Miracle-dz/UniFAR-FTUs huggingface dataset:
Fitts' law as a performance model in human-computer interaction

The theoretical basis for Fitts' law is developed and extended. Several modifications are claimed to improve the model's prediction power in general, and to extend its applicability to movement tasks common on today's interactive computer systems. Original contributions include (a) a correction to the model based on a direct analogy with Shannon's Theorem 17, (b) two methods for accommodating approach angle in the calculation of task difficulty, and (c) an extension of the model to dragging tasks and compound pointing-plus-dragging tasks. In a re-analysis of published data from experiments by Fitts' and others, the Shannon formulation is shown to provide higher correlations than the Fitts' or Welford formulation, particularly when task conditions extend under 3 bits. It is demonstrated that the Shannon formulation cannot yield a negative rating for task difficulty, unlike the Fitts or Welford formulation. Three experiments were conducted. In the first, the mouse, tablet-with-stylus, and trackball were tested on serial pointing and dragging tasks. Model comparisons provided moderate additional evidence of an improved fit using the Shannon formulation. Using the index of performance (in bits/s) as the criterion, the tablet-with-stylus and mouse performed similarly during the pointing tasks; but the tablet-with-stylus was slightly better than the mouse during dragging. The trackball was a poor performer for both tasks. In the second experiment, the mouse was used in a two-dimensional point-select task with rectangular targets. Two models performed significantly better than the status quo model--one substituting for target width the smaller of the target's width or height (the "smaller-of" model), the other substituting the span of the target along an approach vector through the target's centre (the W$\sp\prime$ model). In the third experiment, the mouse was tested in a point-drag-select task. Observations support the claim that Fitts' law can model both pointing and dragging operations, even when they occur as a point-select (button-down) action followed by a drag-select (button-up) action.
GRAPHS, ENTROPY AND GRID COMPUTING: AUTOMATIC COMPARISON OF MALWARE

Nowadays AV laboratories are saturated with huge collections of malware which are received daily. It’s a fact that the industry needs better methods to automatically identify, analyse and classify these volumes of samples. AV laboratories cannot continue working as they did years ago (or even months ago). In this paper we will describe an automated classifi cation system to identify fi les with similar internal structures. We will use graph theory as a way to identify similar functions among malware samples. This system helps to minimize human error and false positive detection. Previous research with graph theory has proven to be useful in fi nding similarities between malware variants [1], however these systems don’t have good performance. To solve the performance problem we will discuss some methods that can be used for this purpose: an algorithm (based on entropy and a custom checksum in order to group similar fi les) and a grid computing system [2].
Early T-BET Expression Ensures an Appropriate CD8+ Lineage–Specific Transcriptional Landscape after Influenza A Virus Infection

Key Points Early T-BET expression is important for early acquisition of CD8+ T cell lineage–specific function. T-BET expression shuts down inappropriate T cell lineage functions in activated CD8+ T cells. Early T-BET expression is required for activation of specific IFN-γ transcriptional enhancers. Virus infection triggers large-scale changes in the phenotype and function of naive CD8+ T cells, resulting in the generation of effector and memory T cells that are then critical for immune clearance. The T-BOX family of transcription factors (TFs) are known to play a key role in T cell differentiation, with mice deficient for the TF T-BET (encoded by Tbx21) unable to generate optimal virus-specific effector responses. Although the importance of T-BET in directing optimal virus-specific T cell responses is accepted, the precise timing and molecular mechanism of action remains unclear. Using a mouse model of influenza A virus infection, we demonstrate that although T-BET is not required for early CD8+ T cell activation and cellular division, it is essential for early acquisition of virus-specific CD8+ T cell function and sustained differentiation and expansion. Whole transcriptome analysis at this early time point showed that Tbx21 deficiency resulted in global dysregulation in early programming events with inappropriate lineage-specific signatures apparent with alterations in the potential TF binding landscape. Assessment of histone posttranslational modifications within the Ifng locus demonstrated that Tbx21−/− CD8+ T cells were unable to activate “poised” enhancer elements compared with wild-type CD8+ T cells, correlating with diminished Ifng transcription. In all, these data support a model whereby T-BET serves to promote appropriate chromatin remodeling at specific gene loci that underpins appropriate CD8+ T cell lineage–specific commitment and differentiation.
Efficacy, safety, and tolerability of bilateral transcranial direct current stimulation combined to a resistance training program in chronic stroke survivors: A double-blind, randomized, placebo-controlled pilot study.

BACKGROUND Transcranial direct current stimulation (tDCS) is a promising tool for stroke rehabilitation. Yet, so far, results from the available clinical trials are inconclusive. OBJECTIVES The primary objective of the present work was to test the efficacy of multiple sessions of tDCS combined with a highly standardized and progressive resistance training program of the affected upper limb in individuals in the chronic phase of recovery after a stroke. Secondary objectives were to test the safety and tolerability of these combined interventions. METHODS This two-arm parallel pilot trial recruited participants that were ≥18 years old, community-dwelling, and had sustained a supratentorial stroke ≥6 months prior to the study. They were allocated using a stratified randomization into two groups: 1) real tDCS + resistance training and 2) sham tDCS + resistance training. The resistance training program targeted the affected upper limb and consisted in 60 minutes of exercises, 3 times/week over 4 weeks. During each session, participants received either real- or sham-tDCS, using a bi-hemispheric montage for the first 20 minutes, and were blinded to the tDCS intervention. Outcome measures of clinical efficacy (Fugl-Meyer Assessment, Box and Block Test, Wolf Motor Function Test, grip strength, modified Ashworth scale and Motor Activity Log) were assessed by a blinded evaluator before and after the 4-week training program. Safety and tolerability were evaluated, respectively, by the number and characteristics of tDCS adverse events and dropout rates with their reasons. RESULTS From the 147 individuals screened for eligibility, 14 participants (68.9±10.0 years old; 70.9±57.6 months post-stroke) met the selection criteria and were allocated to real-tDCS (n = 7) or sham-tDCS (n = 7) groups. Both groups improved on the clinical outcome measures, but these changes were not significantly different between groups (p > 0.17). No dropout occurred throughout the study. Participants frequently reported mild skin tingling during the administration of both real- and sham-tDCS, and no group difference was noted for its frequency and intensity (p > 0.38). One participant having received real-tDCS complained about a mild skin burning sensation after two sessions. The a priori sample size analysis performed on the Fugl-Meyer Assessment scores revealed that 56 participants would be required in a future clinical trial to reach 80% power at a significance level of 0.05. CONCLUSIONS In this pilot study, repeated sessions of bi-hemispheric tDCS coupled with resistance training were found safe and tolerable for individuals at the chronic phase post-stroke. However, the use of tDCS did not result in additional sensorimotor improvements when compared to sham-tDCS. Further research is needed to better assess the clinical benefits of combining non-invasive transcranial stimulation with rehabilitation after a stroke.
A Quantitative HILIC–MS/MS Assay of the Metabolic Response of Huh-7 Cells Exposed to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin

A hydrophilic interaction liquid chromatography (HILIC)–ultra high-pressure liquid chromatography (UHPLC) coupled with tandem mass spectrometry (MS/MS) method was developed and applied to profile metabolite changes in human Huh-7 cells exposed to the potent aryl hydrocarbon receptor (AHR) ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Comparisons of sensitivity (limit of detection as low as 0.01 µM) and reproducibility (84% of compounds had an interday relative standard deviation (RSD) less than 10.0%; 83% of compounds had an intraday RSD less than 15.0%) were assessed for all the metabolites. The exposure of Huh-7 cells to the hepatotoxic carcinogen TCDD at low doses (1 nM and 10 nM for 4 h and 24 h, respectively) was reflected by the disturbance of amino acid metabolism, energy metabolism (glycolysis, TCA cycle), and nucleic acid metabolism. TCDD caused a significant decrease in amino acids such as serine, alanine, and proline while promoting an increase in arginine levels with 24 h treatment. Energy metabolism intermediates such as phosphoenolpyruvate and acetyl–CoA and nucleosides such as UMP, XMP, and CMP were also markedly decreased. These results support the application of HILIC–UHPLC–MS/MS for robust and reliable analysis of the cellular response to environmentally relevant toxicants at lower doses.
DPPA2/4 and SUMO E3 ligase PIAS4 opposingly regulate zygotic transcriptional program

The molecular mechanism controlling the zygotic genome activation (ZGA) in mammals remains poorly understood. The 2-cell (2C)-like cells spontaneously emerging from cultures of mouse embryonic stem cells (ESCs) share some key transcriptional and epigenetic programs with 2C-stage embryos. By studying the transition of ESCs into 2C-like cells, we identified developmental pluripotency associated 2 and 4 (Dppa2/4) as important regulators controlling zygotic transcriptional program through directly up-regulating the expression of double homeobox (Dux). In addition, we found that DPPA2 protein is sumoylated and its activity is negatively regulated by small ubiquitin-like modifier (Sumo) E3 ligase protein inhibitor of activated STAT 4 (PIAS4). PIAS4 is down-regulated during ZGA process and during transitioning of ESCs into 2C-like cells. Depleting Pias4 or overexpressing Dppa2/4 is sufficient to activate 2C-like transcriptional program, whereas depleting Dppa2/4 or forced expression of Pias4 or Sumo2–Dppa2 inhibits 2C-like transcriptional program. Furthermore, ectopic expression of Pias4 or Sumo2–Dppa2 impairs early mouse embryo development. In summary, our study identifies key molecular rivals consisting of transcription factors and a Sumo2 E3 ligase that regulate zygotic transcriptional program upstream of Dux.
The YIN and YANG of lipoproteins in developing and preventing infectious arthritis by Staphylococcus aureus

Rapid bone destruction often leads to permanent joint dysfunction in patients with septic arthritis, which is mainly caused by Staphylococcus aureus (S. aureus). Staphylococcal cell wall components are known to induce joint inflammation and bone destruction. Here, we show that a single intra-articular injection of S. aureus lipoproteins (Lpps) into mouse knee joints induced chronic destructive macroscopic arthritis through TLR2. Arthritis was characterized by rapid infiltration of neutrophils and monocytes. The arthritogenic effect was mediated mainly by macrophages/monocytes and partially via TNF-α but not by neutrophils. Surprisingly, a S. aureus mutant lacking Lpp diacylglyceryl transferase (lgt) caused more severe joint inflammation, which coincided with higher bacterial loads of the lgt mutant in local joints than those of its parental strain. Coinjection of pathogenic S. aureus LS-1 with staphylococcal Lpps into mouse knee joints caused improved bacterial elimination and diminished bone erosion. The protective effect of the Lpps was mediated by their lipid moiety and was fully dependent on TLR2 and neutrophils. The blocking of CXCR2 on neutrophils resulted in total abrogation of the protective effect of the Lpps. Our data demonstrate that S. aureus Lpps elicit innate immune responses, resulting in a double-edged effect. On the one hand, staphylococcal Lpps boost septic arthritis. On the other hand, Lpps act as adjuvants and activate innate immunity, which could be useful for combating infections with multiple drug-resistant strains.
From Webometrics to Altmetrics: One and a Half Decades of Digital Research at Wolverhampton

This article describes and summarises the contributions of the Statistical Cybermetrics Research Group (SCRG) at the University of Wolverhampton in the UK to the information science specialisms of Webometrics and altmetrics. In both cases the group created free computer programs for data gathering and analysis. In Webometrics the SCRG developed counting methods for hyperlink analysis and assessed them for collections of different types of website. In addition, it also developed methods for automatically gathering and analysing text on a large scale, both for web citation analysis and for more general social science purposes. It also developed two Webometric theories. In altmetrics, the SCRG analysed the validity of a range of indicators, including counts of tweets and Mendeley readers for academic articles, finding evidence that they associated with citation counts and hence that they had value as altmetrics. The dual purposes of this paper are to give an overview of a range of methods and free tools for Webometrics and altmetrics, and to give a historical overview of the evolution of one information science research group in the hope that others can learn from its successes and failures. Keywords : altmetrics, webometrics, scientometrics.
Structural basis of specific DNA binding by the transcription factor ZBTB24

Abstract ZBTB24, encoding a protein of the ZBTB family of transcriptional regulators, is one of four known genes—the other three being DNMT3B, CDCA7 and HELLS—that are mutated in immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome, a genetic disorder characterized by DNA hypomethylation and antibody deficiency. The molecular mechanisms by which ZBTB24 regulates gene expression and the biological functions of ZBTB24 are poorly understood. Here, we identified a 12-bp consensus sequence [CT(G/T)CCAGGACCT] occupied by ZBTB24 in the mouse genome. The sequence is present at multiple loci, including the Cdca7 promoter region, and ZBTB24 binding is mostly associated with gene activation. Crystallography and DNA-binding data revealed that the last four of the eight zinc fingers (ZFs) (i.e. ZF5-8) in ZBTB24 confer specificity of DNA binding. Two ICF missense mutations have been identified in the ZBTB24 ZF domain, which alter zinc-binding cysteine residues. We demonstrated that the corresponding C382Y and C407G mutations in mouse ZBTB24 abolish specific DNA binding and fail to induce Cdca7 expression. Our analyses indicate and suggest a structural basis for the sequence specific recognition by a transcription factor centrally important for the pathogenesis of ICF syndrome.
Nucleotide excision repair of abasic DNA lesions

Abstract Apurinic/apyrimidinic (AP) sites are a class of highly mutagenic and toxic DNA lesions arising in the genome from a number of exogenous and endogenous sources. Repair of AP lesions takes place predominantly by the base excision pathway (BER). However, among chemically heterogeneous AP lesions formed in DNA, some are resistant to the endonuclease APE1 and thus refractory to BER. Here, we employed two types of reporter constructs accommodating synthetic APE1-resistant AP lesions to investigate the auxiliary repair mechanisms in human cells. By combined analyses of recovery of the transcription rate and suppression of transcriptional mutagenesis at specifically positioned AP lesions, we demonstrate that nucleotide excision repair pathway (NER) efficiently removes BER-resistant AP lesions and significantly enhances the repair of APE1-sensitive ones. Our results further indicate that core NER components XPA and XPF are equally required and that both global genome (GG-NER) and transcription coupled (TC-NER) subpathways contribute to the repair.
Piezoelectric Response in Hybrid Micropillar Arrays of Poly(Vinylidene Fluoride) and Reduced Graphene Oxide

This study was dedicated to the investigation of poly(vinylidene fluoride) (PVDF) micropillar arrays obtained by soft lithography followed by phase inversion at a low temperature. Reduced graphene oxide (rGO) was incorporated into the PVDF as a nucleating filler. The piezoelectric properties of the PVDF-rGO composite micropillars were explored via piezo-response force microscopy (PFM). Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) showed that α, β, and γ phases co-existed in all studied samples, with a predominance of the γ phase. The piezoresponse force microscopy (PFM) data provided the local piezoelectric response of the PVDF micropillars, which exhibited a temperature-induced downward dipole orientation in the pristine PVDF micropillars. The addition of rGO into the PVDF matrix resulted in a change in the preferred polarization direction, and the piezo-response phase angle changed from −120° to 20°–40°. The pristine PVDF and PVDF loaded with 0.1 wt % of rGO after low-temperature quenching were found to possess a piezoelectric response of 86 and 87 pm/V respectively, which are significantly higher than the |d33eff| in the case of imprinted PVDF 64 pm/V. Thus, the addition of rGO significantly affected the domain orientation (polarization) while quenching increased the piezoelectric response.
Cohort study on the effects of depression on atherosclerotic cardiovascular disease risk in Korea

Objectives Depression has been reported to be a risk factor of cardiovascular disease in the western world, but the association has not yet been studied among Asian populations. The aim of this study was to investigate whether depression increases the risk of developing atherosclerotic cardiovascular disease (ASCVD) in a large Korean cohort study. Design Population based cohort study. Setting Database of National Health Insurance System, Republic of Korea. Participants 481 355 Koreans (260 695 men and 220 660 women) aged 40–80 years who had a biennial health check-up between 2002 and 2005. Main outcome measure The main outcome in this study was the first ASCVD event (hospital admission or death). Results Depression increased the risk of developing ASCVD by 41% for men and 48% for women. In men, 3–4 outpatient visits for depression increased the risk of angina pectoris by 2.12 times (95% CI 1.55 to 2.90) and acute myocardial infarction by 2.29 times (95% CI 1.33 to 3.95). Depression was also associated with stroke in men (HR 1.29, 95% CI 1.19 to 1.39) and in women (HR 1.37, 95% CI 1.29 to 1.46). However, no increased risk of ASCVD was found for men who received 10 or more depressive treatments, compared with those without any outpatient visit for depression. Conclusions In this cohort, depressed people were at increased risk of ASCVD incidence. Therefore, individuals with depression may need routine monitoring of heart health that may prevent their future CVD risk.
TOWARDS A MULTIMEDIA SIMULATION FOR INTERPROFESSIONAL LEARNING: USING ACTIVITY THEORY TO INFORM DESIGN

This thesis reports on a pilot case study that used activity theory in a pre-experimental phase of design-based research. The purpose of this study was to inform the initial design of a multimedia simulation for interprofessional education in the field of health and social care. Five subjects from five different health science disciplines participated in an observational study. Data collection focused on interactions between participants over three problem-based learning (PBL) sessions. Modified grounded theory coding techniques were applied within an activity theory analytic framework to illuminate structural tensions in PBL activity. Interviews with six participants were used to illuminate and corroborate findings. The results suggest three sets of structural tensions that affected interprofessional learning. These tensions suggest opportunities for instructional design improvement in which multimedia simulation could play a key supportive role. Simulation-based design alternatives are presented to resolve these tensions and to suggest new approaches to facilitating interprofessional learning.
Development, Testing and Results of a Patient Medication Experience Documentation Tool for Use in Comprehensive Medication Management Services

The medication experience is an individual’s subjective experience of taking a medication in daily life and can be at the root of drug therapy problems. It is recommended that the patient-centered approach to comprehensive medication management (CMM) starts with an understanding of the patient’s medication experience. This study aims to develop a medication experience documentation tool for use in CMM services, and to understand the usefulness and challenges of using the tool in practice. The tool was developed based on previous research on patients’ medication experiences. It was tested in two rounds by ten CMM pharmacists utilizing the tool as they provided care to patients. Focus groups were conducted to revise the tool after each round and to understand pharmacists’ experiences. The tool was tested for 15 weeks in 407 patient encounters. There was at least one medication experience documented in the electronic medical record 62% of the time. Pharmacists found the tool helpful in raising awareness of the medication experience and motivational interviewing strategies, planning for follow-up visits, as a teaching tool, and making pharmacists realize the fluidity of the medication experience. The tool offered pharmacists a better way to recognize and address medication experiences affecting medication taking behaviors.
Transmission of disorder and etiological information: Effects on health knowledge recollection and health-related cognition

Biased transmission of health knowledge has far-reaching effects on information reproduction and health-related cognitions. We examined whether transmissions of different types of disorder and etiological information influence recollections of health knowledge and evaluations of patients, by simulating the digital transmission of information. Transmission chains of four non-interacting persons (i.e., four generations) were formed. The first generation read three vignettes describing fictitious patients with one of three disorders (physiological, psychological, culture-bound) uniquely paired with one of three etiologies (genetic, environmental, unknown etiology). Next, they evaluated patients’ well-being, rated desired social distance, and recalled the vignettes. These written recollections replaced the original vignettes for a second-generation of participants, whose recollections were used for the third generation and so on. The framing of disorders affected recollections of etiology, in which culture-bound framings resulted in the poorest recall of etiologies. Participants also perceived the culture-bound disorder as the least serious but desired the most social distance from patients diagnosed with it, when compared to other disorders. The study showed that health information is selectively attended to and reproduced, possibly affected by perceived self-relevance. Faulty recollections and framing of disorders affect health cognitions, potentially instigating biased transmission of disorder- and patient-related narratives.