Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple mechanisms are involved in 6‐gingerol‐induced cell growth arrest and apoptosis in human colorectal cancer cells

6‐Gingerol, a natural product of ginger, has been known to possess anti‐tumorigenic and pro‐apoptotic activities. However, the mechanisms by which it prevents cancer are not well understood in human colorectal cancer. Cyclin D1 is a proto‐oncogene that is overexpressed in many cancers and plays a role in cell proliferation through activation by β‐catenin signaling. Nonsteroidal anti‐inflammatory drug (NSAID)‐activated gene‐1 (NAG‐1) is a cytokine associated with pro‐apoptotic and anti‐tumorigenic properties. In the present study, we examined whether 6‐gingerol influences cyclin D1 and NAG‐1 expression and determined the mechanisms by which 6‐gingerol affects the growth of human colorectal cancer cells in vitro. 6‐Gingerol treatment suppressed cell proliferation and induced apoptosis and G1 cell cycle arrest. Subsequently, 6‐gingerol suppressed cyclin D1 expression and induced NAG‐1 expression. Cyclin D1 suppression was related to inhibition of β‐catenin translocation and cyclin D1 proteolysis. Furthermore, experiments using inhibitors and siRNA transfection confirm the involvement of the PKCε and glycogen synthase kinase (GSK)‐3β pathways in 6‐gingerol‐induced NAG‐1 expression. The results suggest that 6‐gingerol stimulates apoptosis through upregulation of NAG‐1 and G1 cell cycle arrest through downregulation of cyclin D1. Multiple mechanisms appear to be involved in 6‐gingerol action, including protein degradation as well as β‐catenin, PKCε, and GSK‐3β pathways. © 2007 Wiley‐Liss, Inc.
Proving testing preorders for process algebra descriptions

Process algebras are rapidly becoming a mathematical model used by verification engineers to extend the description capabilities of finite state machines towards higher abstraction levels. As long as design and verification methodologies at the system level are developed the wide spectrum of equivalence relations that can be defined over processes receives an ever increasing importance. Testing equivalences and testing preorders are particularly suited for formalizing the relationships holding in top-down hierarchical methodologies. The main deterrent to the widespread use of process algebras seems to be the lack of efficient tools. Very efficient algorithmic techniques, based on the adoption of binary decision diagrams, are now being used in different fields. This paper presents algorithms for the proof of testing preorders and equivalences that are, to the best of our knowledge, the first successful attempt to implement testing relations with BDDs. Experimental results show that the the implemented algorithms are able to deal with medium and large-size systems. <<ETX>>
Kiln: Closing the performance gap between systems with and without persistence support

Persistent memory is an emerging technology which allows in-memory persistent data objects to be updated at much higher throughput than when using disks as persistent storage. Previous persistent memory designs use logging or copy-on-write mechanisms to update persistent data, which unfortunately reduces the system performance to roughly half that of a native system with no persistence support. One of the great challenges in this application class is therefore how to efficiently enable atomic, consistent, and durable updates to ensure data persistence that survives application and/or system failures. Our goal is to design a persistent memory system with performance very close to that of a native system. We propose Kiln, a persistent memory design that adopts a nonvolatile cache and a nonvolatile main memory to enable atomic in-place updates without logging or copy-on-write. Our evaluation shows that Kiln can achieve 2× performance improvement compared with NVRAM-based persistent memory with write-ahead logging. In addition, our design has numerous practical advantages: a simple and intuitive abstract interface, microarchitecture-level optimizations, fast recovery from failures, and eliminating redundant writes to nonvolatile storage media.
Differential response patterns in the striatum and orbitofrontal cortex to financial reward in humans: a parametric fMRI study

Responses to monetary reward in humans have been assessed in a number of recent functional imaging studies, and it is clear that the neuronal substrates of financial reinforcement overlap extensively with regions responding to primary reinforcers, such as food. Money has the practical advantage of being an objectively quantifiable reinforcer. In this study, we exploit this advantage using a parametric functional magnetic resonance imaging design to look at the patterns of responding to systematically varying reward values. Twelve healthy volunteers were scanned during performance of a rewarded target detection task, in which the reward value varied between task blocks. We observed three distinct patterns of responding in different regions. Amygdala, striatum, and dopaminergic midbrain responded to the presence of rewards, regardless of value. In contrast, premotor cortex showed a linear increase in response with increasing reward value. Finally, medial and lateral foci of orbitofrontal cortex responded nonlinearly, such that response was enhanced for the lowest and highest reward values relative to the midrange. These results suggest functional distinction in response patterns within a distributed reward system.
Psychopharmacological and other treatments in preschool children with attention-deficit/hyperactivity disorder: current evidence and practice.

OBJECTIVE This article reviews rational approaches to treating attention-deficit/hyperactivity disorder (ADHD) in preschool children, including pharmacological and nonpharmacological treatments. Implications for clinical practice are discussed. DATA SOURCES We searched MEDLINE, PsychINFO, Cumulative Index to Nursing & Allied Health, Educational Resources Information Center, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects for relevant literature published in English from 1967 to 2007 on preschool ADHD. We also reviewed the references cited in identified reports. STUDY SELECTION Studies were reviewed if the sample included at least some children younger than 6 years of age or attending kindergarten, the study participants had a diagnosis of ADHD or equivalent symptoms, received intervention aimed at ADHD symptoms, and included a relevant outcome measure. DATA EXTRACTION Studies were reviewed for type of intervention and outcome relevant to ADHD and were rated for the level of evidence for adequacy of the data to inform clinical practice. CONCLUSIONS The current level of evidence for adequacy of empirical data to inform clinical practice for short-term treatment of ADHD in preschool children is Level A for methylphenidate and Level B for parent behavior training, child training, and additive-free elimination diet.
Reachability analysis of feature interactions: a progress report

Features are added to an existing system to add functionality. A new feature interacts with an existing feature if the behavior of the existing feature is changed by the presence of the new feature. Our research group has started to investigate how to detect feature interactions during the requirements phase of feature development. We have adopted a layered state-transition machine model that prioritizes features and avoids interactions due to non-determinism. We have a tabular notation for specifying behavioral requirements of services and features. Specifications are composed into a reachability graph, and the graph is searched for feature interactions. This paper demonstrates how reachability analysis has been used to automatically detect known control interactions, data interactions, and resource contentions among telephony features.
Multiple antibiotic resistance in Rhizobium japonicum

A total of 48 strains of the soil bacterium Rhizobium japonicum were screened for their response to several widely used antibiotics. Over 60% of the strains were resistant to chloramphenicol, polymyxin B, and erythromycin, and 47% or more of the strains were resistant to neomycin and penicillin G, when tested by disk assay procedures. The most common grouping of resistances in strains was simultaneous resistance to tetracycline, penicillin G, neomycin, chloramphenicol, and streptomycin (25% of all strains tested). The occurrence of multiple drug resistance in a soil bacterium that is not a vertebrate pathogen suggests that chemotherapeutic use of antibiotics is not required for the development of multiple drug resistance.
Global Self-Esteem Across the Life Span: A Cross-Sectional Comparison Between Representative and Self-Selected Internet Samples

The cross-sectional trajectory of global self-esteem across the life span was examined administering the Rosenberg and Single-Item Self-Esteem scales to Estonians (N = 29,463) who were either randomly selected from the National Census to represent the population or self-recruited through the Internet. The results (a) challenge the recent conclusion of a universal age trajectory of self-esteem, (b) demonstrate that self-recruited Internet data collection method is biased compared to random sampling, and (c) present that different self-esteem items have dissimilar trajectories. A variance component analysis confirmed that age differences in self-esteem are relatively small compared to interindividual differences and measurement error.
Planar catadioptric stereo: geometry and calibration

By using mirror reflections of a scene, stereo images can be captured with a single camera (catadioptric stereo). Single camera stereo provides both geometric and radiometric advantages over traditional two camera stereo. In this paper we discuss the geometry and calibration of catadioptric stereo with two planar mirrors and show how the relative orientation, the epipolar geometry and the estimation of the focal length are constrained by planar motion. In addition, we have implemented a real-time system which demonstrates the viability of stereo with mirrors as an alternative to traditional two camera stereo.
Treating Bugs as Allergies: A Safe Method for Surviving Software Failures

Many applications demand availability. Unfortunately, software failures greatly reduce system availability. Previous approaches for surviving software failures suffer from several limitations, including requiring application restructuring, failing to address deterministic software bugs, unsafely speculating on program execution, and requiring a long recovery time. This paper proposes an innovative, safe technique, called Rx, that can quickly recover programs from many types of common software bugs, both deterministic and non-deterministic. Our idea, inspired by allergy treatment in real life, is to rollback the program to a recent checkpoint upon a software failure, and then to reexecute the program in a modified environment. We base this idea on the observation that many bugs are correlated with the execution environment, and therefore can be avoided by removing the "allergen" from the environment. Rx requires few to no modifications to applications and provides programmers with additional feedback for bug diagnosis.
A 7-Deaza-Adenosine Analog Is a Potent and Selective Inhibitor of Hepatitis C Virus Replication with Excellent Pharmacokinetic Properties

ABSTRACT Improved treatments for chronic hepatitis C virus (HCV) infection are needed due to the suboptimal response rates and deleterious side effects associated with current treatment options. The triphosphates of 2′-C-methyl-adenosine and 2′-C-methyl-guanosine were previously shown to be potent inhibitors of the HCV RNA-dependent RNA polymerase (RdRp) that is responsible for the replication of viral RNA in cells. Here we demonstrate that the inclusion of a 7-deaza modification in a series of purine nucleoside triphosphates results in an increase in inhibitory potency against the HCV RdRp and improved pharmacokinetic properties. Notably, incorporation of the 7-deaza modification into 2′-C-methyl-adenosine results in an inhibitor with a 20-fold-increased potency as the 5′-triphosphate in HCV RdRp assays while maintaining the inhibitory potency of the nucleoside in the bicistronic HCV replicon and with reduced cellular toxicity. In contrast, while 7-deaza-2′-C-methyl-GTP also displays enhanced inhibitory potency in enzyme assays, due to poor cellular penetration and/or metabolism, the nucleoside does not inhibit replication of a bicistronic HCV replicon in cell culture. 7-Deaza-2′-C-methyl-adenosine displays promising in vivo pharmacokinetics in three animal species, as well as an acute oral lethal dose in excess of 2,000 mg/kg of body weight in mice. Taken together, these data demonstrate that 7-deaza-2′-C-methyl-adenosine is an attractive candidate for further investigation as a potential treatment for HCV infection.
Simultaneous inhibition of pan-phosphatidylinositol-3-kinases and MEK as a potential therapeutic strategy in peripheral T-cell lymphomas

Peripheral T-cell lymphomas are very aggressive hematologic malignancies for which there is no targeted therapy. New, rational approaches are necessary to improve the very poor outcome in these patients. Phosphatidylinositol-3-kinase is one of the most important pathways in cell survival and proliferation. We hypothesized that phosphatidylinositol-3-kinase inhibitors could be rationally selected drugs for treating peripheral T-cell lymphomas. Several phosphatidylinositol-3-kinase isoforms were inhibited genetically (using small interfering RNA) and pharmacologically (with CAL-101 and GDC-0941 compounds) in a panel of six peripheral and cutaneous T-cell lymphoma cell lines. Cell viability was measured by intracellular ATP content; apoptosis and cell cycle changes were checked by flow cytometry. Pharmacodynamic biomarkers were assessed by western blot. The PIK3CD gene, which encodes the δ isoform of phosphatidylinositol-3-kinase, was overexpressed in cell lines and primary samples, and correlated with survival pathways. However, neither genetic nor specific pharmacological inhibition of phosphatidylinositol-3-kinase δ affected cell survival. In contrast, the pan-phosphatidylinositol-3-kinase inhibitor GDC-0941 arrested all T-cell lymphoma cell lines in the G1 phase and induced apoptosis in a subset of them. We identified phospho-GSK3β and phospho-p70S6K as potential biomarkers of phosphatidylinositol-3-kinase inhibitors. Interestingly, an increase in ERK phosphorylation was observed in some GDC -0941-treated T-cell lymphoma cell lines, suggesting the presence of a combination of phosphatidylinositol-3-kinase and MEK inhibitors. A highly synergistic effect was found between the two inhibitors, with the combination enhancing cell cycle arrest at G0/G1 in all T-cell lymphoma cell lines, and reducing cell viability in primary tumor T cells ex vivo. These results suggest that the combined treatment of pan-phosphatidylinositol-3-kinase + MEK inhibitors could be more effective than single phosphatidylinositol-3-kinase inhibitor treatment, and therefore, that this combination could be of therapeutic value for treating peripheral and cutaneous T-cell lymphomas.
Sorption of Benzo[a]pyrene and Phenanthrene on Suspended Harbor Sediment as a Function of Suspended Sediment Concentration and Salinity: A Laboratory Study Using the Cosolvent Partition Coefficient.

The sorption of benzo[a]pyrene (BaP) and phenanthrene (PHE) on sediment collected in the harbor of Rotterdam was studied in batch experiments using 14 C-labeled compounds. In order to simulate various estuarine conditions, we investigated the effects of various sediment concentrations and salinities on sorption of these compounds. We determined the apparent partitioning as well as the cosolvent partitioning between the liquid and solid phases. The apparent partition coefficient (K p App ) is influenced by the presence of colloids and dissolved organic matter. The influence of these components is minimized by the use of the cosolvent method in which the partition coefficient (K p * ) is determined by extrapolation of the partition coefficients obtained in a variety of solutions with water and methanol. The effect of sediment concentration on sorption was investigated at five different sediment concentrations ranging from 0.064 to 10.8 g/L. In contrast to K p * , K p App was found to be sensitive to the sediment concentration. Log K p * (with K p * in L/kg), determined for different sediment concentrations, was 5.2-6.3 for BaP and 2.8-3.6 for PHE,whereas log K p App was 4.1-5.6 for BaP and 2.9-4.0 for PHE. The salt concentration was varied with dilutions of Milli-Q water and seawater ; the salinity ranged from 0 to 35. The influence of salinity on K p * was small ; the increase in log K p * from freshwater to seawater is approximately 0.2 for BaP and 0.1 for PHE.
Leisure Activity and Depressive Symptoms of Widowed and Married Women in Later Life

Abstract Relatively little evidence is available about how leisure involvement changes with spousal loss, and even less about how leisure activity is associated with the well-being of widows during this transition. Using data from the Americans Changing Lives (ACL) dataset, this study compared 148 widows with an equal number of continuously married women to investigate change in leisure involvement during the transition to widowhood and examine the relationship between leisure and depressive symptoms among the older women. Findings indicated that widows benefited from increased involvement in some activities while this was not necessarily the case for married women. This suggests that change in widows' leisure involvement may be related more to bereavement than to other aging-related changes such as health and disability.
Diversification when It Hurts? The Joint Distributions of Real Estate and Equity Markets

This article examines claims about the diversification benefits of real estate. In particular, does real estate investment in a mixed asset portfolio provide protection when other asset classes are performing badly? Conventional portfolio strategy models utilising covariance statistics may result in a misallocation of capital if correlation structures between assets differ across the distribution of returns. Models of asymmetric dependence using the copula function, drawn from the recent finance literature are used to examine the relationships between real estate and equity at different points in their joint return distributions. For both UK and Global markets, real estate securities and common equities are shown to exhibit strong tail dependence – particularly in the negative tail. This suggests that real estate securities offer, at best, limited diversification protection when it is needed most – when other asset markets are falling. This has implications for allocation strategies in mixed asset portfolios. 1. Paper originally presented to the European Real Estate Society Annual Conference, Dublin, June 2005.
New Insights into Chloramphenicol Biosynthesis in Streptomyces venezuelae ATCC 10712

ABSTRACT Comparative genome analysis revealed seven uncharacterized genes, sven0909 to sven0915, adjacent to the previously identified chloramphenicol biosynthetic gene cluster (sven0916–sven0928) of Streptomyces venezuelae strain ATCC 10712 that was absent in a closely related Streptomyces strain that does not produce chloramphenicol. Transcriptional analysis suggested that three of these genes might be involved in chloramphenicol production, a prediction confirmed by the construction of deletion mutants. These three genes encode a cluster-associated transcriptional activator (Sven0913), a phosphopantetheinyl transferase (Sven0914), and a Na+/H+ antiporter (Sven0915). Bioinformatic analysis also revealed the presence of a previously undetected gene, sven0925, embedded within the chloramphenicol biosynthetic gene cluster that appears to encode an acyl carrier protein, bringing the number of new genes likely to be involved in chloramphenicol production to four. Microarray experiments and synteny comparisons also suggest that sven0929 is part of the biosynthetic gene cluster. This has allowed us to propose an updated and revised version of the chloramphenicol biosynthetic pathway.
Wake redirecting using feedback control to improve the power output of wind farms

In future, a wind turbine will not only be seen as a single systems operating independently, but also as a component of a larger interacting system, the wind farm. To increase the efficiency of a wind farm, two main concepts have been proposed: axial induction control and wake redirecting. This contribution focuses on the latter. Remote sensing technologies in wind energy applications have opened new ways to control wind turbines. In this contribution, a further step is taken by using a remote sensing device for redirecting the wake of a wind turbine. A controller is proposed which uses the yaw actuator of a wind turbine to steer the wake center of the turbine to a desired position. The wake propagation from the wind turbine to the measurement location is modeled with a time delay. This forms a challenging problem for controller design. The controller follows the idea of the internal model principle and uses a model to predict the system behavior avoiding an overestimation of the error. Further, an adaptive filter is proposed in order to filter uncontrollable frequencies from the wake center estimation. The estimation from lidar measurement data is assumed to be perfect. Closed-loop simulations are conducted using the nominal system and a wind farm simulation tool, which was adapted to the scenario. The results are compared to the uncontrolled baseline case and a statically applied yaw offset. They show an increase in the total power output of the wind farm. Together with wake tracking methods, the approach can be considered as a promising step towards closed-loop wind farm control.
Effect of curing lights and bleaching agents on physical properties of a hybrid composite resin.

UNLABELLED The aim of this in vitro study was to evaluate the microhardness (MH) and diametral tensile strength (DTS) of a minifill hybrid composite (Filtek Z250, 3M ESPE), polymerized with halogen lamp or second generation light-emitting diode (LED), submitted to different bleaching agents. Composite resin specimens were randomly polymerized according to experimental groups (halogen, 550 mW/cm(2)/20 seconds; LED, 550 mW/cm(2)/25 seconds) and subdivided into three subgroups (N=8): A, without bleaching (control); H, 35% hydrogen peroxide; and C, 16% carbamide peroxide. After that, the MH test and DTS test were performed. Two-way analysis of variance (whitening x light) and Tukey's tests (alpha=5%) were performed. For DTS, there were no statistical differences among the bleaching agents and the control group; however, the halogen group presented statistically lower DTS (p<0.05) than the LED group. For the MH test, the carbamide peroxide group presented statistically lower MH means (p<0.05) than the control groups, and there were no statistical differences among the light-curing units. Sixteen percent carbamide peroxide reduced the MH of the hybrid composite tested. The second generation LED presented a performance similar to or better than the halogen lamp for hardness and DTS, respectively. CLINICAL SIGNIFICANCE Repolishing of minifill hybrid composite is suggested, as the alteration caused after the contact with 16% carbamide peroxide was limited to the material surface. The second generation light-emitting diode is a good option for a curing light device when the polymerization initiator of composite resin is camphorquinone.