gebhart/patrepeval huggingface dataset:
Ultrahigh Porosity in Metal-Organic Frameworks (2010)

Crystalline solids with extended non-interpenetrating three-dimensional crystal structures were synthesized that support well-defined pores with internal diameters of up to 48 angstroms. The Zn4O(CO2)6 unit was joined with either one or two kinds of organic link, 4,4',4''-[benzene-1,3,5-triyl-tris(ethyne-2,1-diyl)]tribenzoate (BTE), 4,4',44''-[benzene-1,3,5-triyl-tris(benzene-4,1-diyl)]tribenzoate (BBC), 4,4',44''-benzene-1,3,5-triyl-tribenzoate (BTB)/2,6-naphthalenedicarboxylate (NDC), and BTE/biphenyl-4,4'-dicarboxylate (BPDC), to give four metal-organic frameworks (MOFs), MOF-180, -200, -205, and -210, respectively. Members of this series of MOFs show exceptional porosities and gas (hydrogen, methane, and carbon dioxide) uptake capacities. For example, MOF-210 has Brunauer-Emmett-Teller and Langmuir surface areas of 6240 and 10,400 square meters per gram, respectively, and a total carbon dioxide storage capacity of 2870 milligrams per gram. The volume-specific internal surface area of MOF-210 (2060 square meters per cubic centimeter) is equivalent to the outer surface of nanoparticles (3-nanometer cubes) and near the ultimate adsorption limit for solid materials.
Induction of primary NY-ESO-1 immunity: CD8+ T lymphocyte and antibody responses in peptide-vaccinated patients with NY-ESO-1+ cancers (2000)

Cancer-testis antigen NY-ESO-1 is one of the most immunogenic tumor antigens defined to date. Spontaneous humoral and CD8+ T-cell responses to NY-ESO-1 are detected in 40-50% of patients with advanced NY-ESO-1-expressing tumors. A clinical trial was initiated to study the immunological effects of intradermal vaccination with 3 HLA-A2-binding NY-ESO-1 peptides in 12 patients with metastatic NY-ESO-1-expressing cancers. Seven patients were NY-ESO-1 serum antibody negative, and five patients were NY-ESO-1 serum antibody positive at the outset of the study. Primary peptide-specific CD8+ T-cell reactions and delayed-type hypersensitivity responses were generated in four of seven NY-ESO-1 antibody-negative patients. Induction of a specific CD8+ T-cell response to NY-ESO-1 in immunized antibody-negative patients was associated with disease stabilization and objective regression of single metastases. NY-ESO-1 antibody-positive patients did not develop significant changes in baseline NY-ESO-1-specific T-cell reactivity. However, stabilization of disease and regression of individual metastases were observed in three of five immunized patients. These results demonstrate that primary NY-ESO-1-specific CD8+ T-cell responses can be induced by intradermal immunization with NY-ESO-1 peptides, and that immunization with NY-ESO-1 may have the potential to alter the natural course of NY-ESO-1-expressing tumors.
Efficacy of the Carbocyclic 2′-Deoxyguanosine Nucleoside BMS-200475 in the Woodchuck Model of Hepatitis B Virus Infection (1998)

Daily oral treatment with the cyclopentyl 2'-deoxyguanosine nucleoside BMS-200475 at doses ranging from 0.02 to 0.5 mg/kg of body weight for 1 to 3 months effectively reduced the level of woodchuck hepatitis virus (WHV) viremia in chronically infected woodchucks as measured by reductions in serum WHV DNA levels and endogenous hepadnaviral polymerase activity. Within 4 weeks of daily therapy with 0.5 or 0.1 mg of BMS-200475 per kg, endogenous viral polymerase levels in serum were reduced about 1,000-fold compared to pretreatment levels. Serum WHV DNA levels determined by a dot blot hybridization technique were comparably decreased in these treated animals. In the 3-month study, the sera of animals that had undetectable levels of WHV DNA by the dot blot technique were further analyzed by a highly sensitive semiquantitative PCR assay. The results indicate that BMS-200475 therapy reduced mean WHV titers by 10(7)- to 10(8)-fold, down to levels as low as 10(2) to 10(3) virions/ml of serum. Southern blot hybridization analysis of liver biopsy samples taken from animals during and after BMS-200475 treatment showed remarkable reductions in the levels of WHV DNA replicative intermediates and in the levels of covalently closed circular viral DNA. WHV viremia in BMS-200475-treated WHV carriers eventually returned to pretreatment levels after therapy was stopped. These results indicate that BMS-200475 should be evaluated in clinical trials for the therapy of chronic human hepatitis B virus infections.
Bone Morphogenetic Protein-1: The Type I Procollagen C-Proteinase (1996)

Bone morphogenetic proteins (BMPs) are bone-derived factors capable of inducing ectopic bone formation. Unlike other BMPs, BMP-1 is not like transforming growth factor-beta (TGF-beta), but it is the prototype of a family of putative proteases implicated in pattern formation during development in diverse organisms. Although some members of this group, such as Drosophila tolloid (TLD), are postulated to activate TGF-beta-like proteins, actual substrates are unknown. Procollagen C-proteinase (PCP) cleaves the COOH-propeptides of procollagens I, II, and III to yield the major fibrous components of vertebrate extracellular matrix. Here it is shown that BMP-1 and PCP are identical. This demonstration of enzymatic activity for a BMP-1/TLD-like protein links an enzyme involved in matrix deposition to genes involved in pattern formation.
Growth factor receptor kinase inhibitors: recent progress and clinical impact. (2001)

Inhibition of growth factor receptor kinases is one of the most promising therapeutic approaches for the treatment of cancer. This review focuses on the most recent progress in this area, and gives an overview of the compounds currently in the clinic, as well as key preclinical analogs.
Structures of hemicelluloses and pectins in wood and pulp (2005)

This work aims to fill gaps in the present knowledge of the structures of wood polysaccharides of potential importance in mechanical and chemical pulping. The detailed structures of the polysaccharide components from wood that dissolve during mechanical pulping were determined. The structures of polysaccharide components linked to residual lignin in chemical pulp were also determined. Methylation analysis as linkage analysis was further developed and verified for this purpose using the procedure methylation, methanolysis, silylation and GC/MS analysis.\n\nWater-soluble arabinogalactans obtained from spruce and pine heartwood were analyzed using methylation analysis, NMR spectroscopy and carbohydrate composition analysis. The arabinogalactans isolated were acidic and had a backbone of β-(1→3)-linked D-galactopyranose units, highly branched at C6. Water-soluble galactoglucomannans were extracted from spruce wood and TMP. Based on both methylation analysis and NMR spectroscopic analysis, the main C6-branched unit was D-mannopyranose. Some C6-branched D-glucopyranose units were also detected by methylation analysis.\n\nThe polysaccharides that dissolved during oxygen delignification of pine kraft pulp comprised mainly xylan, together with galactans, 1,3-linked glucan, arabinan and glucomannan. This indicated that the glucose units present in the dissolved polysaccharides did not originate from cellulose but from a 1,3-linked glucan. This was a new and unexpected finding indicating that the content of dissolved glucose is not related to the degree of cellulose degradation. Polysaccharides in the corresponding filtrates from birch kraft pulp also contained mainly xylan. An indication was found for the presence of bonds between lignin and position C3 of the backbone units in birch xylan.\n\nResidual lignin-carbohydrate complexes (RLCCs) isolated from spruce and pine kraft pulps contained oligosaccharides representing the main polysaccharides in softwood. In addition, 1,4-linked and 1,3/6-linked galactans were present in considerable amounts, together with smaller amounts of 1,3-linked glucan and 1,5-linked arabinan, and possibly also xyloglucan. 1,4-linked galactan was enriched in the RLCC of spruce fiber surface material. Towards the inner part of the fiber, 1,3/6-linked galactan became the major lignin-bound galactan structure. Some differences related to the alkaline cooking method used were detected in the carbohydrate component of pine pulp RLCCs. Oxygen delignification removed 1,3/6-linked galactan from the inner parts of fiber in preference to 1,4-linked galactan.
The existence of refinement mappings (2003)

Refinement mappings are used to prove that a lower-level specification correctly implements a higher-level one. The authors consider specifications consisting of a state machine (which may be infinite-state) that specifies safety requirements and an arbitrary supplementary property that specifies liveness requirements. A refinement mapping from a lower-level specification S/sub 1/ to higher-level one S/sub 2/ is a mapping from S/sub 1/'s state space to S/sub 2/'s state space that maps steps of S/sub 1/'s state machine steps to steps of S/sub 2/'s state machine and maps behaviors allowed by S/sub 1/ to behaviors allowed by S/sub 2/. It is shown that under reasonable assumptions about the specifications, if S/sub 1/ implements S/sub 2/, then by adding auxiliary variables to S/sub 1/ one can guarantee the existence of a refinement mapping. This provides a completeness result for a practical hierarchical specification method.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A survey of glove-based input (1994)

Clumsy intermediary devices constrain our interaction with computers and their applications. Glove-based input devices let us apply our manual dexterity to the task. We provide a basis for understanding the field by describing key hand-tracking technologies and applications using glove-based input. The bulk of development in glove-based input has taken place very recently, and not all of it is easily accessible in the literature. We present a cross-section of the field to date. Hand-tracking devices may use the following technologies: position tracking, optical tracking, marker systems, silhouette analysis, magnetic tracking or acoustic tracking. Actual glove technologies on the market include: Sayre glove, MIT LED glove, Digital Data Entry Glove, DataGlove, Dexterous HandMaster, Power Glove, CyberGlove and Space Glove. Various applications of glove technologies include projects into the pursuit of natural interfaces, systems for understanding signed languages, teleoperation and robotic control, computer-based puppetry, and musical performance.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
FoxA1 Specifies Unique Androgen and Glucocorticoid Receptor Binding Events in Prostate Cancer Cells (2012)

The forkhead protein FoxA1 has functions other than a pioneer factor, in that its depletion brings about a significant redistribution in the androgen receptor (AR) and glucocorticoid receptor (GR) cistromes. In this study, we found a novel function for FoxA1 in defining the cell-type specificity of AR- and GR-binding events in a distinct fashion, namely, for AR in LNCaP-1F5 cells and for GR in VCaP cells. We also found different, cell-type and receptor-specific compilations of cis-elements enriched adjacent to the AR- and GR-binding sites. The AR pathway is central in prostate cancer biology, but the role of GR is poorly known. We find that AR and GR cistromes and transcription programs exhibit significant overlap, and GR regulates a large number of genes considered to be AR pathway-specific. This raises questions about the role of GR in maintaining the AR pathway under androgen-deprived conditions in castration-resistant prostate cancer patients. However, in the presence of androgen, ligand-occupied GR acts as a partial antiandrogen and attenuates the AR-dependent transcription program. .
Design and Evolution of a Miniature Bcl-2 Binding Protein (2001)

A major challenge for chemical biologists lies in the design of potent and selective ligands for protein surfaces. Here a protein grafting and evolution strategy is used to discover highly potent and specific miniature protein ligands for human Bcl-2 and Bcl-X<sub>L</sub> . Miniature proteins could be used to dissect, modulate, or analyze a single protein function, irrespective of the other functions the protein may regulate within the proteome.
High quality quasi-Bessel beam generated by round-tip axicon (2008)

We study theoretically and experimentally the spatial intensity distribution of the zero-order Bessel beam formed by the axicon which possess a rounded tip. Such a tip generates a refracted beam that interferes with the quasi-Bessel beam created behind the axicon. In turn an undesired intensity modulation occurs that significantly disturbs the unique properties of the quasi-Bessel beam--namely the constant shape of the lateral intensity distribution and the slow variation of the on-axis beam intensity along the beam propagation. We show how the spatial filtration of the beam in the Fourier plane improves this spatial beam distribution and removes the undesired modulation. We use an efficient numerical method based on Hankel transformations to simulate the propagation of the beam behind the axicon and filter. We experimentally measure the intensity distribution of the beam in many lateral planes and subsequently reconstruct the spatial intensity distribution of the beam. Computed and measured beam distributions are compared and the obtained agreement is very good.
DNA‐dependent protein kinase catalytic subunit mediates T‐cell loss in rheumatoid arthritis (2010)

In the autoimmune syndrome rheumatoid arthritis (RA), T cells and T-cell precursors have age-inappropriate shortening of telomeres and accumulate deoxyribonucleic acid (DNA) double strand breaks. Whether damaged DNA elicits DNA repair activity and how this affects T-cell function and survival is unknown. Here, we report that naïve and resting T cells from RA patients are susceptible to undergo apoptosis. In such T cells, unrepaired DNA stimulates a p53-ataxia telangiectasia mutated-independent pathway involving the non-homologous-end-joining protein DNA-protein kinase catalytic subunit (DNA-PKcs). Upregulation of DNA-PKcs transcription, protein expression and phosphorylation in RA T cells co-occurs with diminished expression of the Ku70/80 heterodimer, limiting DNA repair capacity. Inhibition of DNA-PKcs kinase activity or gene silencing of DNA-PKcs protects RA T cells from apoptosis. DNA-PKcs induces T-cell death by activating the JNK pathway and upregulating the apoptogenic BH3-only proteins Bim and Bmf. In essence, in RA, the DNA-PKcs-JNK-Bim/Bmf axis transmits genotoxic stress into shortened survival of naïve resting T cells, imposing chronic proliferative turnover of the immune system and premature immunosenescence. Therapeutic blockade of the DNA-PK-dependent cell-death machinery may rejuvenate the immune system in RA.
Engineered Polymeric Nanoparticles for Receptor-Targeted Blockage of Oxidized Low Density Lipoprotein Uptake and Atherogenesis in Macrophages (2006)

Strategies to prevent the uptake of modified low density lipoproteins (LDLs) by immune cells, a major trigger of inflammation and atherogenesis, are challenged by complex interfacial factors governing LDL receptor-mediated uptake. We examine a new approach based on a family of "nanoblockers", which are designed to examine the role of size, charge presentation, and architecture on inhibition of highly oxidized LDL (hoxLDL) uptake in macrophages. The nanoblockers are macromolecules containing mucic acid, lauryl chloride, and poly(ethylene glycol) that self-assemble into 15-20 nm nanoparticles. We report that the micellar configuration of the macromolecules and the combined display of anionic (carboxylate) groups in the hydrophobic region of the nanoblockers caused the most effective inhibition in the uptake of hoxLDL by IC21 macrophages. The nanoblockers primarily targeted SR-A and CD36, the major scavenger receptors and modulated the "atherogenic" phenotype of cells in terms of the degree of cytokine secretion, accumulation of cholesterol, and "foam cell" formation. These studies highlight the promise of synthetically engineered nanoblockers against oxidized LDL uptake.
Pulsatile Release of Gonadotropin-Releasing Hormone from Hypothalamic Explants Is Restrained by Blockade ofN-Methyl-D,L-Aspartate Receptors* (1989)

We have shown previously that N-methyl-D,L-aspartate (NMDA) and kainate, two neuroexcitatory amino acids acting through distinct receptors, may induce the release of GnRH from hypothalamic explants. However, that effect could have no physiological significance, since very high concentrations (50 mM) of NMDA and kainate were required. Here, using agents blocking the activation of receptors to neuroexcitatory amino acids, we evaluated their possible physiological involvement in the pulsatile release of GnRH from the hypothalamus of 50-day-old male rats in vitro. In control conditions (10 nM glycine and 1 mM mg2+), the release of GnRH in 7.5-min fractions collected for 2-4 h showed an obvious pulsatile pattern. The mean (+/- 1 SD) interval between pulses, identified by PULSAR program, was 34.3 +/- 11.4 min. The stimulation of GnRH release by NMDA (50 mM) added to the medium for 7.5 min could be blocked reversibly in the presence of MK-801 (100 microM) using medium without glycine or enriched with Mg2+ (2 mM). The endogenous pulses of GnRH secretion were abolished in the presence of MK-801 or using increased Mg2+ concentrations as well as in the absence of glycine. In contrast, pulsatile release of GnRH was not affected in the presence of 6,7-dinitroquinoxaline-2,3-dione (0.1 mM), a selective inhibitor of kainate and quisqualate receptors which suppressed the increase in GnRH release induced by kainate (50 mM) without affecting the response to NMDA. These data indicate that the physiological mechanism of pulsatile GnRH secretion in the hypothalamus may involve endogenous neuroexcitatory factors acting through NMDA-sensitive receptors.
A Novel Facile Method of Labeling Octreotide with 18F-Fluorine (2010)

NOTA-octreotide could be labeled rapidly and efficiently with (18)F using a 2-step, 1-pot method. The compound was stable in vivo and showed rapid accretion in somatostatin receptor subtype 2-expressing AR42J tumors in nude mice. This method can be used to label other NOTA-conjugated compounds with (18)F.
Covalent Inhibitors of Interleukin-2 Inducible T Cell Kinase (Itk) with Nanomolar Potency in a Whole-Blood Assay (2012)

We wish to report a strategy that targets interleukin-2 inducible T cell kinase (Itk) with covalent inhibitors. Thus far, covalent inhibition of Itk has not been disclosed in the literature. Structure-based drug design was utilized to achieve low nanomolar potency of the disclosed series even at high ATP concentrations. Kinetic measurements confirmed an irreversible binding mode with off-rate half-lives exceeding 24 h and moderate on-rates. The analogues are highly potent in a cellular IP1 assay as well as in a human whole-blood (hWB) assay. Despite a half-life of approximately 2 h in resting primary T cells, the covalent inhibition of Itk resulted in functional silencing of the TCR pathway for more than 24 h. This prolonged effect indicates that covalent inhibition is a viable strategy to target the inactivation of Itk.
Modification of Food Cariogenicity in Rats by Mineral-rich Concentrates from Milk (1987)

Dairy products, including milk, cheese, and casein, can reduce the caries-causing potential of cariogenic substrates as measured in various animal, plaque acidity, and in vitro systems. Although the mechanisms responsible for protection are not completely identified, substances containing Ca and P may contribute to the protective potential by reducing demineralization and/or promoting remineralization of enamel. Casein may reduce demineralization by forming a protective coat on the enamel surface. By means of a rat model, this study evaluated the ability of three casein-free milk mineral concentrates with various levels of whey protein, calcium, and phosphate to modify the cariogenicity of a powdered diet containing 20% sucrose. Analysis of these data indicates that there were no significant differences among groups for weight gain, total food consumption, or feeding frequency, as monitored by a computer-based infrared activity monitor. All three mineral concentrates significantly reduced buccal caries, and two of the three reduced sulcal caries by from 10 to 30%. The analysis further shows that casein-free milk mineral fractions can modify the cariogenicity of sucrose-containing foods in a rat model.
Drying Rates following Priming Affect Temperature Sensitivity of Germination and Longevity of Lettuce Seeds (2005)

Seed priming (controlled hydration followed by drying) is used to alleviate high temperature inhibition of germination and improve seedling emergence of lettuce ( Lactuca sativa L.) and other species. However, seed priming can also reduce the longevity of seeds during dry storage. Alternative drying methods [i.e., slow drying or moisture content reduction (MCR) before drying] can extend seed longevity compared to conventional rapid drying procedures after priming. Three postpriming drying treatments were tested on `Conquistador' and `Genecorp Green' lettuce seeds: rapid drying, slow drying and MCR (10% fresh weight loss, then held at 100% relative humidity (RH) for 6 hours, followed by rapid drying). The effects of the postpriming treatments on seed quality and longevity were compared based upon standard germination tests, germination rates, thermogradient table tests, controlled deterioration (CD) tests, and headspace volatiles analysis. The latter may be correlated with seed longevity as release of volatiles (e.g., acetaldehyde, ethanol) is associated with lipid peroxidation. While neither slow drying nor MCR before drying restored lettuce seed longevity to that of the control (not primed) seeds, the MCR method generally gave better results in both cultivars compared to rapid drying. Among the CD test conditions used, 50 °C and 75% RH gave the most consistent results for estimating potential longevity. Headspace volatile emissions from both control and primed lettuce seeds were very low and were not well correlated with seed longevity. Alternative postpriming drying regimes can extend seed longevity while retaining the beneficial effects of priming.
Lest We Forget: Celebrating Thirty Years of Clinical Legal Education at William Mitchell College of Law (2003)

Speech given at Reunion of Early Clinic Directors and Participants, March 20, 2003.
Molecular Mechanism and Functional Significance of the MinK Control of the KvLQT1 Channel Activity (1997)

The very slowly activating delayed rectifier K+ channel IKs is essential for controlling the repolarization phase of cardiac action potentials and K+ homeostasis in the inner ear. The IKs channel is formed via the assembly of two transmembrane proteins, KvLQT1 and MinK. Mutations in KvLQT1 are associated with a long QT syndrome that causes syncope and sudden death and also with deafness. Here, we show a new mode of association between ion channel forming subunits in that the cytoplasmic C-terminal end of MinK interacts directly with the pore region of KvLQT1. This interaction reduces KvLQT1 channel conductance from 7.6 to 0.58 picosiemens. However, because MinK also reveals a large number of previously silent KvLQT1 channels (x 60), the overall effect is a large increase (x 4) in the macroscopic K+ current. Conformational changes associated with the KvLQT1/MinK association create very slow and complex activation kinetics without much alteration in the deactivation process. Changes induced by MinK have an essential regulatory role in the development of this K+ channel activity upon repetitive electrical stimulation with a particular interest in tachycardia.
A novel polymorphism in the Fcγ receptor IIB (CD32B) transmembrane region alters receptor signaling (2003)

The differential activity of FCGR2B alleles suggests a novel mechanism of FcgammaRIIb regulation that may influence the risk of autoimmune disease.