Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative analysis of various modularization algorithms and species specific study of VEGF signaling pathways

In biology, signal transduction refers to a process by which a cell converts one kind of signal or stimulus into another. It involves ordered sequences of biochemical reactions inside the cell. These cascades of reactions are carried out by enzymes and activated by second messengers. Signal transduction pathways are complex in nature. Each pathway is responsible for tuning one or more biological functions in the intracellular environment as well as more than one pathway interact among themselves to carry forward a single biological function. Such kind of behavior of these pathways makes understanding difficult. Hence, for the sake of simplicity, they need to be partitioned into smaller modules and then analyzed. We took VEGF signaling pathway, which is responsible for angiogenesis for this kind of modularized study. Modules were obtained by applying the algorithm of Nayak and De (Nayak and De, 2007) for different complexity values. These sets of modules were compared among themselves to get the best set of modules for an optimal complexity value. The best set of modules compared with four different partitioning algorithms namely, Farhat’s (Farhat, 1998), Greedy (Chartrand and Oellermann, 1993), Kernighan-Lin’s (Kernighan and Lin, 1970) and Newman’s community finding algorithm (Newman, 2006). These comparisons enabled us to decide which of the aforementioned algorithms was the best one to create partitions from human VEGF signaling pathway. The optimal complexity value, on which the best set of modules was obtained, was used to get modules from different species for comparative study. Comparison among these modules would shed light on the trend of development of VEGF signaling pathway over these species.
Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium

Background Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality. Methods In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488. Findings We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and <30 nmol/L were 1.15 (1.00–1.29), 1.33 (1.16–1.51), and 1.67 (1.44–1.89), respectively. We observed similar results for cardiovascular mortality, but there was no significant linear association between 25(OH)D and cancer mortality. There was also no significantly increased mortality risk at high 25(OH)D levels up to 125 nmol/L. Interpretation In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths.
Conversion of a capture ELISA to a Luminex xMAP assay using a multiplex antibody screening method.

The enzyme-linked immunosorbent assay (ELISA) has long been the primary tool for detection of analytes of interest in biological samples for both life science research and clinical diagnostics. However, ELISA has limitations. It is typically performed in a 96-well microplate, and the wells are coated with capture antibody, requiring a relatively large amount of sample to capture an antigen of interest . The large surface area of the wells and the hydrophobic binding of capture antibody can also lead to non-specific binding and increased background. Additionally, most ELISAs rely upon enzyme-mediated amplification of signal in order to achieve reasonable sensitivity. Such amplification is not always linear and can thus skew results. In the past 15 years, a new technology has emerged that offers the benefits of the ELISA, but also enables higher throughput, increased flexibility, reduced sample volume, and lower cost, with a similar workflow (1, 2). Luminex xMAP Technology is a microsphere (bead) array platform enabling both monoplex and multiplex assays that can be applied to both protein and nucleic acid applications (3-5). The beads have the capture antibody covalently immobilized on a smaller surface area, requiring less capture antibody and smaller sample volumes, compared to ELISA, and non-specific binding is significantly reduced. Smaller sample volumes are important when working with limiting samples such as cerebrospinal fluid, synovial fluid, etc. (6). Multiplexing the assay further reduces sample volume requirements, enabling multiple results from a single sample. Recent improvements by Luminex include: the new MAGPIX system, a smaller, less expensive, easier-to-use analyzer; Low-Concentration Magnetic MagPlex Microspheres which eliminate the need for expensive filter plates and come in a working concentration better suited for assay development and low-throughput applications; and the xMAP Antibody Coupling (AbC) Kit, which includes a protocol, reagents, and consumables necessary for coupling beads to the capture antibody of interest. (See Materials section for a detailed list of kit contents.) In this experiment, we convert a pre-optimized ELISA assay for TNF-alpha cytokine to the xMAP platform and compare the performance of the two methods (7-11). TNF-alpha is a biomarker used in the measurement of inflammatory responses in patients with autoimmune disorders. We begin by coupling four candidate capture antibodies to four different microsphere sets or regions. When mixed together, these four sets allow for the simultaneous testing of all four candidates with four separate detection antibodies to determine the best antibody pair, saving reagents, sample and time. Two xMAP assays are then constructed with the two most optimal antibody pairs and their performance is compared to that of the original ELISA assay in regards to signal strength, dynamic range, and sensitivity.
Adolescent Resting State Networks and Their Associations with Schizotypal Trait Expression

The rising interest in temporally coherent brain networks during baseline adult cerebral activity finds convergent evidence for an identifiable set of resting state networks (RSNs). To date, little is know concerning the earlier developmental stages of functional connectivity in RSNs. This study's main objective is to characterize the RSNs in a sample of adolescents. We further examine our data from a developmental psychopathology perspective of psychosis-proneness, by testing the hypothesis that early schizotypal symptoms are linked to disconnection in RSNs. In this perspective, this study examines the expression of adolescent schizotypal traits and their potential associations to dysfunctional RSNs. Thirty-nine adolescents aged between 12 and 20 years old underwent an 8-min functional magnetic resonance imaging (fMRI) “resting state” session. In order to explore schizotypal trait manifestations, the entire population was assessed by the Schizotypal Personality Questionnaire (SPQ). After conventional processing of the fMRI data, we applied group-level independent component analysis (ICA). Twenty ICA maps and associated time courses were obtained, among which there were RSNs that are consistent with findings in the literature. We applied a regression analysis at group level between the energy of RSN-associated time courses in different temporal frequency bins and the clinical measures (3 in total). Our results highlight the engagement of six relevant RSNs; (1) a default-mode network (DMN); (2) a dorso-lateral attention network; (3) a visual network (VN); (4) an auditory network (AN); (5) a sensory motor network (SMN); (6) a self-referential network (SRN). The regression analysis reveals a statistically significant correlation between the clinical measures and some of the RSNs, specifically the visual and the AN. In particular, a positive correlation is obtained for the VN in the low frequency range (0.05 Hz) with SPQ measures, while the AN correlates negatively in the high frequency range (0.16–0.19 Hz). Trend-like significance for the SRN may hint to its implication in disorganized thoughts and behaviors during adolescence. Unlike DMN activity in schizophrenic patients, adolescent DMN was unrelated to schizotypal trait expression. This suggests that relationships between the DMN and schizotypy may be modified in later developmental stages of both functional connectivity and psychotic expression. These results are discussed in light of RSNs literature involving children, adults, and individuals with schizophrenia.
Egocentric Mapping of Body Surface Constraints

The relative location of human body parts often materializes the semantics of on-going actions, intentions and even emotions expressed, or performed, by a human being. However, traditional methods of performance animation fail to correctly and automatically map the semantics of performer postures involving self-body contacts onto characters with different sizes and proportions. Our method proposes an egocentric normalization of the body-part relative distances to preserve the consistency of self contacts for a large variety of human-like target characters. Egocentric coordinates are character independent and encode the whole posture space, i.e., it ensures the continuity of the motion with and without self-contacts. We can transfer classes of complex postures involving multiple interacting limb segments by preserving their spatial order without depending on temporal coherence. The mapping process exploits a low-cost constraint relaxation technique relying on analytic inverse kinematics; thus, we can achieve online performance animation. We demonstrate our approach on a variety of characters and compare it with the state of the art in online retargeting with a user study. Overall, our method performs better than the state of the art, especially when the proportions of the animated character deviate from those of the performer.
Driving and dementia: a clinician's guide

With an ageing population and more drivers on the road, the number of drivers with dementia is due to grow exponentially over the next 50 years. Although decisions regarding possession of a driving licence in the UK are made by the Driver and Vehicle Licensing Agency (DVLA), psychiatrists have a duty to advise patients who are unfit to drive to cease driving and to inform the DVLA of patients who pose a risk to the public by continuing to drive when advised not to. This article offers a review of the literature on dementia and driving and summarises the evidence and advice for navigating this minefield. The use of psychological test batteries in clinical practice is discussed, along with the most useful questions to ask in memory clinics. Legal guidance for various countries is considered, as is the important (but often overlooked) issue of helping older people prepare for retirement from driving.
The Biggs And Moore Model In E-Learning: The Role Of Motivation And Collaboration As Moderators

The purpose of this paper is to report the findings of a research conducted to evaluate the effect of e-learning experience on students’ perceived learning outcomes, and more specifically the role of motivation and collaboration as moderators between the elearning experience and the learning outcome. The perceived learning outcome was measured with whether the students perceived to learn more in e-learning vis-a-vis traditional learning context. The participants came from an undergraduate course at Tamk University of Applied Sciences in Tampere, Finland. The Biggs and Moore learning model indicates that the process variables (motivation and collaboration in this study) have a mediating role. It was found out in this study, however, that these process variables have a moderating role rather than mediating role. Specific recommendations for the practitioners are provided, and implications for educators are discussed. Finally suggestions for further research on e-learning are provided.
Explaining Choice Behavior: The Intentional Selection Assumption

How do people decide between several options presented to them? Normative accounts suggest the utilities of options are fixed, but subjective accounts suggest utilities depend on context. In the current paper, we propose a novel model of choice that may help reconcile these accounts. We propose that choice behavior may depend on an “Intentional Selection Assumption”: when people are presented with multiple options, they assume the options were intentionally selected by a person with specific questions in mind. Inferences about the intentional selection of options inform the chooser about the features that are intended to be most relevant. In this way, context can affect the desirability of a particular option, without requiring shifting utilities over features. Two behavioral experiments support the claim that participants are sensitive to intentional selection. We discuss the importance of taking choosers’ assumptions about intentional selection into account in future investigations of choice behavior.
The Role of Titanium Surface Microtopography on Adhesion, Proliferation, Transformation, and Matrix Deposition of Corneal Cells.

PURPOSE Titanium (Ti) is an excellent implantable biomaterial that can be further enhanced by surface topography optimization. Despite numerous data from orthopedics and dentistry, the effect of Ti surface topography on ocular cells is still poorly understood. In light of the recent adaptation of Ti in the Boston Keratoprosthesis artificial cornea, we attempted to perform an extended evaluation of the effect of Ti surface topography on corneal cell adhesion, proliferation, cytotoxicity, transformation, and matrix deposition. METHODS Different surface topographies were generated on medical grade Ti-6Al-4V-ELI (extra-low interstitial), with linearly increased roughness (polished to grit blasted). Biological response was evaluated in vitro using human corneal limbal epithelial (HCLE) cells, stromal fibroblasts (HCF), and endothelial cells (HCEnC). RESULTS None of the Ti surface topographies caused cytotoxicity to any of the three corneal cell types. However, rough Ti surface inhibited HCLE and HCF cell adhesion and proliferation, while HCEnC proliferation was unaffected. Long-term experiments with HCF revealed that rough Ti surface with R(a) (the arithmetic average of the profile height from the mean line) ≥ 1.15 μm suppressed HCF focal adhesion kinase phosphorylation, changed fibroblast morphology, and caused less aligned and reduced deposition of collagen matrix as compared to smooth Ti (R(a) ≤ 0.08 μm). In the presence of transforming growth factor β1 (TGFβ1) stimulation, rough Ti inhibited alpha-smooth muscle actin (α-SMA) expression and collagen deposition, leading to decreased myofibroblast transformation and disorganization of the collagen fibrils as compared to smooth Ti. CONCLUSIONS This study suggests that Ti surface topography regulates corneal cell behavior in a tissue-dependent manner that varies across the corneal strata. Contrary to the accepted paradigm, smooth surface topography can enhance cell adhesion and proliferation and increase matrix deposition by corneal cells.
The Microbiota of Breast Tissue and Its Association with Breast Cancer

ABSTRACT In the United States, 1 in 8 women will be diagnosed with breast cancer in her lifetime. Along with genetics, the environment contributes to disease development, but what these exact environmental factors are remains unknown. We have previously shown that breast tissue is not sterile but contains a diverse population of bacteria. We thus believe that the host's local microbiome could be modulating the risk of breast cancer development. Using 16S rRNA amplicon sequencing, we show that bacterial profiles differ between normal adjacent tissue from women with breast cancer and tissue from healthy controls. Women with breast cancer had higher relative abundances of Bacillus, Enterobacteriaceae and Staphylococcus. Escherichia coli (a member of the Enterobacteriaceae family) and Staphylococcus epidermidis, isolated from breast cancer patients, were shown to induce DNA double-stranded breaks in HeLa cells using the histone-2AX (H2AX) phosphorylation (γ-H2AX) assay. We also found that microbial profiles are similar between normal adjacent tissue and tissue sampled directly from the tumor. This study raises important questions as to what role the breast microbiome plays in disease development or progression and how we can manipulate this for possible therapeutics or prevention. IMPORTANCE This study shows that different bacterial profiles in breast tissue exist between healthy women and those with breast cancer. Higher relative abundances of bacteria that had the ability to cause DNA damage in vitro were detected in breast cancer patients, as was a decrease in some lactic acid bacteria, known for their beneficial health effects, including anticarcinogenic properties. This study raises important questions as to the role of the mammary microbiome in modulating the risk of breast cancer development.
Parental Socioeconomic Status, Childhood Asthma and Medication Use – A Population-Based Study

Background Little is known about how parental socioeconomic status affects offspring asthma risk in the general population, or its relation to healthcare and medication use among diagnosed children. Methods This register-based cohort study included 211,520 children born between April 2006 and December 2008 followed until December 2010. Asthma diagnoses were retrieved from the National Patient Register, and dispensed asthma medications from the Prescribed Drug Register. Parental socioeconomic status (income and education) were retrieved from Statistics Sweden. The associations between parental socioeconomic status and outcomes were estimated by Cox proportional hazard regression. Results Compared to the highest parental income level, children exposed to all other levels had increased risk of asthma during their first year of life (e.g. hazard ratio, HR 1.19, 95% confidence interval, CI 1.09–1.31 for diagnosis and HR 1.17, 95% CI 1.08–1.26 for medications for the lowest quintile) and the risk was decreased after the first year, especially among children from the lowest parental income quintile (HR 0.84, 95% CI 0.77–0.92 for diagnosis, and HR 0.80, 95% CI 0.74–0.86 for medications). Further, compared to children with college-educated parents, those whose parents had lower education had increased risk of childhood asthma regardless of age. Children with the lowest parental education had increased risk of an inpatient (HR 2.07, 95% CI 1.61–2.65) and outpatient (HR 1.32, 95% CI 1.18–1.47) asthma diagnosis. Among diagnosed children, those from families with lower education used fewer controller medications than those whose parents were college graduates. Conclusions Our findings indicate an age-varying association between parental income and childhood asthma and consistent inverse association regardless of age between parental education and asthma incidence, dispensed controller medications and inpatient care which should be further investigated and remedied.
Evaluation of Environmental Factors to Fatigue Performance of Asphalt Mixes

This paper studies the effect of different environmental factors, including the axle load weight, environmental temperature, vehicle speed, and the aging level of asphalt, on the fatigue performance of asphalt mixes based on four-point bending beam fatigue tests. A fractional factorial design method named ”uniform design” was applied in experimental design. The relations of the environmental factors to initial stiffness, fatigue life, phase angle and cumulative dissipated energy were established with the general linear modeling method. It is found that there exists very good correlativity between the environmental factors and the fatigue performance indices of asphalt mixes. The coefficients of total correlation are mainly beyond 0.95. The results indicate that the consideration of the effect of environmental factors is necessary in the fatigue performance evaluation on real asphalt pavement.
RNA unwinding by the Trf4/Air2/Mtr4 polyadenylation (TRAMP) complex

Many RNA-processing events in the cell nucleus involve the Trf4/Air2/Mtr4 polyadenylation (TRAMP) complex, which contains the poly(A) polymerase Trf4p, the Zn-knuckle protein Air2p, and the RNA helicase Mtr4p. TRAMP polyadenylates RNAs designated for processing by the nuclear exosome. In addition, TRAMP functions as an exosome cofactor during RNA degradation, and it has been speculated that this role involves disruption of RNA secondary structure. However, it is unknown whether TRAMP displays RNA unwinding activity. It is also not clear how unwinding would be coordinated with polyadenylation and the function of the RNA helicase Mtr4p in modulating poly(A) addition. Here, we show that TRAMP robustly unwinds RNA duplexes. The unwinding activity of Mtr4p is significantly stimulated by Trf4p/Air2p, but the stimulation of Mtr4p does not depend on ongoing polyadenylation. Nonetheless, polyadenylation enables TRAMP to unwind RNA substrates that it otherwise cannot separate. Moreover, TRAMP displays optimal unwinding activity on substrates with a minimal Mtr4p binding site comprised of adenylates. Our results suggest a model for coordination between unwinding and polyadenylation activities by TRAMP that reveals remarkable synergy between helicase and poly(A) polymerase.
A Web Service for Managing Spatial Context Dedicated to Serious Games on and for Smartphones

The GeoEduc3D project aims to provide educational games for smartphones based on Geomatics and use augmented reality techniques in order to make these games more immersive. To improve the immersive and interactive aspects of those games, we focused on the exploitation of spatial context in this particular application framework (serious games, augmented reality, smart phones, and multi-users environment). Our work has thus led to the design of a solution dedicated to the management of spatial context in a multi-players environment on and for smartphones. Several contributions have been made: modeling spatial context, proposing a service-oriented architecture to manage this context, defining a Web Service Spatial Context (WSCS) and implementation of a WSCS prototype and a mobile client according to an environment exploiting FourSquare, a geo-social application.