gebhart/patrepeval huggingface dataset:
Role of A2A adenosine receptors in inflammation (1998)

A2A adenosine receptors are expressed on immune cells including neutrophils, lymphocytes, eosinophils, monocytes/macrophages, and mast cells. Activation of A2A receptors on these cells stimulates an increase in [cyclic AMP]i and causes a diminution of inflammatory responses. In mast cells, degranulation is inhibited; in neutrophils, adherence is reduced and the release of reactive oxygen species is inhibited; in monocytes, differentiation to macrophages is inhibited and the release of tumor necrosis factor-α is inhibited; and in lymphocytes, TCR-triggered interleukin-2 α chain (CD25) up-regulation is reduced. In vivo, selective adenosine A2A agonists decrease inflammation in both infectious and noninfectious models. High concentrations (micromolar) of the A3 selective agonist, IB-MECA, produce anti-inflammatory responses that are mediated by A2A receptors. Selective activation of A2A adenosine receptors with pharmaceutical agents may be a useful strategy for ameliorating an inappropriate and/or an extensive inflammatory response. Drug Dev. Res. 45:103–112, 1998. © 1998 Wiley-Liss, Inc.
A human systemic lupus erythematosus-related anti-cardiolipin/single-stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51P1 VH gene (1992)

We report the Ig H and L chain V region sequences from the cDNAs encoding a monoclonal human IgG anti-cardiolipin/ssDNA autoantibody (R149) derived from a patient with active SLE. Comparison with the germ-line V-gene repertoire of this patient revealed that R149 likely arose as a consequence of an Ag-driven selection process. The Ag-binding portions of the V regions were characterized by a high number of arginine residues, a property that has been associated with anti-dsDNA autoantibodies from lupus-prone mice and patients with SLE. The VH gene encoding autoantibody R149 was a somatically mutated variant of the 51P1 gene segment, which is frequently associated with the restricted fetal B cell repertoire, malignant CD5 B cells, and natural autoantibodies. These data suggest that in SLE patients a common antigenic stimulus may evoke anti-DNA and anti-cardiolipin autoantibodies and provide further evidence that a small set of developmentally restricted VH genes can give rise to disease-associated autoantibodies through Ag-selected somatic mutations.
Antisense Suppression of Pygopus2 Results in Growth Arrest of Epithelial Ovarian Cancer (2006)

hPygo2 is unexpectedly widely expressed in, and required in the absence of, Wnt signaling for malignant growth of epithelial ovarian cancer, the deadliest gynecologic malignancy. These findings strongly suggest that inhibition of hPygo2 may be of therapeutic benefit for treating this disease.
ADP-ribosyltransferases Parp1 and Parp7 safeguard pluripotency of ES cells (2014)

Embryonic stem (ES) cells are in a dynamic equilibrium of distinct functional states, characterized by the heterogeneous expression of critical pluripotency factors and regulated by a spectrum of reversible histone modifications. Maintenance of this equilibrium is a hallmark of pluripotency. Here we find that the ADP-ribosyltransferases Parp1 and Parp7 play a critical role in safeguarding this state by occupying key pluripotency genes, notably Nanog, Pou5f1, Sox2, Stella, Tet1 and Zfp42, thereby protecting them from progressive epigenetic repression. In the absence of either Parp1 or Parp7, or upon inhibition of the ADP-ribosylating activity, ES cells exhibit a decrease in ground state pluripotency as they cannot maintain the typical heterogeneity characteristic of the metastable state. As a consequence, they display a higher propensity to differentiate. These findings place Parp1 and Parp7 at the genetic-epigenetic interface of pluripotency networks, fine-tuning the transcriptional heterogeneity and thereby determining the developmental plasticity of ES cells.
Toll-like receptors: a growing family of immune receptors that are differentially expressed and regulated by different leukocytes (2000)

Toll is a Drosophila gene essential for ontogenesis and antimicrobial resistance. Several hortologues of Toll have been identified and cloned in vertebrates, namely Toll-like receptors (TLR). Human TLR are a growing family of molecules involved in innate immunity. TLR are structurally characterized by a cytoplasmic Toll/interleukin-1R (TIR) domain and by extracellular leucine-rich repeats. TLR characterized so far activate the MyD88/IRAK signaling cascade, which bifurcates and leads to NF-kappaB and c-Jun/ATF2/TCF activation. Genetic, gene transfer, and dominant-negative approaches have involved TLR family members (TLR2 and TLR4) in lipopolysaccharide recognition and signaling. Accumulating evidence suggests that some TLR molecules are also involved in signaling receptor complexes that recognize components of gram-positive bacteria and mycobacteria. However, the definitive role of other TLR is still lacking. A systematic approach has been used to determine whether different human leukocyte populations selectively or specifically expressed TLR mRNA. Based on expression pattern, TLR can be classified as ubiquitous (TLR1), restricted (TLR2, TLR4, and TLR5), and specific (TLR3). Expression and regulation of distinct though overlapping ligand recognition patterns may underlie the existence of a numerous, seemingly redundant, TLR family. Alternately, the expression of a TLR in a single cell type may indicate a specific role for this molecule in a restricted setting.
Three-dimensional Measurement Of Dental Cast Profiles And Its Applications To Orthodontics (2005)

A computer-controlled apparatus for measuring dental cast profiles h as b een developed. T his apparatus has been applied to the measurement of three-dimensiona l tooth m ovement during orthodontic treatments. T he 3-D movements, including rotations, have been obtained by computer-aided 3-D registration b etween tooth profiles of casts serially taken at different stages of the t reatment. Measurements o ver periods of 70 to 190 days on patients h ave revealed that w e can q uantify the difference in movements due to orthodontic t herapeutics. A feasible a pplication of this t echnique to the measurement of a contacting area of occlusal surface is discussed as well.
Effects of Cortisone and Vitamin A on Wound Healing (1968)

From the Departments of Surgery, University of California School of Medicine, and San Francisco General Hospital, San Francisco
Thermodynamic Properties of Mixtures Containing Ionic Liquids. 2. Activity Coefficients at Infinite Dilution of Hydrocarbons and Polar Solutes in 1-Methyl-3-ethyl-imidazolium Bis(trifluoromethyl-sulfonyl) Amide and in 1,2-Dimethyl-3-ethyl-imidazolium Bis(trifluoromethyl-sulfonyl) Amide Using Gas−Liquid Chromatography (2002)

Activity coefficients at infinite dilution of alkanes, alkenes, and alkylbenzenes as well as of the linear and branched C1−C6 alcohols, acetone, acetonitrile, ethyl acetate, alkyl ethers, and chloromethanes in the ionic liquids 1-methyl-3-ethyl-imidazolium bis(trifluoromethyl-sulfonyl) amide and 1,2-dimethyl-3-ethyl-imidazolium bis(trifluoromethyl-sulfonyl) amide were determined by gas chromatography using the ionic liquids as the stationary phase. The measurements were carried out at different temperatures between 313 K and 363 K. From the temperature dependence of the limiting activity coefficients partial molar excess enthalpies at infinite dilution of the solutes in the ionic liquids have been derived.
Induced immunity against hepatitis B virus (2015)

Prevention of hepatitis B virus (HBV) infection with its consequent development of HBV chronic liver disease and hepatocellular carcinoma is a global mandatory goal. Fortunately, safe and effective HBV vaccines are currently available. Universal hepatitis B surface antigen HBV vaccination coverage is almost done. Growing knowledge based upon monitoring and surveillance of HBV vaccination programs has accumulated and the policy of booster vaccination has been evaluated. This review article provides an overview of the natural history of HBV infection, immune responses and the future of HBV infection. It also summarizes the updated sources, types and uses of HBV vaccines, whether in the preclinical phase or in the post-field vaccination.
Regulation of Pyrimidine Biosynthesis in Saccharomyces cerevisiae (1968)

Biochemical steps of the pyrimidine pathway have been found to be the same in yeast as in bacteria, and all except one step have been characterized. The activities of the first two enzymes, carbamoyl phosphate synthetase and aspartic transcarbamylase, are simultaneously controlled by feedback inhibition and repression. Moreover, these enzymes are coded by the same genetic region (ura-2) and seem to form a single enzymatic complex. The enzymes that follow later in the pathway are induced in a sequential way by the intermediary products and are insensitive to pyrimidine repression. The corresponding genes (ura-4, ura-1, ura-3) are not linked to each other or to ura-2, the gene for carbamoyl phosphate synthetase and aspartic transcarbamylase. Mutants that have simultaneously lost feedback inhibition by uridine triphosphate for carbamoyl phosphate synthetase and for aspartic transcarbamylase have been found and mapped in the gene ura-2.
Insulin stimulates the phosphorylation of Tyr538 and the catalytic activity of PTP1C, a protein tyrosine phosphatase with Src homology-2 domains. (1994)

PTP1C is a non-transmembrane protein-tyrosine phosphatase and contains two Src homology-2 (SH2) domains. Insulin stimulated the tyrosine phosphorylation of PTP1C in human 1M-9 lymphoblast cells, in rat H35 hepatoma cells and in Chinese hamster ovary cells over-expressing both insulin receptors and PTP1C. Insulin also stimulated the tyrosine phosphorylation of a mutant PTP1C lacking SH2 domains in Chinese hamster ovary cells, suggesting that the SH2 domains are not required for insulin-stimulated tyrosine phosphorylation of PTP1C. The insulin receptor tyrosine kinase catalyzed the tyrosine phosphorylation of PTP1C in a cell-free system. Peptide mapping of phosphorylated PTP1C showed that Tyr538 in the C-terminal region was phosphorylated in response to insulin. The tyrosine phosphorylation of PTP1C by the insulin receptor kinase increased phosphatase activity. Furthermore, PTP1C was shown to bind to autophosphorylated insulin receptors through its C-terminal region, but PTP1C did not bind to unphosphorylated receptors. These results suggest that PTP1C is a target protein for the insulin receptor tyrosine kinase and that the C-terminal region of PTP1C may function both in the regulation of phosphatase activity and in the association of PTP1C with autophosphorylated insulin receptors.
PDZBase: a protein–protein interaction database for PDZ-domains (2004)

PDZBase is a database that aims to contain all known PDZ-domain-mediated protein-protein interactions. Currently, PDZBase contains approximately 300 such interactions, which have been manually extracted from > 200 articles. The database can be queried through both sequence motif and keyword-based searches, and the sequences of interacting proteins can be visually inspected through alignments (for the comparison of several interactions), or as residue-based diagrams including schematic secondary structure information (for individual complexes).
Stable chloroplast transformation in potato: use of green fluorescent protein as a plastid marker (1999)

We describe here the development of a reproducible plastid transformation system for potato and regeneration of plants with uniformly transformed plastids. Two distinct tobacco-specific plastid vectors, pZS197 (Prrn/aadA/TpsbA) and pMON30125 (Prrn/GFP/Trps16:PpsbA/aadA/TpsbA), designed for integration into the large single copy and inverted repeat regions of the plastid genome, respectively, were bombarded into leaf explants of potato line FL1607. A total of three transgenic lines were selected out of 46 plates bombarded with pZS197 and three transgenic lines out of 104 plates were obtained with pMON30125. Development of a high frequency leaf-based regenera- tion system, a stringent selection scheme and optimization of biolistic transformation protocol were critical for recovery of plastid transformants. Plastid-expressed green fluorescent protein was used as a visual marker for identification of plastid transformants at the early stage of selection and shoot regeneration. The establishment of a plastid transformation system in potato, which has several advantages over routinely used nuclear transformation, offers new possibilities for genetic improvement of this crop.
Universality in Chaos (2017)

The often repeated statement, that given the initial conditions we know what a deterministic system will do far into the future, is false. Poincaré (1892) knew it was false, and we know it is false, in the following sense: given infinitesimally different starting points, we often end up with wildly different outcomes. Even with the simplest conceivable equations of motion, almost any non-linear system will exhibit chaotic behaviour. A familiar example is turbulence.
Changes in Blood Pressure and Muscle Sympathetic Nerve Activity during Water Drinking in Humans. (2002)

To investigate the possible involvement of the sympathetic nervous system in pressor response during water drinking, muscle sympathetic nerve activity (MSNA), blood pressure (BP), and heart rate (HR) were continuously measured in healthy young volunteers throughout the experiments of a 5-min control, 2 min of drinking 500 ml water, and a 28-min recovery. To avoid the effects of water passing through the oropharyngeal and esophageal regions and/or effects of swallowing, an equal amount of water was directly infused to the stomach through a stomach tube for 2 min. Water drinking caused a transient increase in mean arterial pressure (MAP) and HR immediately after drinking (DeltaMAP, 12.6 +/- 2.1 mmHg; DeltaHR, +19.9 +/- 1.7 beats/min at the peak). An abrupt decrease of MSNA was observed directly during water drinking (Deltaburst rate, -6.9 +/- 1.3 bursts/min; Deltatotal activity, -2,606 +/- 491 U/min), and it increased to the baseline level thereafter. Gastric infusion had little or no effect on MAP, HR, and MSNA. The present study demonstrated that a pressor response during water drinking was associated with the attenuation of MSNA and not generated by gastric infusion of water at the same rate as in this drinking manner. In conclusion, the rapid rise in BP might be caused through stimulations from the oropharyngeal region, swallowing-induced factors, and/or a feedforward mechanism by a central descending signal from the higher brain centers.
Bioinspired Tunable Lens with Muscle‐Like Electroactive Elastomers (2011)

Abstract Optical lenses with tunable focus are needed in several fields of application, such as consumer electronics, medical diagnostics and optical communications. To address this need, lenses made of smart materials able to respond to mechanical, magnetic, optical, thermal, chemical, electrical or electrochemical stimuli are intensively studied. Here, we report on an electrically tunable lens made of dielectric elastomers, an emerging class of “artificial muscle” materials for actuation. The optical device is inspired by the architecture of the crystalline lens and ciliary muscle of the human eye. It consists of a fluid‐filled elastomeric lens integrated with an annular elastomeric actuator working as an artificial muscle. Upon electrical activation, the artificial muscle deforms the lens, so that a relative variation of focal length comparable to that of the human lens is demonstrated. The device combined optical performance with compact size, low weight, fast and silent operation, shock tolerance, no overheating, low power consumption, and possibility of implementation with inexpensive off‐the‐shelf elastomers. Results show that combing bioinspired design with the unique properties of dielectric elastomers as artificial muscle transducers has the potential to open new perspectives on tunable optics.
Synthesis of Heterocycle‐Substituted Pyropheophorbide Derivatives (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Losartan reduces microalbuminuria in hypertensive microalbuminuric type 2 diabetics (2001)

Antihypertensive treatment with losartan exerts a beneficial effect on UAE, a benchmark for measuring the efficacy of therapeutic interventions in diabetic nephropathy, by reducing BP and allowing better diabetes control. The role of other mechanisms influencing the favourable outcome, beyond these measured effects, needs to be assessed in further studies.
Nosocomial Transmissibility of Nipah Virus (2001)

To the Editor-A severe outbreak of fatal viral encephalitis mainly affecting pig farmers occurred in Malaysia in 1999. The outbreak was due to Nipah virus, a novel paramyxovirus Nipah virus was isolated from the upper respiratory tract secretions and urine of 8 of 20 patients with acute encephalitis Mounts et al. [3] found that 3 of 338 health care workers who were exposed to patients during the outbreak were positive for IgG antibodies, as determined by EIA. The 3 positive serum samples did not have an IgM response and were negative for anti-Nipah virus neutralizing antibodies; thus, the authors inferred that the results were likely to be false positives and commented that the lack of nosocomial transmission to the health care workers was somewhat unexpected.
Preclinical Activity of Nanoliposomal Irinotecan Is Governed by Tumor Deposition and Intratumor Prodrug Conversion (2014)

A major challenge in the clinical use of cytotoxic chemotherapeutics is maximizing efficacy in tumors while sparing normal tissue. Irinotecan is used for colorectal cancer treatment but the extent of its use is limited by toxic side effects. Liposomal delivery systems offer tools to modify pharmacokinetic and safety profiles of cytotoxic drugs. In this study, we defined parameters that maximize the antitumor activity of a nanoliposomal formulation of irinotecan (nal-IRI). In a mouse xenograft model of human colon carcinoma, nal-IRI dosing could achieve higher intratumoral levels of the prodrug irinotecan and its active metabolite SN-38 compared with free irinotecan. For example, nal-IRI administered at doses 5-fold lower than free irinotecan achieved similar intratumoral exposure of SN-38 but with superior antitumor activity. Tumor response and pharmacokinetic modeling identified the duration for which concentrations of SN-38 persisted above a critical intratumoral threshold of 120 nmol/L as determinant for antitumor activity. We identified tumor permeability and carboxylesterase activity needed for prodrug activation as critical factors in achieving longer duration of SN-38 in tumors. Simulations varying tumor permeability and carboxylesterase activity predicted a concave increase in tumor SN-38 duration, which was confirmed experimentally in 13 tumor xenograft models. Tumors in which higher SN-38 duration was achieved displayed more robust growth inhibition compared with tumors with lower SN-38 duration, confirming the importance of this factor in drug response. Overall, our work shows how liposomal encapsulation of irinotecan can safely improve its antitumor activity in preclinical models by enhancing accumulation of its active metabolite within the tumor microenvironment.
Multimedia environments for scientists (1991)

This paper addresses the question of how the work of the scientist will change in the new multimedia environments. Scenarios for the process of simulating and analyzing data in such environments are constructed, and some of the underlying models used in their construction are examined. >
Impaired Complex-I Mitochondrial Biogenesis in Parkinson Disease Frontal Cortex (2012)

Parkinson's disease (PD) can include a progressive frontal lobe α-synucleinopathy with disability from cognitive decline and cortico-limbic dysregulation that may arise from bioenergetic impairments. We examined in PD frontal cortex regulation of mitochondrial biogenesis (mitobiogenesis) and its effects on Complex-I. We quantified expression of 33 nuclear genome (nDNA)-encoded and 7 mitochondrial genome (mtDNA)-encoded Complex-I genes, 6 Complex-I assembly factors and multiple mitobiogenesis genes. We related these findings to levels of Complex-I proteins and NADH-driven electron flow in mitochondria from these same specimens reported in earlier studies. We found widespread, decreased expression of nDNA Complex-I genes that correlated in some cases with mitochondrial Complex-I protein levels, and of ACAD9, a Complex-I assembly factor. mtDNA-transcribed Complex-I genes showed ~ constant expression within each PD sample but variable expression across PD samples that correlated with NRF1. Relationships among PGC-1α and its downstream targets NRF1 and TFAM were very similar in PD and CTL and were related to mitochondrial NADH-driven electron flow. MicroRNA arrays revealed multiple miRNA's regulated >2-fold predicted to interact with PGC-1α or its upstream regulators. Exposure of cultured human neurons to NO, rotenone and TNF-alpha partially reproduced mitobiogenesis down-regulation. In PD frontal cortex mitobiogenesis signaling relationships are maintained but down-regulated, correlate with impaired mitochondrial NADH-driven electron flow and may arise from combinations of nitrosative/oxidative stresses, inflammatory cytokines, altered levels of mitobiogenesis gene-interacting microRNA's, or other unknown mechanisms. Stimulation of mitobiogenesis in PD may inhibit rostral disease progression and appearance of secondary symptoms referable to frontal cortex.
Extended Lamivudine Treatment in Patients With Chronic Hepatitis B Enhances Hepatitis B E Antigen Seroconversion Rates: Results After 3 Years of Therapy (2001)

A study in Chinese patients with chronic hepatitis B showed that treatment with lamivudine for 1 year significantly improves liver histology and enhances hepatitis B e antigen (HBeAg) seroconversion compared with placebo. Fifty-eight patients from this 1-year study have received long-term treatment with lamivudine 100 mg; the outcome of 3 years of lamivudine is reported here. Before treatment, all patients had detectable HBeAg. HBeAg seroconversion (HBeAg-negative, anti-HBe-positive), hepatitis B virus (HBV)-DNA suppression, alanine transaminase (ALT) normalization, emergence of YMDD variant HBV, liver histology, and long-term safety were assessed. After 3 years of continuous treatment with lamivudine 100 mg daily, 40% (23 of 58) of patients achieved HBeAg seroconversion. In patients with baseline serum ALT >2 x upper limit of normal (ULN), the rate of HBeAg seroconversion was 65% (17 of 26). Median serum HBV-DNA concentrations were below the level of detection, and median ALT concentrations were within the normal range throughout 3 years of treatment. YMDD variant HBV emerged in 33 of 58 (57%) patients during the 3 years, of whom 9 (27%) achieved HBeAg seroconversion (6 after emergence of YMDD variant HBV). ALT levels and histologic scores after emergence of YMDD variant HBV did not show major deterioration. Lamivudine was well tolerated during 3 years of therapy. In conclusion, these data in Chinese patients with chronic hepatitis B show enhanced seroconversion rates with extended lamivudine treatment. Up to two thirds of patients with moderately elevated pretreatment ALT achieved HBeAg seroconversion after 3 years of therapy.