gebhart/patrepeval huggingface dataset:
Neuronal Nicotinic Acetylcholine Receptors as Targets for Drug Discovery (1997)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTNeuronal Nicotinic Acetylcholine Receptors as Targets for Drug Discovery†Mark W. Holladay, Michael J. Dart, and John K. LynchView Author Information Neurological and Urological Diseases Research D-47W, Abbott Laboratories, Abbott Park, Illinois 60064-3500 Cite this: J. Med. Chem. 1997, 40, 26, 4169–4194Publication Date (Web):December 19, 1997Publication History Received9 June 1997Published online19 December 1997Published inissue 1 December 1997https://pubs.acs.org/doi/10.1021/jm970377ohttps://doi.org/10.1021/jm970377oreview-articleACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views2143Altmetric-Citations373LEARN 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-Alertsclose SUBJECTS:Agonists,Nicotine,Receptors,Rodent models,Screening assays Get e-Alerts
Reliability characteristics of NiSi nanocrystals embedded in oxide and nitride layers for nonvolatile memory application (2008)

The authors provided the reliability characteristics of nonvolatile nickel-silicide nanocrystal memories embedded in oxide and nitride layers for next-generation nonvolatile memory application. The charge trapping layer was deposited by sputtering a commixed target in the argon and oxygen/nitrogen ambiances, and then using a low temperature rapid thermal annealing to form nanocrystals. Transmission electron microscope clearly shows the sharpness and the density of nanocrystals. These proposed memory structures were compared for the charge storage ability, retention, and endurance. In addition, we used a simple simulation of electric field for nonvolatile nanocrystals memory to explain the advantages by using the high-k dielectric.
Expression of immunogenic epitopes of hepatitis B surface antigen with hybrid flagellin proteins by a vaccine strain of Salmonella. (1989)

A nonvirulent Salmonella dublin flagellin-negative, aromatic-dependent live vaccine strain has been used to express hepatitis B virus surface antigen epitopes in an immunogenic form. The envelope proteins of the virion are encoded by the S gene, which contains the pre-S1, pre-S2, and S coding regions. Synthetic oligonucleotides corresponding to amino acid residues S-(122-137) and pre-S2-(120-145) were inserted in-frame into the hypervariable region of a cloned Salmonella flagellin gene, and the recombinant plasmids were introduced into a flagellin-negative aroA mutant live vaccine strain of S. dublin, SL5928. The flagellin gene was expressed in bacteria carrying the plasmids as detected by immunoblotting with anti-flagellin (H1-d) serum. Both the S and pre-S2 epitopes were detected in bacteria carrying the relevant plasmid by immunoblotting with anti-HBs (antibody to hepatitis B virus surface antigen) and anti-peptide antisera. Animals immunized intramuscularly or orally with the live recombinant bacteria developed antibodies specific to these hepatitis B virus epitopes as detected by ELISA.
Picosecond and subpicosecond optoelectronics for measurements of future high speed electronic devices (1983)

The electrooptic effect has been used in conjunction with 100 fs optical pulses to sample electrical transients with an unprecedented resolution of .5 ps and sensitivity of 50-100 µV. The electrooptic material can be used in a traveling wave geometry or in an electrodeless manner. Applications of this technique to the characterization of electrical devices and to the study of short pulse propagation are described.
Highly Stereospecific, Cross-Coupling Reactions of Alkenylsilacyclobutanes (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTHighly Stereospecific, Cross-Coupling Reactions of AlkenylsilacyclobutanesScott E. Denmark and Jun Young ChoiView Author Information Roger Adams Laboratory, Department of Chemistry University of Illinois, Urbana, Illinois 61801 Cite this: J. Am. Chem. Soc. 1999, 121, 24, 5821–5822Publication Date (Web):June 6, 1999Publication History Received15 March 1999Published online6 June 1999Published inissue 1 June 1999https://pubs.acs.org/doi/10.1021/ja9908117https://doi.org/10.1021/ja9908117rapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views3238Altmetric-Citations184LEARN 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:Anions,Byproducts,Chemical reactions,Halogens,Inorganic compounds Get e-Alerts
The performance of the 1987 ARA classification criteria for rheumatoid arthritis in a population based cohort of patients with early inflammatory polyarthritis. American Rheumatism Association. (1998)

. Among patients newly presenting with IP, the 1987 ARA criteria for RA had a low ability to discriminate between patients who developed persistent, disabling, or erosive disease and those who did not. Alternative criteria are required for studies investigating early RA.
Physicochemical and Pharmacokinetic Characterization of Highly Potent Recombinant l-Methionine γ-Lyase Conjugated with Polyethylene Glycol as an Antitumor Agent (2006)

A highly potent recombinant L-methionine gamma-lyase (METase) conjugated with polyethylene glycol (PEG) was characterized physicochemically and pharmacokinetically in vivo and in vitro. Pegylated METase (PEG-METase), which contains pyridoxal 5'-phosphate (PLP) as a cofactor in the molecule, is a potent anticancer agent that can deplete L-methionine from plasma. Although pegylation decreased its specific activity, dithiothreitol (DTT) treatment increased it over three times with the detachment of one PEG moiety modified with a cysteine residue. We can produce DTT-treated PEG-METase on a large scale in sufficient quality for therapeutic use. The superiority of DTT-treated PEG-METase was confirmed by the enhancement of L-methionine depletion and amelioration of pharmacokinetics in mice. The holoenzyme of DTT-treated PEG-METase gave a several times larger area under the plasma concentration curve than that of DTT-untreated PEG-METase, not because of an increase of the half-life but because of high specific activity. Conversely, simultaneous PLP infusion led to a greatly increased half-life of the holoenzyme. DTT-treated PEG-METase administration with PLP infusion was the most useful combination for maximizing the potency of the enzyme. We showed that serum albumin interfered with holoenzyme activity in vitro. The decrease of holoenzyme activity was dependent on the type of serum albumin. We concluded that PLP was released from PEG-METase by serum albumin in vivo and in vitro. The deleterious effect of PLP dissociation from PEG-METase could be improved by supplementing PLP and oleic acid. Their synergistic effect in preventing a decrease of the holoenzyme activity was also observed.
An optimum parallel architecture for high-speed real-time digital signal processing (1988)

The authors describe a parallel processing architecture for real-time digital signal processing that has demonstrated virtually 100% data processing efficiency in a number of areas. The Teamed-Architecture Signal Processor (T-ASP) is a field-proven, commercially available optimal system solution to the extremely high computational and I/O rates encountered in modern digital-signal-processing environments. The design of T-ASP involves the consideration and implementation of many architectural concepts used to enhance the performance of a computer, including programmability, parallel processing, vector processing and pipelining, memory interleaving, double cache memories, multiple high-speed I/O interfaces, and segmentation of the processors for elimination of both CPU and data-handling overhead. The authors discuss hardware architecture design and implementation; hardware management; and software architecture design and implementation.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Thin film shape memory alloy microactuators (1996)

Thin film shape memory alloys (SMAs) have the potential to become a primary actuating mechanism for mechanical devices with dimensions in the micron-to-millimeter range requiring large forces over long displacements. The work output per volume of thin film SMA microactuators exceeds that of other microactuation mechanisms such as electrostatic, magnetic, thermal bimorph, piezoelectric, and thermopneumatic, and it is possible to achieve cycling frequencies on the order of 100 Hz due to the rapid heat transfer rates associated with thin film devices. In this paper, a quantitative comparison of several microactuation schemes is made, techniques for depositing and characterizing Ni-Ti-based shape memory films are evaluated, and micromachining and design issues for SMA microactuators are discussed. The substrate curvature method is used to investigate the thermo-mechanical properties of Ni-Ti-Cu SMA films, revealing recoverable stresses up to 510 MPa, transformation temperatures above 32/spl deg/C, and hysteresis widths between 5 and 13/spl deg/C. Fatigue data shows that for small strains, applied loads up to 350 MPa can be sustained for thousands of cycles. Two micromachined shape memory-actuated devices-a microgripper and microvalve-also are presented.
Heparin prevents antigen-induced airway hyperresponsiveness: interference with IP3-mediated mast cell degranulation? (1994)

We hypothesized that heparin, because of its antiallergic and/or anti-inflammatory properties, modifies airway hyperresponsiveness (AHR). We studied the effects of inhaled heparin on AHR induced by specific antigen or by platelet-activating factor (PAF), a proinflammatory mediator. Specific lung resistance (sRL) was measured in 17 allergic sheep before, immediately after, and serially for up to 2 h after airway challenge with either specific antigen or PAF. Airway responsiveness was expressed as the cumulative provocative dose of carbachol that increased sRL to 4 cmH2O/s [PD4, in breath units (BU; 1 BU = 1 breath of 1% carbachol solution)]. PD4 was determined on a baseline day and on various experimental days 2 h after airway challenge with antigen or PAF, without or after pretreatment with inhaled heparin (1,000 U/kg). Pretreatment with inhaled heparin prevented antigen-induced bronchoconstriction and postantigen AHR. PD4 was 26 +/- 2.6 (SE), 12 +/- 1.7, and 22 +/- 2.8 BU on baseline, antigen control, and postheparin days, respectively. Heparin given immediately after the antigen challenge failed to modify the magnitude and/or duration of antigen-induced bronchoconstrictor response or postantigen AHR. Heparin also failed to prevent PAF-induced changes in sRL and AHR. In vitro heparin inhibited anti-immunoglobin E- and 1,4,5-inositol triphosphate-mediated degranulation of rat peritoneal mast cells without attenuating the effects of the Ca2+ ionophore A-23187. These data suggest that in “acute responders” heparin prevents antigen-induced bronchoconstriction and AHR, possibly by inhibiting 1,4,5-inositol triphosphate-dependent mast cell mediator release and not by its anti-inflammatory action.
Stress and yielding studies using critical refracted longitudinal wave (1996)

This paper presents some of the recent work on stress evaluation using the L{sub CR} ultrasonic technique. A sample of 4140 steel, typically used for turbine components, was tested. The acoustoelastic phenomenon was evaluated using probe sets of three different frequencies, 1MHz, 2.25MHz and 5MHz. Slightly different acoustoelastic constants for each frequency were obtained in the elastic region, at up to 80% yield strength. Data obtained past yield on the same specimen using 5 MHz probe set provided some very interesting results. For all of the tests with loading below the yield point, the return to no-load L{sub CR} travel time variations were within {+-}2 ns, (0.026%). When the load passed the yield point, the return to no-load L{sub CR} travel-time showed a distinct change. A 12.8% residual strain resulted in a 15 ns (0.198%) change in the no-load travel time. These results indicate that the L{sub CR} ultrasonic technique can not only provide the applied and residual stress information, but also may be capable of predicting the prior yield situation in the components.
Expression of C-reactive protein by alveolar macrophages (1996)

C-reactive protein (CRP) is well characterized as one of the serum acute phase proteins, the levels of which increase dramatically after infection. CRP has been shown to be involved in multiple immunoregulatory functions. For example, it activates the classical complement cascade, opsonizes bacteria for phagocytosis, and stimulates phagocytic cells. Although CRP is predominantly produced and secreted by hepatocytes, other cells including subsets of lymphocytes, Kupffer cells, and blood monocytes have been shown to synthesize this protein as well. We hypothesized that CRP may be produced in the lung, and therefore it could function directly in pulmonary host defense. Western blot analysis showed that CRP was present in the lung tissue, lung lavage, and alveolar macrophages. This result was further confirmed by immunohistochemical staining of lung sections that showed the localization of CRP in alveolar macrophages. The CRP mRNA was detected subsequently by reverse-transcriptase PCR (RT-PCR), and a single amplified product was obtained from alveolar macrophages as well as from whole lung tissue. Both were the same size as the amplified product obtained from liver mRNA. Furthermore, in situ hybridization with CRP riboprobe demonstrated specific staining of alveolar macrophages both in lung sections and isolated cells. In addition, in situ hybridization showed that CRP mRNA levels in isolated alveolar macrophages were up-regulated by in vitro LPS stimulation. In summary, these results indicate that CRP is produced by alveolar macrophages, and suggest that CRP may be involved in the pulmonary immune response.
Alzheimer disease: measuring loss of cerebral gray matter with MR imaging. (1991)

The distributions of the cerebral gray matter, the white matter, and the intracranial cerebrospinal fluid (CSF) were measured in 14 patients with Alzheimer disease (AD) and in 14 healthy control subjects. The measurements, derived from two specifically designed magnetic resonance inversion-recovery sequences, compensate for partial signal averaging. The percentage of the gray matter in the brains of AD patients (44.9% +/- 4.4) was significantly lower than in control subjects (50.2% +/- 3.2). The most significant reduction (P less than .001) occurred in the temporal lobes (13.8%) and a central region (12.8); the reduction in frontal lobe (11.2%) and occipital lobe (9.2%) was also statistically significant (P less than .01). There was an increase in the CSF volume in the temporal, occipital, and frontal regions; no region showed a significant difference in the white matter content. The findings of diffuse changes and temporal lobe involvement in AD are consistent with pathologic observations of cortical cell loss.
Chirale 2,2′‐Polyoxaalkano‐9,9′‐spirobifluorene (1979)

Chiral 2,2′‐polyoxaalkano‐9,9′‐spirobifluorenes From 2,2′‐diacetyl‐9,9′‐spirobifluorene (2) , twelve chiral polyethers have been prepared as potential ion‐ and enantiomer‐selective ionophores. The absolute configuration of the polyethers 15 – 17 , 19 – 22 , and 25 has been determined by chemical correlation with vespirenes [11] [29], by circular dichroism, and by X‐ray analysis. The circular dichroism of 15 – 17 , 19 and 21 depends on the size of the macrocycle and indicates that the fluorene chromophores of 19 and 21 with 13‐ and 16‐membered rings respectively deviate considerably from orthogonality.
A Derivative of NADP Mobilizes Calcium Stores Insensitive to Inositol Trisphosphate and Cyclic ADP-ribose (1995)

We have previously shown that alkaline treatment of NADP generates a derivative which can mobilize Ca2+ from sea urchin egg homogenates (Clapper, D. L., Walseth, T. F., Dargie, P. J., and Lee, H. C. (1987) J. Biol. Chem. 262, 9561-9568). In this study, the active derivative was purified and shown by high pressure liquid chromatography to be distinct from NADP and NADPH. However, its proton NMR spectrum was virtually identical to that of NADP. The mass of its molecular ion was measured by high resolution mass spectrometry to be 743.0510, one mass unit larger than the corresponding ion of NADP. These results are consistent with the active derivative being nicotinic acid adenine dinucleotide phosphate (NAADP). Ca2+ release induced by NAADP was saturable with a half-maximal concentration of about 30 nM. The release was specific since NADP and nicotinic acid adenine dinucleotide were ineffective even at 10-40-fold higher concentrations. The NAADP-dependent Ca2+ release showed desensitization and was insensitive to heparin and a specific antagonist of cyclic ADP-ribose (cADPR), 8-amino-cADPR. The release mechanism did not require calmodulin. This is similar to the inositol trisphosphate-sensitive release but distinct from that of cADPR. That the NAADP-sensitive Ca2+ stores were different from those sensitive to inositol trisphosphate- or cADPR was further indicated by their differences in distribution on Percoll density gradients. Microinjection of NAADP into live sea urchin eggs induced transient elevation of intracellular Ca2+ and triggered the cortical reaction, indicating the NAADP-dependent mechanism is operative in intact cells.
Regulated Expression of BAFF-Binding Receptors during Human B Cell Differentiation (2007)

BAFF plays a central role in B-lineage cell biology; however, the regulation of BAFF-binding receptor (BBR) expression during B cell activation and differentiation is not completely understood. In this study, we provide a comprehensive ex vivo analysis of BBRs in human B-lineage cells at various stages of maturation, as well as describe the events that drive and regulate receptor expression. Our data reveal that B-lineage cells ranging from naive to plasma cells (PCs), excluding bone marrow PCs, express BAFF-R uniformly. In contrast, only tonsillar memory B cells (MB) and PCs, from both tonsil and bone marrow tissues, express BCMA. Furthermore, we show that TACI is expressed by MB cells and PCs, as well as a subpopulation of activated CD27(neg) B cells. In this regard, we demonstrate that TACI is inducible early upon B cell activation and this is independent of B cell turnover. In addition, we found that TACI expression requires activation of the ERK1/2 pathway, since its expression was blocked by ERK1/2-specific inhibitors. Expression of BAFF-R and B cell maturation Ag (BCMA) is also highly regulated and we demonstrate that BCMA expression is only acquired in MB cells and in a manner accompanied by loss of BAFF-R expression. This inverse expression coincides with MB cell differentiation into Ig-secreting cells (ISC), since blocking differentiation inhibited both induction of BCMA expression and loss of BAFF-R. Collectively, our data suggest that the BBR profile may serve as a footprint of the activation history and stage of differentiation of normal human B cells.
Application to a Cartilage Targeting Strategy:  Synthesis and in Vivo Biodistribution of 14C-Labeled Quaternary Ammonium−Glucosamine Conjugates (2000)

As part of a cartilage targeting program based on the affinity of the quaternary ammonium (QA) moiety for cartilage, QA derivatives of D-glucosamine (DG), an antirheumatic drug exhibiting a natural tropism for cartilaginous tissues, were designed and evaluated by pharmacokinetic studies. Two QA-DG conjugates were synthesized and labeled with (14)C by cross-linking the QA entity (trimethylammonium or pyridinium) to [(14)C]DG via an amide bond in a two-step procedure. After intravenous injection to male Sprague-Dawley rats, the two (14)C-labeled conjugates exhibited similar pharmacokinetic profiles, but their behavior clearly differed from that of unconjugated DG in several ways. (i) The tissue distribution for the conjugates was more restricted, with a decreased radioactivity level for whole tissues except for kidney, cartilage, and skin. (ii) The radioactivity concentrated more rapidly and strongly in cartilage for the conjugates than for DG for the short times after injection; on the other hand, 1 h after administration, the radioactivity level in cartilage was higher for DG, this result being consistent with the tropism already observed for this compound. (iii) Both conjugates were eliminated predominantly by the urinary route (85%); the radioactivity level in urine for DG was lower (45% of the injected dose), and significant (14)CO(2) was found in expired air, indicating metabolization and utilization of DG for energy-consuming processes. (iv) Blood and plasma kinetics studies displayed an enterohepatic cycle for DG, whereas for the QA conjugates, a rapid disappearance was observed. (v) HPLC analyses of plasma and urine indicated a low degree of metabolization for the conjugates, most of the radioactivity recovered in urine and plasma corresponding to the unchanged molecule. This study demonstrates that the introduction of the QA moiety on DG modifies its biodistribution and lends it a greater specificity for cartilage, at least for short times after injection. These findings justify further work on QA derivatives of other antirheumatic agents.