gebhart/patrepeval huggingface dataset:
Superior Antitumor Response Induced by Large Stress Protein Chaperoned Protein Antigen Compared with Peptide Antigen (2010)

Our previous studies have demonstrated that the natural chaperone complexes of full-length tumor protein Ags (e.g., gp100) and large stress proteins (e.g., hsp110 and grp170) with exceptional Ag-holding capabilities augment potent tumor protective immunity. In this study, we assess the peptide-interacting property of these large chaperones and, for the first time, compare the immunogenicity of the recombinant chaperone vaccines targeting two forms of Ags (protein versus peptide). Both hsp110 and grp170 readily formed complexes with antigenic peptides under physiologic conditions, and the peptide association could be further stimulated by heat shock. The large chaperones displayed similar but distinct peptide-binding features compared with hsp70 and grp94/gp96. Immunization with hsp110- or grp170-tyrosinase-related protein 2 (TRP2(175-192)) peptide complexes effectively primed CD8(+) T cells reactive with TRP2-derived, MHC class I-restricted epitope. However, the tumor protective effect elicited by the TRP2(175-192) peptide vaccine was much weaker than that achieved by full-length TRP2 protein Ag chaperoned by grp170. Furthermore, immunization with combined chaperone vaccines directed against two melanoma protein Ags (i.e., gp100 and TRP2) significantly improved overall anti-tumor efficacy when compared with either of the single Ag vaccine. Lastly, treatment of tumor-bearing mice with these dual Ag-targeted chaperone complexes resulted in an immune activation involving epitope spreading, which was associated with a strong growth inhibition of the established tumors. Our results suggest that high m.w. chaperones are superior to conventional chaperones as a vaccine platform to deliver large protein Ags, and provide a rationale for translating this recombinant chaperoning-based vaccine to future clinical investigation.
Purine Nucleosides. IV. The Synthesis of 6-Halogenated 9-β-D-Ribofuranosylpurines from Inosine and Guanosine1 (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPurine Nucleosides. IV. The Synthesis of 6-Halogenated 9-β-D-Ribofuranosylpurines from Inosine and Guanosine1John F. Gerster, Jesse W. Jones, and Roland K. RobinsCite this: J. Org. Chem. 1963, 28, 4, 945–948Publication Date (Print):April 1, 1963Publication History Published online1 May 2002Published inissue 1 April 1963https://pubs.acs.org/doi/10.1021/jo01039a016https://doi.org/10.1021/jo01039a016research-articleACS PublicationsRequest reuse permissionsArticle Views604Altmetric-Citations89LEARN 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
Application of photodecomposable base concept to 193-nm resists (2000)

This paper reports on the use of trimethyl sulfonium hydroxide as a base additive for 193 nm applications, which is found to stabilize the latent image as well a act as a photodecomposable base. Delay time stability (exposure to post-exposure bake) of formulations consisting of trimethylsulfonium hydroxide is compared to that of a non- photodecomposable base (diethanolamine) in both methacrylate- and cycloolefin-based 193 nm resists. Resist formulations made using the trimethylsulfonium base were stable for more than one hour, while the reference formulation with diethanolamine showed T-top formation within 10 minutes delay time under the same conditions. The trialkylsulfonium hydroxide base additives were found to be photodecomposable by measuring the acid produced upon exposure. Compared to a non- photodecomposable base containing resist, the photodecomposable base containing resist produced more acid in the exposed areas under identical PAG/BASE molar ratios.
Prediction of mortality among emergency medical admissions (2006)

REMS is a better predictor of mortality in emergency medical admissions than RAPS. Age, GCS, and oxygen saturation appear to be the most useful predictor variables. Inclusion of other variables in risk adjustment scores, particularly blood pressure, may reduce their value.
Time Courses of Growth and Remodeling of Porcine Aortic Media During Hypertension: A Quantitative Immunohistochemical Examination (2007)

Arteries undergo marked structural and functional changes in human and experimental hypertension that generally involve smooth muscle cell (SMC) hypertrophy/hyperplasia as well as abnormal extracellular matrix turnover. In this study we examined time courses of changes in SMC activity and matrix protein content in a novel mini-pig aortic coarctation model. Cell proliferation was evaluated by immunostaining of Ki-67, apoptosis was assessed by TUNEL, and phenotypic changes were monitored by immunostaining three SMC contractile markers (caldesmon, calponin, and smoothelin). Changes in medial collagen and elastin were examined by picrosirius red and Verhoeff-van Gieson staining, respectively. LabVIEW-based image analysis routines were developed to objectively and efficiently quantify the (immuno)histochemical results. We found that significant cell proliferation and matrix production occurred in the early stages of this coarctation model and then declined gradually; the SMCs also tended to exhibit a less contractile phenotype following these cellular and extracellular changes. Specifically, different aspects of the phenotypic changes associated with hypertension occurred at different rates: cell proliferation and collagen production occurred early and peaked by 2 weeks, whereas changes in contractile protein expression continued to decrease over the entire 8-week study period. Temporal changes found in this study emphasize the importance of simultaneously tracing time courses of SMC growth and differentiation as well as matrix protein production and content. SMCs are multifunctional, and caution must be used to not overdefine phenotype. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.
Carbohydrate-binding modules: fine-tuning polysaccharide recognition (2004)

The enzymic degradation of insoluble polysaccharides is one of the most important reactions on earth. Despite this, glycoside hydrolases attack such polysaccharides relatively inefficiently as their target glycosidic bonds are often inaccessible to the active site of the appropriate enzymes. In order to overcome these problems, many of the glycoside hydrolases that utilize insoluble substrates are modular, comprising catalytic modules appended to one or more non-catalytic CBMs (carbohydrate-binding modules). CBMs promote the association of the enzyme with the substrate. In view of the central role that CBMs play in the enzymic hydrolysis of plant structural and storage polysaccharides, the ligand specificity displayed by these protein modules and the mechanism by which they recognize their target carbohydrates have received considerable attention since their discovery almost 20 years ago. In the last few years, CBM research has harnessed structural, functional and bioinformatic approaches to elucidate the molecular determinants that drive CBM-carbohydrate recognition. The present review summarizes the impact structural biology has had on our understanding of the mechanisms by which CBMs bind to their target ligands.
Engineering of an anti‐epidermal growth factor receptor antibody to single chain format and labeling by sortase A‐mediated protein ligation (2011)

Sortase-mediated protein ligation is a biological covalent conjugation system developed from the enzymatic cell wall display mechanism found in Staphylococcus aureus. This three-component system requires: (i) purified Sortase A (SrtA) enzyme; (ii) a substrate containing the LPXTG peptide recognition sequence; and (iii) an oligo-glycine acceptor molecule. We describe cloning of the single-chain antibody sc528, which binds to the extracellular domain of the epidermal growth factor receptor (EGFR), from the parental monoclonal antibody and incorporation of a LPETGG tag sequence. Utilizing recombinant SrtA, we demonstrate successful incorporation of biotin from GGG-biotin onto sc528. EGFR is an important cancer target and is over-expressed in human tumor tissues and cancer lines, such as the A431 epithelial carcinoma cells. SrtA-biotinylated sc528 specifically bound EGFR expressed on A431 cells, but not negative control lines. Similarly, when sc528 was labeled with fluorescein we observed antigen-specific labeling. The ability to introduce functionality into recombinant antibodies in a controlled, site-specific manner has applications in experimental, diagnostic, and potentially clinical settings. For example, we demonstrate addition of all three reaction components in situ within a biosensor flow cell, resulting in oriented covalent capture and presentation of sc528, and determination of precise affinities for the antibody-receptor interaction.
Targeted nuclear antisense RNA mimics natural antisense-induced degradation of polyoma virus early RNA. (1994)

We describe a general antisense strategy to inhibit target gene expression. The substitution of a cis-acting ribozyme for a polyadenylylation signal in an antisense expression vector results in the nuclear retention of RNAs and the efficient degradation of their targets. We demonstrate the utility of this system in polyoma virus, where early-strand RNA levels are downregulated in the nucleus by antisense late-strand counterparts. We show that mutations destabilizing these naturally occurring antisense transcripts lead to increased levels of early-strand RNAs. Furthermore, expression in trans of nuclear antisense transcripts lowers early-strand RNA levels and quantitatively mimics the natural regulation.
Pharmacological validation of behavioural measures of akinesia and dyskinesia in a rat model of Parkinson's disease (2002)

In an attempt to define clinically relevant models of akinesia and dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats, we have examined the effects of drugs with high (L-DOPA) vs. low (bromocriptine) dyskinesiogenic potential in Parkinson's disease on three types of motor performance, namely: (i) abnormal involuntary movements (AIMs) (ii) rotational behaviour, and (iii) spontaneous forelimb use (cylinder test). Rats with unilateral 6-OHDA lesions received single daily i.p. injections of L-DOPA or bromocriptine at therapeutic doses. During 3 weeks of treatment, L-DOPA but not bromocriptine induced increasingly severe AIMs affecting the limb, trunk and orofacial region. Rotational behaviour was induced to a much higher extent by bromocriptine than L-DOPA. In the cylinder test, the two drugs initially improved the performance of the parkinsonian limb to a similar extent. However, L-DOPA-treated animals showed declining levels of performance in this test because the drug-induced AIMs interfered with physiological limb use, and gradually replaced all normal motor activities. L-DOPA-induced axial, limb and orolingual AIM scores were significantly reduced by the acute administration of compounds that have antidyskinetic efficacy in parkinsonian patients and/or nonhuman primates (-91%, yohimbine 10 mg/kg; -19%, naloxone 4-8 mg/kg; -37%, 5-methoxy 5-N,N-dimethyl-tryptamine 2 mg/kg; -30%, clozapine 8 mg/kg; -50%, amantadine 40 mg/kg). L-DOPA-induced rotation was, however, not affected. The present results demonstrate that 6-OHDA-lesioned rats do exhibit motor deficits that share essential functional similarities with parkinsonian akinesia or dyskinesia. Such deficits can be quantified using novel and relatively simple testing procedures, whereas rotometry cannot discriminate between dyskinetic and antiakinetic effects of antiparkinsonian treatments.
ModE-Dependent Molybdate Regulation of the Molybdenum Cofactor OperonmoainEscherichia coli (2000)

The expression of the moa locus, which encodes enzymes required for molybdopterin biosynthesis, is enhanced under anaerobiosis but repressed when the bacterium is able to synthesize active molybdenum cofactor. In addition, moa expression exhibits a strong requirement for molybdate. The molybdate enhancement of moa transcription is fully dependent upon the molybdate-binding protein, ModE, which also mediates molybdate repression of the mod operon encoding the high-affinity molybdate uptake system. Due to the repression of moa in molybdenum cofactor-sufficient strains, the positive molybdate regulation of moa is revealed only in strains unable to make the active cofactor. Transcription of moa is controlled at two sigma-70-type promoters immediately upstream of the moaA gene. Deletion mutations covering the region upstream of moaA have allowed each of the promoters to be studied in isolation. The distal promoter is the site of the anaerobic enhancement which is Fnr-dependent. The molybdate induction of moa is exerted at the proximal promoter. Molybdate-ModE binds adjacent to the -35 region of this promoter, acting as a direct positive regulator of moa. The molybdenum cofactor repression also appears to act at the proximal transcriptional start site, but the mechanism remains to be established. Tungstate in the growth medium affects moa expression in two ways. Firstly, it can act as a functional molybdate analogue for the ModE-mediated regulation. Secondly, tungstate brings about the loss of the molybdenum cofactor repression of moa. It is proposed that the tungsten derivative of the molybdenum cofactor, which is known to be formed under such conditions, is ineffective in bringing about repression of moa. The complex control of moa is discussed in relation to the synthesis of molybdoenzymes in the bacterium.
A Nondestructive Prescreening Method for Bone Collagen Content Using Micro-Computed Tomography (2010)

Isolation of bone collagen for radiocarbon dating is a labor-intensive and time-consuming process that sometimes results in unacceptably low protein recovery. In preliminary studies reported here, micro-computed tomography (microCT), a nondestructive technique that uses X-rays to produce high-resolution three-dimensional images of mineralized materials such as bone, offers promise as a suitable prescreening option for bones of questionable preservation. We have found that the bone volume fraction calculated by the scanner software correlates well with collagen recovery in 4 analyzed bones from Etton, United Kingdom.
The Ethnobotanical Approach to Drug Discovery: Strengths and Limitations (2007)

For pharmaceuticals ranging from digitalis to vincristine the ethnobotanical approach to drug discovery has proven successful. The advent of high-throughput, mechanism-based in vitro bioassays coupled with candidate plants derived from pain-staking ethnopharmacological research has resulted in the discovery of new pharmaceuticals such as prostratin, a drug candidate for treatment of human immunodeficiency virus, as well as a variety of novel antiinflammatory compounds. Not all Western diseases are equally likely to be recognized by indigenous peoples. Gastrointestinal maladies, inflammation, skin infections and certain viral diseases are likely to be of high saliency to indigenous healers, whereas diseases such as cancer and cardiovascular illness are unlikely to be easily diagnosed by indigenous peoples. Yet indigenous remedies may indicate pharmacological activity for maladies such as schizophrenia, for which the biochemical mechanisms have yet to be discovered. Ethnopharmacological information can be used to provide three levels of resolution in the search for new drugs: (1) as a general indicator of non-specific bioactivity suitable for a panel of broad screens; (2) as an indicator of specific bioactivity suitable for particular high-resolution bioassays; (3) as an indicator of pharmacological activity for which mechanism-based bioassays have yet to be developed.
Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors. (2001)

Most solid malignancies display interstitial hypertension and a poor uptake of anticancer drugs. Platelet-derived growth factor (PDGF) and the cognate tyrosine kinase receptors are expressed in many tumors. Signaling through PDGFbeta receptors was shown recently to increase interstitial fluid pressure (IFP) in dermis after anaphylaxis-induced lowering of IFP. In this study, we show that treatment with the selective PDGF receptor kinase inhibitor, STI571, formerly known as CGP57148B, decreased the interstitial hypertension and increased capillary-to-interstitium transport of 51Cr-EDTA in s.c. growing rat PROb colonic carcinomas. Furthermore, treatment with an antagonistic PDGF-B oligonucleotide aptamer decreased interstitial hypertension in these tumors. PDGFbeta receptors were expressed in blood vessels and stromal cells but not in the tumor cells of PROb colonic carcinomas. Our study indicates a previously unrecognized role of PDGF receptors in tumor biology, although similar effects of PDGF on IFP have been demonstrated previously in the dermis. The data suggest interference with PDGF receptors, or their ligands, as a novel strategy to increase drug uptake and therapeutic effectiveness of cancer chemotherapy.
Ionophore vom Typ der 3‐Oxapentandiamide (1980)

Ionophores of the Type of 3‐Oxapentane Diamides A series of lipophilic 3‐oxapentane diamides were prepared and their selectivity in membranes was studied. N, N, N′, N′ ‐Tetracyclohexyl‐3‐oxapentane diamide forms 1:2‐ and 1:3‐metal/ligand‐complexes with Mg 2+ and Ca 2+ respectively and induces a selectivity in membranes for Ca 2+ over Mg 2+ by a factor of about 10 4 .
Pneumococcal C-substance, a ribitol teichoic acid containing choline phosphate (1968)

1. Pneumococcal C-substance was isolated from the non-capsulated Pneumococcus 1-192R, A.T.C.C. 12213, by extraction with trichloroacetic acid solution followed by chromatography on DEAE-cellulose (HCO(3) (-) form). 2. The polymer contains 7.0% of phosphorus and 6.0% of nitrogen and is composed of phosphate, N-acetyl-d-galactosamine, d-glucose, N-acetyldiaminotrideoxyhexose, ribitol and choline in the molecular proportions 2:1:1:1:1:1. 3. After acid hydrolysis, d-galactosamine hydrochloride and galactosamine 6-phosphate were isolated in crystalline form and crystalline derivatives of d-glucose and anhydroribitol were obtained. A product of partial acid hydrolysis was provisionally characterized as 6'-O-phosphoryl-[O-beta-d-galactosaminyl-(1'-->6)-d-glucose]. 4. C-substance contains free amino groups accessible to attack by 1-fluoro-2,4-dinitrobenzene and nitrous acid. 5. Choline phosphate and ribitol phosphate are units in the polymer. 6. Treatment with hot alkali gave a fragment comprising phosphate, d-galactosamine, d-glucose, diaminotrideoxyhexose and ribitol in the molecular proportions 2:1:1:1:1. 7. After selective N-acetylation, the fragment contained one of its phosphate groups as a phosphomonoester and one as a phosphodiester, shown by potentiometric titration and by treatment with a phosphomonoesterase. 8. C-substance from seven other strains of Pneumococcus possesses a structure common to that described for the strain 1-192R. 9. Capsular materials from 26 different strains of Pneumococcus were analysed for suspected contamination by C-substance. In 19 cases the presence of C-substance with the normal structure was demonstrated, and in the remaining seven cases the contaminating C-substance was probably similarly constituted. 10. F-substance was isolated and the associated fatty acid material analysed.
Neural network approach to relevance (2002)

It is becoming increasingly recognised in AI and elsewhere that it is important to understand and account for relevance for computational and functional reasons. In this paper the authors give an account of relevance formally, and present a neural network approach to relevance with a focus on how to preserve relevant information and ignore irrelevant information in order to facilitate decision making and thereby to improve performance. This can provide a basis for further discussion of relevance as well as having immediate significance for neural networks. The authors' approach is based on a novel associative network model, Moving Around Landscape (MAL), which is based informally on kinetics and is concerned mainly with information transition under constraints. MAL facilitates accommodating relevance in its dynamics to evolve computations that ignore irrelevant aspects of the environments and preserve relevant information. Experiments on its application to character recognition show that accommodating one kind of relevance (neighbourhood relationship) into MAL enables it to learn relevant internal representations of character images that are comparable in terms of ordinary metrics, such as Hamming distance and Euclidean distance. Thereby character recognition with physical variations is facilitated and the performance of recognition may be improved.
Determination of Plateau Moduli and Entanglement Molecular Weights of Isotactic, Syndiotactic, and Atactic Polypropylenes Synthesized with Metallocene Catalysts (1998)

Metallocene catalysis was employed to prepare model polypropylenes (PP) with very high molecular weights and narrow molecular weight distributions (MWDs) of Mw/Mn ≈ 2, typical for “single site” metallocene catalysts. The viscoelastic properties of PP melts were investigated by means of oscillatory rheometry. Arrhenius and WLF equations were applied to model the influence of temperature on PP rheology. With very high molecular weight polypropylene samples it became possible to determine the onset of the plateau zone, reflecting the rubber-like properties of PP. For the first time plateau moduli and entanglement molecular weights Mes were determined and found to be depend upon stereoregularity. The entanglement molecular weights were found to be 6900 g/mol for isotactic PP, 7050 g/mol for atactic PP, and 2170 g/mol for syndiotactic PP. This influence of stereoregularity was attributed to the different conformations of syndiotactic PP with respect to isotactic and atactic PP in PP melts.