Miracle-dz/UniFAR-FTUs huggingface dataset:
Nucleoprotein structure of the CD4 locus: Implications for the mechanisms underlying CD4 regulation during T cell development

The CD4 gene is regulated in a stage-specific manner during T cell development, being repressed in CD4−CD8− double-negative (DN) and CD8 cells, but expressed in CD4+CD8+ double-positive (DP) and CD4 cells. Furthermore, the expression/repression pattern is reversible in developing (DN and DP) thymocytes, but irreversible in mature (CD4 and CD8) T cells. Here, we explored the molecular mechanisms underlying this complex mode of regulation by examining the nucleoprotein structure of the CD4 locus throughout T cell development and in DN cells lacking the CD4 silencer. In DN cells, the CD4 enhancer is preloaded with multiple transcription activators, but p300 recruitment is impaired by the silencer that is associated with the repressor Runx1. DP cells achieve high-level CD4 expression via a combination of CD4 derepression and true activation, but Runx1 remains bound to the silencer that retains an open chromatin configuration. In CD4 cells, Runx1 dissociates from the silencer that has become less accessible, and CD4 transcription appears to be achieved via a mechanism distinct from that operating in DP cells. In CD8 cells, the CD4 promoter becomes incorporated into heterochromatin-like structure. Our data shed light on the molecular basis of CD4 regulation and provide a conceptual framework for understanding how the same regulatory elements can mediate both reversible and irreversible CD4 regulation.
New Journal of Physics Measurement of the electron ’ s electric dipole moment using YbF molecules : methods and data analysis

We recently reported a new measurement of the electron’s electric dipole moment using YbF molecules (Hudson et al 2011 Nature 473 493). Here, we give a more detailed description of the methods used to make this measurement, along with a fuller analysis of the data. We show how our methods isolate the electric dipole moment from imperfections in the experiment that might mimic it. We describe the systematic errors that we discovered, and the small corrections that we made to account for these. By making a set of additional measurements with greatly exaggerated experimental imperfections, we find upper bounds on possible uncorrected systematic errors which we use to determine the systematic uncertainty in the measurement. We also calculate the size of some systematic effects that have been important in previous electric dipole moment measurements, such as the motional magnetic field effect and the geometric phase, and show them to be negligibly small in the present experiment. Our result is consistent with an electric dipole moment of zero, so we provide upper bounds to its size at various confidence levels. Finally, we review the prospects for future improvements in the precision of the experiment. 1 Author to whom any correspondence should be addressed. Content from this work may be used under the terms of the Creative Commons Attribution-NonCommercialShareAlike 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI. New Journal of Physics 14 (2012) 103051 1367-2630/12/103051+32$33.00 © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft
Draft Genome Sequence, and a Sequence-Defined Genetic Linkage Map of the Legume Crop Species Lupinus angustifolius L

Lupin (Lupinus angustifolius L.) is the most recently domesticated crop in major agricultural cultivation. Its seeds are high in protein and dietary fibre, but low in oil and starch. Medical and dietetic studies have shown that consuming lupin-enriched food has significant health benefits. We report the draft assembly from a whole genome shotgun sequencing dataset for this legume species with 26.9x coverage of the genome, which is predicted to contain 57,807 genes. Analysis of the annotated genes with metabolic pathways provided a partial understanding of some key features of lupin, such as the amino acid profile of storage proteins in seeds. Furthermore, we applied the NGS-based RAD-sequencing technology to obtain 8,244 sequence-defined markers for anchoring the genomic sequences. A total of 4,214 scaffolds from the genome sequence assembly were aligned into the genetic map. The combination of the draft assembly and a sequence-defined genetic map made it possible to locate and study functional genes of agronomic interest. The identification of co-segregating SNP markers, scaffold sequences and gene annotation facilitated the identification of a candidate R gene associated with resistance to the major lupin disease anthracnose. We demonstrated that the combination of medium-depth genome sequencing and a high-density genetic linkage map by application of NGS technology is a cost-effective approach to generating genome sequence data and a large number of molecular markers to study the genomics, genetics and functional genes of lupin, and to apply them to molecular plant breeding. This strategy does not require prior genome knowledge, which potentiates its application to a wide range of non-model species.
Signatures of Reductive Magnetic Mineral Diagenesis From Unmixing of First‐Order Reversal Curves

Diagenetic alteration of magnetic minerals occurs in all sedimentary environments and tends to be severe in reducing environments. Magnetic minerals provide useful information about sedimentary diagenetic processes, which makes it valuable to use magnetic properties to identify the diagenetic environment in which the magnetic minerals occur and to inform interpretations of paleomagnetic recording or environmental processes. We use a newly developed first‐order reversal curve unmixing method on well‐studied samples to illustrate how magnetic properties can be used to assess diagenetic processes in reducing sedimentary environments. From our analysis of multiple data sets, consistent magnetic components are identified for each stage of reductive diagenesis. Relatively unaltered detrital and biogenic magnetic mineral assemblages in surficial oxic to manganous diagenetic environments undergo progressive dissolution with burial into ferruginous and sulfidic environments and largely disappear at the sulfate‐methane transition. Below the sulfate‐methane transition, a weak superparamagnetic to largely noninteracting stable single domain (SD) greigite component is observed in all studied data sets. Moderately interacting stable SD authigenic pyrrhotite and strongly interacting stable SD greigite are observed commonly in methanic environments. Recognition of these characteristic magnetic components enables identification of diagenetic processes and should help to constrain interpretation of magnetic mineral assemblages in future studies. A key question for future studies concerns whether stable SD greigite forms in the sulfidic or methanic zones, where formation in deeper methanic sediments will cause greater delays in paleomagnetic signal recording. Authigenic pyrrhotite forms in methanic environments, so it will usually record a delayed paleomagnetic signal.
Antisense transcripts enhanced by camptothecin at divergent CpG-island promoters associated with bursts of topoisomerase I-DNA cleavage complex and R-loop formation

DNA Topoisomerase I (Top1) is required to relax DNA supercoils generated by RNA polymerases (RNAPs). Top1 is inhibited with high specificity by camptothecin (CPT), an effective anticancer agent, and by oxidative base damage and ribonucleotides in DNA strands, resulting into Top1-DNA cleavage complexes (Top1ccs). To understand how Top1ccs affect genome stability, we have investigated the global transcriptional response to CPT-induced Top1ccs. Top1ccs trigger an accumulation of antisense RNAPII transcripts specifically at active divergent CpG-island promoters in a replication-independent and Top1-dependent manner. As CPT increases antisense transcript levels in the presence of 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, a transcription inhibitor, Top1ccs likely impair antisense RNA degradation. Time-course data showed a burst of Top1ccs increased by CPT at promoter sites and along transcribed regions, causing a transient block of RNAPII at the promoter. Moreover, cell immunofluorescence analyses showed that Top1ccs induce a transient increase of R-loops specifically at highly transcribed regions such as nucleoli in a Top1-dependent manner. Thus, a specific and highly dynamic transcriptional response to Top1ccs occurs at divergent active CpG-island promoters, which may include a transient stabilization of R-loops. The results clarify molecular features of a response pathway leading to transcription-dependent genome instability and altered transcription regulation.
Functional subcellular distribution of β1- and β2-adrenergic receptors in rat ventricular cardiac myocytes

β‐adrenergic stimulation is a key regulator of cardiac function. The localization of major cardiac adrenergic receptors (β1 and β2) has been investigated using biochemical and biophysical approaches and has led to contradictory results. This study investigates the functional subcellular localization of β1‐ and β2‐adrenergic receptors in rat ventricular myocytes using a physiological approach. Ventricular myocytes were isolated from the hearts of rat and detubulated using formamide. Physiological cardiac function was measured as Ca2+ transient using Fura‐2‐AM and cell shortening. Selective activation of β1‐ and β2‐adrenergic receptors was induced with isoproterenol (0.1 μmol/L) and ICI‐118,551 (0.1 μmol/L); and with salbutamol (10 μmol/L) and atenolol (1 μmol/L), respectively. β1‐ and β2‐adrenergic stimulations induced a significant increase in Ca2+ transient amplitude and cell shortening in intact rat ventricular myocytes (i.e., surface sarcolemma and t‐tubules) and in detubulated cells (depleted from t‐tubules, surface sarcolemma only). Both β1‐ and β2‐adrenergic receptors stimulation caused a greater effect on Ca2+ transient and cell shortening in detubulated myocytes than in control myocytes. Quantitative analysis indicates that β1‐adrenergic stimulation is ~3 times more effective at surface sarcolemma compared to t‐tubules, whereas β2‐ adrenergic stimulation occurs almost exclusively at surface sarcolemma (~100 times more effective). These physiological data demonstrate that in rat ventricular myocytes, β1‐adrenergic receptors are functionally present at surface sarcolemma and t‐tubules, while β2‐adrenergic receptors stimulation occurs only at surface sarcolemma of cardiac cells.
Safe planning for human-robot interaction

A two stage planning approach is proposed to address issues of potentially conflicting planning criteria. This paper presents a strategy for improving the safety of human-robot interaction for articulated robots by minimizing a danger criterion during the planning stage. Two formulations of the danger criterion are proposed: a criterion assuming independent factors, and a criterion assuming mutually dependent factors. Simulations of the proposed planning strategy are presented for both 2D and 3D robots.
Contingency management and motivational enhancement: a randomized clinical trial for college student smokers.

INTRODUCTION The efficacy of contingency-management (CM) and motivational enhancement therapy (MET) for college student smoking cessation was examined. METHODS Nontreatment-seeking daily smokers (N = 110) were randomly assigned to 3 weeks of CM versus noncontingent reinforcement (NR) and to three individual sessions of MET versus a relaxation control in a 2 x 2 experimental design. Expired carbon monoxide (CO) samples were collected twice daily for 3 weeks. Participants earned 5 US dollars for providing each sample; additionally, those randomized to CM earned escalating monetary rewards based on CO reductions (Week 1) and smoking abstinence (Weeks 2-3). RESULTS Compared with NR, CM resulted in significantly lower CO levels and greater total and consecutive abstinence during the intervention. Those in the CM and MET groups reported greater interest in quitting smoking posttreatment, but rates of confirmed abstinence at follow-up were very low (4% at 6-month follow-up) and did not differ by group. DISCUSSION Findings support the short-term efficacy of CM for reducing smoking among college students. Future research should explore enhancements to CM in this population, including a longer intervention period and the recruitment of smokers who are motivated to quit.
A Multiobjective Genetic Fuzzy System with Imprecise Probability Fitness for Vague Data

When questionnaires are designed, each factor under study can be assigned a set of different items. The answers to these questions must be merged in order to obtain the level of that input. Therefore, it is typical for data acquired from questionnaires that each of the inputs and outputs are not numbers, but sets of values. In this paper, we represent the information contained in such a set of values by means of a fuzzy number. A fuzzy statistics-based interpretation of the semantic of a fuzzy set is used for this purpose, as we consider that this fuzzy number is a nested family of confidence intervals for the value of the variable. The accuracy of the model is expressed by means of an interval-valued function, derived from a definition of the variance of a fuzzy random variable. A multicriteria genetic learning algorithm, able to optimize this interval-valued function, is proposed. As an example of the application of this algorithm, a practical problem of modeling in marketing is solved
Direct Recordings from Human Anterior Insula Reveal its Leading Role within the Error‐Monitoring Network

Abstract The ability to monitor our own errors is mediated by a network that includes dorsomedial prefrontal cortex (dmPFC) and anterior insula (AI). However, the dynamics of the underlying neurophysiological processes remain unclear. In particular, whether AI is on the receiving or driving end of the error‐monitoring network is unresolved. Here, we recorded intracerebral electroencephalography signals simultaneously from AI and dmPFC in epileptic patients while they performed a stop‐signal task. We found that errors selectively modulated broadband neural activity in human AI. Granger causality estimates revealed that errors were immediately followed by a feedforward influence from AI onto anterior cingulate cortex and, subsequently, onto presupplementary motor area. The reverse pattern of information flow was observed on correct responses. Our findings provide the first direct electrophysiological evidence indicating that the anterior insula rapidly detects and conveys error signals to dmPFC, while the latter might use this input to adapt behavior following inappropriate actions.
Genome-wide analysis of cis-regulatory element structure and discovery of motif-driven gene co-expression networks in grapevine

Abstract Coordinated transcriptional and metabolic reprogramming ensures a plant’s continued growth and survival under adverse environmental conditions. Transcription factors (TFs) act to modulate gene expression through complex cis-regulatory element (CRE) interactions. Genome-wide analysis of known plant CREs was performed for all currently predicted protein-coding gene promoters in grapevine (Vitis vinifera L.). Many CREs such as abscisic acid (ABA)-responsive, drought-responsive, auxin-responsive, and evening elements, exhibit bona fide CRE properties such as strong position bias towards the transcription start site (TSS) and over-representation when compared with random promoters. Genes containing these CREs are enriched in a large repertoire of plant biological pathways. Large-scale transcriptome analyses also show that these CREs are highly implicated in grapevine development and stress response. Numerous CRE-driven modules in condition-specific gene co-expression networks (GCNs) were identified and many of these modules were highly enriched for plant biological functions. Several modules corroborate known roles of CREs in drought response, pathogen defense, cell wall metabolism, and fruit ripening, whereas others reveal novel functions in plants. Comparisons with Arabidopsis suggest a general conservation in promoter architecture, gene expression dynamics, and GCN structure across species. Systems analyses of CREs provide insights into the grapevine cis-regulatory code and establish a foundation for future genomic studies in grapevine.
Plenoptic cameras in surgical robotics: Calibration, registration, and evaluation

Three-dimensional sensing of changing surgical scenes would improve the function of surgical robots. This paper explores the requirements and utility of a new type of depth sensor, the plenoptic camera, for surgical robots. We present a metric calibration procedure for the plenoptic camera and the registration of its coordinate frame to the robot (hand-eye calibration). We also demonstrate the utility in robotic needle insertion and application of sutures in phantoms. The metric calibration accuracy is reported as 1.14 ± 0.80 mm for the plenoptic camera and 1.57 ± 0.90 mm for hand-eye calibration. The accuracy of needle insertion task is 1.79 ± 0.35 mm for the entire robotic system. Additionally, the accuracy of suture placement with the presented system is reported at 1.80 ± 0.43 mm. Finally, we report consistent suture spacing with only 0.11 mm standard deviation between inter-suture distances. The measured accuracy of less than 2 mm with consistent suture spacing is a promising result to provide repeatable leak-free suturing with a robotic tool and a plenoptic depth imager.
Secure Verifier-Based Three-Party Key Exchange in the Random Oracle Model

A Three Party password Authenticated Key Exchange protocol (3PAKE) facilitates two clients to establish authenticated session ke ys via the help of a tr usted server. This approach enhances the scalability of key agreement issue and facilitates users' convenience in distributed environments. In this paper, we show the secur ity weaknesses of previous works, and then propose our new scheme, using password verifiers. The scheme is efficient, and the key indistinguishability is proved re lative to the com putational Diffie-Hellman problem. It is the first provably secure verifier-based 3PAKE protocol.
Artificial Zinc Finger DNA Binding Domains: Versatile Tools for Genome Engineering and Modulation of Gene Expression

Genome editing and alteration of gene expression by synthetic DNA binding activities gained a lot of momentum over the last decade. This is due to the development of new DNA binding molecules with enhanced binding specificity. The most commonly used DNA binding modules are zinc fingers (ZFs), TALE‐domains, and the RNA component of the CRISPR/Cas9 system. These binding modules are fused or linked to either nucleases that cut the DNA and induce DNA repair processes, or to protein domains that activate or repress transcription of genes close to the targeted site in the genome. This review focuses on the structure, design, and applications of ZF DNA binding domains (ZFDBDs). ZFDBDs are relatively small and have been shown to penetrate the cell membrane without additional tags suggesting that they could be delivered to cells without a DNA or RNA intermediate. Advanced algorithms that are based on extensive knowledge of the mode of ZF/DNA interactions are used to design the amino acid composition of ZFDBDs so that they bind to unique sites in the genome. Off‐target binding has been a concern for all synthetic DNA binding molecules. Thus, increasing the specificity and affinity of ZFDBDs will have a significant impact on their use in analytical or therapeutic settings. J. Cell. Biochem. 116: 2435–2444, 2015. © 2015 Wiley Periodicals, Inc.
DNA Repair Gene XRCC1 Polymorphisms and Head and Neck Cancer Risk: An Updated Meta-Analysis Including 16344 Subjects

Background DNA repair gene X-ray repair cross complementing group 1 (XRCC1) plays an important role in the maintenance of the genomic integrity and protection of cells from DNA damage. Sequence variation in XRCC1 gene may alter head and neck cancer (HNC) susceptibility. However, these results are inconclusive. To derive a more precise estimation of the relationship between XRCC1 polymorphism and HNC risk, we undertook a meta-analysis involving 16,344 subjects. Methods A search of the literature by PubMed, Embase, Web of Science and China National Knowledge Infrastructure was performed to identify studies based on the predetermined inclusion criteria. The odds ratio (OR) with 95% confidence interval (CI) was combined using a random-effects model or a fixed-effects model. Results Twenty-nine studies consisting of 6,719 cases and 9,627 controls were identified and analyzed. Overall, no evidence of significant association was observed between XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1 Arg399Gln genotypes and the risk of HNC in any genetic models. Subgroup analyses according to ethnicity, tumor site, publication year, genotyping method also detected no significant association in any subgroup, except that oral cancer was associated with Arg194Trp variant in recessive model. Furthermore, no significant effect of these polymorphisms interacted with smoking on HNC risk was detected but Arg194Trp homozygous variant. Conclusion In conclusion, this meta-analysis suggests that the XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism may not involve in HNC susceptibility. Further studies about gene-gene and gene-environment interactions in different populations are required.
An intensional approach to the specification of test cases for database applications

When testing database applications, in addition to creating in-memory fixtures it is also necessary to create an initial database state that is appropriate for each test case. Current approaches either require exact database states to be specified in advance, or else generate a single initial state (under guidance from the user) that is intended to be suitable for execution of all test cases. The first method allows large test suites to be executed in batch, but requires considerable programmer effort to create the test cases (and to maintain them). The second method requires less programmer effort, but increases the likelihood that test cases will fail in non-fault situations, due to unexpected changes to the content of the database. In this paper, we propose a new approach in which the database states required for testing are specified intensionally, as constrained queries, that can be used to prepare the database for testing automatically. This technique overcomes the limitations of the other approaches, and does not appear to impose significant performance overheads.
Distribution of airway narrowing during hyperpnea-induced bronchoconstriction in guinea pigs.

Increasing minute ventilation of dry gas shifts the principal burden of respiratory heat and water losses from more proximal airway to airways farther into the lung. If these local thermal transfers determine the local stimulus for bronchoconstriction, then increasing minute ventilation of dry gas might also extend the zone of airway narrowing farther into the lung during hyperpnea-induced bronchoconstriction (HIB). We tested this hypothesis by comparing tantalum bronchograms in tracheostomized guinea pigs before and during bronchoconstriction induced by dry gas hyperpnea, intravenous methacholine, and intravenous capsaicin. In eight animals subjected to 5 min of dry gas isocapnic hyperpnea [tidal volume (VT) = 2-5 ml, 150 breaths/min], there was little change in the diameter of the trachea or the main stem bronchi up to 0.75 cm past the main carina (zone 1). In contrast, bronchi from 0.75 to 1.50 cm past the main carina (zone 2) narrowed progressively at all minute ventilations greater than or equal to 300 ml/min (VT = 2 ml). More distal bronchi (1.50-3.10 cm past the main carina; zone 3) did not narrow significantly until minute ventilation was raised to 450 ml/min (VT = 3 ml). The estimated VT during hyperpnea needed to elicit a 50% reduction in airway diameter was significantly higher in zone 3 bronchi [4.3 +/- 0.8 (SD) ml] than in zone 2 bronchi (3.5 +/- 1.1 ml, P less than 0.012). (ABSTRACT TRUNCATED AT 250 WORDS)