Miracle-dz/UniFAR-FTUs huggingface dataset:
A Simplified Combination of DNA Probe Preparation and Fluorescence in situ Hybridization

Fluorescence in situ hybridization (FISH) has found widespread applications in cytogenetics. So far the standard protocols for probe amplification (and simultaneous labeling) by PCR, nick translation and in situ hybridization involve different buffer systems leading to a number of time consuming washing steps even before hybridization. In this manuscript we show a fast technique of a close combination of DNA probe preparation and in situ hybridization (ISH). This method was applied to metaphase chromosomes from human lymphocytes fixed on slides. Two specific repetitive DNA probes, the pUC 1.77 DNA probe and the DYZ 1 repetitive DNA fraction were used, amplified and labeled in different ways. Additional experiments with total genomic male human DNA as the DNA probe suggest that this method may be extended to a large variety of other probes. Moreover the ISH technique described does not require toxic denaturing agents, such as formamide.
Parental psychological control and emotion dysregulation among anxious children: A transactional model

Existing research and theories have consistently highlighted the role of emotion regulation deficits and parental psychological control in the occurrence of childhood anxiety disorders. The aim of the present study was to continue to examine these relationships using observational methods amongst a clinically anxious sample. Additionally, the present study aimed to identify the direction of effects between parental psychological control and emotion dysregulation by examining whether there is a discernible sequence of parent and child behaviors forming a pattern of interaction between parents and their anxious children. This was completed using microanalytic coding methods to observe parental psychological control and child dysregulated emotion in moment-to-moment interactions between parents and their child. Time-window sequential analyses was used to identify whether parents were more likely to display psychological control in response to child dysregulated affect than at other times and whether children were more likely display dysregulated affect in response to parent psychological control than at other times. In a sample of 123 clinically anxious and 53 non-clinical children, ages 8 to 12 years, results indicated that anxious children were observed to display longer durations of dysregulated affect than non-clinical children, and parents of anxious children were observed to display longer durations of psychological control than parents of non-clinical children. Results from time-window sequential analyses indicated that children were more likely display dysregulated affect in response to parent psychological control than at other times. Anxiety disorder status did not moderate this relationship; however, race was found to moderate the relationship when examining a 4-second time-window. Findings support theories highlighting the role of parental psychological control and emotion dysregulation deficits among children with anxiety disorders and further elucidate the nature of parent-child interactions with respect to parental psychological control and emotion dysregulation.
Discovering anomalous patterns in large digital pathology images

Advances in medical imaging technology have created opportunities for computer‐aided diagnostic tools to assist human practitioners in identifying relevant patterns in massive, multiscale digital pathology slides. This work presents Hierarchical Linear Time Subset Scanning, a novel statistical method for pattern detection. Hierarchical Linear Time Subset Scanning exploits the hierarchical structure inherent in data produced through virtual microscopy in order to accurately and quickly identify regions of interest for pathologists to review. We take a digital image at various resolution levels, identify the most anomalous regions at a coarse level, and continue to analyze the data at increasingly granular resolutions until we accurately identify its most anomalous subregions. We demonstrate the performance of our novel method in identifying cancerous locations on digital slides of prostate biopsy samples and show that our methods detect regions of cancer in minutes with high accuracy, both as measured by the ROC curve (measuring ability to distinguish between benign and cancerous slides) and by the spatial precision‐recall curve (measuring ability to pick out the malignant areas on a slide which contains cancer). Existing methods need small scale images (small areas of a slide preselected by the pathologist for analysis, eg, 32 × 32 pixels) and may not work effectively on large, raw digitized images of size 100K × 100K pixels. In this work, we provide a methodology to fill this significant gap by analyzing large digitized images and identifying regions of interest that may be indicative of cancer.
Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study.

CONTEXT The long-term risk for developing hypertension is best described by the lifetime risk statistic. The lifetime risk for hypertension and trends in this risk over time are unknown. OBJECTIVES To estimate the residual lifetime risk for hypertension in older US adults and to evaluate temporal trends in this risk. DESIGN, SETTING, AND PARTICIPANTS Community-based prospective cohort study of 1298 participants from the Framingham Heart Study who were aged 55 to 65 years and free of hypertension at baseline (1976-1998). MAIN OUTCOME MEASURES Residual lifetime risk (lifetime cumulative incidence not adjusted for competing causes of mortality) for hypertension, defined as blood pressure of 140/90 mm Hg or greater or use of antihypertensive medications. RESULTS The residual lifetime risks for developing hypertension and stage 1 high blood pressure or higher (greater-than-or-equal to 140/90 mm Hg regardless of treatment) were 90% in both 55- and 65-year-old participants. The lifetime probability of receiving antihypertensive medication was 60%. The risk for hypertension remained unchanged for women, but it was approximately 60% higher for men in the contemporary 1976-1998 period compared with an earlier 1952-1975 period. In contrast, the residual lifetime risk for stage 2 high blood pressure or higher (greater-than-or-equal to 160/100 mm Hg regardless of treatment) was considerably lower in both sexes in the recent period (35%-57% in 1952-1975 vs 35%-44% in 1976-1998), likely due to a marked increase in treatment of individuals with substantially elevated blood pressure. CONCLUSION The residual lifetime risk for hypertension for middle-aged and elderly individuals is 90%, indicating a huge public health burden. Although the decline in lifetime risk for stage 2 high blood pressure or higher represents a major achievement, efforts should be directed at the primary prevention of hypertension.
Structural Characterization of Partially Disordered Human Chibby: Insights into Its Function in the Wnt-Signaling Pathway†

The Wnt/β-catenin signaling pathway is critical to embryonic development as well as adult tissue regeneration. Dysregulation of this pathway can lead to a variety of human diseases, in particular cancers. Chibby (Cby), a small and highly conserved protein, plays an antagonistic role in Wnt signaling by inhibiting the binding of β-catenin to Tcf/Lef family proteins, a protein interaction that is essential for the transcriptional activation of Wnt target genes. Cby is also involved in regulating intracellular distribution of β-catenin. Phosphorylated Cby forms a ternary complex with 14-3-3 protein and β-catenin, facilitating the export of β-catenin from the nucleus. On the other hand, the antagonistic function of Cby is inhibited upon binding to thyroid cancer-1 (TC-1). To dissect the structure−function relationship of Cby, we have used NMR spectroscopy, ESI-MS, CD, and DLS to extensively characterize the structure of human Cby. Our results show that the 126-residue Cby is partially disordered under nondenaturing conditions. While the N-terminal portion of the protein is predominantly unstructured in solution, the C-terminal half of Cby adopts a coiled-coil structure through self-association. Initial data for the binding studies of Cby to 14-3-3ζ (one of the isoforms in the 14-3-3 family) and TC-1 via these two distinct structural modules have also been obtained. It is noteworthy that in a recent large-scale analysis of the intrinsically disordered proteome of mouse, a substantial number of disordered proteins are predicted to have coiled-coil motif presence in their sequences. The combination of these two molecular recognition features could facilitate disordered Cby in assembling protein complexes via different modes of interaction.
Enhancement of Chemokine Function as an Immunomodulatory Strategy Employed by Human Herpesviruses

Herpes simplex virus (HSV) types 1 and 2 are highly prevalent human neurotropic pathogens that cause a variety of diseases, including lethal encephalitis. The relationship between HSV and the host immune system is one of the main determinants of the infection outcome. Chemokines play relevant roles in antiviral response and immunopathology, but the modulation of chemokine function by HSV is not well understood. We have addressed the modulation of chemokine function mediated by HSV. By using surface plasmon resonance and crosslinking assays we show that secreted glycoprotein G (SgG) from both HSV-1 and HSV-2 binds chemokines with high affinity. Chemokine binding activity was also observed in the supernatant of HSV-2 infected cells and in the plasma membrane of cells infected with HSV-1 wild type but not with a gG deficient HSV-1 mutant. Cell-binding and competition experiments indicate that the interaction takes place through the glycosaminoglycan-binding domain of the chemokine. The functional relevance of the interaction was determined both in vitro, by performing transwell assays, time-lapse microscopy, and signal transduction experiments; and in vivo, using the air pouch model of inflammation. Interestingly, and in contrast to what has been observed for previously described viral chemokine binding proteins, HSV SgGs do not inhibit chemokine function. On the contrary, HSV SgGs enhance chemotaxis both in vitro and in vivo through increasing directionality, potency and receptor signaling. This is the first report, to our knowledge, of a viral chemokine binding protein from a human pathogen that increases chemokine function and points towards a previously undescribed strategy of immune modulation mediated by viruses.
Computer Programs and Methodologies for the Simulation of DNA Sequence Data with Recombination

Computer simulations are useful in evolutionary biology for hypothesis testing, to verify analytical methods, to analyze interactions among evolutionary processes, and to estimate evolutionary parameters. In particular, the simulation of DNA sequences with recombination may help in understanding the role of recombination in diverse evolutionary questions, such as the genome structure. Consequently, plenty of computer simulators have been developed to simulate DNA sequence data with recombination. However, the choice of an appropriate tool, among all currently available simulators, is critical if recombination simulations are to be biologically meaningful. This review provides a practical survival guide to commonly used computer programs and methodologies for the simulation of coding and non-coding DNA sequences with recombination. It may help in the correct design of computer simulation experiments of recombination. In addition, the study includes a review of simulation studies investigating the impact of ignoring recombination when performing various evolutionary analyses, such as phylogenetic tree and ancestral sequence reconstructions. Alternative analytical methodologies accounting for recombination are also reviewed.
Dissection of the internal carotid artery causing Horner syndrome and palsy of cranial nerve XII

A 61-year-old right-handed man presented with a two-day history of a new headache that had developed gradually several hours after he dived into a lake. The headache, which encompassed the entire left side of the head, had a maximal intensity of 10 out of 10 and was described as dull and constant
Experimental Study on Damage Detection in Timber Specimens Based on an Electromechanical Impedance Technique and RMSD-Based Mahalanobis Distance

In the electromechanical impedance (EMI) method, the PZT patch performs the functions of both sensor and exciter. Due to the high frequency actuation and non-model based characteristics, the EMI method can be utilized to detect incipient structural damage. In recent years EMI techniques have been widely applied to monitor the health status of concrete and steel materials, however, studies on application to timber are limited. This paper will explore the feasibility of using the EMI technique for damage detection in timber specimens. In addition, the conventional damage index, namely root mean square deviation (RMSD) is employed to evaluate the level of damage. On that basis, a new damage index, Mahalanobis distance based on RMSD, is proposed to evaluate the damage severity of timber specimens. Experimental studies are implemented to detect notch and hole damage in the timber specimens. Experimental results verify the availability and robustness of the proposed damage index and its superiority over the RMSD indexes.
Predicting Potential Global Distributions of Two Miscanthus Grasses: Implications for Horticulture, Biofuel Production, and Biological Invasions

In many regions, large proportions of the naturalized and invasive non-native floras were originally introduced deliberately by humans. Pest risk assessments are now used in many jurisdictions to regulate the importation of species and usually include an estimation of the potential distribution in the import area. Two species of Asian grass (Miscanthus sacchariflorus and M. sinensis) that were originally introduced to North America as ornamental plants have since escaped cultivation. These species and their hybrid offspring are now receiving attention for large-scale production as biofuel crops in North America and elsewhere. We evaluated their potential global climate suitability for cultivation and potential invasion using the niche model CLIMEX and evaluated the models’ sensitivity to the parameter values. We then compared the sensitivity of projections of future climatically suitable area under two climate models and two emissions scenarios. The models indicate that the species have been introduced to most of the potential global climatically suitable areas in the northern but not the southern hemisphere. The more narrowly distributed species (M. sacchariflorus) is more sensitive to changes in model parameters, which could have implications for modelling species of conservation concern. Climate projections indicate likely contractions in potential range in the south, but expansions in the north, particularly in introduced areas where biomass production trials are under way. Climate sensitivity analysis shows that projections differ more between the selected climate change models than between the selected emissions scenarios. Local-scale assessments are required to overlay suitable habitat with climate projections to estimate areas of cultivation potential and invasion risk.
Controlling amyloid growth in multiple dimensions

The great progress made in defining the structure of protein and peptide amyloid assemblies, particularly the arrangement of peptides in β-sheets, is counterbalanced by the still poor understanding of the higher organization of β-sheets within the fibril and overall fibril/fibril associations. The assembly pathway and basis of amyloid toxicity may well depend on these higher-order structural features. For example, significant evidence points to association between sheets as the rate limiting step in fibril assembly, and a critical metal binding site has now been identified that involves residues from different individual sheets. Here we review experiments that are identifying some of the issues associated with sheet–sheet association by investigating simple model peptides derived from the central core of the Aβ peptide implicated in Alzheimer's disease. These peptides transit between fibril/ribbon/nanotube morphologies in response to assembly conditions, laying the foundation for understanding the folding landscape for these higher order assemblies, revealing potential targets for therapeutic intervention, and opening strategies for the design of highly ordered peptide self-assembled microscale morphologies.
Self-Adaptive Multi-objective Evolutionary Algorithm for Molecular Design

Self-adaptation is an efficient way to control the strategy parameters of an Evolutionary Algorithm automatically during optimization. It is based on implicit evolutionary search in the space of strategy parameters, and has been proven to work well as on-line parameter control method for a variety of strategy parameters, from local to global ones. Our proposed Self-Adaptive Multi-Objective Evolutionary Algorithm is a two level algorithm. The proposed solution is applied on the problem of de novo molecular design. The outer level is the algorithm that is responsible for the self adaptive techniques and is based on Multi-Objective Genetic Algorithm. The inner level is based on the elite Multi-Objective Evolutionary Graph Algorithm. Both the outer and inner algorithms are variations of our previously proposed Multi-Objective Evolutionary Graph Algorithm framework. The outer Multi-Objective Genetic Algorithm operates on a chromosome of elements, while the inner elite Multi-Objective Evolutionary Graph Algorithm operates on molecular graph chromosomes. In general, the proposed solution: (i) searches a larger space, (ii) generates far more solutions per iteration, (iii) evaluates different sets of parameter options for the given problem, and (iv) proposes the fittest parameter sets that should be used for the given problem.
A longitudinal study into the transformation of a university teacher's conceptions of, and approach to, elearning

In seeking to meet the demands placed upon them, many universities are increasing their use of elearning. At the same time, a good deal of research is being undertaken into academic practice using elearning. The research reported in this paper is a longitudinal case study that examines one teacher at The University of Sydney, Australia, as he transformed in his conceptions of, and approach to, teaching using elearning over two years. This research forms part of a larger project with embedded case studies focusing on teachers from the Health Sciences and related disciplines. Data for this case study was collected between February 2007 and December 2008 through semi-structured interviews with the participant and observations of the participant‟s elearning resource. The findings demonstrate that as the participant worked with his elearning resource over two years, he transformed the resource to improve learning and teaching. Through the process, he transformed his conceptions of, and approaches to, elearning, as well as his lesson image. He also came to understand the learning needs and styles of his students and their approaches to elearning. The research provides insight into the role of reflection and support of university teachers in their use of elearning.
Neuropeptide Y Y5 Receptor Promotes Cell Growth through Extracellular Signal-Regulated Kinase Signaling and Cyclic AMP Inhibition in a Human Breast Cancer Cell Line

Overexpression of neuropeptide Y (NPY) and its receptor system has been reported in various types of cancers. NPY Y5 receptor (Y5R) has been implicated in cell growth and angiogenesis. However, the role of Y5R in breast cancer is unknown. To identify the role of Y5R in breast cancer, we screened several breast cancer cell lines to examine the expression of Y5R and its function in breast cancer. All screened cell lines express both Y1 receptor and Y5R except BT-549, which expresses mainly Y5R. Binding studies showed that NPY, Y5R-selective agonist peptide, and Y5R-selective antagonist (CGP71683A) displaced 125I-PYY binding in BT-549 cell membranes in a dose-dependent manner. The displacement studies revealed the presence of two binding sites in Y5R with IC50 values of 29 pmol/L and 531 nmol/L. NPY inhibited forskolin-stimulated cyclic AMP accumulation with an IC50 value of 52 pmol/L. NPY treatment of BT-549 cells induced extracellular signal-regulated kinase phosphorylation but did not alter intracellular calcium. Y5R activation stimulates BT-549 cell growth, which is inhibited by CGP71683A, pertussis toxin, and extracellular signal-regulated kinase blockade. CGP71683A alone induced cell death in a time- and dose-dependent manner in Y5R-expressing cells. The stimulation of MDA MB-231 cell migration by NPY is inhibited by CGP71683A. Together, our results suggest that Y5R plays an important role in cancer cell growth and migration and could be a novel therapeutic target for breast cancer. Mol Cancer Res; 8(4); 604–14. ©2010 AACR.
Dynamical Model for Gamification@Learning

This paper proposes a dynamical model for the gamification@learning and presents its simulation. Based on the theories of Game Design Features (GDF - cool features, fancy graphics, challenging puzzles, and an intriguing setting and story), Key Characteristics of a Learning Game (KCLG - Challenge, Curiosity, Fantasy and Control), a theory of educational environment design model (ARCS - attention, relevance, confidence and satisfaction), and the theoretical background of Gamification labeled as the MDA (Mechanics, dynamics, and aesthetics) framework, four primary factors such as curiosity, challenge, fantasy and control have been originated. By using these four primary factors, the dynamical model for Gamification was developed. In this paper an example for the model is considered and simulated. The example and simulation make the values and characteristics of the four primary factors meaningful. I posit that this dynamical model for the gamification can strengthen the ‘theoretical foundation’ of gamification as well as spread the idea of ‘the pure and right function of game’.
Physical and Psychological Benefits of Written Emotional Expression

Abstract. The last several decades have witnessed a substantial increase in the number of individuals suffering from both diagnosable and subsyndromal mental health problems. Consequently, the development of cost-effective treatment methods, accessible to large populations suffering from different forms of mental health problems, became imperative. A very promising intervention is the method of expressive writing (EW), which may be used in both clinically diagnosable cases and subthreshold symptomatology. This method, in which people express their feelings and thoughts related to stressful situations in writing, has been found to improve participants’ long-term psychological, physiological, behavioral, and social functioning. Based on a thorough analysis and synthesis of the published literature (also including most recent meta-analyses), the present paper presents the expressive writing method, its short- and long-term, intra-and interpersonal effects, different situations and conditions in which it has .