Miracle-dz/UniFAR-FTUs huggingface dataset:
Replication stress induces tumor-like microdeletions in FHIT/FRA3B

Common fragile sites (CFSs) are loci that preferentially exhibit metaphase chromosome gaps and breaks after partial inhibition of DNA synthesis. The fragile site FRA3B, which lies within the FHIT tumor-suppressor gene, is a site of frequent heterozygous and homozygous deletions in many cancer cells and precancerous lesions. The great majority of FHIT and other CFS-associated gene rearrangements in tumors are submicroscopic, intralocus deletions of hundreds of kilobases that often result in inactivation of associated genes. Although CFS instability leads to chromosome gaps and breaks and translocations, there has been no direct evidence showing that CFS instability or replication stress can generate large submicroscopic deletions of the type seen in cancer cells. Here, we have produced FHIT/FRA3B deletions closely resembling those in tumors by exposing human–mouse chromosome 3 somatic hybrid cells to aphidicolin-mediated replication stress. Clonal cell populations were analyzed for deletions by using PCR, array comparative genomic hybridization (aCGH), and FISH. Thirteen percent to 23% of clones exhibited submicroscopic FHIT deletions spanning ≈200–600 kb within FRA3B. Chromosomes with FRA3B deletions exhibited significantly decreased fragility of this locus, with a 2- to 12-fold reduction in metaphase gaps and breaks compared with controls. Sequence analysis showed no regions of homology at breakpoints and suggests involvement of NHEJ in generating the deletions. Our results demonstrate that replication stress induces a remarkably high frequency of tumor-like microdeletions that reduce fragility at a CFS in cultured cells and suggests that similar conditions during tumor formation lead to intralocus deletion and inactivation of genes at CFSs and perhaps elsewhere in the genome.
Robust image filtering using joint static and dynamic guidance

Regularizing images under a guidance signal has been used in various tasks in computer vision and computational photography, particularly for noise reduction and joint upsampling. The aim is to transfer fine structures of guidance signals to input images, restoring noisy or altered structures. One of main drawbacks in such a data-dependent framework is that it does not handle differences in structure between guidance and input images. We address this problem by jointly leveraging structural information of guidance and input images. Image filtering is formulated as a nonconvex optimization problem, which is solved by the majorization-minimization algorithm. The proposed algorithm converges quickly while guaranteeing a local minimum. It effectively controls image structures at different scales and can handle a variety of types of data from different sensors. We demonstrate the flexibility and effectiveness of our model in several applications including depth super-resolution, scale-space filtering, texture removal, flash/non-flash denoising, and RGB/NIR denoising.
Qualitative Spatial Representation and Reasoning: An Overview

The paper is a overview of the major qualitative spatial representation and reasoning techniques. We survey the main aspects of the representation of qualitative knowledge including ontological aspects, topology, distance, orientation and shape. We also consider qualitative spatial reasoning including reasoning about spatial change. Finally there is a discussion of theoretical results and a glimpse of future work. The paper is a revised and condensed version of [33,34].
Do mediated contexts differ in information richness? A comparison of collocated and dispersed meetings

Examines the question of whether or not media differ in the perceptions they generate among users with respect to social presence, communication effectiveness and the communication interface. The study observes these factors over a four-session period among 33 groups performing a collaborative writing task. Groups were assigned to one of three treatments: face-to-face, distributed synchronous and distributed asynchronous. No significant differences were observed between distributed and face-to-face conditions in their patterns of change over time. Results do indicate, however, that mediated contexts differed in terms of perceived social presence, communication effectiveness and the communication interface, when considered on a session-by-session basis.
RRO COMPENSATION OF HARD DISK DRIVES WITH MULTIRATE REPETITIVE PTC

Abstract In this paper, novel repetitive controllers are proposed based on perfect tracking control (PTC) in order to reject high-order repeatable runout (RRO) of hard disk drives. First, the feedback approach of the repetitive PTC (RPTC) is developed with internal model of periodic disturbance. Although this method has performance robustness against small plant variation, the internal model worsens the stability robustness for big modeling error. Then, the feedforward approach of RPTC is introduced with switching mechanism such that the high-order RRO can be rejected without any sacrifice of the closed-loop characteristics. In both approaches, multirate feedforward control is utilized to overcome the unstable zero problem of discrete-time plant. Finally, the advantages and disadvantages are demonstrated through simulations and experiments.
A Unified Multitask Architecture for Predicting Local Protein Properties

A variety of functionally important protein properties, such as secondary structure, transmembrane topology and solvent accessibility, can be encoded as a labeling of amino acids. Indeed, the prediction of such properties from the primary amino acid sequence is one of the core projects of computational biology. Accordingly, a panoply of approaches have been developed for predicting such properties; however, most such approaches focus on solving a single task at a time. Motivated by recent, successful work in natural language processing, we propose to use multitask learning to train a single, joint model that exploits the dependencies among these various labeling tasks. We describe a deep neural network architecture that, given a protein sequence, outputs a host of predicted local properties, including secondary structure, solvent accessibility, transmembrane topology, signal peptides and DNA-binding residues. The network is trained jointly on all these tasks in a supervised fashion, augmented with a novel form of semi-supervised learning in which the model is trained to distinguish between local patterns from natural and synthetic protein sequences. The task-independent architecture of the network obviates the need for task-specific feature engineering. We demonstrate that, for all of the tasks that we considered, our approach leads to statistically significant improvements in performance, relative to a single task neural network approach, and that the resulting model achieves state-of-the-art performance.
Facing the Challenges of Structure-Based Target Prediction by Inverse Virtual Screening

Computational target prediction for bioactive compounds is a promising field in assessing off-target effects. Structure-based methods not only predict off-targets, but, simultaneously, binding modes, which are essential for understanding the mode of action and rationally designing selective compounds. Here, we highlight the current open challenges of computational target prediction methods based on protein structures and show why inverse screening rather than sequential pairwise protein-ligand docking methods are needed. A new inverse screening method based on triangle descriptors is introduced: iRAISE (inverse Rapid Index-based Screening Engine). A Scoring Cascade considering the reference ligand as well as the ligand and active site coverage is applied to overcome interprotein scoring noise of common protein-ligand scoring functions. Furthermore, a statistical evaluation of a score cutoff for each individual protein pocket is used. The ranking and binding mode prediction capabilities are evaluated on different datasets and compared to inverse docking and pharmacophore-based methods. On the Astex Diverse Set, iRAISE ranks more than 35% of the targets to the first position and predicts more than 80% of the binding modes with a root-mean-square deviation (RMSD) accuracy of <2.0 Å. With a median computing time of 5 s per protein, large amounts of protein structures can be screened rapidly. On a test set with 7915 protein structures and 117 query ligands, iRAISE predicts the first true positive in a ranked list among the top eight ranks (median), i.e., among 0.28% of the targets.
A joint model of complex wavelet coefficients for texture retrieval

We present a Copula-based statistical model of complex wavelet coefficient magnitudes for color texture image retrieval. Our model is based on two-parameter Weibull distributions and a multivariate Student t Copula. For similarity measurement we employ a Monte- Carlo approach to approximate the Kullback-Leibler divergence between two models. The experimental retrieval results show that the incorporation of the dependency structure between subbands significantly improves retrieval accuracy compared to previous approaches.
Prevalence and Risk Factors of Asymptomatic Peripheral Arterial Disease in Patients with COPD in Taiwan

Aim Chronic obstructive pulmonary disease (COPD) is an independent risk factor for cardiovascular morbidity and mortality. The aim of this study was to determine the prevalence of asymptomatic peripheral arterial disease (PAD) and the associated risk factors for patients with COPD. Methods This prospective cross-sectional study enrolled 427 COPD patients (mean age: 70.0 years) without PAD symptoms consecutively. Demographic data, lung function and cardiovascular risk factors were recorded. The ankle-brachial index (ABI) was used to detect PAD (ABI<0.90). Results The overall prevalence of asymptomatic PAD in the COPD patients was 8% (2.5% in the younger participants (<65 years of age, n = 118) and 10% in the elderly participants (≥65 years of age, n = 309). The COPD patients with asymptomatic PAD had a significantly higher rate of hyperlipidemia (47.1% vs. 10.4%) and hypertension (79.4% vs. 45.8%) than those without asymptomatic PAD (p<0.05). There was no significant difference in lung function (forced vital capacity and forced expiratory volume in one second) between the two groups. In multivariate logistic regression, hyperlipidemia was the strongest independent factor for PAD (odds ratio (OR): 6.89, p<0.005), followed by old age (OR: 4.80), hypertension (OR: 3.39) and smoking burden (pack-years, OR: 1.02). Conclusions The prevalence of asymptomatic PAD among COPD patients in Taiwan is lower than in Western countries. Hyperlipidemia, old age, hypertension, and smoking burden were the associated cardiovascular risk factors. However, there was no association between lung function and PAD in the COPD patients.
'Authority is everything': A study of the politics of textual ownership

The relationships between text, knowledge and power in the construction of writer identities have been the source of much debate among philosophers,literary scholars and language educators (e.g., Bakhtin 1981; Kristeva 1986; Pennycook 2001). Such interrelationships are played out in the transcultural encounters that occur between students and their lecturers on a daily basis in our contemporary university classrooms. This article explores how two undergraduate students from different language backgrounds, studying at a major Australian university, struggle to deal with the politics of text/knowledge construction in their quest for a sense of ownership and authorial control over the assignments they produce. Data consisting of interviews and assignments by students from different disciplinary fields have been selected from a larger study into plagiarism and intertextuality. Drawing on the work of Bakhtin (1981), Kristeva (1986) and Howard (1992; 1995; 1999), my analysis indicates firstly, that students feel constrained by the homogenising (Holton 2000) forces of the academic writing conventions that they feel obliged to imitate; and secondly, confused by unified and autonomous concepts of authorship and originality that fail to take account of the 'shared' nature of the processes of text/knowledge production. I conclude by suggesting that the development of writer identity needs to be seen as part of the ongoing epistemological negotiations that occur between students and lecturers as they struggle to construct desired meanings across texts. I then consider the implications of these findings for academic writing pedagogy.
Early Arterial Stiffness and Inflammatory Bio-Markers in Normotensive Polycystic Kidney Disease Patients

Background/Aims: Cardiovascular disease is the main cause of morbidity and mortality in autosomal-dominant polycystic kidney disease (ADPKD) patients. To clarify temporal relationship between ADPKD, hypertension and the loss of renal function, we examined these factors in patients with early-stage ADPKD who did not yet have hypertension. Methods: Fifty patients with ADPKD (42% males, 36.6 ± 9.9 years, no blood pressure medication) and 50 healthy controls (44% males, 35.4 ± 6.4 years) were studied cross-sectionally. Pulse wave velocity (PWV), cardiac morphology and function, aortic elastic indexes, estimated glomerular filtration rate (eGFR), 24-hour ambulatory blood pressure, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and highly sensitive C-reactive protein (hs-CRP) were measured in all participants, using conventional methods. Results: Despite a normal blood pressure, aortic stiffness index and pulse wave velocity values were increased in patients compared to controls (6.8 ± 4.7 vs. 5.1 ± 3.3, p = 0.043 and 9.6 ± 1.3 vs. 5.8 ± 1.1 m/s, p < 0.001). In univariate analysis, IL-6, TNF-α, hs-CRP and eGFR were all significantly correlated with PWV. The independence of these correlations were analyzed in a regression model, and showed PWV to be significantly predicted by IL-6, TNF-α and hs-CRP. Conclusion: Increased arterial stiffness and pulse wave velocity are early manifestations of ADPKD appearing before hypertension or reduced eGFR. However, these vascular abnormalities are related to signs of systemic low grade inflammation, suggesting a common pathophysiological mechanism apparently present also in other vascular diseases but yet to be elucidated.
License to laugh : humor in the classroom

Laughter stimulates creativity, reduces stress, and motivates students to perform. These are only some of the benefits that make humor a great tool for the classroom. With practical strategies, simple methods, examples, and classroom-tested activities, this book shows you how to use appropriate humor with students to make learning easier and more fun. Chapters cover how to introduce humor into your teaching repertoire, the benefits and caveats, and how to develop your own unique comic style. With laughter, you will become a more effective educator and make teaching and learning more fun! All Levels.
Gender differences in survival following hospitalisation for COPD

Background Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Gender differences in the clinical expression of COPD are increasingly recognised, but outcome differences have not been systematically examined. Gender differences in survival and rate of rehospitalisation were investigated in a large cohort of elderly patients with chronic airflow obstruction hospitalised for COPD. Methods The databases from the Québec provincial health insurance plan were used. The study population included subjects aged >66 years who received ≥3 prescriptions for respiratory medications in any 1-year period between 1 January 1990 and 31 December 2001. The study cohort consisted of patients with a first hospitalisation for COPD, after selection into the study population. Patients were followed until death or 31 December 2003. The Kaplan–Meier method was used to estimate time to death and time to first hospitalisation for obstructive airways disease (COPD or asthma). The Cox proportional hazards model was used to determine the effect of male gender on all-cause mortality and rehospitalisation. Results The cohort consisted of 19 260 women and 23 893 men with a mean age of 77 years. 11 245 (58.4%) women and 16 754 (70.1%) men died after cohort entry. Male sex was associated with a significantly increased risk of death (adjusted HR 1.45, 95% CI 1.42 to 1.49) and with a significantly increased risk of rehospitalisation for obstructive airways disease (adjusted HR 1.12, 95% CI 1.09 to 1.15). Conclusion Mean survival and time to rehospitalisation for obstructive airways disease are significantly better for female patients.
Low-Cost Task Scheduling for Distributed-Memory Machines

In compile-time task scheduling for distributed-memory systems, list scheduling is generally accepted as an attractive approach, since it pairs low cost with good results. List-scheduling algorithms schedule tasks in order of their priority. This priority can be computed either (1) statically, before the scheduling, or (2) dynamically, during the scheduling. In this paper, we show that list scheduling with statically-computed priorities (LSSP) can be performed at a significantly lower cost than existing approaches, without sacrificing performance. Our approach is general, i.e. it can be applied to any LSSP algorithm. The low complexity is achieved by using low-complexity methods for the most time-consuming parts in list-scheduling algorithms, i.e. processor selection and task selection, preserving the criteria used in the original algorithms. We exemplify our method by applying it to the MCP (Modified Critical Path) algorithm. Using an extension of this method, we can also reduce the time complexity of a particular class of list scheduling with dynamic priorities (LSDP) [including algorithms such as DLS (Dynamic Level Scheduling), ETF (Earliest Task First) and ERT (Earliest Ready Task)]. Our results confirm that the modified versions of the list-scheduling algorithms obtain a performance comparable to their original versions, yet at a significantly lower cost. We also show that the modified versions of the list-scheduling algorithms consistently outperform multi-step algorithms, such as DSC-LLB (Dynamic Sequence Clustering with List Load Balancing), which also have higher complexity and clearly outperform algorithms in the same class of complexity, such as CPM (Critical Path Method).
Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation.

CONTEXT Screening of patients with venous thromboembolism (VTE) for thrombophilic risk factors is common clinical practice. Because of the large number of risk factors, assessing the risk of recurrence in an individual patient is complex. A method covering multicausal thrombophilia is therefore required. OBJECTIVE To investigate the relationship between recurrence of VTE and a simple global coagulation assay measuring thrombin generation. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 914 patients with first spontaneous VTE who were followed up for an average of 47 months after discontinuation of vitamin K antagonist therapy. The study was conducted at the Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria, between July 1992 and July 2005. Thrombin generation was measured by a commercially available assay system. Patients with a previous or secondary VTE; antithrombin, protein C, or protein S deficiencies; presence of lupus anticoagulant; cancer; or pregnancy were excluded. MAIN OUTCOME MEASURE Objectively documented symptomatic recurrent VTE. RESULTS Venous thromboembolism recurred in 100 patients (11%). Patients without recurrent VTE had lower thrombin generation than patients with recurrence (mean [SD], 349.2 [108.0] nM vs 419.5 [110.5] nM, respectively; P<.001). Compared with patients who had thrombin generation greater than 400 nM, the relative risk (RR) of recurrence was 0.42 (95% confidence interval [CI], 0.26-0.67; P<.001) in patients with values between 400 nM and 300 nM; for patients with lower values, the RR was 0.37 (95% CI, 0.21-0.66; P = .001). After 4 years, the probability of recurrence was 6.5% (95% CI, 4.0%-8.9%) among patients with thrombin generation less than 400 nM compared with 20.0% (95% CI, 14.9%-25.1%) among patients with higher values (P<.001). Patients with thrombin generation less than 400 nM, representing two thirds of patients, had a 60% lower RR of recurrence than those with greater values (RR, 0.40; 95% CI, 0.27-0.60; P<.001). CONCLUSION Measurement of thrombin generation identifies patients at low risk for recurrent VTE.
Determination of plasma viral load in HIV‐1 infection by quantitative competitive polymerase chain reaction

ObjectivesTo better characterize viral load profiles through the course of HIV-1 disease and in response to treatment, and to further evaluate quantitative competitive polymerase chain reaction for measurement of viral load, we extended our comparative evaluation of this and other viral load measurements to a total of 118 patients, representing all stages of HIV-1 disease. DesignFor cross-sectional analysis across the spectrum of HIV-1 disease, plasma viral load was evaluated in 112 HIV-1-infected patients by quantitative competitive polymerase chain reaction analysis, plasma p24 antigen assay, plasma immune complex-dissociated p24 antigen assay and an endpoint dilution viral culture. Longitudinal specimens from six additional patients were analyzed, extending from the time of presentation with symptomatic acute HIV-1 infection through up to more than 2 years of follow-up. Longitudinal specimens were also studied for three patients over the period of initiation of zidovudine treatment, for 6 weeks of treatment and following temporary withdrawal of the treatment. MethodsAll measurement techniques were assessed in replicate aliquots of plasma. ResultsQuantitative competitive polymerase chain reaction was the most sensitive measure of viral load, and was best correlated with CD4+ T-cell counts. In longitudinally studied patients, this technique also allowed measurement of plasma virus levels throughout the period of follow-up, even when culture and p24 assays became negative following resolution of acute HIV-1 infection. The quantitative competitive polymerase chain reaction was also able to detect rapid and substantial changes in viral load associated with initiation and temporary withdrawal of antiviral treatment. ConclusionsThe quantitative competitive polymerase chain reaction is promising as a sensitive and accurate method for measuring plasma viral load in HIV-1-infected patients, and is useful for following changes in viral load over the natural history of infection and following treatment intervention. The technique is particularly useful for patients with >200x106 CD4+ T cells/l, in whom other viral markers are typically negative.