gebhart/patrepeval huggingface dataset:
Discovery of Novel Benzoxazinones as Potent and Orally Active Long Chain Fatty Acid Elongase 6 Inhibitors (2009)

A series of benzoxazinones was synthesized and evaluated as novel long chain fatty acid elongase 6 (ELOVL6) inhibitors. Exploration of the SAR of the UHTS lead 1a led to the identification of (S)-1y that possesses a unique chiral quarternary center and a pyrazole ring as critical pharmacophore elements. Compound (S)-1y showed potent and selective inhibitory activity toward human ELOVL6 while displaying potent inhibitory activity toward both mouse ELOVL3 and 6 enzymes. Compound (S)-1y showed acceptable pharmacokinetic profiles after oral dosing in mice. Furthermore, (S)-1y significantly suppressed the elongation of target fatty acids in mouse liver at 30 mg/kg oral dosing.
Effect of astragaloside IV on T, B lymphocyte proliferation and peritoneal macrophage function in mice. (2002)

ASI increased T, B lymphocyte proliferation and antibody production in vivo and in vitro; but inhibited productions of IL-1 and TNF-alpha from peritoneal macrophages in vitro.
Molecular mimicry of photosynthetic energy and electron transfer (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular mimicry of photosynthetic energy and electron transferDevens Gust, Thomas A. Moore, and Ana L. MooreCite this: Acc. Chem. Res. 1993, 26, 4, 198–205Publication Date (Print):April 1, 1993Publication History Published online1 May 2002Published inissue 1 April 1993https://pubs.acs.org/doi/10.1021/ar00028a010https://doi.org/10.1021/ar00028a010research-articleACS PublicationsRequest reuse permissionsArticle Views2854Altmetric-Citations954LEARN 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
Polarization errors associated with zero-order achromatic quarter-wave plates in the whole visible spectral range (2001)

By a combination of quarter-wave plates made of different birefringent materials it is possible to produce achromatic quarter-wave plates whose degree of achromatism is dependant on the dispersions of birefringence and on the thicknesses of the individual quarter-wave plates. These waveplates are widely used in optical instrumentation and the residual errors associated with these devices can be very important in high resolution spectro-polarimetry measurements. The misalignment of optic axis in a double crystal waveplate is one of the main source of error and leads to elliptical eigenpolarization modes in the retarder and the oscillation of its orientation according to the wavelength. This paper will discuss, first, how the characteristics of a quartz-MgF2 quarter-wave plate is affected by such a misalignment. A correlation with the experiment is then achieved in order to highlight the interest of taking a possible tilt error into consideration when doing polarimetric measurements.
Potent Antiscrapie Activities of Degenerate Phosphorothioate Oligonucleotides (2006)

Although transmissible spongiform encephalopathies (TSEs) are incurable, a key therapeutic approach is prevention of conversion of the normal, protease-sensitive form of prion protein (PrP-sen) to the disease-specific protease-resistant form of prion protein (PrP-res). Here degenerate phosphorothioate oligonucleotides (PS-ONs) are introduced as low-nM PrP-res conversion inhibitors with strong antiscrapie activities in vivo. Comparisons of various PS-ON analogs indicated that hydrophobicity and size were important, while base composition was only minimally influential. PS-ONs bound avidly to PrP-sen but could be displaced by sulfated glycan PrP-res inhibitors, indicating the presence of overlapping binding sites. Labeled PS-ONs also bound to PrP-sen on live cells and were internalized. This binding likely accounts for the antiscrapie activity. Prophylactic PS-ON treatments more than tripled scrapie survival periods in mice. Survival times also increased when PS-ONs were mixed with scrapie brain inoculum. With these antiscrapie activities and their much lower anticoagulant activities than that of pentosan polysulfate, degenerate PS-ONs are attractive new compounds for the treatment of TSEs.
Arrays for the Combinatorial Exploration of Cell Adhesion (2004)

A new method for the fabrication of arrays of self-assembled monolayers (SAMs) of alkane thiols (ATs) on gold to combinatorially assay surfaces for cell adhesion is reported. A fluorous SAM, which is both cytophobic and solvophobic, was used as the background between the array features. The resulting solvophobic background permits the application of an assembly after conjugation strategy for fabrication. SAMs containing mixtures of ATs and peptide-terminated ATs were generated. Multiple cell types demonstrated differential and specific binding to these surfaces. Additionally, pluripotent human embryonic stem cells proliferated on surfaces generated by this method.
Mutational inactivation of transforming growth factor beta receptor type II in microsatellite stable colon cancers. (1999)

We previously demonstrated that mutational inactivation of transforming growth factor beta type II receptors (RIIs) is very common among the 13% of human colon cancers with microsatellite instability. These mutations principally cluster in the BAT-RII polyadenine sequence repeat. Among microsatellite stable (MSS) colon cancers, we now find that non-BAT-RII point mutations inactivate RII in another 15% of cases, thus doubling the known number of colon cancers in which RII mutations are pathogenetic. Functional analysis confirms that these mutations inactivate RII signaling. Moreover, another 55% of MSS colon cancers demonstrate a transforming growth factor beta signaling blockade distal to RII. The transforming growth factor beta pathway and RII in particular are major targets for inactivation in MSS colon cancers as well as in colon cancers with microsatellite instability.
Cloning and characterization of the plasma membrane H(+)-ATPase from Candida albicans (1991)

The Candida albicans PMA1 gene was isolated from a genomic library by using a hybridization probe obtained from the PMA1 gene of Saccharomyces cerevisiae. The gene was localized to chromosome III of the Candida genome. An open reading frame of 2,685 nucleotides predicts an amino acid sequence of 895 amino acids that is 83% homologous at both the DNA and protein levels to its S. cerevisiae equivalent. A polyadenylated mRNA transcript of about 4,000 nucleotides contains a highly folded AU-rich leader of 242 nucleotides. The structure of the gene, codon bias, and levels of approximately 100-kDa H(+)-ATPase protein recovered in plasma membranes indicate a highly expressed gene. The plasma membrane ATPase was purified to about 90% homogeneity and appeared to be blocked at the amino terminus. Three hydrophobic membrane sector tryptic fragments from the partially digested ATPase provided internal sequence information for over 50 amino acids, which agrees with the sequence predicted by the cloned gene. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the C. albicans enzyme is about 3 kDa smaller than its Saccharomyces counterpart and was consistent with a predicted Mr of 97,398. Antibodies to the S. cerevisiae whole ATPase or its carboxyl terminus bound to the C. albicans enzyme but with lower avidity. Kinetic analysis showed that the Candida and Saccharomyces ATPases respond to glucose activation-starvation in nonidentical fashions. The amino-terminal domain of the C. albicans ATPase is marked by a net deletion of 23 amino acids in comparison with the S. cerevisiae ATPase. These differences maintain net charge, occur in nonconserved regions of fungal ATPases, and are sufficient to account for the observed difference in electrophoretic mobility between the two yeast ATPases.
Expression of the diphtheria toxin A-chain coding sequence under the control of promoters and enhancers from immunoglobulin genes as a means of directing toxicity to B-lymphoid cells. (1991)

Previous results have shown that cells can be killed by the expression of an introduced gene encoding diphtheria toxin A-fragment (DT-A) and that killing can be targeted using tissue-specific transcriptional regulatory elements. Here, we describe expression plasmids containing the DT-A gene linked with promoters and enhancers from immunoglobulin heavy chain or kappa-light chain genes. When these plasmids were transfected into cultured cells, DT-A was expressed in B-lymphoid cells but not detectably in HeLa cells or fibroblasts. A high specificity for B-cells was confirmed by assaying for luciferase reporter gene expression from a plasmid containing an analogous combination of immunoglobulin heavy chain regulatory elements. A plasmid containing an immunoglobulin-kappa promoter and enhancer was substantially less active in expressing DT-A in a pre-B-cell line than in B-lymphoma cells, suggesting the possibility of targeting DT-A expression to mature, malignant B-cells while sparing normal B-cell progenitors. By means of viral delivery vehicles, the constructs described might be applied in gene therapy for B-cell leukemias or lymphomas.
Dynamic spectrum management for next-generation DSL systems (2002)

The performance of DSL systems is severely constrained by crosstalk due to the electromagnetic coupling among the multiple twisted pairs making up a phone cable. In order to reduce performance loss arising from crosstalk, DSL systems are currently designed under the assumption of worst-case crosstalk scenarios leading to overly conservative DSL deployments. This article presents a new paradigm for DSL system design, which takes into account the multi-user aspects of the DSL transmission environment. Dynamic spectrum management (DSM) departs from the current design philosophy by enabling transceivers to autonomously and dynamically optimize their communication settings with respect to both the channel and the transmissions of neighboring systems. Along with this distributed optimization, when an additional degree of coordination becomes available for future DSL deployment, DSM will allow even greater improvement in DSL performance. Implementations are readily applicable without causing any performance degradation to the existing DSLs under static spectrum management. After providing an overview of the DSM concept, this article reviews two practical DSM methods: iterative water-filling, an autonomous distributed power control method enabling great improvement in performance, which can be implemented through software options in some existing ADSL and VDSL systems; and vectored-DMT, a coordinated transmission/reception technique achieving crosstalk-free communication for DSL systems, which brings within reach the dream of providing universal Internet access at speeds close to 100 Mb/s to 500 m on 1-2 lines and beyond 1 km on 2-4 lines. DSM-capable DSL thus enables the broadband age.
Alterations in the frequency of dendritic cell subsets in the peripheral circulation of patients with squamous cell carcinomas of the head and neck. (2002)

Patients with advanced squamous cell carcinomas of the head and neck (SCCHN) are frequently immunocompromised. Dendritic cells (DCs) are potent antigen-presenting cells that play a role in antitumor immune responses. Using multicolor flow cytometry, the percentages of lineage-negative (LIN(-)) and DR(+) DC precursors, as well as their LIN(-)DR(+)CD11c(+) (myeloid) and LIN(-)DR(+)CD123(+) (lymphoid) subsets, were determined in the peripheral blood of 36 patients with SCCHN before surgery. Peripheral blood mononuclear cells of 28 age- and sex-matched healthy individuals were used as controls. The proportions of LIN(-)DR(+) cells were found to be comparable in the circulation of patients and controls. However, the relative level of DR expression in LIN(-)DR(+) DC was lower in patients than in controls, suggesting a difference in the maturity of DC. The relative proportion of LIN(-)DR(+)CD123(+) cells in the LIN(-)DR(+) subset of DC did not differ significantly in patients compared with normal individuals. However, the percentage of myeloid-derived LIN(-)DR(+)CD11c(+) DCs was significantly lower (P < 0.002) in SCCHN patients than in controls. Of the 13 patients who were restudied 6 weeks after surgery, 9 showed an increase of the myeloid-derived LIN(-)DR(+)CD11c(+) DC subset postoperatively. This observation suggests that deficiency in the myeloid-derived DC precursors in patients with SCCHN is related to the presence of tumor and is reversible. An overall decrease in the myeloid-derived subset of DC could contribute to the failure of SCCHN patients to develop effective antitumor immune responses.
N‐methyl‐D‐aspartate antagonists: Ready for clinical trial in brain ischemia? (1989)

Antagonists of the N-methyl-D-aspartate (NMDA) subclass of glutamate receptors may offer a new approach for the treatment of ischemic brain injury. This strategy is supported by a well-developed scientific foundation and encouraging results in a variety of in vivo and in vitro experimental models. Several specific antagonists, including MK-801, dextrorphan, dextromethorphan, and ketamine, have already been used at low doses in humans for other indications and are potential candidates for Phase I clinical trials.
Oxidation of Silicon Using Electron Cyclotron Resonance Nitrous Oxide Plasma and Its Application to Polycrystalline Silicon Thin Film Transistors (1997)

Electron cyclotron resonance nitrous oxide plasma oxidation has been investigated as a process to grow thin oxide on polycrystalline silicon and (100), (111), and (110) oriented crystalline silicon. In spite of a low thermal budget, plasma oxidation incorporates nitrogen atoms at the silicon/silicon dioxide interface and forms a nitrogen‐rich layer. The incorporated nitrogen atoms are tightly bound to silicon atoms at the interface with N (1s) electron energy of 397.8 eV. The oxidation rate in plasma is less dependent on crystalline orientation in comparison with thermal , and is therefore nearly identical in poly‐ and single‐crystalline‐Si. Polysilicon oxide (polyoxide) grown by plasma oxidation exhibits better electrical properties than thermally grown oxides; this is attributed to the smooth interface between the polyoxide and a poly‐Si film. Polysilicon thin film transistors fabricated with plasma oxide show improved performance, which is attributed not only to the smooth interface but also to oxygen‐ and nitrogen‐plasma passivation.
Analysis of the DNA joining repertoire of Chlorella virus DNA ligase and a new crystal structure of the ligase-adenylate intermediate (2003)

Chlorella virus DNA ligase is the smallest eukaryotic ATP-dependent DNA ligase known; it suffices for yeast cell growth in lieu of the essential yeast DNA ligase Cdc9. The Chlorella virus ligase-adenylate intermediate has an intrinsic nick sensing function and its DNA footprint extends 8-9 nt on the 3'-hydroxyl (3'-OH) side of the nick and 11-12 nt on the 5'-phosphate (5'-PO4) side. Here we establish the minimal length requirements for ligatable 3'-OH and 5'-PO4 strands at the nick (6 nt) and describe a new crystal structure of the ligase-adenylate in a state construed to reflect the configuration of the active site prior to nick recognition. Comparison with a previous structure of the ligase-adenylate bound to sulfate (a mimetic of the nick 5'-PO4) suggests how the positions and contacts of the active site components and the bound adenylate are remodeled by DNA binding. We find that the minimal Chlorella virus ligase is capable of catalyzing non-homologous end-joining reactions in vivo in yeast, a process normally executed by the structurally more complex cellular Lig4 enzyme. Our results suggest a model of ligase evolution in which: (i) a small 'pluripotent' ligase is the progenitor of the much larger ligases found presently in eukaryotic cells and (ii) gene duplications, variations within the core ligase structure and the fusion of new domains to the core structure (affording new protein-protein interactions) led to the compartmentalization of eukaryotic ligase function, i.e. by enhancing some components of the functional repertoire of the ancestral ligase while disabling others.
Analysis and design of large leaky-mode array employing the coupled-mode approach (2001)

This paper presents the coupled-mode approach to the analysis and design of a large leaky-mode array, in which an N-element microstrip array above a common ground plane supports N coupled leaky modes (leaky EH/sub 1/ modes) at the first higher order. Following a brief description of a conventional full-wave nonstandard eigenvalue problem for solving the complex propagation constants, we present the detailed formulation of the coupled-mode approach, clearly showing the transformation of the nonstandard eigenvalue problem into a standard one. Thus, all the eigenvalues (complex propagation constants) and eigenvectors (modal current distributions) are solved simultaneously, regardless of the size of the array (N). Two key issues pertinent to the successful implementation of the proposed coupled-mode approach are addressed: the determination of the coupling coefficients and the uniqueness of the isolated uncoupled leaky mode, which represents the leaky modal solution of a single microstrip, but is derived from a system of coupled leaky-mode solutions provided the coupled microstrips have equal width and spacing. Closed-form expressions for obtaining the coupling coefficients of orders two, three, and four are presented. Theoretical studies of closely coupled microstrip arrays of two, three, and four elements show that the magnitude of the coupling coefficient /sub i,i+j/ between elements i and i+ decreases at the order of 10/sup -j/. These theoretical case studies also lead to the same isolated uncoupled leaky-mode solution as predicted. Furthermore, the dispersion characteristics of the microstrip array at the first higher order obtained by the coupled-mode approach and the full-wave approach agree excellently for all the case studies. Error analyses indicated that at least two coupling coefficients (C/sub i,i+1/ andC/sub i,i+2/) are required for obtaining accurate complex propagation constants with rms errors less than 1% for most of the leaky region of the particular array under investigation. An example of applying the proposed coupled-mode- approach for analyzing a corporate-fed leaky-mode array of eight elements is reported, revealing that only four out of the eight leaky modes are excited. The coupled-mode theory predicts the far-field radiation pattern in the main beam region in excellent agreement with the measured results.
Evaluation of phenylaminopyrimidines as antifungal protein kinase inhibitors (2005)

The effects of diverse phenylaminopyrimidines (PAP), namely PAP-pyridines (type A), PAP-pyrazoles (type B) and PAP-thiazoles (type C), on Neurospora crassa Shear & Dodge has been investigated. The results revealed that type A strongly inhibit the in vitro growth of N crassa, whereas types B and C are much less active. A significant correlation was observed between the Neurospora growth inhibition and the intrinsic activity of type A compounds on the cyclin-dependent protein kinase p34(CDC2) of starfish, suggesting that the target of phenylaminopyrimidines in fungi is a cyclin-dependent protein kinase (CDK). The phenylaminopyrimidine-binding CDKs Phoss (major band) and CDC2 (minor band) involved in phosphorus uptake, glycogen synthesis and the cell cycle were identified from N crassa by affinity chromatography on phenylaminopyrimidine-sepharose. Comparative experiments with different protein kinases revealed the importance of the side chain of phenylaminopyrimidines for their target selectivity. A type B compound was found to selectively inhibit the MAP-kinase OS-2 involved in the osmoregulatory pathway of Neurospora.
Enzyme-Linked Immunosorbent Assay for Detection of Plasmodium falciparum Histidine-Rich Protein 2 in Blood, Plasma, and Serum (2008)

Microscopy, the gold standard for the detection and quantification of malaria parasites in blood, is in many aspects deficient for this purpose. The method is poorly reproducible and can be inaccurate because Plasmodium falciparum parasites sequester for a portion of each asexual cycle. Due to these deficiencies, biomarkers such as P. falciparum histidine-rich protein 2 (PfHRP2) are increasingly being used. In this study, we evaluated the use of a commercial PfHRP2 enzyme-linked immunosorbent assay (ELISA) kit with some procedural modifications. We determined the linear range of the assay, including the lower limits of detection and quantitation, using recombinant PfHRP2 (rPfHRP2). In 10 repeat experiments, the linear range of optical densities (ODs) at 450 to 650 nm was from 0.05 +/- 0.002 to 2.28 +/- 0.042, corresponding to 3.91 to 250 ng/ml of rPfHRP2. The coefficient of variation (CV) at each target concentration ranged from 1.93 to 8.07%. Using cultured parasites, we confirmed the linear range of ODs as well as the association between the PfHRP2 ELISA results and the microscopic parasite densities. For whole-blood samples spiked with cultured, washed, ring-stage-infected red blood cells (iRBCs), the linear range was 11.7 to 750 iRBCs/microl, with CVs of 0.29 to 7.56%. The same spiked samples evaluated by microscopists had similar sensitivities, but the CVs were unacceptably high (20.7 to 161.6%). Stock rPfHRP2 was stable through four freeze-thaw cycles (P < 0.05; paired t test). When different patient sample types at different concentrations within the linear range of the assay are compared, the recoveries of PfHRP2 from blood and serum were within +/-20%, whereas the recoveries from plasma ranged between +35 and -41%. We conclude that PfHRP2 ELISA using whole-blood and serum samples is a suitable adjunct to microscopy and could ultimately benefit malaria intervention trials.
Mechanical Properties of Tendons: Changes With Sterilization and Preservation (1996)

Tendon allografts are commonly used to replace damaged anterior cruciate ligaments (ACL). Some of the sterilization and preservation techniques used by tissue banks with tendon allografts are thought to impair the mechanical properties of graft tissues. The tensile mechanical properties of porcine toe extensor tendons were measured using a dynamic testing machine following either freezing, freeze-drying, freezing then irradiation at 25 kGy (2.5 MRad), freeze-drying then irradiation, or freeze-drying then ethylene oxide gas sterilization. There was a small but significant difference in Young's modulus between the frozen group (0.88 GPa + 0.09 SD) and both the fresh group (0.98 GPa 1 0.12 SD) and the frozen irradiated group (0.97 GPa 1 0.08 SD). No values of Young's modulus were obtained for the freeze-dried irradiated tendons. The ultimate tensile stress (UTS) of the freeze-dried irradiated group (4.7 MPa 1 4.8 SD) was significantly different from both the fresh and the frozen irradiated groups, being reduced by approximately 90 percent. There were no significant changes in UTS or Young's modulus between any of the other groups. If irradiation is to be used to sterilize a tendon replacement for an ACL it must take place after freeze-drying to maintain mechanical properties.