gebhart/patrepeval huggingface dataset:
Clinical pharmacologic observations on 6‐mercaptopurine and 6‐methylthiopurine ribonucleoside (1968)

Gastrointestinal absorption of 6‐mercaptopurine (MP) was incomplete and variable. After a single intravenous iniection, its plasma half‐life was 21 minutes in children and 47 minutes in adults. However, in 6 hours the cumulative urinary excretion of MP in each was about 20 per cent of the administered dose. The passage of MP into the red blood cells and into the cerebrospinal fluid was minimal. MP was 19 per cent bound to plasma protein. In contrast, the study on 6‐methylthiopurine ribonucleoside (MMPR) showed that the highest plasma level of radioactivity in patients on MMPR‐S 35 occurred at 1 to 2 days following both oral and intravenous routes. Gastrointestinal absorption was complete. The half‐life of plasma radioactivity was 5 days. Radioactivity was concentrated within human red blood cells to a 40 to 1 concentration gradient over plasma; the radioactivity was in the form of MMPR 5'‐monophosphate. This anabolite persisted in the red cells for as long as 6 weeks. Excretion of radioactivity was slow and sustained, about 10 per cent daily of the MMPR dose. Only unchanged MMPR was detected in urine during the first day; in later urine samples, principally the 5'‐monophosphate was found. MMPR was largely excluded from the cerebrospinal fluid. It was 39 per cent bound to plasma protein.
Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics. (1996)

The introduction of stochastic methods in pedigree analysis has enabled geneticists to tackle computations intractable by standard deterministic methods. Until now these stochastic techniques have worked by running a Markov chain on the set of genetic descent states of a pedigree. Each descent state specifies the paths of gene flow in the pedigree and the founder alleles dropped down each path. The current paper follows up on a suggestion by Elizabeth Thompson that genetic descent graphs offer a more appropriate space for executing a Markov chain. A descent graph specifies the paths of gene flow but not the particular founder alleles traveling down the paths. This paper explores algorithms for implementing Thompson's suggestion for codominant markers in the context of automatic haplotyping, estimating location scores, and computing gene-clustering statistics for robust linkage analysis. Realistic numerical examples demonstrate the feasibility of the algorithms.
Organocatalytic Ring Opening Polymerization of Trimethylene Carbonate (2006)

A variety of organocatalysts has been surveyed in the ring opening polymerization of trimethylene carbonate. Excellent control was found for several of these catalysts yielding well-defined polycarbonates with molecular weights up to 50 000 g mol-1, polydispersities below 1.08, and high end-group fidelity. Melt or bulk polymerization was accomplished without loss of control of molecular weight or polydispersity, and random ester−carbonate bulk polymerizations were also demonstrated. Furthermore, by combining disparate polymerization techniques using bifunctional initiators, the mild polymerization conditions allow for the preparation of new block copolymers. Hydrogen-bond activation of monomer and initiator/propagating species is proposed as the underlying mechanism, which can be tuned to mitigate adverse side reactions.
Predominant Th2/Tc2 Polarity of Tumor-Infiltrating Lymphocytes in Human Cervical Cancer (2001)

Cytotoxic T lymphocytes (Tc) play a central role in cellular immunity against cancers. The cytotoxic potential of freshly isolated tumor-infiltrating lymphocytes (TILs) is usually not expressed. This suggests the possible existence of as yet unspecified and perhaps complex immunosuppressive factors or cytokines that affect the anti-tumor capacity of these TILs in the tumor milieu. In the present study, we demonstrated for the first time that TILs derived from human cervical cancer tissue consist mainly of Th2/Tc2 phenotypes. In vitro kinetic assays further revealed that cancer cells could direct the tumor-encountered T cells toward the Th2/Tc2 polarity. Cancer cells promote the production of IL-4 and down-regulate the production of IFN-gamma in cancer-encountered T cells. The regulatory effects of cervical cancer cells are mediated mainly by IL-10, and TGF-beta plays only a synergistic role. The cancer-derived effects can be reversed by neutralizing anti-IL-10 and anti-TGF-beta Abs. IL-10 and TGF-beta are present in cancer tissue and weakly expressed in precancerous tissue, but not in normal cervical epithelial cells. Our study strongly suggests important regulatory roles of IL-10 and TGF-beta in cancer-mediated immunosuppression.
Investigation of role for oxidant stress in vascular tolerance development to glyceryl trinitrate in vitro (1997)

1. The role of reactive oxygen species (ROS) during the development of vascular cellular tolerance to glyceryl trinitrate (GTN), was studied in the rat isolated aorta. 2. Nitrate tolerance induced by a 30 min incubation with GTN (30 or 100 microM) in vitro, was not affected by pretreatment with the intracellular superoxide anion scavenger, tiron (10 mM), or the intracellular scavenger of peroxynitrite anion and hydroxyl radical, dimethylsulphoxide (DMSO, 0.2% v v-1). In contrast, pretreatment with the intracellular sulphydryl donor, N-acetyl-L-cysteine (NAC, 1 mM), significantly attenuated GTN-induced tolerance. 3. Pretreatment with a putative inhibitor of oxidant stress-mediated, transcription factor NF-kappa B activation, pyrrolidine dithiocarbamate (PDTC, 50 microM), an inhibitor of gene activation by NF-kappa B, dexamethasone (1 microM) or an inhibitor of protein synthesis, cycloheximide (10 microM), failed to affect tolerance development to GTN. 4. Pretreatment with DMSO (0.2% v v-1) or PDTC (50 microM) depressed non-tolerant vasorelaxation to GTN (1 nM 1 microM) per se. 5. Tiron (10 mM) abolished the reduction of ferricytochrome c by a superoxide anion generating system, assessed photometrically in vitro. In contrast, DMSO (0.2% v v-1), NAC (1 mM) and PDTC (50 microM) were without effect. 6. Our data suggests that neither oxidant stress nor nuclear activation, is important in the development of cellular tolerance to GTN in rat isolated aortic smooth muscle.
A High-Speed Four-Transmitter Four-Receiver MIMO OFDM Testbed: Experimental Results and Analyses (2006)

By adopting multiple-input multiple-output (MIMO) and orthogonal frequency-division multiplexing (OFDM) technologies, indoor wireless systems could reach data rates up to several hundreds of Mbits/s and achieve spectral efficiencies of several tens of bits/Hz/s, which are unattainable for conventional single-input single-output systems. The enhancements of data rate and spectral efficiency come from the fact that MIMO and OFDM schemes are indeed parallel transmission technologies in the space and frequency domains, respectively. To validate the functionality and feasibility of MIMO and OFDM technologies, we set up a four-transmitter four-receiver OFDM testbed in a typical indoor environment, which achieves a peak data rate of 525 Mbits/s and a spectral efficiency of 19.2 bits/Hz/s. The performances including MIMO channel characteristics, bit-error rate against signal-to-noise ratio curves, the impairments of carrier frequency offset and channel estimation inaccuracy, and an asymmetric MIMO scheme are reported and analyzed in this paper.
A low-power low-noise cmos for amplifier neural recording applications (2003)

There is a need among scientists and clinicians for low-noise low-power biosignal amplifiers capable of amplifying signals in the millihertz-to-kilohertz range while rejecting large dc offsets generated at the electrode-tissue interface. The advent of fully implantable multielectrode arrays has created the need for fully integrated micropower amplifiers. We designed and tested a novel bioamplifier that uses a MOS-bipolar pseudoresistor element to amplify low-frequency signals down to the millihertz range while rejecting large dc offsets. We derive the theoretical noise-power tradeoff limit - the noise efficiency factor - for this amplifier and demonstrate that our VLSI implementation approaches this limit by selectively operating MOS transistors in either weak or strong inversion. The resulting amplifier, built in a standard 1.5-μm CMOS process, passes signals from 0.025Hz to 7.2 kHz with an input-referred noise of 2.2 μVrms and a power dissipation of 80 μW while consuming 0.16 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> of chip area. Our design technique was also used to develop an electroencephalogram amplifier having a bandwidth of 30 Hz and a power dissipation of 0.9 μW while maintaining a similar noise-power tradeoff.
Pulmonary Embolism in Outpatients With Pleuritic Chest Pain (1988)

Pleuritic chest pain is a frequent complaint in patients coming to the emergency room, but the proportion of such patients with pulmonary embolism is uncertain. In a prospective study, we evaluated the diagnostic outcomes in 173 consecutive patients who came to the emergency room with pleuritic chest pain. Pulmonary embolism, as demonstrated by angiography or autopsy, was present in 36 (21%). The need for objective testing is clearly indicated by our finding that the sensitivity (85%) and specificity (37%) of predetermined clinical variables for pulmonary embolism were insufficient to allow a definitive treatment decision. Optimal sensitivity and specificity are obtained by using pulmonary angiography in combination with lung scanning. The proportion of patients requiring angiography is substantially reduced, from 43% to 26%, without significant loss of accuracy, if ventilation imaging and impedance plethysmography are used together with perfusion scanning.
Bronchopulmonary afferent nerves (2003)

Vagal afferent nerves are the primary communication pathways between the bronchopulmonary system and the central nervous system. Input from airway afferent nerves to the CNS is integrated in the brainstem and ultimately leads to sensations and various reflex outputs. Afferent nerves innervating the airways can be classified into various distinct phenotypes. However, there is no single classification scheme that takes all features, including conduction velocity, cell body diameter, ganglionic origin, and stimuli to which they respond (modality) into account. At present, bronchopulmonary afferent nerves are typically considered to belong to one of three general categories, namely C-fibres, rapidly adapting stretch receptors (RARs), and slowly adapting stretch receptors (SARs). As our understanding of bronchopulmonary afferent nerves continues to deepen, we are likely to see more sophisticated classification schemes emerge. It is clear that the function of afferent fibres can be substantively influenced by airway inflammation and remodelling. The perturbations and perversions of afferent nerve function that occur during these states almost certainly contributes to many of the signs and symptoms of inflammatory airway disease. A more lucid characterization of bronchopulmonary afferent nerves, and a better understanding of the mechanisms by which these nerves influence pulmonary physiology during health and disease anticipates future research.
Practice Parameters for the Management of Colon Cancer (2012)

Chang, George J. M.D.; Kaiser, Andreas M. M.D.; Mills, Steven M.D.; Rafferty, Janice F. M.D.; Buie, W. Donald M.D
Enzyme replacement therapy in fibroblasts from a patient with cholesteryl ester storage disease (1989)

Enzyme replacement has long been considered only a remote possibility in the treatment of a wide range of genetic disorders, many manifested as lysosomal storage diseases. The complexity of having a particular enzyme gain access to the lysosomal compartment in a specific cell seemed insurmountable. We report here on an attempt to introduce the enzyme cholesteryl esterase into fibroblasts from a patient with cholesteryl ester storage disease (CESD). The enzyme gains access to the lysosomal compartment and the accumulating cholesteryl ester by virtue of being carried into the cell conjugated to a ligand (insulin or apoprotein B [apoB]) that binds to its own specific receptor and is internalized by the well-described process of receptor-mediated endocytosis. Regardless of whether the enzyme enters the cell via the insulin receptor or via the low-density lipoprotein (ApoB) receptor, it can be found associated with a lysosomal fraction and is effective in lowering levels of accumulated substrate, cholesteryl ester. The time course of the substrate degradation and the dependence on the receptor density and receptor density and receptor-ligand interaction indicate that the enzyme is simply being carried to the site of substrate accumulation by virtue of the fact that that is the destination of the ligand (along with its conjugated enzyme) following internalization.
The TRI11 Gene of Fusarium sporotrichioides Encodes a Cytochrome P-450 Monooxygenase Required for C-15 Hydroxylation in Trichothecene Biosynthesis (1998)

Several genes in the trichothecene biosynthetic pathway of Fusarium sporotrichioides have been shown to reside in a gene cluster. Sequence analysis of a cloned DNA fragment located 3.8 kb downstream from TRI5 has led to the identification of the TRI11 gene. The nucleotide sequence of TRI11 predicts a polypeptide of 492 residues (Mr = 55,579) with significant similarity to members of the cytochrome P-450 superfamily. TRI11 is most similar to several fungal cytochromes P-450 (23 to 27% identity) but is sufficiently distinct to define a new cytochrome P-450 gene family, designated CYP65A1. Disruption of TRI11 results in an altered trichothecene production phenotype characterized by the accumulation of isotrichodermin, a trichothecene pathway intermediate. The evidence suggests that TRI11 encodes a C-15 hydroxylase involved in trichothecene biosynthesis.
Morphology of the normal human lens. (1996)

Both TEM and SEM are necessary to obtain a complete description of fiber cells. Cross-sections of fibers give new insights into the lamellar organization of the lens, indicating that each region has characteristic cell shapes and sizes. Furthermore, average dimensions were used to demonstrate that the number of cells and approximate growth rates vary significantly between adjacent regions.
Observation of the cation radicals of pyrrole and of some substituted pyrroles in fast-scan cyclic voltammetry. Standard potentials and lifetimes (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTObservation of the cation radicals of pyrrole and of some substituted pyrroles in fast-scan cyclic voltammetry. Standard potentials and lifetimesClaude P. Andrieux, Pierre Audebert, Phillipe Hapiot, and Jean Michel SaveantCite this: J. Am. Chem. Soc. 1990, 112, 6, 2439–2440Publication Date (Print):March 1, 1990Publication History Published online1 May 2002Published inissue 1 March 1990https://pubs.acs.org/doi/10.1021/ja00162a065https://doi.org/10.1021/ja00162a065research-articleACS PublicationsRequest reuse permissionsArticle Views841Altmetric-Citations102LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
On Kirchhoff's law and its generalized application to absorption and emission by cavities (1965)

Seve ra l a uthurs have ma d e th e ass umption that Kirc hh off's Law hold s fur th e apparent local s pectral e mittan ce and apparent lo ca l s pec tral absorptance of a ny point on th e int e rior s urface of a cav ity. The co rrec tn ess of thi s assumption is d e mo ns trat e d under ce rt ain genera l c unditiun s, and it s pra c ti ca l ap pli cati on to th e ca lc ul a tion of th e tot a l Aux a bso rb ed b y a cav it y or s pacec raft is di sc ussed. A furth er app li ca tion to th e case of a nuni soth e rmal cavity ur spacecra ft is d e riv ed. By thi s d e riv a ti on a n easy methud fur determining th e to tal Au x e mitt ed fru lll s uc h a noni soth e rmal cav ity is found when th e di s tribution of th e appa re nt luca l s pectral e mittance uf th e is uthermal c avity is kn ow n. T he eco nomy and versa tility of thi s methud is s hown by th e ca lc ul at ion of th e total Au x e mitt ed from a noni so lhermal cy lindri ca l cav it y for se veral a rbitra r y cases of te mpe ra ture di s tributi o n o n th e int e rior s urface o f the c avity. Finally, th e int egra l eq uation for a diffu se cav it y whose wall e mittance varies with position on th e wall is tra ns formed to an e quation havi ng a sy mm e tri c kernel.
Characterization of the expression of the Cek8 receptor-type tyrosine kinase during development and in tumor cell lines. (1994)

Cek8 is a receptor-type tyrosine kinase gene that was identified by screening a 10 day chicken embryo library with a DNA probe corresponding to the related kinase Cek4 (Sajjadi & Pasquale, 1993). Here we report the characterization of the Cek8 protein and its expression in embryonic tissues and tumor cell lines. The 120 kd Cek8 protein is detected early in embryogenesis, is developmentally regulated and preferentially, but not exclusively, expressed in neural tissues. In the stage 24 chick embryo, Cek8 immunoreactivity is prominent in the spinal cord and spinal nerves. At embryonic day 6, Cek8 expression becomes concentrated to the ventral portion of the spinal nerves, suggesting a role in axonogenesis of specific subsets of neurons. Cek8 is expressed in nearly all of the tumor cell lines examined, including cell lines derived from tumors of the central nervous system. Although the phosphorylation on tyrosine of Cek8 during development is moderate or undetectable, Cek8 is substantially phosphorylated on tyrosine (and thus presumably activated) in many of the transformed cell lines. Because of its high frequency of expression in tumor cell lines, Cek8 differs from previously investigated Eph-related kinases. However, as we show, Cek8 is not unique among the Eph-related kinases: another member of the Eph subclass, Cek5, has similar patterns of expression and phosphorylation in tumor cells. Based on its binding to a variety of lectin columns, Cek8 contains complex N-linked oligosaccharides. Cross-linking of Cek8 molecules on the cell surface with wheat germ agglutinin caused their rapid phosphorylation on tyrosine. Autophosphorylation on tyrosine is typically the first step in the activation of a receptor tyrosine kinase by a ligand.
Ultraviolet Irradiation Effects in Poly-L-tyrosine and Model Compounds. Identification of Bityrosine as a Photoproduct* (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUltraviolet Irradiation Effects in Poly-L-tyrosine and Model Compounds. Identification of Bityrosine as a Photoproduct*S. S. Lehrer and Gerald D. FasmanCite this: Biochemistry 1967, 6, 3, 757–767Publication Date (Print):March 1, 1967Publication History Published online1 May 2002Published inissue 1 March 1967https://pubs.acs.org/doi/10.1021/bi00855a017https://doi.org/10.1021/bi00855a017research-articleACS PublicationsRequest reuse permissionsArticle Views539Altmetric-Citations165LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Distribution of tamoxifen and its metabolites in rat and human tissues during steady-state treatment. (1991)

A procedure for the extraction of tamoxifen and metabolites from various rat and human tissues was developed and verified. With this method, we determined the drug and metabolite concentrations during one dosing interval in various tissues (brain, fat, liver, heart, lung, kidney, uterus, and testes) of rats given tamoxifen once daily for 3 or 14 days, and in various normal and malignant tissues obtained during surgery or at autopsy from patients with breast cancer treated with tamoxifen. In the rat, the concentrations of tamoxifen and metabolites in most tissues were 8- to 70-fold higher than in serum. The highest levels were observed in lung and liver; substantial amounts were also recovered from kidney and fat. Fluctuations of metabolites and tamoxifen content in most tissues were observed during one dosing interval, corresponding to a ratio of 4:8 between Cmax and Cmin, except in fat and testicular tissues, where the drug concentrations were relatively stable. In addition to tamoxifen, N-desmethyltamoxifen, followed by 4-hydroxytamoxifen, 4-hydroxy-N-desmethyltamoxifen, and N-desdimethyltamoxifen, were abundant in most tissues. In contrast, adipose tissue contained only small amounts of these metabolites. The concentrations of tamoxifen and metabolites found in human normal and malignant tissues confirmed and extended the conclusions made in the experiments with rats. In humans, levels were 10- to 60-fold higher in tissues than in serum, and relatively high concentrations were detected in liver and lung. Additionally, pancreas, pancreatic tumor, and brain metastases from breast cancer and primary breast cancer retained large amounts of drug. Again, the amounts of demethylated and hydroxylated metabolites were high in most tissues, except in fat. Tamoxifen and some metabolites were also present in specimens of skin and bone tissue. In one patient, significant amounts of drugs could be detected in lung, heart, ovary, and intestinal wall 14 months after withdrawal of tamoxifen, demonstrating efficient retention and slow washout of these compounds in human tissue.
Nanoparticles for Imaging and Treating Brain Cancer (2012)

Brain cancer tumors cause disruption of the selective properties of vascular endothelia, even causing disruptions in the very selective blood-brain barrier, which are collectively referred to as the blood-brain-tumor barrier. Nanoparticles (NPs) have previously shown great promise in taking advantage of this increased vascular permeability in other cancers, which results in increased accumulation in these cancers over time due to the accompanying loss of an effective lymph system. NPs have therefore attracted increased attention for treating brain cancer. While this research is just beginning, there have been many successes demonstrated thus far in both the laboratory and clinical setting. This review serves to present the reader with an overview of NPs for treating brain cancer and to provide an outlook on what may come in the future. For NPs, just like the blood-brain-tumor barrier, the future is wide open.