gebhart/patrepeval huggingface dataset:
Tobacco‐specific N ‐nitrosamines and ARECA‐ derived N ‐nitrosamines: Chemistry, biochemistry, carcinogenicity, and relevance to humans (1994)

Nicotine and the minor tobacco alkaloids give rise to tobacco-specific N-nitrosamines (TSNA) during tobacco processing and during smoking. Chemical-analytical studies led to the identification of seven TSNA in smokeless tobacco (< or = 25 micrograms/g) and in mainstream smoke of cigarettes (1.3 micrograms TSNA/cigarette). Indoor air polluted by tobacco smoke may contain up to 24 pg/L of TSNA. In mice, rats, and hamsters, three TSNA, N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are powerful carcinogens; two TSNA are moderately active as carcinogens; and two TSNA appear not to be carcinogenic. The TSNA are procarcinogens, agents that require metabolic activation. The active forms of the carcinogenic TSNA react with cellular components, including DNA, and with hemoglobin (Hb). The Hb adducts in chewers and smokers serve as biomarkers for the uptake and metabolic activation of carcinogenic TSNA and the urinary excretion of NNAL as free alcohol and as glucuronide for the uptake of TSNA. The review presents evidence that strongly supports the concept that TSNA contribute to the increased risk for cancer of the upper digestive tract in tobacco chewers and for the increased risk of lung cancer, especially pulmonary adenocarcinoma, in smokers. The high incidence of cancer of the upper digestive tract especially among men on the Indian subcontinent has been causally associated with chewing of betel quid mixed with tobacco. In addition to the TSNA, the betel quid chewers are exposed to four N-nitrosamines that are formed during chewing from the Areca alkaloids, two of these N-nitrosamines are carcinogens. The article also reviews approaches toward the reduction of the carcinogenic potency of smokeless tobacco, betel quid-tobacco mixtures, and cigarette smoke. Although the safest way to reduce the risk for tobacco-related cancers is to refrain from chewing and smoking, modifications of smokeless tobacco and of cigarettes are indicated to lead to less toxic products. Another more recent approach for reducing the carcinogenic effect of tobacco products is the application of chemopreventive agents, primarily of micronutrients. Future aspects in tobacco carcinogenesis, especially as it relates to TSNA, are expected in the field of molecular biochemistry and in biomarker studies, with the goal of identifying those tobacco and betel quid chewers and tobacco smokers who are at especially high risk for cancer.
Amorphous silica nanoparticles size-dependently aggravate atopic dermatitis-like skin lesions following an intradermal injection (2012)

A particle size reduction in silica particles enhanced IL-18 and TSLP production, which leads to systemic Th2 response and aggravation of AD-like skin lesions as induced by Dp antigen treatment. We believe that appropriate regulation of nanoparticle physicochemical properties, including sizes, is a critical determinant for the design of safer forms of NMs.
The grand challenges of Science Robotics (2018)

One of the ambitions of <i>Science Robotics</i> is to deeply root robotics research in science while developing novel robotic platforms that will enable new scientific discoveries. Of our 10 grand challenges, the first 7 represent underpinning technologies that have a wider impact on all application areas of robotics. For the next two challenges, we have included social robotics and medical robotics as application-specific areas of development to highlight the substantial societal and health impacts that they will bring. Finally, the last challenge is related to responsible innovation and how ethics and security should be carefully considered as we develop the technology further.
Regulation of Dendritic Cell Function by NK Cells: Mechanisms Underlying the Synergism in the Combination Therapy of IL-12 and 4-1BB Activation (2004)

The interactions between NK cells and dendritic cells (DCs) have been previously demonstrated in vitro. In this report, the in vivo cross-regulation between NK cells and DCs was studied in tumor-bearing mice treated with adenoviral vector expressing IL-12 and agonistic anti-4-1BB Abs. NK cells are essential for both tumor rejection and CTL development in the combination therapy (IL-12 plus anti-4-1BB). The numbers and functional activities of both NK cells and DCs in tumor-infiltrating leukocytes were synergistically increased in the IL-12 plus anti-4-1BB-treated mice compared with treatment with either reagent alone. NK depletion in vivo resulted in a significant decrease in the number of DCs in tumor-infiltrating leukocytes, strongly suggesting that NK cells are involved in the activation and expansion of DCs. The mechanism by which IL-12-activated NK cells regulate DC functions is, in part, mediated through the secretion of IFN-gamma that leads to the up-regulation of 4-1BB by DCs. Furthermore, 4-1BB activation in conjunction with IL-12 gene delivery increased tumor infiltration of green fluorescence protein-labeled DCs and enhanced their MHC class II expression. The activation of DCs by NK cells and the subsequent development of antitumoral CTL responses facilitated by 4-1BB-activated DCs may account for the synergistic effects observed in the combination therapy in comparison to adenoviral vector expressing IL-12 or anti-4-1BB treatment alone.
A Limited Set of Human MicroRNA Is Deregulated in Follicular Thyroid Carcinoma (2006)

Our observations show that miR-197 and miR-346 contribute to FTC carcinogenesis. Both miRNAs and their target genes might potentially provide for novel molecular markers and act as novel targets for treatment by interference, which could potentially normalize the deregulated profile of many downstream target genes.
Fast ray tracing by ray classification (1987)

We describe a new approach to ray tracing which drastically reduces the number of ray-object and ray-bounds intersection calculations by means of 5-dimensional space subdivision. Collections of rays originating from a common 3D rectangular volume and directed through a 2D solid angle are represented as hypercubes in 5-space. A 5D volume bounding the space of rays is dynamically subdivided into hypercubes, each linked to a set of objects which are candidates for intersection. Rays are classified into unique hypercubes and checked for intersection with the associated candidate object set. We compare several techniques for object extent testing, including boxes, spheres, plane-sets, and convex polyhedra. In addition, we examine optimizations made possible by the directional nature of the algorithm, such as sorting, caching and backface culling. Results indicate that this algorithm significantly outperforms previous ray tracing techniques, especially for comples environments.
Sources of NADPH in Yeast Vary with Carbon Source (2005)

Production of NADPH in Saccharomyces cerevisiae cells grown on glucose has been attributed to glucose-6-phosphate dehydrogenase (Zwf1p) and a cytosolic aldehyde dehydrogenase (Ald6p) (Grabowska, D., and Chelstowska, A. (2003) J. Biol. Chem. 278, 13984-13988). This was based on compensation by overexpression of Ald6p for phenotypes associated with ZWF1 gene disruption and on the apparent lethality resulting from co-disruption of ZWF1 and ALD6 genes. However, we have found that a zwf1Delta ald6Delta mutant can be constructed by mating when tetrads are dissected on plates with a nonfermentable carbon source (lactate), a condition associated with expression of another enzymatic source of NADPH, cytosolic NADP+-specific isocitrate dehydrogenase (Idp2p). We demonstrated previously that a zwf1Delta idp2Delta mutant loses viability when shifted to medium with oleate or acetate as the carbon source, apparently because of the inadequate supply of NADPH for cellular antioxidant systems. In contrast, the zwf1Delta ald6Delta mutant grows as well as the parental strain in similar shifts. In addition, the zwf1Delta ald6Delta mutant grows slowly but does not lose viability when shifted to culture medium with glucose as the carbon source, and the mutant resumes growth when the glucose is exhausted from the medium. Measurements of NADP(H) levels revealed that NADPH may not be rapidly utilized in the zwf1Delta ald6Delta mutant in glucose medium, perhaps because of a reduction in fatty acid synthesis associated with loss of Ald6p. In contrast, levels of NADP+ rise dramatically in the zwf1Delta idp2Delta mutant in acetate medium, suggesting a decrease in production of NADPH reducing equivalents needed both for biosynthesis and for antioxidant functions.
Antiplasmodial Activity and Cytotoxicity of Bis-, Tris-, and Tetraquinolines with Linear or Cyclic Amino Linkers (2001)

Bisquinoline heteroalkanediamines were structurally modified in order to study the effects of enhanced bulkiness and rigidity on both their activity on strains of Plasmodium falciparum expressing different degrees of chloroquine (CQ) resistance and their cytotoxicity toward mammalian cells. While cyclization yielded molecules of greater rigidity that were not more active than their linear counterparts, they were characterized by an absence of cytotoxicity. Alternatively, dimerization of these compounds led to tetraquinolines that are very potent for CQ-resistant strains and noncytotoxic.
The Influence of Antisense Oligonucleotide-induced RNA Structure on Escherichia coli RNase H1 Activity (1997)

The ability of Escherichia coli RNase H1 to hydrolyze structured substrates containing antisense oligonucleotides preannealed to a 47-mer RNA was compared with its ability to hydrolyze unstructured substrates containing antisense oligonucleotides duplexed with 13-mer RNA. These results demonstrate that when antisense oligonucleotides were bound to structured RNA, the resultant duplexes were cleaved at rates significantly slower than when the same oligonucleotides were bound to unstructured oligoribonucleotides. Structured substrates exhibited fewer cleavage sites, and each cleavage site was cleaved less rapidly than in unstructured substrates. Furthermore, the enzymatic activity of E. coli RNase H1 for the structured substrates was most affected when the cleavage sites corresponding to the enzymatically most active sites on the unstructured substrates were blocked in the structured substrates. Molecular modeling suggests that the observed ablation of RNase H activity was due to the steric hindrance of the enzyme by the structured RNA, i.e. steric interference of the phosphate groups on the substrate and/or the binding site of the enzyme. When chimeric oligonucleotides composed of a five-base deoxynucleotide sequence flanked by chemically modified nucleotides were bound to structured RNA, the resultant duplexes were even worse substrates for RNase H. These results offer further insights into the role of antisense-induced RNA structure on RNase H activity and may facilitate the design of effective antisense oligonucleotides.
An "in-out" strategy using gene targeting and FLP recombinase for the functional dissection of complex DNA regulatory elements: analysis of the beta-globin locus control region. (1993)

The human beta-globin locus control region (LCR) is a complex DNA regulatory element that controls the expression of the cis-linked beta-like globin genes located in the 55 kilobases 3' of the LCR. We have initiated the functional analysis of the LCR by homologous recombination in murine erythroleukemia cell somatic hybrids that carry a single copy of human chromosome 11 on which the beta-globin locus is situated. High-level expression of the human beta-globin gene normally occurs when these hybrid cells are induced to differentiate. We have reported that the insertion of an expressed selectable marker gene (driven by the Friend virus enhancer/promoter) into the LCR disrupts the LCR-mediated regulation of globin transcription. In these cells, beta-globin is no longer expressed when the cells differentiate; instead, expression of the selectable marker gene increases significantly after differentiation. Since present techniques for homologous recombination require the insertion of a selectable marker, further progress in using homologous recombination to analyze the LCR depends on deletion of the selectable marker and demonstration that the locus functions normally after the insertion, expression, and deletion of the selectable marker. Here we show that after precise deletion of the selectable marker by using the FLP recombinase/FRT (FLP recombinase target) system, the locus functions as it did before the homologous recombination event. These studies demonstrate the feasibility of using homologous recombination to analyze the LCR in particular, and other complex cis-regulatory DNA elements in general, in their normal chromosomal context.
Rapid, Portable, Multiplexed Detection of Bacterial Pathogens Directly from Clinical Sample Matrices (2016)

Enteric and diarrheal diseases are a major cause of childhood illness and death in countries with developing economies. Each year, more than half of a million children under the age of five die from these diseases. We have developed a portable, microfluidic platform capable of simultaneous, multiplexed detection of several of the bacterial pathogens that cause these diseases. This platform can perform fast, sensitive immunoassays directly from relevant, complex clinical matrices such as stool without extensive sample cleanup or preparation. Using only 1 µL of sample per assay, we demonstrate simultaneous multiplexed detection of four bacterial pathogens implicated in diarrheal and enteric diseases in less than 20 min.
MRI of myocardial function: motion tracking techniques (1996)

Methods for the noninvasive measurement of three-dimensional myocardial motion with MRI have recently been developed using presaturation tagging and velocity-encoded phase maps. The quality of clinical cardiac MRI studies has also recently improved with the advent of breath-hold scanning. The combination of breath-hold imaging with tagging and velocity-encoding sequences has made the measurement of myocardial wall motion in patients a simple and reproducible exam. These methods make it possible to quantify the severity and extent of regional heart wall motion abnormalities both at rest and during stress. This article reviews the MRI techniques developed for these applications.
Molecular pathogenesis of colorectal cancer (2005)

Colorectal cancer is the third leading cause of cancer-related death in both men and woman in industrialized countries. Major advances have been made in our understanding of molecular events leading to formation of adenomatous polyps and cancer. Most colorectal cancers are sporadic, but a significant proportion (5-6%) has a clear genetic background. It is now widely accepted that colorectal carcinogenesis is a multistep process involving the inactivation of a variety of tumor-suppressor and DNA-repair genes and simultaneous activation of certain oncogenes. In addition, epigenetic alterations through aberrant promoter methylation and histone modification have been found to play a major role in the evolution and progression of a large proportion of sporadic colon cancers. Consequently, it is now apparent that individual colorectal cancers may evolve through diverse molecular pathways. In this article, the authors have summarized the current knowledge of molecular pathogenesis in common hereditary syndromes and sporadic forms of colorectal cancer. Novel molecular diagnostic tools for the early diagnosis and prevention of colorectal cancer that have emerged from these insights are discussed.
Motion field and optical flow: qualitative properties (1989)

It is shown that the motion field the 2-D vector field which is the perspective projection on the image plane of the 3-D velocity field of a moving scene, and the optical flow, defined as the estimate of the motion field which can be derived from the first-order variation of the image brightness pattern, are in general different, unless special conditions are satisfied. Therefore, dense optical flow is often ill-suited for computing structure from motion and for reconstructing the 3-D velocity field by algorithms which require a locally accurate estimate of the motion field. A different use of the optical flow is suggested. It is shown that the (smoothed) optical flow and the motion field can be interpreted as vector fields tangent to flows of planar dynamical systems. Stable qualitative properties of the motion field, which give useful informations about the 3-D velocity field and the 3-D structure of the scene, usually can be obtained from the optical flow. The idea is supported by results from the theory of structural stability of dynamical systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effects of urokinase receptor occupancy on plasmin generation and proteolysis of basement membrane by human tumor cells (1991)

The goal of the present study was to assess the relative importance of receptor-bound and secreted plasminogen activator urokinase (u-PA) in generating cell-surface plasmin and fostering destruction of normal tissue by tumor cells. We first showed that active site-inhibited u-PA could displace endogenous u-PA from the surface of the human colon adenocarcinoma cell line HCT 116. We then prepared expression vectors for u-PA and for a mutant molecule in which the codon for the active site serine residue was changed to encode alanine. Expression of non-functional mutant u-PA decreased the level of cell-bound active u-PA by more than 95% via a mechanism that involved competition for receptor sites. Decreased cell-surface u-PA activity was associated with a decrease in cell-bound plasmin activity to undetectable levels, suggesting that receptor-bound u-PA plays an important role in the generation of plasmin on the cell surface. Transfectants that secreted eightfold to 20-fold elevated levels of active wild-type u-PA showed approximately 50% increases in cell-associated u-PA and only twofold to fourfold increases in cell-associated plasmin, suggesting that the role of secreted u-PA in generating cell-surface plasmin activity was relatively minor. In parent cells and both types of transfectants there was a good correlation between the amount of plasmin bound to the tumor cell surface and the extent to which a basement membrane substrate was degraded. These studies show that receptor-bound u-PA provides an efficient mechanism for plasmin generation on the surface of tumor cells, which, in turn, contributes significantly to their degradative potential.
A randomized trial of electronic versus paper pain diaries in children: impact on compliance, accuracy, and acceptability (2003)

Electronic diary assessment of pain and disability has become increasingly popular in adult chronic pain research but use of this methodology with children has received limited attention. The aim of this study was to compare two formats of a prospective daily diary (handheld computer=e-diary; paper diary=p-diary) on children's compliance, accuracy, and acceptability ratings. Sixty children, ages 8-16 (M=12.3) with headaches or juvenile idiopathic arthritis, were randomized to receive either e-diaries administered via home visits (n=30) or p-diaries (n=30) handed out during clinic visits for return by mail. Results demonstrated significant mean differences in diary entries completed between groups, with children with e-diaries completing more days (M=6.6) compared to children with p-diaries (M=3.8), P<0.001. Diaries returned by children in the p-diary group contained significantly more errors and omissions compared to diaries returned by children in the e-diary group (which contained none), P<0.001. Children rated both diary formats as highly acceptable and easy to use. A significant gender x diary format interaction (P<0.01) was found for compliance where boys demonstrated greater compliance with the e-diary format. Findings demonstrated that the e-diary was feasible to use with children and showed significantly greater compliance and accuracy in diary recording compared to traditional paper diaries in a population of children with recurrent pain.
A Model of the Information Seeking and Decision Making of Online Coin Buyers (2010)

Introduction. The Everyday Life Information Seeking approach suggests that much information behaviour takes place in non-work settings, for example in the pursuit of leisure activities such as hobbies. This study focuses on a community of collectors to examine how they gather information to decide whether to purchase an item for their collection when the target item has an ambiguous or deficient description. Method. Manual scanning of eBay and other online discussion board for coin buyers led to 187 postings indicating an attempt to reach a purchase decision, or to authenticate a purchased coin, through solicitation or posting of advice. Analysis. Postings were coded as to whether they dealt with 1. Ambiguous images in a listing, 2. Ambiguous statements in a listing, 3. Information missing from a listing, or 4. Sharing of other information (not restricted to a coin listing) that might possibly be used to make a purchase decision or authentication. Results. Using the example postings and the investigator's earlier experiences, a model of coin buyer decision making was created, outlining the different paths and strategies that collectors may take when faced with uncertainties. Conclusion. The Internet facilitates access to both documentary reference material, as well as human information sources. The formation of virtual communities is made possibly, alongside existing face-to-face communities of hobbyists. Further studies of collectors could benefit from comparisons of information behaviour in both virtual and actual worlds.
Stereo- and regiospecificcis,cis-muconate cycloisomerization byRhodococcus rhodochrousN75 (2003)

cis,cis-Muconate cycloisomerase was purified to homogeneity from cells of Rhodococcus rhodochrous N75 grown at the expense of benzoate and p-toluate as the sole sources of carbon. A single cycloisomerase was found to be induced in this organism with no isoforms being detected when R. rhodochrous N75 was grown on either benzoate or p-toluate as the sole source of carbon. The enzyme is hexameric with a single subunit Mr of 40,000. cis,cis-Muconate cycloisomerase from R. rhodochrous N75 displayed strict regio- and stereospecificity whereby cis,cis-muconate is cycloisomerized to (4S)-muconolactone and 2-methyl- and 3-methyl-substituted muconates are cycloisomerized to 2-methyl- and 4-methyl-substituted muconolactones by 1,4- and 3,6-cycloisomerization, respectively.
Acceleration of Fracture Healing in Nonhuman Primates by Fibroblast Growth Factor-2 (2001)

One of the greatest needs in the clinical bone field is a bioactive agent to stimulate bone formation. We previously reported that fibroblast growth factor-2 (FGF-2) exhibited strong anabolic actions on bone formation in models of rodents and dogs. Aiming at a clinical application, this study was undertaken to clarify the effect of a single local application of recombinant human FGF-2 on fracture healing in nonhuman primates. After a fracture was created at the midshaft of the right ulna of animals and stabilized with an intramedullary nail, gelatin hydrogel alone (n = 10) or gelatin hydrogel containing 200 microg FGF-2 (n = 10) was injected into the fracture site. Although 4 of 10 animals treated with the vehicle alone remained in a nonunion state even after 10 weeks, bone union was complete at 6 weeks in all 10 animals treated with FGF-2. Significant differences in bone mineral content and density at the fracture site between the vehicle and FGF-2 groups were seen at 6 weeks and thereafter. FGF-2 also increased the mechanical property of the fracture site. We conclude that FGF-2 accelerates fracture healing and prevents nonunion in primates, and therefore propose that it is a potent bone anabolic agent for clinical use.