Miracle-dz/UniFAR-FTUs huggingface dataset:
Protection against aflatoxin B1-induced hepatocarcinogenesis in F344 rats by 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz): predictive role for short-term molecular dosimetry.

Previous studies have demonstrated that dietary administration of the schistosomicidal drug 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz) ameliorates the hepatotoxicity of aflatoxin B1 (AFB1). Notably, mortality, altered hepatic function, hepatic AFB1-DNA adduct levels, and expression of hepatic enzyme-altered foci were markedly reduced in the rat by concurrent feeding of oltipraz during exposures to AFB1. Collectively, these studies prompted us to evaluate the chemoprotective properties of oltipraz against AFB1-induced liver cancer. In addition, preliminary molecular dosimetry studies were undertaken to determine the utility of measurements of urinary aflatoxin-N7-guanine excretion as a marker of relative risk for hepatocarcinogenesis in AFB1-exposed rats. For the carcinogenesis studies, 5-wk-old male F344 rats were randomly divided into two groups. One group (55 rats) received the AIN-76A diet, and the other group (56 rats) received the AIN-76A diet supplemented with 0.075% oltipraz. The oltipraz-supplemented diet was fed for 4 wk. Beginning 1 wk after starting the experimental diets, all rats in both groups received 25 micrograms of AFB1/rat/day by gavage for 5 days per wk over the next 2 wk. One wk following cessation of dosing with AFB1, oltipraz was removed from the diet, and all rats were fed the AIN-76A diet for the remainder of the experiment. At 3 mo after dosing, livers of ten sentinel rats from each group were analyzed for the burden of gamma-glutamyltranspeptidase-positive foci. In accord with previous findings, rats fed the oltipraz-supplemented diet exhibited substantial reductions in the focal burden (97% reduction; P less than 0.05) of these AFB1-induced lesions. The remaining rats were maintained for the cancer study until they became moribund or the termination of the experiment at 23 mo. Gross liver lesions were identified at autopsy and confirmed by microscopic evaluation. An 11% incidence of hepatocellular carcinoma was observed in the AFB1-treated, control diet-fed rats. An additional 9% of this group had hepatocellular adenomas. Oltipraz afforded complete protection against both AFB1-induced hepatocellular neoplasms. Using Kaplan-Meier survival analyses, rats in the oltipraz group had a significantly (P less than 0.02) longer life span and an increased survival free of liver tumors (P less than 0.0002). Molecular dosimetry studies used rats fed either the oltipraz-supplemented or control diet for 1 wk and then challenged with a single dose of AFB1 to examine the initial rates of 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 excreted in the urine. (ABSTRACT TRUNCATED AT 400 WORDS)
3D crowd surveillance and analysis using laser range scanners

In this study, we present a novel system for crowd surveillance and quantified analysis based on laser range scanners. By mounting a laser scanner at a swinging platform, the spatial information of passengers inside the area of interest can be reconstructed in a form of 3D points. Multiple laser scanners are integrated together by semi-auto calibration procedures. Background map is generated through histogram analysis of scan maps, and is further applied for 3D moving object detection. An improved version of mean-shift clustering algorithm is proposed to extract individual passengers efficiently. In addition, quantified crowdness analysis is conducted from different aspects to indicate the situation inside the surveillance area according to the extraction results of passengers. The proposed system was tested in a central subway station in Tokyo and experimental results demonstrate the effectiveness of our proposed system.
Thinking Forward: Future-oriented Thinking among Patients with Tobacco-associated Thoracic Diseases and Their Surrogates.

RATIONALE The goal of shared decision making is to match patient preferences, including evaluation of potential future outcomes, with available management options. Yet, it is unknown how patients with smoking-related thoracic diseases or their surrogates display future-oriented thinking. OBJECTIVES To document prevalent themes in patients' and potential surrogate decision makers' future-oriented thinking when facing preference-sensitive choices. METHODS We conducted 44 scenario-based semistructured interviews among a diverse group of outpatients with smoking-associated thoracic diseases and potential surrogates for whom one of three preference-sensitive decisions would be medically relevant. Using content analysis, we documented prevalent themes to understand how these individuals display future-oriented thinking. MEASUREMENTS AND MAIN RESULTS Patients and potential surrogates generally expressed expectations for future outcomes but also acknowledged their limitations in doing so. When thinking about potential outcomes, decision makers relied on past experiences, including those only loosely related; perceived familiarity with treatment options; and spirituality. The content of these expectations included effects on family, emotional predictions, and prognostication. For surrogates, a tension existed between hope-based and fact-based expectations. CONCLUSIONS Patients and surrogates may struggle to generate expectations, and these future-oriented thoughts may be based on loosely related past experiences or unrealistic optimism. These tendencies may lead to errors, preventing selection of treatments that promote true preferences. Clinicians should explore how decision makers engage in future-oriented thinking and what their expectations are as a component of the shared decision-making process. Future research should evaluate whether targeted guidance in future-oriented thinking may improve outcomes important to patients.
Immunosuppressants in advanced clinical development for organ transplantation and selected autoimmune diseases

Immunosuppressants dampen the immune response or restore balance among immune system components. They are primarily used to prevent allograft rejection after organ transplantation and to prevent or treat disease flares in autoimmune diseases. Immunosuppressants available at present include the calcineurin inhibitors (cyclosporin, tacrolimus), antimetabolites (azathioprine, leflunomide, methotrexate, mycophenolate mofetil), antiproliferatives (sirolimus), monoclonal antibodies to T lymphocyte (basiliximab, daclizumab, muromonab-CD3) and anticytokines (anakinra, etanercept, infliximab). The immunosuppressive market grows at a rate of > 10% yearly, with total sales in 2001 of US$2.7 billion. Immunotherapy in transplantation and autoimmune diseases is tending towards the use of multi-drug regimens tailored for the individual patient. At least 23 new immunosuppressants are currently in advanced clinical testing or preregistration, and can be divided into three groups. First, emerging drugs targeting intracellular ligands in immune cells are primarily analogues of currently-marketed agents, which attempt to provide improved pharmaceutical or safety profiles compared with the prototype compound. They are largely being developed in organ transplantation. Second, emerging drugs targeting cell surface ligands on immune cells attempt to antagonise novel molecular sites to interfere with immune cell activation via costimulatory signals, immune cell adhesion to tissues or the vasculature and immune cell trafficking. These agents are being primarily developed in rheumatoid arthritis, psoriasis and/or multiple sclerosis. Finally, emerging drugs acting as anticytokines, which largely follow on from the success of those on the market, by antagonising the function of tumour necrosis factor or a narrow selection of interleukins. All are being assessed in rheumatoid arthritis. Drug development of immunosuppressants is increasingly attempting to intervene in disease progression over the long term. These efforts bring with them trial design and regulatory issues, such as what markers can be used as trial outcome measures, over what duration do trials need to be conducted and what labelling claims are allowed. With the intensive activity in this field, it is likely that several new drugs will reach the market in the coming decade. One caveat, however, is that emerging immunosuppressants that are likely to capture a reasonable share of this increasingly-fragmented market must demonstrate the ability to achieve disease remission or long-term slowing of disease progression.
The Small GTPases Rho and Rac Are Required for the Establishment of Cadherin-dependent Cell–Cell Contacts

Cadherins are calcium-dependent cell–cell adhesion molecules that require the interaction of the cytoplasmic tail with the actin cytoskeleton for adhesive activity. Because of the functional relationship between cadherin receptors and actin filament organization, we investigated whether members of the Rho family of small GTPases are necessary for cadherin adhesion. In fibroblasts, the Rho family members Rho and Rac regulate actin polymerization to produce stress fibers and lamellipodia, respectively. In epithelial cells, we demonstrate that Rho and Rac are required for the establishment of cadherin-mediated cell–cell adhesion and the actin reorganization necessary to stabilize the receptors at sites of intercellular junctions. Blocking endogenous Rho or Rac selectively removed cadherin complexes from junctions induced for up to 3 h, while desmosomes were not perturbed. In addition, withdrawal of cadherins from intercellular junctions temporally precedes the removal of CD44 and integrins, other microfilament-associated receptors. Our data showed that the concerted action of Rho and Rac modulate the establishment of cadherin adhesion: a constitutively active form of Rac was not sufficient to stabilize cadherindependent cell–cell contacts when endogenous Rho was inhibited. Upon induction of calcium-dependent intercellular adhesion, there was a rapid accumulation of actin at sites of cell–cell contacts, which was prevented by blocking cadherin function, Rho or Rac activity. However, if cadherin complexes are clustered by specific antibodies attached to beads, actin recruitment to the receptors was perturbed by inhibiting Rac but not Rho. Our results provide new insights into the role of the small GTPases in the cadherin-dependent cell– cell contact formation and the remodelling of actin filaments in epithelial cells.
Removal efficiency of calcium hydroxide intracanal medicament with RinsEndo system in comparison with passive ultrasonic irrigation, an in vitro study

Background: Different techniques have been introduced to improve removing the calcium hydroxide intra-canal dressing. The purpose of this study was to compare the efficiency of passive ultrasonic irrigation (PUI) and RinsEndo system in the removal of calcium hydroxide from root canal system. Materials and Methods: Access cavities were prepared in 50 single-rooted anterior teeth. Cleaning and shaping were done using the Flexmaster rotary system up to size no. 30, 6%. The canals were filled with injectable calcium hydroxide (calcipex). After 7 days, the calcium hydroxide were retrieved using RinsEndo system in Group 1 (n = 20), with PUI system in Group 2 (n = 20). In positive control group (n = 5), no irrigation was performed. In negative control group (n = 5), root canals were not filled with any medicament. Following the removal of the calcium hydroxide with these two systems, teeth were split buccolingually into two sections and every third of the root canals was evaluated under stereomicroscope (×30) to analyze the residual medicament in each segment. Data were analyzed using the Kruskal-Wallis and Mann-Whitney tests (P < 0.05). Results: There was no significant difference in the removal of calcium hydroxide between RinsEndo and PUI at cervical (P = 0.67), middle (P = 0.51) and apical (P = 0.75) part of the root canals. Conclusion: None of the irrigation techniques was able to completely remove calcium hydroxide from the root canal system.
Choosing the Method of Crystallization to Obtain Optimal Results

Anyone who has ever attempted to crystallise a protein or other biological macromolecule has encountered at least one, if not all of the following scenarios: No crystals at all, tiny low quality crystals; phase separation; amorphous precipitate and the most frustrating; large, beautiful crystals that do not diffract at all. In this paper we review a number of simple ways to overcome such problems, which have worked well in our hands and in other laboratories. It brings together information that has been dispersed in various publications and lectures over the years and includes further information that has not been previously published.
ADVISOR SUITE - A Knowledge-Based Sales Advisory-System

In many domains, a large variety of comparable products and services from different manufacturers is available on the market. As a result, customers are increasingly overwhelmed when they have to choose the products that match their personal needs and preferences because the selection process in many cases requires deep technical knowledge about the product features. In the online sales channel, recommender systems have already been successfully applied as an additional means for improved customer guidance. Real-world sales advisory, however, can be a knowledge-intensive task, where the customer preferences and the suitable sets of products have to be determined in an interactive dialogue. In this paper we present ADVISOR SUITE, a now-commercialized system for building such intelligent, personalized sales advisory applications. The system consistently follows a knowledge-based approach where all required development activities - from the definition of the user model and the recommendation rules, up to the personalization of the dialogue flow as well as user interface generation - are based on simple conceptual models and declarative knowledge representation. All these tasks are also supported by a set of graphical tools comprehensible for non-programmers, which leads to significant reductions in development and maintenance costs. Experiences from several commercial instantiations of the presented system are discussed in the final sections.
The GTPase Arf1p and the ER to Golgi cargo receptor Erv14p cooperate to recruit the golgin Rud3p to the cis-Golgi

Rud3p is a coiled-coil protein of the yeast cis-Golgi. We find that Rud3p is localized to the Golgi via a COOH-terminal domain that is distantly related to the GRIP domain that recruits several coiled-coil proteins to the trans-Golgi by binding the small Arf-like GTPase Arl1p. In contrast, Rud3p binds to the GTPase Arf1p via this COOH-terminal “GRIP-related Arf-binding” (GRAB) domain. Deletion of RUD3 is lethal in the absence of the Golgi GTPase Ypt6p, and a screen of other mutants showing a similar genetic interaction revealed that Golgi targeting of Rud3p also requires Erv14p, a cargo receptor that cycles between the endoplasmic reticulum and Golgi. The one human protein with a GRAB domain, GMAP-210 (CEV14/Trip11/Trip230), is known to be on the cis-Golgi, but the COOH-terminal region that contains the GRAB domain has been reported to bind to centrosomes and γ-tubulin (Rios, R.M, A. Sanchis, A.M. Tassin, C. Fedriani, and M. Bornens. 2004. Cell. 118:323–335). In contrast, we find that this region binds to the Golgi in a GRAB domain–dependent manner, suggesting that GMAP-210 may not link the Golgi to γ-tubulin and centrosomes.
Antimicrobial Resistance.

Importance The development of antibiotics is considered among the most important advances of modern science. Antibiotics have saved millions of lives. However, antimicrobial resistance (AMR) threatens this progress and presents significant risks to human health. Objective To identify factors associated with AMR, the current epidemiology of important resistant organisms, and possible solutions to the AMR problem. Data Sources, Study Selection, and Data Synthesis PubMed (2000-2016), NIH REPORTER, and ClinicalTrials.gov databases were searched for articles and entries related to AMR, focusing on epidemiology, clinical effects of AMR, discovery of novel agents to treat AMR bacterial infections, and nonpharmacological strategies to eliminate or modify AMR bacteria. In addition to articles and entries found in these databases, selected health policy reports and public health guidance documents were reviewed. Of 217 articles, databases, and reports identified, 103 were selected for review. Results The increase in AMR has been driven by a diverse set of factors, including inappropriate antibiotic prescribing and sales, use of antibiotics outside of the health care sector, and genetic factors intrinsic to bacteria. The problem has been exacerbated by inadequate economic incentives for pharmaceutical development of new antimicrobial agents. A range of specific AMR concerns, including carbapenem- and colistin-resistant gram-negative organisms, pose a clinical challenge. Alternative approaches to address the AMR threat include new methods of antibacterial drug identification and strategies that neutralize virulence factors. Conclusions and Relevance Antimicrobial resistance poses significant challenges for current clinical care. Modified use of antimicrobial agents and public health interventions, coupled with novel antimicrobial strategies, may help mitigate the effect of multidrug-resistant organisms in the future.
Holographic Data Storage

Research into and the development of data storage devices is a race to keep up with the continuing demand for more capacity, more density, and faster readout rates. Improvements in conventional memory technologies-magnetic hard disk drives, optical disks, and semiconductor memories-have managed to keep pace with the demand for bigger, faster memories. However, there is strong evidence that these two-dimensional surface storage technologies are approaching fundamental limits. An alternative approach for next-generation memories is to store data in three dimensions. This article describes developments in holographic 3D memories, in which high density is achieved by superimposing many holograms within the same volume of recording material. Holographic storage is a promising candidate for next-generation storage. Research has demonstrated that holographic storage systems with desirable properties can be engineered. The next step is to build these systems at costs competitive with those of existing technologies and to optimize the storage media.
Does Logarithm Transformation of Microarray Data Affect Ranking Order of Differentially Expressed Genes?

A common practice in microarray analysis is to transform the microarray raw data (light intensity) by a logarithmic transformation, and the justification for this transformation is to make the distribution more symmetric and Gaussian-like. Since this transformation is not universally practiced in all microarray analysis, we examined whether the discrepancy of this treatment of raw data affect the "high level"analysis result. In particular, whether the differentially ex-pressed genes as obtained by t-test, regularized t-test, or logistic regression have altered rank orders due to presence or absence of the transformation. We show that as much as 20%-40% of significant genes are "discordant" (significant only in one form of the data and not in both), depending on the test being used and the threshold value for claiming significance. The t-test is more likely to be affected by logarithmic transformation than logistic regression, and regularized t-test more affected than t-test. On the other hand, the very top ranking genes (e.g. upto top 20-50 genes, depending on the test) are not affected by the logarithmic transformation.
The tecnological business intelligence capabilities and business intelligence system flexibility — The underlying relationship

Existing studies of business intelligence (BI) assume that the characteristics of business intelligence systems (BIS), called BI capabilities, are critically important for BI implementation project success. In this paper we hypothesize that technological BI Capabilities have more complex interrelationship than it is supposed to be in the contemporary academic literature devoted to the field of BI. We also pay special attention to the relationship between technological BI Capabilities and BIS Flexibility. The results demonstrate that understanding relationship between technological BI capabilities is crucial to the analysis of the reasons of BI implementation projects success and failure. We believe that our study will contribute to the knowledge of both the professionals and academics in the field.
Randomized multidimensional search trees: further results in dynamic sampling

The use of randomization in dynamic search structures by means of a technique called dynamic sampling is investigated. In particular, an efficient algorithm for dynamic (logarithmic time) point location in 3-D partitions induced by a set of possibly interesting polygons in R/sup 3/ is given. The expected running time of the algorithm on a random sequence of updates is close to optimal. Efficient algorithms for dynamic nearest-k-neighbor queries and half space range queries in R/sup d/ are also given. <<ETX>>
Death and the Family

The author constructs measures to investigate the impact of declining mortality during the twentieth century on the structure of the American family. "Rather than attempting to summarize the total impact of mortality upon a cohort the present study develops hypothetical situations to provide insights into the dynamic role of death in family life. " The role of mortality as an independent variable producing change in parent-child bonds orphanhood divorce and fertility rates the number of dependent elderly persons and widowhood is analyzed (EXCERPT)