Miracle-dz/UniFAR-FTUs huggingface dataset:
Biochemical and cellular characteristics of the 3′ → 5′ exonuclease TREX2

TREX2 is an autonomous nonprocessive 3′ → 5′ exonuclease, suggesting that it maintains genome integrity. To investigate TREX2's biochemical and cellular properties, we show that endogenous TREX2 is expressed widely in mouse tissues and human cell lines. Unexpectedly, endogenous human TREX2 is predominantly expressed as a 30-kDa protein (not 26 kDa, as previously believed), which is likely encoded by longer isoforms (TREX2L1 and/or TREX2L2) that possess similar capacity for self-association, DNA binding and catalytic activity. Site-directed mutagenesis analysis shows that the three functional activities of TREX2 are distinct, yet integrated. Mutation of amino acids putatively important for homodimerization significantly impairs both DNA binding and exonuclease activity, while mutation of amino acids (except R163) in the DNA binding and exonuclease domains affects their corresponding activities. Interestingly, however, DNA-binding domain mutations do not impact catalytic activity, while exonuclease domain mutations diminish DNA binding. To understand TREX2 cellular properties, we find endogenous TREX2 is down regulated during G2/M and nuclear TREX2 displays a punctate staining pattern. Furthermore, TREX2 knockdown reduces cell proliferation. Taken together, our results suggest that TREX2 plays an important function during DNA metabolism and cellular proliferation.
The Association between Economic Status and Depressive Symptoms: An Individual and Community Level Approach

Objective The study was conducted to investigate the association between economic status and depressive symptoms by comparing the prevalence rates of depressive symptoms at community level and analyzing the possibility of depressive symptoms at individual level. Methods A survey was conducted from November, 2006 to November, 2007 on 966 and 992 representative subjects recruited by stratified clustered sampling in two regions located in Seoul. We used a standardized questionnaire including the Center for Epidemiologic Studies-Depression and questions on the socioeconomic characteristics. The adjusted prevalence rates of depressive symptoms were compared at community level, and multiple logistic regression analysis was performed to determine the association between depressive symptoms and economic statuses at individual level among each region. Results The adjusted prevalence of depressive symptoms was higher in the region with a high socioeconomic status (23.1%) than in the region with a lower economic status (16.6%)(p<0.001). However, logistic regression analysis of individual level revealed that a higher economic status was significantly associated with a lower possibility of depressive symptoms among the females in the low economic status region. This tendency was not observed among the males in both of the regions. Conclusion The association between economic status and depressive symptoms was found to be different when it was approached at community level or individual level. In addition, the association of two variables was different by gender at individual level. Further studies that consider the third mediators are needed to determine the association between the two variables.
An Empirical Methodology to Evaluate Vulnerability Discovery Models

Vulnerability discovery models (VDMs) operate on known vulnerability data to estimate the total number of vulnerabilities that will be reported after a software is released. VDMs have been proposed by industry and academia, but there has been no systematic independent evaluation by researchers who are not model proponents. Moreover, the traditional evaluation methodology has some issues that biased previous studies in the field. In this work we propose an empirical methodology that systematically evaluates the performance of VDMs along two dimensions (quality and predictability) and addresses all identified issues of the traditional methodology. We conduct an experiment to evaluate most existing VDMs on popular web browsers' vulnerability data. Our comparison shows that the results obtained by the proposed methodology are more informative than those by the traditional methodology. Among evaluated VDMs, the simplest linear model is the most appropriate choice in terms of both quality and predictability for the first 6-12 months since a release date. Otherwise, logistics-based models are better choices.
Factors Influencing Overuse of Breast Cancer Screening: A Systematic Review.

BACKGROUND Excessive breast cancer screening with mammography or other modalities often burdens patients with false-positive results and costs. Yet, screening patients beyond the age at which they will benefit or at too frequent intervals persists. This review summarizes the factors associated with overuse of breast cancer screening. METHODS We searched Medline and Embase from January 1998 to March 2017 for articles addressing the overuse of breast cancer screening and hand-searched the reference lists of included articles. Studies were included if they were written in English, pertained to a U.S. population, and identified a factor associated specifically with overuse of breast imaging. Paired reviewers independently screened abstracts, extracted data, and assessed quality. RESULTS We included 15 studies: 3 cohort, 5 cross-sectional, 6 surveys, and 1 in-depth interview. White women (non-Hispanic) were less vulnerable than other racial groups to overuse in 3 of 5 studies. Physician specialty was consistently associated with screening overuse in three of three studies. Abundant access to primary care and a patient desire for screening were associated with breast cancer screening overuse. Lower self-confidence, lower risk taking tendencies, higher perception of conflict in expert recommendations, and a belief in screening effectiveness were clinician traits associated with overuse of screening in the surveys. CONCLUSIONS The literature supports that liberal access to care and clinicians' recommendations to screen, possibly influenced by conflicting guidelines, increase excessive breast cancer screening. Overuse might conceivably be reduced with more concordance across guidelines, physician education, patient involvement in decision-making, thoughtful insurance restrictions, and limitations on the supply of services; however, these will need careful testing regarding their impact.
Major ion chemistry and weathering control in a high altitude basin : Alaknanda River, Garhwal Himalaya, India

Abstract An analytical study of major cations and anions of the glacier fed Alaknanda River and its tributaries has been carried out to assess the weathering and geochemical processes in the high altitude river basin. The Alaknanda and its tributaries were sampled during pre-monsoon (June 1992) and post-monsoon (October 1992) season for the present hydrogeochemical study. Calcium and magnesium are the major cations, accounting for 85% of the total cations. Among the anions, bicarbonate is the most dominant (78%) with minor contribution from sulphate (19%) and chloride (3%). The average (Ca+Mg)/HCO3 equivalent ratio of 1.2, a relatively high contribution of (Ca+Mg) to the total cations (TZ+) and high (Ca+Mg)/(Na+K) ratio indicate that the carbonate weathering could be the primary source of the major ions to these waters. Wide seasonal and spatial variations are observed in the total dissolved solids (TDS) and total suspended matter (TSM) concentration in the Alaknanda river basin. The chemical denudation r.
Student Perceptions on Language Learning in a Technological Environment: Implications for the New Millennium

This article presents survey data from beginning Spanish classes using a combination of technologies: Internet activities, CD-ROM, electronic pen pals, and threaded discussions. Goals of the study were to determine students' perceptions of (a) the role and importance of the instructor in technology-enhanced language learning (TELL), (b) the accessibility and relevance of the lab and the individual technological components in student learning, and (c) the effects of the technology on the foreign language learning experiences. Students attributed an important role to instructors and perceived that cultural knowledge, listening and reading skills, and independent learning skills were enhanced but were divided in their perceptions about the learning or interest values of the individual components. Implications are presented that may be useful to universities developing technology enhanced instruction.
Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata

Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA) being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC) and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.
Heregulin, a new regulator of telomere length in human cells

The growth factor heregulin (HRG) promotes breast cancer (BC) tumorigenesis and metastasis and differentially modulates BC cell responses to DNA-damaging agents via its dual extracellular and nuclear localization. Given the central role of telomere dysfunction to drive carcinogenesis and to alter the chemotherapeutic profile of transformed cells, we hypothesized that an unanticipated nuclear function of HRG might be to regulate telomere length. Engineered overexpression of the HRGβ2 isoform in non-aggressive, HRG-negative MCF-7 BC cells resulted in a significant shortening of telomeres (up to 1.3 kb) as measured by Southern blotting of telomere terminal restriction fragments. Conversely, antisense-mediated suppression of HRGβ2 in highly aggressive, HRG-overexpressing MDA-MB-231 and Hs578T cells increased telomere length up to 3.0 kb. HRGβ2 overexpression promoted a marked upregulation of telomere-binding protein 2 (TRF2) protein expression, whereas its knockdown profoundly decreased TRF2 expression. Double staining of endogenous HRGβ2 with telomere-specific peptide nucleic acid probe/fluorescence in situ hybridization (PNA/FISH) revealed the partial localization of HRG at the chromosome ends. Moreover, a predominantly nucleoplasmic staining pattern of endogenous HRGβ2 appeared to co-localize with TRF2 and, concomitantly with RAP1, a telomere regulator that specifically interacts with TRF2. Small interfering RNA-mediated knockdown of HRG decreased the expression of TRF2 and RAP1, decreased their presence at chromosome ends, and coincidentally resulted in the formation of longer telomeres. This study uncovers a new function for HRGβ2 in controlling telomere length, in part due to its ability to regulate and interact with the telomere-associated proteins TRF2 and RAP1.
Towards Completeness via Proof Search in the Linear Time µ-calculus : The case of Büchi inclusions

Modal µ-calculus is one of the central languages of logic and verification, whose study involves notoriously complex objects: automata over infinite structures on the model-theoretical side; infinite proofs and proofs by (co)induction on the proof-theoretical side. Nevertheless, axiomatizations have been given for both linear and branching time µ-calculi, with quite involved completeness arguments. We come back to this central problem, considering it from a proof search viewpoint, and provide some new completeness arguments in the linear time µ-calculus. Our results only deal with restricted classes of formulas that closely correspond to (non-alternating) ω-automata but, compared to earlier proofs, our completeness arguments are direct and constructive. We first consider a natural circular proof system based on sequent calculus, and show that it is complete for inclusions of parity automata expressed as formulas, making use of Safra’s construction directly in proof search. We then consider the corresponding finitary proof system, featuring (co)induction rules, and provide a partial translation result from circular to finitary proofs. This yields completeness of the finitary proof system for inclusions of sufficiently deterministic parity automata, and finally for arbitrary Büchi automata.
Bonding of hexagonal BN to transition metal surfaces: An ab initio density-functional theory study

Hexagonal h-BN/metal interfaces for different 3d ,4 d, and 5d metals are studied in terms of ab initio density functional theory. The trends across the periodic table of the bonding of h-BN to the metal surfaces are discussed. We show that the binding energy between h-BN and the metal surface decreases with the filling of the d shell and is largest for 4d elements. For all studied metals the N atom is repelled from the metal surface, whereas the B atom is attracted to it. The strength of attraction/repulsion of B and N atoms depends on their position relative to the underlying metal atoms, and only when N sits on-top of the metal and B occupies fcc or hcp hollow sites the B-attraction dominates the N repulsion and h-BN is bound to the surface. The structure of the h-BN/metal interface is a result of the balance between these forces and the lattice mismatch.
Children's and adults' multimodal interaction with 2D conversational agents

Few systems combine both Embodied Conversational Agents (ECAs) and multimodal input. This research aims at modeling the behavior of adults and children during their multimodal interaction with ECAs. A Wizard-of-Oz setup was used and users were video-recorded while interacting with 2D ECAs in a game scenario with speech and pen as input modes. We found that frequent social cues and natural Human-Human syntax condition the verbal interaction of both groups with ECAs. Multimodality accounted for 21% of inputs: it was used for integrating conversational and social aspects (by speech) into task-oriented actions (by pen). We closely examined temporal and semantic integration of modalities: most of the time, speech and gesture overlapped and produced complementary or redundant messages; children also tended to produce concurrent multimodal inputs, as a way of doing several things at the same time. Design implications of our results for multimodal bidirectional ECAs and game systems are discussed.
Optimizing management of chronic obstructive pulmonary disease in the upcoming decade

Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and mortality. Caring for patients with COPD, particularly those with advanced disease who experience frequent exacerbations, places a significant burden on health care budgets, and there is a global need to reduce the financial and personal burden of COPD. Evolving scientific evidence on the natural history and clinical course of COPD has fuelled a fundamental shift in our approach to the disease. The emergence of data highlighting the heterogeneity in rate of lung function decline has altered our perception of disease progression in COPD and our understanding of appropriate strategies for the management of stable disease. These data have demonstrated that early, effective, and prolonged bronchodilation has the potential to slow the rate of decline in lung function and to reduce the frequency of exacerbations that contribute to functional decline. The goals of therapy for COPD are no longer confined to controlling symptoms, reducing exacerbations, and maintaining quality of life, and slowing disease progression is now becoming an achievable aim. A challenge for the future will be to capitalize on these observations by improving the identification and diagnosis of patients with COPD early in the course of their disease, so that effective interventions can be introduced before the more advanced, disabling, and costly stages of the disease. Here we critically review emerging data that underpin the advances in our understanding of the clinical course and management of COPD, and evaluate both current and emerging pharmacologic options for effective maintenance treatment.
Dbx1 triggers crucial molecular programs required for midline crossing by midbrain commissural axons

Axon guidance by commissural neurons has been well documented, providing us with a molecular logic of how midline crossing is achieved during development. Despite these advances, knowledge of the intrinsic genetic programs is still limited and it remains obscure whether the expression of a single transcription factor is sufficient to activate transcriptional programs that ultimately enable midline crossing. Here, we show in the mouse that the homeodomain transcription factor Dbx1 is expressed by a subset of progenitor cells that give rise to commissural neurons in the dorsal midbrain. Gain- and loss-of-function analyses indicate that the expression of Dbx1 alone is sufficient and necessary to trigger midline crossing in vivo. We also show that Robo3 controls midline crossing as a crucial downstream effector of the Dbx1-activated molecular programs. Furthermore, Dbx1 suppresses the expression of the transcriptional program for ipsilateral neuron differentiation in parallel. These results suggest that a single transcription factor, Dbx1, has an essential function in assigning midline-crossing identity, thereby contributing crucially to the establishment of the wiring laterality in the developing nervous system.
Differences in Commercial Database Reported Earnings: Implications for Inferences Concerning Analyst Forecast Rationality, the Association between Prices and Earnings, and Firm Reporting Discretion

Significant changes in mean and median analysts’ forecasts errors documented in recent studies are not synchronized across commercial forecast databases over time and are, in large part, a function of the definitions and procedures that determine the reported earnings component of earnings surprises. In this study we describe a number of complications researchers face in drawing inferences from forecast error metrics that are based on reported earnings numbers supplied by the major forecast data providers (FDPs) First Call, Zacks and I/B/E/S rather than metrics based on commonly used definitions of Compustat reported earnings. We show how differences across and intertemporal changes in FDP practices can have an important impact on inferences drawn in studies concerning analyst rationality, the association between stock prices and earnings news, firm earnings management, and stock market mispricing. We illustrate the importance of researchers’ choice of reported earnings data on inferences with examples from the literatures on earnings response coefficients (Bradshaw, Moberg and Sloan [2000]), analyst forecast rationality (Matsumoto [1999] and Brown [1999]), and value relevance of earnings (Collins, Maydew and Weiss [1997]).
An Introduction to Effectus Theory

Effectus theory is a new branch of categorical logic that aims to capture the essentials of quantum logic, with probabilistic and Boolean logic as special cases. Predicates in effectus theory are not subobjects having a Heyting algebra structure, like in topos theory, but `characteristic' functions, forming effect algebras. Such effect algebras are algebraic models of quantitative logic, in which double negation holds. Effects in quantum theory and fuzzy predicates in probability theory form examples of effect algebras. This text is an account of the basics of effectus theory. It includes the fundamental duality between states and effects, with the associated Born rule for validity of an effect (predicate) in a particular state. A basic result says that effectuses can be described equivalently in both `total' and `partial' form. So-called `commutative' and `Boolean' effectuses are distinguished, for probabilistic and classical models. It is shown how these Boolean effectuses are essentially extensive categories. A large part of the theory is devoted to the logical notions of comprehension and quotient, which are described abstractly as right adjoint to truth, and as left adjoint to falisity, respectively. It is illustrated how comprehension and quotients are closely related to measurement. The paper closes with a section on `non-commutative' effectus theory, where the appropriate formalisation is not entirely clear yet.
Effect of Water Acceleration on Downstream Migratory Behavior and Passage of Atlantic Salmon Smolts and Juvenile American Shad at Surface Bypasses

Abstract Behavior and passage rate of smolts of Atlantic salmon Salmo salar and juvenile American shad Alosa sapidissima were compared between a standard (sharp-crested) and a modified surface bypass weir that employs uniform flow velocity increase (1 m·s−1·m−1 of linear distance). Within the first 30 min after release, significantly more smolts passed the modified weir than the standard weir, but no differences in passage rate between weir types were noted for juvenile American shad. More Atlantic salmon smolts and juvenile American shad were passed by the modified weir in groups of two or more than were passed by the standard weir. Mean lengths of passed and nonpassed smolts were not significantly different between weir types, but American shad passed by the sharp-crested weir were significantly smaller than nonpassed fish. Most individuals of both species that passed the modified weir maintained positive rheotaxis and strong swimming throughout the length of the weir. In addition to acceleration, visua.
Improving the performance of machine learning classifiers for Breast Cancer diagnosis based on feature selection

This paper proposed a comprehensive algorithm for building machine learning classifiers for Breast Cancer diagnosis based on the suitable combination of feature selection methods that provide high performance over the Area Under receiver operating characteristic Curve (AUC). The new developed method allows both for exploring and ranking search spaces of image-based features, and selecting subsets of optimal features for feeding Machine Learning Classifiers (MLCs). The method was evaluated using six mammography-based datasets (containing calcifications and masses lesions) with different configurations extracted from two public Breast Cancer databases. According to the Wilcoxon Statistical Test, the proposed method demonstrated to provide competitive Breast Cancer classification schemes reducing the number of employed features for each experimental dataset.