Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutation-selection models of coding sequence evolution with site-heterogeneous amino acid fitness profiles

Modeling the interplay between mutation and selection at the molecular level is key to evolutionary studies. To this end, codon-based evolutionary models have been proposed as pertinent means of studying long-range evolutionary patterns and are widely used. However, these approaches have not yet consolidated results from amino acid level phylogenetic studies showing that selection acting on proteins displays strong site-specific effects, which translate into heterogeneous amino acid propensities across the columns of alignments; related codon-level studies have instead focused on either modeling a single selective context for all codon columns, or a separate selective context for each codon column, with the former strategy deemed too simplistic and the latter deemed overparameterized. Here, we integrate recent developments in nonparametric statistical approaches to propose a probabilistic model that accounts for the heterogeneity of amino acid fitness profiles across the coding positions of a gene. We apply the model to a dozen real protein-coding gene alignments and find it to produce biologically plausible inferences, for instance, as pertaining to site-specific amino acid constraints, as well as distributions of scaled selection coefficients. In their account of mutational features as well as the heterogeneous regimes of selection at the amino acid level, the modeling approaches studied here can form a backdrop for several extensions, accounting for other selective features, for variable population size, or for subtleties of mutational features, all with parameterizations couched within population-genetic theory.
Le concept de Business Model au travers de la littérature

The concept of "Business Model" emerged from the mid 90s with the rise of eCommerce and more generally of the "new economy". The mutations responsible of its development are technological, economic and regulatory. Then, the concept of business model was built by successive additions and sedimentation of many papers, reports and books that came to define its meaning over time. In addition to its ability to explain why some firms perform better than others, this concept opens up many ways and applications for entrepreneurship research.
A five-stage process for the development and validation of a systematic observation instrument

The primary purpose of this study was to develop and validate a System for Observing the Teaching of Games in Physical Education (SOTG-PE). Primary pilot testing of the SOTG-PE was conducted in a large, selective, all-boys secondary school in the north-west of England. Two hundred and eighty three pupils aged 11–16 volunteered as participants for the pilot testing phase of this study. The SOTG-PE coded 1379 minutes of physical education games lessons across three games categories, including invasion, net/wall and striking and fielding. In addition, the teaching interactions of four full-time teachers of physical education and one pre-service teacher were also coded. The inter-observer and intra-observer mean re-test coefficients suggest that the SOTG-PE is valid for evaluating and recording child activity, lesson context and teacher interactions during various physical education games lessons in the UK.
Representations of Streetscape Perceptions Through Manifold Learning in the Space of Hough Arrays

This study is part of a project which investigates computational principles which underlie perception and representation of architectural streetscape character. Some of the principles can be associated with fundamental concepts in brain theory and Gestalt psychology. For the experimental analysis streetscapes were represented by sequences of digital images of house facades which were prepared by a team of researchers from architecture. Two methods for non-linear dimensionality reduction, isomap and maximum variance unfolding, were applied to a set of Hough arrays (for lines) of the given images. An analysis of the extracted "streetmanifolds" revealed groupings of house facades with similar visual character and proportions. Comparative tests were conducted on a simple cylinder shaped example manifold to evaluate the geometric stability of the two dimensionality reduction methods. All experiments addressed variations of the distance metric and the neighbourhood parameter
Can Good Concept Mappers be Good Problem Solvers in Science

Abstract Problem solving is an enduring issue in science education, ostensibly because science in itself, is basically concerned with problem solving‐‐exploring the universe and seeking answers to intriguing phenomena in nature. Remarkable strides have been made in psychology about recording the minutiae of problem solving as a cognitive process. Concept mapping, a meta‐learning tool, is appearing on the scene as a potential pathway for promoting the acquisition of problem‐solving skills. Drawing 40 subjects from a pool of students who experienced cooperative and individualistic concept‐mapping experiences for six months and adjudged to be good concept mappers, this study found the concept‐mapping group to be significantly more successful in solving three biological problems than 20 subjects who served as control. Written and think‐aloud procedures and interviews were conducted as part of the administration of the Biology Problem Solving Test. No statistically significant difference was found between stud.
Regulation of phospholipase D1 subcellular cycling through coordination of multiple membrane association motifs

The signaling enzyme phospholipase D1 (PLD1) facilitates membrane vesicle trafficking. Here, we explore how PLD1 subcellular localization is regulated via Phox homology (PX) and pleckstrin homology (PH) domains and a PI4,5P2-binding site critical for its activation. PLD1 localized to perinuclear endosomes and Golgi in COS-7 cells, but on cellular stimulation, translocated to the plasma membrane in an activity-facilitated manner and then returned to the endosomes. The PI4,5P2-interacting site sufficed to mediate outward translocation and association with the plasma membrane. However, in the absence of PX and PH domains, PLD1 was unable to return efficiently to the endosomes. The PX and PH domains appear to facilitate internalization at different steps. The PH domain drives PLD1 entry into lipid rafts, which we show to be a step critical for internalization. In contrast, the PX domain appears to mediate binding to PI5P, a lipid newly recognized to accumulate in endocytosing vesicles. Finally, we show that the PH domain–dependent translocation step, but not the PX domain, is required for PLD1 to function in regulated exocytosis in PC12 cells. We propose that PLD1 localization and function involves regulated and continual cycling through a succession of subcellular sites, mediated by successive combinations of membrane association interactions.
A Dual of the Cycle Theorem and its Application to Molecular Complexity

The duality alluded to in the title is that between the faces and vertices of a graph embedded on a surface. Its recognition in the context of the five Platonic solids is classic. Algebraically, it is present in the equation for Euler’s Polyhedron Theorem and in the various extensions thereof. The Cycle Theorem (CT) establishes a formula for the number of spanning trees contained in a graph embedded on a surface. It is based on the mutual incidences of its cycles (circuits which also carry a sense of direction), i.e., of sub-graphs of the Cn type, endorsed with a sense. These appear (though not exclusively) as the boundaries of faces, so that, so to speak, the Cycle Theorem establishes a result which is essentially about vertices via relations between faces. Among several possible duals of the Cycle Theorem there might thus be one that establishes a relation which is essentially about faces via relations between vertices. In order to formulate one, we define, for an embedded graph, a feature concerning faces that is dual to a spanning tree. We call it a ladder. A formula is presented for the number of ladders contained in a graph which, in some cases, introduces the concept of ‘artificial vertices’. It is based on the mutual incidences of its vertices. Its form is clearly analogous, or ‘dual’, to the Cycle Theorem formula for spanning trees, previously proposed (in this journal — 2004) by three of the present authors, together with Klein and Sachs. A new index is proposed, which involves ladders. We call it the Patency Index of a graph; its numerical value may be related to molecular complexity. It is effectively the dual of, and is entirely analogous to, the Spanning-Tree Density Index which was earlier (2003) proposed, defined and applied to molecular graphs by one of the present authors and Trinajstić.
Report on the DB/IR panel at SIGMOD 2005

This paper summarizes the salient aspects of the SIGMOD 2005 panel on "Databases and Information Retrieval: Rethinking the Great Divide". The goal of the panel was to discuss whether we should rethink data management systems architectures to truly merge Database (DB) and Information Retrieval (IR) technologies. The panel had very high attendance and generated lively discussions.
Multimedia COMMONS Workshop 2016 (MMCommons'16): Datasets, Evaluation, and Reproducibility

Leveraged wisely, new datasets can inspire new multimedia methods and algorithms, as well as catalyze innovations in how their efficacy, efficiency, and generalizability can be evaluated. The availability of very large multimedia datasets like the Yahoo-Flickr Creative Commons 100 Million has offered unique opportunities for advancing the state of the art in multimedia processing, analysis, search, and visualization. The Multimedia Commons Initiative has been developing a community around the YFCC100M, including associated annotation and evaluation efforts. In addition to research in several multimedia subfields, including computer vision, image processing, and video content analysis, the YFCC100M and Multimedia Commons resources have been used in various competitions and benchmarks, such as the MediaEval Placing Task and the ACM Multimedia Grand Challenge competition. With additional annotation and curation, the data has the potential to enable major leaps forward in research. As use of the YFCC100M and the Multimedia Commons resources broadens across the multimedia community, the MMCommons'16 workshop offered an opportunity for researchers to share new research results, compare approaches, and coordinate efforts to maximize the scientific benefit of the initiative. In particular, the Multimedia Commons data has the potential to provide both inspiration and concrete resources to pursue some important "meta-research" questions, such as how to measure the scalability, generalizability, and reproducibility of methods across datasets, whether we need to rethink our evaluation paradigms as the field moves in new directions, and how annotation strategies affect the impact of benchmarks and data challenges using that data.
Conditions for synchronization and chaos in networks of -cells

Abstract The insulin producing and releasing pancreatic β-cells play a key role in glucose homeostasis. The proper function of these cells is characterized by a spiking-bursting activity in their membrane potential. It is known that these cells are coupled with each other and that this coupling can induce synchronization. This fact maybe relevant in the mechanisms of blood glucose regulation. However, not much is known about conditions of synchronization, nor about the topology of real-world β-cell network. Also about the conditions for the emergence of chaotic bursting in networks of β-cells not much is known. We investigate these phenomena in terms of complex network theory as model of β-cells networks, in which synchronization and emergence of chaotic bursting occurs.
Fetal and perinatal mortality, United States, 2004.

OBJECTIVES This report presents 2004 fetal and perinatal mortality data by a variety of characteristics, including maternal age, marital status, race, Hispanic origin and state of residence; and by infant birthweight, gestational age, plurality and sex. Trends in fetal and perinatal mortality are also examined. METHODS Descriptive tabulations of data are presented and interpreted. RESULTS In 2004, there were 25,655 reported fetal deaths of 20 weeks of gestation or more in the United States. The U.S. fetal mortality rate was 6.20 fetal deaths of 20 weeks of gestation or more per 1,000 live births and fetal deaths, not significantly different from the rate of 6.23 in 2003. The fetal mortality rate for non-Hispanic black women (11.25) was 2.3 times the rate for non-Hispanic white women (4.98), whereas the rate for Hispanic women (5.43) was 9 percent higher than the rate for non-Hispanic white women. Fetal and perinatal mortality rates have declined slowly but steadily from 1990 to 2004. Fetal mortality rates for 28 weeks of gestation or more have declined substantially whereas those for 20-27 weeks of gestation have not declined. Fetal mortality rates are elevated for a number of groups, including teenagers, women aged 35 years and over, unmarried women, and multiple deliveries. In 2004, one-half of fetal deaths of 20 weeks of gestation or more occurred between 20 and 27 weeks of gestation.
Pharmacogenomic variation of CYP2D6 and the choice of optimal adjuvant endocrine therapy for postmenopausal breast cancer: a modeling analysis.

BACKGROUND Adjuvant endocrine treatment with aromatase inhibitors improves disease-free survival compared with tamoxifen in postmenopausal women with estrogen receptor-positive breast cancer. This difference could be due to differences in tamoxifen metabolism because levels of endoxifen, the active tamoxifen metabolite, vary with the number of mutant alleles, including the *4 allele, of the gene encoding cytochrome P450 2D6 (CYP2D6). METHODS We created a Markov model to determine whether tamoxifen or aromatase inhibitor monotherapy maximized 5-year disease-free survival for patients with the wild-type CYP2D6 genotype (wt/wt). Annual risks of recurrence with aromatase inhibitors and tamoxifen in breast cancer patients who were not selected by CYP2D6 genotype were derived from the Breast International Group 1-98 trial. Genotype frequencies and the hazard ratio for cancer recurrence on tamoxifen among patients with the *4/*4 genotype relative to the wt/wt or wt/*4 genotypes (HR(*4/*4) = 1.86) were based on data from an analysis of the North Central Cancer Treatment Group trial of adjuvant tamoxifen. We explored the impact of CYP2D6(*4) heterozygosity on disease-free survival for wt/wt patients by studying a range of effect (ie, recurrence on tamoxifen) estimates, from no effect of the single mutation (Eff(wt/*4) = 0, recurrence rate in wt/*4 patients same as that in wt/wt patients) to complete effect (Eff(wt/*4) = 1 recurrence rate in wt/*4 patients same as that in *4/*4 patients). RESULTS With HR(*4/*4) = 1.86 and Eff(wt/*4) = 0.5, the 5-year disease-free survival of tamoxifen-treated patients with no mutations (wt/wt) was 83.9%, that is, essentially the same as that (84.0%) for genotypically unselected patients who were treated with aromatase inhibitors. With greater HR(*4/*4) estimates, disease-free survival with tamoxifen exceed that with aromatase inhibitors in wt/wt patients, even at lower assumed Eff(wt/*4) ratios. CONCLUSIONS Modeling suggests that among patients who are wild type for CYP2D6, 5-year disease-free survival outcomes are similar to or perhaps even superior with tamoxifen than with aromatase inhibitors. Endocrine therapy tailored to CYP2D6 genotype could be considered for women who are newly diagnosed with breast cancer, particularly those who have with concerns about either the relative toxicity or the increased cost of aromatase inhibitors.
The Problem Behaviour Checklist: short scale to assess challenging behaviours

Background Challenging behaviour, especially in intellectual disability, covers a wide range that is in need of further evaluation. Aims To develop a short but comprehensive instrument for all aspects of challenging behaviour. Method In the first part of a two-stage enquiry, a 28-item scale was constructed to examine the components of challenging behaviour. Following a simple factor analysis this was developed further to create a new short scale, the Problem Behaviour Checklist (PBCL). The scale was subsequently used in a randomised controlled trial and tested for interrater reliability. Scores were also compared with a standard scale, the Modified Overt Aggression Scale (MOAS). Results Seven identified factors – personal violence, violence against property, self-harm, sexually inappropriate, contrary, demanding and disappearing behaviour – were scored on a 5-point scale. A subsequent factor analysis with the second population showed demanding, violent and contrary behaviour to account for most of the variance. Interrater reliability using weighted kappa showed good agreement (0.91; 95% CI 0.83–0.99). Good agreement was also shown with scores on the MOAS and a score of 1 on the PBCL showed high sensitivity (97%) and specificity (85%) for a threshold MOASscore of 4. Conclusions The PBCL appears to be a suitable and practical scale for assessing all aspects of challenging behaviour. Declaration of interest None. Copyright and usage © 2016 The Royal College of Psychiatrists. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
Reconsidering the Relationship Between Alcohol and Lethal Violence

Prior event-based research regarding the relationship between alcohol and violence suffers from important limitations, including the absence of a comparison group, an inappropriate comparison group, or a comparison group that could be considered appropriate but does not control for potential confounders. To overcome such limitations, we use a matched pair design. Drawing on interviews with men imprisoned for an aggravated assault or homicide committed in response to a conflict with another man, we examine matched pairs of violent and nonviolent conflicts nested within respondents. The results suggest that guns mediate the relationship between alcohol and lethal male-male violence.
Can Elite Tournament Professional Golfers Prevent Habitual Actions in Their Putting Actions?

INTRODUCTION The mechanisms underlying successful putting are not yet completely understood. As compared with the complexity of the full swing, the movement requirements in putting seem to be limited. Surprisingly, even for many PGA Tour players, consistent putting is a problem, and very often the short putts are even more challenging. More than that, movement disturbances occurring in golf such as “yips” are more often found in easy shots such as putting. The problems involved in learning and executing a smooth and consistent putting stroke might be better understood if the mechanisms behind motor learning and motor control are considered. Our research suggests that many putting problems are related to an elevated level of movement control as a consequence of the obviously high precision demands.
[Pregnancy and myeloid leukemia treated with imatinib. Development and monitoring of a patient].

BACKGROUND Imatinib has changed the natural history of chronic myeloid leukemia. There are women with chronic myeloid leukemia in reproductive age with pregnancy desires. The aim of this case was to report the course and outcome of pregnancy in a patient with chronic myeloid leukemia diagnosis treated with imatinib. CLINICAL CASE A 32 year old female with diagnosis of chronic myeloid leukemia with follow-up of 11 years. She received standard treatment, but she reported poor adherence; therefore, she received imatinib therapy two years after the diagnosis. The patient stopped the treatment herself because she was looking to be pregnant. She presented amenorrhea, which lasted for six weeks; pregnancy was confirmed. During a period of 10 months, she remained untreated and there were no symptoms of leukemia progression. The pregnancy was terminated by cesarean section at 35.5 weeks of gestation. The product was born healthy. In the post-cesarean visit, the lab showed a cell blood count which reported: hemoglobin 8.7 g/dL, hematocrit 25 %, white blood cell 22,000/mL, platelets 170,000/mL. Since October the patient resumed imatinib 600 mg/day. CONCLUSIONS The prolonged period of treatment with imatinib had no effect on the pregnancy and the product. The molecular monitoring showed the need to reinstall the treatment once the pregnancy finished. The efficacy and safety of treatment allows patients to fulfill life projects that seemed distant in other time.
Genetic Diversity and Population Structure of Basmati Rice (Oryza sativa L.) Germplasm Collected from North Western Himalayas Using Trait Linked SSR Markers

One hundred forty one basmati rice genotypes collected from different geographic regions of North Western Himalayas were characterized using 40 traits linked microsatellite markers. Number of alleles detected by the abovementioned primers were 112 with a maximum and minimum frequency of 5 and 2 alleles, respectively. The maximum and minimum polymorphic information content values were found to be 0.63 and 0.17 for the primers RM206 and RM213, respectively. The genetic similarity coefficient for the most number of pairs ranged between of 0.2-0.9 with the average value of 0.60 for all possible combinations, indicating moderate genetic diversity among the chosen genotypes. Phylogenetic cluster analysis of the SSR data based on distance divided all genotypes into four groups (I, II, III and IV), whereas model based clustering method divided these genotypes into five groups (A, B, C, D and E). However, the result from both the analysis are in well agreement with each other for clustering on the basis of place of collection and geographic region, except the local basmati genotypes which clustered into three subpopulations in structure analysis comparison to two clusters in distance based clustering. The diverse genotypes and polymorphic trait linked microsatellites markers in the present study will be used for the identification of quantitative trait loci/genes for different economically important traits to be utilized in molecular breeding programme of rice in the future.
Human cerebrospinal fluid increases the excitability of pyramidal neurons in the in vitro brain slice

The cerebrospinal fluid contains numerous neuromodulators at ambient levels but whether, and how, they affect the activity of central neurons is unknown. This study provides experimental evidence that human cerebrospinal fluid (hCSF) increases the excitability of hippocampal and neocortical pyramidal neurons. Hippocampal CA1 pyramidal neurons in hCSF displayed lowered firing thresholds, depolarized resting membrane potentials and reduced input resistance, mimicking properties of pyramidal neurons recorded in vivo. The excitability‐increasing effect of hCSF on CA1 pyramidal neurons was entirely occluded by intracellular application of GTPγS, suggesting that neuromodulatory effects were mediated by G‐protein coupled receptors. These results indicate that the CSF promotes spontaneous excitatory neuronal activity, and may help to explain observed differences in the activity of pyramidal neurons recorded in vivo and in vitro.
The economic burden of heart failure

Heart failure, a major cause of morbidity and mortality among the elderly, is a serious public health problem. As the population ages and the prevalence of heart failure increases, expenditures related to the care of these patients will climb dramatically. As a result, the health care industry must develop strategies to contain this staggering economic burden. Strategies may include adopting approaches for preventing heart failure and implementing new treatment modalities with proven efficacy into large‐scale clinical practice. Successful implementation of these strategies will require intensive physician and patient education and development of innovative approaches to fund support services.