Miracle-dz/UniFAR-FTUs huggingface dataset:
p190A RhoGAP Is a Glycogen Synthase Kinase-3-β Substrate Required for Polarized Cell Migration*

The Rho GTPases are critical regulators of the actin cytoskeleton and are required for cell adhesion, migration, and polarity. Among the key Rho regulatory proteins in the context of cell migration are the p190 RhoGAPs (p190A and p190B), which function to modulate Rho signaling in response to integrin engagement. The p190 RhoGAPs undergo complex regulation, including phosphorylation by several identified kinases, interactions with phospholipids, and association with a variety of cellular proteins. Here, we have identified an additional regulatory mechanism unique to p190A RhoGAP that involves priming-dependent phosphorylation by glycogen synthase-3-β (GSK-3β), a kinase previously implicated in establishing cell polarity. We found that p190A-deficient fibroblasts exhibit a defect in directional cell migration reflecting a requirement for GSK-3β-mediated phosphorylation of amino acids in the C-terminal “tail” of p190A. This phosphorylation leads to inhibition of p190A RhoGAP activity in vitro and in vivo. These studies identify p190A as a novel GSK-3β substrate and reveal a mechanism by which GSK-3β contributes to cellular polarization in directionally migrating cells via effects on Rho GTPase activity.
Mamdani type controller design for MIMO systems with case study

This paper looks into the intelligent control system design using fuzzy logic for Multiple Input Multiple Output (MIMO) systems, with a case study application of a depyrogenation tunnel [1]. Depyrogenation tunnels are widely and specifically used in pharmaceutical filling process for removing pyrogens adhere to containers (sterilization treatment of containers mainly). As part of the research process this paper presents the fuzzy logic controller design process based on Mamdani inference, as well as the case study for performance analysis and comparison of the designed controller with previous research result using decoupling control method.
Effects of the penalty on the penalized weighted least-squares image reconstruction for low-dose CBCT

Statistical iterative reconstruction (SIR) algorithms have shown potential to substantially improve low-dose cone-beam CT (CBCT) image quality. The penalty term plays an important role in determining the performance of SIR algorithms. In this work, we quantitatively evaluate the impact of the penalties on the performance of a statistics-based penalized weighted least-squares (PWLS) iterative reconstruction algorithm for improving the image quality of low-dose CBCT. Three different edge-preserving penalty terms, exponential form anisotropic quadratic (AQ) penalty (PWLS-Exp), inverse square form AQ penalty (PWLS-InverseSqr) and total variation penalty (PWLS-TV), were compared against the conventional isotropic quadratic form penalty (PWLS-Iso) using both computer simulation and experimental studies. Noise in low-dose CBCT can be substantially suppressed by the PWLS reconstruction algorithm and edges are well preserved by both AQ- and TV-based penalty terms. The noise-resolution tradeoff measurement shows that the PWLS-Exp exhibits the best spatial resolution of all the three anisotropic penalty terms at matched noise level for reconstructing high-contrast objects. For the reconstruction of low-contrast objects, the TV-based penalty outperforms the AQ-based one with better resolution preservation at matched noise levels. Different penalty terms may be used for better edge preservation at different targeted contrast levels.
Fiberoptic Endoscopic Dysphagia Severity Scale Predicts Outcome after Acute Stroke

Background and Purpose: Fiberoptic endoscopic evaluation of swallowing (FEES) is a suitable method for dysphagia assessment after acute stroke. Recently, we developed the fiberoptic endoscopic dysphagia severity scale (FEDSS) for acute stroke patients, grading dysphagia into 6 severity codes (1 to 6; 1 being best). The purpose of this study was to investigate the impact of the FEDSS as a predictor of outcomes at 3 months and intermediate complications during acute treatment. Methods: A total of 153 consecutive first-ever acute stroke patients were enrolled. Dysphagia was classified according to the FEDSS, assessed within 24 h after admission. Intermediate outcomes were pneumonia and endotracheal intubation. Functional outcome was measured by the modified Rankin Scale (mRS) at 3 months. Multivariate regression analysis was used to identify whether the FEDSS was an independent predictor of outcome and intercurrent complications. Analyses were adjusted for sex, age and National Institutes of Health Stroke Scale (NIH-SS) on admission. Results: The FEDSS was found to predict the mRS at 3 months as well as but independent from the NIH-SS. For each additional point on the FEDSS, the likelihood of dependency at 3 months (mRS ≥ 3) raised by ∼50%. Each increase of 1 point on the FEDSS conferred a more than 2-fold increased chance of developing pneumonia. The odds for the necessity of endotracheal intubation raised by a factor of nearly 2.5 with each additional point on the FEDSS. Conclusions: The FEDSS strongly and independently predicts outcome and intercurrent complications after acute stroke. Thus, a baseline FEES examination provides valuable prognostic information for the treatment of acute stroke patients.
Do individuals consider expected income when valuing health states?

Objectives: The purpose of this study was to empirically explore whether individuals take their expected income into consideration when directly valuing predefined health states. This was intended to help determine how to handle productivity costs due to morbidity in a cost-effectiveness analysis. Methods: Two hundred students each valued four hypothetical health states by using time trade-off (TTO) and a visual analogue scale (VAS). The students were randomly assigned to two groups. One group was simply asked, without mentioning income, to value the different health states (the non-income group). The other group was explicitly asked to consider their expected income in relation to the health states in their valuations (the income group). Results: For health states that are usually assumed to have a large effect on income, the valuations made by the income group seemed to be lower than the valuations made by the non-income group. Among the students in the non-income group, 96 percent stated that they had not thought about their expected income when they valued the health states. In the income group, 40 percent believed that their expected income had affected their valuations of the health states. Conclusion: The results show that, as long as income is not mentioned, most individuals do not seem to consider their expected income when they value health states. This indicates that productivity costs due to morbidity are not captured within individuals' health state valuations. These findings, therefore, suggest that productivity costs due to morbidity should be included as a cost in cost-effectiveness analyses.
Gene therapy for type 1 diabetes mellitus in rats by gastrointestinal administration of chitosan nanoparticles containing human insulin gene.

AIM To study the expression of human insulin gene in gastrointestinal tracts of diabetic rats. METHODS pCMV.Ins, an expression plasmid of the human insulin gene, wrapped with chitosan nanoparticles, was transfected to the diabetic rats through lavage and coloclysis, respectively. Fasting blood glucose and plasma insulin levels were measured for 7 d. Reverse transcription polymerase chain reaction (RT-PCR) analysis and Western blot analysis were performed to confirm the expression of human insulin gene. RESULTS Compared with the control group, the fasting blood glucose levels in the lavage and coloclysis groups were decreased significantly in 4 d (5.63 +/- 0.48 mmol/L and 5.07 +/- 0.37 mmol/L vs 22.12 +/- 1.31 mmol/L, respectively, P < 0.01), while the plasma insulin levels were much higher (32.26 +/- 1.81 microIU/mL and 32.79 +/- 1.84 microIU/mL vs 14.23 +/- 1.38 microIU/mL, respectively, P < 0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and coloclysis groups. CONCLUSION Human insulin gene wrapped with chitosan nanoparticles can be successfully transfected to rats through gastrointestinal tract, indicating that chitosan is a promising non-viral vector.
Implementing the Single Assessment Process: Opportunities and challenges

The Single Assessment Process (SAP) has been introduced as part of the National Service Framework for Older People and has major implications for health and social care. The aim of this study was to evaluate a pilot introduction of the Single Assessment Process in the South-East of England. A qualitative case study design incorporating observation and semi-structured interviews were used to collect data. Assessment visits were observed and recorded, and interviews were carried out with older people and their carers (n = 9), health and social care practitioners, operational managers, and other key individuals involved in the pilot (n = 26). Overall the evaluation found three major themes that had an impact on the implementation of the Single Assessment Process. These were: the process of implementing policy and change, the health and social care boundary, and communication and sharing of assessments. Front-line practitioners (street-level bureaucrats) had a major impact on the SAP implementation, particularly through their reluctance to engage with the process, work together and share assessments. Success of the national SAP implementation will depend on the extent to which those working directly with older people can be engaged in the policy process.
Memory access profiling for HEVC encoders

In this work we present a framework that profiles HEVC (High Efficiency Video Coding) encoders modules focusing on cache memory performance and energy. This framework considers the HEVC reference software (HM) and analyzes the impact of some coding parameters on the cache hierarchy. HEVC was proposed in 2013, presenting new video coding techniques to deal with the demand for higher resolutions. The tools included in the HEVC increase significantly the computational effort and energy consumption required to encode videos when compared to its predecessor, H.264/AVC. For this analysis we used the proposed framework MAP-HEVC (Memory Access Profiling for HEVC) considering seven different video coding configurations and four video resolutions. In the prediction module, the results showed that using Full Search (FS) results in 75% more accesses than using Test Zonal (TZ) Search. The results also suggest that using 16×16 search ranges is a very viable option to reduce the memory accesses achieving a better compression. For the residual coding, the Rate-Distortion Optimized Quantization (RDOQ) was evaluated and our analysis showed that this tool adds 10% more accesses to the memory.
Direct and indirect cross-tolerance of alloreactive T cells by dendritic cells retained in the immature stage.

BACKGROUND Rejection of allografts entails the direct and indirect cross-recognition of donor major histocompatibility complex molecules by recipient alloreactive T cells. The ability to manipulate the state of dendritic cell (DC) maturation in vitro has enabled us to induce tolerance specifically targeting the alloreactive T-cell compartment. In this study, the immunoregulatory effect of alloantigen presentation by ex vivo-generated donor and recipient DCs retained in immature stage was investigated. METHODS Dendritic cell were generated by culturing monocytes with granulocyte-macrophage colony-stimulating factor and interleukin-4. Ex vivo-generated tolerogenic DCs were characterized by flow cytometry and confocal microscopy. Recipient T-cell responses to donor or recipient DCs loaded with donor-derived apoptotic cells were assessed in a two-step culture system. RESULTS Dendritic cells maintained their phagocytic and endocytic activities, and had significantly reduced capacity to prime recipient T cells. Moreover, primary coculture of recipient T cells with donor tolerogenic DCs rendered alloantigen-specific T cells hyporesponsive to a subsequent challenge with donor immunogenic DCs as evidenced by decreased proliferation and cytokine secretion. Importantly, recipient tolerogenic DCs loaded with donor-derived apoptotic cells were able to cross-tolerize recipient T cells. This was revealed by alloantigen-specific T-cell hyporesponsiveness on restimulation with the recipient immunogenic DCs loaded with different tissue-derived apoptotic cells obtained from the same donor. CONCLUSIONS Dendritic cells retained in immature stage induce direct and most importantly indirect cross-tolerance of alloantigen-specific T cells. It may be likely that administration of donor and/or recipient DCs could be one means with which to promote tolerance induction in acute and chronic phases of organ transplant.
Safety and effectiveness of tacrolimus add-on therapy for rheumatoid arthritis patients without an adequate response to biological disease-modifying anti-rheumatic drugs (DMARDs): Post-marketing surveillance in Japan

Abstract Objectives: Post-marketing surveillance (PMS) was conducted to assess the safety and effectiveness of tacrolimus (TAC) add-on therapy for patients with rheumatoid arthritis (RA) and an inadequate response to biological disease-modifying anti-rheumatic drugs (DMARDs). Methods: Patients with RA from 180 medical sites across Japan were registered centrally with an electronic investigation system. The observational period was 24 weeks from the first day of TAC administration concomitantly with biological DMARDs. Results: Safety and effectiveness populations included 624 and 566 patients, respectively. Patients were predominantly female (81.1%), with a mean age of 61.9 years. Overall, 125 adverse drug reactions (ADRs) occurred in 94 patients (15.1%), and 15 serious ADRs occurred in 11 patients (1.8%). These incidences were lower compared with previously reported incidences after TAC treatment in PMS, and all of the observed ADRs were already known. A statistically significant improvement was observed in the primary effectiveness variable of Simplified Disease Activity Index after TAC treatment; 62.7% of patients achieved remission or low disease activity at week 24. Conclusions: TAC is well tolerated and effective when used as an add-on to biological DMARDs in Japanese patients with RA who do not achieve an adequate response to biological DMARDs in a real-world clinical setting.
Disinfection alternatives for contact surfaces and toys at child care centers

Child care surfaces are vehicles for disease-causing organisms. Disinfectant procedures prevent microbial dispersion. This study reports the effectiveness of CITRUS Farm Edition® (CFE), Clorox® GreenWorks™ (CGW) and Clorox® Anywhere® (CA) against Salmonella Typhimurium and Staphylococcus aureus inoculated (1 ml of 9Log10 CFU/ml) on a high chair and ball toy. Disinfectants were sprayed and bacteria recovered from surfaces by sponge method. Exposing an inoculated high chair to CA resulted in the highest reduction of S. aureus (3.92 Log10) and S. Typhimurium (3.22 Log10). CGW reduced S. aureus and S. Typhimurium by 2.84 and 2.12 Log10 from the inoculated high chair, while the inoculated ball toy showed a 2.50 and 1.80 Log10 reduction, respectively. CFE showed the lowest reduction with 1.42 and 1.53 Log10 of S. aureus and S. Typhimurium from the inoculated ball toy. CA was the best disinfectant no matter which bacteria or surface was analyzed. Emphasis on the effectiveness of disinfectant products is needed to be included in child care center infection control programs.
RNA‐induced silencing attenuates G protein‐mediated calcium signals

Phospholipase Cβ (PLCβ) is activated by G protein subunits in response to environmental stimuli to increase intracellular calcium. In cells, a significant portion of PLCβ is cytosolic, where it binds a protein complex required for efficient RNA‐induced silencing called C3PO (component 3 promoter of RISC). Binding between C3PO and PLCβ raises the possibility that RNA silencing activity can affect the ability of PLCβ to mediate calcium signals. By use of human and rat neuronal cell lines (SK‐N‐SH and PC12), we show that overexpression of one of the main components of C3PO diminishes Ca2+ release in response to Gαq/PLCβ stimulation by 30 to 40%. In untransfected SK‐N‐SH or PC12 cells, the introduction of siRNA(GAPDH) [small interfering RNA(glyceraldehyde 3‐phosphate dehydrogenase)] reduces PLCβ‐mediated calcium signals by ~30%, but addition of siRNA(Hsp90) (heat shock protein 90) had little effect. Fluorescence imaging studies suggest an increase in PLCβ‐C3PO association in cells treated with siRNA(GAPDH) but not siRNA(Hsp90). Taken together, our studies raise the possibility that Ca2+ responses to extracellular stimuli can be modulated by components of the RNA silencing machinery. —Philip, F. , Sahu, S. , Golebiewska, U. , Scarlata, S. RNA‐induced silencing attenuates G protein‐mediated calcium signals. FASEB J. 30, 1958–1967 (2016). www.fasebj. org
Therapist empathy, combined behavioral intervention, and alcohol outcomes in the COMBINE research project.

OBJECTIVE Common factors such as therapist empathy play an important role in treatment for addictive behaviors. The present study was a secondary analysis designed to evaluate the relation between therapist empathy and alcohol treatment outcomes in data from a large, multisite, randomized controlled trial. METHOD Audio-recorded psychotherapy sessions for 38 therapists and 700 clients had been randomly selected for fidelity coding from the combined behavioral intervention condition of Project COMBINE. Sessions were evaluated by objective raters for both specific content (coping with craving, building social skills, and managing negative mood) and relational components (empathy level of the therapist). Multilevel modeling with clients nested within therapists evaluated drinks per week at the end of treatment. RESULTS Approximately 11% of the variance in drinking was accounted for by therapists. A within-therapist effect of empathy was detected (B = -0.381, SE = 0.103, p < .001); more empathy than usual was associated with subsequent decreased drinking. The Social and Recreational Counseling module (B = -0.412, SE = 0.124, p < .001), Coping with Cravings and Urges module (B = -0.362, SE = 0.134, p < .01), and the Mood Management module (B = -0.403, SE = 0.138, p < .01) were also associated with decreased drinking. No between-therapist effect was detected, and the Empathy × Module Content interactions were not significant. CONCLUSIONS The results of the study appear consistent with the hypothesis that skills building and therapist empathy are independent contributions to the overall benefit derived from the combined behavioral intervention.
Oxidative Stress-Induced Dysfunction of Müller Cells During Starvation.

PURPOSE Müller cells support retinal neurons with essential functions. Here, we aim to examine the impact of starvation and oxidative stress on glutamate uptake and mitochondrial function in Müller cells. METHODS Cultured human retinal Müller cells (MIO-M1) were exposed to H2O2 and additional starvation for 24 hours. Effects of starvation and H2O2 on glutamate uptake and mitochondrial function were assessed by kinetic glutamate uptake assays and Seahorse assays, respectively. Cell survival was evaluated by cell viability assays. mRNA and protein expressions were assessed by quantitative PCR and Western blot. RESULTS Starvation of Müller cells increased the glutamate uptake capacity as well as the expression of the most abundant glutamate transporter, EAAT1. Mitochondrial and glycolytic activity were diminished in starved Müller cells despite unaffected cell viability. Simultaneous starvation and exposure to oxidative stress resulted in a reduced glutamate uptake and a collapsed mitochondrial function. In Müller cells with intact energy supply, the glutamate uptake and mitochondrial function were unaffected after exposure to oxidative stress. CONCLUSIONS Here, we identify an increased susceptibility toward oxidative stress in starved Müller cells in spite of unaffected viability and an apparent decreased ability to transport glutamate. Solely exposure to oxidative stress did not affect Müller cell functions. Thus, our study suggests an increased susceptibility of Müller cells in case of more than one cellular stressor. Extrapolating these findings, age-related neurodegenerative retinal diseases may be the result of impaired Müller cell function.
Partial Remission of Resistant Nephrotic Syndrome After Oral Galactose Therapy

Focal segmental glomerulosclerosis is sometimes associated with a circulating permeability factor. It was proposed that this factor interacts with the sugars of the glycocalyx, and its high affinity for galactose was shown on the basis of chromatographic studies. Galactose inactivates it and seems to lead to its clearance from plasma. A toddler with a nephrotic syndrome resistant to corticosteroids was admitted. A renal biopsy revealed minimal change disease with deposition of immunoglobulin M. Immunosuppressive therapy with pulses of cyclophosphamide, low‐dose combination immunosuppressive therapy, and later with mycophenolate mofetil failed to induce remission. A renal biopsy six years later showed transformation to FSGS. After unsuccessful treatment with monthly pulses of cyclophosphamide, we began therapy with tacrolimus, which showed no effect. After two months, we added oral galactose to tacrolimus for one month, after which proteinuria decreased by 50%. Seven months later, galactose was again added for six months, after which proteinuria remained below 2 g/24 h and the plasma albumin and cholesterol concentrations normalized. An adolescent girl with a nephrotic syndrome resistant to corticosteroids was admitted. A renal biopsy revealed mesangioproliferative glomerulonephritis with C1q nephropathy. Therapy with tacrolimus failed to induce remission. After six months, we added galactose for three months, which reduced proteinuria to 0.76 g/24 h. After the discontinuation of galactose therapy, proteinuria increased to 2.48 g/24 h, despite further treatment with tacrolimus. It seems that oral galactose at a dose of 0.2 g/kg twice a day could be a promising new and nontoxic therapy for the treatment of resistant nephrotic syndrome.
Evidence-based practice guidelines for instructing individuals with neurogenic memory impairments: What have we learned in the past 20 years?

This article examines the instructional research literature pertinent to teaching procedures or information to individuals with acquired memory impairments due to brain injury or related conditions. The purpose is to evaluate the available evidence in order to generate practice guidelines for clinicians working in the field of cognitive rehabilitation. A systematic review of the instructional literature from 1986 to 2006 revealed 51 studies meeting search criteria. Studies were analysed and coded within the following four key domains: Population Sample, Intervention, Study Design, and Treatment Outcomes. Coding included 17 characteristics of the population sample; seven intervention parameters; five study design features; and five treatment outcome parameters. Interventions that were evaluated included systematic instructional techniques such as method of vanishing cues and errorless learning. The majority of the studies reported positive outcomes in favour of systematic instruction. However, issues related to the design and execution of effective instruction lack clarity and require further study. The interaction between the target learning objective and the individual learner profile is not well understood. The evidence review concludes with clinical recommendations based on the instructional literature and a call to clinicians to incorporate these methods into their practice to maximise patient outcomes.