Miracle-dz/UniFAR-FTUs huggingface dataset:
Continuous Zebularine Treatment Effectively Sustains Demethylation in Human Bladder Cancer Cells

ABSTRACT During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Recently, we reported that zebularine [1-(β-d-ribofuranosyl)-1,2-dihydropyrimidin-2-one] acts as an inhibitor of DNA methylation and exhibits chemical stability and minimal cytotoxicity both in vitro and in vivo. Here we show that continuous application of zebularine to T24 cells induces and maintains p16 gene expression and sustains demethylation of the 5′ region for over 40 days, preventing remethylation. In addition, continuous zebularine treatment effectively and globally demethylated various hypermethylated regions, especially CpG-poor regions. The drug caused a complete depletion of extractable DNA methyltransferase 1 (DNMT1) and partial depletion of DNMT3a and DNMT3b3. Last, sequential treatment with 5-aza-2′-deoxycytidine followed by zebularine hindered the remethylation of the p16 5′ region and gene resilencing, suggesting the possible combination use of both drugs as a potential anticancer regimen.
Structural Basis of Cooperativity in Human UDP-Glucose Dehydrogenase

Background UDP-glucose dehydrogenase (UGDH) is the sole enzyme that catalyzes the conversion of UDP-glucose to UDP-glucuronic acid. The product is used in xenobiotic glucuronidation in hepatocytes and in the production of proteoglycans that are involved in promoting normal cellular growth and migration. Overproduction of proteoglycans has been implicated in the progression of certain epithelial cancers, while inhibition of UGDH diminished tumor angiogenesis in vivo. A better understanding of the conformational changes occurring during the UGDH reaction cycle will pave the way for inhibitor design and potential cancer therapeutics. Methodology Previously, the substrate-bound of UGDH was determined to be a symmetrical hexamer and this regular symmetry is disrupted on binding the inhibitor, UDP-α-D-xylose. Here, we have solved an alternate crystal structure of human UGDH (hUGDH) in complex with UDP-glucose at 2.8 Å resolution. Surprisingly, the quaternary structure of this substrate-bound protein complex consists of the open homohexamer that was previously observed for inhibitor-bound hUGDH, indicating that this conformation is relevant for deciphering elements of the normal reaction cycle. Conclusion In all subunits of the present open structure, Thr131 has translocated into the active site occupying the volume vacated by the absent active water and partially disordered NAD+ molecule. This conformation suggests a mechanism by which the enzyme may exchange NADH for NAD+ and repolarize the catalytic water bound to Asp280 while protecting the reaction intermediates. The structure also indicates how the subunits may communicate with each other through two reaction state sensors in this highly cooperative enzyme.
Human Values Compatible with Sustainable Development

The values that people hold are the most important factor in deciding whether they endorse sustainable development. At the same time value orientations are likely to change over long time periods. International long-term research conducted by Ronald Inglehart in the second half of the twentieth century tried to capture the shift from material to post-material values. With respect to a sustainable lifestyle the research revealed a problem: there is a relationship between post-materialistic attitudes and the level of GDP. What can be done to preserve the quality of the environment and at the same time allow countries to develop economically? Czech environmentalist Josef Vavroušek defined a framework of key values that are typical for an industrial society. He assigned alternative values to them that should be compatible with sustainable living. The values of Euro-American culture and civilization stem from the heritage of Judaism and Christianity, which find fundamental ethical importance in the Ten Commandments. Modern times, however, bring new challenges and it is not easy to distinguish between what is good (or what is still acceptable) and what is not; for example, genetic engineering, experiments on humans, polluting the environment and lives in excessive wealth.
Multi-domain physical system modeling and control based on meta-modeling and graph rewriting

A methodology is presented which enables the specification and synthesis of software tools to aid in plant and controller modeling for multi-domain (electrical, mechanical, hydraulic, and thermal) physical systems. The methodology is based on meta-modeling and graph rewriting. The plant is modeled in a domain-specific formalism called the Real World Visual Model (RWVM). Such a model is successively transformed to an Idealized Physical Model (IPM), to an Acausal Bond Graph (ABG), and finally to a Causal Bond Graph (CBG). A Modelica (www.modelica.org) model, consisting of a Causal (algebraic and differential equation) Block Diagram (CBD), is generated from the CBG. All transformations are explicitly modeled using Graph Grammars. A PID controller model, specified in Modelica as a CBD is subsequently integrated with the plant model. AToM3 (atom3.cs.mcgill.ca), A Tool for Multi-formalism and Meta Modeling is used to meta-model and synthesize visual modeling environments for the RWVM, IPM, ABG, and CBG formalisms as well as for transformations between them. The entire process of modeling, transformation, and simulation is demonstrated by means of a hoisting device example. Our methodology drastically reduces development time (of the modeling tool an indirectly of the domain-specific models), integrates model checking via Bond Graph causal analysis, and facilitates management and reuse of meta-knowledge by explicitly modeling formalisms and transformations.
Expert based prediction of user preferences

Two influential strands in Recommender systems (RS) are the collaborative filtering and content based filtering that by taking into account user communities or interaction history suggest to the active user interesting items. However, the aforementioned approaches do not work well when confronted with new users with few interactions; or with the addition of new items. In such cases, the guidance of an expert could help the active user. In this paper we provide a definition of expert users that can be reduced into two components the expertise and the contribution. The former is related to the content of items evaluated by an expert and the latter refers to the influence of the expert to the users of a RS. In particular, contribution is learnt with the aid of a perceptron. Experts users are defined for values of the features of the items. Furthermore, we have studied the temporal evolution of the experts, as new users, new items, or new item evaluations are added into the system. Moreover, we have compared the proposed expert based method with a stereotype based method, since for both methods a minimal interaction of the active user with the RS suffices. The data originated from the MovieLens set with enhancements from the IMDB.
Spatially Coupled Turbo-Like Codes

In this paper, we introduce the concept of spatially coupled turbo-like codes (SC-TCs) as the spatial coupling of a number of turbo-like code ensembles. In particular, we consider the spatial coupling of parallel concatenated codes, introduced by Berrou et al., and that of serially concatenated codes (SCCs), introduced by Benedetto et al. Furthermore, we propose two extensions of braided convolutional codes (BCCs), and a class of turbo-like codes which have an inherent spatially coupled structure, to higher coupling memories, and show that these yield improved belief propagation (BP) thresholds as compared with the original BCC ensemble. We derive the exact density evolution (DE) equations for SC-TCs and analyze their asymptotic behavior on the binary erasure channel. We also consider the construction of families of rate-compatible SC-TC ensembles. Our numerical results show that the threshold saturation of the BP decoding threshold to the maximum a posteriori threshold of the underlying uncoupled ensembles occurs for large enough coupling memory. The improvement of the BP threshold is especially significant for SCCs and BCCs, whose uncoupled ensembles suffer from a poor BP threshold. For a wide range of code rates, SC-TCs show close-to-capacity performance as the coupling memory increases. We further give a proof of threshold saturation for SC-TC ensembles with identical component encoders. In particular, we show that the DE of SC-TC ensembles with identical component encoders can be properly rewritten as a scalar recursion. This allows us to define potential functions and prove threshold saturation using the proof technique recently introduced by Yedla et al.
A singing style modeling system for singing voice synthesizers

This paper describes a method of modeling singing styles by a statistical method. In this system, singing expression parameters consisting of melody and dynamics which are derived from F0 and power are modeled by context-dependent Hidden Markov Models (HMMs.) A modeling method of the parameters are optimized for dealing with them. Since parameters we focus on are essential but general ones for singing synthesizers, generated parameters from the trained models may be possible to be applied to many of them. In the experiment, we trained singing style models by using singing recording with much expressive style, then parameters were generated for songs not included in training data and actually applied to our singing synthesizer VOCALOID. As a result, the style was well perceived in the synthesized sound with good synthetic quality
Software Requirements Specification for Imaging Systems

This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder
Hemispheric Shape of European and Japanese Brains: 3-D MRI Analysis of Intersubject Variability, Ethnical, and Gender Differences

Hemispheric shape is studied using magnetic resonance imaging and 3-D reconstructions in right-handed, male and female, European and Japanese subjects. Japanese hemispheres are relatively shorter, but wider than European hemispheres. Regions of maximal intersubject variability in hemispheric shape are present in the occipital and temporal lobes in each sample. Deviations from this general pattern are found in the (i) right inferior parietal lobule (European hemispheres are more variable than Japanese), (ii) lower third of the pre- and postcentral gyri (female Japanese hemispheres are less variable than the other samples), (iii) right inferior frontal gyrus (male European hemispheres are more variable than the other samples), and (iv) polar part of the frontal lobe (female European hemispheres are less variable than the other samples). The distribution of intersubject variability between the hemispheres is less asymmetric in female than male brains. Male Japanese hemispheres are shorter but wider than female Japanese hemispheres, whereas European hemispheres show the inverse gender relations. These results demonstrate that hemispheric shape shows a considerable intersubject variability, which is not randomly distributed over the cortical surface but displays distinct regions of higher variability. Despite this intersubject variability significant interethnic- and gender-related differences in hemispheric shape are present, which may be relevant if individual brains have to be warped to a single or mean reference brain or realistic brain models are to be constructed.
IMMUNOLOGIC TOLERANCE AFTER SPECIFIC IMMUNIZATION

Specific immunologic tolerance to bovine serum albumin (BSA) was induced in approximately one-half of the rabbits that had been primarily immunized and were prepared for a secondary antibody response to BSA. The state of tolerance lasted for several months in the majority of rabbits and was not easily terminated by immunization with human serum albumin followed by BSA.
The Reliability and Validity of Key Informant Data from Dyadic Relationships in Marketing Channels

Key informant reports from both sides of a set of wholesaler-retailer dyads are analyzed to investigate the convergent and discriminant validity of the measures. These measures, derived from a political economy model, describe the structural form and collective sentiments within the dyadic interaction. The results indicate that the structural form measures have convergent and discriminant validity. However, the sentiments variables fail to show adequate validity. The methodological and theoretical implications of the results are assessed.
Adaptive Feature Abstraction for Translating Video to Language

A new model for video captioning is developed, using a deep three-dimensional Convolutional Neural Network (C3D) as an encoder for videos and a Recurrent Neural Network (RNN) as a decoder for captions. We consider both "hard" and "soft" attention mechanisms, to adaptively and sequentially focus on different layers of features (levels of feature "abstraction"), as well as local spatiotemporal regions of the feature maps at each layer. The proposed approach is evaluated on three benchmark datasets: YouTube2Text, M-VAD and MSR-VTT. Along with visualizing the results and how the model works, these experiments quantitatively demonstrate the effectiveness of the proposed adaptive spatiotemporal feature abstraction for translating videos to sentences with rich semantics.
Vasoactivity of Verapamil in the Canine Hindlimb and Sympathetic Nervous System Interaction

Since enhanced sensitivity to verapamil in essential hypertension has been noted, a relationship between verapamil and the sympathetic nervous system has been suggested. It has also been noted that both verapamil and lumbar sympathectomy appear to decrease the vasospasm seen in Raynaud's phenomenon. To further investigate the possible interrelationship between verapamil and the sympathetic nervous system, a unilateral lumbar sympathectomy was performed on eight dogs. Two weeks later the femoral artery blood flow response to intra-arterial verapamil was compared on the sympathectomy limb side and the non-sympathectomy limb side, Blood flow measurements were done without surgical trauma by video dilution technique. Although baseline femoral artery blood flow was unchanged and equal on both sides following sympathectomy (4.6% of cardiac output), there was a significant rise, p<0.05, in the blood flow response to verapamil on the side of sympathectomy. Therefore, sympathectomy appears to enhance the calcium channel blocking properties of verapamil
Stakeholders, networks and links in early childhood policy: Network analysis and the Transition to School: Position Statement

The importance of a positive start to school has been highlighted in a range of national and international research. This has stimulated considerable ongoing research attention, as well as initiatives across policy and practice, all with the aim of promoting a positive transition to school for all children. Despite the common interests across these sectors, the links and/or relationships between and among research, policy and practice remain unclear. This article maps the potential online users of the Transition to School: Position Statement – a document developed collaboratively by researchers, policymakers and practitioners – and organisations whose ambit includes transition to school. Using network analysis, the authors identify the online network of stakeholders involved in the field of early childhood and the links between these, before considering how such links might influence discourse and policy formation around transition to school. The analysis highlights weak cross-sectoral links and online networks dominated by government departments and agencies. Implications of these results are explored and the potential for digital research methods in research about transition to school is considered.
Social Learning and Self-Control

Social learning theory is one of the most prominent general theories of crime. Yet recent research has called into question its applicability to all offenders. Specifically, the influence of antisocial peers has been found to exert a stronger effect among those individuals evincing higher levels of criminal propensity (deemed social amplification), whereas other components of the theory have either not been shown to interact with criminal propensity or not been tested. This study examines several social learning theory components to determine whether its influence is dependent on an individual’s level of self-control. Results suggest little support for the social amplification hypothesis as the components of social learning theory were found to operate similarly across individuals regardless one’s level of self-control. Implications for criminological theory are discussed.
Molecular Tools for the Selective Detection of Nine Diatom Species Biomarkers of Various Water Quality Levels

Our understanding of the composition of diatom communities and their response to environmental changes is currently limited by laborious taxonomic identification procedures. Advances in molecular technologies are expected to contribute more efficient, robust and sensitive tools for the detection of these ecologically relevant microorganisms. There is a need to explore and test phylogenetic markers as an alternative to the use of rRNA genes, whose limited sequence divergence does not allow the accurate discrimination of diatoms at the species level. In this work, nine diatom species belonging to eight genera, isolated from epylithic environmental samples collected in central Italy, were chosen to implement a panel of diatoms covering the full range of ecological status of freshwaters. The procedure described in this work relies on the PCR amplification of specific regions in two conserved diatom genes, elongation factor 1-a (eEF1-a) and silicic acid transporter (SIT), as a first step to narrow down the complexity of the targets, followed by microarray hybridization experiments. Oligonucleotide probes with the potential to discriminate closely related species were designed taking into account the genetic polymorphisms found in target genes. These probes were tested, refined and validated on a small-scale prototype DNA chip. Overall, we obtained 17 highly specific probes targeting eEF1-a and SIT, along with 19 probes having lower discriminatory power recognizing at the same time two or three species. This basic array was validated in a laboratory setting and is ready for tests with crude environmental samples eventually to be scaled-up to include a larger panel of diatoms. Its possible use for the simultaneous detection of diatoms selected from the classes of water quality identified by the European Water Framework Directive is discussed.
Common features and differences in the transcriptome of large cell anaplastic lymphoma and classical Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES Anaplastic large cell lymphoma (ALCL) and classical Hodgkin's lymphoma (HL) are derived from different cell types, namely T cells and B cells, respectively. However, both lymphomas share a similar cytological and immunohistochemical tumor cell phenotype with little resemblance to their cells of origin. DESIGN AND METHODS In this study, the transcriptional profiles of ALCL cell lines, primary ALCL tumor cells from peripheral blood and HL cell lines were compared to each other and to normal B-cell subsets, B non-Hodgkin's lymphomas (NHL) and B NHL- and Epstein-Barr virus (EBV)-transformed B-cell lines in order to establish their relationship at the transcriptional level and to identify genes with possible pathobiological impact. Expression of some of the genes identified was confirmed in microdissected primary tumor cells by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS HL samples clustered separately from ALCL samples, but HL and ALCL were found to be more closely related to each other than to any normal or malignant B-cell sample in the dataset. Their relationship was determined to a large extent, but not exclusively, by lack of expression of B-cell antigens and by the over-expression of mRNA encoding activation markers and structural proteins. Apart from established differences between HL and ALCL, further genes of interest could be identified that distinguish both entities from each other and from the other samples. The differential expression of PRAME, DDR2, SOCS3 and CEBPD in HL and ALCL was confirmed in primary tumor tissue by immunohistochemistry and/or RT-PCR. INTERPRETATION AND CONCLUSIONS At a transcriptional level HL is more closely related to Alk+ ALCL than to the B-NHL or B-cell samples investigated, although it is a B-cell derived lymphoma. The newly identified genes discriminating HL and ALCL may be pathobiologically important and may serve as possible therapeutic targets.
Towards a Region-Level Automatic Image Annotation Benchmark ∗

Automatic image annotation at region-level consists of the task of assigning labels to regions within segmented images. This is a very important task for the development and improvement of image retrieval methods. Many image annotation methods have been proposed so far, reporting relatively good results on this task. However the lack of benchmark collections have caused that region-level methods are often evaluated using image-level collections. On the other hand, a few region-level collections are available, although these are small and composed of unrealistic images; which difficult the evaluation of the expected annotation performance on real collections. In this paper we propose the creation of a benchmark collection for the evaluation of region-level automatic image annotation methods, in order to provide a valuable resource to the image annotation and retrieval communities. We describe a methodology for creating such a benchmark and present some work we have performed towards building it; work in progress and future directions are also discussed. The main goal of this paper is to obtain feedback from the benchmarking community as well as to establish collaborations and to contact sponsors in order to carry out this exhaustive, but very important, task.
Practical Application of Iterative Decomposition of Water and Fat with Echo Asymmetry and Least-Squares Estimation (IDEAL) Imaging in Minimizing Metallic Artifacts

Iterative decomposition of water and fat with echo asymmetry and the least-squares estimation (IDEAL) is a recently developed method for robust separation of fat and water with very high signal-to-noise-ratio (SNR) efficiency. In contrast to conventional fat-saturation methods, IDEAL is insensitive to magnetic field (B0 and B1) inhomogeneity. The aim of this study was to illustrate the practical application of the IDEAL technique in reducing metallic artifacts in postoperative patients with metallic hardware. The IDEAL technique can help musculoskeletal radiologists make an accurate diagnosis particularly in musculoskeletal imaging by reducing metallic artifacts, enabling the use of contrast enhancement, improving SNR performance, and providing various modes of MR images with one scan parameter.