gebhart/patrepeval huggingface dataset:
Anti-A 42- and anti-A 40-specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model (2005)

Accumulation and aggregation of amyloid beta peptide 1-42 (Abeta42) in the brain has been hypothesized as triggering a pathological cascade that causes Alzheimer disease (AD). To determine whether selective targeting of Abeta42 versus Abeta40 or total Abeta is an effective way to prevent or treat AD, we compared the effects of passive immunization with an anti-Abeta42 mAb, an anti-Abeta40 mAb, and multiple Abeta(1-16) mAbs. We established in vivo binding selectivity of the anti-Abeta42 and anti-Abeta40 mAbs using novel TgBRI-Abeta mice. We then conducted a prevention study in which the anti-Abeta mAbs were administered to young Tg2576 mice, which have no significant Abeta deposition, and therapeutic studies in which mAbs were administered to Tg2576 or CRND8 mice with modest levels of preexisting Abeta deposits. Anti-Abeta42, anti-Abeta40, and anti-Abeta(1-16) mAbs attenuated plaque deposition in the prevention study. In contrast, anti-Abeta42 and anti-Abeta40 mAbs were less effective in attenuating Abeta deposition in the therapeutic studies and were not effective in clearing diffuse plaques following direct injection into the cortex. These data suggest that selective targeting of Abeta42 or Abeta40 may be an effective strategy to prevent amyloid deposition, but may have limited benefit in a therapeutic setting.
Solution and Solid-State Structures of Phosphine Adducts of Monomeric Zinc Bisphenoxide Complexes. Importance of These Derivatives in CO2/Epoxide Copolymerization Processes (2000)

Phosphine derivatives of the monomeric zinc phenoxide complexes, (phenoxide)2ZnLn, where phenoxide equals 2,6-di-tert-butylphenoxide, 2,4,6-tri-tert-butylphenoxide, and 2,6-diphenylphenoxide and n = 1 or 2, have been synthesized from the reaction of Zn[N(SiMe3)2]2 and the corresponding phenol followed by the addition of phosphine. The complexes have been characterized in solution by 31P NMR spectroscopy and in selected instances in the solid-state by X-ray crystallography. The small, basic phosphine, PMe3, provided the only case of an isolated complex possessing two phosphine ligands (i.e., n = 2). For all other larger phosphines only the monophosphine adducts were obtained. Furthermore, only fairly basic phosphines were found to bind to zinc, e.g., whereas PPh3 (pKa = 2.73) was ineffective, PPh2Me (pKa = 4.57) did form a strong bond to zinc. The solid-state structures of the monophosphine adducts consist of a near-trigonal planar geometry about the zinc center, where the average P-Zn-O angles are larger than the O-Zn-O angles. On the other hand, the bisphosphine adduct, Zn(O-2,4,6-tBu3C6H2)(2).2PMe3, is a distorted tetrahedral structure with O-Zn-O and P-Zn-P bond angles of 108.8(2) degrees and 107.1(9) degrees, respectively. Competitive phosphine binding studies monitored by 31P NMR spectroscopy provided a relative binding order of PPh3 approximately PtBu3 << PPh2Me < PCy3 < PMe2Ph < PnBu3 < PEt3 < PMe3. Hence, the relative binding of basic phosphine ligands at these congested zinc sites is largely determined by their steric requirements. All phosphine adducts, with the exception of PMe2Ph and PMe3, were found to undergo slow self-exchange (< 600 s-1) with free phosphine by 31P NMR spectroscopy. However, the two small phosphines, PMe2Ph (cone angle = 122 degrees) and PMe3 (cone angle = 118 degrees), were shown to undergo rapid exchange presumably via an associative mechanism. Although there was no kinetic preferences for PCy3 binding to cadmium vs zinc, cadmium was thermodynamically favored by about a factor of 2.5. The addition of up to 3 equiv of PCy3 to the Zn(O-2,6-tBu2C6H3)2 or Zn(O-2,4,6-tBu3C6H2)2 derivatives did not significantly alter the reactivity of these catalysts for the copolymerization of cyclohexene oxide (CHO) and CO2 to high-molecular weight poly(cyclohexene carbonate). However, the presence of PCy3 greatly retarded their ability to homopolymerize CHO to polyether or to afford polyether linkages during the copolymerization of CHO/CO2.
Eigengene-based linear discriminant model for tumor classification using gene expression microarray data (2006)

R code for the ELDA algorithm is available from author upon request.
Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density (1988)

A correlation-energy formula due to Colle and Salvetti [Theor. Chim. Acta 37, 329 (1975)], in which the correlation energy density is expressed in terms of the electron density and a Laplacian of the second-order Hartree-Fock density matrix, is restated as a formula involving the density and local kinetic-energy density. On insertion of gradient expansions for the local kinetic-energy density, density-functional formulas for the correlation energy and correlation potential are then obtained. Through numerical calculations on a number of atoms, positive ions, and molecules, of both open- and closed-shell type, it is demonstrated that these formulas, like the original Colle-Salvetti formulas, give correlation energies within a few percent.
RAV1, a novel DNA-binding protein, binds to bipartite recognition sequence through two distinct DNA-binding domains uniquely found in higher plants (1999)

We have cloned and characterized two novel DNA binding proteins designated RAV1 and RAV2 from Arabidopsis thaliana. RAV1 and RAV2 contain two distinct amino acid sequence domains found only in higher plant species. The N-terminal regions of RAV1 and RAV2 are homologous to the AP2 DNA-binding domain present in a family of transcription factors represented by the Arabidopsis APETALA2 and tobacco EREBP proteins, while the C-terminal region exhibits homology to the highly conserved C-terminal domain, designated B3, of VP1/ABI3 transcription factors. Binding site selection assays using a recombinant glutathione S-transferase fusion protein have revealed that RAV1 binds specifically to bipartite recognition sequences composed of two unrelated motifs, 5'-CAACA-3' and 5'-CACCTG-3', separated by various spacings in two different relative orientations. Analyses using various deletion derivatives of the RAV1 fusion protein show that the AP2 and B3-like domains of RAV1 bind autonomously to the CAACA and CACCTG motifs, respectively, and together achieve a high affinity and specificity of binding. From these results, we suggest that the AP2 and B3-like domains of RAV1 are connected by a highly flexible structure enabling the two domains to bind to the CAACA and CACCTG motifs in various spacings and orientations.
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation (2020)

The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we determined a 3.5-angstrom-resolution cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophysical and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Additionally, we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.
Respiratory bacterial infections in cystic fibrosis (2013)

Chronic, pulmonary infections remain the single most prominent cause of the increased morbidity and mortality in CF. After the increasing efficiency of anti-P. aeruginosa treatment, newer pathogens have been identified, with individual clinical characteristics. Microbiological surveillance is very important in keeping the patients stable. Samples from both the lower and upper respiratory tract (nasal sampling) should be investigated and both infection sites should be treated.
TRAIL receptor signaling and therapeutics (2010)

Cancer therapeutics targeting the TRAIL/TRAIL receptor signaling pathway hold great promise for molecularly targeted pro-apoptotic anti-cancer therapy.
Monoclonal Antibodies to Pertussis Toxin: Utilization as Probes of Toxin Function (1989)

Six monoclonal antibodies (MAbs) to pertussis toxin (PT) have been generated and characterized. Five of these MAbs (3CX4, 3C4D, 6D11C, 6FX1, and X2X5) interact with determinants on the catalytic subunit (S1) of PT, and one (6DX3) is specific for subunit S4. The MAbs are divided into three groups based upon their ability to neutralize the effects of PT in a Chinese hamster ovary (CHO) cell assay. Three of the MAbs (3CX4, 3C4D and 6D11C) had high neutralization titers, one MAb (6FX1) displayed weak neutralizing activity, and two MAbs (X2X5 and 6DX3) had no neutralizing ability. The combination of one of the high titer MAbs (3CX4) with the low titer MAb (6FX1) resulted in a synergistic enhancement of neutralizing capability. F(ab')2 fragments prepared from MAb's 3CX4 and X2X5 displayed activities in the CHO-cell assay which were identical to the native MAb's. The ability of the MAbs to neutralize PT in the CHO-cell toxin neutralization assay correlated with their ability to inhibit the in vitro ADP-ribosylation of PT. A competition ELISA method demonstrated that this panel of MAbs recognizes at least four separate epitopes on the PT molecule. Biotin-conjugated MAbs were shown to be useful reagents to probe the interaction of pertussis toxin with fetuin.
Pak-Family Kinases Regulate Cell and Actin Polarization Throughout the Cell Cycle of Saccharomyces cerevisiae (1999)

During the cell cycle of the yeast Saccharomyces cerevisiae, the actin cytoskeleton and cell surface growth are polarized, mediating bud emergence, bud growth, and cytokinesis. We have determined whether p21-activated kinase (PAK)-family kinases regulate cell and actin polarization at one or several points during the yeast cell cycle. Inactivation of the PAK homologues Ste20 and Cla4 at various points in the cell cycle resulted in loss of cell and actin cytoskeletal polarity, but not in depolymerization of F-actin. Loss of PAK function in G1 depolarized the cortical actin cytoskeleton and blocked bud emergence, but allowed isotropic growth and led to defects in septin assembly, indicating that PAKs are effectors of the Rho-guanosine triphosphatase Cdc42. PAK inactivation in S/G2 resulted in depolarized growth of the mother and bud and a loss of actin polarity. Loss of PAK function in mitosis caused a defect in cytokinesis and a failure to polarize the cortical actin cytoskeleton to the mother-bud neck. Cla4-green fluorescent protein localized to sites where the cortical actin cytoskeleton and cell surface growth are polarized, independently of an intact actin cytoskeleton. Thus, PAK family kinases are primary regulators of cell and actin cytoskeletal polarity throughout most or all of the yeast cell cycle. PAK-family kinases in higher organisms may have similar functions.
Electromyography: Some Methodological Problems and Issues (1993)

The purpose of this review is to discuss electromyography (EMG) and some of the problems and issues that are encountered during the recording and interpretation of EMG data. Recordings of electrical activity of muscles can be contaminated by interference from the electrical supply, mechanical artifacts, stimulus artifacts, and activity of other muscles. The advantages and disadvantages of surface electromyography and intramuscular EMG are compared and contrasted, and precautions to be taken when recording and interpreting these data are described. Surface electromyography is usually more susceptible to artifacts than is intramuscular EMG. It is possible, however, to make useful recordings with the surface electrodes from large superficial muscles if appropriate precautions are observed. Intramuscular electrodes, on the other hand, may be preferred for recording the activity from small peripheral muscles or muscles located deep within the body.
Electron trapping and detrapping characteristics of arsenic-implanted SiO2 layers (1980)

The electron trapping and detrapping properties of As+-implanted thermally grown SiO2 layers incorporated into metal-silicon dioxide-silicon (MOS) structures have been studied. The samples were charged using avalanche injection from the silicon substrate or internal photoemission from either interface. The charge state of the MOS devices was investigated using capacitance-vs-voltage (C-V) and photocurrent-vs-voltage (photo I-V) measurements. After a 1×1013 As+/cm2 implant and a 1000 °C anneal in N2 for 30 min, a dominant (in terms of trapping probability) trapping center with a capture cross section of (1–2) ×10−15 cm2 is found, together with various other centers with cross sections of (1–4) ×10−17, (2–5) ×10−16, and (0.4–1.6) ×10−14 cm2, respectively. The sum of the trap densities for the various centers with cross sections in the range 10−15–10−16 cm2 is equal to 0.7–1 times the ion fluence, independent of ion energy (10–100 keV), avalanche injection current (5×10−11–5×10−10 A), and oxide thickness (490–1430 Å). The dominant trap density is proportional to the ion fluence over our experimental range (3×1012–1×1014 As+/cm2). Increasing the anneal temperature from 600 to 1100 °C gradually decreases the electron trapping rate, without extensively changing the dominant-trap parameters. The negative-charge distribution centroid (measured with respect to the Al-SiO2 interface) is shown to be proportional to the ion energy but does not depend on trapped charge density (4×1011−1×1013 cm−2), ion fluence (3×1012−1×1014 cm−2), injection mechanism (avalanche injection or internal photoemission), oxide thickness (490–1430 Å), anneal temperature (600–1100–°C), or ambient temperature (83–295 K). The charge centroids were found to be in excellent agreement with the experimentally determined (SIMS) ion distribution centroids, but systematically larger (up to 40%) than the values predicted by the theory of Lindhard, Scharff and Schio/tt (LSS). It is shown that optical excitation removes the trapped negative charge from the trapping centers in a homogeneous way (i.e., with constant charge centroid). From the detrapping experiments, an effective photoionization cross section is determined as a function of photon energy with an absorption threshold of 3.3 eV. This is corroborated by a model which assumes that the electron trapping is related to the implanted arsenic ions, incorporated into the SiO2-network at oxygen-sites. Isothermal detrapping experiments (in the range 100–250 °C) and thermally stimulated current measurements are reported. Both experiments can be modeled by assuming a Gaussian trap distribution around a median thermal trap depth Em=1.2–1.3 eV with a standard deviation ΔE=0.2 eV.
Enzymatic conversion of racemic methionine to the L-enantiomer (1990)

We have developed an enzymatic method for conversion of racemic methionine to the L-enantiomer with a yield of >95% and >99% enantiomeric excess; the method has been applied to the conversion of DL-alanine and DL-leucine to the L-enantiomers.
Single-molecule mechanics of mussel adhesion (2006)

The glue proteins secreted by marine mussels bind strongly to virtually all inorganic and organic surfaces in aqueous environments in which most adhesives function poorly. Studies of these functionally unique proteins have revealed the presence of the unusual amino acid 3,4-dihydroxy-L-phenylalanine (dopa), which is formed by posttranslational modification of tyrosine. However, the detailed binding mechanisms of dopa remain unknown, and the chemical basis for mussels' ability to adhere to both inorganic and organic surfaces has never been fully explained. Herein, we report a single-molecule study of the substrate and oxidation-dependent adhesive properties of dopa. Atomic force microscopy (AFM) measurements of a single dopa residue contacting a wet metal oxide surface reveal a surprisingly high strength yet fully reversible, noncovalent interaction. The magnitude of the bond dissociation energy as well as the inability to observe this interaction with tyrosine suggests that dopa is critical to adhesion and that the binding mechanism is not hydrogen bond formation. Oxidation of dopa, as occurs during curing of the secreted mussel glue, dramatically reduces the strength of the interaction to metal oxide but results in high strength irreversible covalent bond formation to an organic surface. A new picture of the interfacial adhesive role of dopa emerges from these studies, in which dopa exploits a remarkable combination of high strength and chemical multifunctionality to accomplish adhesion to substrates of widely varying composition from organic to metallic.
A Phase I Trial of Radioimmunotherapy with 131I-A5B7 Anti-CEA Antibody in Combination with Combretastatin-A4-Phosphate in Advanced Gastrointestinal Carcinomas (2009)

This is believed to be the first trial reporting the combination of radioimmunotherapy and vascular disruptive agent; each component was shown to function, and myelosuppression was dose-limiting. Optimal dose and timing of CA4P, and moderate improvements in the performance of radioimmunotherapy seem necessary for efficacy.
Pteridines. XXXIII. Unequivocal total synthesis of L-erythro-Biopterin (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPteridines. XXXIII. Unequivocal total synthesis of L-erythro-BiopterinEdward C. Taylor and Peter A. JacobiCite this: J. Am. Chem. Soc. 1974, 96, 21, 6781–6782Publication Date (Print):October 1, 1974Publication History Published online1 May 2002Published inissue 1 October 1974https://pubs.acs.org/doi/10.1021/ja00828a052https://doi.org/10.1021/ja00828a052research-articleACS PublicationsRequest reuse permissionsArticle Views204Altmetric-Citations26LEARN 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
A multigene predictor of metastatic outcome in early stage hormone receptor-negative and triple-negative breast cancer (2010)

Abstract Introduction Various multigene predictors of breast cancer clinical outcome have been commercialized, but proved to be prognostic only for hormone receptor (HR) subsets overexpressing estrogen or progesterone receptors. Hormone receptor negative (HRneg) breast cancers, particularly those lacking HER2/ErbB2 overexpression and known as triple-negative (Tneg) cases, are heterogeneous and generally aggressive breast cancer subsets in need of prognostic subclassification, since most early stage HRneg and Tneg breast cancer patients are cured with conservative treatment yet invariably receive aggressive adjuvant chemotherapy. Methods An unbiased search for genes predictive of distant metastatic relapse was undertaken using a training cohort of 199 node-negative, adjuvant treatment naïve HRneg (including 154 Tneg) breast cancer cases curated from three public microarray datasets. Prognostic gene candidates were subsequently validated using a different cohort of 75 node-negative, adjuvant naïve HRneg cases curated from three additional datasets. The HRneg/Tneg gene signature was prognostically compared with eight other previously reported gene signatures, and evaluated for cancer network associations by two commercial pathway analysis programs. Results A novel set of 14 prognostic gene candidates was identified as outcome predictors: CXCL13, CLIC5, RGS4, RPS28, RFX7, EXOC7, HAPLN1, ZNF3, SSX3, HRBL, PRRG3, ABO, PRTN3, MATN1. A composite HRneg/Tneg gene signature index proved more accurate than any individual candidate gene or other reported multigene predictors in identifying cases likely to remain free of metastatic relapse. Significant positive correlations between the HRneg/Tneg index and three independent immune-related signatures (STAT1, IFN, and IR) were observed, as were consistent negative associations between the three immune-related signatures and five other proliferation module-containing signatures (MS-14, ONCO-RS, GGI, CSR/wound and NKI-70). Network analysis identified 8 genes within the HRneg/Tneg signature as being functionally linked to immune/inflammatory chemokine regulation. Conclusions A multigene HRneg/Tneg signature linked to immune/inflammatory cytokine regulation was identified from pooled expression microarray data and shown to be superior to other reported gene signatures in predicting the metastatic outcome of early stage and conservatively managed HRneg and Tneg breast cancer. Further validation of this prognostic signature may lead to new therapeutic insights and spare many newly diagnosed breast cancer patients the need for aggressive adjuvant chemotherapy.
Gene therapy strategies for tumor antiangiogenesis (1998)

Based on the concept that solid tumors cannot grow without the generation of new blood vessels, there is growing interest in the use of antiangiogenesis agents to inhibit tumor growth. This review summarizes the concepts of using gene transfer vectors to provide high concentration of antiangiogenic proteins within an organ. While there are many challenges that must be met before antiangiogenesis can be used to effectively treat human tumors, gene transfer strategies have the potential to provide sustained, high, local concentrations of antiangiogenic mediators specifically targeted to organs containing tumors, minimizing systemic toxicity. Antiangiogenesis gene therapy strategies will most likely be effective in a state of low tumor burden, where this "genetic tourniquet" can provide trans (i.e., acting in the extracellular milieu as opposed to within tumor cells) suppression of the growth of endothelial cells in the milieu of micrometastases.
Cell Cycle Regulation in the Yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe (1991)

CONTENTS INTRODUCTION 227 THE yEASTS ... 228 Saccharomyces cerevisiae. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... ....... . . . . . . ....... . . . . . . . . . . . .... . . . . . . . . . . ........ 228 Schizosaccharomyces pombe 231 Too l s o f Ge ne tic s 232 REGULATION OF CELL CYCLE PROGRESSION ..••• 235 GljS Tr a n sitio n....... 236 G2jM Tra nsitio n . . . . . . . . . . . ........ 243 Exit fro m the Cyc le ......... . . . ......... . . . . . . .. 249 CONCLUSIONS . . ........ . .... . . 250