Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel linear motif filtering protocol reveals the role of the LC8 dynein light chain in the Hippo pathway

Protein-protein interactions (PPIs) formed between short linear motifs and globular domains play important roles in many regulatory and signaling processes but are highly underrepresented in current protein-protein interaction databases. These types of interactions are usually characterized by a specific binding motif that captures the key amino acids shared among the interaction partners. However, the computational proteome-level identification of interaction partners based on the known motif is hindered by the huge number of randomly occurring matches from which biologically relevant motif hits need to be extracted. In this work, we established a novel bioinformatic filtering protocol to efficiently explore interaction network of a hub protein. We introduced a novel measure that enabled the optimization of the elements and parameter settings of the pipeline which was built from multiple sequence-based prediction methods. In addition, data collected from PPI databases and evolutionary analyses were also incorporated to further increase the biological relevance of the identified motif hits. The approach was applied to the dynein light chain LC8, a ubiquitous eukaryotic hub protein that has been suggested to be involved in motor-related functions as well as promoting the dimerization of various proteins by recognizing linear motifs in its partners. From the list of putative binding motifs collected by our protocol, several novel peptides were experimentally verified to bind LC8. Altogether 71 potential new motif instances were identified. The expanded list of LC8 binding partners revealed the evolutionary plasticity of binding partners despite the highly conserved binding interface. In addition, it also highlighted a novel, conserved function of LC8 in the upstream regulation of the Hippo signaling pathway. Beyond the LC8 system, our work also provides general guidelines that can be applied to explore the interaction network of other linear motif binding proteins or protein domains.
ING 2 Regulates the Onset of Replicative Senescence by Induction of p 300-Dependent p 53 Acetylation †

ING2 Regulates the Onset of Replicative Senescence by Induction of p300-Dependent p53 Acetylation† Remy Pedeux, Sagar Sengupta, Jiang Cheng Shen, Oleg N. Demidov, Shin’ichi Saito, Hitoshi Onogi, Kensuke Kumamoto, Stephen Wincovitch, Susan H. Garfield, Mary McMenamin, Makoto Nagashima, Steven R. Grossman, Ettore Appella, and Curtis C. Harris* Laboratory of Human Carcinogenesis, Laboratory of Cell Biology, and Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Department of Surgery, Toho University Sakura Hospital, Sakura, Japan; Departments of Cancer Biology and Medicine, University of Massachusetts Medical School, Worcester, Massachusetts; and National Institute of Immunology, Aruna Asaf Marg, New Delhi, India
Abrasion phenomena of the contact tip in consumable electrode arc welding

ABSTRACT In GMA welding, presently, fluctuation of the tip of welding wire has been able to restrain precisely, and metal transfer also has been able to regulate periodically, that is stable arc-like TIG welding has been realized. Then at this stage, reduction of contact tip abrasion is the most important subject to maintain arc stability for a long time. In this investigation, many factors are evaluated with abrasion amount, and new material of contact tip is recommended. Results obtained are as follows. Using uncoated welding wire increases contact tip abrasion rapidly as to Cu-coated welding wire. On the contrary, other welding conditions concerning contact point have almost no influence. Under the same current, the abrasion of contact tip is reduced accordingly as welding wire feeding rate becomes higher. Therefore, the abrasion is accelerated violently at the time of arc ignition because of heat accumulation at the contact point by wire stopping and high current which is needed for arc ignition. That is the welding wire which is induced to contact point with room temperature has considerable influence to cool the contact point. As a measure to reduce the abrasion at arc ignition, shortening the period of high current is effective. To cool the contact point positively, thermoelectromotive force was applied. Constantan (Cu-455Ni) has low thermoelectromotive force and high melting point than Fe. So, Cu–Ni alloy (Cu-43.3%Ni-0.92%Mn) was selected and examined as the contact tip material. The abrasion of Cu–Ni alloy contact tip becomes less than about two-tenth of the abrasion of Cu–Cr contact tip. As the conclusion, the best mixed measures which are effective to reduce the contact tip abrasion are using Cu-coated welding wire, wire retract type arc ignition and Cu–Ni alloy contact tip.
Oxidative Stress and Inflammation Induced by Environmental and Psychological Stressors: A Biomarker Perspective

SIGNIFICANCE The environment can elicit biological responses such as oxidative stress (OS) and inflammation as a consequence of chemical, physical, or psychological changes. As population studies are essential for establishing these environment-organism interactions, biomarkers of OS or inflammation are critical in formulating mechanistic hypotheses. Recent Advances: By using examples of stress induced by various mechanisms, we focus on the biomarkers that have been used to assess OS and inflammation in these conditions. We discuss the difference between biomarkers that are the result of a chemical reaction (such as lipid peroxides or oxidized proteins that are a result of the reaction of molecules with reactive oxygen species) and those that represent the biological response to stress, such as the transcription factor NRF2 or inflammation and inflammatory cytokines. CRITICAL ISSUES The high-throughput and holistic approaches to biomarker discovery used extensively in large-scale molecular epidemiological exposome are also discussed in the context of human exposure to environmental stressors. FUTURE DIRECTIONS We propose to consider the role of biomarkers as signs and to distinguish between signs that are just indicators of biological processes and proxies that one can interact with and modify the disease process. Antioxid. Redox Signal. 28, 852-872.
Development of a dosing nomogram for continuous-infusion meropenem in critically ill patients based on a validated population pharmacokinetic model

Background Optimal antibiotic exposure is a vital but challenging prerequisite for achieving clinical success in ICU patients. Objectives To develop and externally validate a population pharmacokinetic model for continuous-infusion meropenem in critically ill patients and to establish a nomogram based on a routinely available marker of renal function. Methods A population pharmacokinetic model was developed in NONMEM® 7.3 based on steady-state meropenem concentrations (CSS) collected during therapeutic drug monitoring. Different serum creatinine-based markers of renal function were compared for their influence on meropenem clearance (the Cockcroft-Gault creatinine clearance CLCRCG, the CLCR bedside estimate according to Jelliffe, the Chronic Kidney Disease Epidemiology Collaboration equation and the four-variable Modification of Diet in Renal Disease equation). After validation of the pharmacokinetic model with independent data, a dosing nomogram was developed, relating renal function to the daily doses required to achieve selected target concentrations (4/8/16 mg/L) in 90% of the patients. Probability of target attainment was determined for efficacy (CSS ≥8 mg/L) and potentially increased likelihood of adverse drug reactions (CSS >32 mg/L). Results In total, 433 plasma concentrations (3.20-48.0 mg/L) from 195 patients (median/P0.05 - P0.95 at baseline: weight 77.0/55.0-114 kg, CLCRCG 63.0/19.6-168 mL/min) were used for model building. We found that CLCRCG best described meropenem clearance (CL = 7.71 L/h, CLCRCG = 80 mL/min). The developed model was successfully validated with external data (n = 171, 73 patients). According to the nomogram, daily doses of 910/1480/2050/2800/3940 mg were required to reach a target CSS = 8 mg/L in 90% of patients with CLCRCG = 20/50/80/120/180 mL/min, respectively. A low probability of adverse drug reactions (<0.5%) was associated with these doses. Conclusions A dosing nomogram was developed for continuous-infusion meropenem based on renal function in a critically ill population.
The Development and Validation of the Game User Experience Satisfaction Scale (GUESS)

Objective: The aim of this study was to develop and psychometrically validate a new instrument that comprehensively measures video game satisfaction based on key factors. Background: Playtesting is often conducted in the video game industry to help game developers build better games by providing insight into the players’ attitudes and preferences. However, quality feedback is difficult to obtain from playtesting sessions without a quality gaming assessment tool. There is a need for a psychometrically validated and comprehensive gaming scale that is appropriate for playtesting and game evaluation purposes. Method: The process of developing and validating this new scale followed current best practices of scale development and validation. As a result, a mixed-method design that consisted of item pool generation, expert review, questionnaire pilot study, exploratory factor analysis (N = 629), and confirmatory factor analysis (N = 729) was implemented. Results: A new instrument measuring video game satisfaction, called the Game User Experience Satisfaction Scale (GUESS), with nine subscales emerged. The GUESS was demonstrated to have content validity, internal consistency, and convergent and discriminant validity. Conclusion: The GUESS was developed and validated based on the assessments of over 450 unique video game titles across many popular genres. Thus, it can be applied across many types of video games in the industry both as a way to assess what aspects of a game contribute to user satisfaction and as a tool to aid in debriefing users on their gaming experience. Application: The GUESS can be administered to evaluate user satisfaction of different types of video games by a variety of users.
A Mobile, Avatar-Based App for Improving Body Perceptions Among Adolescents: A Pilot Test

Background One barrier to effectively treating weight issues among adolescents is that they tend to use social comparison instead of objective measures to evaluate their own health status. When adolescents correctly perceive themselves as overweight, they are more likely to adopt healthy lifestyle behaviors. Objective The purpose of this pilot test was to develop and assess acceptability and usability of an avatar-based, theoretically derived mobile app entitled Monitor Your Avatar (MYA). Methods The MYA app was engineered for high school adolescents to identify, using avatars, what they thought they looked like, what they wanted to look like, and what they actually looked like based on body measurements. Results The MYA app was pilot-tested with male and female adolescents aged 15-18 years to assess for acceptability and usability. A total of 42 students created and viewed their avatars. The majority of the adolescents were female (28/42, 67%), age 16 years (16/42, 38%), white (35/42, 83%), non-Hispanic (36/42, 86%), in grade 10 (20/42, 48%), healthy weight for females (23/28, 82%), and obese for males (7/14, 50%). The adolescents had positive reactions to the avatar app and being able to view avatars that represented them. All but one student (41/42, 98%) indicated some level of comfort viewing the avatars and would use the app in the future to see how their bodies change over time. Conclusions Avatar-based mobile apps, such as the MYA app, provide immediate feedback and allow users to engage with images that are personalized to represent their perceptions and actual body images. This pilot study adds to the increasing but limited research of using games to improve health outcomes among high school adolescents. There is a need to further adapt the MYA app and gather feedback from a larger number of high school adolescents, including those from diverse backgrounds.
Estrogen Receptor β as a Therapeutic Target in Breast Cancer Stem Cells

Abstract Background: Breast cancer cells with tumor-initiating capabilities (BSCs) are considered to maintain tumor growth and govern metastasis. Hence, targeting BSCs will be crucial to achieve successful treatment of breast cancer. Methods: We characterized mammospheres derived from more than 40 cancer patients and two breast cancer cell lines for the expression of estrogen receptors (ERs) and stem cell markers. Mammosphere formation and proliferation assays were performed on cells from 19 cancer patients and five healthy individuals after incubation with ER-subtype selective ligands. Transcriptional analysis was performed to identify pathways activated in ERβ-stimulated mammospheres and verified using in vitro experiments. Xenograft models (n = 4 or 5 per group) were used to study the role of ERs during tumorigenesis. Results: We identified an absence of ERα but upregulation of ERβ in BSCs associated with phenotypic stem cell markers and responsible for the proliferative role of estrogens. Knockdown of ERβ caused a reduction of mammosphere formation in cell lines and in patient-derived cancer cells (40.7%, 26.8%, and 39.1%, respectively). Gene set enrichment analysis identified glycolysis-related pathways (false discovery rate < 0.001) upregulated in ERβ-activated mammospheres. We observed that tamoxifen or fulvestrant alone was insufficient to block proliferation of patient-derived BSCs while this could be accomplished by a selective inhibitor of ERβ (PHTPP; 53.7% in luminal and 45.5% in triple-negative breast cancers). Furthermore, PHTPP reduced tumor initiation in two patient-derived xenografts (75.9% and 59.1% reduction in tumor volume, respectively) and potentiated tamoxifen-mediated inhibition of tumor growth in MCF7 xenografts. Conclusion: We identify ERβ as a mediator of estrogen action in BSCs and a novel target for endocrine therapy.
Unitization and grouping mediate dissociations in memory for new

Quatre experiences visent a expliquer les aspects explicites et implicites de la memoire en terme de deux facteurs: l'unification (structuration en un tout coherent de plusieurs items separes) et le groupement (associations entre des representations separees). Elles mettent en œuvre les associations nouvelles par des mots et par leur utilisation dans des phrases et dans des histoires
How Automated Recommendations Affect the Playlist Creation Behavior of Users

Modern music platforms like Spotify support users to create new playlists through interactive tools. Given an empty or initial playlist, these tools often recommend additional songs, which could be included in the playlist based, e.g., on the title of the playlist or the set of tracks that are already in the playlist. In this work, we analyze in which ways the recommendations of such playlist construction support tools influence the behavior of users and the characteristics of the resulting playlists. We report the results of a between-subjects user study involving 123 subjects. Our analysis shows that users provided with recommendation support were more engaged and explored more alternatives than the control group. Presumably influenced by the recommender, they also picked significantly less popular items, which leads to a higher potential for discovery. The effort required to browse the additional alternatives, however, increased the users' perceived difficulty of the process.
Significance of preoperative butyrylcholinesterase level as an independent predictor of survival in patients with upper urinary tract urothelial carcinoma treated with nephroureterectomy

Objectives Butyrylcholinesterase (BChE) is an alpha-glycoprotein synthesized in the liver. Its serum levels are reportedly correlated with disease activity in patients with cancer. The aim of this study was to estimate the potential prognostic significance of preoperative serum BChE levels in patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Methods Of the 220 patients with UTUC who underwent RNU between 1995 and 2016 at Hirosaki University Hospital, 149 patients with available laboratory data were included for analysis. Covariates included age, sex, preoperative laboratory data, clinical T and N grades, tumor grade, tumor location and preoperative chemotherapy. Univariate and multivariate analyses were performed to identify clinical factors associated with overall survival (OS) and disease-free survival (DFS). Univariate analysis was performed using the Kaplan-Meier and log-rank methods, and the multivariate analysis was performed using a Cox proportional hazard model. Results The median BChE level was 276 U/l and the optimal cut-off point for the serum BChE level was determined to be 218 IU/ml. The 5-year OS and DFS rates were 81.0% and 73.7%, respectively. The 5-year OS and DFS rates were significantly greater in the BChE ≥ 218 than <218 U/l groups (86.6% vs. 53.7%, P < 0.001 and 76.4% vs. 58.3%, P = 0.049, respectively). In multivariate analysis, BChE levels were most significantly associated with OS, whereas BChE level and tumor grade were significantly associated with DFS. Conclusions This study validated preoperative serum BChE levels as an independent prognostic factor for UTUC after RNU.
Long-Term Outcomes of Patients with Stent Tips Embedded into Internal Carotid Artery Branches during Aneurysm Coiling

BACKGROUND AND PURPOSE: During stent-assisted coiling of ICA aneurysms, stent tips are sometimes unintentionally embedded into ICA branches. Stent tips can be visualized because they have radiopaque markers. Concerns regarding stent tip misplacement include risks of artery perforation and occlusion. The aim of this study was to evaluate the long-term outcomes of ICA branches with embedded stent tips. MATERIALS AND METHODS: ICA branches with embedded stent tips were identified among 35 patients with unruptured ICA aneurysms treated with stent-assisted coiling between November 2003 and November 2014. Patient clinical and angiographic outcomes associated with the embedded stent tip were analyzed. RESULTS: Most of the 35 studied aneurysms were paraclinoid ICA aneurysms (n = 30). The most commonly involved ICA branch was the posterior communicating artery (26 patients, 74.3%), followed by the anterior choroidal artery (8 patients, 22.9%) and ophthalmic artery (1 patient, 2.9%). During the follow-up period (38.6 ± 17.9 months), no new neurologic deficits developed. Neither hemorrhagic nor thromboembolic events occurred. Angiography was performed during the final follow-up evaluation at a mean of 32.7 ± 18.0 months, and all ICA branches with embedded stent tips showed patent blood flow without severe luminal narrowing. CONCLUSIONS: In our experience, placement of a stent tip into ICA branches during stent-assisted coiling was not associated with any major adverse events.
Concept-based document models using explicit semantic analysis

explicit semantic analysis (ESA) is a novel method that represents the meaning of texts in a high-dimensional space of concepts derived from Wikipedia. Several different ESA-based retrieval models have been proposed. However, these approaches depended on the performance of pseudo relevance feedback. In this paper, we propose a concept-based retrieval model under the language modeling framework. By means of concept mapping using explicit semantic analysis, the original documents are translated into conceptual representations, which are subsequently used to update the document models. The concept-based document model is evaluated on the TREe Ad Hoc Track (Disks 1, 2, and 3) collections. Experiment results show significant improvements with respect to the baseline models.
Time-Invariant Quasi-Cyclic Spatially Coupled LDPC Codes Based on Packings

This paper presents two packings derived from balanced incomplete block designs to construct quasi-cyclic spatially coupled LDPC convolutional codes (SC-LDPC-CCs). The construction gives time-invariant codes, since the sub-blocks corresponding to each time instant of the parity-check matrix are identical. Moreover, it provides flexible design rates and constraint lengths. Simulation results show that the proposed packing-based SC-LDPC-CCs outperform the existing time-invariant codes and perform closely to the time-varying protograph-based codes.
Early and long-term outcomes of mitral valve repair for Barlow's disease: a single-centre 16-year experience.

OBJECTIVES Following mitral valve repair for Barlow's disease, recurrent mitral regurgitation (MR) is believed to occur frequently and is mainly attributed to disease progression. METHODS Between January 2000 and December 2015, 180 patients (40% women, mean age 58.7 ± 13.5 years) with Barlow's disease underwent mitral valve repair. To provide a longitudinal assessment of mitral valve repair durability, a multistate model for interval-censored observations (4 states: 1, Grade 0/1+ MR; 2, Grade 2+ MR; 3, Grade 3+/4+ MR; 4, reintervention/death) was developed. The mechanism of recurrent MR was assessed echocardiographically. RESULTS Early mortality was 1.7%. After hospital discharge, 6 late reinterventions were performed. With death as a competing risk, the 10-year overall reintervention-free survival and reintervention rates were 79.8% (95% confidence interval 72.7-87.6%) and 4.5% (95% confidence interval 2.0-10.2%), respectively. Echocardiographic follow-up was available for 165 (93%) of hospital survivors with a total of 480 examinations. The incidence of both recurrent Grade 2+ and Grade 3+/4+ MR was relatively low up to 10 years after surgery. Grade 2+ MR did not always progress to higher regurgitation grade during the follow-up period. Grade 3+/4+ regurgitation was highly associated with valve-related morbidity and mortality. Recurrent MR (≥Grade 2+) was predominantly related to the technical aspects of valve repair. CONCLUSIONS Despite the complex valve abnormalities observed in patients with Barlow's disease, mitral valve repair can be performed with good early and late outcomes and low rates of recurrence of MR up to 10 years after surgery. Early and late valve repair durability is good and remains stable over time, suggesting that underlying disease progression has limited clinical significance.