gebhart/patrepeval huggingface dataset:
NATURAL HISTORY OF CERVICAL SQUAMOUS INTRAEPITHELIAL LESIONS (1998)

Objective To define the strengths and weaknesses of existing research on the natural history of cervical squamous intraepithelial lesions (SIL) and to estimate rates of progression and regression without treatment. Data Sources Studies of women whose cervical smears showed squamous atypia or worse and who were observed for a minimum of 6 months were identified by a search of MEDLINE from 1966 to 1996, Current Contents, the Federal Research in Progress database, and references of review articles and identified studies, and by experts in the field. Methods of Study Selection Fifteen of 81 studies were eligible for data extraction. To be eligible, studies had to report a minimum of 6 months' follow-up without treatment; relate entry cytologic findings to outcomes; and report entry cytologic findings so that the study population could be stratified into categories of atypical cells of undetermined significance (ASCUS), low-grade SIL, or high-grade SIL. Studies published before 1970 were excluded. Tabulation, Integration, and Results Eligible studies, representing 27,929 patients, were stratified according to entry cytologic findings. The following rates of progression to high-grade SIL at 24 months were found: ASCUS, 7.13% (95% confidence interval [CI] 0.8%, 13.5%); low-grade SIL, 20.81% (6.08%, 35.55%); and high-grade SIL, 23.37% (12.82%, 32.92%). The following rates of invasive cancer at 24 months were found: ASCUS, 0.25% (0%, 2.25%); low-grade SIL, 0.15% (0%, 0.71%); and high-grade SIL, 1.44% (0%, 3.95%). The following rates of regression to normal were found: ASCUS, 68.19% (57.51%, 78.86%); low-grade SIL, 47.39% (35.92%, 58.86%); and high-grade SIL, 35.03% (16.57%, 53.49%). Study heterogeneity was not explained by regression analysis of study level variables. Conclusion Our findings for borderline and low-grade abnormal cervical cytologic results suggest a relatively low risk of invasive cervical cancer with observation up to 24 months and support the clinical policy of early colposcopy for high-grade lesions.
Caffeine modulates the effects of DNA-intercalating drugs in vitro: a flow cytometric and spectrophotometric analysis of caffeine interaction with novantrone, doxorubicin, ellipticine, and the doxorubicin analogue AD198. (1991)

Exposure of L1210 cells to DNA-intercalating antitumor drugs Novantrone (mitoxantrone; 20 ng/ml), doxorubicin (0.5 micrograms/ml), ellipticine (5 micrograms/ml), or the doxorubicin analogue AD198 (0.4 micrograms/ml), for 1 h, results in inhibition of cell proliferation, arrest of cells in the G2 phase of the cell cycle, and an increase in the number of cells entering higher DNA ploidy. These effects are significantly reduced when 5 mM concentrations of the methylxanthines caffeine or pentoxifylline are present either simultaneous with, or, in some cases, when added for 1 h immediately following pulse exposure to the drug. Both caffeine and pentoxifylline alone (5 mM) have little effect on cell growth or cell cycle progression. The possible mechanism of cell protection against intercalating drugs provided by caffeine was studied spectrophotometrically by measuring the interaction between Novantrone and the caffeine chromophore and in a model system using permeabilized L1210 cells and measuring the effect of caffeine in reducing binding of the intercalating dye acridine orange to cellular DNA and RNA. The data indicate that the observed protection of cells against intercalating drugs by caffeine or pentoxifylline is most likely a consequence of the direct interaction between the methylxanthines and the planar aromatic molecules of the intercalating drugs: formation of caffeine-drug complexes in solution effectively lowers the concentration of the free drug and thereby reduces its pharmacological activity. The principle of selective entrapment of the intercalator by compounds like caffeine may be considered in designing strategies to modulate the activity of intercalating drugs in vivo, e.g., in lowering drug toxicity when inadvertently applied at too high doses.
Perspectives for the use of structural information and chemical genetics to develop inhibitors of Janus kinases (2010)

Gain-of-function mutations in the genes encoding Janus kinases have been discovered in various haematologic diseases. Jaks are composed of a FERM domain, an SH2 domain, a pseudokinase domain and a kinase domain, and a complex interplay of the Jak domains is involved in regulation of catalytic activity and association to cytokine receptors. Most activating mutations are found in the pseudokinase domain. Here we present recently discovered mutations in the context of our structural models of the respective domains. We describe two structural hotspots in the pseudokinase domain of Jak2 that seem to be associated either to myeloproliferation or to lymphoblastic leukaemia, pointing at the involvement of distinct signalling complexes in these disease settings. The different domains of Jaks are discussed as potential drug targets. We present currently available inhibitors targeting Jaks and indicate structural differences in the kinase domains of the different Jaks that may be exploited in the development of specific inhibitors. Moreover, we discuss recent chemical genetic approaches which can be applied to Jaks to better understand the role of these kinases in their biological settings and as drug targets.
Effects of r‐metHuG‐CSF on polymorphonuclear leucocyte kinetics and function in patients on continuous ambulatory peritoneal dialysis (1998)

End-stage renal failure (ESRF) patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are immunocompromised and exhibit abnormal circulating polymorphonuclear leucocyte (PMN) function, including reduced phagocytosis and intracellular killing. Six uraemic patients on CAPD were each given 300 microg granulocyte colony stimulating factor (G-CSF) every day for 5 d and PMN function tests were performed daily. By day 5 of the study CD11b expression was significantly decreased in response to N-formylmethionylleucylphenylalanine (fMLP) and opsonized Staphylococcus epidermidis stimulation, and expression of L-selectin (CD62L) was significantly decreased in response to opsonized Staphylococcus epidermidis stimulation. Further, superoxide anion production and Fc gammaRI (CD64) expression were found to be significantly increased and Fc gammaRII (CD16) expression was lowered. Circulating white cell and PMN counts were significantly elevated in response to treatment. Administration of G-CSF did not appear to have corrected the abnormalities in phagocytosis and intracellular killing. This study suggests that G-CSF does no harm to ESRF patients and influences uraemic PMN function in a manner that is comparable to its effects on PMN in non-uraemic subjects.
Partial Purine Deprivation Causes Sporulation of Bacillus subtilis in the Presence of Excess Ammonia, Glucose and Phosphate (1979)

In strains of Bacillus subtilis able to synthesize purines de novo, massive sporulation is suppressed by the combination of excess ammonia, glucose and phosphate. Purine auxotrophs, blocked in the general or the guanine-specific portion of the branched purine pathway, sporulated in such a medium when the purine required for normal growth was removed from the medium. The resulting spore titre and the sporulation frequency increased with the residual growth rate in the purine-free medium, i.e. with the leakiness of the purine mutation. Sporulation was further increased by allowing residual growth in growth-limiting amounts of guanosine. None-leaky purine mutants blocked before 5'-phosphoribosyl-5-amino-4-imidazole carboxamide also sporulated well when supplied with 5-amino-4-imidazole carboxamide at concentrations (2 mM) that supported growth at a suboptimal rate.
BetalainsA New Class of Dietary Cationized Antioxidants (2001)

Antioxidant nutrients from fruits and vegetables are believed to be a class of compounds that exert their effects in humans by preventing oxidative processes which contribute to the onset of several degenerative diseases. This study found a new class of dietary cationized antioxidants in red beets (Beta vulgaris L.). These antioxidants are betalains, and the major one, betanin, is a betanidin 5-O-beta-glucoside. Linoleate peroxidation by cytochrome c was inhibited by betanin, betanidin, catechin, and alpha-tocopherol with IC(50) values of 0.4, 0.8, 1.2, and 5 microM, respectively. In addition, a relatively low concentration of betanin was found to inhibit lipid peroxidation of membranes or linoleate emulsion catalyzed by the "free iron" redox cycle, H(2)O(2)-activated metmyoglobin, or lipoxygenase. The IC(50) inhibition of H(2)O(2)-activated metmyoglobin catalysis of low-density lipoprotein oxidation by betanin was <2.5 microM and better than that of catechin. Betanin and betanidin at very small concentrations were found to inhibit lipid peroxidation and heme decomposition. During this reaction, betanidin was bleached completely, but betanin remained unchanged in its absorption. This difference seems to derive from differing mechanisms of protection by these two compounds. The high affinity of betanin and betanidin for membranes was demonstrated by determining the rate of migration of the compounds through a dialysis tube. Betanin bioavailability in humans was demonstrated with four volunteers who consumed 300 mL of red beet juice, containing 120 mg of the antioxidant. The betacyanins were absorbed from the gut and identified in urine after 2-4 h. The calculated amount of betacyanins found in the urine was 0.5-0.9% of that ingested. Red beet products used regularly in the diet may provide protection against certain oxidative stress-related disorders in humans.
Synthesis of N -3(4-(4-chlorophenyl thiazole-2-yl)-(2-(amino)methyl)-quinazoline-4(3 H )-one and their derivatives for antitubercular activity (2006)

A new series of N-3[4-(4-chlorophenyl thiazole-2-yl)-2-amino methyl] quinazoline-4(3H)-one and their derivatives are synthesized. The structures of the title compounds are confirmed on the basis of IR and 'H NMR. The compounds are screened for their antitubercular activity, using H 37 Rv strain on L J medium. All the compounds have showed moderate to promising antitubercular activity.
Cardiac Grafting of Engineered Heart Tissue in Syngenic Rats (2002)

EHTs can be employed for tissue grafting approaches and might serve as graft material to repair diseased myocardium.
Cell cycle arrest of cdc mutants and specificity of the RAD9 checkpoint. (1993)

In eucaryotes a cell cycle control called a checkpoint ensures that mitosis occurs only after chromosomes are completely replicated and any damage is repaired. The function of this checkpoint in budding yeast requires the RAD9 gene. Here we examine the role of the RAD9 gene in the arrest of the 12 cell division cycle (cdc) mutants, temperature-sensitive lethal mutants that arrest in specific phases of the cell cycle at a restrictive temperature. We found that in four cdc mutants the cdc rad9 cells failed to arrest after a shift to the restrictive temperature, rather they continued cell division and died rapidly, whereas the cdc RAD cells arrested and remained viable. The cell cycle and genetic phenotypes of the 12 cdc RAD mutants indicate the function of the RAD9 checkpoint is phase-specific and signal-specific. First, the four cdc RAD mutants that required RAD9 each arrested in the late S/G2 phase after a shift to the restrictive temperature when DNA replication was complete or nearly complete, and second, each leaves DNA lesions when the CDC gene product is limiting for cell division. Three of the four CDC genes are known to encode DNA replication enzymes. We found that the RAD17 gene is also essential for the function of the RAD9 checkpoint because it is required for phase-specific arrest of the same four cdc mutants. We also show that both X- or UV-irradiated cells require the RAD9 and RAD17 genes for delay in the G2 phase. Together, these results indicate that the RAD9 checkpoint is apparently activated only by DNA lesions and arrests cell division only in the late S/G2 phase.
Single image dehazing (2008)

In this paper we present a new method for estimating the optical transmission in hazy scenes given a single input image. Based on this estimation, the scattered light is eliminated to increase scene visibility and recover haze-free scene contrasts. In this new approach we formulate a refined image formation model that accounts for surface shading in addition to the transmission function. This allows us to resolve ambiguities in the data by searching for a solution in which the resulting shading and transmission functions are locally statistically uncorrelated. A similar principle is used to estimate the color of the haze. Results demonstrate the new method abilities to remove the haze layer as well as provide a reliable transmission estimate which can be used for additional applications such as image refocusing and novel view synthesis.
Low p27Kip1 expression is an independent adverse prognostic factor in patients with multiple myeloma. (2003)

Low p27(Kip1) expression is an independent adverse prognostic factor in patients with MM. The proposed risk score might be useful for risk-adapted treatment in the future.
Characterization of a Soluble Cytoplasmic Antigen Reactive with Sera from Patients with Systemic Lupus Erythmatosus (1969)

Summary A tissue antigen reactive with sera from SLE patients has been partially characterized. The antigen is a soluble cytoplasmic component which is present in a variety of human tissues and is distinct from known nuclear antigens. It is an acidic macromolecule which has the electrophoretic mobility of an α1 globulin and is resistant to most proteolytic enzymes including trypsin, pepsin and chymotrypsin. Antigenicity is destroyed by 0.02 M periodate and by 0.001 M parahydroxy mercuribenzoate. Antibodies to this antigen have been found in 40% of unselected LE sera and were absent from a large number of sera from normal persons and from the sera of patients with other connective tissue disorders.
La situació dels andalusins (Musulmans i Batejats) a Mallorca després de la Conquesta Catalana de 1230 (1994)

Soto i Company Ricardo. La situació dels andalusins (Musulmans i Batejats) a Mallorca després de la Conquesta Catalana de 1230. In: Mélanges de la Casa de Velázquez, tome 30-1, 1994. Antiquité-Moyen-Age. pp. 167-206.
A Novel Role of Complement: Mice Deficient in the Fifth Component of Complement (C5) Exhibit Impaired Liver Regeneration (2001)

Components of innate immunity have recently been implicated in the regulation of developmental processes. Most strikingly, complement factors appear to be involved in limb regeneration in certain urodele species. Prompted by these observations and anticipating a conserved role of complement in mammalian regeneration, we have now investigated the involvement of complement component C5 in liver regeneration, using a murine model of CCl(4)-induced liver toxicity and mice genetically deficient in C5. C5-deficient mice showed severely defective liver regeneration and persistent parenchymal necrosis after exposure to CCl(4.) In addition, these mice showed a marked delay in the re-entry of hepatocytes into the cell cycle (S phase) and diminished mitotic activity, as demonstrated, respectively, by the absence of 5-bromo-2'-deoxyuridine incorporation in hepatocytes, and the rare occurrence of mitoses in the liver parenchyma. Reconstitution of C5-deficient mice with murine C5 or C5a significantly restored hepatocyte regeneration after toxic injury. Furthermore, blockade of the C5a receptor (C5aR) abrogated the ability of hepatocytes to proliferate in response to liver injury, providing a mechanism by which C5 exerts its function, and establishing a critical role for C5aR signaling in the early events leading to hepatocyte proliferation. These results support a novel role for C5 in liver regeneration and strongly implicate the complement system as an important immunoregulatory component of hepatic homeostasis.
Kinetics of plasmin inhibition in the presence of a synthetic tripeptide substrate. The reaction with pancreatic trypsin inhibitor and two forms of α 2-plasmin inhibitor (1981)

The progressive inhibition of plasmin by pancreatic trypsin inhibitor and by alpha 2-plasmin inhibitor in the presence of D-valyl-L-leucyl-L-lysine 4-nitroanilide was investigated. The kinetics with plasmin were compared with those with miniplasmin. The kinetic properties of two functionally different forms of alpha 2-plasmin inhibitor described by Clemmensen [(1979) in The Physiological Inhibitors of Coagulation and Fibrinolysis (Collen. D., Wiman, B &amp; Verstraete, M., eds.), pp 131-136, Elsevier, Amsterdam] were characterized. The two forms differ in their plasminogen-binding capability, and this difference can account for a difference in secondary site interaction suggested from the kinetics. The binding of inhibitor to miniplasmin is a simple pseudo-first-order reaction with both pancreatic trypsin inhibitor and the two alpha 2-plasmin inhibitor forms. Such simple kinetics are also observed for the reaction between plasmin and the non-plasminogen-binding form of alpha 2-plasmin inhibitor. More complicated kinetics are obtained for the reaction between plasmin and the alpha 2-plasmin inhibitor form that binds to plasminogen. With both forms of the alpha 2-plasmin inhibitor, a complex stable to acetic acid/urea and gel electrophoresis is present and fully developed 15 s after initiation of the reaction with plasmin.
A Powerful o-Quinone Dimethide Strategy for Intermolecular Diels−Alder Cycloadditions (2000)

Conrotatory thermal fragmentation of trans-1,2-disilyloxybenzocyclobutenes generates o-quinone dimethides at remarkably low temperatures. Smooth stereoselective Diels−Alder cycloaddition with a range of dienophiles provides hydronaphthalene derivatives in excellent yield. Direct oxidative desilylation of the adducts affords the corresponding naphthoquinones. Substitution of the benzene nucleus with an electron-releasing methoxyl group directs the cycloaddition to give good control of regioselectivity in the expected direction. A short synthesis of the aglycon of the anticancer antibiotic idarubicin is presented.
Phase II study of methotrexate, vinblastine, doxorubicin, and cisplatin in patients with squamous cell carcinoma of the upper respiratory or alimentary passages of the head and neck (2002)

Methotrexate, vinblastine, doxorubicin, and cisplatin is an active chemotherapy regimen in patients with recurrent or metastatic squamous cell cancer arising from the upper respiratory or alimentary passages of the head and neck.
On the regioselectivity of Wittig reactions with unsymmetrically substituted succinic anhydrides (1989)

Phosphorane ylids react readily with succinic anhydrides to give enol-lactones. With highly substituted succinic anhydrides, condensations occur at the less substituted carbonyl group, suggesting that the reaction is sterically controlled. This, however, is not the case in monosubstituted anhydrides where effects other than steric become dominant. Condensation of phosphorane 1a with methoxysuccinic anhydride occurs selectively at the carbonyl group adjacent to the substituent. Stabilization of the transition state through complexation between the oxygen atom of the substituent and an electron-deficient phosphorus of the ylid is proposed. Keywords: cyclic anhydrides, Wittig reaction, regioselectivity, stabilized ylid.
Nanofluidic Biosensing for β-Amyloid Detection Using Surface Enhanced Raman Spectroscopy (2008)

Trace detection of the conformational transition of beta-amyloid peptide (Abeta) from a predominantly alpha-helical structure to beta-sheet could have a large impact in understanding and diagnosing Alzheimer's disease. We demonstrate how a novel nanofluidic biosensor using a controlled, reproducible surface enhanced Raman spectroscopy active site was developed to observe Abeta in different conformational states during the Abeta self-assembly process as well as to distinguish Abeta from confounder proteins commonly found in cerebral spinal fluid.
Thin Silica Film with a Network Structure as Prepared by Surface Sol-Gel Transcription on the Poly(styrene-b-4-vinylpyridine) Polymer Film (2003)

Abstract Sol-gel polycondensation of tetraethyl orthosilicate (TEOS) was carried out on the cast film of poly(styrene-b-4-vinylpyridine) under basic (benzylamine), acidic (AcOH), and neutral (no catalyst) conditions. It was found that only under the acidic and neutral conditions, the phase-separated periodic structure of the copolymer is finely transcribed into the silica. This is a new, convenient method to create the thin, mosaic film from inorganic materials.
Competing in Global Product Innovation: Is Antitrust Immunity Necessary? (1990)

One hears many cries that antitrust should be curtailed in the interest of improving United States competitiveness.There can be no doubt that the country's economic position has been slipping for a considerable time.Calls for change are always viewed more seriously when there is agreement that the situation is deteriorating.This article is an essay of the author's reactions to the revisionists.It opines that antitrust generally functions well and that other adjustments ought to be considered before further changes are made to it.Antitrust is truly an American contribution to world law.Although the concept of restraint of trade existed in England before the Sherman Act, 1 the shape of modem law comes from that act.As the United States prospered, it became an increasingly demanding proponent of its utility.Its message was influential.Antitrust now appears in the national laws of most free market countries. 2It is prominent in the European Community where it provides a second layer over the national laws on the same subject. 3 Even Japan, a country that has made only modest use of its law, has recently appeared more interested in its enforcement. 4 Unfortunately, the United States has fallen on harder times in its international trade.In a number of industries in which Ameri-
Detrimental role of granulocyte-colony stimulating factor in neuromyelitis optica: clinical case and histological evidence (2012)

In a recent study, administration of granulocyte colony stimulating factor (G-CSF) increased neuromyelitis optica (NMO) lesions in mice. Here we report a patient whose first episode of NMO may have been exacerbated by inadvertent administration of G-CSF. Histological examination of brain and spinal cord samples from three other NMO patients revealed markedly increased expression of G-CSF in neurons located in and around the lesions, with little or no expression in multiple sclerosis lesions or normal white matter. Taken together, these cases support a detrimental role for G-CSF in NMO pathogenesis.
High pressure processing of foods (1995)

Brings together reviews on the effects of high pressure on microbiological, chemical and structural properties of foods and food ingredients, and discusses the engineering aspects of the process. Topics covered include the potential of high pressure processing; the development of high pressure technology; the microbe as a high pressure target; kinetics of high pressure inactivation of microorganisms; effects of high pressure on vegetative pathogens; microbial inactivation mechanisms; high pressure effects on biomolecules; high pressure effects on milk and meat; high pressure effects of plant derived foods; vessel design; experimental scale rigs; production equipment for commercial use; continuous systems; etc. Of interest to students, researchers, and those in the food and drink industry