Miracle-dz/UniFAR-FTUs huggingface dataset:
PASSion: a pattern growth algorithm-based pipeline for splice junction detection in paired-end RNA-Seq data

Motivation: RNA-seq is a powerful technology for the study of transcriptome profiles that uses deep-sequencing technologies. Moreover, it may be used for cellular phenotyping and help establishing the etiology of diseases characterized by abnormal splicing patterns. In RNA-Seq, the exact nature of splicing events is buried in the reads that span exon–exon boundaries. The accurate and efficient mapping of these reads to the reference genome is a major challenge. Results: We developed PASSion, a pattern growth algorithm-based pipeline for splice site detection in paired-end RNA-Seq reads. Comparing the performance of PASSion to three existing RNA-Seq analysis pipelines, TopHat, MapSplice and HMMSplicer, revealed that PASSion is competitive with these packages. Moreover, the performance of PASSion is not affected by read length and coverage. It performs better than the other three approaches when detecting junctions in highly abundant transcripts. PASSion has the ability to detect junctions that do not have known splicing motifs, which cannot be found by the other tools. Of the two public RNA-Seq datasets, PASSion predicted ∼ 137 000 and 173 000 splicing events, of which on average 82 are known junctions annotated in the Ensembl transcript database and 18% are novel. In addition, our package can discover differential and shared splicing patterns among multiple samples. Availability: The code and utilities can be freely downloaded from https://trac.nbic. nl/passion and ftp://ftp.sanger. ac.uk/pub/zn1/passion Contact: y.zhang@lumc.nl; k.ye@lumc.nl Supplementary information: Supplementary data are available at Bioinformatics online.
Core episodic encoding and retrieval processes revealed by dynamics of neural activity

The capacity to remember the past is dependent on neural processing that occurs not only when an event is experienced but also when it becomes reinstated into awareness at a later point in time. Neural networks that span the medial temporal lobes (MTL), prefrontal cortex, and posterior cortical regions support the formation and retrieval of memories. However, the specificity of processing that occurs during learning and retrieval of encoded information is not well understood. To elucidate whether common or distinct processing during encoding and retrieval best predict memory performance, we administered a delayed free recall task to 187 neurosurgical patients implanted with subdural or intraparenchymal depth electrodes. We identified biomarkers of memory success that were jointly predictive of both successful memory formation and recall, in the form of increased high frequency activity in prefrontal, MTL, and inferior parietal cortices, accompanied by widespread decreases in low frequency power. These findings demonstrate that in the presence of distinct neural systems that support episodic encoding and retrieval of memories, variability in neural activity within a putative core memory network shapes the ability to remember the past.
Exploring the Homeostatic and Sensory Roles of the Immune System

Immunology developed under the notion of the immune system exists to fight pathogens. Recently, the discovery of interactions with commensal microbiota that are essential to human health initiated a change in this old paradigm. Here, we argue that the immune system has major physiological roles extending far beyond defending the host. Immune and inflammatory responses share the core property of sensing, defining the immune system also as a sensory system. The inference with the immune system collects, interprets, and stores information, while creating an identity of self, places it in close relationship to the nervous system, which suggests that these systems may have a profound evolutionary connection.
Connective tissue growth factor is increased in plasma of type 1 diabetic patients with nephropathy.

OBJECTIVE Connective tissue growth factor (CTGF) is strongly upregulated in fibrotic disorders and has been hypothesized to play a role in the development and progression of diabetes complications. The aim of the present study was to investigate the possible association of plasma CTGF levels in type 1 diabetic patients with markers relevant to development of diabetes complications. RESEARCH DESIGN AND METHODS Plasma CTGF levels (full-length and NH2-terminal fragments) were determined in 62 well-characterized patients with type 1 diabetes and in 21 healthy control subjects. Correlations of these plasma CTGF levels with markers of glycemic control, platelet activation, endothelial activation, nephropathy, and retinopathy were investigated. RESULTS -Elevated plasma NH2-terminal fragment of CTGF (CTGF-N) levels were detected in a subpopulation of type 1 diabetic patients and were associated with diabetic nephropathy. Stepwise regression analysis revealed contribution of albuminuria, creatinine clearance, and duration of diabetes as predictors of plasma CTGF-N level. Elevation of plasma CTGF-N levels in patients with retinopathy was probably due to renal comorbidity. CONCLUSIONS Plasma CTGF-N levels are elevated in type 1 diabetic patients with nephropathy and appear to be correlated with proteinuria and creatinine clearance. Further studies will be needed to determine the relevance of plasma CTGF as a clinical marker and/or pathogenic factor in diabetic nephropathy.
A balanced likelihood ratio approach for analyzing rare events in a tandem Jackson network

Balanced likelihood ratio importance sampling methods were originally developed for the analysis of fault-tolerant systems. The paper provides a basis for adapting this approach to analyze the rare event probability that total system size reaches a bound before returning to zero in tandem Jackson networks. An optimal importance sampling distribution for the single server case is derived through direct application of the balanced likelihood ratio approach. The generalization of this approach to larger systems is explored via a two-node tandem Jackson network. A general heuristic approach is outlined along with certain open questions whose answers could lead to a more robust solution. Asymptotic characteristics of the proposed importance sampling approach for the two-node network are discussed. Bounded relative error is only possible under certain conditions. Numerical results illustrate the benefits of the approach.
Data Similarity-Aware Computation Infrastructure for the Cloud

The cloud is emerging for scalable and efficient cloud services. To meet the needs of handling massive data and decreasing data migration, the computation infrastructure requires efficient data placement and proper management for cached data. In this paper, we propose an efficient and cost-effective multilevel caching scheme, called MERCURY, as computation infrastructure of the cloud. The idea behind MERCURY is to explore and exploit data similarity and support efficient data placement. To accurately and efficiently capture the data similarity, we leverage a low-complexity locality-sensitive hashing (LSH). In our design, in addition to the problem of space inefficiency, we identify that a conventional LSH scheme also suffers from the problem of homogeneous data placement. To address these two problems, we design a novel multicore-enabled locality-sensitive hashing (MC-LSH) that accurately captures the differentiated similarity across data. The similarity-aware MERCURY, hence, partitions data into the L1 cache, L2 cache, and main memory based on their distinct localities, which help optimize cache utilization and minimize the pollution in the last-level cache. Besides extensive evaluation through simulations, we also implemented MERCURY in a system. Experimental results based on real-world applications and data sets demonstrate the efficiency and efficacy of our proposed schemes.
Large-scale offloading in the Internet of Things

Large-scale deployments of IoT devices are subject to energy and performance issues. Fortunately, offloading is a promising technique to enhance those aspects. However, several problems still remain open regarding cloud deployment and provisioning. In this paper, we address the problem of provisioning offloading as a service in large-scale IoT deployments. We design and develop an AutoScaler, an essential component for our offloading architecture to handle offloading workload. In addition, we also develop an offloading simulator to generate dynamic offloading workload of multiple devices. With this toolkit, we study the effect of task acceleration in different cloud servers and analyze the capacity of several cloud servers to handle multiple concurrent requests. We conduct multiple experiments in a real testbed to evaluate the system and present our experiences and lessons learned. From the results, we find that the AutoScaler component introduces a very small overhead of ≈150 milliseconds in the total response time of a request, which is a fair price to pay to empower the offloading architectures with multi-tenancy ability and dynamic horizontal scaling for IoT scenarios.
Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: The deoxyhemoglobin dilution model

The relationship between blood oxygenation level‐dependent (BOLD) MRI signals, cerebral blood flow (CBF), and oxygen consumption (CMRO2) in the physiological steady state was investigated. A quantitative model, based on flow‐dependent dilution of metabolically generated deoxyhemoglobin, was validated by measuring BOLD signals and relative CBF simultaneously in the primary visual cortex (V1) of human subjects (N = 12) during graded hypercapnia at different levels of visual stimulation. BOLD and CBF responses to specific conditions were averaged across subjects and plotted as points in the BOLD‐CBF plane, tracing out lines of constant CMRO2. The quantitative deoxyhemoglobin dilution model could be fit to these measured iso‐CMRO2 contours without significant (P ≤ 0.05) residual error and yielded MRI‐based CMRO2 measurements that were in agreement with PET results for equivalent stimuli. BOLD and CBF data acquired during graded visual stimulation were then substituted into the model with constant parameters varied over plausible ranges. Relative changes in CBF and CMRO2 appeared to be coupled in an approximate ratio of ∼2:1 for all realistic parameter settings. Magn Reson Med 42:849–863, 1999. © 1999 Wiley‐Liss, Inc.
The Power to be Moral: Affirming Israelis’ and Palestinians’ Agency Promotes Prosocial Tendencies across Group Boundaries

Based on recent extensions of the needs-based model of reconciliation, we argue that in conflicts characterized by mutual transgressions, such as the Israeli–Palestinian conflict, group members prioritize their agency-related over morality-related needs. Optimistically, however, two studies conducted among Israeli Jews (Study 1) and West Bank Palestinians (Study 2) found that addressing group members’ pressing need for agency by affirming their in-group's strength, competence, and self-determination brought their moral considerations to the fore, leading to stronger prosocial tendencies across group boundaries. These studies suggest that group members need to feel secure and agentic in order to allow their otherwise unprioritized moral needs to come into play. Practically, our insights regarding the positive effects of agency affirmation can be used in the planning of interventions by dialog group facilitators, mediators, or group leaders who wish to encourage members to relinquish some power in order to exhibit greater morality toward their out-group.
Progesterone receptor isoforms PRA and PRB differentially contribute to breast cancer cell migration through interaction with focal adhesion kinase complexes

Conditionally expressed progesterone receptor isoforms PRA and PRB enhance breast cancer cell migration through interaction with focal adhesion kinase (FAK) and differential regulation of FAK phosphorylation and turnover. PRB-stimulated migration is reduced by progestins, which is prevented by PR antagonists or agonist-bound PRA.
School autonomy and 21st century skills in the Israeli educational system: Discrepancies between the declarative and operational levels

Purpose The purpose of this paper is to analyze two parallel processes in the Israeli educational system: first, the idea of school autonomy, exploring its origins and its pedagogical implications and effectiveness; and second, the development of the progressive education evident mainly in the cognitive domain of twenty-first century skills (21st CS), focussing on fostering “deep knowledge” and children’s thinking skills. The manuscript explores the various “waves” of progressive pedagogies that have taken place in the Israeli school system over the years, describing and analyzing the processes that characterize them. Design/methodology/approach Based on a historical perspective, the paper describes chronologically the main developments related to school autonomy and 21st CS policy initiatives, based on a literature review and analysis of policy documents. Findings The review indicates that the Israeli educational system is still caught in the “centralization trap,” inhibiting major changes in the patterns of central control and degrees of freedom granted to school-level educators. As for school pedagogy, it is evident that most of the changes in pedagogy suggested by the numerous policy documents over the years have not resulted in sustainable, system-wide change. In both issues a large disparity is evident between declarations about innovative pedagogies and school autonomy and their actual implementation. Originality/value The review reflects the idiosyncratic articulation of policy plans conducted by the Ministry of Education, producing discrepancies and incongruences at the school level. Some implications of the “declarative culture” created are further discussed.
Quality of life outcomes following transdiagnostic group cognitive-behavioral therapy for anxiety

Individuals with anxiety disorders experience decrements in quality of life (QoL), though it is seldom assessed as an outcome in treatment studies. This study examined QoL as an outcome following transdiagnostic group cognitive-behavioral therapy (TGCBT) for anxiety. Treatment-seeking adults (N = 129; Mage = 33.1; 47.4% female) with social phobia, panic disorder, and/or generalized anxiety disorder rated their QoL by self-report before and after participating in TGCBT. Using general linear modeling, QoL was found to be similar across diagnostic groups both prior to and following treatment, with the exception that individuals diagnosed with social phobia scored significantly lower than the others in social functioning–related QoL following treatment. Otherwise, these groups improved similarly in overall QoL and achievement-, social functioning-, and personal growth-related QoL following 12 weeks of TGCBT. Thus, QoL significantly improves following transdiagnostic group treatment and represents a valuable o.
Model specification and inflation forecast uncertainty

Three classes of inflation models are discussed: Standard Phillips curves, New Keynesian Phillips curves and Incomplete Competition models. Their relative merits in explaining and forecasting inflation are investigated theoretically and empirically. We establish that Standard Phillips-curve forecasts are robust to types of structural breaks that harm the Incomplete Competion model forecasts, but exaggerate forecast uncertainty in periods with no breaks. As the potential biases in after-break forecast errors for the Incomplete Competition model can be remedied by intercept corrections, it offers the best prospect of successful inflation forecasting.
The “Id” Knows More than the “Ego” Admits: Neuropsychoanalytic and Primal Consciousness Perspectives on the Interface Between Affective and Cognitive Neuroscience

It is commonly believed that consciousness is a higher brain function. Here we consider the likelihood, based on abundant neuroevolutionary data that lower brain affective phenomenal experiences provide the “energy” for the developmental construction of higher forms of cognitive consciousness. This view is concordant with many of the theoretical formulations of Sigmund Freud. In this reconceptualization, all of consciousness may be dependent on the original evolution of affective phenomenal experiences that coded survival values. These subcortical energies provided a foundation that could be used for the epigenetic construction of perceptual and other higher forms of consciousness. From this perspective, perceptual experiences were initially affective at the primary-process brainstem level, but capable of being elaborated by secondary learning and memory processes into tertiary-cognitive forms of consciousness. Within this view, although all individual neural activities are unconscious, perhaps along with secondary-process learning and memory mechanisms, the primal sub-neocortical networks of emotions and other primal affects may have served as the sentient scaffolding for the construction of resolved perceptual and higher mental activities within the neocortex. The data supporting this neuro-psycho-evolutionary vision of the emergence of mind is discussed in relation to classical psychoanalytical models.
Strain Modal Testing of a Helicopter Tail Boom

This paper reports current stage of the research whose aim is to apply computer aided testing and modelling technique in order to aid the helicopters structural dynamics properties investigation methodology. The considered approach might be useful for application to helicopters design formulation, prototyping and modification, technical state monitoring and prediction, and assembly quality control. The state of the art of the helicopters structural dynamics investigations is surveyed and some results application directions are discussed. The main results and general conclusions of the standard ground modal testing of the PZL Sokol helicopter is presented. The preliminary results of the displacement and strain modal testing of a prototype helicopter separate tail boom is described. This testing was performed with aim of investigation of the standard modal analysis approach enhancing with strain modal testing and selection of the response only measurement data identification method. Some technical problems encountered during experimental work are addressed. The results of application of the theoretical structural dynamics behaviour modelling with use of the FE technique as a supplement to the experimental techniques are considered. Finally the in-flight modal testing procedure which is about to start is characterised.
Deliberation in the Wilderness: Displacing Symbolic Politics

The environmental benefits of deliberative democracy are increasingly cited, but not well understood. Nor are the processes involved in arriving at deliberated policy preferences in contrast to those under the status quo. Analysis of the Far North Queensland Citizens' Jury (FNQCJ) reveals that the difference reflects as much a move away from a non-deliberative status quo as toward a deliberative ideal. Before deliberation, symbolic arguments proffered by political interests resulted in deep fracturing of an underlying environmental consensus. The deliberative process served to dissipate symbolic claims, liberating citizens to formulate their own judgements based largely on this pre-existing environmental concern. The findings suggest a focus for deliberative democracy in displacing symbolic politics that disenfranchises both nature and humans.
Phosphorylation in the serine/threonine 2609–2647 cluster promotes but is not essential for DNA-dependent protein kinase-mediated nonhomologous end joining in human whole-cell extracts

Previous work suggested that phosphorylation of DNA-PKcs at several serine/threonine (S/T) residues at positions 2609–2647 promotes DNA-PK-dependent end joining. In an attempt to clarify the role of such phosphorylation, end joining was examined in extracts of DNA-PKcs-deficient M059J cells. Joining of ends requiring gap filling prior to ligation was completely dependent on complementation of these extracts with exogenous DNA-PKcs. DNA-PKcs with either S/T → A or S/T → D substitutions at all six sites in the 2609–2647 cluster also supported end joining, but with markedly lower efficiency than wild-type protein. The residual end joining was greater with the S/T → D-substituted than with the S/T → A-substituted protein. A specific inhibitor of the kinase activity of DNA-PK, KU57788, completely blocked end joining promoted by wild type as well as both mutant forms of DNA-PK, while inhibition of ATM kinase did not. The fidelity of end joining was not affected by the mutant DNA-PKcs alleles or the inhibitors. Overall, the results support a role for autophosphorylation of the 2609–2647 cluster in promoting end joining and controlling the accessibility of DNA ends, but suggest that DNA-PK-mediated phosphorylation at other sites, on either DNA-PKcs or other proteins, is at least as important as the 2609–2647 cluster in regulating end joining.
Response properties of place cells in the hippocampus of freely moving pigeons

Place cells are considered to be the basic unit of cognitive maps, which play an important role in spatial cognition for many animals. To investigate the neural mechanisms underlying spatial cognition in birds, we designed four spatial cognitive tasks with or without goals, using pigeons as an animal model. We examined place cells in the hippocampus of 12 pigeons while they performed each task. We measured their spatial response properties and comparatively analyzed place field properties between tasks with and without goals using qualitative and quantitative measures. The results revealed that the reliability of place fields increased when the presence of a goal was clearer, and that place fields were more easily activated in tasks with a goal compared with those with no goal. In addition, we found that place cells in the hippocampus generally possessed multiple place fields, with an average of 2.7 place fields for each place cell. Place fields recorded simultaneously were always located in a similar position, and most exhibited overlapping regions. These results will be helpful for extending our understanding of the mechanisms underlying spatial cognition in different species, and provide a foundation for future studies investigating three-dimensional spatial cognition and navigation mechanisms in pigeons.