gebhart/patrepeval huggingface dataset:
The shared tumor-associated antigen cytochrome P450 1B1 is recognized by specific cytotoxic T cells (2003)

Cytochrome P450 1B1 (CYP1B1), a drug-metabolizing extrahepatic enzyme, was recently shown to be overexpressed in multiple types of cancer. Such tumor-associated genes may be useful targets for anticancer therapy, particularly cancer immunotherapeutics. We identified HLA-A*0201-binding peptides and a naturally processed and presented T-cell epitope capable of inducing CYP1B1-specific cytotoxic T lymphocytes (CTLs) in HLA-A2 transgenic mice. Furthermore, the induction of CYP1B1-specific T cells was demonstrated in healthy donors and cancer patients. These T cells efficiently lysed target cells pulsed with the cognate peptide. More important, HLA-A2-matched tumor cell lines and primary malignant cells were also recognized by CYP1B1-specific CTLs. These findings form the basis of a phase 1 clinical trial exploring a DNA-based vector encoding CYP1B1 for widely applicable cancer immunotherapy conducted at the Dana-Farber Cancer Institute.
Real-Time Imaging of HIF-1α Stabilization and Degradation (2009)

HIF-1alpha is overexpressed in many human cancers compared to normal tissues due to the interaction of a multiplicity of factors and pathways that reflect specific genetic alterations and extracellular stimuli. We developed two HIF-1alpha chimeric reporter systems, HIF-1alpha/FLuc and HIF-1alpha(DeltaODDD)/FLuc, to investigate the tightly controlled level of HIF-1alpha protein in normal (NIH3T3 and HEK293) and glioma (U87) cells. These reporter systems provided an opportunity to investigate the degradation of HIF-1alpha in different cell lines, both in culture and in xenografts. Using immunofluorescence microscopy, we observed different patterns of subcellular localization of HIF-1alpha/FLuc fusion protein between normal cells and cancer cells; similar differences were observed for HIF-1alpha in non-transduced, wild-type cells. A dynamic cytoplasmic-nuclear exchange of the fusion protein and HIF-1alpha was observed in NIH3T3 and HEK293 cells under different conditions (normoxia, CoCl2 treatment and hypoxia). In contrast, U87 cells showed a more persistent nuclear localization pattern that was less affected by different growing conditions. Employing a kinetic model for protein degradation, we were able to distinguish two components of HIF-1alpha/FLuc protein degradation and quantify the half-life of HIF-1alpha fusion proteins. The rapid clearance component (t(1/2) approximately 4-6 min) was abolished by the hypoxia-mimetic CoCl2 MG132 treatment and deletion of ODD domain, and reflects the oxygen/VHL-dependent degradation pathway. The slow clearance component (t(1/2) approximately 200 min) is consistent with other unidentified non-oxygen/VHL-dependent degradation pathways. Overall, the continuous bioluminescence readout of HIF-1alpha/FLuc stabilization in vitro and in vivo will facilitate the development and validation of therapeutics that affect the stability and accumulation of HIF-1alpha.
A role for the C2 domain of factor VIII in binding to von Willebrand factor (1994)

We examined the possibility that the C2 domain, amino acid residues 2173-2332, of factor VIII (fVIII) contains a binding site for von Willebrand factor (vWf) to clarify previous data showing that some monoclonal and human inhibitor antibodies with epitopes in C2 prevent fVIII-vWf binding. We constructed a fusion protein, glutathione S-transferase-C2, which binds to immobilized vWf in a dose-dependent saturable fashion, suggesting that the fVIII C2 domain contains a binding site for vWf. This site was further localized by testing the effect of a synthetic peptide on fVIII-vWf binding. Peptide 2303-2332, consisting of a previously identified phosphatidyl-serine binding site, prevented fVIII binding to vWf, suggesting that the sites for fVIII binding to vWf or phosphatidylserine have some overlap. The effect of anti-C2 domain antibodies further supported these observations. The inhibition of fVIII binding to vWf by monoclonal antibody NMC-VIII/5 IgG or F(ab)'2 (epitope within residues 2170-2327) and by inhibitor antibody MU IgG or Fab' (epitope within residues 2248-2312) was demonstrated by a fluid-phase binding assay and enzyme-linked immunosorbent assay. Two monoclonal antibodies with epitopes within amino acid residues 2170-2218 or 2248-2285, which do not overlap the phosphatidylserine binding site, did not have any inhibitory effect. Our data suggest that the previously described antagonistic binding of vWf and phospholipid to fVIII is due to the involvement of some C2 domain amino acids in both processes.
Deblurring Images: Matrices, Spectra and Filtering (2007)

The <i>Journal of Electronic Imaging</i> (JEI), copublished bimonthly with the Society for Imaging Science and Technology, publishes peer-reviewed papers that cover research and applications in all areas of electronic imaging science and technology.
High-performance and area-efficient stacked transformers for RF CMOS integrated circuits (2003)

A solenoid layout technique is used to increase the magnetic coupling between the coils in multi-level spiral transformers. Using this technique, transformers with the following performance are measured: (a) magnetic coupling with coupling factor k>0.95 and insertion loss s/sub 21/ better than 0.8 dB at 5 GHz; (b) self-resonant frequency f/sub res/>15 GHz with peak Q>10. The effect of high and low resistive substrates is discussed with measured results. Using this structure, the size of the transformer can be reduced from 50 to 400%.
Use of the zero norm with linear models and kernel methods (2003)

We explore the use of the so-called zero-norm of the parameters of linear models in learning. Minimization of such a quantity has many uses in a machine learning context: for variable or feature selection, minimizing training error and ensuring sparsity in solutions. We derive a simple but practical method for achieving these goals and discuss its relationship to existing techniques of minimizing the zero-norm. The method boils down to implementing a simple modification of vanilla SVM, namely via an iterative multiplicative rescaling of the training data. Applications we investigate which aid our discussion include variable and feature selection on biological microarray data, and multicategory classification. 1.
Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis (2001)

These findings implicate the proangiogenic cytokine VEGF in the persistence of inflammatory arthritis, and support the hypothesis that expansion of the synovial vasculature is important for the development of joint destruction in RA.
Nanoparticle-induced vascular blockade in human prostate cancer (2010)

The tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) specifically homes to tumors by binding to fibrin and fibrin-associated clotted plasma proteins in tumor vessels. Previous results show that CREKA-coated superparamagnetic iron oxide particles can cause additional clotting in tumor vessels, which creates more binding sites for the peptide. We have used this self-amplifying homing system to develop theranostic nanoparticles that simultaneously serve as an imaging agent and inhibit tumor growth by obstructing tumor circulation through blood clotting. The CREKA nanoparticles were combined with nanoparticles coated with another tumor-homing peptide, CRKDKC, and nanoparticles with an elongated shape (nanoworms) were used for improved binding efficacy. The efficacy of the CREKA peptide was then increased by replacing some residues with nonproteinogenic counterparts, which increased the stability of the peptide in the circulation. Treatment of mice bearing orthotopic human prostate cancer tumors with the targeted nanoworms caused extensive clotting in tumor vessels, whereas no clotting was observed in the vessels of normal tissues. Optical and magnetic resonance imaging confirmed tumor-specific targeting of the nanoworms, and ultrasound imaging showed reduced blood flow in tumor vessels. Treatment of mice with prostate cancer with multiple doses of the nanoworms induced tumor necrosis and a highly significant reduction in tumor growth.
Heparan sulphate synthetic and editing enzymes in ovarian cancer (2007)

Several angiogenic growth factors including fibroblast growth factors 1 and 2 (FGF1 and FGF2) depend on heparan sulphate (HS) for biological activity. We previously showed that all cellular elements in ovarian tumour tissue synthesised HS but biologically active HS (i.e. HS capable of binding FGF2 and its receptor) was confined to ovarian tumour endothelium. In this study, we have sought to explain this observation. Heparan sulphate sulphotransferases 1 and 2 (HS6ST1 and HS6ST2) attach sulphate groups to C-6 of glucosamine residues in HS that are critical for FGF2 activation. These enzymes were strongly expressed by tumour cells, but only HS6ST1 was found in endothelial cells. Immunostaining with the 3G10 antibody of tissue sections pretreated with heparinases indicated that HS proteoglycans were produced by tumour and endothelial cells. These results indicated that, in contrast to the endothelium, HS produced by tumour cells may be modified by cell-surface heparanase (HPA1) or endosulphatase (SULF). Protein and RNA analysis revealed that HPA1 was strongly expressed by ovarian tumour cells in eight of ten specimens examined. HSULF-1, which removes specific 6-O-sulphate groups from HS, was abundant in tumour cells but weakly expressed in the endothelium. If this enzyme was responsible for the lack of biologically active HS on the tumour cell surface, we would expect exogenous FGF2 binding to be preserved; we showed previously that this was indeed the case although FGF2 binding was reduced compared to the endothelium and stroma. Thus, the combined effects of heparanase and HSULF could account for the lack of biologically active HS in tumour cells rather than deficiencies in the biosynthetic enzymes.
Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q. (1991)

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterized by an early age of onset, usually before 25 years of age, and an autosomal dominant mode of inheritance. The largest and best-studied MODY pedigree is the RW family. The majority of the diabetic subjects in this pedigree has a reduced and delayed insulin-secretory response to glucose, and it has been proposed that this abnormal response is the manifestation of the basic genetic defect that leads to diabetes. Using DNA from members of the RW family, we tested more than 75 DNA markers for linkage with MODY. A DNA polymorphism in the adenosine deaminase gene (ADA) on the long arm of chromosome 20 was found to cosegregate with MODY. The maximum logarithm of odds (lod score) for linkage between MODY and ADA was 5.25 at a recombination fraction of 0.00. These results indicate that the odds are greater than 178,000:1 that the gene responsible for MODY in this family is tightly linked to the ADA gene on chromosome 20q.
Expression of Heat Shock Protein 70 and c-myc Protein in Human Breast Cancer: an Immunohistochemical Study (1991)

The major heat shock protein, HSP70, protects cells from a variety of stressful stimuli, while c-myc protein allegedly stimulates the expression of HSP70 by transacting on the HSP70 promotor. The present study was aimed at correlating the expression of HSP70 with that of c-myc protein in benign and malignant breast lesions. Indirect immunoperoxidase and immunoblotting techniques using monoclonal antibodies were employed. Fresh frozen sections were prepared from five fibroadenomas and 59 breast carcinomas. Immunohistochemically, both substances were localized in the nuclei and/or cytoplasm of normal and neoplastic epithelial cells. The stromal cells were positive for c-myc protein but negative for HSP70. The expressions of HSP70 and c-myc protein were comparable to each other in the malignant cells from 37 (63%) carcinomas. In 17 (29%) carcinomas, c-myc protein expression predominated over that of HSP70, whereas in five (8%) carcinomas, HSP70 was predominant. Carcinomas with high-grade nuclear atypia often showed negative HSP70 staining, whereas tumors with nuclear HSP70 localization tended to accompany lower-grade nuclear atypia. A similar relation was also observed between c-myc protein expression and nuclear atypia of the tumor. All five fibroadenomas and most of the non-neoplastic epithelial cells adjacent to cancer showed strong reactivities with both substances. Immunoblot analysis for HSP70 revealed a clear, single band in the extract of tumors with strong HSP70 staining, but no, or only faint, bands were seen in the extract of immunohistochemically HSP70-negative carcinomas. The discrepancy between the expressions of each substance in a certain percentage of breast carcinomas may suggest the presence of HSP70 production mechanisms other than the c-myc protein-triggered promotor pathway.
Macrophage inflammatory protein-1α is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor κB ligand (2001)

A complementary DNA expression library derived from marrow samples from myeloma patients was recently screened and human macrophage inflammatory protein-1alpha (hMIP-1alpha) was identified as an osteoclastogenic factor expressed in these samples. hMIP-1alpha enhanced osteoclast (OCL) formation in human marrow cultures and by highly purified OCL precursors in a dose-dependent manner (5-200 pg/mL). Furthermore, hMIP-1alpha enhanced OCL formation induced by human interleukin-6 (IL-6), which is produced by marrow stromal cells when they interact with myeloma cells. hMIP-1alpha also enhanced OCL formation induced by parathyroid hormone-related protein (PTHrP) and receptor activator of nuclear factor kappaB ligand (RANKL), factors also implicated in myeloma bone disease. Time-course studies revealed that the hMIP-1alpha acted during the last 2 weeks of the 3-week culture period. Reverse transcription-polymerase chain reaction analysis showed that the chemokine receptors for hMIP-1alpha (CCR1 and CCR5) were expressed by human bone marrow and highly purified early OCL precursors. Furthermore, hMIP-1alpha did not increase expression of RANKL. These data demonstrate that hMIP-1alpha is an osteoclastogenic factor that appears to act directly on human OCL progenitors and acts at the later stages of OCL differentiation. These data further suggest that in patients with myeloma, MIP-1alpha produced by myeloma cells, in combination with RANKL and IL-6 that are produced by marrow stromal cells in response to myeloma cells, enhances OCL formation through their combined effects on OCL precursors. (Blood. 2001;97:3349-3353)
High quality 16 kb/s voice transmission: The subband coder approach (2005)

This paper describes a high quality 16 kb/s subband coder using quadrature mirror filters (QMF). In this algorithm, the partitioning of the speech band into subbands is performed via a bank of eight bandpass filters whose coefficients are derived from a QMF tree structure. Due to the special properties of the QMF, no significant spectral distortions are introduced in the band-splitting and reconstruction processes. To enable a more efficient encoding of the subband waveforms, an adaptive bit assignment scheme is incorporated which allocates the number of quantizer bits according to the distribution of subband energies.
Arming Tumor-Reactive T Cells with Costimulator B7-1 Enhances Therapeutic Efficacy of the T Cells (2006)

T cells ectopically expressing costimulators are pathogenic and contribute to autoimmunity against self-antigens. Given that tumor antigens are often self-antigen or mutated self-antigens, we hypothesize that neoexpressing a costimulator on tumor-reactive T cells may likewise enhance their reactivity to tumor. To test this hypothesis, we have expressed B7-1 on OT-1 CD8+ T-cell receptor transgenic T cells via protein transfer (or protein "painting"). Naïve OT-1 T cells, after being painted with B7-1, can self-costimulate themselves, elicit enhanced proliferative and CTL responses to E.G7-ovalbumin tumor cells (expressing a cognate antigen), and become resistant to CD4+CD25+ regulatory T-cell-mediated suppression. Importantly, these T cells, when coimplanted with E.G7-ovalbumin tumor cells into a syngeneic host, are three to nine times more potent than are control T cells (mock painted with human IgG) in inhibiting tumor growth. Further, on transfer into mice bearing established E.G7-ovalbumin tumors, B7-1-painted ex vivo-amplified OT-1 T cells induced complete tumor regression in 65% of treated mice, whereas the control T cells did so in only 28% of treated mice. Finally, on transfer into mice bearing less immunogenic 4T1 breast tumors, B7-1-painted tumor-reactive CD8+ T cells improved the survival of treated mice to a greater extent than did the control T cells. Hence, this study establishes that arming tumor-reactive T cells with a costimulator can enhance their antitumor efficacy.
Synthesis and topical antiinflammatory activity of some steroidal [16.alpha.,17.alpha.-d]-isoxazolidines (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and topical antiinflammatory activity of some steroidal [16.alpha.,17.alpha.-d]-isoxazolidinesMichael J. Green, Robert L. Tiberi, Richard Friary, Barry N. Lutsky, Joseph Berkenkoph, Xiomara Fernandez, and Margaret MonahanCite this: J. Med. Chem. 1982, 25, 12, 1492–1495Publication Date (Print):December 1, 1982Publication History Published online1 May 2002Published inissue 1 December 1982https://pubs.acs.org/doi/10.1021/jm00354a020https://doi.org/10.1021/jm00354a020research-articleACS PublicationsRequest reuse permissionsArticle Views354Altmetric-Citations30LEARN 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
Adeno-Associated Virus Gene Transfer to Mouse Retina (1998)

Ocular gene transfer may provide a means for arresting the retinal degeneration characteristic of many inherited causes of blindness, including retinitis pigmentosa (RP). Previously, we have shown in immunodeficient animals that recombinant adeno-associated virus (rAAV) mediates transduction of photoreceptors as well as the retinal pigment epithelium (RPE) following subretinal injection. In this study we extend these observations and show that highly purified recombinant AAV vectors encoding the reporter gene LacZ transduce photoreceptors in an immunocompetent mouse strain following subretinal injection and efficiently transduce ganglion cells after intravitreal injection. Levels of transduction increase over time. Sublethal gamma-irradiation is shown to facilitate this process.
A Software Architecture to Support Misuse Intrusion Detection (1995)

Misuse Intrusion Detection has traditionally been understood in the literature as the detection of specific, precisely representable techniques of computer system abuse. Pattern matching is well disposed to the representation and detection of such abuse. Each specific method of abuse can be represented as a pattern and many of these can be matched simultaneously against the audit logs generated by the OS kernel. Using relatively high level patterns to specify computer system abuse relieves the pattern writer from having to understand and encode the intricacies of pattern matching into a misuse detector. Patterns represent a declarative way of specifying what needs to be detected, instead of specifying how it should be detected. We have devised a model of matching based on Colored Petri Nets specifically targeted for misuse intrusion detection. In this paper we present a software architecture for structuring a pattern matching solution to misuse intrusion detection. In the context of an object oriented prototype implementation we describe the abstract classes encapsulating generic functionality and the inter-relationships between the classes.
Role of Alpha/Beta Interferon in Venezuelan Equine Encephalitis Virus Pathogenesis: Effect of an Attenuating Mutation in the 5′ Untranslated Region (2001)

Venezuelan equine encephalitis virus (VEE) is an important equine and human pathogen of the Americas. In the adult mouse model, cDNA-derived, virulent V3000 inoculated subcutaneously (s.c.) causes high-titer peripheral replication followed by neuroinvasion and lethal encephalitis. A single change (G to A) at nucleotide 3 (nt 3) of the 5' untranslated region (UTR) of the V3000 genome resulted in a virus (V3043) that was avirulent in mice. The mechanism of attenuation by the V3043 mutation was studied in vivo and in vitro. Kinetic studies of virus spread in adult mice following s.c. inoculation showed that V3043 replication was reduced in peripheral organs compared to that of V3000, titers in serum also were lower, and V3043 was cleared more rapidly from the periphery than V3000. Because clearance of V3043 from serum began 1 to 2 days prior to clearance of V3000, we examined the involvement of alpha/beta interferon (IFN-alpha/beta) activity in VEE pathogenesis. In IFN-alpha/betaR(-/-) mice, the course of the wild-type disease was extremely rapid, with all animals dying within 48 h (average survival time of 30 h compared to 7.7 days in the wild-type mice). The mutant V3043 was as virulent as the wild type (100% mortality, average survival time of 30 h). Virus titers in serum, peripheral organs, and the brain were similar in V3000- and V3043-infected IFN-alpha/betaR(-/-) mice at all time points up until the death of the animals. Consistent with the in vivo data, the mutant virus exhibited reduced growth in vitro in several cell types except in cells that lacked a functional IFN-alpha/beta pathway. In cells derived from IFN-alpha/betaR(-/-) mice, the mutant virus showed no growth disadvantage compared to the wild-type virus, suggesting that IFN-alpha/beta plays a major role in the attenuation of V3043 compared to V3000. There were no differences in the induction of IFN-alpha/beta between V3000 and V3043, but the mutant virus was more sensitive than V3000 to the antiviral actions of IFN-alpha/beta in two separate in vitro assays, suggesting that the increased sensitivity to IFN-alpha/beta plays a major role in the in vivo attenuation of V3043.