Miracle-dz/UniFAR-FTUs huggingface dataset:
Quantitative analysis of TALE–DNA interactions suggests polarity effects

Transcription activator-like effectors (TALEs) have revolutionized the field of genome engineering. We present here a systematic assessment of TALE DNA recognition, using quantitative electrophoretic mobility shift assays and reporter gene activation assays. Within TALE proteins, tandem 34-amino acid repeats recognize one base pair each and direct sequence-specific DNA binding through repeat variable di-residues (RVDs). We found that RVD choice can affect affinity by four orders of magnitude, with the relative RVD contribution in the order NG > HD ∼ NN ≫ NI > NK. The NN repeat preferred the base G over A, whereas the NK repeat bound G with 103-fold lower affinity. We compared AvrBs3, a naturally occurring TALE that recognizes its target using some atypical RVD-base combinations, with a designed TALE that precisely matches ‘standard’ RVDs with the target bases. This comparison revealed unexpected differences in sensitivity to substitutions of the invariant 5′-T. Another surprising observation was that base mismatches at the 5′ end of the target site had more disruptive effects on affinity than those at the 3′ end, particularly in designed TALEs. These results provide evidence that TALE–DNA recognition exhibits a hitherto un-described polarity effect, in which the N-terminal repeats contribute more to affinity than C-terminal ones.
How to Handle Split Antecedents in Tamil?

Resolution of the anaphoric entities in natural language text is very much essential to extract the complete information from the text. In this paper, we present a methodology to resolve one of the difficult pronouns, plural pronouns with split antecedents in Tamil. We have used a salience measure based approach with salience factors obtained from sub-categorization information of nouns and selectional restriction rules of the verbs. We have evaluated our approach with Tamil novel corpus and the results are encouraging.
A Systematic Approach and Guidelines to Developing a Triple Graph Grammar

Engineering processes are often inherently concurrent, involving multiple stakeholders working in parallel, each with their own tools and artefacts. Ensuring and restoring the consistency of such artefacts is a crucial task, which can be appropriately addressed with a bidirectional transformation (bx ) language. Although there exist numerous bx languages, often with corresponding tool support, it is still a substantial challenge to learn how to actually use such bx languages. Triple Graph Grammars (TGGs) are a fairly established bx language for which multiple and actively developed tools exist. Learning how to master TGGs is, however, currently a frustrating undertaking: a typical paper on TGGs dutifully explains the basic "rules of the game" in a few lines, then goes on to present the latest groundbreaking and advanced results. There do exist tutorials and handbooks for TGG tools but these are mainly focussed on how to use a particular tool (screenshots, tool workflow), often presenting exemplary TGGs but certainly not how to derive them systematically. Based on 20 years of experience working with and, more importantly, explaining how to work with TGGs, we present in this paper a systematic approach and guidelines to developing a TGG from a clear, but unformalised understanding of a bx.
Domestic incense burning and nasopharyngeal carcinoma: A case‐control study in Hong Kong Chinese

Incense burning is a powerful producer of carcinogens and has been considered as a risk factor for nasopharyngeal carcinoma (NPC). We conducted a case‐control study and case‐only analyses to investigate the effect of incense burning and its interaction with genetic background on NPC risk among Hong Kong Chinese. Between June 2010 and December 2012, we recruited 352 incident cases of NPC and 410 controls. We collected information on lifelong practice of domestic incense burning via interviews and genotyped 80 single nucleotide polymorphisms (SNPs) in DNA repair genes. We observed an increased NPC risk associated with daily burning in women [Adjusted OR = 2.49, 95% confidence interval (CI): 1.33, 4.66] but not in men. The adjusted OR for daily burning with poor ventilation was 2.08 (95% CI: 1.02, 4.24), while that with good ventilation was 1.35 (95% CI: 0.92, 1.98). Interactions between 2 SNPs (rs2074517 and rs4771436) and incense burning were significantly associated with NPC risk and tended to have a SNP exposure‐response effect. Evidence for gene‐environment interactions supported the knowledge that NPC is a multi‐factorial disease resulting from the joint effects of environmental exposures and inherited susceptibility. Environ. Mol. Mutagen. 55:751–756, 2014. © 2014 Wiley Periodicals, Inc.
A New Method for Data Hiding Domain Classification

Data hiding domain identification is very important for further steganalysis. A statistic feature-based method is advocated for identifying the hiding domain in this research. Different features in different domains that can reflect well statistical changes due to data hidden are extracted. In order to obtain better classification results, a process of adding noise is introduced to extract the feature that can classify spatial and DCT domain hiding. Based on the “one-against-one” SVM classifier, the experiment is implemented and the proposed method has performed satisfied classification results.
Immune Cell Phenotyping Using Flow Cytometry

Fluorescent immunophenotyping uses fluorescently‐conjugated antibodies to identify, characterize and quantify distinct subpopulations of cells within heterogeneous single‐cell populations, either in the context of tissue (using fluorescence and imaging microscopy) or in a single‐cell suspension (using multiparameter imaging microscopy, imaging cytometry, and/or flow cytometry). Flow cytometry is an optical, laser‐based technology which analyzes the physical and fluorescent properties of cells in suspension in real‐time as they flow through the instrument. This approach has a number of advantages over other techniques that can be used for characterizing cell populations in single‐cell suspensions, in that it can nonsubjectively interrogate up to millions of cells and acquire data on the presence of different cell subpopulations and phenotypical changes within these populations in seconds. This unit describes basic procedures for the direct and indirect immunofluorescent staining of surface and intracellular proteins that are expressed by lymphoid cells which have been isolated from tissues or blood. Protocols for the resolution of dead cells and for the fixation of cells are also included. This unit also provides essential information relating to the selection and titration of antibodies, fluorochrome choice, spectral overlap and compensation, the use of controls, and the standardization of data acquisition and analysis. It also highlights new technologies and platforms that can be used to interrogate the presence of cell subpopulations and their phenotype to an even greater depth. © 2015 by John Wiley & Sons, Inc.
Rumen microbial communities influence metabolic phenotypes in lambs

The rumen microbiota is an essential part of ruminants shaping their nutrition and health. Despite its importance, it is not fully understood how various groups of rumen microbes affect host-microbe relationships and functions. The aim of the study was to simultaneously explore the rumen microbiota and the metabolic phenotype of lambs for identifying host-microbe associations and potential biomarkers of digestive functions. Twin lambs, separated in two groups after birth were exposed to practices (isolation and gavage with rumen fluid with protozoa or protozoa-depleted) that differentially restricted the acquisition of microbes. Rumen microbiota, fermentation parameters, digestibility and growth were monitored for up to 31 weeks of age. Microbiota assembled in isolation from other ruminants lacked protozoa and had low bacterial and archaeal diversity whereas digestibility was not affected. Exposure to adult sheep microbiota increased bacterial and archaeal diversity independently of protozoa presence. For archaea, Methanomassiliicoccales displaced Methanosphaera. Notwithstanding, protozoa induced differences in functional traits such as digestibility and significantly shaped bacterial community structure, notably Ruminococcaceae and Lachnospiraceae lower up to 6 folds, Prevotellaceae lower by ~40%, and Clostridiaceae and Veillonellaceae higher up to 10 folds compared to microbiota without protozoa. An orthogonal partial least squares-discriminant analysis of urinary metabolome matched differences in microbiota structure. Discriminant metabolites were mainly involved in amino acids and protein metabolic pathways while a negative interaction was observed between methylotrophic methanogens Methanomassiliicoccales and trimethylamine N-oxide. These results stress the influence of gut microbes on animal phenotype and show the potential of metabolomics for monitoring rumen microbial functions.
Localization of the Site on the Complement Component C1q Required for the Stimulation of Neutrophil Superoxide Production (*)

C1q, the recognition subunit of the classical complement pathway, interacts with specific cell surface molecules via its collagen-like region (C1q-CLR). This binding of C1q to neutrophils triggers the generation of toxic oxygen species. To identify the site on C1q that interacts with the neutrophil C1q receptor, C1q was isolated, digested with pepsin to produce C1q-CLR, and further cleaved with either trypsin or endoproteinase Lys-C. The resulting fragments were separated by gel filtration chromatography and analyzed functionally (activation of the respiratory burst in neutrophils) and structurally. Cleavage of C1q-CLR with endoproteinase Lys-C did not alter its ability to trigger neutrophil superoxide production. However, when C1q-CLR was incubated with trypsin under conditions permitting optimal cleavage, the ability of C1q-CLR to stimulate superoxide production in neutrophils was completely abrogated. Fractionation of the digests obtained with the two enzymes and identification by amino acid sequencing permitted localization of the receptor interaction site to a specific region of the C1q-CLR. Circular dichroism analyses demonstrated that cleavage by trypsin does not denature the remaining uncleaved collagen-like structure, suggesting that after trypsin treatment, the loss of activity was not due to a loss of secondary structure of the molecule. However, irreversible heat denaturation of C1q-CLR also abrogated all activity. Thus, a specific conformation conferred by the collagen triple helix constitutes the functional receptor interaction site. These data should direct the design of future specific therapeutic reagents to selectively modulate this response.
A large reservoir of sulfate and sulfonate resides within plasma cells from Ascidia ceratodes, revealed by X-ray absorption near-edge structure spectroscopy.

The study of sulfur within the plasma cells of Ascidia ceratodes [Carlson, R. M. K. (1975) Proc. Natl. Acad. Sci. U.S.A. 72, 2217-2221; Frank, P., Carlson, R. M. K. , & Hodgson, K. O. (1986) Inorg. Chem. 25, 470-478; Hedman, B. , Frank, P., Penner-Hahn, J. E. , Roe, A. L. , Hodgson, K. O. , Carlson, R. M. K. , Brown, G. , Cerino, J., Hettel, R. , Troxel, T. , Winick, H. , & Yang, J. (1986) Nucl. Instrum. Methods Phys. Res., Sect. A 246, 797-800] has been extended with X-ray absorption near-edge structure (XANES) spectroscopy. An intense absorption feature at 2482.4 eV and a second feature at 2473.7 eV indicate a large endogenous sulfate concentration, as well as smaller though significant amounts of thiol or thioether sulfur, respectively. A strong shoulder was observed at 2481.7 eV on the low-energy side of the sulfate absorption edge, deriving from a novel type of sulfur having a slightly lower oxidation state than sulfate sulfur. The line width of the primary transition on the sulfur edge of a vanadium (III) sulfate solution was found to be broadened relative to that of sodium sulfate, possibly deriving from the formation of the VSO4+ complex ion [Britton, H. T. S. , & Welford, G. (1940) J. Chem. Soc. , 761-764; Duffy, J. A. , & Macdonald, W. J. D. (1970) J. Chem. Soc. , 977-980; Kimura, T. , Morinaga, M. , & Nakano, J. (1972) Nippon Kagaku Zaishi, 664-667]. Similar broadening appears to characterize the oxidized sulfur types in vanadocytes. A very good linear correlation between oxidation state and peak position (in electronvolts) was found for a series of related sulfur compounds. This correlation was used to determine a 5+ oxidation state for the additional sulfur type at 2481.7 eV. (ABSTRACT TRUNCATED AT 250 WORDS)
Lazy User Theory: A Dynamic Model to Understand User Selection of Products and Services

In this paper we suggest that a user will most often choose the solution that will fulfill her (information) needs with the least effort. We call this "lazy user behavior". We suggest that the principle components responsible for solution selection are the user need and the user state. User need is the user's detailed (information) need (urgency, type, depth, etc.) and user state is the situation, in which the user is at the moment of the need (location, time, etc.); the user state limits the set of available solutions (devices) to fulfill the user need. We present the lazy user theory of solution selection, two mBusiness case examples, and discuss the implications of lazy user behavior on user selection of products and services. Implications on the design of new products and services are also discussed.
Alternative Splicing of Titin Restores Diastolic Function in an HFpEF-Like Genetic Murine Model (TtnΔIAjxn).

RATIONALE Patients with heart failure with preserved ejection fraction (HFpEF) experience elevated filling pressures and reduced ventricular compliance. The splicing factor RNA-binding motif 20 (RBM20) regulates the contour length of titin's spring region and thereby determines the passive stiffness of cardiomyocytes. Inhibition of RBM20 leads to super compliant titin isoforms (N2BAsc) that reduce passive stiffness. OBJECTIVE To determine the therapeutic potential of upregulating compliant titin isoforms in an HFpEF-like state in the mouse. METHODS AND RESULTS Constitutive and inducible cardiomyocyte-specific RBM20-inhibited mice were produced on a Ttn(ΔIAjxn) background to assess the effect of upregulating compliant titin at the cellular and organ levels. Genetic deletion of the I-band-A-band junction (IAjxn) in titin increases strain on the spring region and causes a HFpEF-like syndrome in the mouse without pharmacological or surgical intervention. The increased strain represents a mechanical analog of deranged post-translational modification of titin that results in increased passive myocardial stiffness in patients with HFpEF. On inhibition of RBM20 in Ttn(ΔIAjxn) mice, compliant titin isoforms were expressed, diastolic function was normalized, exercise performance was improved, and pathological hypertrophy was attenuated. CONCLUSIONS We report for the first time a benefit from upregulating compliant titin isoforms in a murine model with HFpEF-like symptoms. Constitutive and inducible RBM20 inhibition improves diastolic function resulting in greater tolerance to exercise. No effective therapies exists for treating this pervasive syndrome; therefore, our data on RBM20 inhibition are clinically significant.
Paying attention to reading: The neurobiology of reading and dyslexia

Abstract Extraordinary progress in functional brain imaging, primarily advances in functional magnetic resonance imaging, now allows scientists to understand the neural systems serving reading and how these systems differ in dyslexic readers. Scientists now speak of the neural signature of dyslexia, a singular achievement that for the first time has made what was previously a hidden disability, now visible. Paralleling this achievement in understanding the neurobiology of dyslexia, progress in the identification and treatment of dyslexia now offers the hope of identifying children at risk for dyslexia at a very young age and providing evidence-based, effective interventions. Despite these advances, for many dyslexic readers, becoming a skilled, automatic reader remains elusive, in great part because though children with dyslexia can be taught to decode words, teaching children to read fluently and automatically represents the next frontier in research on dyslexia. We suggest that to break through this “fluency” barrier, investigators will need to reexamine the more than 20-year-old central dogma in reading research: the generation of the phonological code from print is modular, that is, automatic and not attention demanding, and not requiring any other cognitive process. Recent findings now present a competing view: other cognitive processes are involved in reading, particularly attentional mechanisms, and that disruption of these attentional mechanisms play a causal role in reading difficulties. Recognition of the role of attentional mechanisms in reading now offer potentially new strategies for interventions in dyslexia. In particular, the use of pharmacotherapeutic agents affecting attentional mechanisms not only may provide a window into the neurochemical mechanisms underlying dyslexia but also may offer a potential adjunct treatment for teaching dyslexic readers to read fluently and automatically. Preliminary studies suggest that agents traditionally used to treat disorders of attention, particularly attention-deficit/hyperactivity disorder, may prove to be an effective adjunct to improving reading in dyslexic students.
Adaptive genetic markers discriminate migratory runs of Chinook salmon (Oncorhynchus tshawytscha) amid continued gene flow

Neutral genetic markers are routinely used to define distinct units within species that warrant discrete management. Human‐induced changes to gene flow however may reduce the power of such an approach. We tested the efficiency of adaptive versus neutral genetic markers in differentiating temporally divergent migratory runs of Chinook salmon (Oncorhynchus tshawytscha) amid high gene flow owing to artificial propagation and habitat alteration. We compared seven putative migration timing genes to ten microsatellite loci in delineating three migratory groups of Chinook in the Feather River, CA: offspring of fall‐run hatchery broodstock that returned as adults to freshwater in fall (fall run), spring‐run offspring that returned in spring (spring run), and fall‐run offspring that returned in spring (FRS). We found evidence for significant differentiation between the fall and federally listed threatened spring groups based on divergence at three circadian clock genes (OtsClock1b, OmyFbxw11, and Omy1009UW), but not neutral markers. We thus demonstrate the importance of genetic marker choice in resolving complex life history types. These findings directly impact conservation management strategies and add to previous evidence from Pacific and Atlantic salmon indicating that circadian clock genes influence migration timing.
3D sorghum reconstructions from depth images enable identification of quantitative trait loci regulating shoot architecture

Dissecting the genetic basis of complex traits is aided by frequent and non-destructive measurements. Advances in range imaging technologies enable the rapid acquisition of three-dimensional (3D) data from an imaged scene. A depth camera was used to acquire images of Sorghum bicolor, an important grain, forage, and bioenergy crop, at multiple developmental timepoints from a greenhouse-grown recombinant inbred line population. A semi-automated software pipeline was developed and used to generate segmented, 3D plant reconstructions from the images. Automated measurements made from 3D plant reconstructions identified quantitative trait loci (QTL) for standard measures of shoot architecture such as shoot height, leaf angle and leaf length, and for novel composite traits such as shoot compactness. The phenotypic variability associated with some of the QTL displayed differences in temporal prevalence; for example, alleles closely linked with the sorghum Dwarf3 gene, an auxin transporter and pleiotropic regulator of both leaf inclination angle and shoot height, influence leaf angle prior to an effect on shoot height. Furthermore, variability in composite phenotypes that measure overall shoot architecture, such as shoot compactness, is regulated by loci underlying component phenotypes like leaf angle. As such, depth imaging is an economical and rapid method to acquire shoot architecture phenotypes in agriculturally important plants like sorghum to study the genetic basis of complex traits.
Connecting dynamic epistemic and temporal epistemic logics

We give a relation between a logic of knowledge and change, with a semantics on Kripke models, and a logic of knowledge and time, with a semantics on interpreted systems. In particular, given an epistemic state (pointed Kripke model with equivalence relations) and a formula in a dynamic epistemic logic (a logic describing the consequences of epistemic actions), we construct an interpreted system relative to that epistemic state and that formula that satisfies the translation of the formula into a temporal epistemic logic. The construction involves that the protocol that is implicit in the dynamic epistemic formula, i.e., the set of sequences of actions being executed to evaluate the formula, is made explicit. We first focus on the logic of knowledge and change that is known as public announcement logic, then generalize our results to a dynamic epistemic logic.
A LARGE CONTAINMENT CAPSULE FOR NUCLEAR REACTOR IRRADIATION OF EXPLOSIVE MATERIALS

Abstract : The design and development of a large explosive containment capsule for the irradiation of up to 80 grams of explosive materials is described. The capsule will fully protect its surroundings, e.g., the core of a nuclear reactor, if its explosive content detonates. The minimum safety factor of two was used. The capsule contains provisions for the containment of gases produced by detonation or burning of the explosive material and the minimizing of any shock wave propagated outside the capsule. Also, provisions are made to monitor pressure or gas evolution and the temperature of the test material during irradiation. Dynamic pressure pulse and stress-strain measurement tests were conducted and are described. Analytical calculations were made for comparison with experimental data, first to determine the validity of the calculations and then to obtain information on configurations not actually tested.
Cognitive ERPs in Depressive and Anxiety Disorders during Tonal and Phonetic Oddball Tasks

This report compares event-related brain potentials (ERPs) of patients having a depressive disorder alone (n=58), an anxiety disorder alone (n=22), comorbidity of these disorders (n=18), and healthy controls (n=49). ERPs were recorded from 30 electrode sites during auditory oddball tasks using consonant-vowel syllables (phonetic) or complex tones (tonal). Overlapping ERP components were identified and measured using covariance-based principal components analysis. An early P3 subcomponent (P315) was larger in patients having an anxiety disorder alone when compared to depressed patients with or without an anxiety disorder and healthy controls, whereas a late P3 subcomponent (P400) was larger in patients having comorbidity of anxiety and depressive disorders than in the other groups. Also, the N2-P3 complex showed task-dependent hemispheric asymmetries, including larger N2-P3 amplitude over left than right temporoparietal sites during the phonetic oddball task. This hemispheric asymmetry was greatest in patients having a depressive disorder alone and smallest in patients having an anxiety disorder alone. The opposite nature of the alterations of hemispheric asymmetry and early P3 amplitude in depressive and anxiety disorders underscores the importance of taking comorbidity with anxiety into account in studies of cognitive ERPs in depressive disorders.