gebhart/patrepeval huggingface dataset:
Differential killing of CD56-expressing cells by drug-conjugated human antibodies targeting membrane-distal and membrane-proximal non-overlapping epitopes (2016)

CD56 (NCAM, neural cell adhesion molecule) is over-expressed in many tumor types, including neuroblastoma, multiple myeloma, small cell lung cancer, ovarian cancer, acute myeloid leukemia, NK-T lymphoma, neuroendocrine cancer and pancreatic cancer. Using phage display, we identified 2 high-affinity anti-CD56 human monoclonal antibodies (mAbs), m900 and m906, which bound to spatially separated non-overlapping epitopes with similar affinity (equilibrium dissociation constant 2.9 and 4.5 nM, respectively). m900 bound to the membrane proximal fibronectin type III-like domains, whereas m906 bound to the N-terminal IgG-like domains. m906 induced significant down-regulation of CD56 in 4 neuroblastoma cell lines tested, while m900-induced downregulation of CD56 was much lower. Antibody-drug conjugates (ADCs) made by conjugation with a highly potent pyrrolobenzodiazepine dimer (PBD) exhibited killing activity that correlated with CD56 down-regulation, and to some extent with in vivo binding ability of the antibodies. The m906PBD ADC was much more potent than m900PBD, likely due to higher CD56-mediated downregulation and stronger binding to cells. Treatment with m906PBD ADC resulted in very potent cytotoxicity (IC50: 0.05–1.7 pM). These results suggest a novel approach for targeting CD56-expressing neuroblastoma cells. Further studies in animal models and in humans are needed to find whether these antibodies and their drug conjugates are promising candidate therapeutics.
Aromatase: Contributions to Physiology and Disease in Women and Men (2016)

Aromatase (estrogen synthetase; EC 1.14.14.1) catalyzes the demethylation of androgens' carbon 19, producing phenolic 18-carbon estrogens. Aromatase is most widely known for its roles in reproduction and reproductive system diseases, and as a target for inhibitor therapy in estrogen-sensitive diseases including cancer, endometriosis, and leiomyoma (141, 143). However, all tissues contain estrogen receptor-expressing cells, the majority of genes have a complete or partial estrogen response element that regulates their expression (61), and there are plentiful nonreceptor effects of estrogens (79); therefore, the effect of aromatase through the provision of estrogen is almost universal in terms of health and disease. This review will provide a brief but comprehensive overview of the enzyme, its role in steroidogenesis, the problems that arise with its functional mutations and mishaps, the roles in human physiology of aromatase and its product estrogens, its current clinical roles, and the effects of aromatase inhibitors. While much of the story is that of the consequences of the formation of its product estrogens, we also will address alternative enzymatic roles of aromatase as a demethylase or nonenzymatic actions of this versatile molecule. Although this short review is meant to be thorough, it is by no means exhaustive; rather, it is meant to reflect the cutting-edge, exciting properties and possibilities of this ancient enzyme and its products.
Synthesis of Substituted Pyrimidine Hydrazine Acids (PHA) and Their Use in Peptide Recognition (2006)

Substituted pyrimidine-hydrazine-acids (PHA) were prepared from orotic acid in five synthetic steps and high yields.Their geometry of hydrogen bond acceptor and donor sites make them suitable for the molecular recognition of peptide β-sheets.In non-protic solvents the PHA unit emits at around 420 nm after irradiation at 281 nm.The emission intensity decreases upon peptide binding and signals the binding event.Peptides consisting of PHAs and natural amino acids or a turn structure motif were prepared.The investigation of the intramolecular binding pattern by NMR spectroscopy revealed the expected interaction of the PHA and peptide β-sheet.Scheme 5: HMBC-spectrum of 6a in deuterated DMSO.However, the X-Ray structure of 6a does not show the assumed intramolecular hydrogen bond of the proton on hydrazine nitrogen and the pyrimidin nitrogen.The temperature dependence of the 1 H NMR chemical shift of the NH 2 proton (-5.15 ppb/K) in 10 mmol solution CDCl 3 reflects its state of hydrogen bonding.The course of the subsequent substitution in 2-position with N-nucleophiles depends on the halogen atom.Chlorine substitution occurs only when activated with DMAP in situ.
Synthesis and Evaluation of Bishydroquinone Derivatives of (−)-Saframycin A:  Identification of a Versatile Molecular Template Imparting Potent Antiproliferative Activity (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSynthesis and Evaluation of Bishydroquinone Derivatives of (−)-Saframycin A: Identification of a Versatile Molecular Template Imparting Potent Antiproliferative ActivityAndrew G. Myers and Alleyn T. PlowrightView Author Information Department of Chemistry and Chemical Biology Harvard University, Cambridge, Massachusetts 02138 Cite this: J. Am. Chem. Soc. 2001, 123, 21, 5114–5115Publication Date (Web):May 8, 2001Publication History Received5 February 2001Published online8 May 2001Published inissue 1 May 2001https://pubs.acs.org/doi/10.1021/ja0103086https://doi.org/10.1021/ja0103086rapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views731Altmetric-Citations46LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Amides,Assays,Modification,Pharmaceuticals,Reaction products Get e-Alerts
Effect of HMG-CoA Reductase Inhibitors on Coronary Artery Disease as Assessed by Electron-Beam Computed Tomography (1998)

The extent to which the volume of atherosclerotic plaque decreased, stabilized, or increased was directly related to treatment with HMG-CoA reductase inhibitors and the resulting serum LDL cholesterol levels. These changes can be determined noninvasively by electron-beam CT and quantified with use of a calcium-volume score.
A comparison of the activities of lacticin 3147 and nisin against drug-resistant Staphylococcus aureus and Enterococcus species (2009)

Nisin is more effective against S. aureus whereas lacticin 3147 possesses greater potency against VRE. The modifications responsible for the vancomycin-resistant phenotypes of hVISA and VISA strains also provide protection against the two lantibiotics.
A Model of Silicon Carbide Chemical Vapor Deposition (1991)

We present a model describing the interacting gas phase and surface chemistry present during the steady‐state chemical vapor deposition (CVD) of silicon carbide . In this work, we treat the case of steady‐state deposition of from silane and propane mixtures in hydrogen carrier gas at one atmosphere pressure. Epitaxial deposition is assumed to occur on a pre‐existing epitaxial silicon carbide crystal. Pyrolysis of and is modeled by 83 elementary gas‐phase reactions. A set of 36 reactions of gas‐phase species with the surface is used to simulate the deposition process. Rates for the gas/surface reactions were obtained from experimental measurements of sticking coefficients in the literature and theoretical estimates. Our results represent the first simulation of a silicon carbide deposition process that includes detailed descriptions of both the gas phase and surface reactions. The chemical reaction mechanism is also combined with a model of a rotating disk reactor (RDR), which is a convenient way to study the interaction of chemical reactions with fluid mechanics. Transport of species from the gas to the surface is accounted for using multicomponent transport properties. Predictions of deposition rates as a function of susceptor temperature, disk rotation rate, and reactant partial pressure are presented. In addition, velocity, temperature, and concentration profiles normal to the heated disk for 41 gas‐phase species are determined using reactor conditions typical of epitaxial silicon carbide deposition on silicon substrates.
Magnesium Motorcycle Wheels For Racing Applications (2000)

The main portion of wheels (approx. 70%) used for the 2000 world championship are made of magnesium sandast alloy AZ91. Further 20% are carbon fibre compound wheels exclusively fitted on Aprilia motorcycles. Only 10% are forged magnesium wheels, however, the demand is increasing due to high weight saving potential compared to the sand cast version.
High power laser cutting of CFRP, and laser direct joining of CFRP to metal (2010)

CFRP possesses an extremely high specific strength, and thus the development of cutting and joining technology of CFRP is expected for the increase in applications in various industrial fields. To obtain fine cut quality in CFRP, high-quality disk lasers are applied to various types and kinds of CFRP. It was understood that fine cut quality could be produced in some CFRP with a small focused laser beam at an extremely fast speed. Joints between Type 304 plate (of 3 mm thickness and 30 mm width) and CFRP sheet (of 2 mm thickness and 20 mm width) were produced with a disc laser. The joint possessed a high shear tensile load of about 4800 N, and the fracture occurred in the CFRP near the lap joint.
Galileo Signal Generation. Simulation Analysis (2009)

Projecte realitzat eb col.laboracio amb el Department of Computer and Electronic Engineering. University of Limerick
Fast-Start (2001)

Availability requirements for database systems are more stringent than ever before with the widespread use of databases as the foundation for ebusiness. This paper highlights Fast-Start™ Fault Recovery, an important availability feature in Oracle, designed to expedite recovery from unplanned outages. Fast-Start allows the administrator to configure a running system to impose predictable bounds on the time required for crash recovery. For instance, fast-start allows fine-grained control over the duration of the roll-forward phase of crash recovery by adaptively varying the rate of checkpointing with minimal impact on online performance. Persistent transaction locking in Oracle allows normal online processing to be resumed while the rollback phase of recovery is still in progress, and fast-start allows quick and transparent rollback of changes made by uncommitted transactions prior to a crash.
Synthesis and characterization of N2-(p-n-butylphenyl)-2'-deoxyguanosine and its 5'-triphosphate and their inhibition of HeLa DNA polymerase .alpha. (1984)

N2-(p-n-Butylphenyl)-2'-deoxyguanosine (BuPdG) and its 5'-triphosphate (BuPdGTP), expected to be inhibitors of eukaryotic DNA polymerase alpha, have been synthesized. BuPdG was synthesized by two methods and characterized by 1H NMR and by chemical relation to guanosine. Direct synthesis involving silylated N2-(p-n-butylphenyl)guanine (BuPG) and 1-chloro-3,5-di-p-toluoyl-2-deoxyribofuranose in the presence of trimethylsilyl trifluoromethanesulfonate gave one alpha and two beta isomers of deoxyribonucleoside as determined by 1H NMR. However, NMR and UV spectra were equivocal in distinguishing between 7 and 9 isomers. The identity of the desired 9-beta-BuPdG was ultimately proved by its independent synthesis from the corresponding ribonucleoside. 1H NMR spectra of the O'-acetylated ribonucleosides of BuPG showed characteristic patterns of O'-acetylated guanosines, and their identity was proved by relating the products of the reaction of isomeric O'-acetylated 2-bromoinosines with p-n-butylaniline and with ammonia: the 2-bromoinosine which gave guanosine also gave the suspected 9-beta-ribonucleoside, BuPGr, and that which gave N7-beta-ribofuranosylguanine also gave the 7-beta isomer of BuPGr. BuPGr was transformed in a multistep procedure to give BuPdG, identical with the major beta isomer obtained by direct deoxynucleoside synthesis. The 5'-monophosphate of BuPdG was obtained by treatment of the nucleoside with phosphoryl chloride in trimethyl phosphate; the monophosphate reacted as the phosphoimidazolyl derivative with pyrophosphate to yield the 5'-triphosphate, BuPdGTP.(ABSTRACT TRUNCATED AT 250 WORDS)
Experimental demonstration of high-power fast-rise-time switching in silicon junction semiconductors (1976)

Experimental results are presented demonstrating fast turn-on and high power-handling capability in light-activated silicon junction (PNPN) devices. Rise time to 2 ns, rate of current rise to 760 kA/μs, and switched power level of 10 MW were demonstrated.
Contribution of PAI-1 in cardiovascular pathology. (2004)

Plasminogen activator inhibitor-1 (PAI-1), is a serpin whose major function is to negate plasminogen activation and impair fibrinolysis. It occurs in plasma and tissues. Studies in genetically modified mice indicate that PAI-1 might be involved in thrombosis, vascular healing and atherosclerosis although contradictory findings have been obtained in the latter two processes. Differences between results depend on the types and the lengths of the models and underline the fact that besides its role in regulating fibrinolysis, PAI-1 plays a role in several cellular processes independent of plasminogen activation. In patients, high plasma PAI-1 levels worsen the prognosis of myocardial infarction in the acute phase and have been considered as a risk factor for coronary heart disease. The predictive capacity of PAI-1 is mainly related to several metabolic covariates which constitute the metabolic syndrome (MS). This syndrome is associated with increased cardiovascular morbidity and mortality and is becoming one of the major health problems as its prevalence is growing rapidly. Accelerated atherothrombotic process in the MS is attributed not only to metabolic abnormalities but also to a specific inflammatory state which leads to increased plasma PAI-1 levels. Modifying PAI-1 expression by PAI-1 inhibitors may open a new field of research and may reveal the true role of PAI-1 in atherosclerotic and insulin resistance processes.
The Kinship Theory of Genomic Imprinting (2000)

▪ Abstract The inclusive fitness effect attributable to an allele can be divided into an effect on matrilineal kin when the allele is maternally derived and an effect on patrilineal kin when paternally derived. However, the allele is not subject to selection on its effects on patrilineal kin when maternally derived nor on its effects on matrilineal kin when paternally derived. As a result, natural selection may favor alleles with effects that differ, depending on the allele's parental origin. At autosomal loci, this process is predicted to lead to the silencing of alleles when inherited from one or the other parent. At X-linked loci subject to random X inactivation, the process is predicted to lead to quantitative differences of expression between maternal and paternal alleles but not to complete silencing of one allele. The implications of this theory and some challenges to the theory are reviewed.
Changes in Molecular Size Distribution of Cellulose during Attack by White Rot and Brown Rot Fungi (1992)

The kinetics of cotton cellulose depolymerization by the brown rot fungus Postia placenta and the white rot fungus Phanerochaete chrysosporium were investigated with solid-state cultures. The degree of polymerization (DP; the average number of glucosyl residues per cellulose molecule) of cellulose removed from soil-block cultures during degradation by P. placenta was first determined viscosimetrically. Changes in molecular size distribution of cellulose attacked by either fungus were then determined by size exclusion chromatography as the tricarbanilate derivative. The first study with P. placenta revealed two phases of depolymerization: a rapid decrease to a DP of approximately 800 and then a slower decrease to a DP of approximately 250. Almost all depolymerization occurred before weight loss. Determination of the molecular size distribution of cellulose during attack by the brown rot fungus revealed single major peaks centered over progressively lower DPs. Cellulose attacked by P. chrysosporium was continuously consumed and showed a different pattern of change in molecular size distribution than cellulose attacked by P. placenta. At first, a broad peak which shifted at a slightly lower average DP appeared, but as attack progressed the peak narrowed and the average DP increased slightly. From these results, it is apparent that the mechanism of cellulose degradation differs fundamentally between brown and white rot fungi, as represented by the species studied here. We conclude that the brown rot fungus cleaved completely through the amorphous regions of the cellulose microfibrils, whereas the white rot fungus attacked the surfaces of the microfibrils, resulting in a progressive erosion.
Spontaneous REM Sleep Is Modulated By the Activation of the Pedunculopontine Tegmental GABA<sub>B</sub> Receptors in the Freely Moving Rat (2004)

Considerable evidence suggests that the neurotransmitter gamma-aminobutyric acid (GABA)-ergic system and pedunculopontine tegmentum (PPT) in the brain stem are critically involved in the regulation of rapid-eye-movement (REM) sleep. GABA and its various receptors are normally present in the PPT cholinergic cell compartment. The aim of this study was to identify the role of GABA and its receptors in the regulation of REM sleep. To achieve this aim, specific receptors were activated differentially by local microinjection of selective GABA receptor agonists into the PPT while quantifying its effects on REM sleep in freely moving chronically instrumented rats (n = 21). The results demonstrated that when GABAB receptors were activated by local microinjection of a GABAB receptor selective agonist, baclofen, spontaneous REM sleep was suppressed in a dose-dependent manner. The optimum dose for REM sleep reduction was 1.5 nmol. In contrast, when GABAA and GABAC receptors were activated by microinjecting their receptor selective agonists, isoguvacine (ISGV) and cis-4-aminocrotonic acid (CACA), respectively, the total percentages of REM sleep did not change compared with the control values. In another eight freely moving rats, effects of baclofen application was tested on firing rates of REM-on cells (n = 12). Of those 12 neurons, 11 stopped firing immediately after application of baclofen [latency: 50 +/- 14 s (SD)] and remained almost silent for 130 +/- 12 min. Findings of the present study provide direct evidence that the PPT GABAB receptors and REM-on cells are involved in the regulation of REM sleep.
Microbial adherence to and invasion through proteoglycans (1997)

A large array of glycoproteins, glycolipids, and proteoglycans decorate the surfaces of animal cells. These glycoconjugates mediate many fundamental cellular processes, including cell-cell and cell-matrix adhesion, motility, growth, and signaling (28, 110). Over time, many pathogenic microorganisms have learned to exploit cell surface glycoconjugates as receptors for attachment, a process which ultimately facilitates tissue colonization and invasion. The interaction of specific proteins on the surface of microorganisms (adhesins) with carbohydrate chains on the glycoconjugate (receptors) enables the microbes to take their first step towards establishing an infection. This review concentrates on proteoglycans as adhesion receptors for bacteria, viruses, and parasites. Microbial binding to glycolipids and glycoproteins also occurs and has been discussed elsewhere (27, 40, 61–63, 85, 94). Proteoglycans are ubiquitous among animal cells, and as discussed below, their carbohydrate chains (glycosaminoglycans) bind many different protein ligands. Different experimental criteria have been used to establish a role for proteoglycans in attachment and invasion of host cells, including direct binding measurements, identification of microbial carbohydrate-binding proteins, competition studies with defined polysaccharides, loss of adhesion upon enzymatic removal of host glycans, and altered adherence to animal cell mutants with defective glycosaminoglycan biosynthesis. Overall, the experimental evidence for microbial adhesion to host cell proteoglycans is compelling, and future molecular studies may provide a basis for designing therapeutic strategies based on these interactions.
THE EFFECT OF LIVER TRANSPLANTATION IN A 13-YEAR-OLD BOY WITH ERYTHROPOIETIC PROTOPORPHYRIA (1988)

A 13-year-old boy who had had recurrent photosensitive skin reactions due to erythropoietic protoporphyria from 18 months of age, suddenly developed rapidly progressive hepatic failure with increasing cholestatic jaundice and variceal bleeding. Liver biopsy confirmed extensive protoporphyrin deposition with cirrhosis, and so orthotopic liver transplantation was performed. Postoperatively his skin rash settled within 72 hr, and in spite of subsequent exposure to the sun he has had no further skin reaction or blistering, although he does still have some itching. He made a good recovery and was able to return to school within six months of operation. Prior to liver transplantation, the hepatic ferrochelatase activity was reduced to only 0.81 nmol zinc-protoporphyrin formed/mg protein/hr (controls 3.30 +/- 1.00 nmol zinc-protoporphyrin formed/mg protein/hr, while the red cell protoporphyrin level was markedly elevated at 188 mumol/L red cells (normal less than 1.6 mumol/L red cells). The free plasma porphyrin level of 0.95 mumol/L (normal less than 0.02 mumol/L), and the urinary and fecal porphyrin levels were also raised. Following liver grafting these elevated porphyrin levels fell rapidly, with the red cell protoporphyrin level dropping to 10% of its preoperative value, and the rest returning to virtually normal within three months of operation.
Scrotal haematoma: the most common complication of no-scalpel vasectomy. (2010)

the most common complication of no-scalpel vasectomy was scrotal haematoma and other complications are wound infection, scrotal sinus, vasectomy failure and sperm granuloma. Key words: no scalpel vasectomy, scrotal haematoma, scrotal sinus, sperm granuloma.
Ritter's reaction of poly(acrylonitrile) (1981)

Abstract The course of Ritter's reaction of atactic poly(acrylonitrile) with N ‐hydroxymethylamides of acetic, benzoic and benzenesulfonic acids and with N ‐hydroxymethylimides of succinic, phthalic and o ‐sulfobenzoic acids were examined in tetramethylene sulfone under conditions where benzyl alcohol, isopropyl alcohol and triphenylmethanol appear as nonreactive. The reaction systems have a stronger tendency towards crosslinking than that exhibited under comparable conditions by solutions of poly( N ‐benzamidomethylacrylamide), poly( N ‐phthalimidomethylacrylamide) and poly( N ‐ o ‐sulfobenzamidomethylacrylamide) prepared as reference standards by the solution polymerization of the N ‐substituted acrylamides in methanol with dibenzoyl peroxide as initiator.