Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigation of the Effects of the Short QT Syndrome D172N Kir2.1 Mutation on Ventricular Action Potential Profile Using Dynamic Clamp

The congenital short QT syndrome (SQTS) is a cardiac condition that leads to abbreviated ventricular repolarization and an increased susceptibility to arrhythmia and sudden death. The SQT3 form of the syndrome is due to mutations to the KCNJ2 gene that encodes Kir2.1, a critical component of channels underlying cardiac inwardly rectifying K+ current, IK1. The first reported SQT3 KCNJ2 mutation gives rise to the D172N Kir2.1 mutation, the consequences of which have been studied on recombinant channels in vitro and in ventricular cell and tissue simulations. The aim of this study was to establish the effects of the D172N mutation on ventricular repolarization through real-time replacement of IK1 using the dynamic clamp technique. Whole-cell patch-clamp recordings were made from adult guinea-pig left ventricular myocytes at physiological temperature. Action potentials (APs) were elicited at 1 Hz. Intrinsic IK1 was inhibited with a low concentration (50 µM) of Ba2+ ions, which led to AP prolongation and triangulation, accompanied by a ∼6 mV depolarization of resting membrane potential. Application of synthetic IK1 through dynamic clamp restored AP duration, shape and resting potential. Replacement of wild-type (WT) IK1 with heterozygotic (WT-D172N) or homozygotic (D172N) mutant formulations under dynamic clamp significantly abbreviated AP duration (APD90) and accelerated maximal AP repolarization velocity, with no significant hyperpolarization of resting potential. Across stimulation frequencies from 0.5 to 3 Hz, the relationship between APD90 and cycle length was downward shifted, reflecting AP abbreviation at all stimulation frequencies tested. In further AP measurements at 1 Hz from hiPSC cardiomyocytes, the D172N mutation produced similar effects on APD and repolarization velocity; however, resting potential was moderately hyperpolarized by application of mutant IK1 to these cells. Overall, the results of this study support the major changes in ventricular cell AP repolarization with the D172N predicted from prior AP modelling and highlight the potential utility of using adult ventricular cardiomyocytes for dynamic clamp exploration of functional consequences of Kir2.1 mutations.
Colonic Leucine-Rich Repeat Kinase 2 Expression Is Increased and Associated With Disease Severity in Patients With Parkinson’s Disease

Background Mutations in leucine-rich repeat kinase 2 (LRRK2) comprise a common genetic risk factor for Parkinson’s disease (PD) and inflammatory bowel disease (IBD). We investigated the expression of LRRK2 in colonic biopsies obtained from a cohort of PD patients and healthy controls. Methods A cohort of 51 PD patients and 40 age- and gender-matched controls who have colonic biopsied samples were recruited. Among these participants, 26 individuals (12 PD patients and 14 controls) had a series of colon biopsies. For the patients with PD, the first biopsies were taken before the PD diagnosis. The colonic expression of LRRK2 was assayed by immunohistochemical staining. Results The fraction of LRRK2-positive cells among the total cell count in biopsied colonic tissues was significantly higher in PD patients than controls (0.81% ± 0.53% vs. 0.45% ± 0.39%; P = 0.02). Colonic LRRK2 immunoreactivity was higher in those with LRRK2 genetic variants compared to those with wild type LRRK2 (2.44% ± 1.15% vs. 0.21 ± 0.13%, P < 0.01). Age had no effect on LRRK2 expression (P = 0.96). LRRK2 expression correlated with disease severity in regards to motor symptoms measured by the UPDRS part III scores (r = 6335, P < 0.001) and cognitive dysfunction measured by the mini-mental status examination scores (r = -0.5774, P < 0.001). PD patients in the prodromal phase had a steeper increase in colonic LRRK2 expression compared to controls during the serial colon biopsy assessment (P < 0.01). Conclusion Colonic LRRK2 expression was increased in PD patients compared to controls, and the expression level correlated with disease severity.
People Who Die by Suicide Without Receiving Mental Health Services: A Systematic Review

Introduction The majority of people who die by suicide have never seen a mental health professional or been diagnosed with a mental illness. To date, this majority group has largely been ignored, with most existing research focusing on predictors of suicide such as past suicide attempts. Identifying the characteristics of people who die by suicide without receiving services, often with a fatal first attempt, is crucial to reduce suicide rates through guiding improvements to service pathways and “just in time” interventions. Methods In this systematic review, PsycInfo, PubMed, CINAHL, and Web of Science were searched for peer-reviewed articles published from 1980 to 1st March 2021. Included studies examined predictors of non-receipt of formal mental health services among people who died by suicide. Data were extracted from published reports and the quality of included studies was assessed using a modified version of the Joanna Briggs Institute Checklist for Analytical Cross Sectional Studies. This review was registered with PROSPERO, CRD 42021226543. Results Sixty-seven studies met inclusion criteria, with sample sizes ranging from 39 to 193,152 individuals. Male sex, younger or older age, and rural location were consistently associated with non-receipt of mental health services. People not receiving mental health services were also less likely to have a psychiatric diagnosis, past suicidal behavior or contact with general health services, and more likely to use violent means of suicide. There was some evidence that minority ethnicity and psychosocial stressors were associated with service non-receipt. Conclusion People who die by suicide without receiving mental health services are likely to have diverse profiles, indicating the need for multifaceted approaches to effectively support people at risk of suicide. Identifying the needs and preferences of individuals who are at risk of suicide is crucial in developing new support pathways and services, and improving the quality of existing services. Systematic Review Registration http://www.crd. york.ac. uk/PROSPERO/display_record. asp? ID=CRD42021226543.
Topology optimization of irregular flow domain by parametric level set method in unstructured mesh

In this study, we present a novel method for the topology optimization of the irregular flow domain using a parametric level set method (PLSM). Some improvement was applied on the CS-RBFs (radial basis functions with compact support)-based PLSM to make it suitable for nonuniform mesh, expanding the range field of engineering application of the PLSM. The optimization problem is solved by a gradient-based algorithm with Stokes equations as state constraints, and the objective is set to minimize the power dissipation subject to the volume constraint of flow channels. A PLSM is introduced to avoid the direct solving of the Hamilton–Jacobi partial differential equation, which can have the potential to break through the restriction of relying on structured meshes because no finite difference scheme is required. Then, a self-adaption support radius approach is presented to allow the parametric level set to be evolved on the nonuniformed mesh, which can expand the application of the PLSM to more complicated engineering problems with irregular geometric shapes. A volume integration scheme is applied during the design sensitivity analysis to calculate the shape derivatives, allowing the nucleation of new holes. Numerical examples in two and three dimensions are provided to demonstrate the effectiveness of the proposed method.
Understanding the Value of Digital Archival Collections to Faculty at Maynooth University Library

Abstract This article first defines what constitutes a “Special Collection” and what constitutes a “digital archival collection”. Some background on the evolution of surrogate primary sources, from microfilm, through online databases to Open Access resources is presented. The article then explores the literature relating to the management and use of Digital Archival Collections and other digital primary sources. Some contextual information on Maynooth University and our digital primary sources is given. The article goes on to report on a consultation with faculty members who offer their insights on using DACs. The findings of the consultation process, which broadly show a strong appreciation of the merits of these resources, but mainly as an enhanced surrogate are discussed. The article concludes with some considerations of what these findings mean for collection development and what needs to be done to further stimulate engagement with these resources in Maynooth University.
dsRNA-induced condensation of antiviral proteins promotes PKR activation

Mammalian cells respond to dsRNA in multiple manners. One key response to dsRNA is the activation of PKR, an eIF2α kinase, which triggers translational arrest and the formation of stress granules. However, the process of PKR activation in cells is not fully understood. In response to increased endogenous or exogenous dsRNA, we observed that PKR forms novel cytosolic condensates, referred to as dsRNA-induced foci (dRIFs). dRIFs contain dsRNA, form in proportion to dsRNA, and are enhanced by longer dsRNAs. dRIFs also enrich several other dsRNA-binding proteins including ADAR1, Stau1, NLRP1, and PACT. Strikingly, dRIFs correlate with and form prior to translation repression by PKR and localize to regions of cells where PKR activation is initiated. We suggest that dRIF formation is a mechanism cells utilize to enhance the sensitivity of PKR activation in response to low levels of dsRNA, or to overcome viral inhibitors of PKR activation.
RefZ and Noc Act Synthetically to Prevent Aberrant Divisions during Bacillus subtilis Sporulation

The DNA-binding protein RefZ and its binding sites (RBMs) are conserved in sequence and location on the chromosome across the Bacillus genus and contribute to the timing of polar FtsZ-ring assembly during sporulation. Only a small number of noncoding and nonregulatory DNA motifs are known to be conserved in chromosomal position in bacteria, suggesting there is strong selective pressure for their maintenance; however, a refZ deletion mutant sporulates efficiently, providing no clues as to their functional significance. ABSTRACT During sporulation, Bacillus subtilis undergoes an atypical cell division that requires overriding mechanisms that protect chromosomes from damage and ensure inheritance by daughter cells. Instead of assembling between segregated chromosomes at midcell, the FtsZ-ring coalesces polarly, directing division over one chromosome. The DNA-binding protein RefZ facilitates the timely assembly of polar Z-rings and partially defines the region of chromosome initially captured in the forespore. RefZ binds to motifs (RBMs) located proximal to the origin of replication (oriC). Although refZ and the RBMs are conserved across the Bacillus genus, a refZ deletion mutant sporulates with wild-type efficiency, so the functional significance of RefZ during sporulation remains unclear. To further investigate RefZ function, we performed a candidate-based screen for synthetic sporulation defects by combining ΔrefZ with deletions of genes previously implicated in FtsZ regulation and/or chromosome capture. Combining ΔrefZ with deletions of ezrA, sepF, parA, or minD did not detectably affect sporulation. In contrast, a ΔrefZ Δnoc mutant exhibited a sporulation defect, revealing a genetic interaction between RefZ and Noc. Using reporters of sporulation progression, we determined the ΔrefZ Δnoc mutant exhibited sporulation delays after Spo0A activation but prior to late sporulation, with a subset of cells failing to divide polarly or activate the first forespore-specific sigma factor, SigF. The ΔrefZ Δnoc mutant also exhibited extensive dysregulation of cell division, producing cells with extra, misplaced, or otherwise aberrant septa. Our results reveal a previously unknown epistatic relationship that suggests refZ and noc contribute synthetically to regulating cell division and supporting spore development. IMPORTANCE The DNA-binding protein RefZ and its binding sites (RBMs) are conserved in sequence and location on the chromosome across the Bacillus genus and contribute to the timing of polar FtsZ-ring assembly during sporulation. Only a small number of noncoding and nonregulatory DNA motifs are known to be conserved in chromosomal position in bacteria, suggesting there is strong selective pressure for their maintenance; however, a refZ deletion mutant sporulates efficiently, providing no clues as to their functional significance. Here, we find that in the absence of the nucleoid occlusion factor Noc, deletion of refZ results in a sporulation defect characterized by developmental delays and aberrant divisions.
Design of sensor and actuator multi model fault detection and isolation system using state space neural networks

This paper deals with the application of state space neural network model to design a Fault Detection and Isolation diagnostic system. The work describes approach based on multimodel solution where the SIMO process is decomposed into simple models (SISO and MISO). With such models it is possible to generate different residual signals which later can be evaluated with simple thresholding method into diagnostic signals. Further, such diagnostic signals with the application of Binary Diagnostic Table (BDT) can be used to fault isolation. All data used in experiments is obtain from the simulator of the real-time laboratory stand of Modular Servo under Matlab/Simulink environment.
COVID-19 Pandemic School Closure and Reopening Impacts

 While limited, the literature indicates that school closures contribute to the effectiveness of non-pharmaceutical interventions (NPIs) for reducing Coronavirus Disease 2019 (COVID-19) transmission. In the majority of modelling studies, school closures reduced the reproductive number (R0) of COVID-19 and reduced the total or cumulative number of cases. Some models estimated that school closures, while effective, did not impact R0 as much as other NPIs.
Bioactive Hepatic Peptide Improves Immune Function by Inducing Autophagy in Stomach Cancer-Bearing Nude Mice

Background: Bioactive Hepatic Peptide (BHP), a kind of bioactive peptide from goat liver, can regulate immune function in healthy mice. However, how the tumor-bearing mice? We investigated the effect of BHP on the immune function of gastric cancer-bearing nude mice and its possible underlying mechanism. Methods: Nude mice were inoculated into the neck with human BGC-823 gastric cancer cells to establish the subcutaneous transplanted tumor model group. The percentage of peripheral blood lymphocytes was measured by flow cytometry. Hematoxylin-Eosin (HE) staining was used. The mRNA expression levels were measured by real-time fluorescence quantitative PCR and the protein expression of NF-κB, TNFα, Beclin1, LC3B, Akt1, COX-2 were determined by immunohistochemistry and Enzyme-Linked Immunosorbent Assay (ELISA). Results: BHP could inhibit tumor cell proliferation, improve the percentage of NK cells/B lymphocytes, phagocytic index and phagocytic percentage and reduce the degree of inflammatory infiltration in tumor-bearing nude mice. BHP could significantly decrease the mRNA and protein expression of NF-κB, TNF-α in spleen and AKT1 and COX-2 in tumor tissue, but it could significantly increase the mRNA and protein expression of Beclin1 and LC3B (LC3) in tumor tissue (P<0.05). The levels of NFκB, TNFα and COX-2 were significantly lower in the serum of nude mice treated with BHP (P<0.05). The level of Beclin1 increased significantly after BHP treatment (P<0.05). Conclusion: BHP may down regulate NF-κB/AKT1 to inhibit inflammation and induce autophagy, thus enhancing the immune function and antitumor effect of tumor-bearing nude mice. These findings support BHP as an immune-boosting health food/drug for cancer patients.
Understanding Green Purchasing Behavior Through Environmental Attitude: An Empirical Study on Innisfree Consumers

Lately, consumers are increasingly aware of their purchase behaviors in modern times. They are cognizant of the fact that their consumption habits may have a detrimental effect on environmental sustainability. Marketers have made numerous efforts to develop environmentally friendly products for their customers. This, however, results in a boomerang effect, where customers develop a negative attitude towards the process and label it as greenwashing. Aimed to fill in the knowledge and research object gaps regarding this issue, specifically in Medan, this research assessed how environmental attitude toward green purchasing behavior is influenced by numerous antecedents, including interpersonal influence, altruism, and environmental knowledge. Structural Equation Modelling analysis is employed to assess the relationship between variables. This research indicates that altruism and environmental knowledge have a positive effect on environmental attitude, and that environmental attitude has a positive effect on green purchasing behavior. However, interpersonal influence has a negative effect on environmental attitudes. This shows that marketers should consider these variables when developing an effective campaign capable of eliciting a positive attitude about the environment among the population.
Factors contributing to the unsustainability of community-based development projects in the Oshana region of Namibia

The Government of Namibia has been promoting and supporting sustainable community-based development projects since independence in 1990. Since the independence, many donors funded CBDPs that have been initiated in the Oshana Region of Namibia. However, it has been noted that once the donor funds are withdrawn from these CBDPs, communities fail to sustain these projects and are eventually forced to revert to conditions of destitution and deprivation. The aim of this study was to explore factors contributing to the unsustainability of community-based development in the Oshana region of Namibia. Qualitative approach with a phenomenological design using the semistructured interviews were used to collect the data from the 16 participants from the Oshana region of Namibia. The data from participants was analyzed using content analysis method and data reduction. The result of the study shows that the reasons for initiating the community development programmes rested on the need to respond to HIV/AIDS and unemployment, food security and government needs. The factors that contributed to the unsustainability were found to be climate change, lack of finances, lack of land, lack of qualified management staff, lack of security and lack of empowerment opportunities. Among the measures to reverse the trends of unsustainability, the study found the need for mentors, use of local language for training purposes, the need to involve beneficiaries from the beginning of the projects. The study recommends, the need to empower the project members, to develop policies and implement them as well as enact the monitoring and evaluation mechanisms.
Magnetically assisted statistical assembly of III-V heterostructures on silicon : initial process and technology development

This work is the initial investigation of magnetically assisted statistical assembly (MASA), a novel silicon Im-V integration technique developed at M.I. T. Initially procedures for processing optoelectronic devices into magnetically sensitive 40 micron discs were performed and refined. Cobalt palladium thin films were obtained and their magnetic properties were studied. An initial procedure was developed to easily integrate these patterned, magnetized films with 60-micron diameter, 5-micron deep recesses. Pill devices were then integrated into these magnetically attractive recesses. The studied showed optoelectronic pills with magnetic layers could be successfully produced and collected. Assembly using these pills was performed and showed improved recess filling yields over the non-magnetic assembly, though more investigation needs to be done. MASA was shown to offer promise as a viable and promising technique for mixed device integration. Thesis Supervisor: Clifton G. Fonstad, Jr. Title: Professor of Electrical Engineering
COMPETITOR COST ASSESSMENT AND PROFITABILITY OF QUOTED NIGERIAN MANUFACTURING FIRMS: A CRITICAL REGRESSION

Competitor accounting involves exploring markets, formulating strategies, and establishing market patterns for sustained industry leadership. This study examined the effect of competitor cost assessment (component of competitor accounting) on the profitability (net profit margin and return on equity) of quoted manufacturing firms in Nigeria. Anex-post facto design was adopted, with a sample of 92 out of 120 firms, drawn using TaroYamene formula and random numbers table. Financial data of the firms for the period 2012-2016, published in the Nigerian Stock Exchange Fact Book, were collected and analysed using descriptive and inferential tools; aided by Statistical Package for Social Sciences (SPSS) version 22. The results revealed that competitor cost assessment significantly affects the net profit margin (firm average index=19.63%>industry average of 5%) and the return on equity (firm average index=20.02%>industry average of 5%). The inferential statistics are significant at 95% confidence level (D-W=2.299, R=0.42, p-value=0.00<0.05). The study, therefore, concludes that competitor cost assessment significantly affects the profitability of quoted manufacturing companies in Nigeria. Based on this conclusion, it is recommended that managers of the firms should ensure efficient competitor cost analysis for sustained cost leadership and enhanced financial performance. Also, a special unit anchored by professionals in the accounts and marketing departments of the firms should be charged with the responsibility of conducting continuous competitor accounting assessment, in line with financial reporting best practices, to strategically promote business growth and keep pace with trends in the industry. Research Article Open Access
Nonlinear multiphase flow in hydrophobic porous media

Abstract Multiphase flow in porous materials is conventionally described by an empirical extension to Darcy's law, which assumes that the pressure gradient is proportional to the flow rate. Through a series of two-phase flow experiments, we demonstrate that even when capillary forces are dominant at the pore scale, there is a nonlinear intermittent flow regime with a power-law dependence between pressure gradient and flow rate. Energy balance is used to predict accurately the start of the intermittent regime in hydrophobic porous media. The pore-scale explanation of the behaviour based on the periodic filling of critical flow pathways is confirmed through 3D micron-resolution X-ray imaging.
THE ROLE OF CUSTOMER SATISFACTION AND PRICE FAIRNESS IN MEDIATING THE INFLUENCE OF SERVICE QUALITY ON WORD OF MOUTH

This study has a purpose to explain the role of customer satisfaction and price fairness in mediating the influence of service quality on word of mouth. There were 112 respondents as the sample in this study. The sampling method used was the purposive sampling method. This research used the Partial Least Square (PLS) analysis technique. The results of this study revealed that service quality, price fairness and customer satisfaction have a significant and positive influence on word of mouth. Service quality and price fairness have a significant and positive influence on customer satisfaction. Service quality has a significant and positive influence on price fairness. Customer satisfaction and price fairness are able to partially mediate the influence of service quality on word of mouth. The implication of this research is that to improve the word of mouth behavior of PT.TIKI customers, it is necessary to evaluate and improve their service quality, customer satisfaction and price fairness.