Miracle-dz/UniFAR-FTUs huggingface dataset:
Phenobarbital-Responsive Nuclear Translocation of the Receptor CAR in Induction of the CYP2B Gene

ABSTRACT The constitutively active receptor (CAR) transactivates a distal enhancer called the phenobarbital (PB)-responsive enhancer module (PBREM) found in PB-inducible CYP2B genes. CAR dramatically increases its binding to PBREM in livers of PB-treated mice. We have investigated the cellular mechanism of PB-induced increase of CAR binding. Western blot analyses of mouse livers revealed an extensive nuclear accumulation of CAR following PB treatment. Nuclear contents of CAR perfectly correlate with an increase of CAR binding to PBREM. PB-elicited nuclear accumulation of CAR appears to be a general step regulating the induction of CYP2B genes, since treatments with other PB-type inducers result in the same nuclear accumulation of CAR. Both immunoprecipitation and immunohistochemistry studies show cytoplasmic localization of CAR in the livers of nontreated mice, indicating that CAR translocates into nuclei following PB treatment. Nuclear translocation of CAR also occurs in mouse primary hepatocytes but not in hepatocytes treated with the protein phosphatase inhibitor okadaic acid. Thus, the CAR-mediated transactivation of PBREM in vivo becomes PB responsive through an okadaic acid-sensitive nuclear translocation process.
Fast tests for the common causality of time-of-arrival events from their mutual Minkowski distances

A problem with geolocation of a transmitter based on time difference of arrival measurements across a widely distributed receiver array is the association of time-of-arrival events with a single transmission. This is due to the possibility that some of the reception events correspond to some previous or subsequent transmission, or even that they correspond to a transmission from another source. In this paper we consider fast methods for screening out unfeasible associations based on the application of distance geometry in Minkowski space.
Managing Dual Business Models in Emerging Markets: An Ambidexterity Perspective

Research on dual business models has highlighted the challenge for firms when they compete with different business models in a market. Drawing from ambidexterity literature, we investigate the question of how firms integrate or separate business models at the level of value chain activities, which constitute the core operational activities within each business model. We employ a qualitative research approach based on 11 case studies of Western firms that implemented a low‐cost business model in parallel to their premium business model in emerging markets. We find that firms may become ambidextrous in their business models by means of domain separation. In doing so, firms may separate value chain activities to address different additional customer segments in emerging markets. This study contributes to the emerging topic of dual business models and provides the ground for future research on ambidexterity in a global context.
Peripheral blood leukocyte telomere length and mortality among 64,637 individuals from the general population.

BACKGROUND Short telomeres in peripheral blood leukocytes are associated with older age and age-related diseases. We tested the hypotheses that short telomeres are associated with both increased cancer mortality and all-cause mortality. METHODS Individuals (n = 64637) were recruited from 1991 onwards from two Danish prospective cohort studies: the Copenhagen City Heart Study and the Copenhagen General Population Study. All had telomere length measured by quantitative polymerase chain reaction and the genotypes rs1317082 (TERC), rs7726159 (TERT), and rs2487999 (OBFC1) determined. The sum of telomere-shortening alleles from these three genotypes was calculated. We conducted Cox regression analyses and instrumental variable analyses using the allele sum as an instrument. All statistical tests were two-sided. RESULTS Among 7607 individuals who died during follow-up (0-22 years, median = 7 years), 2420 had cancer and 2633 had cardiovascular disease as causes of death. Decreasing telomere length deciles were associated with increasing all-cause mortality (P(trend) = 2*10(-15)). The multivariable-adjusted hazard ratio of all-cause mortality was 1.40 (95% confidence interval [CI] = 1.25 to 1.57) for individuals in the shortest vs the longest decile. Results were similar for cancer mortality and cardiovascular mortality. Telomere length decreased 69 base pairs (95% CI = 61 to 76) per allele for the allele sum, and the per-allele hazard ratio for cancer mortality was 0.95 (95% CI = 0.91 to 0.99). Allele sum was not associated with cardiovascular, other, or all-cause mortality. CONCLUSION Short telomeres in peripheral blood leukocytes were associated with high mortality in association analyses. In contrast, genetically determined short telomeres were associated with low cancer mortality but not with all-cause mortality.
Multiple Roles of Charged Amino Acids in Cytoplasmic Loop 7 for Expression and Function of the Multidrug and Organic Anion Transporter MRP1 (ABCC1)

Multidrug resistance protein MRP1 mediates the ATP-dependent efflux of many chemotherapeutic agents and organic anions. MRP1 has two nucleotide binding sites (NBSs) and three membrane spanning domains (MSDs) containing 17 transmembrane helices linked by extracellular and cytoplasmic loops (CL). Homology models suggest that CL7 (amino acids 1141-1195) is in a position where it could participate in signaling between the MSDs and NBSs during the transport process. We have individually replaced eight charged residues in CL7 with Ala, and in some cases, an amino acid with the same charge, and then investigated the effects on MRP1 expression, transport activity, and nucleotide and substrate interactions. A triple mutant in which Glu1169, Glu1170, and Glu1172 were all replaced with Ala was also examined. The properties of R1173A and E1184A were comparable with those of wild-type MRP1, whereas the remaining mutants were either poorly expressed (R1166A, D1183A) or exhibited reduced transport of one or more organic anions (E1144A, D1179A, K1181A, 1169AAQA). Same charge mutant D1183E was also not expressed, whereas expression and activity of R1166K were similar to wild-type MRP1. The moderate substrate-selective changes in transport activity displayed by mutants E1144A, D1179A, K1181A, and 1169AAQA were accompanied by changes in orthovanadate-induced trapping of [α-32P]azidoADP by NBS2 indicating changes in ATP hydrolysis or release of ADP. In the case of E1144A, estradiol glucuronide no longer inhibited trapping of azidoADP. Together, our results demonstrate the extreme sensitivity of CL7 to mutation, consistent with its critical and complex dual role in both the proper folding and transport activity of MRP1.
Evaluating Pulling Effects in Oscillators Due to Small-Signal Injection

This paper presents a hybrid numerical-analytical approach to evaluate and quantify injection pulling effects in RF oscillators. The method employs the Floquet nu1(t) eigenvector to project the perturbation signal into the phase domain. An original closed-form expression for the frequency shift induced by small-signal harmonic perturbations is derived. It is shown that such closed-form expression accurately predicts frequency shift under weak pulling, quasi-lock, as well as locked conditions. An estimation of the main spectrum components of the pulled response is also derived. The proposed macromodeling approach has the peculiarity to be applicable to any oscillator topology.
AW-ELM-based Crouch Gait recognition after ischemic stroke

Crouch Gait (CG) can be observed in the hemiplegia persons after ischemic stroke. Walking with Crouch Gait (CG) shown a large gaits disorder. This paper explores the use of adaptive wavelet extreme learning machine (AW-ELM) to classifying different gait conditions for hemiplegia and healthy subjects. Three participants having a Crouch Gait problem with categories of Mild, Moderate, and Severe gait conditions, also, one Healthy person are used their data in this work. The recognition system extracting number of time and frequency domain features for dimensionality reduction. While for the classification stage, the common Extreme Learning Machine (ELM) classifiers are used. AW-ELM achieved maximum testing accuracy up to 91.149 % and with using majority vote post-processing the accuracy achieves 91.547 %.
Evolutionary Consequences of Coevolving Targets

Most evolutionary optimization models incorporate a fitness evaluation that is based on a predefined static set of test cases or problems. In the natural evolutionary process, selection is of course not based on a static fitness evaluation. Organisms do not have to combat every existing disease during their lifespan; organisms of one species may live in different or changing environments; different species coevolve. This leads to the question of how information is integrated over many generations. This study focuses on the effects of different fitness evaluation schemes on the types of genotypes and phenotypes that evolve. The evolutionary target is a simple numerical function. The genetic representation is in the form of a program (i.e., a functional representation, as in genetic programming). Many different programs can code for the same numerical function. In other words, there is a many-to-one mapping between genotypes (the programs) and phenotypes. We compare fitness evaluation based on a large static set of problems and fitness evaluation based on small coevolving sets of problems. In the latter model very little information is presented to the evolving programs regarding the evolutionary target per evolutionary time step. In other words, the fitness evaluation is very sparse. Nevertheless the model produces correct solutions to the complete evolutionary target in about half of the simulations. The complete evaluation model, on the other hand, does not find correct solutions to the target in any of the simulations. More important, we find that sparse evaluated programs are better generalizable compared to the complete evaluated programs when they are evaluated on a much denser set of problems. In addition, the two evaluation schemes lead to programs that differ with respect to mutational stability; sparse evaluated programs are less stable than complete evaluated programs.
Validating Software Reliability Early through Statistical Model Checking

Conventional software reliability assessment validates a system's reliability only at the end of development, resulting in costly defect correction. A proposed framework employs statistical model checking (SMC) to validate reliability at an early stage. SMC computes the probability that a target system will satisfy functional-safety requirements. The framework compares the allocated reliability goal with the calculated reliability using the probabilities and relative weight values for the functional-safety requirements. Early validation can prevent the propagation of reliability allocation errors and design errors at later stages, thereby achieving safer, cheaper, and faster development of safety-critical systems.
Bacterial Biofilm Removal Using Static and Passive Ultrasonic Irrigation

Background: The aim of the present study was to evaluate the efficiency of two irrigating techniques - static and dynamic (passive ultrasonic instrumentation) irrigation in the elimination of bacterial biofilm. Materials and Methods: Forty extracted human permanent maxillary central incisors teeth with straight roots and single canals, were randomly allocated to two groups for static irrigation and passive ultrasonic irrigation (PUI). The root canal irrigant used was 2.5 % sodium hypochlorite. The root canals were prepared to tip sizes (20, 40) and tapers (0.04, 0.08). Using system GT instruments (Dentsply Malliefer, Switerzland). The teeth were split longitudinally into two, stained collagen was applied to the canal surfaces and the tooth reassembled for static and PUI. Digital images of the canal surface were taken before and after irrigation with 9, 18, 27 and 37 mL solution. The digital images were analyzed using ImageJ software (National Institute of Health, USA) to quantify residual canal coverage by the stained collagen. The data were analyzed using linear regression models and subjected to statistical analysis. Results: The mean percentage of canal surface with residual collagen increased with the coronal level of canal, decrease in apical size and taper of canal preparation and decrease in the volume of the irrigant. There was less residual collagen after PUI compared with static irrigation. The canal surface facing the open side port of the needle had less residual collagen after irrigation than the opposing surface. Conclusion: The stained collagen biomolecular film could not be removed completely either by passive ultrasonic instrumentation or static irrigation. The PUI was found to be more effective in the removal of collagen, especially in the apical part of the root canal.
Towards Developing a New I-P Technology Adoption Framework: A Research Road Map

While several studies have been conducted relating to the acceptability and use of Smart National Identity Card (SNIC), research in determining factors that influence the citizens' acceptance and use of health information application in (SNIC) has not yet been conducted. This paper presents a new paradigm of individual level technology acceptance and use framework known as I-P (Individual-Privacy) to study the acceptance and use of health information application in SNIC. Furthermore, the prior literatures discovered that there are factors such as trust, perceived risk, Privacy concern and perceived credibility need to be incorporated into technology adoption models. Therefore, this research contributes to the body of knowledge towards acceptance and use of SNIC applications from e-government perspective by providing a clear understanding on interrelationships of both technology adoption and privacy calculus factors in predicting health information application in SNIC acceptance and use. This study applies extended Unified Theory of Acceptance and Use of Technology (UTAUT2) along with the privacy calculus model as the foundation information system theories. Nevertheless it is argued that UTAUT2 is a broad framework of technology adoption. For that reason, this study integrates the UTAUT2 with privacy calculus model and adds perceived credibility as a new variable to support the existing UTAUT2 model. The research framework and recommendations of this study may enable to establish better innovative e-health services as to cover the desires of the citizens through the use of health information application embedded in all in one card. Initial results to assess the validity of measurement items are presented in this paper. Further statistical analysis will be conducted in the future to provide proof and empirically validate the I-P framework.
The Study on Performance of Streaming Media under Different Overlay Topology

With the wide use of streaming media, overlay, which is the base of streaming media transmission, has become a hot research area. While the topology of overlay changes from traditional tree to mesh, there still remains a lack of research on how different topologies under different physical networks will impact on the performance of streaming media transmission. This paper will fill up this gap, and present an overlay topology choosing strategy. We build tree as well as mesh overlay topology based on different network topologies, which are gained from GT-ITM using the Transit-Stub model. We use TORM and PowerP2P as the instances of tree and mesh topology transport protocols respectively. We analyze and compare the simulation results got through NS2, find out the relationship between delay, throughput and the distributing of the nodes, the overlay topology we choose. Based on these results, this paper proposes a strategy on how to choose an overlay topology when the distributing of the nodes is known. It can be a guide when someone wants to deploy a transmission of the streaming media on a network.
Business Responses to Environmental and Social Protection Policies: Towards a Framework for Analysis

This conceptual paper seeks to advance neo-institutional work that has tradi- tionally portrayed environmental and social protection policies as constraints followed by businesses. Drawing from the policy sciences literature, we propose that in the United States, businesses tend to show increasing resistance as the protective policy process moves from initiation to selection and growing cooperation thereafter. Most importantly, we also contribute to the neo-institutional theory literature by positing that this inverted U-shaped policy process-business response relationship proposed for the U.S. context may be moderated by variations in the level of democracy, system of interest representation, regulatory approach, and national income.
Whole Genome Transcript Profiling of Drug Induced Steatosis in Rats Reveals a Gene Signature Predictive of Outcome

Drug induced steatosis (DIS) is characterised by excess triglyceride accumulation in the form of lipid droplets (LD) in liver cells. To explore mechanisms underlying DIS we interrogated the publically available microarray data from the Japanese Toxicogenomics Project (TGP) to study comprehensively whole genome gene expression changes in the liver of treated rats. For this purpose a total of 17 and 12 drugs which are diverse in molecular structure and mode of action were considered based on their ability to cause either steatosis or phospholipidosis, respectively, while 7 drugs served as negative controls. In our efforts we focused on 200 genes which are considered to be mechanistically relevant in the process of lipid droplet biogenesis in hepatocytes as recently published (Sahini and Borlak, 2014). Based on mechanistic considerations we identified 19 genes which displayed dose dependent responses while 10 genes showed time dependency. Importantly, the present study defined 9 genes (ANGPTL4, FABP7, FADS1, FGF21, GOT1, LDLR, GK, STAT3, and PKLR) as signature genes to predict DIS. Moreover, cross tabulation revealed 9 genes to be regulated ≥10 times amongst the various conditions and included genes linked to glucose metabolism, lipid transport and lipogenesis as well as signalling events. Additionally, a comparison between drugs causing phospholipidosis and/or steatosis revealed 26 genes to be regulated in common including 4 signature genes to predict DIS (PKLR, GK, FABP7 and FADS1). Furthermore, a comparison between in vivo single dose (3, 6, 9 and 24 h) and findings from rat hepatocyte studies (2 h, 8 h, 24 h) identified 10 genes which are regulated in common and contained 2 DIS signature genes (FABP7, FGF21). Altogether, our studies provide comprehensive information on mechanistically linked gene expression changes of a range of drugs causing steatosis and phospholipidosis and encourage the screening of DIS signature genes at the preclinical stage.
Phenomenology, astrophysics and cosmology of theories with submillimeter dimensions and TeV scale quantum gravity

We recently proposed a solution to the hierarchy problem not relying on low-energy supersymmetry or technicolor. Instead, the problem is nullified by bringing quantum gravity down to the TeV scale. This is accomplished by the presence of n{ge}2 new dimensions of submillimeter size, with the SM fields localized on a 3-brane in the higher dimensional space. In this paper we systematically study the experimental viability of this scenario. Constraints arise both from strong quantum gravitational effects at the TeV scale, and more importantly from the production of massless higher dimensional gravitons with TeV suppressed couplings. Theories with n{gt}2 are safe due mainly to the infrared softness of higher dimensional gravity. For n=2, the six dimensional Planck scale must be pushed above {approximately}30thinspTeV to avoid cooling SN 1987A and distortions of the diffuse photon background. Nevertheless, the particular implementation of our framework within type I string theory can evade all constraints, for any n{ge}2, with string scale m{sub s}{approximately}1thinspTeV. We also explore novel phenomena resulting from the existence of new states propagating in the higher dimensional space. The Peccei-Quinn solution to the strong CP problem is revived with a weak scale axion in the bulk. Gauge fields in the bulk canmore » mediate repulsive forces {approximately}10{sup 6}{endash}10{sup 8} times stronger than gravity at submillimeter distances, as well as help stabilize the proton. Higher-dimensional gravitons produced on our brane and captured on a different {open_quotes}fat{close_quotes} brane can provide a natural dark matter candidate. {copyright} {ital 1999} {ital The American Physical Society}« less
A closer look at the spatial architecture of aphid clones

Nearly 25 years ago, Ellstrand & Roose (1987) reviewed what was known at the time of the genetic structure of clonal plant species. What is the relationship between space and clonal fitness, they asked. What is the best way for a clone to grow within its ecological neighbourhood? The pot had been stirred 10 years previously by Janzen (1977) , who pointed out how little we know about the population biology of clonal organisms like dandelions and aphids. He wondered whether, like good curries, outward appearances masked common ingredients. Because in no small part of the advent of molecular ecology, we know more about clonal life histories today, particularly in plants ( van Dijk 2003 ; Vallejo‐Marín et al. 2010 ). Surprisingly, studies of the spatial architecture of aphid clones have been comparably rare. In this issue of Molecular Ecology, Vantaux et al. characterize the fine‐scale distribution of the black bean aphid (Aphis fabae) and in so doing, help to fill that gap. They describe a moderate degree of intermingling between aphid clones over a growing season—A. fabae clones are ‘sticky’, but only a bit. By mixing, clones directly compete with each other as well. The results of Vantaux et al. (2011) will help to integrate evolutionary patterns in aphids with the appropriate ecological scales out of which those patterns emerge.
New insights into the QuikChangeTM process guide the use of Phusion DNA polymerase for site-directed mutagenesis

The QuikChangeTM site-directed mutagenesis method is popular but imperfect. An improvement by using partially overlapping primers has been reported several times; however, it is incompatible with the proposed mechanism. The QuikChangeTM method using complementary primers is proposed to linearly amplify a target plasmid with the products annealing to produce double-stranded DNA molecules with 5′-overhangs. The overhang annealing is supposed to form circular plasmids with staggered breaks, which can be repaired in Escherichia coli after transformation. Here, we demonstrated that the PCR enzyme fills the 5′-overhangs in the early cycles, and the product is then used as the template for exponential amplification. The linear DNA molecules with homologous ends are joined to generate the plasmid with the desired mutations through homologous recombination in E. coli. The correct understanding is important to method improvements, guiding us to use partially overlapping primers and Phusion DNA polymerase for site-directed mutagenesis. Phusion did not amplify a plasmid with complementary primers but used partially overlapping primers to amplify the plasmid, producing linear DNA molecules with homologous ends for site-directed mutagenesis.