Miracle-dz/UniFAR-FTUs huggingface dataset:
Nrf2 is increased by CYP2E1 in rodent liver and HepG2 cells and protects against oxidative stress caused by CYP2E1

Induction of CYP2E1 by ethanol is one pathway through which ethanol generates oxidative stress. Nrf2 is a transcription factor that regulates important antioxidant and phase II detoxification genes. Nrf2 induction by CYP2E1 and its importance in the adaptive response to increased oxidative stress caused by CYP2E1 was studied. Increases in Nrf2 protein and mRNA were observed in livers or hepatocytes of chronic alcohol‐fed mice or rats and of pyrazole‐treated rats or mice, conditions known to elevate CYP2E1. HepG2 cells expressing CYP2E1 (E47 cells) showed increased Nrf2 mRNA and protein expression compared with control HepG2 C34 cells. Nrf2 is activated in E47 cells as shown by an increase in nuclear Nrf2 levels and Nrf2–antioxidant‐responsive element binding activity, and upregulation of Nrf2‐regultated genes, glutamate cysteine ligase catalytic subunit (GCLC), and heme oxygenase 1 (HO‐1). Increases in Nrf2 protein and mRNA are blocked by inhibitors of CYP2E1 activity and a reactive oxygen species (ROS) scavenger, N‐acetylcysteine, which decrease ROS levels as well as Nrf2 mRNA induction. Upregulation of GCLC and HO‐1 in E47 cells is dependent on Nrf2 and is prevented by siRNA‐Nrf2. Blocking Nrf2 by siRNA‐Nrf2 decreases glutathione and increases ROS and lipid peroxidation, resulting in decreased mitochondrial membrane potential and loss of cell viability of E47 cells but not C34 cells. These results suggest that Nrf2 is activated and that levels of protein and mRNA are increased when CYP2E1 is elevated. In conclusion, Nrf2 plays a key role in the adaptive response against increased oxidative stress caused by CYP2E1. (HEPATOLOGY 2006;43:144–153.)
Changes in sex hormone‐binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome

Background: Mild hypoandrogenism in men, usually defined by low levels of testosterone, is a peculiar feature of abdominal obesity that independently predicts the development of insulin resistance and diabetes mellitus. Little is known about the short‐ and long‐term effects of weight loss on sex steroids in abdominally obese men, however.
Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts

Lynch syndrome (LS) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers, and is caused by a mutation in one of the mismatch repair genes: MLH1, MSH2, MSH6 or PMS2. In 2007, a group of European experts (the Mallorca group) published guidelines for the clinical management of LS. Since then substantial new information has become available necessitating an update of the guidelines. In 2011 and 2012 workshops were organised in Palma de Mallorca. A total of 35 specialists from 13 countries participated in the meetings. The first step was to formulate important clinical questions. Then a systematic literature search was performed using the Pubmed database and manual searches of relevant articles. During the workshops the outcome of the literature search was discussed in detail. The guidelines described in this paper may be helpful for the appropriate management of families with LS. Prospective controlled studies should be undertaken to improve further the care of these families.
A Common Thrombomodulin Amino Acid Dimorphism Is Associated with Myocardial Infarction

Summary Endothelial dysfunction and haemostatic imbalance are believed to be important aetiological factors in the development of acute coronary syndromes. Thrombomodulin (TM) is an integral membrane protein crucial for normal endothelial function and activation of the protein C anticoagulant pathway. We have investigated the importance of a common C/T dimorphism in the TM gene (nucleotide 1418) for development of premature myocardial infarction (MI). The C/T dimorphism predicts an Ala455 to Val replacement in the sixth EGF-like domain of TM. The dimorphism was investigated in 97 MI survivors and 159 healthy controls. The C allele was significantly more frequent among patients than controls (p = 0.035). The allele frequency for the C allele was 0.82 in the patients and 0.72 in the control group. The plasma concentration of TM was investigated among healthy controls but was not related to the C/T dimorphism. In conclusion, the association of the C allele with premature MI, suggests that the TM gene and the C/T dimorphism may be aetiological factors involved in the pathogenesis of MI. Possibly, the Ala455 to Val replacement may affect the function of the TM molecule and the activation of the protein C anticoagulant pathway.
Estimating the Proportion of Pneumonia Attributable to Pneumococcus in Kenyan Adults: Latent Class Analysis

Background: Community-acquired pneumonia is a common cause of hospitalization among African adults, and Streptococcus pneumoniae is assumed to be a frequent cause. Pneumococcal conjugate vaccine is currently being introduced into childhood immunization programs in Africa. The case for adult vaccination is dependent on the contribution of the pneumococcus to the hospital pneumonia burden. Methods: Pneumococcal diagnosis is complex because there is no gold standard, and culture methods are invalidated by antibiotic use. We used latent class analysis to estimate the proportion of pneumonia episodes caused by pneumococcus. Furthermore, we extended this methodology to evaluate the effect of antimicrobial treatment on test accuracies and the prevalence of the disease. The study combined data from 5 validation studies of pneumococcal diagnostic tests performed on 281 Kenyan adults with pneumonia. Results: The proportion of pneumonia episodes attributable to pneumococcus was 0.46 (95% confidence interval = 0.36–0.57). Failure to account for the effect of antimicrobial exposure underestimates this proportion as 0.32. A history of antibiotic exposure was a poor predictor of antimicrobial activity in patients' urine. Blood culture sensitivity for pneumococcus was estimated at 0.24 among patients with antibiotic exposure, and 0.75 among those without. Conclusions: The large contribution of pneumococcus to adult pneumonia provides a strong case for the investigation of pneumococcal vaccines in African adults.
Using Informal Knowledge in Formal Domains: Intuitions and Notations Sometimes Clash.

External representations have a great impact on what and how students learn. One key manner in which environments can operate upon novices' knowledge is through helping them ground their problem solving in an understanding of the situation embodied by the problem. In this paper, students' difficulties in microeconomics problem solving were investigated, along with the ways traditional representations such as supply and demand graphs interfere with students' situational understanding. Fourteen gifted students in grades 7 through 9 were videotaped solving a few economics problems similar to those found in typical introductory economics courses. How they used the diagrams to help themselves construct an understanding of the situation was studied. It was found that students who experienced minor impasses relied on the notation to overcome them, even though that sometimes led the students into worse errors. In contrast, when the notation did not offer any support for the reasoning, students fell back on reasoning about the situation in the world and were often more successful. Based on these results, it is argued that not only must the initial problem solving in a domain be based on novices' understanding of the world, but also that the notation used for the problem solving must encourage students to use this understanding to guide planning and to overcome impasses throughout the problem solving. Eight figures illustrate study data. (Contains 27 references.) (Author/SLD) **************************************************1. ,-,-*************** Reproductions supplied by EDRS are the best that can be made from the original document. *************************************************************** U.S. DEPARTMENT Of EDUCATION Office or Educational Research and Improvismed EDUCATiONAL RESOURCES INFORMATION CENTER (ERIC) This document has been reproduced as received from the person or ofganization originating a 0 Minor changes have Peon made to improve reproduction oustrty Points of view or opinions staled in ihis docv ment do not necessarily represent official OERI position or pohcy "PERMISSION TO REPRODUCE THIS MATERIAL HAS BEEN GRANTED BY DO 06146 TO THE EDUCATIONAL RESOURCES INFORMATION CENTER (ERIC). " Using informal knowledge in formal domains: Intuitions and notations sometimes clash Douglas C. Merrill, Brian J. Reiser The School of Education and Social Policy Northwestern University Date: March 27, 1994 Poster presented at AERA. 1994. Address correspondence to: (After April 18, 1994) Douglas C. Merrill (Before April 18. 1994) Douglas C. Merrill SESP Northwestern University 2115 North Campus Drive Evanston. IL 60208-2610 e-mail: dmerrillAils.nwu. edu The RAND Corporation 1700 Main Street Santa Monica. CA 90407-2138 e-mail: dmerrilltirand.org RUNNING HEAD: INTUITIONS AND NOTATIONS
Automated drowsiness detection for improved driving safety

Several approaches were proposed for the detection and prediction of drowsiness. The approaches can be categorized as estimating the ﬁtness of duty, modeling the sleep-wake rhythms, measuring the vehicle based performance and online operator monitoring. Computer vision based online operator monitoring approach has become prominent due to its predictive ability of detecting drowsiness. Previous studies with this approach detect driver drowsiness primarily by making preassumptions about the relevant behavior, focusing on blink rate, eye closure, and yawning. Here we employ machine learning to datamine actual human behavior during drowsiness episodes. Automatic classiﬁers for 30 facial actions from the Facial Action Coding system were developed using machine learning on a separate database of spontaneous expressions. These facial actions include blinking and yawn motions, as well as a number of other facial movements. In addition, head motion was collected through automatic eye tracking and an accelerometer. These measures were passed to learning-based classiﬁers such as Adaboost and multinomial ridge regression. The system was able to predict sleep and crash episodes during a driving computer game with 96% accuracy within subjects and above 90% accuracy across subjects. This is the highest prediction rate reported to date for detecting real drowsiness. Moreover, the analysis revealed new information about human behavior during drowsy driving
Effect of 2-hydroxybenzoate on the maintenance of naphthalene-degrading pseudomonads in seeded and unseeded soil

The addition of specific nontoxic inducers of catabolic operons to contaminated sites is an approach that may enhance the efficiency of in situ biodegradation. We determined the genetic response of six pseudomonads to salicylate (also known as 2-hydroxybenzoate) added directly to 50 g of nonsterile soil samples. The strains, isolated from a polyaromatic hydrocarbon-contaminated soil, metabolized naphthalene as the sole source of available carbon, and their DNA sequences show significant homology to the nahAB genes of the degradative plasmid NAH7. Duplicate nonsterile soil cultures were incubated for up to 30 days. Experimental soil cultures were seeded with naphthalene-degrading strains (10(8) CFU g-1) originally isolated from the soil and amended with salicylate (16 or 160 micrograms g-1). Soil samples were analyzed periodically for the population density of heterotrophic bacteria and naphthalene degraders and for the abundance of the naphthalene-degradative genotype in the bacterial community. At 160 micrograms g-1, salicylate sustained the density of naphthalene degraders at the introduced density for 30 days in addition to producing a two- to sixfold increase in the occurrence in the bacterial community of DNA sequences homologous to the nah operon. No change in recoverable bacterial population densities was observed when soil samples were amended with 16 micrograms of salicylate g-1, but this concentration of salicylate induced a significant increase in the level of nah-related genes in the population.
The Escherichia coli Subtilase Cytotoxin A Subunit Specifically Cleaves Cell-surface GRP78 Protein and Abolishes COOH-terminal-dependent Signaling

Background: GRP78 is aberrantly expressed on the surface of many different tumor cells where it functions as a growth factor-like receptor. Results: SubA cleavage of cell-surface GRP78 abrogates signaling initiated by ligation of the GRP78 COOH-terminal. Conclusion: SubA specifically cleaves cell-surface GPR78. Significance: SubA is a powerful tool that can be used to specifically probe the functions of cell-surface GPR78. GRP78, a molecular chaperone with critical endoplasmic reticulum functions, is aberrantly expressed on the surface of cancer cells, including prostate and melanoma. Here it functions as a pro-proliferative and anti-apoptotic signaling receptor via NH2-terminal domain ligation. Auto-antibodies to this domain may appear in cancer patient serum where they are a poor prognostic indicator. Conversely, GRP78 COOH-terminal domain ligation is pro-apoptotic and anti-proliferative. There is no method to disrupt cell-surface GRP78 without compromising the total GRP78 pool, making it difficult to study cell-surface GRP78 function. We studied six cell lines representing three cancer types. One cell line per group expresses high levels of cell-surface GRP78, and the other expresses low levels (human hepatoma: Hep3B and HepG2; human prostate cancer: PC3 and 1-LN; murine melanoma: B16F0 and B16F1). We investigated the effect of Escherichia coli subtilase cytoxin catalytic subunit (SubA) on GRP78. We report that SubA specifically cleaves cell-surface GRP78 on HepG2, 1-LN, and B16F1 cells without affecting intracellular GRP78. B16F0 cells (GRP78low) have lower amounts of cleaved cell-surface GRP78. SubA has no effect on Hep3B and PC3 cells. The predicted 28-kDa GRP78 COOH-terminal fragment is released into the culture medium by SubA treatment, and COOH-terminal domain signal transduction is abrogated, whereas pro-proliferative signaling mediated through NH2-terminal domain ligation is unaffected. These experiments clarify cell-surface GRP78 topology and demonstrate that the COOH-terminal domain is necessary for pro-apoptotic signal transduction occurring upon COOH-terminal antibody ligation. SubA is a powerful tool to specifically probe the functions of cell-surface GRP78.
Comparison between normalizations for SVM — GMM supervectors speaker verification

This paper presents a comparison between several features normalization methods, and a comparison between different types of Gaussian Mixture Model (GMM) based supervectors normalizations for robust Speaker Verification. We implemented the methods of normalizations as a part of speaker verification system using Support Vector Machine (SVM) classifier and GMM-based supervectors. When implementing the speaker recognition system, we used Mel Frequency Cepstral Coefficients (MFCC) feature extraction. A valid question is which features normalization to use, if any. We examine the most common methods of feature normalizations, such as: Feature Warping mapping, and Cepstral Mean Subtraction (CMS) normalization with and without variance normalization. These methods were compared to features without normalization at all, and to a basic [-1, 1] normalization. In addition, we applied few types of normalizations to the GMM-mean supervectors, in order to improve the performance of the SVM classifier. All comparisons of the speaker verification system had been done in terms of DET curve, EER (Equal Error Rate) and Min. DCF. The best results we achieved were on combined supervector normalizations of Universal Background Model (UBM) Standard Deviation (STD) and [-1, 1] normalization. The type of the MFCC normalization has no big influence on the verification performance. The best results were: EER about 5.0% and MIN. DCF of 0.02.
Persistence of Environmental DNA in Freshwater Ecosystems

The precise knowledge of species distribution is a key step in conservation biology. However, species detection can be extremely difficult in many environments, specific life stages and in populations at very low density. The aim of this study was to improve the knowledge on DNA persistence in water in order to confirm the presence of the focus species in freshwater ecosystems. Aquatic vertebrates (fish: Siberian sturgeon and amphibian: Bullfrog tadpoles) were used as target species. In control conditions (tanks) and in the field (ponds), the DNA detectability decreases with time after the removal of the species source of DNA. DNA was detectable for less than one month in both conditions. The density of individuals also influences the dynamics of DNA detectability in water samples. The dynamics of detectability reflects the persistence of DNA fragments in freshwater ecosystems. The short time persistence of detectable amounts of DNA opens perspectives in conservation biology, by allowing access to the presence or absence of species e.g. rare, secretive, potentially invasive, or at low density. This knowledge of DNA persistence will greatly influence planning of biodiversity inventories and biosecurity surveys.
Bacteria use type-IV pili to slingshot on surfaces

Bacteria optimize the use of their motility appendages to move efficiently on a wide range of surfaces prior to forming multicellular bacterial biofilms. The “twitching” motility mode employed by many bacterial species for surface exploration uses type-IV pili (TFP) as linear actuators to enable directional crawling. In addition to linear motion, however, motility requires turns and changes of direction. Moreover, the motility mechanism must be adaptable to the continually changing surface conditions encountered during biofilm formation. Here, we develop a novel two-point tracking algorithm to dissect twitching motility in this context. We show that TFP-mediated crawling in Pseudomonas aeruginosa consistently alternates between two distinct actions: a translation of constant velocity and a combined translation-rotation that is approximately 20× faster in instantaneous velocity. Orientational distributions of these actions suggest that the former is due to pulling by multiple TFP, whereas the latter is due to release by single TFP. The release action leads to a fast “slingshot” motion that can turn the cell body efficiently by oversteering. Furthermore, the large velocity of the slingshot motion enables bacteria to move efficiently through environments that contain shear-thinning viscoelastic fluids, such as the extracellular polymeric substances (EPS) that bacteria secrete on surfaces during biofilm formation.
Antibiotic Resistance Gene Abundances Associated with Waste Discharges to the Almendares River near Havana, Cuba

Considerable debate exists over the primary cause of increased antibiotic resistance (AR) worldwide. Evidence suggests increasing AR results from overuse of antibiotics in medicine and therapeutic and nontherapeutic applications in agriculture. However, pollution also can influence environmental AR, particularly associated with heavy metal, pharmaceutical, and other waste releases, although the relative scale of the “pollution” contribution is poorly defined, which restricts targeted mitigation efforts. The question is “where to study and quantify AR from pollution versus other causes to best understand the pollution effect”. One useful site is Cuba because industrial pollution broadly exists; antibiotics are used sparingly in medicine and agriculture; and multiresistant bacterial infections are increasing in clinical settings without explanation. Within this context, we quantified 13 antibiotic resistance genes (ARG; indicators of AR potential), 6 heavy metals, 3 antibiotics, and 17 other organic pollutants at 8 locations along the Almendares River in western Havana at sites bracketing known waste discharge points, including a large solid waste landfill and various pharmaceutical factories. Significant correlations (p < 0.05) were found between sediment ARG levels, especially for tetracyclines and β-lactams (e.g., tet(M), tet(O), tet(Q), tet(W), blaOXA), and sediment Cu and water column ampicillin levels in the river. Further, sediment ARG levels increased by up to 3 orders of magnitude downstream of the pharmaceutical factories and were highest where human population densities also were high. Although explicit links are not shown, results suggest that pollution has increased background AR levels in a setting where other causes of AR are less prevalent.
Language change across the lifespan: /r/ in Montreal French

We address the articulation between language change in the historical sense and language change as experienced by individual speakers through a trend and panel study of the change from apical to dorsal /r/ in Montreal French. The community as a whole rapidly advanced its use of dorsal [R]. Most individual speakers followed across time were stable after the critical period, with phonological patterns set by the end of adolescence. A sizeable minority, however, made substantial changes. The window of opportunity for linguistic modification in later life may be expanded with rapid change in progress when linguistic variables take on social significance.
Integrating Information Sources Using Context Logic

It is essential to reduce the cost of integrating information sources and to provide a path that allows for incremental integration that can be responsive to users’ demands. This paper presents an approach to integrating disparate heterogeneous information sources that uses context logic. Our use of context logic reduces the up-front cost of integration, provides an incremental integration path, and allows semantic conflicts within a single information sources or between information sources to be expressed and resolved.
Detecting Adverse Drug Events in Discharge Summaries Using Variations on the Simple Bayes Model

Detection and prevention of adverse events and, in particular, adverse drug events (ADEs), is an important problem in health care today. We describe the implementation and evaluation of four variations on the simple Bayes model for identifying ADE-related discharge summaries. Our results show that these probabilistic techniques achieve an ROC curve area of up to 0.77 in correctly determining which patient cases should be assigned an ADE-related ICD-9-CM code. These results suggest a potential for these techniques to contribute to the development of an automated system that helps identify ADEs, as a step toward further understanding and preventing them.
Art in the Elementary Schools: It's More Than Fingerpainting.

A study.examined the process of putting together a class play and assessed how the performance of the play affected the self-esteem of a first-grade class. Subje,cts, 21 students representing diverse demographic factors, completed two self-esteem measures (a self-evaluation instrument and an interview) before and after the theater production. Over a 2-week period, the students cast the parts, made the props and invitations, studied theatrical vocabulary, memorized their lines (each student had a speaking part), mastered the elements of theater-like expression, conducted a dress rehearsal, and performed the play for other first-grade classes and for parents. Results indicated that, as measured by both instruments: (1) the self-esteem of the Afro-American students increased after the production, but not to an extent greater than the increase in self-esteem of the white students; (2) the self-esteem of female students rose more than that of the male students; and (3) the self-esteem of the class as a whole rose. (Contains 54 references and 2 tables data.) (RS) *********************************************************************** Reproductions supplied by EDRS are the best that can be made from the original document. ***********************************************************************