity specifies that a pair of examples probably have different class labels. We present a semi-supervised classification algorithm that learns from dissimilarity and similarity information on labeled and unlabeled data. Our approach uses a novel graphbased encoding of dissimilarity that results in a convex problem, and can handle both binary and multiclass classification. Experiments on several tasks are promising.
An-effective lagrangian relaxation approach for multiple-mode crude oil transportation optimization

In this paper, an crude oil transportation planning problem for an oil distributor is studied, in which crude oil is transported by tankers and pipelines from an unlimited supply center to a set of customer harbors to satisfy their dynamic demands over multiple periods. In the problem, inventory level and shortage level of crude oil at each customer are limited; both fully loaded and partially loaded tankers are allowed in the transportation of crude oil, and part of the tankers may be rented from a third party. The objective is to determine in each period the schedule of tankers and pipelines and the number of tankers of each type to be rented/returned at the supply center in order to minimize the total logistics cost. After formulating the problem as a mixed integer programming problem, we generalize an existing Lagrangian relaxation approach that only allows fully loaded tanks to one that allows both fully loaded and partially loaded tankers of the problem. Numerical experiments show that the new approach can find a near optimal solution of the problem of large size in a reasonable computation time.
Mechanical Thrombolysis in Acute Ischemic Stroke With Endovascular Photoacoustic Recanalization

Background and Purpose— We present the results of endovascular photoacoustic recanalization (EPAR) treatment for acute ischemic stroke from the Safety and Performance Study at 6 centers in Europe and North America. The objectives of mechanical thrombolysis are rapid vessel recanalization and minimal use of chemical thrombolysis. Methods— This study was a prospective, nonrandomized study. The National Institutes of Health Stroke Scale (NIHSS) score and the modified Rankin Scale (mRS) score were recorded before treatment. The presence of recanalization was assessed by angiography. To measure outcome, follow-up examinations were performed at 24 hours, 7 days, and 30 days after stroke onset. Results— Thirty-four patients (median NIHSS 19) were enrolled. Ten patients had internal carotid artery occlusion, 12 patients had middle cerebral artery occlusion, 11 patients had vertebrobasilar occlusion, and 1 patient had posterior cerebral artery occlusion. The overall recanalization rate was 41.1% (14/34). Complete EPAR treatment was possible in 18 patients (median NIHSS 18), with vessel recanalization in 11 patients (61.1%) after EPAR. The average lasing time was 9.65 minutes. Incomplete EPAR treatment (16/34, median NIHSS 19) was defined as intention to treat with EPAR and that the EPAR microcatheter entered the patient. Additional treatment with intraarterial application of rTPA occurred in 13 patients. An adverse event associated with use of the device occurred in 1 patient. Symptomatic hemorrhages occurred in 2 patients (5.9%). The mortality rate was 38.2%. Conclusions— This study demonstrates the safety and technical feasibility of EPAR. This new technique may provide another treatment option in the therapeutic armamentarium for patients with acute ischemic stroke.
International Conference on Parallel Processing Efficient Routing and Broadcasting in Recursive Interconnection Networks

The WK-Recursive Network (WKRN) is a hierarchical interconnection network that is recursively defined and has excellent properties for scalable message-passing multicom­ puter systems. In this paper, we present efficient routing and broadcasting schemes in a WKRN. For efficient rout­ ing, we define the MP-graph between the source and des­ tination nodes of the message. For efficient broadcasting, we define the EDHP-graph and the NDST-graph. The MP-graph can also be used for message routing in the presence of faulty nodes. Similarly, the EDHP-graph (the NDST-graph) can be used for message broadcast in the presence of faulty links (nodes). Fault-tolerant communica­ tion schemes using these graphs have the advantage that no information about the presence or location of faulty compo­ nents is required. Moreover, the MP-graph and the NDSTgraph can be used under different fault models. We analyze the communication delays for message routing (broadcast) along MP-graphs (EDHP-graphs and NDST-graphs) under fault-free and faulty conditions.