gebhart/patrepeval huggingface dataset:
Discovery ofN-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide, an Agonist of the α7 Nicotinic Acetylcholine Receptor, for the Potential Treatment of Cognitive Deficits in Schizophrenia:  Synthesis and Structure−Activity Relationship (2006)

N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (14, PHA-543,613), a novel agonist of the alpha7 neuronal nicotinic acetylcholine receptor (alpha7 nAChR), has been identified as a potential treatment of cognitive deficits in schizophrenia. Compound 14 is a potent and selective alpha7 nAChR agonist with an excellent in vitro profile. The compound is characterized by rapid brain penetration and high oral bioavailability in rat and demonstrates in vivo efficacy in auditory sensory gating and, in an in vivo model to assess cognitive performance, novel object recognition.
The Genetics of Colorectal Cancer (2002)

Colon cancer is a common disease that can be sporadic, familial, or inherited. Recent advances have contributed to the understanding of the molecular basis of these various patterns of colon cancer. Germline genetic mutations are the basis of inherited colon cancer syndromes; an accumulation of somatic mutations in a cell is the basis of sporadic colon cancer; and, in Ashkenazi Jewish persons, a mutation that was previously thought to be a polymorphism may cause familial colon cancer. Mutations of three different classes of genes have been described in colon cancer etiology: oncogenes, suppressor genes, and mismatch repair genes. Knowledge of many of the specific mutations responsible for colon carcinogenesis allows an understanding of the phenotypic manifestations observed and forms the basis of genetic testing for inherited disease. Although genetic testing is possible and available, it is only an adjunct to the clinical management of persons at risk for colon cancer and patients with colon cancer. As a result of advances in the understanding of the molecular causes of colon cancer and the availability of colon cancer screening methods such as colonoscopy, it should be possible to prevent the vast majority of colon cancer in our society. Practicing clinicians should recognize the patterns of clinical colon cancer, understand its causes, and be able to use genetic testing and endoscopic screening for prevention.
Stable genetic transformation of intact Nicotiana cells by the particle bombardment process (1988)

We show that the genetic transformation of Nicotiana tabacum can be achieved by bombarding intact cells and tissues with DNA-coated particles. Leaves or suspension culture cells were treated with tungsten microprojectiles carrying plasmid DNA containing a neomycin phosphotransferase gene. Callus harboring the foreign gene was recovered from the bombarded tissue by selection on medium containing kanamycin. Kanamycin-resistant plants have subsequently been regenerated from the callus derived from leaves. Transient expression of an introduced beta-glucuronidase gene was used to assess the efficiency of DNA delivery by microprojectiles. The frequency of cells that were stably transformed with the neomycin phosphotransferase gene was a few percent of the cells that transiently expressed the beta-glucuronidase gene. These results show that gene transfer by high-velocity microprojectiles is a rapid and direct means for transforming intact plant cells and tissues that eliminates the need for production of protoplasts or infection by Agrobacterium.
Hyperspectral Imaging System Modeling (2003)

■ To support hyperspectral sensor system design and parameter trade-off investigations, Lincoln Laboratory has developed an analytical end-to-end model that forecasts remote sensing system performance. The model uses statistical descriptions of scene class reflectances and transforms them to account for the effects of the atmosphere, the sensor, and any processing operations. System-performance metrics can then be calculated on the basis of these transformed statistics. The model divides a remote sensing system into three main components: the scene, the sensor, and the processing algorithms. Scene effects modeled include the solar illumination, atmospheric transmittance, shade effects, adjacency effects, and overcast clouds. Modeled sensor effects include radiometric noise sources, such as shot noise, thermal noise, detector readout noise, quantization noise, and relative calibration error. The processing component includes atmospheric compensation, various linear transformations, and a number of operators used to obtain detection probabilities. Models have been developed for several imaging spectrometers, including the airborne Hyperspectral Digital Imagery Collection Experiment (HYDICE) instrument, which covers the reflective solar spectral region from 0.4 to 2.5 μm. This article presents the theory and operation of the model, and provides example parameter trade studies to show the utility of the model for system design and sensor operation applications.
Embryonic stem cells stably transfected with mRAR beta 2-lacZ exhibit specific expression in chimeric embryos (1992)

Using the embryonic stem (ES) cell/chimera approach, we have studied the activity of the mouse retinoic acid receptor beta 2 (mRAR beta 2) promoter during ES cell differentiation and during embryonic development. Stable ES clones were isolated after introduction of a 1.8 kb mRAR beta 2-lacZ expression cassette. LacZ expression in these stable clones was specifically induced by retinoic acid (RA) in a similar fashion as the endogenous RAR beta 2 gene. Following introduction of three different ES clones into blastocysts, an integration-independent mRAR beta 2-lacZ expression pattern was obtained in chimeric embryos similar to that described by in situ hybridization and transgenic studies. Moreover, mRAR beta 2-lacZ expression was also detected at some additional sites not described before, e.g. body wall, ureter, mesonephric duct and optic stalk. Maternal RA administration at 8.5 days of pregnancy extended lacZ expression to more anterior and posterior regions. Transgenic mice were generated from germ-line transmission of the transfected ES cells; expression pattern and changes in expression upon RA induction in these transgenic embryos were identical to those in chimeric embryos. We conclude that by using the ES/chimera approach, the proximal 1.8 kb of the mRAR beta 2 promoter produces a reliable and reproducible expression pattern of the reporter gene, and that the ES cell/chimera approach is invaluable for the study of gene expression and regulation.
The significance of detection of minimal residual disease in childhood acute lymphoblastic leukaemia (1993)

In acute lymphoblastic leukaemia (ALL), minimal residual disease (MRD) can be defined as disease occurring at a subclinical level and beyond detection by conventional methods of assessment. Application of the polymerase chain reaction (PCR) to the hypervariable segment of the immunoglobulin heavy chain (IgH) gene, allows detection of MRD at a level of one leukaemic cell in 10(4)-10(5) normal marrow cells. We have performed a retrospective study using this technique in the assessment of children with precursor B-cell ALL in whom the clinical outcome is known. In the early treatment period MRD is commonly detected in children who remain in complete remission on subsequent follow up. Thus, the detection of MRD at this time may have little value in the prediction of future relapse. However, at the end of treatment, children who remain in complete remission have no evidence of MRD. Conversely, detectable MRD at this time would seem to predict for future relapse, though this can be a delayed event. Remarkably, in two children who suffered a bone marrow relapse 8.5 and 9 years after completing therapy for their initial disease, MRD was detected, in their end of initial treatment marrow samples. Clearly PCR technology is changing the definition of the remission state in childhood ALL, and may have predictive value in the assessment of children who are at a high risk of future relapse. Large prospective studies of molecular monitoring are now required to confirm these preliminary results.
Experimenting in picoliter microvials (1998)

The use of nanotechnology to produce nanoliter vials for mass spectrometry led to the creation of these even smaller vials for investigating single cells.
Oligodeoxyribonucleotides Synthesis: Phosphoramidite Approach (2003)

The development of deoxyribonucleoside phosphoramidite derivatives for the synthesis of oligodeoxyribonucleotides was first described by Beaucage and Caruthers (1) in 1981. The conceptual basis of this methodology emerged as a modification of the “phosphorodichloridite” coupling procedure reported earlier by Letsinger and coworkers (2). Essentially, the approach involved the reaction of the protected deoxyribonucleosides 1a–d (Fig. 1) with chloro-(N,N-dimethylamino) methoxyphosphine (2) in the presence of N,N-diisopropylethylamine. The rapid reaction yielded the deoxyribonucleoside phosphoramidites 3a–d (Fig. 1), which were isolated by precipitation and stored as dry powders.
Germline variable region gene segment derivation of human monoclonal anti-Rh(D) antibodies. Evidence for affinity maturation by somatic hypermutation and repertoire shift. (1992)

To date, there has been no systematic study of the process of affinity maturation of human antibodies. We therefore sequenced the variable region genes (V genes) of 14 human monoclonal antibodies specific for the erythrocyte Rh(D) alloantigen and determined the germline gene segments of origin and extent of somatic hypermutation. These data were correlated with determinations of antibody affinity. The four IgM antibodies (low affinity) appear to be derived from two germline heavy chain variable region gene segments and one or two germline light chain variable region gene segments and were not extensively mutated. The 10 IgG antibodies (higher affinity) appear to be derived from somatic hypermutation of these V gene segments and by use of new V gene segments or V gene segment combinations (repertoire shift). Affinity generally increased with increasing somatic hypermutation; on average, there were 8.9 point mutations in the V gene segments of the four IgM antibodies (Ka = 1-4 x 10(7)/M-1) compared with 19 point mutations in the V gene segments of the 10 IgG antibodies. The four highest affinity antibodies (Ka = 0.9-3 x 10(9)/M-1) averaged 25.5 point mutations. The use of repertoire shift and somatic hypermutation in affinity maturation of human alloantibodies is similar to data obtained in inbred mice immunized with haptens.
The SM 22 promoter directs tissue-specific expression in arterial but not in venous or visceral smooth muscle cells in transgenic mice (1996)

The transcriptional signals underlying smooth muscle differentiation are currently unknown. We report here the complete sequence and characterization of the single mouse gene for the smooth muscle-specific protein SM 22 and the transcriptional activity of its promoter in cultured smooth muscle cells in vitro and in transgenic mice. In the transgenic animals, promoter constructs ranging in length from 445 to 2126 bp directed reporter expression initially in the heart and the somites of embryos and subsequently in the arteries of the vascular system, but in none of the visceral muscles, nor in the veins. Expression in the heart was spatially restricted to the presumptive right ventricle and outflow tract and disappeared in the adult. Likewise, expression in the somites was only transitory and was not observed after about 14.5 days post coitum in the embryo. In the adult mouse, SM 22 promoter activity persisted in the smooth muscle cells of the arteries and was still notably absent from other smooth muscles, despite the ubiquitous presence of the endogenous SM 22 protein. These findings on the transcriptional activity of a smooth muscle promoter in vivo reveal the existence of different differentiation programmes for smooth muscle cells in the veins and the arteries and raise the expectation of a further subdivision of programmes among the visceral muscles.
Postoperative episodic oxygen desaturation in the sleep apnoea syndrome (1991)

We describe a patient with sleep apnoea syndrome who showed severe episodic hypoxaemia in the late postoperative period. The sleep apnoea syndrome should be studied further to evaluate its significance as a surgical risk factor.
Mild procedure for the conversion of epoxides to allylic alcohols. First organoselenium reagent (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMild procedure for the conversion of epoxides to allylic alcohols. First organoselenium reagentK. B. Sharpless and R. F. LauerCite this: J. Am. Chem. Soc. 1973, 95, 8, 2697–2699Publication Date (Print):April 1, 1973Publication History Published online1 May 2002Published inissue 1 April 1973https://pubs.acs.org/doi/10.1021/ja00789a055https://doi.org/10.1021/ja00789a055research-articleACS PublicationsRequest reuse permissionsArticle Views4372Altmetric-Citations451LEARN 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 Get e-Alerts
Profluorescent Nitroxides as Sensitive Probes of Oxidative Change and Free Radical Reactions† (2011)

This paper presents a review on the use of tethered nitroxide–fluorophore molecules as probes of oxidative change and free radical generation and reaction. The proximity of the nitroxide free radical to the fluorophore suppresses the normal fluorescence emission process. Nitroxide free radical scavenging, metabolism or redox chemistry return the system to its natural fluorescent state and so these tethered nitroxide–fluorophore molecules are described as being profluorescent. A survey of profluorescent nitroxides found in the literature is provided as well as background on the mechanism of action and applications of these compounds as fluorometric probes within the fields of biological, materials and environmental sciences.
Association of 2' - 5' oligoribonucleotides (1992)

Oligoribonucleotides with 2'-5' linkages have been synthesized on solid support. UV melting and CD experiments indicate complementary strands associate to give complexes with melting temperatures 30 to 40 degrees C lower than for duplexes formed by 3'-5' oligoribonucleotides with the same sequence. UV melting and imino proton NMR spectra and NOEs for (2'-5') CGGCGCCG are consistent with formation of an antiparallel duplex. The results suggest greater duplex stability was one factor favoring 3'-5' over 2'-5' linkages in evolution.
Killing of cutaneous microbial species by photodynamic therapy (2001)

Overall, these results indicate that APDT of the skin may represent a useful alternative to conventional antimicrobial treatment.
Determination of C-Reactive Protein: Comparison of Three High-Sensitivity Immunoassays (2003)

Atherosclerosis is an inflammatory condition (1), and progression to atherothrombotic events is associated with systemic evidence of low-grade inflammation. Circulating concentrations of C-reactive protein (CRP) within the range previously considered to be normal have been shown to predict future cardiovascular events independently in initially healthy individuals as well as in patients with manifest atherosclerotic disease, even in the absence of hyperlipidemia (2)(3)(4). The detection of such subclinical inflammation requires high-sensitivity methods for CRP measurement. Recently, we reported on the analytical performance of a new sensitive solid-phase monoclonal-polyclonal IRMA (5). This assay has a very low analytical detection limit of 0.05 mg/L, and in a cohort study, CRP determined by this method showed a strong linear association with future coronary endpoints (4). Here we compare the performance of the IRMA specifically designed to evaluate the low CRP range with that of an ultrasensitive latex-enhanced immunonephelometric test and an immunoturbidimetric assay in a large case–control study. Additionally, we estimated the risk for coronary artery disease (CAD) given an increased CRP concentration as determined by the three assays.

The cases consisted of 312 patients 40–68 years of age with clinically stable CAD, who underwent elective coronary angiography in the Department of Cardiology at the University of Ulm Medical Centre and who had one or more epicardial coronary stenoses of ≥50% in luminal diameter. Voluntary blood donors (n = 476) from the local blood bank served as controls. In these individuals, symptomatic CAD was excluded by the Rose questionnaire. Venous blood was obtained under standardized conditions in the morning before diagnostic coronary angiography in cases and after blood donation in controls. EDTA-plasma specimens were centrifuged at 3000 g for 10 min, immediately aliquoted, and frozen at −70 °C until analysis. Cases and controls were “frequency matched” by age and gender, …
TISSUE ENGINEERING (1995)

RETURN TO ISSUEPREVNewsNEXTTISSUE ENGINEERINGJEFFREY A. HUBBELL and ROBERT LANGERView Author Information California Institute of Technology Massachusetts Institute of TechnologyCite this: Chem. Eng. News 1995, 73, 11, 42–54Publication Date (Print):March 13, 1995Publication History Published online12 November 2010Published inissue 13 March 1995https://pubs.acs.org/doi/10.1021/cen-v073n011.p042https://doi.org/10.1021/cen-v073n011.p042newsACS PublicationsCopyright © 1995 American Chemical SocietyArticle Views175Altmetric-Citations95LEARN 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 options SUBJECTS:Bioengineering and biotechnology,Chemical engineering and industrial chemistry Get e-Alerts
Stereocontrolled Synthesis of α-Amino-α′-alkoxy Ketones by a Copper-Catalyzed Cross-Coupling of Peptidic Thiol Esters and α-Alkoxyalkylstannanes (2011)

A stereocontrolled synthesis of α-amino-α'-alkoxy ketones is described. This pH-neutral copper(I) thiophene-2-carboxylate (CuTC)-catalyzed cross-coupling of amino acid thiol esters and chiral nonracemic α-alkoxyalkylstannanes gives α-amino-α'-alkoxy ketones in good to excellent yields with complete retention of configuration at the α-amino- and α-alkoxy-substituted stereocenters.
In Vitro Assembly of PB2 with a PB1-PA Dimer Supports a New Model of Assembly of Influenza A Virus Polymerase Subunits into a Functional Trimeric Complex (2005)

Influenza virus RNA-dependent RNA polymerase is a heterotrimeric complex of PB1, PB2, and PA. We show that the individually expressed PB2 subunit can be assembled with the coexpressed PB1-PA dimer in vitro into a transcriptionally active complex. Furthermore, we demonstrate that a model viral RNA promoter can bind to the PB1-PA dimer prior to assembly with PB2. Our results are consistent with a recently proposed model for the sequential assembly of viral RNA polymerase complex in which the PB1-PA dimeric complex and the PB2 monomer are transported into the nucleus separately and then assembled in the nucleus.
Spatially regulated expression of three receptor tyrosine kinase genes during gastrulation in the zebrafish (1994)

We describe the isolation and early developmental expression of three novel zebrafish genes (rtk1-3) that encode members of the eph family of receptor tyrosine kinases. At the onset of gastrulation, rtk1 is expressed in the shield region corresponding to the future dorsal side of the embryo. As gastrulation proceeds, both rtk1 and rtk2 are expressed within the axial hypoblast along the entire axis of the embryo. After the gastrula stage is complete, expression of both genes is maintained in precursor cells of the notochord in the tail bud but is downregulated in other regions of the axial hypoblast, rtk3 is expressed in anterior axial hypoblast including the 'pillow' at the anterior tip of the hypoblast and in paraxial tissue in posterior regions of the embryo. We show that the precise spatial regulation of expression of rtk genes, ntl and goosecoid along the anteroposterior axis is maintained in embryos that have no dorsoventral axis. This indicates that the mechanisms that regulate gene expression along the anteroposterior and dorsoventral axes of the hypoblast may be independent.