Miracle-dz/UniFAR-FTUs huggingface dataset:
Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on family history.

BACKGROUND Heritable mutations of the breast cancer gene BRCA1 are rare, occurring in fewer than 1% of women in the general population, and therefore account for a small proportion of cases of breast and ovarian cancers. Nevertheless, the presence of such mutations is highly predictive of the development of these cancers. PURPOSE We developed and applied a mathematic model for calculating the probability that a woman with a family history of breast and/or ovarian cancer carries a mutation of BRCA1. METHODS AND RESULTS As a basis for the model, we use Mendelian genetics and apply Bayes' theorem to information on the family history of these diseases. Of importance are the exact relationships of all family members, including both affected and unaffected members, and ages at diagnosis of the affected members and current ages of the unaffected members. We used available estimates of BRCA1 mutation frequencies in the general population and age-specific incidence rates of breast and ovarian cancers in carriers and noncarriers of mutations to estimate the probability that a particular member of the family carries a mutation. This probability is based on cancer statuses of all first- and second-degree relatives. We first describe the model by considering single individuals: a woman diagnosed with breast and/or ovarian cancer and also a woman free of cancer. We next considered two artificial and two actual family histories and addressed the sensitivity of our calculations to various assumptions. Particular relationships of family members with and without cancer can have a substantial impact on the probability of carrying a susceptibility gene. Ages at diagnosis of affected family members and their types of cancer are also important. A woman with two primary cancers can have a probability of carrying a mutation in excess of 80%, even with no other information about family history. The number and relationships of unaffected members, along with their current ages or ages at death, are critical determinants of one's carrier probability. An affected woman with several cancers in her family can have a probability of carrying a mutation that ranges from close to 100% to less than 5%. CONCLUSION Our model gives informative and specific probabilities that a particular woman carries a mutation. IMPLICATIONS This model focuses on mutations in BRCA1 and assumes that all other breast cancer is sporadic. With the cloning of BRCA2, we now know that this assumption is incorrect. We have adjusted the model to include BRCA2, but the use of this version must await publication of penetrance data for BRCA2, including those for male breast cancer that are apparently associated with BRCA2 but not with BRCA1. The current model is, nevertheless, appropriate and useful. Of principal importance is its potential and that of improved versions for aiding women and their health care providers in assessing the need for genetic testing.
The Comparison between Native Speakers of Indonesian and BIPA Learners in Producing Email Requests

This study examined a comparison between Native Speakers (NS) of Indonesian and Indonesian language as a foreign language (Bahasa Indonesia untuk Penutur Asing - BIPA) learners in making email requests. In particular, this study analysed the different aspects of pragmatics of variations in structure and politeness in emails. This study involved nine NS of Indonesian who were studying master’s level programs at the University of Melbourne, and eighteen BIPA learners who took the subject Indonesian 4 in Semester 2, 2018 at the University of Melbourne. Participants wrote an email request based on a given scenario, which was requesting leave in the context of a workplace in Indonesia. The data were obtained by providing participants a description of the scenario, which prompted them to write an email request asking permission to take time off work. However, participants had freedom in terms of the style and structure of the email. In general, this study aimed to examine how their pragmatics varies, especially in terms of structure and politeness.
Wind of Change Challenges Toxicological Regulators

Background: In biomedical research, the past two decades have seen the advent of in vitro model systems based on stem cells, humanized cell lines, and engineered organotypic tissues, as well as numerous cellular assays based on primarily established tumor-derived cell lines and their genetically modified derivatives. Objective: There are high hopes that these systems might replace the need for animal testing in regulatory toxicology. However, despite increasing pressure in recent years to reduce animal testing, regulators are still reluctant to adopt in vitro approaches on a large scale. It thus seems appropriate to consider how we could realistically perform regulatory toxicity testing using in vitro assays only. Discussion and Conclusion: Here, we suggest an in vitro–only approach for regulatory testing that will benefit consumers, industry, and regulators alike.
Intellectual capital and business performance in the Portuguese banking industry

Previous empirical studies confirm that intellectual capital has a significant and substantive impact on performance. The purpose of this research is to examine the inter-relationships and interactions among intellectual capital components and business performance in the Portuguese banking industry. The concept of relational capital was extended to include 'stakeholder orientation' items. Model development and hypothesis testing was conducted using PLS on a sample of 253 respondents from 53 organisations. Results show a confirmation of previous studies as it relates to hypothesis testing but a difference in psychometric item evaluation given the unique geographical and sectoral context. Recommendations are then made for researchers and practitioners.
14 new eclipsing white dwarf plus main-sequence binaries from the SDSS and Catalina surveys

We report on the search for new eclipsing white dwarf plus main-sequence (WDMS) binaries in the light curves of the Catalina surveys. We use a colour-selected list of almost 2000 candidate WDMS systems from the Sloan Digital Sky Survey, specifically designed to identify WDMS systems with cool white dwarfs and/or early M-type main-sequence stars. We identify a total of 17 eclipsing systems, 14 of which are new discoveries. We also find three candidate eclipsing systems, two main-sequence eclipsing binaries and 22 non-eclipsing close binaries. Our newly discovered systems generally have optical fluxes dominated by the main-sequence components, which have earlier spectral types than the majority of previously discovered eclipsing systems. We find a large number of ellipsoidally variable binaries with similar periods, near 4 h, and spectral types M2–3, which are very close to Roche lobe filling. We also find that the fraction of eclipsing systems is lower than found in previous studies and likely reflects a lower close binary fraction among WDMS binaries with early M-type main-sequence stars due to their enhanced angular momentum loss compared to fully convective late M-type stars, hence causing them to become cataclysmic variables quicker and disappear from the WDMS sample. Our systems bring the total number of known detached, eclipsing WDMS binaries to 71.
Structural surface overlap and derivational complexity in crosslinguistic transfer: Acquisition of English genitive alternation by Egyptian Arabic-speaking learners

This article adopts the surface overlap and derivational complexity hypotheses to study crosslinguistic transfer in the adult second language (L2) acquisition of English genitive alternation (between the s-genitives and the of genitives) by intermediate and advanced Egyptian Arabic-speaking learners. While the s-genitive (e.g. the boy’s shirt) and the of-genitive (e.g. the shirt of the boy) are allowed in principle to denote possession, the s-genitive is the native option when the possessor is human and the possessum is nonhuman. In standard syntactic analyses, the s-genitive is held to be more complex than the of-genitive, since it involves raising the possessor in the determiner phrase (DP). Egyptian Arabic is also known for its genitive alternation; it uses the synthetic genitive (the construct state), and the analytic genitive (the free state) that both overlap partially or significantly with the of-genitive. The results of an elicited production task showed that the intermediate group tended to produce the of-genitives in contexts in which the s-genitives were the target construction. The advanced group, on the other hand, produced the more complex s-genitives. These findings suggest that the surface overlap involved between the of-genitives and the corresponding genitive constructions in Egyptian Arabic conspired to trigger this crosslinguistic transfer. Also, resorting to the overlapping of-genitive option can be viewed as a strategy to avoid the more complex s-genitive option. The results of the advanced group imply that the acquisition of English genitive alternation undergoes two developmental stages. In the first, learners favor the less complex and overlapping of-genitives. In the second, they acquire the syntactic derivation in the s-genitives that raises the possessor in the DP.
The Cancer Stem Cell Marker CD133 Interacts with Plakoglobin and Controls Desmoglein-2 Protein Levels

The pentaspan membrane glycoprotein CD133 (also known as prominin-1) has been widely used as a marker for both cancer and normal stem cells. However, the function of CD133 has not been elucidated. Here we describe a cancer stem cell line established from clear cell carcinoma of the ovary (CCC) and show that CD133 interacts with plakoglobin (also known as γ-catenin), a desmosomal linker protein. We further demonstrate that knockdown of CD133 by RNA interference (RNAi) results in the downregulation of desmoglein-2, a desmosomal cadherin, and abrogates cell-cell adhesion and tumorigenicity of CCC stem cells. We speculate that CD133 may be a promising target for cancer chemotherapy.
Reprints Available Directly from the Publisher Photocopying Permitted by License Only Cell Kinetics of Regenerating Liver after 70% Hepatectomy in Rats 2-color Flow Cytometric Analysis

Two-color flow cytometric (FCM) analysis using anti-bromodeoxyuridine (BrdU) monoclonal antibody (MoAb) was used to investigate the cell kinetics of regenerating liver after 70% partial hepatectomy in rats. Three peaks were seen in DNA histograms of rat hepatocyte nuclei, corresponding to diploid(2c), tetraploid(4c), and octaploid(8c). These proportions changed in the course of regeneration which were clearly demonstrated by DNA histograms using flow cytometry. The proportion of diploid, tetraploid, and octaploid nuclei in control liver were 49.3 + 1.6%, 45.0+ 7.4%, and 1.7+0.7%, respectively. A significant change occurred at 24 hours after hepatectomy, as FCM revealed 25.9+ 1.1% diploid, 54.5 + 1.2% tetraploid, and 9.0 + 0.9% octaploid. This shift to polyploid nuclei persisted until 72 hours, and then gradually returned to the pattern of control liver. The S-phase nuclei which incorporated BrdU increased rapidly at 24 hours to a peak of 11.3+0.9%, and gradually decreased to 5. This 2-color FCM analysis made a detailed analysis of the cell kinetics in regenerating hepatocytes possible, and may be applied in investigations of various aspects of liver regeneration.
Significant contribution of the 3′→5′ exonuclease activity to the high fidelity of nucleotide incorporation catalyzed by human DNA polymerase ϵ

Most eukaryotic DNA replication is performed by A- and B-family DNA polymerases which possess a faithful polymerase activity that preferentially incorporates correct over incorrect nucleotides. Additionally, many replicative polymerases have an efficient 3′→5′ exonuclease activity that excises misincorporated nucleotides. Together, these activities contribute to overall low polymerase error frequency (one error per 106–108 incorporations) and support faithful eukaryotic genome replication. Eukaryotic DNA polymerase ϵ (Polϵ) is one of three main replicative DNA polymerases for nuclear genomic replication and is responsible for leading strand synthesis. Here, we employed pre-steady-state kinetic methods and determined the overall fidelity of human Polϵ (hPolϵ) by measuring the individual contributions of its polymerase and 3′→5′ exonuclease activities. The polymerase activity of hPolϵ has a high base substitution fidelity (10−4–10−7) resulting from large decreases in both nucleotide incorporation rate constants and ground-state binding affinities for incorrect relative to correct nucleotides. The 3′→5′ exonuclease activity of hPolϵ further enhances polymerization fidelity by an unprecedented 3.5 × 102 to 1.2 × 104-fold. The resulting overall fidelity of hPolϵ (10−6–10−11) justifies hPolϵ to be a primary enzyme to replicate human nuclear genome (0.1–1.0 error per round). Consistently, somatic mutations in hPolϵ, which decrease its exonuclease activity, are connected with mutator phenotypes and cancer formation.
The Role of Neuroticism and Experiential Avoidance in Predicting Anxiety and Depression Symptoms: Mediating Effect of Emotion Regulation

Background Preliminary evidence supports the role of neuroticism, experiential avoidance and emotion regulation in anxiety and depression; however, the mechanism of these relationships is not known well. Objectives The present study mainly aimed to assess the mediating role of emotion regulation in the relationship between neuroticism and experiential avoidance and anxiety and depression symptoms. Materials and Methods By convenient sampling, 316 students from Tehran University of Medical Sciences, Iran University of Social Welfare and Rehabilitation Sciences and University of Tehran were selected and measures of experiential avoidance, neuroticism, emotion regulation, worry, anxiety and depression were administered among them, 2014-2015. Path analysis via regression according to Baron and Kenny evaluative criteria was used for data analysis. Results Experiential avoidance and neuroticism predicted anxiety, and depression symptoms and the predictions were mediated by emotion regulation and worry. Conclusions Emotion regulation deficits have an outstanding role in the mechanism of anxiety and depression which are so comorbid and further studies are needed to evaluate emotion regulation with more advanced methods and along with other transdiagnostic components.
THE TRAVELING SALESMAN PROBLEM: A NEURAL NETWORK PERSPECTIVE

This paper surveys the "neurally" inspired problem-solving approaches to the traveling salesman problem, namely, the Hopfield-Tank network, the elastic net and the self-organizing map. The latest achievements in the neural network domain are reported and numerical comparisons are provided with the classical solution approaches of operations research. An extensive bibliography with more than one hundred references is also included. (A)
A Dozen Colliding-Wind X-Ray Binaries in the Star Cluster R136 in the 30 Doradus Region

We analyzed archival Chandra X-ray observations of the central portion of the 30 Doradus region in the Large Magellanic Cloud. The image contains 20 X-ray point sources with luminosities between 5 × 1032 and 2 × 1035 ergs s-1 (0.2-3.5 keV). A dozen sources have bright WN Wolf-Rayet or spectral type O stars as optical counterparts. Nine of these are within ~3.4 pc of R136, the central star cluster of NGC 2070. We derive an empirical relation between the X-ray luminosity and the parameters for the stellar wind of the optical counterpart. The relation gives good agreement for known colliding-wind binaries in the Milky Way Galaxy and for the identified X-ray sources in NGC 2070. We conclude that probably all identified X-ray sources in NGC 2070 are colliding-wind binaries and that they are not associated with compact objects. This conclusion contradicts earlier studies where it was argued, using ROSAT data, that two earlier discovered X-ray sources are accreting black hole binaries. Five of the 18 brightest stars in R136 are not visible in our X-ray observations. These stars either are single, have low-mass companions, or have very wide orbits. The resulting binary fraction among early-type stars is then unusually high (at least 70%).
Molecular Mechanisms and Function Prediction of Long Noncoding RNA

The central dogma of gene expression considers RNA as the carrier of genetic information from DNA to protein. However, it has become more and more clear that RNA plays more important roles than simply being the information carrier. Recently, whole genome transcriptomic analyses have identified large numbers of dynamically expressed long noncoding RNAs (lncRNAs), many of which are involved in a variety of biological functions. Even so, the functions and molecular mechanisms of most lncRNAs still remain elusive. Therefore, it is necessary to develop computational methods to predict the function of lncRNAs in order to accelerate the study of lncRNAs. Here, we review the recent progress in the identification of lncRNAs, the molecular functions and mechanisms of lncRNAs, and the computational methods for predicting the function of lncRNAs.
OLDER WOMEN'S PERCEPTIONS OF ETHICAL DILEMMAS IN ADULT PROTECTIVE SERVICES: AN EXPLORATORY STUDY

by EMILY K. DAKIN This study examined older women’s perceptions of the definition of elder maltreatment and of three ethical dilemmas within Adult Protective Services: mandatory reporting and involuntary protective services (both of which illustrate the larger freedom versus protection dilemma); and the criminalization of elder maltreatment. Older women’s ethical decision-making processes in responding to these dilemmas were also examined. An exploratory study was conducted utilizing a focus group design which consisted of a pilot focus group, eight focus groups, and a final member-check group. The eight focus groups were comprised of two working-class Caucasian groups, two working class-African American groups, one high socioeconomic status Caucasian group, one high socioeconomic status African American group, and two Latina groups. All of the study’s 88 participants were women age 60 or older. Participants espoused a broad definition of elder maltreatment that included physical neglect, emotional neglect, physical abuse, verbal abuse, financial abuse, societal maltreatment, maltreatment by family and strangers, and abuse within nursing
NMDA Receptors in the Developing Brain and Effects of Noxious Insults

This review covers normal expression of the NMDA receptor in the fetus and newborn, and then the response of the NMDA receptors within the central nervous system (CNS) during early development, to noxious stimuli. In the research setting, hypoxia is a commonly studied noxious stimulus that has been studied in a variety of contexts, including isolated hypoxia, or hypoxia combined with ischemia or hypercapnia, and delivered in single or repeated doses (intermittent stimuli). We review differences and commonalities between these experimental paradigms, and the sequelae of a common outcome, which is cell death, possibly through excitotoxic mechanisms. Finally, based on current literature, we will examine potential directions for clinical therapeutic interventions. By highlighting knowledge gaps in this field, we hope to encourage future research focusing on clinically relevant problems and outcomes in this area.
Impact of Wireless Channel on VoIP QoS and Admission Regions in IEEE 802.11g WLANs

In this paper, we evaluate the impact of the wireless channel and physical layer parameters on the performance of VoIP traffic in IEEE 802.11g networks. The wireless channel is modeled using a finite state Markov chain based on an adaptive modulation and coding scheme. The transition probabilities encompass the effects of the time-varying wireless channel, such as the Doppler frequency and the operating SNR, and the physical layer target packet error rate. This model is implemented inthe NS-2 tool and used to analyze the QoS (delay and packetdrop rate) of real-time multimedia traffic in realistic wireless channels. Numerical results showing the physical layer impact on the number of supported VoIP calls in an 802.11g network are presented. We also demonstrate that the admission region in the presence of mixed VoIP and data remains linear, even after considering the complex wireless channel effects.
Choice Modelling and the Transfer of Environmental Values

The focus of this unique collection of case studies is the validity and accuracy of benefit transfer using choice modelling, rather than the traditional focus of transferring results from contingent valuation and travel cost models. The book includes a simple guide to using choice modelling results in a benefit transfer process, an overview of the theoretical issues involved, and a number of case studies from Australia, Finland, New Zealand, the UK and the US. The conclusion is that the benefit transfer process is not straightforward, but that use of the choice modelling technique allows for more ‘automatic’ adjustment of values by the factors that frame the case study of interest.
A theory of a saliency map in primary visual cortex (V1) tested by psychophysics of colour–orientation interference in texture segmentation

It has been proposed that V1 creates a bottom-up saliency map, where saliency of any location increases with the firing rate of the most active V1 output cell responding to it, regardless the feature selectivity of the cell. Thus, a red vertical bar may have its saliency signalled by a cell tuned to red colour, or one tuned to vertical orientation, whichever cell is the most active. This theory predicts interference between colour and orientation features in texture segmentation tasks where bottom-up processes are significant. The theory not only explains existing data, but also provides a prediction. A subsequent psychophysical test confirmed the prediction by showing that segmentation of textures of oriented bars became more difficult as the colours of the bars were randomly drawn from more colour categories.
Novel subcellular localization for α-synuclein: possible functional consequences

α-synuclein (α-syn) is one of the genes that when mutated or overexpressed causes Parkinson’s Disease (PD). Initially, it was described as a synaptic terminal protein and later was found to be localized at mitochondria. Mitochondria-associated membranes (MAM) have emerged as a central endoplasmic reticulum (ER) subcellular compartments where key functions of the cell occur. These domains, enriched in cholesterol and anionic phospholipids, are where calcium homeostasis, lipid transfer, and cholesterol metabolism are regulated. Some proteins, related to mitochondrial dynamics and function, are also localized to this area. Several neurodegenerative diseases have shown alterations in MAM functions and resident proteins, including Charcot Marie-Tooth and Alzheimer’s disease (AD). We have recently reported that MAM function is downregulated in cell and mouse models of PD expressing pathogenic mutations of α-syn. This review focuses on the possible role of α-syn in these cellular domains and the early pathogenic features of PD that could be explained by α-syn-MAM disturbances.