Miracle-dz/UniFAR-FTUs huggingface dataset:
Age-related regulation and region-specific distribution of ion channel subunits promoting atrial fibrillation in human left and right atria.

AIMS Age-induced changes and electrical remodelling are important components of the atrial fibrillation (AF) substrate. To study regional distribution and age-dependent changes in gene expression that may promote AF in human atria. METHODS AND RESULTS Human left atrial (LA) and right atrial (RA) tissue samples were obtained from donor hearts unsuitable for transplantation and from patients undergoing mitral valve repair. Atrial fibrillation was mimicked in vitro by tachypacing of human atrial tissue slices. Ionic currents were studied by the whole-cell patch-clamp technique; gene expression was analysed by real-time qPCR and immunoblotting. Both healthy RA and RA from older patients showed greater CACNA1c mRNA and CaV1.2 protein expression than LA. No age-dependent changes of Kir2.1 expression in both atria were seen. Remodelling occurred in a qualitatively similar manner in RA and LA. IK1 and Kir2.1 protein expression increased with AF. MiR-1, miR-26a, and miR-26b were down-regulated with AF in both atria. ICa,L was decreased. CACNA1c and CACNA2b expression decreased and miR-328 increased in RA and LA during AF. Ex vivo tachypacing of human atrial slices replicated these findings. There were age-dependent increases in miR-1 and miR-328, while miR-26a decreased with age in atrial tissues from healthy human donor hearts. CONCLUSION Features of electrical remodelling in man occur in a qualitatively similar manner in both human atria. Age-related miR-328 dysregulation and reduced ICa,L may contribute to increased AF susceptibility with age.
Design of a speed meter interferometer proof-of-principle experiment

The second generation of large scale interferometric gravitational wave (GW) detectors will be limited by quantum noise over a wide frequency range in their detection band. Further sensitivity improvements for future upgrades or new detectors beyond the second generation motivate the development of measurement schemes to mitigate the impact of quantum noise in these instruments. Two strands of development are being pursued to reach this goal, focusing both on modifications of the well-established Michelson detector configuration and development of different detector topologies. In this paper, we present the design of the worldʼs first Sagnac speed meter (SSM) interferometer, which is currently being constructed at the University of Glasgow. With this proof-of-principle experiment we aim to demonstrate the theoretically predicted lower quantum noise in a Sagnac interferometer compared to an equivalent Michelson interferometer, to qualify SSM for further research towards an implementation in a future generation large scale GW detector, such as the planned Einstein telescope observatory.
In Vitro Deamination of Cytosine to Uracil in Single-stranded DNA by Apolipoprotein B Editing Complex Catalytic Subunit 1 (APOBEC1)*

Apolipoprotein B-editing complex catalytic subunit 1 (APOBEC1) is the catalytic component of an RNA-editing complex that deaminates C6666 → U in apolipoprotein B RNA in gastrointestinal tissue, thereby generating a premature stop codon. Whereas RNA is the physiological substrate of APOBEC1, recent experiments have strongly indicated that, when expressed in bacteria, APOBEC1 and some of its homologues can deaminate cytosine in DNA. Indeed, genetic evidence demonstrates that the physiological function of activation-induced deaminase, a B lymphocyte-specific APOBEC1 homologue, is to perform targeted deamination of cytosine within the immunoglobulin locus, thereby triggering antibody gene diversification. However, biochemical evidence of in vitro DNA deamination by members of the APOBEC family is still needed. Here, we show that deamination of cytosine to uracil in DNA can be achieved in vitro using partially purified APOBEC1 from extracts of transformed Escherichia coli. Thus, APOBEC1 can deaminate cytosine in both RNA and DNA. Strikingly, its activity on DNA is specific for single-stranded DNA and exhibits dependence on local sequence context.
Modern Concepts in Regenerative Therapy for Ischemic Stroke: From Stem Cells for Promoting Angiogenesis to 3D-Bioprinted Scaffolds Customized via Carotid Shear Stress Analysis

Ischemic stroke is associated with a tremendous economic and societal burden, and only a few therapies are currently available for the treatment of this devastating disease. The main therapeutic approaches used nowadays for the treatment of ischemic brain injury aim to achieve reperfusion, neuroprotection and neurorecovery. Therapeutic angiogenesis also seems to represent a promising tool to improve the prognosis of cerebral ischemia. This review aims to present the modern concepts and the current status of regenerative therapy for ischemic stroke and discuss the main results of major clinical trials addressing the effectiveness of stem cell therapy for achieving neuroregeneration in ischemic stroke. At the same time, as a glimpse into the future, this article describes modern concepts for stroke prevention, such as the implantation of bioprinted scaffolds seeded with stem cells, whose 3D geometry is customized according to carotid shear stress.
A high gain and low-offset current-mode instrumentation amplifier using differential difference current conveyors

In this work, a current-mode high CMRR and low offset instrumentation amplifier is proposed. In the structure, only differential difference current conveyors (DDCC) are employed. The offset of the instrumentation amplifier is suppressed using an integrator feedback stage. The CMRR of the system is simulated using mismatch models for the DDCC elements employed. The CMRR of the instrumentation amplifier is independent of resistor mismatches and high CMRR is achieved if good matching of the differential transistors of each current conveyor is provided. The proposed instrumentation amplifier is designed using 0. 35μm technology and simulated using HSPICE. The designed instrumentation amplifier provides high CMRR with low offset and it is especially suitable for AC coupled measurements. The simplicity of the design structure is the main advantage of the provided design where only DDCC elements are required for high CMRR and high output swing.
The effects of propofol on brain electrical activity, neurologic outcome, and neuronal damage following incomplete ischemia in rats.

This study compares the effects of propofol and fentanyl/N2O on spontaneous brain electrical activity, neurologic outcome, and neuronal damage due to incomplete cerebral ischemia in rats. Thirty Sprague-Dawley rats were assigned to one of three groups: group 1 (n = 10) received 70% N2O in O2 plus fentanyl (bolus 10 micrograms.kg-1, infusion 25 micrograms.kg-1.h-1); group 2 (n = 10) received 70% N2 in O2 and propofol (infusion 0.8-1.2 mg.kg-1.min-1) adjusted to maintain EEG burst suppression during ischemia; group 3 (n = 10) was anesthetized with propofol and received 6 ml.kg-1 10% glucose intraperitoneally 15 min before the start of ischemia. Incomplete cerebral ischemia was produced by right common carotid artery occlusion combined with hemorrhagic hypotension (35 mmHg) for 30 min. Arterial blood gases, pH, and rectal temperature were kept constant in all groups. Plasma glucose was lower during ischemia in propofol-anesthetized rats compared to that in fentanyl/N2O- (P = 0.009) and glucose-loaded propofol-treated rats (P = 0.008). Neurologic outcome and brain tissue injury were significantly better in propofol-anesthetized compared to fentanyl/N2O-anesthetized rats (P less than 0.05). Elevated plasma glucose in propofol-treated rats resulted in similar neurologic outcome and histopathologic injury as seen in propofol-anesthetized rats given no glucose. Recovery of EEG theta-alpha activity after ischemia was inversely correlated to neurologic deficit (fentanyl/N2O: r = -0.71; propofol: r = -0.83; P less than 0.01). These results show that propofol improves neurologic outcome and decreases neuronal damage from incomplete cerebral ischemia when compared to fentanyl/N2O. This effect is not dependent on plasma glucose. (ABSTRACT TRUNCATED AT 250 WORDS)
Pathogenesis of simian varicella virus

Simian varicella virus (SVV) is closely related to varicella‐zoster virus (VZV) and induces a natural varicella‐like disease in nonhuman primates. Therefore, simian varicella is a useful model to investigate varicella pathogenesis and to evaluate antiviral therapies. In this report, we review recent studies on SVV pathogenesis and latency. Experimental infection of African green monkeys is followed by a 7–10 day incubation period during which a viremia disseminates the virus throughout the body. Clinical disease is characterized by fever and vesicular skin rash. Pneumonia and hepatitis may occur during more severe infections. Examination of acutely infected tissues reveals histopathology including necrosis and hemorrhage in the skin, lung, liver, and spleen. In contrast, the neural ganglia exhibit minimal histopathology. SVV DNA, immediate early, early, and late gene transcripts, and viral antigens are detected in the tissues of acutely infected monkeys. Host immune responses are induced which resolve the acute infection within 21 days. During or after acute infection, SVV establishes latent infection in the ganglia of surviving monkeys. The virus may reactivate later in life to cause secondary disease and viral transmission to susceptible monkeys. J. Med. Virol. 70:S4–S8, 2003. © 2003 Wiley‐Liss, Inc.
Opposition to Nonprescription Naloxone Access: Measurement and Psychosocial Predictors

Abstract Background: Access of naloxone has been increased in recent years, yet opposition to unrestricted availability persists. Objectives: To validate a measure of opposition to the policy of nonprescription naloxone and foster a better understanding of the characteristics of individuals who oppose such a policy. Methods: Respondents from a crowdsource platform (N = 621) responded to an instrument developed to assess opposition to nonprescription naloxone. Construct validity was assessed by examining the relationship of the opposition scale with measures of social distance, belief in a just world, right wing authoritarianism, social dominance orientation (SDO), perceptions of the degree of threat to the nation presented by opioid users, past exposure to opioid misuse, and conservative political ideology. Results: A 9-item measure of opposition emerged (α=.96). Opposition to nonprescription naloxone was generally associated with construct validation variables as expected. In a regression analysis that adjusted for demographic characteristics, opposition was most strongly related to authoritarianism, the perception that opioid users present a threat to our nation, the belief that we live in a just world, social dominance orientation, greater perceived social distance between self and opioid users, and past experiences with users. Opposition scores differentiated those who supported versus opposed specific policies regarding naloxone access and were particularly high among Republicans. Most respondents did not oppose policies on nonprescription naloxone access. Conclusions/Importance: The instrument developed provides a reliable and valid tool that enables future investigations into understanding and overcoming the psychological, social, and political foundations of opposition to expanded naloxone access.
Biomedical Information Extraction Techniques

Information Extraction includes extraction of structured information from semi-structured or unstructured sources. This paper presents two information extraction frameworks, first framework deal with text retrieval, which takes out relational concepts from huge text. In this system deep parser and term recognizer are used to obtain predicate argument structures and ontological identifiers respectively. Query language used in this framework does not yield links (syntactic dependencies) between couple of words in a sentence, and it only gives an easy query generation component so usefulness of the system is restricted. Second framework overcomes the limitation of text retrieval framework. Second framework deal with incremental information extraction in which in between output of each text processing module is stored so there is no need to reapply extraction to the entire text corpus in case of new extraction object appeared or a module is upgraded. Performing such kind of incremental extraction can result in enormous reduction of processing time.
Efficient Extraction of Carotenoids from Sargassum muticum Using Aqueous Solutions of Tween 20

The replacement of synthetic compounds by natural products witnesses an increasing demand from the pharmaceutical, cosmetic, food and nutraceutical industries. Included in the set of natural raw materials that are poorly explored are the macroalgae. Despite the detailed characterization and identification of most relevant biomolecules that are present in the main macroalgae species, there remains a lack of efficient and economically viable processes available to meet the needs of the markets. In this work, an efficient and single-step process, based on aqueous solutions of Tween 20, to recover carotenoids from Sargassum muticum, an invasive brown macroalgae species present in the Portuguese coast, is proposed and optimized allowing an extraction yield of 2.78 ± 0.4 mgcarotenoids.gdried mass−1, which is shown to increase the extraction efficiency by 38% when compared with traditional methods.
Cochlear Implants in Prelingually Deaf Children

All private and public residential and day schools for the deaf in the U.S. that have 100 or more students were surveyed to see how many prelingually deafened students they had with cochlear implants and how many of these students were still using the device. Responses came from 70% (45 of 64) of those schools surveyed. Of the 151 implanted children identified, 71 (47%) were no longer using the cochlear implant. Of the remaining 80 children (53%) still wearing the device, we could not specifically determine by survey the percentage who derived significant benefit from the device and the percentage who did not. However, numerous comments by those returning the questionnaires indicated despondency over the results of the implant.
Human Mutation

Funding information NIH, Grant/Award Numbers: U41 HG007346, R13 HG006650 Abstract In silico approaches are routinely adopted to predict the effects of genetic variants and their relation to diseases. The critical assessment of genome interpretation (CAGI) has established a common framework for the assessment of available predictors of variant effects on specific problems and our group has been an active participant of CAGI since its first edition. In this paper, we summarize our experience and lessons learned from the last edition of the experiment (CAGI‐5). In particular, we analyze prediction performances of our tools on five CAGI‐5 selected challenges grouped into three different categories: prediction of variant effects on protein stability, prediction of variant pathogenicity, and prediction of complex functional effects. For each challenge, we analyze in detail the performance of our tools, highlighting their potentialities and drawbacks. The aim is to better define the application boundaries of each tool.
Identification of Developmentally Specific Enhancers for Tsix in the Regulation of X Chromosome Inactivation

ABSTRACT X chromosome inactivation silences one of two X chromosomes in the mammalian female cell and is controlled by a binary switch that involves interactions between Xist and Tsix, a sense-antisense pair of noncoding genes. On the future active X chromosome, Tsix expression suppresses Xist upregulation, while on the future inactive X chromosome, Tsix repression is required for Xist-mediated chromosome silencing. Thus, understanding the binary switch mechanism depends on ascertaining how Tsix expression is regulated. Here we have taken an unbiased approach toward identifying Tsix regulatory elements within the X chromosome inactivation center. First, we defined the major Tsix promoter and found that it cannot fully recapitulate the developmental dynamics of Tsix expression, indicating a requirement for additional regulatory elements. We then delineated two enhancers, one classical enhancer mapping upstream of Tsix and a bipartite enhancer that flanks the major Tsix promoter. These experiments revealed the intergenic transcription element Xite as an enhancer of Tsix and the repeat element DXPas34 as a component of the bipartite enhancer. Each enhancer contains DNase I-hypersensitive sites and appears to confer developmental specificity to Tsix expression. Characterization of these enhancers will facilitate the identification of trans-acting regulatory factors for X chromosome counting and choice.
Echinacea extracts modulate the production of multiple transcription factors in uninfected cells and rhinovirus‐infected cells

Extracts of Echinacea purpurea are widely used for the prevention and treatment of common colds, coughs, bronchitis and other upper respiratory infections, many of which are caused by rhinoviruses (RVs). Recent reports have indicated that rhinoviruses can stimulate the release of various pro‐inflammatory cytokines and chemokines from cultured nasal and bronchial human epithelial cells, and several transcription factors (TFs) have been implicated in this process.
Characterization of Phospholipids in Membrane Vesicles Derived from Pseudomonas aeruginosa

Many Gram-negative bacteria release membrane vesicles (MVs), but their phospholipid properties are poorly understood. Phosphatidylglycerol was present at high levels in MVs derived from Pseudomonas aeruginosa, but not in the cellular outer membrane. The ratio of stearic acid in MVs was high compared to that in the cellular outer membrane. These findings suggest that membrane rigidity is associated with MV biogenesis.
Mechanism of penicillin action: penicillin and substrate bind covalently to the same active site serine in two bacterial D-alanine carboxypeptidases.

It has been hypothesized that penicillin acts as a structural analog of the acyl-D-alanyl-D-alanine terminus of nascent bacterial cell wall and that it consequently binds to and acylates the active site of the enzyme(s) that crosslinks the cell wall to form an inactive penicilloyl enzyme [Tipper, D.J. & Strominger, J.L. (1965) Proc. Natl. Acad. Sci. USA 64, 1133-1138]. This study directly proves that penicillin acylates the active site of two penicillin-sensitive enzymes, D-alanine carboxypeptidases from Bacillus stearothermophilus and Bacillus subtilis. Active site peptides were generated by chemical or enzymatic cleavage of these carboxypeptidases after covalently labeling with [14C]penicillin G or after trapping an acyl-enzyme intermediate derived from the depsipeptide substrate. [14C]diacetyl-L-lysyl-D-alanyl-D-lactate. The amino acid sequences of the penicillin- and substrate-labeled peptides were identical. Both penicillin and substrate were covalently bound via an ester linkage to the same active site residue, a serine at position 36 of the B. stearothermophilus carboxypeptidase and the corresponding serine in the B. subtilis carboxypeptidase. The two D-alanine carboxypeptidases showed significant homology around the active site. Moreover, homology between these two enzymes and four beta-lactamases of known sequence suggests that these two groups of enzymes are evolutionally related.
Towards Performance Prediction for Stream Processing Applications

Stream processing systems have become the major engine whenever data processing with low latency or real-time capability is required. Meeting the performance demands of these systems in terms of latency, throughput and resource utilization is hence crucial to ensure stable operation and correct functioning. Current performance modeling approaches target this issue by predicting performance characteristics on the architecture level, e.g by measuring existing deployments as a whole and estimating the impact of related changes. However, these approaches neglect the actual application logic of the streaming system and are hence neither able to identify bottlenecks in the processing behavior nor to predict performance during development. In this paper we propose a more comprehensive performance modeling approach that considers both, the deployment architecture and the actual implementation logic of stream processing systems on the example of the SAP HANA Streaming Analytics Server. For this means, we derive a performance model based on the actual source code of the stream processing solution and compare the simulation of our model with the actual measurements. Our results show that the approach provides much better findings allowing to identify bottlenecks in the application logic and to predict the point in time when an over-queuing situation occurs to provide valuable insights for both developers and performance analysts.
Enhancing Scientific Reasoning and Explanation Skills with Conversational Agents

This paper investigates the use of conversational agents to scaffold on-line collaborative learning discussions through an approach called Academically Productive Talk (APT). In contrast to past work on dynamic support for collaborative learning, which has involved using agents to elevate the conceptual depth of collaborative discussion by leading students in groups through directed lines of reasoning, this APT based approach lets students follow their own lines of reasoning and promotes productive practices such as deep explaination and refinement of ideas. The study provides evidence that one form of the support, namely the Revoicing support, lead to significantly more learning within an online collaborative learning activity and resulted in higher quality explanations for predictions within that session.
Determinants of Abnormal Cervical Cancer Screening Follow-Up And Invasive Cervical Cancer Among Uninsured and Underinsured Women in New Jersey

Abstract:Objectives. To identify determinants of follow-up care and diagnosis of invasive cervical cancer among uninsured/underinsured women screened for cervical cancer. Methods. We examined the associations between health care facility, area-level, and individual-level factors on the outcomes of interest in retrospective cohort of women from the New Jersey Cancer Education and Early Detection Program (2000–2015). Results. Women screened at department of health clinics (aOR:3.11, 95% CI: 2.30–4.20) and health care system-affiliated clinics (aOR:1.71, 95% CI: 1.11–2.64) had higher odds of lacking follow-up care compared with women in private physician practices. Similarly, women residing in areas with the highest unemployment had higher odds of lacking follow-up (aOR:1.48, 95% CI: 1.07–2.06). Delays in follow-up care were higher for women born in Central/South American countries compared with U.S.-born women (aOR: 1.46, 95% CI: 1.12–1.92). Conclusions. Improved outreach efforts and multilevel strategies are needed to address the persistent barriers to appropriate follow-up care for underserved women.