Miracle-dz/UniFAR-FTUs huggingface dataset:
Multi-Faceted Characterization of a Novel LuxR-Repressible Promoter Library for Escherichia coli

The genetic elements regulating the natural quorum sensing (QS) networks of several microorganisms are widely used in synthetic biology to control the behaviour of single cells and engineered bacterial populations via ad-hoc constructed synthetic circuits. A number of novel engineering-inspired biological functions have been implemented and model systems have also been constructed to improve the knowledge on natural QS systems. Synthetic QS-based parts, such as promoters, have been reported in literature, to provide biological components with functions that are not present in nature, like modified induction logic or activation/repression by additional molecules. In this work, a library of promoters that can be repressed by the LuxR protein in presence of the QS autoinducer N-3-oxohexanoyl-L-homoserine lactone (AHL) was reported for Escherichia coli, to expand the toolkit of genetic parts that can be used to engineer novel synthetic QS-based systems. The library was constructed via polymerase chain reaction with highly constrained degenerate oligonucleotides, designed according to the consensus -35 and -10 sequences of a previously reported constitutive promoter library of graded strength, to maximize the probability of obtaining functional clones. All the promoters have a lux box between the -35 and -10 regions, to implement a LuxR-repressible behaviour. Twelve unique library members of graded strength (about 100-fold activity range) were selected to form the final library and they were characterized in several genetic contexts, such as in different plasmids, via different reporter genes, in presence of a LuxR expression cassette in different positions and in response to different AHL concentrations. The new obtained regulatory parts and corresponding data can be exploited by synthetic biologists to implement an artificial AHL-dependent repression of transcription in genetic circuits. The target transcriptional activity can be selected among the available library members to meet the design specifications of the biological system.
Mitochondria-Associated Endoplasmic Reticulum Membranes in Insulin Signaling

Hepatic insulin resistance is a key feature of type 2 diabetes, and the consequent dysregulation of glucose and lipid output from the liver are important contributors to the observed hyperglycemia and hyperlipidemia. While excessive lipid accumulation (1) and defective signaling by protein kinase C (2) have been implicated in the past, the full panoply of molecular mechanisms involved is still not defined. Deeper insights would therefore be welcome in the quest to identify new therapeutic approaches to the disease (3). Mitochondrial metabolism and its dysfunction are well-known to contribute to metabolic dyshomeostasis in type 2 diabetes, with impaired glucose oxidation resulting from a failure to fully activate the intramitochondrial pyruvate dehydrogenase (PDH) complex (4). Originally described as sites for the exchange of phospholipids between organelles (5), mitochondria-associated membranes (MAMs) represent close contact sites through which endoplasmic reticulum (ER) communicates with mitochondria supporting the transfer not only of lipids but also the exchange of calcium (Ca2+) ions and other species. MAMs play important roles in several signal transduction pathways and the relevance of the ER–mitochondria interface to human diseases, including Alzheimer disease, cancer, and lysosomal storage disease (6), is slowly emerging. In this issue, Tubbs et al. (7) demonstrate the potential importance of MAM integrity in insulin action and resistance in hepatocytes. The association between ER and mitochondrial homeostasis and insulin signaling has …
Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22

Objectives Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. Methods A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. Results With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p=9.2×10−9), thereby confirming its role as a susceptibility locus for OA. Conclusion The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, β), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
Efficient Channel Allocation for Wireless Local-Area Networks

We define techniques to improve the usage of wireless spectrum in the context of wireless local area networks (WLANs) by defining better channel allocation methods among interfering access points (APs). We do this by identifying new ways of channel re-use that are based on realistic interference scenarios in WLAN environments. This problem can typically be modeled as a graph coloring algorithm, where the APs represent vertices and the number of available channels represent colors. We show in this paper that such a formulation is unable to gain maximal benefits in WLANs. Instead we define a weighted variant of the graph coloring problem that takes into account realistic channel interference observed in wireless environments, as well as the impact of such interference on wireless users. We prove that the weighted graph coloring problem is NP-hard and propose scalable and fault tolerant distributed algorithms that achieve significantly better performance than existing techniques for channel allocation. Through detailed simulations we study the performance of the algorithms under various topologies and channel conditions. In particular, we show that the techniques achieve up to 45.5% reduction in the number of clients affected by interference for IEEE 802.11b/g networks with sparse topologies. The algorithms scale well with the size and density of the underlying topology. We also evaluate the algorithms on an in-building wireless testbed (consisting of 20 APs) and demonstrate that the algorithms achieve a 40% reduction in the interference by using partially overlapping channels when an insufficient number of nonoverlapping channels are available.
Up‐regulation of cardiac nitric oxide synthase 1‐derived nitric oxide after myocardial infarction in senescent rats

Nitric oxide (NO) has been implicated in the development of heart failure, although the source, significance, and functional role of the different NO synthase (NOS) isoforms in this pathology are controversial. The presence of a neuronal‐type NOS isoform (NOS1) in the cardiac sarcoplasmic reticulum has been recently discovered, leading to the hypothesis that NOS1‐derived NO may notably alter myocardial inotropy. However, the regulation and role(s) of NOS1 in cardiac diseases remain to be determined. Using an experimental model of myocardial infarction (MI) in senescent rats, we demonstrated a significant increase in cardiac NOS1 expression and activity in MI, coupled with the translocation of this enzyme to the sarcolemma through interactions with caveolin‐3. The enhanced NOS1 activity counteracts the decrease in cardiac NOS3 expression and activity observed in heart failure. We demonstrated an increased interaction between NOS1 and its regulatory protein HSP90 in post‐MI hearts, a potential mechanism for the higher NOS1 activity in this setting. Finally, preferential in vivo inhibition of NOS1 activity enhanced basal post‐MI left ventricular dysfunction in senescent rats. These results provide the first evidence that increased NOS1‐derived NO production may play a significant role in the autocrine regulation of myocardial contractility after MI in aging rats.
Cooperative Signaling between Slit2 and Ephrin-A1 Regulates a Balance between Angiogenesis and Angiostasis

ABSTRACT Slit proteins induce cytoskeletal remodeling through interaction with roundabout (Robo) receptors, regulating migration of neurons and nonneuronal cells, including leukocytes, tumor cells, and endothelium. The role of Slit2 in vascular remodeling, however, remains controversial, with reports of both pro- and antiangiogenic activity. We report here that cooperation between Slit2 and ephrin-A1 regulates a balance between the pro- and antiangiogenic functions of Slit2. While Slit2 promotes angiogenesis in culture and in vivo as a single agent, Slit2 potently inhibits angiogenic remodeling in the presence of ephrin-A1. Slit2 stimulates angiogenesis through mTORC2-dependent activation of Akt and Rac GTPase, the activities of which are inhibited in the presence of ephrin-A1. Activated Rac or Akt partially rescues vascular assembly and motility in costimulated endothelium. Taken together, these data suggest that Slit2 differentially regulates angiogenesis in the context of ephrin-A1, providing a plausible mechanism for the pro- versus antiangiogenic functions of Slit2. Our results suggest that the complex roles of Slit-Robo signaling in angiogenesis involve context-dependent mechanisms.
Design and Analysis of a Compact Reversible Ternary Systolic Array

Multi-valued logic synthesis is a very promising and affluent research area at present because of allowing designers to build much more efficient computers than the existing classical ones. In this regard, research on ternary logic synthesis has got impetus in the recent years. Many existing literature are mainly perceptive to the realization of efficient ternary reversible processors. This research is based on the design of a reversible systolic array, one of the best examples of the parallel processing, using micro level ternary Toffoli gate. General architecture of the ternary reversible systolic array multiplier is shown along with example. Lower bound for the quantum cost and the garbage outputs in terms of entire circuit entire circuit is calculated here to establish the compactness of the design. Finally, comparative result shown that the proposed circuit outperforms the existing one both in terms of number of gates and Quantum cost analysis.
High-throughput image search via single-trial event detection in a rapid serial visual presentation task

We describe a method, using linear discrimination, for detecting single-trial EEG signatures of object recognition events in a rapid serial visual presentation (RSVP) task. We record EEG using a high spatial density array (87 electrodes) during the rapid presentation (50-200 msec per image) of natural images. Subjects were instructed to release a button when they recognized a target image (an image with a person/people). Trials consisted of 100 images each, with a 50% chance of a single target being in a trial. Subject EEG was analyzed on a single-trial basis with an optimal spatial linear discriminator learned at multiple time windows after the presentation of an image. Linear discrimination enables the estimation of a forward model and thus allows for an approximate localization of the discriminating activity. Results show multiple loci for discriminating activity (e.g. motor and visual). Using these detected EEG signatures, we show that in many cases we can detect targets more accurately than the overt response (button release) and that such signatures can be used to prioritize images for high-throughput search.
Multilocus sequence typing of IncN plasmids.

OBJECTIVES Incompatibility group N (IncN) plasmids have been associated with the dissemination of antimicrobial resistance and are a major vehicle for the spread of bla(VIM-1) in humans and bla(CTX-M-1) in animals. A plasmid multilocus sequence typing (pMLST) scheme was developed for rapid categorization of IncN plasmids. METHODS Twelve fully sequenced IncN plasmids available at GenBank were analysed in silico for selecting the loci for the IncN-specific pMLST. A total of 58 plasmids originating from different reservoirs (human, pig, poultry, cattle and horses) and geographic regions (Italy, Greece, Denmark, UK and The Netherlands) were classified by DNA sequencing of the amplicons obtained for the repA, traJ and korA loci. RESULTS Eleven sequence types (STs) were defined on the basis of allele sequences of the three selected loci. Most plasmids carrying bla(CTX-M-1) (24/27) isolated in different countries from both animals and humans belonged to ST1, suggesting dissemination of an epidemic plasmid through the food chain. Fifteen of 17 plasmids carrying bla(VIM-1) from Klebsiella pneumoniae and Escherichia coli, isolated during a 5 year period in Greece were assigned to ST10, suggesting that spread and persistence of this particular IncN-carrying bla(VIM-1) lineage in Greece. CONCLUSIONS This study proposes the use of pMLST as a suitable and rapid method for identification of IncN epidemic plasmid lineages. The recent spread of bla(CTX-M-1) among humans and animals seems to be associated with the dissemination of an epidemic IncN plasmid lineage.
Missing Relations Incorporating Relational Constructs Into Models of Culture

A5 an increasing number of organizations reach across national boundaries, organizational research increasingly addresses the question ofhow national culture influences individual behavior (Erez & Earley, 1993; Hofstede, 1991). Researchers face a choice among numerous definitions of culture and methods for studying it that have been developed in different academic disciplines (Keesing, 1974). As the diversity of chapters in this volume attests, researchers in different subfields oforganizational behavior have chosen different methodological paths and have arrived at different insights. The path chosen by most micro-level organizational behavior researchers is to study “subjective culture,” that is, to conceptualize culture as existing in an individual’s mental representations rather than in external structures and artifacts (Triandis, 1967, 1972, 1995). Cultural differences in values, beliefs, and attitudes are assessed through inventories such as those traditionally used to measure personality differences. Moreover, just as generalizations about personality were made in terms
Improving Participatory Urban Infrastructure Monitoring through Spatio-Temporal Analytics

Internet-enabled, location aware smart phones with sensor inputs have led to novel applications exploiting unprecedented high levels of citizen participation in dense metropolitan areas. Especially the possibility to make oneself heard on issues, such as broken traffic lights, potholes or garbage, has led to a high degree of participation in Urban Infrastructure Monitoring. However, citizens often repeatedly report duplicates instead of complementing information, leading to bottlenecks in manual processing by municipal authorities. Spatio-temporal clustering can serve as an essential tool to group and rank similar (e.g., duplicate) reports. Current data mining techniques could be used by municipal departments to manually process the most representative reports, but the mandatory parameter selection can be unintuitive, time consuming and error-prone. In this work, we therefore present a novel framework for clustering spatio-temporal data. We first apply an intuitive transformation of the data into a graph and subsequently use well-established graph clustering techniques to detect similar reports. We evaluate our method on two real-world data-sets from different mobile issue tracking platforms. As one of these datasets includes labels for duplicate reports, we can show how our framework outperforms existing techniques in our examplary use-case (duplicate detection).
Parameter Estimation With Partial Forgetting Method

Abstract The paper proposes a new estimating algorithm for linear parameter varying systems with slowly time-varying parameters when the rate of change of individual parameters is different. It introduces a true probability density function, describing ideally the behaviour of parameters. However, as it is unknown, we search for its best approximation. A convex combination of point estimates, defined by individual hypotheses about the true probability density function, is then approximated by a single density. That serves as the best available description of parameters’ behaviour and it is therefore suitable e.g. for prediction purposes.
Cramer-Rao Lower Bounds for the Joint Delay-Doppler Estimation of an Extended Target

The problem of the Cramer-Rao Lower Bounds (CRLBs) for the joint time delay and Doppler stretch estimation of an extended target is considered in this paper. Integral representations of the CRLBs for both the time delay and the Doppler stretch are derived. To facilitate computation and analysis, series representations and approximations of the CRLBs are introduced. According to these series representations, the impact of several waveform parameters on the estimation accuracy is investigated and reveals that the CRLB of the Doppler stretch is inversely proportional to the effective time-bandwidth product of the waveform. This conclusion generalizes a previous result in the narrowband case. The popular wideband ambiguity function (WBAF)-based delay-Doppler estimator is evaluated and compared with the CRLBs through numerical experiments. Our results indicate that the WBAF estimator, which was originally derived from a single scatterer model, is not suitable for the parameter estimation of an extended target.
Risk of Stroke in Elderly Dialysis Patients

Despite the current knowledge about the risk of stroke and its related factors in general population, this issue in elderly patients receiving dialysis remains unresolved. Firstly, to compare the risk of stroke between hemodialysis (HD) and peritoneal dialysis (PD), data on 13,065 incident dialysis patients (aged ≥ 65 years; 10,675 in HD and 2,390 in PD) were retrieved from the Korean Health Insurance dataset. Secondly, to identify the risk factors of stroke amongst various clinical and laboratory parameters in HD, 980 elderly patients were retrospectively analyzed using an independent prospective cohort from 31 dialysis centers. For a mean duration of 1.8 years (maximum of 5 years), the risk of all cardiovascular diseases (ischemic heart disease and stroke) did not differ between HD and PD. However, when analyses were conducted separately by subtype, the risk of stroke, not ischemic heart disease, was significantly higher in HD patients than in PD patients. When the risk factors of stroke were probed after HD for a mean duration of 2.6 years (maximum of 7 years), the absolute dependence on social support, a previous history of cardiovascular disease, high levels of low-density lipoprotein cholesterol, and the use of a high number of anti-hypertensive drugs were identified as being significant. Based on the discrepancy of stroke risk between modalities and the HD-tailored risk factors of stroke, the monitoring and management of these factors may be a key strategy to reduce the risk of stroke in elderly patients receiving dialysis.
The Ansamycin Antibiotic, Rifamycin SV, Inhibits BCL6 Transcriptional Repression and Forms a Complex with the BCL6-BTB/POZ Domain

BCL6 is a transcriptional repressor that is over-expressed due to chromosomal translocations, or other abnormalities, in ∼40% of diffuse large B-cell lymphoma. BCL6 interacts with co-repressor, SMRT, and this is essential for its role in lymphomas. Peptide or small molecule inhibitors, which prevent the association of SMRT with BCL6, inhibit transcriptional repression and cause apoptosis of lymphoma cells in vitro and in vivo. In order to discover compounds, which have the potential to be developed into BCL6 inhibitors, we screened a natural product library. The ansamycin antibiotic, rifamycin SV, inhibited BCL6 transcriptional repression and NMR spectroscopy confirmed a direct interaction between rifamycin SV and BCL6. To further determine the characteristics of compounds binding to BCL6-POZ we analyzed four other members of this family and showed that rifabutin, bound most strongly. An X-ray crystal structure of the rifabutin-BCL6 complex revealed that rifabutin occupies a partly non-polar pocket making interactions with tyrosine58, asparagine21 and arginine24 of the BCL6-POZ domain. Importantly these residues are also important for the interaction of BLC6 with SMRT. This work demonstrates a unique approach to developing a structure activity relationship for a compound that will form the basis of a therapeutically useful BCL6 inhibitor.
Response inhibition moderates the relationship between implicit associations and drinking behavior.

BACKGROUND Contemporary dual-process models of alcohol abuse propose that alcohol abuse develops because of dysfunctions in the impulsive system, which generates automatic impulses to drink alcohol, and disruptions in the reflective system, which becomes unable to inhibit the influence of these automatic impulses. Based on these insights, this study investigated whether individual differences in the ability of the reflective system to exert response inhibition moderate the relationship between automatic cognitive processes and drinking behavior. Specifically, it was examined whether the interaction between implicit alcohol-related associations and response inhibition predicted drinking behavior. METHODS Seventy-one university students completed the study online via the Internet. Implicit alcohol associations with positive affect and with arousal were assessed with variants of the Implicit Association Test. Response inhibition was measured using the original Stroop task. Participants also reported their weekly alcohol use and alcohol-related problems. RESULTS As predicted, implicit associations were unrelated to drinking behavior when response inhibition was high. In contrast, when response inhibition was low, stronger implicit associations between alcohol and positive affect predicted increased alcohol use and alcohol-related problems. CONCLUSIONS These findings indicate that the relationship between automatic cognitive processes, originating in the impulsive system, and drinking behavior depends on individual differences in response inhibition exerted by the reflective system. As prolonged alcohol abuse is known to impair response inhibition, alcohol abusers may benefit from interventions that increase response inhibition, thereby restoring inhibitory control over automatic impulses.
A Role-Based RSA Key Management Approach in a Hierarchy Scheme

The role-based hierarchical key assignment problem is to assign sensitive keys to security role-based classes in a partially ordered hierarchy so that legal data accesses among classes could be enforced according to the role's privileges. In role-based RSA key hierarchy management scheme, each user is assigned the role which could derive the RSA key corresponding to the assigned role-based class and its successors' classes in order to access specific contents of resources. In this paper, a role-based RSA key management scheme in a hierarchy scheme is proposed, which both RSA algorithm and Akl approach are combined to the scheme. The scheme provides an easy implement approach and a simple key storage manner to increase the availability of role-based access control scheme. Finally, the security analyses are also presented in this paper.