gebhart/patrepeval huggingface dataset:
Formation of a host range mutant of the lymphotropic strain of minute virus of mice during persistent infection in mouse L cells (1984)

Minute virus of mice (i), the lymphotropic strain of minute virus of mice, established a persistent infection in normally restrictive L cells. The carrier state, which lasted 150 days, exhibited three clearly distinguishable stages. During the early stage (days 1 to 10 postinfection), small amounts of virus were formed. A "crisis" then developed that lasted 50 to 60 days and was characterized by massive cell lysis and high titers of virus. This was followed by a 70- to 80-day period in which small but stable quantities of virus were produced. Virus shed by the carrier culture during the latter phase had acquired an altered host range, namely, it had lost its ability to replicate in T-lymphocyte cell lines and had adapted to growth in L cells. Virus isolated at this time from a single plaque in L cells, designated hr301, was shown to possess similar host range properties. No differences, however, could be found between the DNAs of minute virus of mice (i) and of hr301 by restriction enzyme analysis, suggesting that the mutation that affected the viral host range did not involve an extensive region of the viral genome.
Noninvasive reconstruction of the three-dimensional ventricular activation sequence during pacing and ventricular tachycardia in the canine heart (2011)

Single-beat imaging of myocardial activation promises to aid in both cardiovascular research and clinical medicine. In the present study we validate a three-dimensional (3D) cardiac electrical imaging (3DCEI) technique with the aid of simultaneous 3D intracardiac mapping to assess its capability to localize endocardial and epicardial initiation sites and image global activation sequences during pacing and ventricular tachycardia (VT) in the canine heart. Body surface potentials were measured simultaneously with bipolar electrical recordings in a closed-chest condition in healthy canines. Computed tomography images were obtained after the mapping study to construct realistic geometry models. Data analysis was performed on paced rhythms and VTs induced by norepinephrine (NE). The noninvasively reconstructed activation sequence was in good agreement with the simultaneous measurements from 3D cardiac mapping with a correlation coefficient of 0.74 ± 0.06, a relative error of 0.29 ± 0.05, and a root mean square error of 9 ± 3 ms averaged over 460 paced beats and 96 ectopic beats including premature ventricular complexes, couplets, and nonsustained monomorphic VTs and polymorphic VTs. Endocardial and epicardial origins of paced beats were successfully predicted in 72% and 86% of cases, respectively, during left ventricular pacing. The NE-induced ectopic beats initiated in the subendocardium by a focal mechanism. Sites of initial activation were estimated to be ∼7 mm from the measured initiation sites for both the paced beats and ectopic beats. For the polymorphic VTs, beat-to-beat dynamic shifts of initiation site and activation pattern were characterized by the reconstruction. The present results suggest that 3DCEI can noninvasively image the 3D activation sequence and localize the origin of activation of paced beats and NE-induced VTs in the canine heart with good accuracy. This 3DCEI technique offers the potential to aid interventional therapeutic procedures for treating ventricular arrhythmias arising from epicardial or endocardial sites and to noninvasively assess the mechanisms of these arrhythmias.
Molecular cloning of human cathepsin O, a novel endoproteinase and homologue of rabbit OC2 (1995)

A 1670-bp cDNA coding for a novel human cysteine protease has been isolated from a monocyte-derived macrophage cDNA library. This cDNA predicts a 329-amino acid preprocathepsin with more than 50% identity to both human cathepsin S and cathepsin L and 94% identity to a rabbit cDNA, termed OC2, recently isolated from osteoclasts. Based on its high homology to OC2, we have named the human enzyme cathepsin O. Cathepsin O mRNA was identified as a single approximately 1.7 kb transcript in cultures of 15-day-old monocyte-derived macrophages, but was not expressed in human monocytes or alveolar macrophages. When transfected into COS-7 cells, cathepsin O displayed potent endoprotease activity against fibrinogen at acid pH. This novel endoprotease may play an important role in extracellular matrix degradation.
Enhancement of Radiation Cytotoxicity by UCN-01 in Non-small Cell Lung Carcinoma Cells (2004)

Thoracic ionizing radiation is a standard component of combined-modality therapy for locally advanced non-small cell lung cancer. To improve low 5-year survival rates (5- 15%), new strategies for enhancing the effectiveness of ionizing radiation are needed. The kinase inhibitor UCN-01 has multiple cell cycle effects, including abrogation of DNA damage-induced S- and G(2)-phase arrest, which may limit DNA repair prior to mitosis. To test the hypothesis that therapy-induced cell cycle effects would have an impact on the efficacy of a combination of UCN-01 plus ionizing radiation, the cell cycle responses of the non-small cell lung cancer cell lines Calu1 (TP53-null) and A549 (wild-type TP53) to 2 Gy ionizing radiation were correlated with clonogenic survival after irradiation plus UCN-01. Irradiated cells were exposed to UCN-01 simultaneously and at 3-h increments after irradiation. In Calu1 cells but not A549 cells, sequence-dependent potentiation of radiation by UCN-01 was observed, with maximal interaction occurring when UCN-01 was administered 6 h after irradiation. This coincided with the postirradiation time with the greatest depletion of cells from G(1). Abrogation of G(2) arrest was observed regardless of TP53 status. The role of TP53 was investigated using siRNA to achieve gene silencing. These studies demonstrated that radiation plus UCN-01 was more effective in cells with diminished TP53 activity, associated with a reduced G(1) checkpoint arrest. These studies indicate that simultaneous elimination of multiple DNA damage-induced checkpoints in G(1), S and G(2) may enhance the effects of radiation and that drug scheduling may have an impact on clinical efficacy.
Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma (2016)

Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovector-based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma.
Identification of human myocardial proteins separated by two‐dimensional electrophoresis using an effective sample preparation for mass spectrometry (1996)

Peptide mass fingerprinting is a powerful tool for the identification of proteins separated by two-dimensional gel electrophoresis (2-DE). The identification of in-gel digested proteins by peptide mass fingerprinting was significantly improve in comparison to blot-digests by using a peptide-collecting device. This device allows the effective purification and concentration of enzymatic digests of low-intensity spots without expensive equipment and is described in detail. Sensitivity in the fmol range was demonstrated by unequivocal identification of bovine serum albumin after sodium dodecyl sulfate--polyacrylamide gel electrophoresis. Furthermore the high performance liquid chromatography pattern of in-gel digests indicated a 2- to 3-fold higher yield of the separated peptides. Therefore, a higher amount of the peptides was available to perform N-terminal sequencing. The identification of 16 proteins from a high-resolution 2-DE gel map of human myocardium tissue has been achieved by means of this technique. Three of these proteins were associated with changes in spot intensity with dilated cardiomyopathy.
Detection of anomalous computer session activity (2003)

The authors discusses Wisdom and Sense (W&S), a computer security anomaly detection system. W&S is statistically based. It automatically generates rules from historical data and, in terms of those rules, identifies computer transactions that are at variance with historically established usage patterns. Issues addressed include how W&S generates rules from a necessarily small sample of all possible transactions, how W&S deals with inherently categorical data, and how W&S assists system security officers in their review of audit logs. Preliminary results with W&S show that the software does periodically detect anomalies of high interest even in data though to be free of such events.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Lamotrigine augmentation of serotonin reuptake inhibitors in treatment-resistant obsessive–compulsive disorder: a double-blind, placebo-controlled study (2012)

The present 16-week double-blind, randomized, placebo-controlled trial had the aim to explore the efficacy of lamotrigine add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of patients with treatment-resistant obsessive-compulsive disorder (OCD) receiving serotonin reuptake inhibitors (SRIs). After clinical and neurocognitive assessments, patients were randomly allocated to receive, in a double-blind design, 100 mg/day of lamotrigine or a placebo. A final sample of 33 patients completed the study. The results obtained indicate that lamotrigine added to stable SRI treatment substantially improved obsessive-compulsive (Yale-Brown Obsessive Compulsive Scale: obsessions, p < 0.0001; compulsions, p < 0.0001; total score, p < 0.0001), and affective symptoms (Hamilton Rating Scale for Depression p < 0.0001). Regarding cognitive functions, improvement was observed only in Semantic Fluency (p = 0.004). The findings provide evidence that lamotrigine augmentation of SRI treatment is well tolerated and may be proposed as an effective therapeutic strategy to improve outcome in treatment-resistant OCD.
THE DESIGN OF OPTIMUM MULTIFACTORIAL EXPERIMENTS (1946)

THE DESIGN OF OPTIMUM MULTIFACTORIAL EXPERIMENTS Get access R. L. PLACKETT, R. L. PLACKETT Search for other works by this author on: Oxford Academic Google Scholar J. P. BURMAN J. P. BURMAN Search for other works by this author on: Oxford Academic Google Scholar Biometrika, Volume 33, Issue 4, June 1946, Pages 305–325, https://doi.org/10.1093/biomet/33.4.305 Published: 01 June 1946
Susceptibility of normal human lymphocytes to infection with HTLV-III/LAV. (1986)

Normal human peripheral blood lymphocytes were tested for their susceptibility to infection with retroviruses isolated from patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Of 10 normal individuals tested, lymphocytes from all subjects became infected and produced virus as detected by assay for Mg+2-dependent reverse transcriptase. Lymphocytes from different individuals were demonstrated to be either high or low producers of reverse transcriptase after infection. The kinetics of virus production were similar in cells from both high- and low-producing individuals. A significant correlation was observed between high and low viral-producing lymphocytes and expression of the Leu-3/T4 (CD4) surface molecule. Mitogen-stimulated peripheral blood lymphocytes exposed to HTLV-III/LAV manifested productive viral infection, as reflected by the appearance of early syncytia, followed by reverse transcriptase. Unstimulated peripheral blood lymphocyte cultures displayed late syncytia but no detectable reverse transcriptase upon exposure to virus. The addition of anti-human interferon-alpha did not appear to have an appreciable effect on viral production in normal peripheral blood lymphocytes exposed to the virus.
Human Brain Nicotinic Receptors, their Distribution and Participation in Neuropsychiatric Disorders (2002)

Mapping of nicotinic acetylcholine receptor (nAChR) subtypes and subunits in human brain is far from complete, however it is clear that multiple subunits are present (including alpha3, alpha4, alpha5, alpha6 and alpha7, beta2, alpha3 and beta4) and that these receptors are not solely distributed on neurones, but also on cerebral vasculature and astrocytes. It is important to elucidate subunit composition of receptors associated with different cell types and pathways within the human CNS in terms of potential nicotinic therapy for a range of both developmental and age-related disorders in which nAChR attenuation occurs. Reductions in nAChRs are reported in Alzheimer's and Parkinson's diseases, dementia with Lewy bodies, schizophrenia and autism, but may not be associated with reduced cortical cholinergic innervation observed in vascular dementia or occur at an early stage in Down's syndrome. Changes in nAChR expression in neuropsychiatric disorders appear to be brain region and subtype specific and have been shown in some instances to be associated with pathology and symptomatology. It is likely that deficits in alpha4-containing receptors predominate in cortical areas in Alzheimer's disease and autism, whereas reduction of alpha7 receptors may be more important in schizophrenia. Changes in astrocytic and vascular nAChR expression in neurodegenerative diseases should also be considered. Studies using both animal models and human autopsy tissue suggest that nAChRs can play a role in neuroprotection against age-related pathology. It is possible that the development of nAChR subtype specific drugs may lead to advances in therapy for both age-related and psychiatric disorders.
A novel syndrome of variant leukocyte adhesion deficiency involving defects in adhesion mediated by β1 and β2 integrins (2001)

Leukocyte adhesion deficiency type I (LAD-1) is a disorder associated with severe and recurrent bacterial infections, impaired extravascular targeting and accumulation of myeloid leukocytes, altered wound healing, and significant morbidity that is caused by absent or greatly diminished surface expression of integrins of the beta2 class. We report clinical features and analysis of functions of cells from a patient with a myelodysplastic syndrome and infectious complications similar to those in the severe form of LAD-1, but whose circulating neutrophils displayed normal levels of beta2 integrins. Analysis of adhesion of these cells to immobilized ligands and to endothelial cells and assays of cell-cell aggregation and chemotaxis demonstrated a profound defect in adhesion mediated by beta2 integrins indicative of a variant form of LAD-1. A novel cell line established from Epstein-Barr virus-transformed lymphoblasts from the subject demonstrated deficient beta2 integrin-dependent adhesive function similar to that of the primary leukocytes. In addition, these cells had markedly impaired beta1 integrin-dependent adhesion. Sequence analysis and electrophoretic mobility of beta1 and beta2 proteins from the cell line demonstrated that the defects were not a result of structural abnormalities in the integrin subunit chains themselves and suggest that the adhesive phenotype of these cells is due to one or more abnormalities of inside-out signaling mechanisms that regulate the activity of integrins of these classes. These features define a unique LAD-1 variant syndrome that may reveal important insights that are generally relevant to inside-out signaling of integrins, a molecular process that is as yet incompletely understood.
Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer (2005)

In 2002, we reported the initial results of a trial comparing radical prostatectomy with watchful waiting in the management of early prostate cancer. After three more years of follow-up, we report estimated 10-year results.
Routing and flow control in high-speed wide-area networks (1990)

The routing and flow control techniques developed for wide-area, local-area, and metropolitan-area networks are surveyed. A classification that shows the characteristics that are desirable for high-speed wide-area networks is developed. On the basis of the classification, techniques that should and should not be considered for future high-speed networks are identified. In particular, an attempt is made to determine the effect of increasing transmission rates on the routing and flow control algorithms that are used in packet-switched networks.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
486. Aryl-2-halogenoalkylamines. Part XII. Some carboxylic derivatives of NN-di-2-chloroethylaniline (1953)

J. L. Everett, J. J. Roberts and W. C. J. Ross, J. Chem. Soc., 1953, 2386 DOI: 10.1039/JR9530002386
Polyisobutylene‐based polyurethanes with unprecedented properties and how they came about (2011)

Abstract This highlight concerns the birth, development, and present status of unique polyurethanes consisting of polyisobutylene soft segments and conventional hard segments (PIB‐based PUs) exhibiting unprecedented combinations of mechanical properties and oxidative/hydrolytic/biological stability. Impetus for developments was to improve the rather poor chemical resistance of conventional polyurethanes by replacing their soft segments with polyisobutylene segments. Research started in the 1980s with the synthesis of α,ω‐polyisobutylene diols (HO‐PIB‐OH) by the inifer technique and preparation of PIB‐based PUs, which indeed exhibited outstanding stabilities, however, had poor mechanical properties. Because of cumbersome early techniques and expensive reagents, worldwide research and industrial interest waned and developments went into hibernation. Recent discoveries, including living isobutylene polymerization, improved end‐functionalizations, inexpensive ingredients, and new insight into PU morphology, lead to simple and less expensive synthesis strategies and, consequently, to resumption of fundamental and applied research. Presently, we can produce kilogram quantities of polyurethanes and polyureas with unprecedented combinations of excellent physical–mechanical–environmental–biological and processing properties. This highlight focuses on facts and insights, which occurred since the discovery and shaped developments. These events are worth reviewing and analyzing because they illustrate how contemporary academic research is driven by curiosity (fun) and economic considerations (money). © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011
Concise Total Synthesis of (−)‐Calycanthine, (+)‐Chimonanthine, and (+)‐Folicanthine (2007)

Conjoined twins: An efficient and convergent strategy for the synthesis of the dimeric hexahydropyrroloindole alkaloids, (+)-chimonanthine, (+)-folicanthine, and (−)-calycanthine, is described. The simultaneous formation of the vicinal quaternary stereocenters by using a reductive dimerization reaction provides an access to the optically active key intermediate on a gram scale. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2007/z700705_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Identification of the microsporidian Encephalitozoon hellem using immunoglobulin G monoclonal antibodies. (1998)

Identification of microsporidian agents to the species level is important. Since certain therapeutic agents (eg, fumagillin, albendazole) are efficacious in treating E hellem infections of the cornea, as well as urogenital and respiratory infections caused by E hellem, a quick and definitive identification of the organism is important so that successful therapy may be instituted. An IIF test using the MAbs described here would therefore be invaluable in the quick identification of this parasite.
Clinical strain of Staphylococcus aureus inactivates and causes efflux of macrolides (1996)

Searching through a collection of 124 Staphylococcus aureus clinical strains, we found one isolate, strain 01A1032, that inactivates 14- and 16-membered macrolides. The products of inactivation were purified from supernatant fluids of cultures exposed to erythromycin for 3 h and were found to be identical to products of inactivation from Escherichia coli strains that encode either an EreA or EreB esterase. Further, strain 01A1032 was shown to be resistant to azithromycin, a 15-membered macrolide, by an alternate mechanism, efflux. Thus, strain 01A1032 harbors determinants encoding an esterase activity that hydrolyzes 14- and 16-membered macrolides and a macrolide efflux system.
Structural roles of acetylcholinesterase variants in biology and pathology (1999)

Apart from its catalytic function in hydrolyzing acetylcholine, acetylcholinesterase (AChE) affects cell proliferation, differentiation and responses to various insults, including stress. These responses are at least in part specific to the three C-terminal variants of AChE which are produced by alternative splicing of the single ACHE gene. 'Synaptic' AChE-S constitutes the principal multimeric enzyme in brain and muscle; soluble, monomeric 'readthrough' AChE-R appears in embryonic and tumor cells and is induced under psychological, chemical and physical stress; and glypiated dimers of erythrocytic AChE-E associate with red blood cell membranes. We postulate that the homology of AChE to the cell adhesion proteins, gliotactin, glutactin and the neurexins, which have more established functions in nervous system development, is the basis of its morphogenic functions. Competition between AChE variants and their homologs on interactions with the corresponding protein partners would inevitably modify cellular signaling. This can explain why AChE-S exerts process extension from cultured amphibian, avian and mammalian glia and neurons in a manner that is C-terminus-dependent, refractory to several active site inhibitors and, in certain cases, redundant to the function of AChE-like proteins. Structural functions of AChE variants can explain their proliferative and developmental roles in blood, bone, retinal and neuronal cells. Moreover, the association of AChE excess with amyloid plaques in the degenerating human brain and with progressive cognitive and neuromotor deficiencies observed in AChE-transgenic animal models most likely reflects the combined contributions of catalytic and structural roles.
SR141716A, a potent and selective antagonist of the brain cannabinoid receptor (1994)

SR141716A is the first selective and orally active antagonist of the brain cannabinoid receptor. This compound displays nanomolar affinity for the central cannabinoid receptor but is not active on the peripheral cannabinoid receptor. In vitro, SR141716A antagonises the inhibitory effects of cannabinoid receptor agonists on both mouse vas deferens contractions and adenylyl cyclase activity in rat brain membranes. After intraperitoneal or oral administration SR141716A antagonises classical pharmacological and behavioural effects of cannabinoid receptor agonists. This compound should prove to be a powerful tool for investigating the in vivo functions of the anandamide/cannabinoid system.