Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting cardiac β-adrenergic signaling via GRK2 inhibition for heart failure therapy

Cardiac cells, like those of the other tissues, undergo regulation through membrane-bound proteins known as G protein-coupled receptors (GPCRs). β-adrenergic receptors (βARs) are key GPCRs expressed on cardiomyocytes and their role is crucial in cardiac physiology since they regulate inotropic and chronotropic responses of the sympathetic nervous system (SNS). In compromised conditions such as heart failure (HF), chronic βAR hyperstimulation occurs via SNS activation resulting in receptor dysregulation and down-regulation and consequently there is a marked reduction of myocardial inotropic reserve and continued loss of pump function. Data accumulated over the last two decades indicates that a primary culprit in initiating and maintain βAR dysfunction in the injured and stressed heart is GPCR kinase 2 (GRK2), which was originally known as βARK1 (for βAR kinase). GRK2 is up-regulated in the failing heart due to chronic SNS activity and targeting this kinase has emerged as a novel therapeutic strategy in HF. Indeed, its inhibition or genetic deletion in several disparate animal models of HF including a pre-clinical pig model has shown that GRK2 targeting improves functional and morphological parameters of the failing heart. Moreover, non-βAR properties of GRK2 appear to also contribute to its pathological effects and thus, its inhibition will likely complement existing therapies such as βAR blockade. This review will explore recent research regarding GRK2 inhibition; in particular it will focus on the GRK2 inhibitor peptide known as βARKct, which represents new hope in the treatment against HF progression.
Review of methods used to estimate the abundance of feral cats.

The views and opinions expressed in this publication are those of the authors and do not necessarily reflect those of the Commonwealth Government or the Minister for the Environment and Heritage. Project and client Feral cats are believed to be responsible for the extinction or decline of native marsupials and birds in Australia and are listed as a known or perceived threatening process for 58 native species under the Environmental Protection and Biodiversity Conservation (EPBC) Act 1999. Although many agencies and organisations commit significant resources to managing feral cats, there is little reliable information on the impacts of feral cats, or on the benefits of controlling feral cats: this situation is at least partly due to uncertainly about our ability to accurately and precisely estimate the relative or absolute abundance of feral cats, or the kill rates of control operations. The Department of the Environment and Heritage (DEH) commissioned the Arthur Rylah Institute for Environmental Research to review and evaluate the methods used to estimate the abundance of feral cats. Objectives The objectives of this study were: 1. Review and evaluate the methods used (in Australia and overseas) to determine the abundance of feral cats. 2. Provide a clear description of the methods used, the advantages and disadvantages of each method, and relative costs. 3. Discuss how animal welfare issues influence the use of these methods. 4. Provide a bibliography of the reference material reviewed. 5. Identify and prioritise the gaps in existing knowledge. 6. Provide recommendations as to areas of future research activity that will address those gaps identified in existing knowledge. Methods • The general requirements for estimators of feral cat abundance were identified. • A recent survey of feral cat control in Australia was used to identify the methods used to monitor feral cats in control operations. • The national and international published and unpublished literature was reviewed to identify, 1) the various methods used to estimate feral cat abundance, and 2) new methods that could potentially be used to estimate feral cat abundance. Results • Two methods have been widely used to estimate feral cat abundance in Australia: track counts and spotlight counts. The costs of the two methods are similar, but data suggest that track counts are a more useful estimator of feral cat abundance than spotlight counts. Neither of these methods has any animal welfare issues. • Although both cage and leg-hold traps have …
Major depression in Cyprus amid financial crisis: prevalence and correlates

ABSTRACT Major depression is a common mental health disorder and one of the most pressing public health concerns worldwide. No nationwide survey, which investigates the prevalence of a particular mental disorder, has ever been conducted in Cyprus. The present study aims to fill this gap by attempting to explore the prevalence and correlates of major depression in Cyprus amid financial crisis. A random and representative sample of 600 adult Cypriots participated in the study. The presence of major depression was assessed with the pertinent module of the Structured Clinical Interview (SCI-D), while the Index of Personal Economical Distress (IPED) was employed in order to measure participants’ degree of financial strain. One-month prevalence of major depression was found to be 11.5%. A substantial proportion of the sample reported difficulties in paying household bills (40.9%), clothing (38.9%) and the supermarket (37.1%). Furthermore, female gender, divorced/widowed family status, low educational attainment, unemployment and financial hardship were found to be risk factors for major depression; whereas social networks and institutional trust were found to act in a protective manner. The present study suggests that the impact of financial crisis on mental health is unequally distributed among the general population in Cyprus, rendering certain subgroups particularly vulnerable.
Multi-objective differential evolution - algorithm, convergence analysis, and applications

The revival of multi-objective optimization (MOO) is mostly due to the recent development of evolutionary multi-objective optimization that allows the generation of the whole Pareto optimal front. Several evolutionary algorithms have been developed for this purpose. This paper focuses on the recent development of differential evolution (DE) algorithms for the multi-objective optimization purposes. Although there are a few other papers on the extension of DE concept to the MOO domain, this paper is intended to provide an overall picture of one specific multi-objective differential evolution (MODE) algorithm. In the MODE, the DE concept for the continuous single-objective optimization is extended to MOO for both continuous and discrete problems (C-MODE and D-MODE, respectively). The MODE is modeled in the context of Markov framework and global random search. Convergence properties are developed for both C-MODE and D-MODE. In particular, a set of parameter-setting guidelines for the C-MODE is derived based on the mathematical analysis. An application of the D-MODE to the planning of design, supply, and manufacturing resources in product development is also reported in this paper
Neural Substrates of Action Event Knowledge

Human concepts can be roughly divided into entities (prototypically referred to in language by nouns) and events (prototypically referred to in language by verbs). While much work in cognitive neuroscience has investigated how the brain represents different categories of entities, less attention has been given to the more basic distinction between entities and events. We used functional magnetic resonance imaging to examine brain activity while subjects performed a conceptual matching task that required them to access knowledge of objects and actions, using either pictures or words. Since action events involve movement through space, we hypothesized that accessing knowledge of actions would cause greater activation in brain regions involved in motion or spatial processing. In comparison to objects, accessing knowledge of actions through pictures was accompanied by increased activity bilaterally in the human MT/MST and nearby regions of the lateral temporal cortex. Accessing knowledge of actions through words activated areas just anterior and dorsal to area MT/MST on the left, within the posterior aspect of the middle and superior temporal gyri. We propose that the lateral occipital temporal cortex contains a mosaic of neural regions that processes different kinds of motion, ranging from the perception of objects moving in the world to the conception of movement implied in action verbs. The lateral occipital temporal cortex mediates the perceptual and conceptual features of action events, similar to the way that the ventral occipital temporal cortex processes the perceptual and conceptual features of entities.
Protective effects of Annona muricata Linn. (Annonaceae) leaf aqueous extract on serum lipid profiles and oxidative stress in hepatocytes of streptozotocin-treated diabetic rats.

Extracts from various morphological parts of Annona muricata Linn. (Annonaceae) are widely used medicinally in many parts of the world for the management, control and/or treatment of a plethora of human ailments, including diabetes mellitus (DM). The present study was undertaken to investigate the possible protective effects of A. muricata leaf aqueous extract (AME) in rat experimental paradigms of DM. The animals used were broadly divided into four (A, B, C and D) experimental groups. Group A rats served as 'control' animals and received distilled water in quantities equivalent to the administered volumes of AME and reference drugs' solutions intraperitoneally. Diabetes mellitus was induced in Groups B and C rats by intraperitoneal injections of streptozotocin (STZ, 70 mg kg(-1)). Group C rats were additionally treated with AME (100 mg kg(-1) day(-1), p.o. ) as from day 3 post STZ injection, for four consecutive weeks. Group D rats received AME (100 mg kg(-1) day(-1) p.o. ) only for four weeks. Post-euthanization, hepatic tissues were excised and processed biochemically for antioxidant enzymes and lipid profiles, such as catalase (CAT), reactive oxygen species (ROS), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS), triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL), respectively. Treatment of Groups B and C rats with STZ (70 mg kg(-1) i. p.) resulted in hyperglycaemia, hypoinsulinaemia, and increased TBARS, ROS, TC, TG and LDL levels. STZ treatment also significantly decreased (p<0.05) CAT, GSH, SOD, GSH-Px activities, and HDL levels. AME-treated Groups C and D rats showed significant decrease (p<0.05) in elevated blood glucose, ROS, TBARS, TC, TG and LDL. Furthermore, AME treatment significantly increased (p<0.05) antioxidant enzymes' activities, as well as serum insulin levels. The findings of this laboratory animal study suggest that A. muricata extract has a protective, beneficial effect on hepatic tissues subjected to STZ-induced oxidative stress, possibly by decreasing lipid peroxidation and indirectly enhancing production of insulin and endogenous antioxidants.
Local Property Restoring

In this paper we present the new notion of local restoring of properties. A restorer gets implicit access, in the form of oracle queries, to a function (which may correspond to an object such as a graph, a code or a matrix) that is close to having a property, such as function monotonicity or graph bipartiteness. The restorer then, using a small number of queries to the function, can locally compute the value of a “corrected” function in any desired point. The corrected function is required to be both close to the original function and strictly have the property. In the case of error correcting codes, this corresponds to local self-correcting. Here we extend the definition and study for general functions and properties. We define the new notion and go on to give restorers for properties in the dense graph model: Bipartiteness and ρ-Clique, and for function monotonicity. We also show some general relations between property restoring and other notions such as property testing and tolerant property testing.
In your eyes only: deficits in executive functioning after frontal TMS reflect in eye movements

This study investigated the roles of the right and left dorsolateral prefrontal (rDLPFC, lDLPFC) and the medial frontal cortex (MFC) in executive functioning using a theta burst transcranial magnetic stimulation (TMS) approach. Healthy subjects solved two visual search tasks: a number search task with low cognitive demands, and a number and letter search task with high cognitive demands. To observe how subjects solved the tasks, we assessed their behavior with and without TMS using eye movements when subjects were confronted with specific executive demands. To observe executive functions, we were particularly interested in TMS-induced changes in visual exploration strategies found to be associated with good or bad performance in a control condition without TMS stimulation. TMS left processing time unchanged in both tasks. Inhibition of the rDLPFC resulted in a decrease in anticipatory fixations in the number search task, i.e., a decrease in a good strategy in this low demand task. This was paired with a decrease in stimulus fixations. Together, these results point to a role of the rDLPFC in planning and response selection. Inhibition of the lDLPFC and the MFC resulted in an increase in anticipatory fixations in the number and letter search task, i.e., an increase in the application of a good strategy in this task. We interpret these results as a compensatory strategy to account for TMS-induced deficits in attentional switching when faced with high switching demands. After inhibition of the lDLPFC, an increase in regressive fixations was found in the number and letter search task. In the context of high working memory demands, this strategy appears to support TMS-induced working memory deficits. Combining an experimental TMS approach with the recording of eye movements proved sensitive to discrete decrements of executive functions and allows pinpointing the functional organization of the frontal lobes.
Phase II study of panobinostat in combination with bevacizumab for recurrent glioblastoma and anaplastic glioma.

BACKGROUND Panobinostat is a histone deacetylase inhibitor with antineoplastic and antiangiogenic effects in glioma that may work synergistically with bevacizumab. We conducted a multicenter phase II trial of panobinostat combined with bevacizumab in patients with recurrent high-grade glioma (HGG). METHODS Patients with recurrent HGG were treated with oral panobinostat 30 mg 3 times per week, every other week, in combination with bevacizumab 10 mg/kg every other week. The primary endpoint was a 6-month progression-fee survival (PFS6) rate for participants with recurrent glioblastoma (GBM). Patients with recurrent anaplastic glioma (AG) were evaluated as an exploratory arm of the study. RESULTS At interim analysis, the GBM arm did not meet criteria for continued accrual, and the GBM arm was closed. A total of 24 patients with GBM were accrued prior to closure. The PFS6 rate was 30.4% (95%, CI 12.4%-50.7%), median PFS was 5 months (range, 3-9 months), and median overall survival (OS) was 9 months (range, 6-19 months). Accrual in the AG arm continued to completion, and a total of 15 patients were enrolled. The PFS6 rate was 46.7% (range, 21%-73%), median PFS was 7 months (range, 2-10 months), and median OS was 17 months (range, 5 months-27 months). CONCLUSIONS This phase II study of panobinostat and bevacizumab in participants with recurrent GBM did not meet criteria for continued accrual, and the GBM cohort of the study was closed. Although it was reasonably well tolerated, the addition of panobinostat to bevacizumab did not significantly improve PFS6 compared with historical controls of bevacizumab monotherapy in either cohort.
Examining the Relationship Among Self-Reported Assertiveness, Perceived Discrimination, and College Environment in a National Sample of Black Women Law Students

The purpose of our study was to examine college environment, defined as whether law students entered law school from a historically Black college or university or a traditionally White institution, as a moderator of the relationship between gender discrimination and assertiveness. Using a national sample of 402 incoming Black women law students and multiple-group confirmatory factor analysis (CFA) with covariates, the authors also tested whether college environment moderated the relationship between racial discrimination and assertiveness. CFA models with covariates were used to further investigate whether racial discrimination and gender discrimination interact to influence assertiveness. Results indicated that college environment did not moderate the relationship between gender discrimination and assertiveness. College environment also did not moderate the relationship between racial discrimination and assertiveness. Additional results revealed a significant interaction between racial and gender discrimination, whereby racial discrimination was positively related to assertiveness among students who experienced gender discrimination. Findings suggest that irrespective of college environment, racism and sexism intersect to enhance assertiveness and may increase students’ academic success. However, law school administrators should ultimately seek to reduce incidents of racism and sexism because students’ assertive responses could make them vulnerable to mental health risks and to further acts of discrimination.
Study of highly-excited string states at the Large Hadron Collider

In TeV-scale gravity scenarios with large extra dimensions, black holes may be produced at future colliders. Good arguments have been made for why general relativistic black holes may be just out of reach of the Large Hadron Collider (LHC). However, in weakly coupled string theory, highly excited string states--string balls--could be produced at the LHC with high rates and decay thermally, not unlike general relativistic black holes. In this paper, we simulate and study string ball production and decay at the LHC. We specifically emphasize the experimentally detectable similarities and differences between string balls and general relativistic black holes at a TeV scale.
Key considerations for measuring allelic expression on a genomic scale using high‐throughput sequencing

Differences in gene expression are thought to be an important source of phenotypic diversity, so dissecting the genetic components of natural variation in gene expression is important for understanding the evolutionary mechanisms that lead to adaptation. Gene expression is a complex trait that, in diploid organisms, results from transcription of both maternal and paternal alleles. Directly measuring allelic expression rather than total gene expression offers greater insight into regulatory variation. The recent emergence of high‐throughput sequencing offers an unprecedented opportunity to study allelic transcription at a genomic scale for virtually any species. By sequencing transcript pools derived from heterozygous individuals, estimates of allelic expression can be directly obtained. The statistical power of this approach is influenced by the number of transcripts sequenced and the ability to unambiguously assign individual sequence fragments to specific alleles on the basis of transcribed nucleotide polymorphisms. Here, using mathematical modelling and computer simulations, we determine the minimum sequencing depth required to accurately measure relative allelic expression and detect allelic imbalance via high‐throughput sequencing under a variety of conditions. We conclude that, within a species, a minimum of 500–1000 sequencing reads per gene are needed to test for allelic imbalance, and consequently, at least five to 10 millions reads are required for studying a genome expressing 10 000 genes. Finally, using 454 sequencing, we illustrate an application of allelic expression by testing for cis‐regulatory divergence between closely related Drosophila species.
A recursive resolution-enhancement using multiframe SRR based on meridian filter with Meridian-Tikhonov regularization

The real noise model corrupting the observed images is unknown and usually random statistical model. Consequently, classical SRR (Super Resolution Reconstruction) algorithms using median (L1) and mean (L2) filtering structures may degrade the reconstructed image sequence rather than enhance it. The mathematical analysis [1] demonstrates that the meridian filtering structure exhibits more robust characteristic than that of median (L1) and mean (L2) filtering structures. For applying on images that are corrupted by any noise models at several noise power, a recursive resolution-enhancement using a multiframe SRR is proposed. The stochastic framework (using maximum a posteriori or maximum likelihood estimator) has been applied to the proposed SRR algorithm. The Meridian filter is used for removing outliers in the data and for measuring the difference between the projected estimating of the HR image and each LR image. Due to the ill-pose condition, Tikhonov and Meridian-Tikhonov regularization are compulsively incorporated to remove artifacts from the final answer and improve the rate of convergence. In experimental section, numerical experiments are carried out on synthetic data by using the proposed SRR algorithm. Both of the peak signal-to-noise ratio (PSNR) and virtual images are used to measure the quality of an image. The performance of proposed methods compared with other SRR algorithms based on L1 and L2 norm is demonstrated on several noise models (such as Noiseless, AWGN, Poisson Noise, Salt&Pepper Noise and Speckle Noise) at different noise power.
Cognition and Event‐Related Potentials

Department of Neuroscience Albert Einstein College of Medicine Bronx, New York 10461 Department of Psychiatry Veterans Administration Hospital Palo Alto, California 94305 ‘Institute for Perception Soesterberg, the Netherlands dDepartment of Psychology University of North Carolina Greensboro, North Carolina 2741 2 Department of Neurosciences University of California San Diego, California 92093 /Department of Psychology University of Helsinki 00170 Helsinki 17. Finland gDepartment of Neurology University of California Irvine, California 92668 Hospital de la Salpetriere F-75634 Paris, Cedex 13, France ‘ Nebraska Psychiatric Institute Omaha, Nebraska 68106 RISTO NAATANEN! JOHN POLICH: BERNARD
History of the introduction of spectral analysis of blood pressure variability recorded continually and non-invasively from finger arteries

The review shows the significance of blood pressure regulation studies conducted during several decades at the Department of Physiology, Faculty of Medicine, Masaryk University, Brno. Continuous non-invasive blood pressure measurement was first introduced and patented here and, with the obtained data, the first spectral analysis of blood pressure was performed. This method was used in many different physiological studies on the relationship of blood pressure regulation to circulatory parameters, breathing, and baroreflex sensitivity. The article deals with studies on risk stratification of sudden cardiac death according to decreased baroreflex sensitivity, 24-hour heart rate variability, the amount of extrasystoles and late potentials. Importance of the new method of determination of one summation risk index is described here. A summary of the new conception of the relationship between low baroreflex sensitivity and hypertension is presented. Here, not only pathological changes of the vessel wall but also increased sympathetic activity and genetic predisposition play a role. Importance of studies conducted in young adults is highlighted, as inherited BRS decrease contributes to earlier blood pressure increase in the young. This research is highly topical, since prevention of hypertension in childhood is possible. Recent studies are dedicated to blood pressure regulation in young diabetics.