gebhart/patrepeval huggingface dataset:
Phakometry and lens tilt and decentration using a custom-developed Purkinje imaging apparatus: validation and measurements (2006)

We present a Purkinje imaging system for phakometry and measurement of tilt and decentration of crystalline and intraocular lenses (IOLs). Crystalline lens radii of curvature were estimated by using both a merit function and the equivalent mirror approaches. Tilts and decentrations were estimated by using Phillips's linear analysis. We present a complete validation of the technique through exhaustive computer simulations and control experiments, and measurements in 17 normal eyes (mean age 26.67 +/- 2.31) and nine postcataract surgery eyes (mean age 74 +/- 2.3). Crystalline lens radii ranged from 12.7 to 8.81 mm and from -5.64 to -7.09 mm for anterior and posterior surfaces, respectively. Crystalline lens tilt ranged from 2.8 to -2.87 deg horizontally and from 2.58 to -1 deg vertically. Crystalline lens decentration ranged from 0.09 to 0.45 mm horizontally and from 0.09 to -0.22 mm vertically. IOL tilt ranged from 3.6 to -1.51 deg horizontally and from 5.97 to -1.85 deg vertically. IOL decentration ranged from 0.53 to -0.31 mm horizontally and from 0.13 to -0.96 mm vertically.
The novel GLP ‐1‐gastrin dual agonist, ZP3022 , increases β‐cell mass and prevents diabetes in db/db mice (2012)

The novel GLP-1-gastrin dual agonist, ZP3022, improved glycaemic control in db/db mice, and pancreatic islet and β-cell mass increased significantly following treatment with ZP3022 compared with vehicle.
Toward gene therapy for growth hormone deficiency via salivary gland expression of growth hormone (2013)

This study demonstrates that mutagenesis of therapeutic proteins normally destined for the regulated secretory pathway may result in their secretion via the constitutive secretory pathway into the circulation for potential therapeutic benefit.
Autoantigen-pulsed dendritic cells induce tolerance to experimental allergic encephalomyelitis (EAE) in Lewis rats (2000)

Dendritic cells (DC) can modulate the nature of immune responses in a stimulatory or tolerogenic fashion. Great attention has been given to the induction of immunity to tumour and infection. In this study, bone marrow-derived DC from healthy Lewis rats were pulsed in vitro with encephalitogenic myelin basic protein peptide 68-86 (MBP 68-86), and injected subcutaneously (1 x 106/rat) into normal Lewis rats. Upon observation of the rats pretreated in this way for 4 weeks, when no clinical signs of EAE occurred, these rats were immunized with MBP 68-86 and Freund's complete adjuvant. The pretreated rats failed to develop clinical EAE. This tolerance was associated with augmented proliferative responses, interferon-gamma secretion, inducible nitric oxide synthase (iNOS) expression and NO production. The frequency of apoptotic cells was increased in the rats receiving MBP 68-86-pulsed DC compared with unpulsed control DC. Few infiltrating inflammatory cells were observed in spinal cord sections from rats that had received MBP 68-86-pulsed DC. The data are compatible with the interpretation that MBP 68-86-pulsed DC induce tolerance to EAE possibly through up-regulation of iNOS expression and NO production, which mediate cell apoptosis, thereby reducing infiltration of inflammatory cells within the central nervous system.
Generation of Substituted Styrenes via Suzuki Cross-Coupling of Aryl Halides with 2,4,6-Trivinylcyclotriboroxane (2002)

The synthesis of functionalized styrene derivatives can be readily achieved utilizing a Suzuki cross-coupling protocol between aryl halides and 2,4,6-trivinylcyclotriboroxane-pyridine complex. The scope and limitations of the procedure were demonstrated by investigation of an array of ortho-substituted aryl halides.
Geographical distribution of cases of Creutzfeldt-Jakob disease in England and Wales 1970-84. (1990)

Two hundred and sixty seven patients with a definite or probable diagnosis of Creutzfeldt-Jakob disease (CJD) were identified in an attempt to ascertain all cases of the disease in England and Wales in the period 1970-84. No evidence of space-time clustering of dates and places of onset was found for these cases. Two age- and sex-matched controls were selected for 72 of the 122 cases diagnosed in the period 1980-84 and life histories of places of residence were obtained for these cases and the controls. No evidence was found that cases had lived closer to each other than had controls at any time in their lives, except that there was an excess of cases born in London. The study does not provide supportive evidence for case-to-case transmission of CJD being an important component in the aetiology of the disease.
Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications (2018)

Abstract Targeted protein degradation has arisen as a powerful strategy for drug discovery allowing the targeting of undruggable proteins for proteasomal degradation. This approach most often employs heterobifunctional degraders consisting of a protein-targeting ligand linked to an E3 ligase recruiter to ubiquitinate and mark proteins of interest for proteasomal degradation. One challenge with this approach, however, is that only few E3 ligase recruiters currently exist for targeted protein degradation applications, despite the hundreds of known E3 ligases in the human genome. Here, we utilized activity-based protein profiling (ABPP)-based covalent ligand screening approaches to identify cysteine-reactive small-molecules that react with the E3 ubiquitin ligase RNF4 and provide chemical starting points for the design of RNF4-based degraders. The hit covalent ligand from this screen reacted with either of two zinc-coordinating cysteines in the RING domain, C132 and C135, with no effect on RNF4 activity. We further optimized the potency of this hit and incorporated this potential RNF4 recruiter into a bifunctional degrader linked to JQ1, an inhibitor of the BET family of bromodomain proteins. We demonstrate that the resulting compound CCW 28-3 is capable of degrading BRD4 in a proteasome- and RNF4-dependent manner. In this study, we have shown the feasibility of using chemoproteomics-enabled covalent ligand screening platforms to expand the scope of E3 ligase recruiters that can be exploited for targeted protein degradation applications.
Characterization of Recombinant Perlecan Domain I and Its Substitution by Glycosaminoglycans and Oligosaccharides (1997)

Recombinant mouse perlecan domain 1(173 residues) was produced in transfected embryonic kidney cells and purified from the culture medium on DEAE-cellulose. It was shown to be modified by glycosaminoglycans and could be partially separated into two protein pools which were either substituted with heparan sulfate (fragment IA) or, to a smaller extent (20%), with chondroitin/dermatan sulfate or a mixture of both glycosaminoglycans (fragment IB). The average molecular mass of the glycosaminoglycans was about 8-10 kDa and, thus, smaller than in tissue-derived perlecans. Sequence and carbohydrate analyses localized the heparan sulfate attachment site to three Ser residues within SGD consensus sequences. Furthermore, the N-terminal part of fragment IA contained six Thr/Ser residues substituted by branched galactosamine-containing oligosaccharides and an N-substituted Asn residue. Fragment I was also shown to contain unique immunological epitopes which are not dependent on glycosaminoglycans and are shared by tissue-derived perlecan. Circular dichroism demonstrated a distinct alpha helix (20%) and beta structure (60%) in fragment IA, consistent with predictions of a novel SEA protein module located in the C-terminal part of domain I.
Wound fluids: a reflection of the state of healing. (2000)

Analyzing acute and chronic wound fluids provides an important and intriguing insight into the wound milieu. This review outlines some of the salient features of wound repair and the wound fluid environment. Most studies support the premise that the contents of the wound fluid reflect the status of the wound and can be indicative of whether a wound is on the course of a normal or impaired response to injury. For example, chronic wound fluids often differ from acute wound fluids in their proliferative effects on cells active in healing as well as their proteolytic effects. The authors discuss various cytokines, growth factors, proteinases, and protease inhibitors within wound fluids as well as their effect on wound repair. This review also presents confounding factors affecting interpretation of wound fluid studies, suggesting that further studies need to elucidate mechanisms whereby wound fluids either enhance or inhibit wound repair. So far, wound fluid analysis has yielded tantalizing glimpses of the teeming wound environment. What wound fluid contents tell us about the wound or its clinical care is not yet certain.
How green is blue hydrogen? (2021)

Abstract Hydrogen is often viewed as an important energy carrier in a future decarbonized world. Currently, most hydrogen is produced by steam reforming of methane in natural gas (“gray hydrogen”), with high carbon dioxide emissions. Increasingly, many propose using carbon capture and storage to reduce these emissions, producing so‐called “blue hydrogen,” frequently promoted as low emissions. We undertake the first effort in a peer‐reviewed paper to examine the lifecycle greenhouse gas emissions of blue hydrogen accounting for emissions of both carbon dioxide and unburned fugitive methane. Far from being low carbon, greenhouse gas emissions from the production of blue hydrogen are quite high, particularly due to the release of fugitive methane. For our default assumptions (3.5% emission rate of methane from natural gas and a 20‐year global warming potential), total carbon dioxide equivalent emissions for blue hydrogen are only 9%‐12% less than for gray hydrogen. While carbon dioxide emissions are lower, fugitive methane emissions for blue hydrogen are higher than for gray hydrogen because of an increased use of natural gas to power the carbon capture. Perhaps surprisingly, the greenhouse gas footprint of blue hydrogen is more than 20% greater than burning natural gas or coal for heat and some 60% greater than burning diesel oil for heat, again with our default assumptions. In a sensitivity analysis in which the methane emission rate from natural gas is reduced to a low value of 1.54%, greenhouse gas emissions from blue hydrogen are still greater than from simply burning natural gas, and are only 18%‐25% less than for gray hydrogen. Our analysis assumes that captured carbon dioxide can be stored indefinitely, an optimistic and unproven assumption. Even if true though, the use of blue hydrogen appears difficult to justify on climate grounds.
Testosterone and/or Low Estradiol (1998)

These findings indicate that pretreatment of female mice with DHT depresses macrophage function after trauma-hemorrhage, which mimics the changes seen in normal male mice subjected to trauma-hemorrhage. We propose, therefore, that high testosterone and/or low estradiol levels are responsible for producing the immune depression in male mice after trauma-hemorrhage. Testosterone receptor blocking agents, e.g., flutamide, and/or estradiol administration should thus be useful adjuncts for preventing immune depression in male trauma patients.
Stroke Pattern Analysis and Synthesis (2006)

Abstract We present a synthesis technique that can automatically generate stroke patterns based on a user‐specified reference pattern. Our method is an extension of texture synthesis techniques to vector‐based patterns. Such an extension requires (a) an analysis of the pattern properties to extract meaningful pattern elements (defined as clusters of strokes) and (b) a synthesis algorithm based on similarities in the detected stroke clusters. Our method is based on results from human vision research concerning perceptual organization. The resulting synthesized patterns effectively reproduce the properties of the input patterns, and can be used to fill both 1D paths and 2D regions. Categories and Subject Descriptors (according to ACM CCS): I.3.7 [Computer Graphics]: Color, shading, shadowing, and texture I.3.4 [Computer Graphics]: Paint systems
Intracellular platelet‐activating factor regulates eicosanoid generation in guinea‐pig resident peritoneal macrophages (1989)

1. The role of intracellular platelet-activating factor (Paf) in arachidonic acid (AA) mobilization from guinea-pig peritoneal macrophages has been investigated by use of the potent and selective Paf receptor antagonists, WEB 2086 and CV 6209. 2. Adherent macrophages contained cell-associated Paf which was increased by exposure to formyl-methionyl-leucyl-phenylalanine (fMLP), endotoxin and the ionophore, A23187. However, only endotoxin and A23187 caused release of detectable amounts of Paf into the extracellular medium. 3. Exogenous Paf and each of the above stimuli mobilized previously incorporated [14C]-AA and increased the generation of prostacyclin (PGI2) in resident macrophages. 4. WEB 2086 (10-100 microM) and CV 6209 (0.1-10 microM) reduced both basal and stimulated PGI2 generation and WEB 2086 inhibited the mobilization of [14C]-AA. In addition, WEB 2086 (10 microM) inhibited fMLP-and Paf-induced superoxide anion generation. Responses to A23187 were not inhibited by either antagonist. 5. Activation of macrophages by fMLP caused a short burst of intracellular Paf generation but none was detected in the supernatants. The time-course of PGI2 synthesis followed closely that of Paf. 6. These data suggest that intracellular Paf generation is important for subsequent AA mobilization and may have a wider role in signal transduction processes.
A practical, convergent method for glycopeptide synthesis (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA practical, convergent method for glycopeptide synthesisShimon T. Cohen-Anisfeld and Peter T. Lansbury Jr.Cite this: J. Am. Chem. Soc. 1993, 115, 23, 10531–10537Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/ja00076a010https://doi.org/10.1021/ja00076a010research-articleACS PublicationsRequest reuse permissionsArticle Views1529Altmetric-Citations214LEARN 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
Molecular Profiling of Inflammatory Breast Cancer (2004)

Our study has identified a limited number of signaling pathways that require inappropriate activation for IBC development. Some of the up-regulated genes identified here could offer useful diagnostic or prognostic markers and could form the basis of novel therapeutic strategies.
Approximate structure preserving semantic matching (2008)

Typical ontology matching applications, such as ontology integration, focus on the computation of correspondences holding between the nodes of two graph-like structures, e.g., between concepts in two ontologies. However, there are applications, such as web service integration, where we may need to establish whether full graph structures correspond to one another globally, preserving certain structural properties of the graphs being considered. The goal of this paper is to provide a new matching operation, called structure preserving matching. This operation takes two graph-like structures and produces a set of correspondences between those nodes of the graphs that correspond semantically to one another, (i) still preserving a set of structural properties of the graphs being matched, (ii) only in the case if the graphs are globally similar to one another. We present a novel approximate structure preserving matching approach that implements this operation. It is based on a formal theory of abstraction and on a tree edit distance measure. We have evaluated our solution with encouraging results.
Phase 1 Trial of Wilms Tumor 1 (WT1) Peptide Vaccine and Gemcitabine Combination Therapy in Patients With Advanced Pancreatic or Biliary Tract Cancer (2010)

An open-labeled, dose-escalation phase 1 trial of Wilms tumor 1 (WT1) vaccine and gemcitabine (GEM) combination therapy for patients with advanced pancreatic cancer or biliary tract cancer was performed. The primary end point was evaluation of toxicity, safety, and optimal immunologic dose of vaccine. Human leukocyte antigen (HLA)-A 0201, HLA-A 0206, and/or HLA-A 2402-positive patients with inoperable advanced pancreatic or biliary tract cancer who had not previously been treated with GEM were eligible for this study. Six doses of GEM and 4 doses of WT1 peptide (1 or 3 mg) emulsified in Montanide adjuvant were administered over 2 months. Twenty-five patients (13 male and 12 female) were enrolled. Nine patients had inoperable advanced pancreatic cancer, 8 had gallbladder cancer, 4 had intrahepatic, and 4 had extrahepatic bile duct cancer. The adverse events were comparable to those with GEM alone. Delayed-type hypersensitivity test was positive after vaccination in 2 patients, and WT1-specific T cells in peptide-stimulated culture were detected by tetramer assay in 59% (13 of 22) of patients. The disease control rate at 2 months was 89% for pancreatic cancer and 50% for biliary tract cancer. With a median follow-up time of 259 days, the median survival time for biliary tract cancer was 288 days, and that for pancreatic cancer was 259 days. Although objective clinical efficacy was not apparent, the safety of WT1 vaccine and GEM combination therapy was confirmed in this study.
Differential rates of conversion of rat proinsulins I and II. Evidence for slow cleavage at the B-chain/C-peptide junction of proinsulin II (1991)

Rat proinsulin I is converted into insulin more rapidly than is proinsulin II. To study this further, rat islets were labelled (10 min) and conversion kinetics of the labelled proinsulins were monitored during a 120 min chase. Proinsulins, conversion intermediates and both insulins were separated by h.p.l.c. The accumulation of des-64,65-(split proinsulin II) during the chase suggests that the B-chain/C-peptide junction of proinsulin II is cleaved more slowly than the equivalent site on proinsulin I. This accounts for the differential kinetics of conversion of proinsulins I and II, and is presumed to be caused by one (or more) of the amino acid replacements which distinguish the two proinsulins.
A novel mechanism for controlling the activity of alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein. Multiple regulatory sites for 39-kDa receptor-associated protein. (1992)

The alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) consists of two polypeptides, 515 and 85 kDa, that are noncovalently associated. A 39-kDa polypeptide, termed the receptor-associated protein (RAP), interacts with the 515-kDa subunit after biosynthesis of these molecules and remains associated on the cell surface. This molecule regulates ligand binding of alpha 2MR/LRP (Herz, J., Goldstein, J. L., Strickland, D. K., Ho, Y. K., and Brown, M. S. (1991) J. Biol. Chem. 266, 21232-21238). Titration and binding studies indicate that RAP binds to two equivalent binding sites on alpha 2MR/LRP, with a KD of 14 nM. Heterologous ligand displacement experiments demonstrated that RAP completely inhibits the binding of 125I-activated alpha 2M to human fibroblasts and to the purified alpha 2MR/LRP, with a Ki of 23 and 26 nM, respectively. A direct correlation between the degree of binding of RAP to the receptor and the degree of ligand inhibition was observed, indicating that as the RAP binding sites are saturated, alpha 2MR/LRP loses its ability to bind ligands. Thus, the amount of RAP bound to alpha 2MR/LRP dictates the level of receptor activity. A model is proposed in which alpha 2MR/LRP contains multiple ligand binding sites, each regulated by a separate RAP site.
Overview of sciDB (2010)

SciDB [4, 3] is a new open-source data management system intended primarily for use in application domains that involve very large (petabyte) scale array data; for example, scientific applications such as astronomy, remote sensing and climate modeling, bio-science information management, risk management systems in financial applications, and the analysis of web log data. In this talk we will describe our set of motivating examples and use them to explain the features of SciDB. We then briefly give an overview of the project 'in flight', explaining our novel storage manager, array data model, query language, and extensibility frameworks.
The Structure, Function and Application of the Hammerhead Ribozyme (1997)

The hammerhead ribozyme is one of the smallest ribozymes known and catalyses the site-specific hydrolysis of a phosphodiester bond. This small ribozyme is of interest for two reasons. It offers a convenient system to study the structure/function relationship of a nucleotide sequence, and is a potential vehicle for the inhibition of gene expression. The first part of the review summarizes the sequence requirements of the hammerhead, its three-dimensional structure and the proposed mechanism, in addition to ribozyme specificity and turnover. The second part of the review focuses on the in vivo application of the ribozyme. The processes involved in designing ribozymes for efficient cleavage in vivo are described, together with possible delivery strategies.
Mutant EL-4 thymoma cells polyclonally activate murine and human B cells via direct cell interaction. (1985)

In this report we show that three mutagenized sublines of (murine) EL-4 thymoma cells can constitutively activate human and/or murine B cells via an MHC-nonrestricted cell-cell interaction. The activation signal is not by itself mitogenic but renders B cells capable of proliferating in response to interleukin 2 (IL 2). In addition, one of the mutant EL-4 sublines can constitutively respond by release of IL 2 in the presence of IL 1-containing macrophage (P388D1) supernatant. The exact relationships between these functional properties of the mutant EL-4 thymoma cells and those associated with activated normal T helper-cells remain to be established. However, the EL-4 cells provide a unique system to study in parallel murine and human B cell responses. In particular, the following observations were made during the present study. First, anti-Ig antibodies (anti-Ig) were required for B cell activation in conjunction with two EL-4 sublines acting only on murine B cells, whereas with a third subline acting on both murine and human B cells, anti-Ig was not required. Anti-Ig by itself did not lead to significant B cell activation in the absence of mutant EL-4 (or normal T) cells. Second, the growth factor-stimulated proliferation of EL-4-activated B cells, following separation of the B cells from the EL-4 cells, lasted only 2 days. These results, thus, indicate that the requirement for a surface Ig-mediated B cell activation signal depends on the quality/intensity of a direct T cell signal and that cell-cell interactions may exert a more stringent control over the growth factor responsiveness of B cells as compared with T cells.