gebhart/patrepeval huggingface dataset:
Prostate-specific membrane antigen: current and future utility. (1998)

Prostate cancer is the most common cancer and the second leading cause of cancer-related death among men. New prostatic markers are needed to increase diagnostic and prognostic effectiveness. One such new marker is prostate-specific membrane antigen (PSMA). PSMA is a highly prostate-restricted membrane glycoprotein that is expressed in normal prostatic epithelial cells and elevated in prostate cancers, especially in poorly differentiated, metastatic, and hormone refractory carcinomas. It has been measured in serum with immunocompetitive and Western blot assays, and its levels have been found to be correlated with the prediction of treatment failure and disease prognosis. Reverse transcriptase-polymerase chain reaction (RT-PCR) assays with primers specific for PSMA have been shown to be more effective than PSA-specific primers in detecting hematogenous circulating prostate cancer cells; however, no clear benefit in patient staging or utility as a predictor of clinical outcome or response to treatment has so far been obtained using RT-PCR methods. PSMA is currently utilized as an immunoscintigraphic target using the antibody conjugate CYT-356 (ProstaScint; Cytogen, Princeton, NJ) and has been shown to have clinical value, particularly in detecting occult prostate cancer. Another current application of PSMA is in immunotherapy of prostate cancer, in which promising results have been obtained in a phase I trial, and a phase II trial is underway. The research summarized in this article indicates that PSMA is an excellent target for diagnostic and therapeutic applications in prostate cancer.
Crystallization and identification of an assembly defect of recombinant antenna complexes produced in transgenic tobacco plants (1996)

A chimeric Lhcb gene encoding light-harvesting chlorophyll a/b-binding protein (LHCII) was expressed in transgenic tobacco plants. To separate native from recombinant LHCII, the protein was extended by six histidines at its C terminus. Recombinant LHCII was isolated by detergent-mediated monomerization of pure trimers followed by affinity-chromatography on Ni(2+)-NTA-agarose (NTA is nitrilotriacetic acid). Elution with imidazole yielded recombinant monomers that formed trimers readily after dilution of the detergent without further in vitro manipulations. LHCII subunits showed the typical chlorophyll a/b ratio at all steps of purification indicating no significant loss of pigments. Transgenic tobacco overexpressed amounts of recombinant protein that corresponded to about 0.7% of total LHCII. This yield suggested that expression in planta might be an alternative to the expression of eukaryotic membrane proteins in yeast. Recombinant LHCII was able to form two-dimensional crystals after addition of digalactolipids, which diffracted electrons to 3.6-A resolution. LHCII carrying a replacement of Arg-21 with Gln accumulated to only 0.004% of total thylakoid proteins. This mutant was monomeric in the photosynthetic membrane probably due to the deletion of the phosphatidylglycerol binding site and was degraded by the plastidic proteolytic system. Exchange of Asn-183 with Leu impaired LHCII biogenesis in a similar way presumably due to the lack of a chlorophyll a binding site.
Multi-Angle Effector Function Analysis of Human Monoclonal IgG Glycovariants (2015)

Therapeutic performance of recombinant antibodies relies on two independent mechanisms: antigen recognition and Fc-mediated antibody effector functions. Interaction of Fc-fragment with different FcR triggers antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity and determines longevity of the antibody in serum. In context of therapeutic antibodies FcγRs play the most important role. It has been demonstrated that the Fc-attached sugar moiety is essential for IgG effector functionality, dictates its affinity to individual FcγRs and determines binding to different receptor classes: activating or inhibitory. In this study, we systematically analyze effector functions of monoclonal IgG1 and its eight enzymatically engineered glycosylation variants. The analysis of interaction of glycovariants with FcRs was performed for single, as well as for antigen-bound antibodies and IgGs in a form of immune complex. In addition to functional properties we addressed impact of glycosylation on the structural properties of the tested glycovariants. We demonstrate a clear impact of glycosylation pattern on antibody stability and interaction with different FcγRs. Consistent with previous reports, deglycosylated antibodies failed to bind all Fcγ-receptors, with the exception of high affinity FcγRI. The FcγRII and FcγRIIIa binding activity of IgG1 was observed to depend on the galactosylation level, and hypergalactosylated antibodies demonstrated increased receptor interaction. Sialylation did not decrease the FcγR binding of the tested IgGs; in contrast, sialylation of antibodies improved binding to FcγRIIa and IIb. We demonstrate that glycosylation influences to some extent IgG1 interaction with FcRn. However, independent of glycosylation pattern the interaction of IgG1 with a soluble monomeric target surprisingly resulted in an impaired receptor binding. Here, we demonstrate, that immune complexes (IC), induced by multimeric ligand, compensated for the decreased affinity of target bound antibody towards FcRs, showing the importance of the IC-formation for the FcR- mediated effector functions.
Personalizing search via automated analysis of interests and activities (2005)

We formulate and study search algorithms that consider a user's prior interactions with a wide variety of content to personalize that user's current Web search. Rather than relying on the unrealistic assumption that people will precisely specify their intent when searching, we pursue techniques that leverage implicit information about the user's interests. This information is used to re-rank Web search results within a relevance feedback framework. We explore rich models of user interests, built from both search-related information, such as previously issued queries and previously visited Web pages, and other information about the user such as documents and email the user has read and created. Our research suggests that rich representations of the user and the corpus are important for personalization, but that it is possible to approximate these representations and provide efficient client-side algorithms for personalizing search. We show that such personalization algorithms can significantly improve on current Web search.
Role of the CD40‐CD40 ligand interaction in CD4+ T cell contact‐dependent activation of monocyte interleukin‐1 synthesis (1994)

Most studies of the induction of cytokine synthesis in monocytes have employed an exogenous triggering agent such as lipopolysaccharide. However, in nonseptic inflammatory responses (e.g. rheumatoid arthritis) monocyte activation occurs as a result of T cell-generated signals. In previous reports, we and others have demonstrated that contact-dependent T cell-generated signals are capable of contributing to macrophage activation. We have shown that plasma membranes from anti-CD3 activated purified peripheral CD4+ T cells (TmA) but not from resting CD4+ cells (TmR) induce monocytes to synthesize interleukin (IL)-1 in the absence of co-stimulatory cytokines. Studies to determine the expression kinetics of the molecule(s) unique to activated CD4+ T cells which interact with monocytes to induce IL-1 revealed that optimal expression occurred at 6 h post activation. This matched the previously reported kinetics of expression of CD40 ligand (CD40L) on activated peripheral T cells, implicating the CD40-CD40L interaction as a candidate for the initiator of the IL-1 signaling event. The ability of TmA to induce IL-1 synthesis in resting monocytes could be markedly reduced by addition of a monoclonal anti-CD40L antibody, 5c8. In addition, a monoclonal anti-CD40 IgM (BL-C4) proved dramatic in its ability to induce resting monocytes to synthesize IL-1. In summary, these results demonstrate that the CD40-CD40L interaction provides a critical component of CD4+ T cell contact-dependent activation of monocyte IL-1 synthesis.
Phase-shifting mask topography effects on lithographic image quality (1993)

The impact of phase-shifting mask topography on wafer exposure was studied via simulations and experimentation using phase-shifting masks fabricated by etching the quartz to define the shifted areas. The influence of the refractive index of the chromium layer was shown to be minimal and for all the simulations, the refractive index was assumed to be 2.5 - 2.0 j at 248 nm. As the chromium profiles marginally influence the linewidth of the resist patterns, the simulated intensity assumes vertical profiles. Moreover, it was shown experimentally and using simulations that the quartz profiles have a large impact on the wafer results. For vertical quartz profiles, the intensity of the light going through the etched portion of the mask is lower than that going through the unetched portion of the mask and varies with feature size. The consequences are that 0 degree(s) and 180 degree(s) phases cannot be interchanged blindly during the layout of a phase-shifting mask and that the pinhole phase-defect repair technique consisting in etching 360 degree(s) phase slots in the quartz will not yield the same intensity profile as a defect- free region. These problems can be addressed either by optimizing the quartz profiles or by biasing the size of the features depending on the type of pattern.
Down-Regulation of prostate-specific antigen expression by ligands for peroxisome proliferator-activated receptor gamma in human prostate cancer. (2000)

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily. Recent studies found that ligand-activated PPARgamma regulated differentiation and clonal growth of several types of cancer cells, including prostate cancer, suggesting that PPARgamma could be a tumor suppressor. Troglitazone was a widely used antidiabetic drug that activates PPARgamma. Recently, we reported that this agent had antiprostate cancer effects in vitro and in vivo. In this study, we administered troglitazone for over 1.5 years to an individual with occult recurrent prostate cancer. Using the prostate-specific antigen (PSA) levels as a surrogate marker of the disease, the oral administration of troglitazone (600-800 mg/day) reduced the increase velocity of PSA levels, suggesting clinical efficacy of troglitazone in prostate cancer. PSA promoter/ enhancer reporter assays showed that the PPARgamma ligands troglitazone (10(-5) M), pioglitazone (10(-5) M), or 15-deoxy-delta12,14-prostaglandin J2 (10(-5) M) down-regulated androgen-stimulated reporter gene activity in LNCaP cells, a prostate cancer cell line. The PSA promoter contains androgen receptor response elements (AREs). Reporter gene studies showed that troglitazone inhibited androgen activation of the AREs in the PSA regulatory region. Consistent with inhibition of gene expression, 2 days of incubation of LNCaP with troglitazone dramatically suppressed PSA protein expression without suppressing AR expression, suggesting that troglitazone inhibited ARE activation by a mechanism other than down-regulation of expression of the AR. Taken together, ligands of PPARgamma may be a useful therapeutic approach for the treatment of prostate cancer and may be acting, in part, by inhibiting transactivation of androgen-responsive genes.
In vivo blocking effects of a humanized antibody to human interleukin-6 receptor on interleukin-6 function in primates. (1998)

A humanized antibody to human interleukin-6 (IL-6) receptor, MRA, which was constructed by grafting the complementary determining regions, is expected to be useful as a therapeutic agent for IL-6-related diseases, especially multiple myeloma. We examined the ability of MRA to block the in vivo function of IL-6 and its serum concentration profile in primates. Cynomolgus monkeys were intravenously administered with MRA at doses of 0 (vehicle) or 5 mg/kg, then subcutaneously injected with human IL-6 at a dose of 5 micrograms/kg, once a day for 7 days. The injections of IL-6 increased blood platelet counts two-fold and elevated serum C-reactive protein levels to 0.15 to 0.17 mg/ml. These IL-6-induced typical responses were completely inhibited by single pretreatment with MRA. Serum concentrations of MRA were maintained for a long period; some even at one week after administration, were regarded as having sufficient levels to inhibit the myeloma cell growth. These findings suggest that MRA may be effective in the treatment of IL-6-related diseases.
Immunization of Balb/c Mice with a Monoclonal Anti-DNA Antibody Induces an Anti-Idiotypic Antibody Reactive with a Cell-Surface DNA Binding Protein (1993)

DNA binds to cell-surface proteins on human and murine leukocytes and induces secretion of the cytokine interleukin 6 (IL-6). Cell-surface DNA binding molecules have been shown to serve as target antigens for the production of autoantibodies in patients with systemic lupus erythematosus (SLE), and in lupus-prone mice. Recent studies have demonstrated that a subset of anti-anti-DNA antibodies, isolated from patients with SLE, are idiotypically related to antibodies reactive with a cell-surface DNA binding molecule. We now report that immunization of normal mice with a murine monoclonal anti-DNA antibody induces an anti-idiotypic response which has reactivity with a cell-surface DNA binding molecule. An anti-idiotypic anti-DNA monoclonal antibody (LB17) was isolated from the spleen of an immunized mouse. This monoclonal antibody blocked the binding of DNA to murine splenocytes and mimicked the functional effect of DNA by stimulating the secretion of IL-6. These experiments provide further evidence for an idiotypic connectivity between antibodies to cell-surface DNA binding proteins and anti-DNA antibodies. It is hypothesized that this idiotypic system is part of the network of natural autoantibodies and that its perturbation may give rise to pathogenic antibodies.
Synthesis of homologs of 4,5-dihydroxy- and 4-hydroxy-5-oxohexanoic acid .gamma.-lactones (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of homologs of 4,5-dihydroxy- and 4-hydroxy-5-oxohexanoic acid .gamma.-lactonesMark J. Hoekman, Gian L. Fagan, A. Dinsmoor Webb, and Richard E. KepnerCite this: J. Agric. Food Chem. 1982, 30, 5, 920–924Publication Date (Print):September 1, 1982Publication History Published online1 May 2002Published inissue 1 September 1982https://pubs.acs.org/doi/10.1021/jf00113a028https://doi.org/10.1021/jf00113a028research-articleACS PublicationsRequest reuse permissionsArticle Views272Altmetric-Citations9LEARN 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
Coronary Bypass Surgery with Internal-Thoracic-Artery Grafts — Effects on Survival over a 15-Year Period (1996)

As compared with saphenous-vein coronary bypass grafts, internal-thoracic-artery grafts conferred a survival advantage throughout a 15-year follow-up period. The survival advantage increased with time, suggesting that the initial selection of the conduit was a more important factor in survival than problems appearing long after surgery, such as the progression of coronary disease.
Molecular cloning of the cDNAs for the four subunits of mouse DNA polymerase alpha-primase complex and their gene expression during cell proliferation and the cell cycle. (1993)

The DNA polymerase alpha-primase complex purified from mouse FM3A cells is composed of four polypeptides with molecular masses of 180, 68, 54, and 46 kDa. The largest subunit has DNA polymerase activity, the two smallest subunits have DNA primase activity, and the function of the 68-kDa subunit is unknown. We have isolated the cDNAs of the four subunits by low stringency hybridization and reverse transcription polymerase chain reaction and determined their nucleotide sequences. The predicted amino acid sequence of the 180-kDa subunit shows 88, 38, 34, and 32% identity to those of the catalytic subunits of human, Drosophila melanogaster, Schizosaccharomyces pombe, and Saccharomyces cerevisiae DNA polymerase alpha, respectively, and contains seven regions whose orders and sequences are highly conserved among viral and other eukaryotic DNA polymerases. The deduced amino acid sequence of the 68-kDa subunit shows 25% identity to that of the 73-kDa subunit of D. melanogaster DNA polymerase alpha-primase, shows no significant sequence similarity to any other protein in the data bases, but contains a potential phosphorylation site(s) for cdc2 kinase. The amino acid sequence of the 54-kDa subunit shows 32% identity to that of the large subunit of S. cerevisiae DNA primase. During activation of quiescent Swiss mouse 3T3 cells to proliferate, the levels of mRNA of the four subunits of the DNA polymerase alpha-primase complex increased before DNA synthesis. In growing mouse FM3A cells, the transcripts of the four subunits are present throughout the cell cycle and increase slightly prior to the S phase.
Serotonin-stimulated aortic endothelial cells secrete a novel T lymphocyte chemotactic and growth factor (1994)

Atherosclerotic lesions contain multiple cell types including smooth muscle cells, macrophages, and T lymphocytes. The development of an extralymphatic T lymphocyte focus of inflammation in this condition requires chemoattractant-induced cell migration and growth factor-induced cell activation. In a previous study, we described a novel 13-15-kDa T lymphocyte-specific chemotactic cytokine, endothelial cell-derived lymphocyte chemoattractant activity (ED-LCA), secreted by serotonin-stimulated bovine aortic endothelial cells that is distinct from previously identified endothelial cell-derived interleukins (IL) 1, 6, and 8. Because of the association between T lymphocyte chemotactic and growth factor activity, in the current study we investigated the effect of ED-LCA on T cell growth. We assessed its capacity to induce markers of the passage of T cells from the resting (G0) state into the G1 phase of the cell cycle, such as receptors for IL-2 (IL-2R) and transferrin (TFR) and class II major histocompatibility complex antigens (HLA-DR). Incubation of G0 freshly isolated human T lymphocytes for 48 h with chromatographically resolved, partially purified ED-LCA resulted in a threefold increase in expression of the p55 subunit of IL-2R, a threefold increase in TFR, and a twofold increase in HLA-DR. Passage into the G1 phase of the cell cycle was confirmed by cell cycle analysis employing acridine orange. Evaluation of CD4+ and CD8+ T cell subsets by double-antibody labeling demonstrated that the p55 subunit of IL-2R was induced in both T cell subsets. Although incubation of human T cells with ED-LCA alone did not induce proliferation, addition of exogenous IL-2 to T cells pulsed with ED-LCA for 24 h caused a proliferative response with a stimulation index of 3. By up-regulating functional cell surface receptors for IL-2, ED-LCA is a competence growth factor for T lymphocytes and primes them to respond to IL-2. By virtue of its effect on T cells, as a chemotactic and competence factor, this endothelial cell-derived mitoattractant could participate with other T cell growth factors like IL-2 in the recruitment and amplification of the extralymphatic T cell component of atherosclerosis.
Sustained cardiomyocyte DNA synthesis in whole embryo cultures lacking the TSC2 gene product (1997)

Tuberous sclerosis complex (TSC) is characterized by the appearance of nonmalignant tumors that affect a wide spectrum of organs, including the heart. TSC disease-causing genes have been identified on chromosomes 9 (TSC1) and 16 (TSC2). This study examined the impact of the TSC2 gene product on cardiomyocyte proliferation and terminal differentiation. We took advantage of the observation that Eker rats carry a germ-line TSC2 mutation. Rats heterozygous for the mutation (TSC2EK/+) are predisposed to renal carcinoma, whereas animals homozygous for the mutation (TSC2EK/EK) die in utero during midgestation. Spontaneously contractile cardiomyocytes were observed after multiple passages of whole embryo cultures prepared from embryonic day 12.5 TSC2EK/EK fetuses but not from TSC2EK/+ or wild-type fetuses. The TSC2EK/EK cardiomyocytes continued to actively synthesize DNA after as many as eight passages. Cytological, ultrastructural, and molecular analyses indicated that the TSC2EK/EK cardiomyocytes retained a highly differentiated phenotype similar to that observed for normal rat cardiomyocytes during late embryonic and early neonatal life. These results suggested that the TSC2 gene product is required for normal cardiomyocyte cell-cycle withdrawal and terminal differentiation.
Acylation of guanidines and guanylhydrazones (1967)

A number of acyl derivatives of guanidines and guanylhydrazones have been synthesized and evaluated for their antibacterial activity. The synthesis of some of the guanidines and guanylhydrazones is discussed.
Dose-dependent neuroprotection by 17β-estradiol after cardiac arrest and cardiopulmonary resuscitation (2005)

We conclude that E2 has a critical dosing effect on neuronal survival, physiologic levels of E2 are neuroprotective after cardiac arrest/cardiopulmonary resuscitation, and acute exposure is sufficient for brain resuscitation.
Natural and Engineered Cystine Knot Miniproteins for Diagnostic and Therapeutic Applications (2011)

Cystine knot miniproteins define a class of peptides in the size range of approximately 28-35 amino acid residues that often combine high chemical and biological stability with high potency and selectivity. They share a common structural motif that is defined by three intramolecular disulfide bonds that gives rise to a very stable scaffold. Members of this family cover a broad spectrum of natural bioactivities ranging from antimicrobial and antiviral activities to selective blockage or activation of ion channels, cell surface receptors and extracelluar proteases. In recent years, the spectrum of natural bioactivities of this class of miniproteins was further expanded by application of protein design and directed evolution technologies. Miniproteins have been developed that inhibit platelet aggregation, block asthma-related proteases, act as growth factor mimics or address human tumor targets. Recent reports on miniproteins binding to cancer specific targets indicate that these biomolecules due to their particularly high in vivo stability, high target affinity, good tissue distribution, and fast body clearance are very promising agents that can be endowed with important beneficial features for imaging and therapeutic applications. With the first cystine-knot miniprotein already marketed as an analgesic, more candidates can be expected to find their way into the clinic for diagnostic and therapeutic applications over next years.