gebhart/patrepeval huggingface dataset:
In vitro priming of tumor-reactive cytolytic T lymphocytes by combining IL-10 with B7-CD28 costimulation (1995)

Naive spleen cells from syngeneic mice generated tumor-reactive CTL following three cycles of in vitro culturing with IL-10 and cells from the P815 mouse mastocytoma that expressed the B7-1 or B7-2 costimulator. Unpurified as well as CD8-enriched naive splenocytes could be used for priming. The in vitro primed CTL were CD8+, and their recognition was MHC class I restricted. Both IL-10 and B7-transfected P815 cells were required for the priming. However, a combination of exogenous IL-10 and IL-2 in the presence of B7-negative wild-type P815 cells also induced tumor-reactive CTL. Injection of the neutralizing anti-IL-10 mAb JES-2A5 into mice reduced their ability to mount a primary CTL response after immunization with B7-1+ P815 cells, and inclusion of this mAb in the in vitro cultures inhibited a secondary CTL response. Adoptive transfer of the in vitro primed CTL had a therapeutic effect in mice with P815 established as an ascites tumor. Our results underscore an important role of IL-10 in the induction of a tumor-specific CTL response.
Neutron reflectivity studies of the surface-induced ordering of diblock copolymer films (1989)

Neutron reflectivity from annealed thin films of the poly(styrene-b-deuterated methylmethacrylate), P(S-b-D-MMA), reveals the formation of a multilayered morphology parallel to the film surface. This multilayer forms so that PS locates, preferentially, at the air/copolymer and D-PMMA at the substrate/copolymer interfaces with layer thicknesses at these interfaces one-half that found in the bulk. P(D-S-b-MMA) of lower molecular weight shows the first evidence of surface-induced ordering of copolymers in the phase mixed state characterized by an exponentially damped cosine function.
The changing landscape of treatment options for metastatic castrate-resistant prostate cancer: challenges and solutions for physicians and patients. (2012)

Four recently approved drugs (cabazitaxel, sipuleucel-T, abiraterone, and denosumab), along with emerging therapies, bone-building therapies, hormonal treatments, and immunotherapies, have all demonstrated promise in advanced prostate cancer. It appears that the best outcomes will be achieved from the sequential use of multiple agents.
Expression of proinflammatory and proangiogenic cytokines in patients with head and neck cancer. (1999)

Altered immune, inflammatory, and angiogenesis responses are observed in patients with head and neck squamous cell carcinoma (HNSCC), and many of these responses have been linked with aggressive malignant behavior and a decrease in prognosis. In this study, we examined the hypothesis that HNSCC cells produce cytokines that regulate immune, inflammatory, and angiogenesis responses. We identified important regulatory cytokines in supernatants of well-defined and freshly cultured HNSCC cell lines by ELISA and determined whether these cytokines are detected in tumor cell lines and tissue specimens by immunohistochemistry. The serum concentration of the cytokines and cytokine-dependent acute phase inflammatory responses (i.e., fibrinogen, C-reactive protein, and erythrocyte sedimentation rate) from patients with HNSCC was determined, and the potential relationship of serum cytokine levels to tumor volume was analyzed. Cytokines interleukin (IL)-1alpha, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor were detected in similar concentration ranges in the supernatants of a panel of established University of Michigan squamous cell carcinoma (UM-SCC) cell lines and supernatants of freshly isolated primary HNSCC cultures. Evidence for the expression of IL-1alpha, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, and VEGF in HNSCC cells within tumor specimens in situ was obtained by immunohistochemistry. In a prospective comparison of the cytokine level and cytokine-inducible acute-phase proteins in serum, we report that cytokines IL-6, IL-8, and VEGF were detected at higher concentrations in the serum of patients with HNSCC compared with patients with laryngeal papilloma or age-matched control subjects (at P < 0.05). The serum concentrations of IL-8 and VEGF were found to be weakly correlated with large primary tumor volume (R2 = 0.2 and 0.4, respectively). Elevated IL-1- and IL-6-inducible acute-phase responses were also detected in cancer patients but not in patients with papilloma or control subjects (at P < 0.05). We therefore conclude that cytokines important in proinflammatory and proangiogenic responses are detectable in cell lines, tissue specimens, and serum from patients with HNSCC. These cytokines may increase the pathogenicity of HNSCC and prove useful as biomarkers or targets for therapy.
Back-Propagation Neural Network based predictive control for biomimetic robotic fish (2008)

This paper presents a practical swimming data prediction method for a free-swimming, three-link robotic fish. Since a full hydrodynamic model for fish swimming is very complex and intractable, the primitive swimming data generated by a Central Pattern Generator controller is fed into a Back-Propagation Neural Network (BPNN) for trimming. After the process of training, the BPNN is able to predict the actual swimming data for various swimming patterns without dynamic modeling. Preliminary simulation and experimental results on swimming control show the effectiveness of the proposed prediction method as well as its potential for other flexible link-based robots.
The personal electronic program guide---towards the pre-selection of individual TV programs (1996)

Digital and interactive TV systems will bring hundreds of TV program channels to the people. Then, the use of existing strategies for channel selection will fail: It is neither possible to select the program by "sur@g" through the channels, nor by using printed program guides.
Canine neutrophil margination mediated by lectin adhesion molecule-1 in vitro (1991)

The contributions of the canine neutrophil lectin adhesion molecule-1 (LECAM-1) (canine homologue of the murine MEL-14 Ag) in neutrophil-endothelial cell adhesion and transendothelial migration were studied using anti-LECAM-1 mAb, CL2/6, and SL1 under static conditions and at wall shear stresses of up to 1.85 dynes/cm2 (dpc). Both mAb were found to inhibit attachment of neutrophils to cytokine-stimulated canine jugular vein endothelium. The inhibitory effects of the anti-LECAM-1 mAb were more evident at a wall shear stress of 1.85 dpc (greater than 50%) than at 0.23 dpc or under static conditions (approximately 30%). In contrast the anti-CD18 mAb, R15.7, exhibited higher inhibitory ability at the lower shear stress and under static conditions with marginal inhibition of adhesion at 1.85 dpc. Anti-LECAM-1 and anti-CD18 mAb showed additive inhibitory effects at the lower wall shear stress and under static conditions. Chemotactic stimulation of the neutrophils caused rapid down-regulation of LECAM-1 from the neutrophil surface and reduced adhesion by 60% at a wall shear stress of 1.85 dpc. This inhibition was not additive to anti-LECAM-1 mAb. Pretreatment with CL2/6 or SL1 did not affect trans-endothelial migration of adherent neutrophils under any experimental conditions tested. Anti-CD18 mAb, however, blocked transendothelial migration by 98% and 56% under static condition and at a wall shear stress of 0.23 dpc, respectively. The results in this report indicate that canine LECAM-1 is involved in the initial adhesion of unstimulated neutrophils to cytokine-stimulated endothelial cells under flow, but in contrast to CD18-integrins, plays no role in the transendothelial migration.
Mitochondrial permeabilization relies on BH3 ligands engaging multiple prosurvival Bcl-2 relatives, not Bak (2007)

The Bcl-2 family regulates apoptosis by controlling mitochondrial integrity. To clarify whether its prosurvival members function by sequestering their Bcl-2 homology 3 (BH3)-only ligands or their multidomain relatives Bak and Bax, we analyzed whether four prosurvival proteins differing in their ability to bind specific BH3 peptides or Bak could protect isolated mitochondria. Most BH3 peptides could induce temperature-dependent cytochrome c release, but permeabilization was prevented by Bcl-x(L), Bcl-w, Mcl-1, or BHRF1. However, their protection correlated with the ability to bind Bak rather than the added BH3 peptide and could be overcome only by BH3 peptides that bind directly to the appropriate prosurvival member. Mitochondria protected by both Bcl-x(L)-like and Mcl-1 proteins were disrupted only by BH3 peptides that engage both. BH3-only reagents freed Bak from Bcl-x(L) and Mcl-1 in mitochondrial and cell lysates. The findings support a model for the control of apoptosis in which certain prosurvival proteins sequester Bak/Bax, and BH3-only proteins must neutralize all protective prosurvival proteins to allow Bak/Bax to induce mitochondrial disruption.
A Brassica oleracea Gene Expressed in a Variety-Specific Manner May Encode a Novel Plant Transmembrane Receptor (2001)

The species Brassica oleracea includes several agricultural varieties characterized by the proliferation of different types of meristems. Using a combination of subtractive hybridization and PCR (polymerase chain reaction) techniques we have identified several genes which are expressed in the reproductive meristems of the cauliflower curd (B. oleracea var. botrytis) but not in the vegetative meristems of Brussels sprouts (B. oleracea var. gemmifera) axillary buds. One of the cloned genes, termed CCE1 (CAULIFLOWER CURD EXPRESSION 1) shows specific expression in the botrytis variety. Preferential expression takes place in this variety in the meristems of the curd and in the stem throughout the vegetative and reproductive stages of plant growth. CCE1 transcripts are not detected in any of the organs of other B. oleracea varieties analyzed. Based on the nucleotide sequence of a cDNA encompassing the complete coding region, we predict that this gene encodes a transmembrane protein, with three transmembrane domains. The deduced amino acid sequence includes motifs conserved in G-protein-coupled receptors (GPCRs) from yeast and animal species. Our results suggest that the cloned gene encodes a protein belonging to a new, so far unidentified, family of transmembrane receptors in plants. The expression pattern of the gene suggests that the receptor may be involved in the control of meristem development/arrest that takes place in cauliflower.
S/P and T/P phosphorylation is critical for tau neurotoxicity in Drosophila (2007)

The microtubule-associated protein tau is hyperphosphorylated abnormally in AD and related neurodegenerative disorders. Many phospho epitopes created by proline directed kinases (SP/TP sites) show relative specificity for disease states. To test whether phosphorylation at the disease-associated SP/TP sites affects tau toxicity in vivo, we expressed a form of tau in Drosophila in which all SP/TP sites are mutated to alanine. We find that blocking phosphorylation at SP/TP motifs markedly reduces tau toxicity in vivo. Using phosphorylation-specific antibodies, we identify a positive correlation between increased phosphorylation at disease-associated sites and neurotoxicity. We use the phosphorylation-incompetent version of tau to show that kinase and phosphatase modifiers of tau neurotoxicity, including cdk5/p35, the JNK kinase hemipterous and PP2A act via SP/TP phosphorylation sites. We provide direct evidence in an animal model system to support the role of phosphorylation at SP/TP sites in playing a critical role in tau neurotoxicity.
ChemInform Abstract: Synthesis and Chemistry of Guanidine Derivatives (1992)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Identification of mammalian-adapting mutations in the polymerase complex of an avian H5N1 influenza virus (2015)

Avian influenza viruses of the H5N1 subtype pose a serious global health threat due to the high mortality (>60%) associated with the disease caused by these viruses and the lack of protective antibodies to these viruses in the general population. The factors that enable avian H5N1 influenza viruses to replicate in humans are not completely understood. Here we use a high-throughput screening approach to identify novel mutations in the polymerase genes of an avian H5N1 virus that confer efficient polymerase activity in mammalian cells. Several of the identified mutations (which have previously been found in natural isolates) increase viral replication in mammalian cells and virulence in infected mice compared with the wild-type virus. The identification of amino-acid mutations in avian H5N1 influenza virus polymerase complexes that confer increased replication and virulence in mammals is important for the identification of circulating H5N1 viruses with an increased potential to infect humans.
Rapid Diagnosis of Pharyngitis Caused by Group A Streptococci (2004)

Although commercial rapid antigen detection tests (RADTs) are more expensive than blood agar plate (BAP) cultures, the advantage they offer is the speed with which they provide results. Rapid identification and consequent prompt treatment of patients with pharyngitis due to group A beta-hemolytic streptococci (GABHS) can reduce the risk of spread of GABHS, can allow patients to return to school or work sooner, and may reduce the acute morbidity of this illness. In most studies, RADTs have been compared with BAP cultures as the criterion standard. However, these comparisons are complicated by the fact that there is no universally accepted procedure for performing a BAP culture. The great majority of the RADTs that are currently available have a high specificity (i.e., 95% or greater) and a sensitivity of between 70 and 90% compared with BAP cultures. Few published studies have compared the performance of various RADTs to each other or examined the performance of various RADTs in the office setting. There is also relatively little published information about how physicians in practice actually use RADTs, but the available information suggests that many physicians do not follow recommended guidelines. While the development of easy-to-perform RADTs for the diagnosis of GABHS pharyngitis has altered clinical practice substantially, only limited data about cost-effectiveness are currently available.
Regulatory Mechanism of The Induction of Regulatory T Cells through Growth Factors Released by Human Mesenchymal Stem Cells (2018)

Mesenchymal stem cells (MSCs) undergo self-renewal and differentiation into multiple lineages. They exert anti-inflammatory and immunomodulatory effects via either cell-cell contact or via the production of soluble factors. Various anti-inflammatory and immunomodulatory mechanisms have been identified using experimental murine MSCs. The most representative mechanism is the induction of FOXP3+ regulatory T cells (Treg cells) via the production of transforming growth factor (TGF)-β, which has also been reported in human MSCs. Recent studies have demonstrated that insulin-like growth factor (IGF) is also involved in the induction of FOXP3+ Treg cells. We previously demonstrated that the induction of FOXP3+ Treg cells by IGF is suppressed by the expression of IGF-binding protein-4 (IGFBP-4), which is an inhibitor of IGF. Because human MSCs produce both IGFs and IGFBP4, they may be considered to maintain immunological homeostasis by positive regulation of Treg cells through the production of growth factors as well as by a negative regulatory mechanism. Although human MSCs have already been applied in regenerative therapy and autoimmune disease treatment, control of their positive and negative regulatory mechanisms is expected to lead to more efficient clinical applications.
Capecitabine plus Irinotecan (XELIRI regimen) compared to 5-FU/LV plus Irinotecan (FOLFIRI regimen) as neoadjuvant treatment for patients with unresectable liver-only metastases of metastatic colorectal cancer: a randomised prospective phase II trial (2009)

Current Controlled Trials ISRCTN19912492.
Detecting and responding to hypoxia (2002)

Adaptation to hypoxia is a topic of considerable clinical relevance, as it influences the pathophysiology of anaemia, polycythaemia, tissue ischaemia and cancer. A growing number of physiologically relevant genes are regulated in response to changes in intracellular oxygen tension. These include genes encoding erythropoietin, vascular endothelial growth factor and tyrosine hydroxylase. Studies on the regulation of the erythropoietin gene have provided insights into the common mechanism of oxygen sensing and signal transduction, leading to activation of the hypoxia-inducible transcription factor 1 (HIF-1). Activation of HIF-1 by hypoxia depends on rescue of its alpha-subunit from oxygen-dependent degradation in the proteasome, allowing it to form a heterodimer with HIF-1 beta. This then translocates to the nucleus. There, HIF-1 assembles with a highly conserved orphan nuclear receptor, HNF-4, and a critical transcriptional adaptor, p300. This complex binds to a 3' enhancer on the erythropoietin gene, enabling transcription of erythropoietin. HIF-1 also activates other genes, the cis-acting elements of which contain cognate hypoxia response elements. There is growing evidence that the oxygen sensor is a flavohaem protein and that the signal transduction pathway involves changes in the level of intracellular reactive oxygen intermediates. We have recently cloned a novel fusion protein called cytochrome b5/b5 reductase, which is a cyanide-insensitive NADPH oxidase and, therefore, a candidate to be the oxygen sensor. This flavohaem protein is widely expressed in cell lines and tissues, with localization in the perinuclear space. In the presence of oxygen and iron, it may induce oxidative modifications that target HIF-1 alpha for ubiquitination and degradation.
Stem Cell Factor Influences Mast Cell Mediator Release in Response to Eosinophil-Derived Granule Major Basic Protein (1998)

Abstract Stem cell factor (SCF) is an important mast cell growth, differentiation, and survival factor. We investigated whether SCF influenced the response of mouse mast cells to an IgE-independent stimulus, eosinophil-derived granule major basic protein (MBP). Mouse bone marrow cultured mast cells (BMCMC) were derived in either concanavalin-stimulated mouse spleen conditioned medium (CM) or SCF. The cloned growth, factor-independent mast cell line Cl.MC/C57.1 was also studied. BMCMC in SCF exhibited cytochemical staining properties, protease and histamine content, and increased serotonin uptake consistent with more mature differentiated mast cells as compared with BMCMC in CM or Cl.MC/ C57.1 cells. BMCMC in SCF released serotonin,14C-labeled arachidonic acid metabolites and tumor necrosis factor-α (TNF-α) on stimulation with MBP, while no response was seen from either BMCMC in CM or Cl.MC/C57.1 cells. All three mast cell populations released mediators on stimulation with the cationic MBP analog, poly-L-arginine, indicating that the cationic charge did not explain the selective response of BMCMC in SCF to eosinophil-derived granule MBP. These findings show that SCF significantly influences mast cell differentiation and the responsiveness of mast cells to eosinophil-derived granule MBP. © 1998 by The American Society of Hematology.
Preclinical Murine Models for Lung Cancer: Clinical Trial Applications (2015)

Murine models for the study of lung cancer have historically been the backbone of preliminary preclinical data to support early human clinical trials. However, the availability of multiple experimental systems leads to debate concerning which model, if any, is best suited for a particular therapeutic strategy. It is imperative that these models accurately predict clinical benefit of therapy. This review provides an overview of the current murine models used to study lung cancer and the advantages and limitations of each model, as well as a retrospective evaluation of the uses of each model with respect to accuracy in predicting clinical benefit of therapy. A better understanding of murine models and their uses, as well as their limitations may aid future research concerning the development and implementation of new targeted therapies and chemotherapeutic agents for lung cancer.
The epithelial cell surface antigen 17–1A, a target for antibody‐mediated tumor therapy: Its biochemical nature, tissue distribution and recognition by different monoclonal antibodies (1986)

The antigen defined by MAb 17-1A, raised against colorectal cancer cells and currently used in immunotherapy trials, is a 37 kDa protein containing N-linked glycans as demonstrated by inhibition of glycosylation with tunicamycin. The 17-1A antigen (17-1A Ag) is broadly distributed in normal epithelial tissues and is also found in various types of carcinoma. Quantitative differences in expression between normal and malignant tissues were only apparent in gastric carcinomas. After immunizing mice with fresh colon carcinoma tissue, 4 MAbs were obtained that showed the same tissue reaction pattern as MAb 17-1A and recognized the 17-1A Ag as judged from precipitation and immunoblotting experiments. MAbs M72 and M74 reacted with an anti-idiotypic serum directed against the original MAb 17-1A and were able to block 17-1A binding. In contrast, M77 and M79 are directed against a different epitope. This makes them potentially interesting for passive immunotherapy in regimens involving a combination of MAbs.
Opportunities for mesoscopics in thermometry and refrigeration: Physics and applications (2006)

This review presents an overview of the thermal properties of mesoscopic structures. The discussion is based on the concept of electron energy distribution, and, in particular, on controlling and probing it. The temperature of an electron gas is determined by this distribution: refrigeration is equivalent to narrowing it, and thermometry is probing its convolution with a function characterizing the measuring device. Temperature exists, strictly speaking, only in quasiequilibrium in which the distribution follows the Fermi-Dirac form. Interesting nonequilibrium deviations can occur due to slow relaxation rates of the electrons, e.g., among themselves or with lattice phonons. Observation and applications of nonequilibrium phenomena are also discussed. The focus in this paper is at low temperatures, primarily below $4\phantom{\rule{0.3em}{0ex}}\mathrm{K}$, where physical phenomena on mesoscopic scales and hybrid combinations of various types of materials, e.g., superconductors, normal metals, insulators, and doped semiconductors, open up a rich variety of device concepts. This review starts with an introduction to theoretical concepts and experimental results on thermal properties of mesoscopic structures. Then thermometry and refrigeration are examined with an emphasis on experiments. An immediate application of solid-state refrigeration and thermometry is in ultrasensitive radiation detection, which is discussed in depth. This review concludes with a summary of pertinent fabrication methods of presented devices.
Immunoexpression of matrix metalloproteinase‐2 and matrix metalloproteinase‐9 in the metastasis of squamous cell carcinoma of the human tongue (2010)

Our results imply that MMP-2 and/or MMP-9 play an important role in invasion and metastasis in tongue cancer, and that analysis of MMP expression and/or activity in primary tumours may have a predictive value for the actual or potential presence of cervical metastases.