gebhart/patrepeval huggingface dataset:
Use of combination of monoclonal antibodies directed against three distinct epitopes of a tumor‐associated antigen: Analysis of cell binding and internalization (1991)

Three monoclonal antibodies (MAbs), MOv17, MOv18 and MOv19 with tumor-restricted specificity for human ovarian carcinoma, were tested alone or in double combination with the aim of analyzing their binding and internalization behavior on different in vitro cell lines. Biochemical studies indicated that the 3 MAbs were directed against 3 epitopes of the same 38 kDa surface molecule. By immuno-electron-microscopy they exhibited a different internalization behavior since MOv17 induced evident endocytosis through coated vesicles, whereas MOv18 gave rise to occasional uncoated vesicles and MOv19 was completely unable to promote internalization of the relevant molecule. When tested 2 by 2 there was a binding synergy in one of the 9 possible combinations (125I-labelled MOv18 and unlabelled MOv19), but no change in the internalization behavior. The binding synergy, which was highly reproducible, was temperature-dependent and was also evident on glutaraldehyde-fixed cells. A metabolism involvement is therefore unlikely. This could be attributed to an easier accessibility of the CaMOv18 due to a conformational change of the molecule after MOv19 MAb binding.
Electrochromism in Photochromic Dithienylcyclopentenes (2003)

Both photochromic and unprecedented electrochromic properties have been observed for a class of 1,2-bis(3-thienyl)cyclopentene derivatives bearing either a thiophene or a phenyl group attached to the reactive carbon centers. These compounds can be interconverted between their colorless ring-open and colored ring-closed states using UV and visible light, respectively. They can also be catalytically transformed from their ring-closed states to their ring-open states through electrochemical or chemical oxidation.
Synthesis and Biological Evaluation of the 1-Arylpyrazole Class of σ1 Receptor Antagonists: Identification of 4-{2-[5-Methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862) (2012)

The synthesis and pharmacological activity of a new series of 1-arylpyrazoles as potent σ(1) receptor (σ(1)R) antagonists are reported. The new compounds were evaluated in vitro in human σ(1)R and guinea pig σ(2) receptor (σ(2)R) binding assays. The nature of the pyrazole substituents was crucial for activity, and a basic amine was shown to be necessary, in accordance with known receptor pharmacophores. A wide variety of amines and spacer lengths between the amino and pyrazole groups were tolerated, but only the ethylenoxy spacer and small cyclic amines provided compounds with sufficient selectivity for σ(1)R vs σ(2)R. The most selective compounds were further profiled, and compound 28, 4-{2-[5-methyl-1-(naphthalen-2-yl)-1H-pyrazol-3-yloxy]ethyl}morpholine (S1RA, E-52862), which showed high activity in the mouse capsaicin model of neurogenic pain, emerged as the most interesting candidate. In addition, compound 28 exerted dose-dependent antinociceptive effects in several neuropathic pain models. This, together with its good physicochemical, safety, and ADME properties, led compound 28 to be selected as clinical candidate.
Sequence similarities and cross-idiotypic specificity of L chains among human monoclonal IgM kappa with anti-gamma-globulin activity. (1985)

The complete amino acid sequence of five light chain variable (V) regions of human monoclonal IgM kappa rheumatoid factors (RF) was determined, and their cross-reactive idiotypes (CRI) were characterized with antibodies induced by immunization with synthetic peptides PSL2 and PSL3, corresponding to the second and third complementarity-determining regions (CDR) of the SIE light chain. Together with two additional RF studied previously, all seven RF belong to the V kappa IIIb sub-subgroup. The region encoded by the V kappa gene segment (positions 1 to 95) in all seven proteins was virtually identical in primary structure, whereas the sequence from positions 96 to 108 defined the usage of the J kappa 1 gene in three proteins and the J kappa 2 gene in four of them. Position 96 contributed by the recombination of the V kappa and J kappa gene segments showed the presence of four different amino acid residues. Both anti-PSL2 and anti-PSL3 bind efficiently to all separated L chains when analyzed by the Western blot technique, and the binding was inhibited specifically by the corresponding peptides. The results reveal that the majority of human IgM-RF light chains are derived from a single germ line V kappa gene or a family of closely related V kappa III germ line genes, and express two "primary structure-dependent" CRI, which are largely dependent on the amino acid sequence of the second and third light chain CDR.
Variability Among Human Umbilical Vein Endothelial Cultures (1995)

Article MetricsDownloadsCitationsNo data available.012AugSepOctNovDecJan900Total6 Months12 MonthsTotal number of downloads for the most recent 6 whole calendar months.
A Technique for Perfusion of the Previable Human Fetus (1958)

Summary A perfusion technique of the previable human fetus is described in detail. The fetuses survived 5–12 hours. ECG, blood pressure, and blood flow were recorded simultaneously. Examples of the oxygen consumption of hypo‐ and normo‐thermic fetuses are presented. Description d'une technique de perfusion du fætus humain préviable. Description détaillée d'une technique de perfusion du fætus humain préviable. Les foetus survécurent de 5 à 12 heures. L'ECG, la pression artérielle et le débit sanguin furent enregistrés simultanément. II est cité des exemples de la consommation d'oxy‐gène de fætus hypothermiques et normothermiques. Beschreibung einer Perfusionstechnik für den noch nicht lebensfähigen menschlichen Foetus. Eine Perfusionstechnik für den noch nicht lebensfähigen menschlichen Foetus wird ausführlich beschrieben. Die Foeten blieben 5–12 Stunden am Leben. EKG, Blutdruck und Blutströmungsgeschwindigkeit wurden gleichzeitig registriert. Beispiele von Sauer‐stoffverbrauch von hypo‐ und normothermischen Foeten werden angeführt. Descripción de una técnica de perfusión en el feto humano previable. Descripción detallada de una técnica de perfusión en el feto humano previable. Los fetos sobrevivieron durante 5 a 12 horas. El ECG, la presión y la circulateón sanguínea, fueron registrados simultáneamente. Expositión de ejemplos del consumo de oxígeno en fetos hipo‐ y normotérmicos.
DNA double-crossover molecules (1993)

DNA molecules containing two crossover sites between helical domains have been suggested as intermediates in recombination processes involving double-strand breaks. We have modeled these double-crossover structures in an oligonucleotide system. Whereas the relative orientations of the helical domains must be specified in designing these molecules, there are two broad classes of the molecules, the parallel, DP, and antiparallel, DA, molecules. The distance between crossover points must be specified as multiples of half-turns, in order to avoid torsional stress in this system; hence, there are two further subdivisions, those double-crossover molecules separated by odd, O, and even, E, numbers of half-turns. In addition, the parallel molecules with odd numbers of half-turns between crossovers must be divided into those with an excess major or wide-groove separation, W, or those with an excess minor- or narrow-groove separation, N. We have constructed models of all five of these classes, DAE, DAO, DPE, DPOW, and DPON. DPE molecules containing 1 and 2 helical turns between crossovers have been constructed; the DAE molecule contains 1 turn between crossovers, and the DAO, DPOW, and DPON molecules contain 1.5 helical turns between crossovers. None of the parallel molecules is well-behaved; the molecules either dissociate or form multimers when visualized on native polyacrylamide gels. In contrast, antiparallel molecules form single bands when assayed in this fashion. Hydroxyl radical autofootprinting analysis of these molecules reveals protection at expected sites of crossover and of occlusion, suggesting that all the complexes contain linear helix axes that are roughly coplanar between crossovers. However, the DPOW molecule and the DPE molecule with 2 turns between crossovers show decreased protection in the portion between crossovers, suggesting that their helices may bow in response to charge repulsion. We conclude that the helices between parallel double crossovers must be shielded from each other or distorted from linearity if they are to participate in recombination. We have analyzed the possibilities of branch migration and crossover isomerization in double-crossover molecules. Parallel molecules need no sequence symmetry beyond homology to branch migrate, but the sequence symmetry requirements for antiparallel molecules restrict migration to directly repetitive segments that iterate the sequence between crossovers. Crossover isomerization appears to be a very complex process in parallel double-crossover molecules, suggesting that it may be catalyzed by topoisomerases if it occurs within the cell.
Calculating Visions: Kennedy, Johnson, and Civil Rights. (1993)

In June 1963, in the midst of national turmoil brought about by civil rights demonstrations, John Kennedy sent his administration's first major civil rights bill to the Congress. Still unsure about this move, he asked his brother Robert, Do you think we did the right thing? Within days of assuming the presidency, Lyndon Johnson publicly committed himself to civil rights as a memorial to his predecessor. Privately he told Georgia's Senator Richard Russell, the leader of the South in Congress, Dick, you've got to get out of my way. I'm going to run you over. President Johnson would not compromise or equivocate on civil rights. John Kennedy of Massachusetts yielded to the pressure of events and became an ally of the movement, despite his fear that supporting civil rights could cost him votes in Congress and the nation. Lyndon Johnson of Texas, whom liberals loathed because he often gutted their prize legislation, became the committed champion of civil rights. Together their administrations became synonymous with the Second Reconstruction, though neither president had a prior record of strong civil rights commitment. Mark Stern explains how each man pursued power and votes, and ultimately redirected his own course of action and altered the nation's future.
ChemInform Abstract: HETEROCYCLIC SEVEN‐MEMBERED‐RING COMPOUNDS. XXIII. SYNTHESIS AND THERMOLYSIS BEHAVIORS OF 2‐METHYL‐4‐PHENYL‐1‐BENZOTHIEPINS (1979)

Abstract Ausgehend vom 2‐Methyl‐epoxyketon (I) wird durch Ringerweiterung das Diketon (II) gebildet, von dem aus die gewünschten Titelverbindungen (IIIa) sowie über den Enolether (IVa) die Titelverbindungen (IIIb) und (IIIc) durch Acetylierung bzw. Alkylierung erhalten werden.
Risk stratification in unstable angina. Prospective validation of the Braunwald classification (1995)

<h3>Objectives.</h3> —To validate the Braunwald classification of unstable angina as a predictor of in-hospital cardiac complications; to determine which factors of the Braunwald classification contributed significantly to this prediction; and to devise a method of combining these predictive factors into an overall odds ratio for complications. <h3>Design.</h3> —A validation cohort of consecutive patients followed prospectively for in-hospital cardiac complications including myocardial infarction and death. <h3>Setting.</h3> —A community-based academic medical center. <h3>Patients.</h3> —A total of 393 patients admitted consecutively to the coronary care and intermediate care units with unstable angina. <h3>Main Outcome Measures.</h3> —Major cardiac complications including death, myocardial infarction, congestive heart failure, cardiogenic shock, and severe ventricular dysrhythmias. <h3>Results.</h3> —Multiple logistic regression analysis identified four clinical factors used in the Braunwald classification that predicted the in-hospital occurrence of major cardiac complications: (1) myocardial infarction within less than 14 days (odds ratio [OR], 5.72; 95% confidence interval [CI], 1.92 to 16.97); (2) need for intravenous nitroglycerin (OR, 2.33; 95% CI, 1.31 to 4.17); (3) lack of β-blocker or calcium channel blocker prior to admission (OR, 3.83; 95% CI, 1.55 to 9.42); and (4) baseline ST depression (OR, 2.81; 95% CI, 1.45 to 5.47). Two other clinical factors, diabetes and age, were also significant predictors. Validation of this model using parametric and nonparametric bootstrap techniques revealed excellent agreement between the CIs for adjusted ORs derived from the multiple logistic regression and those derived from the bootstrap. <h3>Conclusions.</h3> —The classification of unstable angina proposed by Braunwald includes four factors that predict risk of major in-hospital cardiac complications. Specific factors used in this classification can be combined with diabetes and age to better stratify risk of major cardiac complications in this disorder using a simpler model. (<i>JAMA</i>. 1995;273:136-141)
Synthetic analogues of polynucleotides. Part XII. Synthesis of thymidine derivatives containing an oxyacetamido- or an oxyformamido-linkage instead of a phosphodiester group (1974)

The dinucleotide analogue thymidinylacetamido-[3′(O)→ 5′(C)]-5′-deoxythymidine was synthesised. The compound showed a hypochromic effect of about 10% at 268 nm. At pH 6·0–7·5 and 20° the compound was stable; in M-sodium hydroxide at 37° it was 50% hydrolysed after 3·4 h. 5′-Azido-5′-deoxythymidine was converted into its 3′-O-carboxymethyl derivative and this was reduced to give 5′-amino-3′-O-carboxymethyl-5′-deoxythymidine. Attempts to polymerise this compound were unsuccessful because of the ready formation of a lactam. Thymidinylformamido-[3′(O)→ 5′(C)]-5′-deoxythymidine was also synthesised. It showed a hypochromic effect of about 8% at 267 nm and was more stable to alkali than the acetamido-compound.
Yeast Saccharomyces cerevisiae selectable markers in pUC18 polylinkers (1990)

Abstract A set of plasmids was constructed that contain the yeast selectable markers HIS3 , LEU2 , TRP1 or URA3 embedded in the multiple cloning site of pUC18.
The Niagara Internet Query System. (2001)

: Many projections envision a future in which the Internet is populated with a vast number of Web-accessible XML files---a &amp;quot;World-Wide Database&amp;quot;. Recently, there has been a great deal of research into XML query languages to enable the execution of database-style queries over these XML files. However, merely being an XML query-processing engine does not render a system suitable for querying the Internet. A truly useful system must provide mechanisms to (a) find the XML files that are relevant to a given query, and (b) deal with remote data sources that either provide unpredictable data access and transfer rates, or are infinite streams, or both. The Niagara Internet Query System was designed from the bottom-up to provide these mechanisms. It finds relevant XML documents by using a novel collaboration between the Niagara XML-QL query processor and the Niagara &amp;quot;text-in-context&amp;quot; XML search engine. To handle infinite streams and data sources with unpredictable rates, it supports a...
Filtering of Muscle Artifact from the Electroencephalogram (1979)

When recorded by surface electrodes, the electroencephalogram (EEG) may contain unwanted signals due to depolarization of scalp muscles and various electrochemical effects at the surface-metal junction. The former artifacts, in particular, are difficult to remove by linear filtering. This design study indicates that a state-of-the-art non-linear filter which includes a matched-filter detector with likelihood-ratio decision logic can give significant performance improvement over a third-order linear low-pass filter typical of existing equipment. The same approach can be applied to related electrophysiological filtering problems.
Acidities and homolytic bond dissociation energies of the αC—H bonds in ketones in DMSO (1990)

Equilibrium acidities in DMSO are reported for nine cycloalkanones, acetone, acetophenone, and 19 of their α-substituted derivatives. Oxidation potentials in DMSO for the conjugate bases of most of these ketones are also reported. Combination of these E OX (A − ) and pK HA values gives estimates of the homolytic bond dissociation energies (BDEs) of the acidic C—H bonds in the ketones. The ΔBDEs, relative to the BDE of CH 3 -H, or a parent ketone, provide a measure of the radical stabilization energies (RSEs) of the corresponding radicals. The effects of successive α-Me and α-Ph substitutions on RSEs, relative to those of CH 3 COCH 2 -H or PhCOCH 2 -H, are similar to those reported in the gas phase for methane. The RSE for the MeĊHCOPh radical, relative to CH 3 • is 17 kcal/mol, which is smaller than the sum of the RSEs of the MeCH 2 • and PhCOCH 2 • radicals relative to CH 3 • (7 + 12 = 19), contrary to the prediction of the captodative postulate. When G in PhCOCH 2 G is PhCO, CH 3 CO, or CN the ΔBDEs (relative to PhCOCH 2 -H) are 0, 1, and 3 respectively; for MeCOCH 2 SO 2 Ph, PhCOCH 2 SO 2 Ph, and PhCOCH 2 NMe 3 + the ΔBDEs are −5, −2, and −4, respectively. The BDEs in C 5 , C 6 , C 7 , C 8 , C 10 , and C 12 cycloalkanones are within ±2.5 kcal/mol of that of 3-pentanone. Acetophenones bearing meta or para substituents all have BDEs of 93-94 kcal/mol. Ketone radical cations, [RCOR′] +• , appear to be superacids with estimated [Formula: see text] values below −25. Keywords: acidities, bond dissociation energies, ketones.
N-Heterocyclic Carbene-Stabilized Palladium Complexes as Organometallic Catalysts for Bioorthogonal Cross-Coupling Reactions (2014)

A small library of water-soluble N-heterocyclic carbene (NHC)-stabilized palladium complexes was prepared and applied for cross-couplings of biomolecules under mild conditions in water. Pd-NHC complexes bearing hydrophilic groups were demonstrated to be efficient catalysts for the Suzuki-Miyaura coupling of various unnatural amino acids and proteins bearing p-iodophenyl functional groups. We further utilized this catalytic system for the rapid bioorthogonal labeling of proteins on the surfaces of mammalian cells. These results demonstrated that NHC-stabilized metal complexes have potential utility in cellular systems.
Chromosomal location of the genes encoding the leukocyte adhesion receptors LFA-1, Mac-1 and p150,95. Identification of a gene cluster involved in cell adhesion. (1988)

The adhesion receptors Mac-1, LFA-1, and p150,95 are cell surface alpha/beta heterodimers that play a key role in leukocyte adhesion processes. The genes for Mac-1, LFA-1, and p150,95 alpha subunits have been located to chromosome 16 by means of Southern blot analysis using a series of somatic cell hybrids. Chromosomal in situ hybridization has demonstrated that the genes for the three alpha subunits map to the short arm of chromosome 16, between bands p11 and p13.1, defining a cluster of genes involved in leukocyte adhesion. The gene encoding the LFA-1/Mac-1/p150,95 beta subunit, and defective in leukocyte adhesion deficiency, has been located on chromosome 21, band q22. The leukocyte adhesion receptor alpha and beta subunits are mapped to chromosomal regions that have been shown to be involved in cytogenetic rearrangements in certain patients with acute myelomonocytic leukemia and the blast phase of chronic myelogenous leukemia, respectively.
Identification and characterization of a complete carnitine biosynthesis pathway in Candida albicans (2009)

Carnitine is an essential metabolite that enables intracellular transport of fatty acids and acetyl units. Here we show that the yeast Candida albicans can synthesize carnitine de novo, and we identify the 4 genes of the pathway. Null mutants of orf19.4316 (trimethyllysine dioxygenase), orf19.6306 (trimethylaminobutyraldehyde dehydrogenase), and orf19.7131 (butyrobetaine dioxygenase) lacked their respective enzymatic activities and were unable to utilize fatty acids, acetate, or ethanol as a sole carbon source, in accordance with the strict requirement for carnitine-mediated transport under these growth conditions. The second enzyme of carnitine biosynthesis, hydroxytrimethyllysine aldolase, is encoded by orf19.6305, a member of the threonine aldolase (TA) family in C. albicans. A strain lacking orf19.6305 showed strongly reduced growth on fatty acids and was unable to utilize either acetate or ethanol, but TA activity was unaffected. Growth of the null mutants on nonfermentable carbon sources is restored only by carnitine biosynthesis intermediates after the predicted enzymatic block in the pathway, which provides independent evidence for a specific defect in carnitine biosynthesis for each of the mutants. In conclusion, we have genetically characterized a complete carnitine biosynthesis pathway in C. albicans and show that a TA family member is mainly involved in the aldolytic cleavage of hydroxytrimethyllysine in vivo.
Sensing Antimonite and Arsenite at the Subattomole Level with Genetically Engineered Bioluminescent Bacteria (1997)

A highly sensitive and selective optical sensing system for antimonite has been developed using genetically engineered bacteria. The basis of this system is the ability of certain bacteria to survive in environments that are contaminated with antimonite, arsenite, and arsenate. The survival is conferred to the bacteria by the ars operon, which consists of five genes that code for three structural proteins, ArsA, ArsB, and ArsC, and two regulatory proteins, ArsD and ArsR. ArsA, ArsB, and ArsC form a protein pump system that extrudes antimonite, arsenite, and arsenate once these anions reach the cytoplasm of the bacterium. A method was developed for monitoring antimonite and arsenite by using a single plasmid that incorporates the regulatory gene of the extrusion system, arsR, and the genes of bacterial luciferase, luxA and luxB. In the designed plasmid, ArsR regulates the expression of bacterial luciferase in a manner that is dependent on the concentration of antimonite and arsenite in the sample. Thus, the bioluminescence emitted by luciferase can be related to the concentration of antimonite and arsenite in the sample. Concentrations for antimonite and arsenite in the order of 10(-5) M, which corresponds to subattomole levels, can be detected. This bacterial-based sensing system is highly selective for antimonite and arsenite.
Oral Insulin Delivery: How Far are We? (2013)

Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The mainbarriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized.