gebhart/patrepeval huggingface dataset:
Presentation of tumor antigens. (1999)

Dendritic cells, with their extraordinary capacity for initiating primary and secondary T-lymphocyte responses, may be pivotal in the development of immunotherapeutic strategies for multiple myeloma. Although host lymphocytes are able to recognize tumor-associated antigens (TAAs), many tumors are able to avoid dendritic cell-mediated immune surveillance. One reason may be that the tumor environment inhibits the maturation and activation of dendritic cells. A recently developed strategy to use dendritic cells in immunotherapy involves removing them from the tumor, pulsing them in vitro with antigen, and reinfusing them into the patient to generate responding T cells in vivo. Methods for reliably obtaining dendritic cells for therapeutic use are currently being investigated. Among other efforts to induce T-cell-mediated immunity against cancer, the presentation of tumor antigens by the tumor cells themselves is being investigated. Issues to be resolved include defects of antigen presentation by tumor cells and whether all cells present the same set of peptides. Moreover, as long as all the tumor antigens have not been identified, the tumor cell itself remains the primary source of unknown antigens and, therefore, is a worthwhile subject for study. Phase I trials of immunotherapy using adenovirus-infected autologous plasma cells have recently been undertaken. The adenoviral vectors carry genes with therapeutic potential, including interleukin-2 (IL-2), interleukin-12, and B7-1. Initial results showed that the vector can be readily detected in tumor cells at 13 days postinjection, and IL-2 expression was evident at 7 days. The chief side effect reported was inflammation.
Induction of Genes Mediating Interferon-dependent Extracellular Trap Formation during Neutrophil Differentiation (2004)

Interferons (IFNs) are cytokines that possess potent anti-viral and immunoregulatory activities. In contrast, their potential role(s) in anti-bacterial defense and neutrophil activation mechanisms is less well explored. By comparing gene expression patterns between immature and mature human neutrophils, we obtained evidence that intracellular proteases and other anti-bacterial proteins are produced at earlier stages of maturation, whereas the genes for receptors and signaling molecules required for the release of these effector molecules are preferentially induced during terminal differentiation. For instance, mature neutrophils strongly expressed genes that increase their responses to type I and type II IFNs. Interestingly, granulocyte/macrophage colony-stimulating factor was identified as a repressor of IFN signaling components and consequently of IFN-responsive genes. Both IFN-alpha and IFN-gamma induced strong tyrosine phosphorylation of STAT1 in mature but not in immature neutrophils. Functional in vitro studies suggested that IFNs act as priming factors on mature neutrophils, allowing the formation of extracellular traps upon subsequent stimulation with complement factor 5a (C5a). In contrast, both IFN-alpha and IFN-gamma had only little capacity to prime immature cells in this system. Moreover, both IFNs did not have significant anti-proliferative effects on immature neutrophils. These data contribute to our understanding regarding changes of gene expression during neutrophil differentiation and IFN-mediated anti-bacterial defense mechanisms.
Expression of Neutrophil Gelatinase-associated Lipocalin Regulates Epithelial Morphogenesis in Vitro (2005)

Growth factors such as hepatocyte growth factor (HGF) are highly up-regulated during development and following renal injury and are known to induce marked morphogenic actions in cultured tubular epithelial cells, including scattering, migration, single cell branching morphogenesis, and multicellular branching tubulogenesis. In the present study, we demonstrate that HGF stimulates epithelial cells to express neutrophil gelatinase-associated lipocalin (Ngal), a member of the lipocalin family of secreted proteins that has recently been shown to participate in mesenchymal-epithelial transformation via its ability to augment cellular iron uptake. At concentrations below those found to mediate iron transport, purified Ngal can induce a promigratory and probranching effect that is dependent on ERK activation. The suppression of Ngal expression using short hairpin RNA results in increased cyst formation by tubular cells. However, the simultaneous addition of Ngal and HGF leads to direct association of the two proteins, and results in a partial inhibition of HGF-mediated activation of c-Met and the downstream MAPK and phosphatidylinositol 3-kinase signaling pathways. This inhibitory effect down-regulates HGF-stimulated single cell migration, and limits branching morphogenesis at both the single cell and multicellular level. These experiments demonstrate that the local expression of Ngal can play a regulatory role in epithelial morphogenesis by promoting the organization of cells into tubular structures while simultaneously negatively modulating the branching effects of HGF.
Fluorine-18-antimyosin monoclonal antibody fragments: preliminary investigations in a canine myocardial infarct model. (1992)

The purpose of this study was to determine in a canine model whether selective myocardial infarct uptake of 18F-labeled antimyosin monoclonal antibody fragments could be achieved in a time frame compatible with the short half-life of this nuclide. Antimyosin monoclonal antibody fragments were labeled with 18F using a succinimidyl [18F]fluorobenzylamine ester acylation agent. Six dogs had myocardial infarction induced by coronary artery occlusion and were reperfused prior to the intravenous administration of 0.6-4.7 mCi of 18F-labeled F(ab')2 (two dogs) or Fab (four dogs). Analysis of tissues obtained 2-4 hr after antibody administration revealed infarct:normal myocardium uptake ratios as high as 14-21:1 for F(ab')2 and 9-12:1 for Fab. Even with Fab, however, prolonged 18F activity in the blood pool interfered with delineation of infarcts by PET imaging. In one dog, perfusion imaging with [13N]ammonia before antimyosin administration was performed, and regions of normal and ischemic myocardium were determined. With these regions of interest, infarct:normal myocardium uptake ratios calculated from the 18F-labeled Fab images increased from 1.5:1 at 1 hr to 4.0:1 at 5 hr. We conclude that 18F-labeled antimyosin fragments may be of value for hot-spot imaging of damaged myocardium with PET; however, blood-pool subtraction techniques will probably be required.
I-PLA2 Activation during Apoptosis Promotes the Exposure of Membrane Lysophosphatidylcholine Leading to Binding by Natural Immunoglobulin M Antibodies and Complement Activation (2002)

Deficiency of serum immunoglobulin (Ig)M is associated with the development of a lupus-like disease in mice. Recent studies suggest that classical complement components facilitate the clearance of apoptotic cells and that failure to do so predisposes mice to lupus. Since IgM is a potent activator of the classical complement pathway, we examined IgM binding to dying cells. IgM, but not IgG, bound to apoptotic T cells through the Fab' portion of the antibody. Exposure of apoptotic cell membranes to phospholipase (PL) A2 increased, whereas PLD reduced, IgM binding and complement activation. Absorption studies combined with direct plate binding assays, revealed that IgM antibodies failed to bind to phosphatidyl lipids, but did recognize lysophosphatidylcholine and the phosphorylcholine head group. Both iPLA(2) and cPLA(2) are activated during apoptosis. Since inhibition of iPLA2, but not cPLA2, attenuated IgM binding to apoptotic cells, these results strongly suggest that the endogenous calcium independent PLA(2), iPLA(2), is involved in the hydrolysis of plasma membrane phospholipids and exposure of the epitope(s) recognized by IgM. We propose that recognition of dying cells by natural IgM antibodies is, in part, responsible for complement activation on dying cells leading to their safe clearance.
Modeling and deadlock control of automated guided vehicle systems (2004)

This paper presents a colored resource-oriented Petri net (CROPN) modeling method to deal with conflict and deadlock arising in automated guided vehicles (AGV) systems. It can handle both bidirectional and unidirectional paths. The former offer additional flexibility, efficiency, and cost saving when compared with the latter. Yet, they exhibit more challenging AGV management problems. Unlike jobs that can enter and leave automated manufacturing systems, AGVs always stay in the system. By modeling nodes with places and lanes with transitions, the proposed method can construct CROPN models for changing AGV routes. A control policy suitable for real-time implementation is presented.
Molecular classification of multiple tumor types (2001)

Using gene expression data to classify tumor types is a very promising tool in cancer diagnosis. Previous works show several pairs of tumor types can be successfully distinguished by their gene expression patterns (Golub et al. 1999, Ben-Dor et al. 2000, Alizadeh et al. 2000). However, the simultaneous classification across a heterogeneous set of tumor types has not been well studied yet. We obtained 190 samples from 14 tumor classes and generated a combined expression dataset containing 16063 genes for each of those samples. We performed multi-class classification by combining the outputs of binary classifiers. Three binary classifiers (k-nearest neighbors, weighted voting, and support vector machines) were applied in conjunction with three combination scenarios (one-vs-all, all-pairs, hierarchical partitioning). We achieved the best cross validation error rate of 18.75% and the best test error rate of 21.74% by using the one-vs-all support vector machine algorithm. The results demonstrate the feasibility of performing clinically useful classification from samples of multiple tumor types.
alpha-Actinin and vinculin are PIP2-binding proteins involved in signaling by tyrosine kinase. (1994)

Western blot analysis of Balb/c 3T3 cell lysates by an antibody specific to phosphatidylinositol 4,5-bisphosphate (PIP2) showed that several proteins exist in a PIP2-bound form. Among them, two proteins, 100 and 115 kDa in molecular mass, were detected as PIP2 abundant proteins. These were identified as alpha-actinin and vinculin by their antibodies. In Balb/c 3T3 cells, alpha-actinin in the cytoskeleton contains PIP2, while alpha-actinin in cytosol does not. The levels of PIP2 bound to alpha-actinin decrease in response to platelet-derived growth factor (PDGF). Similarly, PIP2 bound to vinculin is decreased upon stimulation with PDGF. By immunofluorescent staining, PIP2 was found to be present densely in the central areas around nuclei, microfilament bundles, and focal contacts, where alpha-actinin and vinculin are distributed. PDGF stimulation decreases the intensity of PIP2 staining in these areas. In this paper we suggest that tyrosine kinase-activated phospholipase C hydrolyzes PIP2 bound to alpha-actinin and vinculin, leading to the simultaneous generation of second messengers and reorganization of the cytoskeleton.
Re-evaluating the burden of rabies in Africa and Asia. (2005)

Rabies remains an important yet neglected disease in Africa and Asia. Disparities in the affordability and accessibility of post-exposure treatment and risks of exposure to rabid dogs result in a skewed distribution of the disease burden across society, with the major impact falling on those living in poor rural communities, in particular children.
Phosphonic Acid Analogs of Nucleoside Phosphates. I. The Synthesis of 5″-Adenylyl Methylenediphosphonate, a Phosphonic Acid Analog of ATP (1963)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhosphonic Acid Analogs of Nucleoside Phosphates. I. The Synthesis of 5″-Adenylyl Methylenediphosphonate, a Phosphonic Acid Analog of ATPTerrell C. Myers, Kaname. Nakamura, and James W. FlesherCite this: J. Am. Chem. Soc. 1963, 85, 20, 3292–3295Publication Date (Print):October 1, 1963Publication History Published online1 May 2002Published inissue 1 October 1963https://pubs.acs.org/doi/10.1021/ja00903a053https://doi.org/10.1021/ja00903a053research-articleACS PublicationsRequest reuse permissionsArticle Views351Altmetric-Citations75LEARN 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
Fluorescent, Siderophore-Based Chelators. Design and Synthesis of a Trispyrenyl Trishydroxamate Ligand, an Intramolecular Excimer-Forming Sensing Molecule Which Responds to Iron(III) and Gallium(III) Metal Cations (1996)

Two pyrene-labeled hydroxylamines, 5-Bn and 5-Bz, O-protected with the benzyl and the benzoyl group, respectively, have been prepared for the generation of siderophore-based new chelators incorporating both the pyrene chromophore and the hydroxamic acid functionality. 5-Bz formed the starting point toward the synthesis of the tripod-shaped trishydroxamate, 1. That trichromophoric ligand displays remarkable fluorescence emission properties (dual emission: "monomer" and excimer type) which are markedly and selectively modified by binding Fe(NO(3))(3) and Ga(NO(3))(3). Ferric ions induce a quasi total quenching of the pyrene fluorescence, whereas the nonquenching Ga(III) cations are observed to affect the value of the excimer-to-monomer fluorescence intensity ratio. Ethylenediaminetetraacetic acid (EDTA) competition reactions yielded an estimated value of 3.8 for log K of the complex LFe in methanol/water (80/20 v/v), where K = ([LFe][H(+)](3))/([LH(3)][Fe(3+)]) and L is the ligand in its totally deprotonated form. Compound 1 is the prototype of a new class of photoresponsive molecular systems which could act as sensitive probes for metal cation detection and recognition.
Comparison of Seven Techniques for Typing International Epidemic Strains of Clostridium difficile : Restriction Endonuclease Analysis, Pulsed-Field Gel Electrophoresis, PCR-Ribotyping, Multilocus Sequence Typing, Multilocus Variable-Number Tandem-Repeat Analysis, Amplified Fragment Length Polymorphism, and Surface Layer Protein A Gene Sequence Typing (2007)

Using 42 isolates contributed by laboratories in Canada, The Netherlands, the United Kingdom, and the United States, we compared the results of analyses done with seven Clostridium difficile typing techniques: multilocus variable-number tandem-repeat analysis (MLVA), amplified fragment length polymorphism (AFLP), surface layer protein A gene sequence typing (slpAST), PCR-ribotyping, restriction endonuclease analysis (REA), multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). We assessed the discriminating ability and typeability of each technique as well as the agreement among techniques in grouping isolates by allele profile A (AP-A) through AP-F, which are defined by toxinotype, the presence of the binary toxin gene, and deletion in the tcdC gene. We found that all isolates were typeable by all techniques and that discrimination index scores for the techniques tested ranged from 0.964 to 0.631 in the following order: MLVA, REA, PFGE, slpAST, PCR-ribotyping, MLST, and AFLP. All the techniques were able to distinguish the current epidemic strain of C. difficile (BI/027/NAP1) from other strains. All of the techniques showed multiple types for AP-A (toxinotype 0, binary toxin negative, and no tcdC gene deletion). REA, slpAST, MLST, and PCR-ribotyping all included AP-B (toxinotype III, binary toxin positive, and an 18-bp deletion in tcdC) in a single group that excluded other APs. PFGE, AFLP, and MLVA grouped two, one, and two different non-AP-B isolates, respectively, with their AP-B isolates. All techniques appear to be capable of detecting outbreak strains, but only REA and MLVA showed sufficient discrimination to distinguish strains from different outbreaks.
Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus (2009)

The neuroprotective role for antenatal magnesium sulphate therapy given to women at risk of preterm birth for the preterm fetus is now established. The number of women needed to be treated to benefit one baby by avoiding cerebral palsy is 63 (95% confidence interval 43 to 87). Given the beneficial effects of magnesium sulphate on substantial gross motor function in early childhood, outcomes later in childhood should be evaluated to determine the presence or absence of later potentially important neurological effects, particularly on motor or cognitive function.
Azoic Diazo Components Containing Phenyl Morpholine Ring. (1959)

モルホリン環を置換基の一つとして有する種々の芳香族アミノ化合物を合成し, これをナフトール染料の顕色剤として利用してモメンを染色し,その色調および堅ろう度をしらべた。すなわち,塩素,臭素,ニトロ,メトキシ,エトキシ,ベンゾイルアミノの各基を一つあるいは二つ有する置換アミノフェニルモルホリン類を合成し,市販ナフトールAS類とモメン上で顕色し染色布について,その反射スペクトルから色度解析を行った結果,臭素基あるいは塩素基のみを有するアミノフェニルモルホリン類は茶色系に,臭素基あるいは塩素基とニトロ基を有するものは赤色に,エトキシ基,メトキシ基を有するものは紫系に,ベンゾイルアミノ基を有するものは紫～ 青色系にそれぞれ顕色することがわかった。臭素基およびニトロ基を有するものの一部をのぞいてはいずれも各種の堅ろう度はすぐれていた。
Genetic polymorphism of the human organic solute carrier protein 1 (hOSCP1) gene in Japanese patients with non-viral liver carcinoma (2014)

Human organic solute carrier protein 1 (hOSCP1) is a Na(+)-independent multispecific organic solute transporter. To date, several studies have revealed that gene mutations of the transporters are likely to be associated with some diseases; however, there are no data concerning the genetic polymorphism of the hOSCP1 gene in Japanese patients with non-viral liver carcinoma (LC). In the present study, we isolated genomic DNA from a normal portion of LC, and analyzed 41 single nucleotide polymorphisms (SNPs) chosen from a database of SNPs (dbSNPs). We found genotype frequencies for 2 non-synonymous SNPs [rs34409118 (Thr(131) → Ala) and rs1416840 (Ile(219) → Thr)] and 1 synonymous SNP [rs16822954 (Ser(193) → Ser)] to be statistically significant when compared with dbSNPs. No statistical significance was observed in rs2275477 (Gly(307) → Arg) in the hOSCP1 gene. With respect to the allele frequency, we also observed rs34409118 to be statistically significant. Interestingly, we found that non-viral LC patients do not carry heterozygous mutations in rs1416840 (A/G) and rs16822954 (A/G), suggesting that a non-carrier of heterozygous mutations in these two SNPs might be a biomarker for susceptibility for non-viral LC in Japanese. Further analyses of patients with hOSCP1 variants may elucidate the relationship between the hOSCP1 gene and susceptibility of non-viral LC in Japanese patients.
Administration of noncytolytic IL-10/Fc in murine models of lipopolysaccharide-induced septic shock and allogeneic islet transplantation. (1995)

Numerous studies have suggested the potential application of IL-10 as an anti-inflammatory and as an antirejection agent. Unfortunately, cytokines have short circulating t1/2 We developed a murine IL-10/Fc gamma 2a immunoligand that possesses the biologic functions of IL-10 and the long circulating t1/2 in vivo, characteristic of Igs. We mutated the Fc gamma 2a fragment to render the immunoligand ineffective in directing Ab-dependent cell-mediated cytotoxicity and complement-directed cytolysis (noncytolytic IL-10/Fc (IL-10/Fc2-)). In terms of IL-10 activity, IL-10/Fc2- was as effective as rIL-10 mole per mole in preventing lethal septic shock, but the immunoligand had a prolonged period of efficacy in accord with its extended circulating half-life. Contrary to expectations, IL-10/Fc2- treatment tended to accelerate the destruction of islet cell allografts and increase the levels of granzyme B gene expression in local draining lymph nodes. These data suggest that the enhanced cytotoxic activity of allograft-destroying CTLs may contribute to the accelerated allograft rejection. Finally, our studies suggest that a noncytolytic IL-10/Fc fusion protein provides a useful tool to study the biologic effects of IL-10 in vivo and may provide a useful agent for the prevention and treatment of septic shock.
Thrombospondin: phenomenology to function. (1989)

Since the initial description of thrombospondin in 1971, our knowledge of the protein has reached a point where some understanding of its physiologic and pathologic roles has accrued. Thrombospondin is a multifunctional glycoprotein whose demonstrated affinities for multiple ligands make it a versatile molecule that can participate in mediating or modulating cell adhesion, fibrin polymerization, fibrinolysis, and development. The recently defined primary structure will make an understanding of the functional aspects of this molecule more accessible, and the next several years promises to define the role of thrombospondin in human biology.
Three‐Dimensional Flexible Electronics Enabled by Shape Memory Polymer Substrates for Responsive Neural Interfaces (2012)

Planar electronics processing methods have enabled neural interfaces to become more precise and deliver more information. However, this processing paradigm is inherently 2D and rigid. The resulting mechanical and geometrical mismatch at the biotic-abiotic interface can elicit an immune response that prevents effective stimulation. In this work, a thiol-ene/acrylate shape memory polymer is utilized to create 3D softening substrates for stimulation electrodes. This substrate system is shown to soften <i>in vivo</i> from more than 600 to 6 MPa. A nerve cuff electrode that coils around the vagus nerve in a rat and that drives neural activity is demonstrated.
Screening for ovarian cancer (2000)

Whilst the majority of patients with ovarian cancer present with advanced stage disease and have a poor prognosis, the outlook for women with stage I disease is relatively good. An effective screening test for early stage ovarian cancer may therefore result in a significant improvement in ovarian cancer statistics. Extremely high specificity is an essential requirement of any potential screening test in view of the need for surgical investigation of women with a positive test result. No single test has yet demonstrated sufficient specificity when used alone to screen apparently healthy postmenopausal women. A multimodal approach incorporating serum CA-125 measurement, pelvic examination and real time ultrasonography has achieved high levels of specificity. The sensitivity of this screening programme for early stage ovarian cancer is currently under investigation.