gebhart/patrepeval huggingface dataset:
Particulate naturally processed peptides prime a cytotoxic response against human melanoma in vitro. (1996)

For an efficient antitumor cytotoxic response, tumor antigenic peptides need to be presented by professional antigen-presenting cells in association with MHC class I molecules. We established in vitro short-term human CTL lines from healthy and melanoma-bearing subjects, using as antigen-presenting cells autologous adherent cells after phagocytosis of latex beads coated with melanoma peptides. Melanoma peptides were obtained by acid extraction of melanoma cells that matched with donor peripheral blood mononuclear cells, at least for one HLA-A allele. The cytotoxic activity of the lines was specific for the melanoma from which peptides were obtained and for melanoma sharing HLA alleles. These results demonstrate that a complex mixture of naturally processed melanoma peptides conjugated to a phagocytic substrate that targets them into the MHC class I pathway of adherent cells can prime a CTL response in healthy subjects in vitro, and that peptides from allogeneic tumors may be used to propagate CTL in melanoma patients. Our data support the feasibility of active and passive vaccination procedures with nonliving vaccines in cancer patients.
Synthesis of some N-carboxylic acid derivatives of 3-phenoxypyrrolidines, 4-phenoxypiperidines, and 3-phenoxynortropanes with muscle relaxant and anticonvulsant activities (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of some N-carboxylic acid derivatives of 3-phenoxypyrrolidines, 4-phenoxypiperidines, and 3-phenoxynortropanes with muscle relaxant and anticonvulsant activitiesRobert F. Boswell Jr., Grover C. Helsley, Robert L. Duncan Jr., William H. Funderburk, and David N. JohnsonCite this: J. Med. Chem. 1974, 17, 9, 1000–1008Publication Date (Print):September 1, 1974Publication History Published online1 May 2002Published inissue 1 September 1974https://pubs.acs.org/doi/10.1021/jm00255a020https://doi.org/10.1021/jm00255a020research-articleACS PublicationsRequest reuse permissionsArticle Views190Altmetric-Citations10LEARN 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
Nasal Immunization with Diphtheria Toxoid Conjugated‐CD52 Core Peptide Induced Specific Antibody Production in Genital Tract of Female Mice (2002)

These results indicate that the CMIS could induce Ig and IgA class antibodies reactive to CD52 core peptide in the female genital tract. Intranasal immunization of a sperm-specific antigen would be a promising regimen for a safe and easy contraceptive vaccine.
Separation and Characterization of Glyeolaldehyde Dehydrogenase Isozymes inEscherichia coliB (1978)

Glyeolaldehyde dehydrogenase, an enzyme involved in vitamin B6 biosynthesis, was partially purified from the wild type strain of Escherichia coli B. The enzyme was separated into three fractions (glyeolaldehyde dehydrogenases A, B and C) by DEAE-cellulose column chromatography. The enzymes B and C, which were eluted by 0.1 m potassium phosphate buffer plus 0.1 m NaCl and by that plus 0.2 m NaCl, respectively, lacked in the cell-free extract of a pyridoxine auxotrophic strain, E. coli B WG3, The enzyme A, which was eluted by 0.1 m potassium phosphate buffer has a broad specificity for substrate. On the other hand, the enzyme B or C is relatively specific to glyeolaldehyde. The enzymes A, B and C could be defined as isozymes with enzymatic characterization.
Generation of M-ary signals using a single Mach Zehnder interferometer (2009)

A method is presented for generating M-ary signals by introducing direct digital driving combined with a single Multi-Electrode Mach-Zehnder interferometer. It is characterized by using two-level driving signals and thus eliminating the need for complex analog driving circuits. Example of generating square 16-QAM constellation is given. It is shown that using a total of 10 electrode segments achieves close-to-ideal performance.
Mapping the site on human IgG for binding of the MHC class I-related receptor, FcRn (1999)

The analysis of the pharmacokinetics of wild-type and mutated Fc fragments derived from human IgG1 indicates that Ile253, His310 and His435 play a central role in regulating serum half-life in mice. Reduced serum half-life of the recombinant, mutated fragments correlates with decreased binding to the MHC class I-related neonatal Fc receptor, FcRn. In addition, the analysis of an Fc fragment in which His435 is mutated to Arg435 demonstrates that the sequence difference at this position between human IgG1 (His435) and IgG3 (Arg435) most likely accounts for the shorter serum half-life of IgG3 relative to IgG1. In contrast to His310 and His435, the data indicate that His433 does not play a role in regulating the serum half-life of human IgG1. Thus, the interaction site of mouse FcRn on human and mouse IgG1 involves the same conserved amino acids located at the CH2-CH3 domain interface of the IgG molecule. The sequence similarities between mouse and human FcRn suggest that these studies have direct relevance to understanding the factors that govern the pharmacokinetics of therapeutic IgG.
Disruption of CXCR2-Mediated MDSC Tumor Trafficking Enhances Anti-PD1 Efficacy (2014)

Suppression of the host's immune system plays a major role in cancer progression. Tumor signaling of programmed death 1 (PD1) on T cells and expansion of myeloid-derived suppressor cells (MDSCs) are major mechanisms of tumor immune escape. We sought to target these pathways in rhabdomyosarcoma (RMS), the most common soft tissue sarcoma of childhood. Murine RMS showed high surface expression of PD-L1, and anti-PD1 prevented tumor growth if initiated early after tumor inoculation; however, delayed anti-PD1 had limited benefit. RMS induced robust expansion of CXCR2(+)CD11b(+)Ly6G(hi) MDSCs, and CXCR2 deficiency prevented CD11b(+)Ly6G(hi) MDSC trafficking to the tumor. When tumor trafficking of MDSCs was inhibited by CXCR2 deficiency, or after anti-CXCR2 monoclonal antibody therapy, delayed anti-PD1 treatment induced significant antitumor effects. Thus, CXCR2(+)CD11b(+)Ly6G(hi) MDSCs mediate local immunosuppression, which limits the efficacy of checkpoint blockade in murine RMS. Human pediatric sarcomas also produce CXCR2 ligands, including CXCL8. Patients with metastatic pediatric sarcomas display elevated serum CXCR2 ligands, and elevated CXCL8 is associated with diminished survival in this population. We conclude that accumulation of MDSCs in the tumor bed limits the efficacy of checkpoint blockade in cancer. We also identify CXCR2 as a novel target for modulating tumor immune escape and present evidence that CXCR2(+)CD11b(+)Ly6G(hi) MDSCs are an important suppressive myeloid subset in pediatric sarcomas. These findings present a translatable strategy to improve the efficacy of checkpoint blockade by preventing trafficking of MDSCs to the tumor site.
Alzheimer’s disease: diagnostics, prognostics and the road to prevention (2010)

Alzheimer's disease (AD) presents one of the leading healthcare challenges of the 21st century, with a projected worldwide prevalence of >107 million cases by 2025. While biomarkers have been identified, which may correlate with disease progression or subtype for the purpose of disease monitoring or differential diagnosis, a biomarker for reliable prediction of late onset disease risk has not been available until now. This deficiency in reliable predictive biomarkers, coupled with the devastating nature of the disease, places AD at a high priority for focus by predictive, preventive and personalized medicine. Recent data, discovered using phylogenetic analysis, suggest that a variable length poly-T sequence polymorphism in the TOMM40 gene, adjacent to the APOE gene, is predictive of risk of AD age-of-onset when coupled with a subject's current age. This finding offers hope for reliable assignment of disease risk within a 5-7 year window, and is expected to guide enrichment of clinical trials in order to speed development of preventative medicines.
Tumor Cell Killing Enabled by Listeriolysin O-liposome-mediated Delivery of the Protein Toxin Gelonin (2003)

Gelonin is a type I plant toxin that has potential as an effective anti-tumor agent by virtue of its enzymatic capacity to inactivate ribosomes and arrest protein synthesis, thereby effectively limiting the growth of cancer cells. Being a hydrophilic macromolecule, however, gelonin has limited access to its target subcellular compartment, the cytosol; it is effectively plasma membrane-impermeant and subject to rapid degradation within endosomes and lysosomes upon cellular uptake as it lacks the membrane-translocating capability that is typically provided by a disulfide-linked B polypeptide found in the type II toxins (e.g. ricin). These inherent characteristics generate the need for the development of a specialized cytosolic delivery strategy for gelonin as an effective anti-tumor therapeutic agent. Here we describe an efficient means of delivering gelonin to the cytosol of B16 melanoma cells. Gelonin was co-encapsulated inside pH-sensitive liposomes with listeriolysin O, the pore-forming protein that mediates escape of the intracellular pathogen Listeria monocytogenes from the endosome into the cytosol. In in vitro experiments, co-encapsulated listeriolysin O enabled liposomal gelonin-mediated B16 cell killing with a gelonin IC50 of approximately 0.1 nM with an extreme efficiency requiring an incubation time of only 1 h. By contrast, cells treated with equivalent concentrations of unencapsulated gelonin or gelonin encapsulated alone in pH-sensitive liposomes exhibited no detectable cytotoxicity. Moreover, treatment by direct intratumor injection into subcutaneous solid tumors of B16 melanoma in a mouse model showed that pH-sensitive liposomes containing both listeriolysin O and gelonin were more effective than control formulations in curtailing tumor growth rates.
Effects of media and electrode materials on the electrochemical reduction of dioxygen (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffects of media and electrode materials on the electrochemical reduction of dioxygenDonald T. Sawyer, Glaico. Chiericato, Charles T. Angelis, Edward J. Nanni, and Tohru. TsuchiyaCite this: Anal. Chem. 1982, 54, 11, 1720–1724Publication Date (Print):September 1, 1982Publication History Published online1 May 2002Published inissue 1 September 1982https://pubs.acs.org/doi/10.1021/ac00248a014https://doi.org/10.1021/ac00248a014research-articleACS PublicationsRequest reuse permissionsArticle Views2380Altmetric-Citations353LEARN 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
Exacerbation of symptoms of autoimmune disease in patients receiving alpha-interferon therapy (1990)

The occurrence of autoimmune disease in patients receiving alpha-interferon (alpha-IFN) therapy has been reported in several studies; these include autoimmune thyroiditis, thrombocytopenia, anemia, exacerbation of psoriasis, and the occurrence of sarcoidosis. The primary mechanism presumably is the emergence of autoantibodies to various structural proteins or receptors. Two studies have recently shown that a significant percentage of patients treated with recombinant alpha-interferon (r alpha-IFN) do form autoantibodies. The authors report six additional cases of development or exacerbation of autoimmune phenomena in patients receiving alpha-IFN therapy. Five of these patients developed symmetric polyarthropathies and the sixth had thyroiditis. The presence of a history of underlying autoimmune disease or baseline serologic abnormalities in five of these patients, including the patient who developed thyroiditis, suggests that alpha-IFN treatment can lead to the exacerbation of an underlying subclinical autoimmune process.
Utilization of Early Invasive Management Strategies for High-Risk Patients With Non–ST-Segment Elevation Acute Coronary Syndromes (2004)

Use of early invasive management within 48 hours of presentation, predictors of early invasive management, and in-hospital mortality. Results Of the 17,926 patients analyzed, 8037 (44.8%) underwent early cardiac catheterization less than 48 hours following presentation. Predictors of early invasive management included cardiology care, younger age, lack of prior or current congestive heart failure, lack of renal insufficiency, ischemic electrocardiographic changes, positive cardiac markers, white race, and male sex. Patients treated with early invasive management were more likely to be treated with medications and interventions recommended by the ACC/AHA guidelines and had a lower risk of in-hospital mortality after adjusting for differences in clinical characteristics and after comparing propensity-matched pairs (2.5% vs 3.7%, P<.001). Conclusions An early invasive management strategy is not utilized in the majority of high-risk patients with NSTE ACS. This strategy appears to be reserved for patients without significant comorbidities and those cared for by cardiologists and is associated with a lower risk of in-hospital mortality.
High Sensitivity and Analyte Capture with Desorption/Ionization Mass Spectrometry on Silylated Porous Silicon (2004)

Silylation chemistry on porous silicon provides for ultrahigh sensitivity and analyte specificity with desorption/ionization on silicon mass spectrometry (DIOS-MS) analysis. Here, we report that the silylation of oxidized porous silicon offers a DIOS platform that is resistant to air oxidation and acid/base hydrolysis. Furthermore, surface modification with appropriate hydrophobic silanes allows analytes to absorb to the surface via hydrophobic interactions for direct analyte extraction from complex matrixes containing salts and other nonvolatile interferences present in the sample matrix. This enables rapid cleanup by simply spotting the sample onto the modified DIOS target and removing the liquid phase containing the interferences. This approach is demonstrated in the analysis of protein digests and metabolites in biofluids, as well as for the characterizing of inhibitors from their enzyme complex. An unprecedented detection limit of 480 molecules (800 ymol) for des-Arg(9)-bradykinin is reported on a pentafluorophenyl-functionalized DIOS chip.
Effects of SiO2 nanoparticles on HFL‐I activating ROS‐mediated apoptosis via p53 pathway (2011)

Silicon dioxide nanoparticles (SiO(2) NPs) have attracted increasing interest as nanovehicles for delivering drugs, genes and bio-active molecules into cells. However, it is still unknown whether SiO(2) NPs could cause side-effects to normal cells. In the present study, human lung fibroblasts (HFL-Is) were directly exposed to two different sizes of SiO(2) NPs. The effect of size and concentration on cell response was studied by analyzing the cell viability, the ratio of apoptosis and the pathway of cell injury. The results demonstrated that a size-associated and a dose-dependent toxicity of HFL-Is was induced by SiO(2) NPs. Meanwhile, the expression of reactive oxygen species in HFL-I was significantly increased. This activation effect was accompanied by upregulation of p53 expression, release of cytochrome C from chondriosomes, inhibition of Bcl2, and activation of Bax and caspase 9. These findings implied that SiO(2) NPs might induce apoptosis of HFL-Is by stimulating reactive oxygen species release and subsequently causing the activation of p53 pathway in vitro.
2A peptides provide distinct solutions to driving stop-carry on translational recoding (2011)

Expression of viral proteins frequently includes non-canonical decoding events ('recoding') during translation. '2A' oligopeptides drive one such event, termed 'stop-carry on' recoding. Nascent 2A peptides interact with the ribosomal exit tunnel to dictate an unusual stop codon-independent termination of translation at the final Pro codon of 2A. Subsequently, translation 'reinitiates' on the same codon, two individual proteins being generated from one open reading frame. Many 2A peptides have been identified, and they have a conserved C-terminal motif. Little similarity is present in the N-terminal portions of these peptides, which might suggest that these amino acids are not important in the 2A reaction. However, mutagenesis indicates that identity of the amino acid at nearly all positions of a single 2A peptide is important for activity. Each 2A may then represent a specific solution for positioning the conserved C-terminus within the peptidyl-transferase centre to promote recoding. Nascent 2A peptide:ribosome interactions are suggested to alter ribosomal fine structure to discriminate against prolyl-tRNA(Pro) and promote termination in the absence of a stop codon. Such structural modifications may account for our observation that replacement of the final Pro codon of 2A with any stop codon both stalls ribosome processivity and inhibits nascent chain release.
Isolation and characterization of Tri3, a gene encoding 15-O-acetyltransferase from Fusarium sporotrichioides (1996)

An acetyltransferase gene (Tri3) was isolated from Fusarium sporotrichioides by complementation of a previously identified Tri3- mutant and shown to be closely linked to three other trichothecene biosynthetic pathway genes. Comparison of the Tri3 sequence with its cDNA revealed the presence of four introns. The Tri3 cDNA contains a 1,539-bp open reading frame that encodes a protein with a molecular mass of 57,418 Da. Regulation of Tri3 transcription in liquid cultures appeared identical to that of other trichothecene pathway genes. Disruption of the Tri3 gene resulted in the accumulation of deacetylated calonectrins rather than T-2 toxin. The results of whole-cell feeding experiments with Tri3- strains suggested that 15-O-acetylation is blocked. Cell-free feeding experiments confirmed that Tri3- strains are able to acetylate a trichothecene C-3 hydroxyl group but are unable to acetylate a trichothecene C-15 hydroxyl group. Our results show that Tri3 encodes an acetyltransferase that converts 15-decalonectrin to calonectrin.
Routing and link-layer protocols for multi-channel multi-interface ad hoc wireless networks (2006)

Wireless technologies, such as IEEE 802.11a, that are used in ad hoc networks provide for multiple non-overlapping channels. Most ad hoc network protocols that are currently available are designed to use a single channel. However, the available network capacity can be increased by using multiple channels. This paper presents new protocols specifically designed to exploit multiple channels. Our protocols simplify the use of multiple channels by using multiple interfaces, although the number of interfaces per host is typically smaller than the number of channels. We propose a link layer protocol to manage multiple channels, and it can be implemented over existing IEEE 802.11 hardware. We also propose a new routing metric for multi-channel multi-interface networks, and the metric is incorporated into an on-demand routing protocol that operates over the link layer protocol. Simulation results demonstrate the effectiveness of the proposed approach in significantly increasing network capacity, by utilizing all the available channels, even when the number of interfaces per host is smaller than the number of channels.
Integration, expression and germ-line transmission of foreign growth hormone genes in medaka (Oryzias latipes). (1993)

Gene constructs consisting of human growth hormone (hGH) gene driven by promoter/regulatory sequence of mouse metallothionein (mMT), viral thymidine kinase (vTK), rat cholecystokinin (rCCK), or chicken beta-actin (cBA) gene were injected into the cytoplasm of fertilized medaka eggs via the micropyle. More than 49% of the injected embryos survived at hatching. Up to 26% of the survivors showed integration of the introduced gene construct, as determined by polymerase chain reaction analysis and subsequent confirmation by Southern blot hybridization of the genomic DNA. A significant fraction of F1 progeny, derived from crosses between transgenic founders and the nontransgenic individuals, inherited the transgene. Expression of hGH gene was also observed in some of the P1 founders and F1 transgenic progeny carrying mMT-hCG or cBA-hGH gene. Furthermore, the growth performance of the P1 mMT-hGH and cBA-hGH transgenic founders and F1 cBA-hGH F1 transgenic progeny was significantly greater than their full sibling, nontransgenic individuals. In addition to the microinjection experiment, a gene construct containing the long-terminal repeat (LTR) sequence of avian Rous sarcoma virus (RSV) and rainbow trout (rt) GH2 cDNA was introduced into embryos of medaka by electroporation using an exponential decay electroporator. Approximately 70% of the electroporated embryos survived at hatching, and 20% of the survived individuals integrated RSVLTR-rtGH2 cDNA into their genomes. These two techniques will greatly enhance the ability to study regulation of gene expression in transgenic animals during differentiation and development.
A meta-analysis of reverse transcriptase-polymerase chain reaction for tyrosinase mRNA as a marker for circulating tumor cells in cutaneous melanoma. (2001)

The lack of data on the outcome of stage I, II, and III patients who were RT-PCR positive and the low prevalence of RT-PCR positivity in patients with known stage IV disease limit the applicability of this test at this time. Ongoing and future studies on a quantitative RT-PCR, amplification of multiple melanoma-associated antigens, and use of the test as a prognostic indicator might improve the utility of this molecular serologic tool.