gebhart/patrepeval huggingface dataset:
p53 Autoantibodies in Patients with Primary Ovarian Cancer Are Associated with Higher Age, Advanced Stage and a Higher Proportion of p53-Positive Tumor Cells (1999)

Autoantibodies (AAb) directed against the nuclear phosphoprotein p53 can be detected in patients with various forms of cancer. The objective was to determine the prevalence of p53 AAb at the time of diagnosis in ovarian cancer patients and to correlate the presence of p53 AAb with clinicopathological parameters. Sera of 83 patients were analyzed by an ELISA using p53 expressed from a human wild-type cDNA. p53 AAb were detectable at all stages. The overall prevalence was 46%. p53 AAb were more frequent in patients with higher age (p = 0.014), postmenopausal status (p = 0.050), or advanced tumor stage (p = 0.046). p53 AAb positivity was related to the proportion of cells positive in immunohistochemistry but not with the staining intensity. In bivariate analysis, patients with p53 AAb had a 1.96-fold risk for relapse (95% confidence interval 1.02-3.78).
Modular Synthesis of Chiral Phosphine‐Phosphite‐Ligands from Phenolic Precursors: A New Approach to Bidentate Chelate Ligands Exploiting a PO to PC Migration Rearrangement (2008)

Abstract An efficient and modular approach to bidentate phosphine‐phosphite ligands formally derived from a 6‐alkyl‐2‐phosphanylphenol, a chiral diol and phosphorus trichloride has been developed. In a key step, a borane‐protected phosphinite, prepared from an o ‐bromophenol by O ‐phosphanylation, is reacted with n ‐butyllithium to afford the corresponding ortho ‐phosphanylphenol (as the stable borane adduct) through bromine‐lithium exchange and anionic migration rearrangement. Treatment with phosphorus trichloride in the presence of a base and subsequent reaction of the in situ formed dichlorophosphite with a chiral diol (such as TADDOL or BINOL) affords the target P,P ligands in good overall yield (up to 60% over 4 steps). In contrast to an earlier approach, the new methodology is very general and tolerates bulky ortho ‐substituents. The reliability of the operationally convenient protocol was demonstrated in the synthesis of a library of 16 new phosphine‐phosphite ligands, starting from different ortho ‐alkylphenols. The modular concept opens a rapid access to a broad variety of ligands and might be useful in the search for and structural optimization of suitable ligands for specific chirogenic transition metal‐catalyzed transformations.
The data access and transfer support in a local heterogeneous network (HMINET) (1979)

The following paper presents a local heterogeneous network, the HMINET. The adopted software architecture identifies a data access and transfer level. The higher level applications afford a mechanism for data access and transfer to alleviate the effects of the incompatibilities and the differences between the data management systems. The paper describes the major problems and design decisions we adopted for the Data Access and Transfer System (DATS).
The Culture of Streptococcus pneumoniue (1962)

SUMMARY: In the fluid culture of Streptococcus pneumoniue in glucose + serum broth the pa.rt played by the serum appeared to be solely the regulation of pH value, and may be substituted by a suitable amount of sodium carbonate. The reason for the autolysis experienced in the fluid culture of pneumococci would appear to be due to hydrogen peroxide production. The addition of cysteine to a glucose + carbonate broth precluded the autolytic effect either by the cysteine giving an anaerobic condition of growth or by destroying H2O2.
Reduction of circulating redox-active iron by apotransferrin protects against renal ischemia-reperfusion injury1 (2004)

Redox-active iron is released into the circulation in the course of renal I/R. Reducing the amount of circulating redox-active iron by treatment with apotransferrin protects against renal I/R injury, inhibiting oxidative stress, inflammation, and loss of function. Apotransferrin could be used in the treatment of acute renal failure, as seen after transplantation of ischemically damaged organs.
Antibody Production to Aggregated Human γg-Globulin in Acquired Hypogammaglobulinemia (1968)

A patient with acquired hypogammaglobulinemia, who suffered "anaphylactic shock" after intramuscular administration of commercially prepared human γG-globulin (HGG), was found on gel diffusion analysis to have precipitating antibody specific for the aggregated form of HGG. The antibody was principally of the γG-globulin type, and could be differentiated from classic rheumatoid factor by a number of hemagglutination technics. Unlike rheumatoid factor, the antibody failed to agglutinate sheep red cells sensitized with rabbit γG-globulin antibody, nor would it agglutinate latex particles coated with native HGG. The antibody readily agglutinated human A cells coated with homologous human γG-globulin antibody, however, and also agglutinated latex particles coated with aggregated HGG. Because of the specificity of this antibody, its coincident appearance and its increase after a period of considerable γ-globulin "immunization," it is postulated that its occurrence resulted from the administration of γG-globulin aggregates present in the preparations used for therapy.
New approaches and technologies in drug design and discovery (1995)

Traditional and novel approaches to drug design and screening techniques and strategies are described, and the potential benefits of new technologies are discussed. Sophisticated new approaches and technologies in the discovery and design of new drugs are replacing the traditional methods. Rational or structure-based methods of drug design and discovery that integrate techniques of x-ray crystallography, computational chemistry, and nuclear magnetic resonance spectroscopy are becoming the predominant methods. New technologies and methods for drug screening may yield significant savings in time and money, as well as increased diversity and specificity of lead compounds. Intense research activity is now being focused on small-molecule structure-based drug design, in which drugs would mimic the complex molecular interactions of natural proteins. The new approaches and technologies hold promise for dramatic therapeutic advances, particularly in the areas of transcriptionally active drugs and gene therapy. Rapid advances in drug design and screening, brought about through new technologies, may yield significant therapeutic advances and cost-effective therapies.
The active site of lysosomal sphingomyelinase: Evidence for the involvement of hydrophobic and ionic groups (1983)

The natural substrate for sphingomyelinase contains hydrophobic and polar moieties. In this study, we have employed pH rate studies and examined hydrophobic compounds and phosphorylated esters for their effect on sphingomyelinase activity in an attempt to determine some of the kinetic properties of this enzyme. Sphingomyelinase, purified from human placentae, undergoes noncompetitive inhibition by octylglucoside and Nonidet P-40, two nonionic detergents containing terminal octyl groups. The effect of these detergents at the hydrophobic binding site is somewhat different from that of Triton X-100, which contains an isooctyl terminal group, and this may serve to identify a structural basis for the effects. Sphingomyelinase activity is also modulated by several nucleotides. Inhibition by 5'-adenosine monophosphate (5'-AMP) is also noncompetitive. Other nucleotide monophosphates (such as 5'-uridine monophosphate (5'-UMP), 5'-cytidine monophosphate (5'-CMP), 2'-adenosine monophosphate (2'-AMP), and 3'-adenosine monophosphate (3'-AMP) and phosphorylated intermediates (such as phosphorylcholine, phosphorylethanolamine and hexose phosphates) have a lower inhibitory effect. The data suggest that the inhibition by 5'-AMP involves the combined effect of the phosphate group and the purine ring, structural requirements which may also be satisfied by bis(4-methylumbelliferyl)phosphate, a synthetic enzyme substrate. Studies of pH rate indicate that the maximal velocity for the hydrolysis of sphingomyelin is independent of pH over the range 3.5-6.2 while the Km value shows a pH dependence. The Km value is lowest from pH 4.0-5.2 and rises at pH values outside this range. The log Vmax/Km and pKm relationships, when plotted as a function of pH, have been used to identify the dissociation constants for the binding of sphingomyelin by the enzyme. These occur at pK values of 4.1 and 5.5. The activity of sphingomyelinase is also reduced when the enzyme is photooxidized in the presence of methylene blue or rose bengal and carbamylated by diethylpyrocarbonate (DEPC). These results are interpreted to show that 1). the enzyme contains a hydrophobic binding site which involves linear aliphatic moieties containing at least eight carbon atoms; 2) two ionic groups are involved in formation of the enzyme substrate complex, one of which is presumed to be the carboxylate group of aspartate or glutamate (represented by pK 4.1) and the second may be the protonated imidazolium group of histidine (represented by pK 5.5); and 3) since the maximal velocity shows no pH dependence, the interactions involving the hydrophobic and ionic groups affect only the binding of the substrate to the enzyme and formation of the enzyme-substrate complex.
Didemnins and Tunichlorin: Novel Natural Products from the Marine Tunicate Trididemnum solidum (1988)

Didemnins A, B, and C, cyclic depsipeptides previously reported by our laboratory from the Caribbean tunicate Trididemnum solidum, have now been synthesized and, in the process, their structures have been revised to include the new amino acid (3S,4R,5S)-isostatine,C2H5CH(CH3)CHNH2CHOHCH2COOH. All other isomers of isostatine have also been prepared. Didemnin B is currently in Phase II clinical trials as an anticancer agent, and the antineoplastic activity, as well as the antiviral and immunosuppressive activities, of the didemnins are reviewed. A highly unusual porphynoid has also been isolated from T. solidum. The compound has been named tunichlorin and is apparently the first nickel-containing chlorin (and only the second nickel-containing porphyrin-related compound) identified from a living organism.
Use of folding modulators to improve heterologous protein production in Escherichia coli (2009)

Despite the fundamental importance of E. coli in the manufacture of a wide range of biotechnological and biomedical products, extensive process and/or target optimisation is routinely required in order to achieve functional yields in excess of low mg/l levels. Molecular chaperones and folding catalysts appear to present a panacea for problems of heterologous protein folding in the organism, due largely to their broad substrate range compared with, e.g., protein-specific mutagenesis approaches. Painstaking investigation of chaperone overproduction has, however, met with mixed - and largely unpredictable - results to date. The past 5 years have nevertheless seen an explosion in interest in exploiting the native folding modulators of E. coli, and particularly cocktails thereof, driven largely by the availability of plasmid systems that facilitate simultaneous, non-rational screening of multiple chaperones during recombinant protein expression. As interest in using E. coli to produce recombinant membrane proteins and even glycoproteins grows, approaches to reduce aggregation, delay host cell lysis and optimise expression of difficult-to-express recombinant proteins will become even more critical over the coming years. In this review, we critically evaluate the performance of molecular chaperones and folding catalysts native to E. coli in improving functional production of heterologous proteins in the bacterium and we discuss how they might best be exploited to provide increased amounts of correctly-folded, active protein for biochemical and biophysical studies.
Accumulation of abnormal prion protein in mice infected with Creutzfeldt-Jakob disease via intraperitoneal route: a sequential study. (1993)

We immunohistochemically studied the location of abnormal prion protein in the central nervous system and visceral organs at the clinical and preclinical stages of mice infected with Creutzfeldt-Jakob disease via intraperitoneal route. Abnormal prion protein was diffusely distributed in the central nervous system. The sequential study showed that its stainings were first detected 120 days after inoculation, were found in all mice after 180 days, and were the most intense and widespread after 270 days. There was no restricted involvement at the early stages nor rostrally dominant distribution of the stainings that had been found in mice infected via intracerebral route. Abnormal prion protein was also located in the follicular dendritic cells in the spleen, lymph nodes, intestinal Peyer's patch, and thymus. Its stainings were first detected in the spleen, lymph nodes, and Peyer's patch 14 or 30 days after inoculation. In the thymus, however, the stainings were first detected after 210 days in the germinal centers formed in the medulla.
(−)-Spiro[1-azabicyclo[2.2.2]octane-3,5‘-oxazolidin-2‘-one], a Conformationally Restricted Analogue of Acetylcholine, Is a Highly Selective Full Agonist at the α7 Nicotinic Acetylcholine Receptor (2000)

Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha 7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2. 2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha 7 nicotinic receptor, which is highly selective for the rat alpha 7 nicotinic receptor over the alpha 4 beta 2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha 7 nicotinic receptor affinity.
A yeast-based genomic strategy highlights the cell protein networks altered by FTase inhibitor peptidomimetics (2010)

This work provides a view of how FTIs globally affect cell activity. It suggests that the chromosome segregation machinery and Aurora A association with the kinetochore as well as TORC1-S6K downstream effectors are among the ultimate targets affected by the transcriptional deregulation caused by FTI peptidomimetics. Moreover, it stresses the importance of monitoring the MDR response in patients treated with FTIs.
A Proposed New Brain Injury Tolerance for Minor Traumatic Brain Injury (2001)

Abstract Traumatic brain injuries constitute a significant portion of injury resulting from automotive collisions, motorcycle crashes, and sports collisions. Brain injuries not only represent a serious trauma for those involved but also place an enormous burden on society, often exacting a heavy economical, social, and emotional price. Development of intervention strategies to prevent or minimize these injuries requires a complete understanding of injury mechanism, response and tolerance level. In this study, an attempt is made to delineate actual injury causation and establish a meaningful injury criterion through the use of the actual field accident data. Twenty-four actual field head-to-head collisions that occurred in professional football games were duplicated using a validated finite element human head model. The injury predictors and injury levels were analyzed based on resulting brain tissue responses and were correlated with the site and occurrence of MTBI. Prediction indicated that the shear deformation around the brainstem region could be an injury predictor for concussion. Statistical analyses were performed to establish the new brain injury tolerance level and to further reduce brain injury severity.
A mobile networking system based on internet protocol(IP) (1993)

Due to advances in wireless communication technology there is a growing demand for providing continuous network access to the users of portable computers, regardless of their location. Existing network protocols cannot meet this requirement since they were designed with the assumption of a static network topology where hosts do not change their location over time. Based on IP&amp;apos;s Loose Source Route option, we have developed a scheme for providing transparent network access to mobile hosts. Our scheme is easy to implement, requires no changes to the existing set of hosts and routers, and achieves optimal routing in most cases. An outline of the proposed scheme is presented and a reference implementation is described. 1 Introduction In the last two years, we have witnessed two major changes in computer technology. First, portable computers which are as powerful as some desktop workstations in terms of computing power, memory, display, and disk storage, are beginning to appear. Second, wit...
Reviews British Wood-Engraved Book Illustration 1904–1940. A Break with Tradition. By SELBORNEJOANNA, Oxford, The Clarendon Press, 1998xxiii + 433. pp +212 black-and-white illustrations £70 ISBN 0 19 817408 X (2000)

Journal Article Reviews Get access British Wood-Engraved Book Illustration 1904–1940. A Break with Tradition. By JOANNA SELBORNE, Oxford, The Clarendon Press, 1998 xxiii + 433. pp +212 black-and-white illustrations £70 ISBN 0 19 817408 X PAUL GOLDMAN PAUL GOLDMAN Shaftesbury Search for other works by this author on: Oxford Academic Google Scholar The Library, Volume 1, Issue 1, March 2000, Pages 91–93, https://doi.org/10.1093/library/1.1.91 Published: 01 March 2000
Discovery of MFH290: A Potent and Highly Selective Covalent Inhibitor for Cyclin-Dependent Kinase 12/13 (2020)

Genetic depletion of cyclin-dependent kinase 12 (CDK12) or selective inhibition of an analog-sensitive CDK12 reduces DNA damage repair gene expression, but selective inhibition of endogenous CDK12 is difficult. Here, we report the development of MFH290, a novel cysteine (Cys)-directed covalent inhibitor of CDK12/13. MFH290 forms a covalent bond with Cys-1039 of CDK12, exhibits excellent kinome selectivity, inhibits the phosphorylation of serine-2 in the C-terminal domain (CTD) of RNA-polymerase II (Pol II), and reduces the expression of key DNA damage repair genes. Importantly, these effects were demonstrated to be CDK12-dependent as mutation of Cys-1039 rendered the kinase refractory to MFH290 and restored Pol II CTD phosphorylation and DNA damage repair gene expression. Consistent with its effect on DNA damage repair gene expression, MFH290 augments the antiproliferative effect of the PARP inhibitor olaparib.
Antimineralocorticoid Action of Progesterone in the Rat: Correlation of the Effect on Electrolyte Excretion and Interaction with Renal Mineralocorticoid Receptors* (1978)

The ability of progesterone to increase sodium excretion only in the presence of active mineralocorticoids has led to the suggestion that progesterone antagonizes mineralocorticoid action at the renal tubular level. We have examined the effects of progesterone and aldosterone on sodium and potassium excretion in adrenalectomized rats and have compared these results with the ability of progesterone to inhibit the binding of aldosterone to cytoplasmic and nuclear mineralocorticoid receptors. The administration of aldosterone to saline-loaded, adrenalectomized male rats resulted in a dose-dependent fall in the urinary sodium to potassium ratio with a near maximum effect produced by 1 μg aldosterone. Progesterone alone in doses of 10, 100, and 1000 μg had no significant effect on the sodium to potassium ratio, but when administered simultaneously with 1 μg aldosterone, the same concentrations of progesterone inhibited the effect of aldosterone in a dose-dependent manner; 1 mg progesterone completely blocked the effect of 1 μg aldosterone. Scatchard analysis of [3H]aldosterone binding to renal receptors in vitro in the presence of progesterone indicated that progesterone inhibited the binding of [3H]aldosterone to both mineralocorticoid and glucocorticoid receptors. Progesterone was -25% as active as aldosterone in inhibiting the formation of [3H]aldosterone complexes with renal cytoplasmic receptors and produced proportional decreases in the binding of [3H]aldosterone to Tris-extractable nuclear receptors and KCl-extractable chromatinbound receptors. The comparison of these in vitro receptor studies and in vivo bioassays suggests that progesterone-induced natriuresis results from inhibition of aldosterone binding to renal mineralocorticoid receptors. (Endocrinology102: 1686, 1978)
Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. (1992)

Decreased fibrinolytic capacity has been suggested to accelerate the process of arterial atherogenesis by facilitating thrombosis and fibrin deposition within developing atherosclerotic lesions. Type 1 plasminogen activator inhibitor (PAI-1) is the primary inhibitor of tissue-type plasminogen activator and has been found to be increased in a number of clinical conditions generally defined as prothrombotic. To investigate the potential role of this inhibitor in atherosclerosis, we examined the expression of PAI-1 mRNA in segments of 11 severely diseased and 5 relatively normal human arteries obtained from 16 different patients undergoing reconstructive surgery for aortic occlusive or aneurysmal disease. Densitometric scanning of RNA (Northern) blot autoradiograms revealed significantly increased levels of PAI-1 mRNA in severely atherosclerotic vessels (mean densitometric value, 1.7 +/- 0.28 SEM) compared with normal or mildly affected arteries (mean densitometric value, 0.63 +/- 0.09 SEM; P less than 0.05). In most instances, the level of PAI-1 mRNA was correlated with the degree of atherosclerosis. Analysis of adjacent tissue sections from the same patients by in situ hybridization demonstrated an abundance of PAI-1 mRNA-positive cells within the thickened intima of atherosclerotic arteries, mainly around the base of the plaque. PAI-1 mRNA could also be detected in cells scattered within the necrotic material and in endothelial cells of adventitial vessels. In contrast to these results, PAI-1 mRNA was visualized primarily within luminal endothelial cells of normal-appearing aortic tissue. Our data provide initial evidence for the increased expression of PAI-1 mRNA in severely atherosclerotic human arteries and suggest a role for PAI-1 in the progression of human atherosclerotic disease.
CloudLines: Compact Display of Event Episodes in Multiple Time-Series (2011)

We propose incremental logarithmic time-series technique as a way to deal with time-based representations of large and dynamic event data sets in limited space. Modern data visualization problems in the domains of news analysis, network security and financial applications, require visual analysis of incremental data, which poses specific challenges that are normally not solved by static visualizations. The incremental nature of the data implies that visualizations have to necessarily change their content and still provide comprehensible representations. In particular, in this paper we deal with the need to keep an eye on recent events together with providing a context on the past and to make relevant patterns accessible at any scale. Our technique adapts to the incoming data by taking care of the rate at which data items occur and by using a decay function to let the items fade away according to their relevance. Since access to details is also important, we also provide a novel distortion magnifying lens technique which takes into account the distortions introduced by the logarithmic time scale to augment readability in selected areas of interest. We demonstrate the validity of our techniques by applying them on incremental data coming from online news streams in different time frames.