gebhart/patrepeval huggingface dataset:
CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8+T cells (2013)

Increased numbers of tumor-infiltrating macrophages correlate with poor disease outcome in patients affected by several types of cancer, including breast and prostate carcinomas. The colony stimulating factor 1 receptor (CSF1R) signaling pathway drives the recruitment of tumor-associated macrophages (TAMs) to the neoplastic microenvironment and promotes the differentiation of TAMs toward a pro-tumorigenic phenotype. Twelve clinical trials are currently evaluating agents that target the CSF1/CSF1R signaling pathway as a treatment against multiple malignancies, including breast carcinoma, leukemia, and glioblastoma. The blockade of CSF1R signaling has been shown to greatly decrease the number of macrophages in a tissue-specific manner. However, additional mechanistic insights are needed in order to understand how macrophages are depleted and the global effects of CSF1R inhibition on other tumor-infiltrating immune cells. Using BLZ945, a highly selective small molecule inhibitor of CSF1R, we show that CSF1R inhibition attenuates the turnover rate of TAMs while increasing the number of CD8<sup>+</sup> T cells that infiltrate cervical and breast carcinomas. Specifically, we find that BLZ945 decreased the growth of malignant cells in the mouse mammary tumor virus-driven polyomavirus middle T antigen (MMTV-PyMT) model of mammary carcinogenesis. Furthermore, we show that BLZ945 prevents tumor progression in the keratin 14-expressing human papillomavirus type 16 (K14-HPV-16) transgenic model of cervical carcinogenesis. Our results demonstrate that TAMs undergo a constant turnover in a CSF1R-dependent manner, and suggest that continuous inhibition of the CSF1R pathway may be essential to maintain efficacious macrophage depletion as an anticancer therapy.
Leishmania donovani infection in scid mice: lack of tissue response and in vivo macrophage activation correlates with failure to trigger natural killer cell-derived gamma interferon production in vitro (1992)

Infection of immunocompetent mice with Leishmania donovani is characterized by the development of a tissue granulomatous response, in vivo macrophage activation, and a predominantly Th1-type CD4+ T-cell response. To determine whether a recently described T-cell-independent pathway of gamma interferon (IFN-gamma) production involving the collaboration of macrophages and natural killer (NK) cells contributed to this pattern of events, we have investigated the responses of scid mice to L. donovani infection. The multiplication of parasites in the livers of scid mice progressed at a rate equivalent to that seen in BALB/c mice over the first 14 days of infection, but by day 28 scid mice had a fivefold-higher parasite burden. This infection was not, however, accompanied by any demonstrable histological response in the liver or by elevated major histocompatibility complex class II expression on splenic macrophages. In vitro, L. donovani was unable to trigger IFN-gamma production from scid spleen cell cultures under conditions which allowed efficient triggering by bacterial stimuli. Although L. donovani also failed to stimulate the release of tumor necrosis factor, an important macrophage-derived cofactor for IFN-gamma secretion by NK cells, exogenous recombinant tumor necrosis factor alpha could not restore the IFN-gamma response. Even with the potent synergistic effect of exogenous interleukin-2, L. donovani was unable to stimulate this pathway to the same extent as Listeria monocytogenes. Indeed, L. donovani inhibited the response to L. monocytogenes in a dose-dependent fashion. Experiments involving the transfer of supernatants and the use of neutralizing monoclonal antibodies have failed to find evidence that interleukin-10 is involved in this inhibition. These data suggest that NK cell-derived IFN-gamma is unlikely to participate in the early regulation of visceral leishmaniasis in the mouse.
Decay-accelerating factor expression on either effector or target cells inhibits cytotoxicity by human natural killer cells (1992)

Previous studies have shown that freshly isolated CD16+ NK cells are deficient in the expression of decay-accelerating factor (DAF), or CD55, a membrane regulator of C3 activation. In this study we investigated the significance, for NK cell-mediated lysis, of DAF expression on the target and effector cells. The effect of DAF expression on the susceptibility of NK cell targets was investigated by several means: first, DAF- cell lines were cloned from K562; second, the cloned DAF- cells were reconstituted with exogenous purified DAF; and third, anti-DAF F(ab')2 was used to block DAF function on the DAF+ K562 cells. Consistently, the presence of DAF in the target cell membrane, either naturally occurring or experimentally incorporated, afforded the target cell protection against lysis, and this protection could be blocked with anti-DAF. Similarly, targets for antibody-dependent cell-mediated cytotoxicity with exogenous DAF incorporated in their plasma membrane became less sensitive to antibody-dependent cell-mediated cytotoxicity by NK cells compared with the same target cells without incorporated DAF in their membranes. DAF incorporated in the plasma membranes of the effector NK cells made the NK cells less effective at killing K562 targets. The known function of DAF is to regulate C3 activation, and we were able to demonstrate that the isolated NK cell is capable of releasing C3. It is also possible that the participation of DAF in NK cell function represents a new, noncomplement-dependent function for DAF.
Immunoglobulin genes and diversity: what we have learned from domestic animals (2012)

This review focuses on the diversity of immunoglobulin (Ig) genes and Ig isotypes that are expressed in domestic animals. Four livestock species-cattle, sheep, pigs, and horses-express a full range of Ig heavy chains (IgHs), including μ, δ, γ, ϵ, and α. Two poultry species (chickens and ducks) express three IgH isotypes, μ, υ, and α, but not δ. The κ and λ light chains are both utilized in the four livestock species, but only the λ chain is expressed in poultry. V(D)J recombination, somatic hypermutation (SHM), and gene conversion (GC) are three distinct mechanisms by which immunoglobulin variable region diversity is generated. Different domestic animals may use distinct means to diversify rearranged variable regions of Ig genes.
Emerging role of NF-κB signaling in the induction of senescence-associated secretory phenotype (SASP) (2011)

The major hallmark of cellular senescence is an irreversible cell cycle arrest and thus it is a potent tumor suppressor mechanism. Genotoxic insults, e.g. oxidative stress, are important inducers of the senescent phenotype which is characterized by an accumulation of senescence-associated heterochromatic foci (SAHF) and DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS). Interestingly, senescent cells secrete pro-inflammatory factors and thus the condition has been called the senescence-associated secretory phenotype (SASP). Emerging data has revealed that NF-κB signaling is the major signaling pathway which stimulates the appearance of SASP. It is known that DNA damage provokes NF-κB signaling via a variety of signaling complexes containing NEMO protein, an NF-κB essential modifier, as well as via the activation of signaling pathways of p38MAPK and RIG-1, retinoic acid inducible gene-1. Genomic instability evoked by cellular stress triggers epigenetic changes, e.g. release of HMGB1 proteins which are also potent enhancers of inflammatory responses. Moreover, environmental stress and chronic inflammation can stimulate p38MAPK and ceramide signaling and induce cellular senescence with pro-inflammatory responses. On the other hand, two cyclin-dependent kinase inhibitors, p16INK4a and p14ARF, are effective inhibitors of NF-κB signaling. We will review in detail the signaling pathways which activate NF-κB signaling and trigger SASP in senescent cells.
Activator-protein-1 binding potentiates the hypoxia-induciblefactor-1-mediated hypoxia-induced transcriptional activation of vascular-endothelial growth factor expression in C6 glioma cells (1997)

The endothelial cell-specific mitogen vascular-endothelial growth factor (VEGF) plays a key role in both physiological and pathological angiogenesis. The up-regulation of VEGF expression in response to reduced oxygen tension occurs through transcriptional and post-transcriptional mechanisms. To investigate the molecular mechanisms of transcriptional activation by hypoxia (1% oxygen), fine mapping of a hypoxia-responsive region of the human VEGF promoter was carried out using luciferase reporter-gene constructs in C6 glioma cells. Here, we report that the binding site of hypoxia-inducible factor 1 (HIF1) is crucial for the hypoxic induction of VEGF gene expression. However, an enhancer subfragment containing the HIF1 binding site was not sufficient to confer full hypoxia responsiveness. Addition of upstream sequences restored the full sensitivity to hypoxia induction. This potentiating effect is due to activator protein 1 binding. The 'potentiating' sequences are unable to confer hypoxia responsiveness on their own. Our results strongly suggest that in C6 glioma cells a complex array of trans-acting factors facilitates full transcriptional induction of VEGF gene expression by hypoxia.
Quantization of continuous arm movements in humans with brain injury (1999)

Segmentation of apparently continuous movement has been reported for over a century by human movement researchers, but the existence of primitive submovements has never been proved. In 20 patients recovering from a single cerebral vascular accident (stroke), we identified the apparent submovements that composed a continuous arm motion in an unloaded task. Kinematic analysis demonstrated a submovement speed profile that was invariant across patients with different brain lesions and provided experimental verification of the detailed shape of primitive submovements. The submovement shape was unaffected by its peak speed, and to test further the invariance of shape with speed, we analyzed movement behavior in a patient with myoclonus. This patient occasionally made involuntary shock-like arm movements, which occurred near the maximum capacity of the neuromuscular system, exhibited speed profiles that were comparable to those identified in stroke patients, and were also independent of speed.
Rhodium(III)-Catalyzed C–H Olefination for the Synthesis of ortho-Alkenyl Phenols Using an Oxidizing Directing Group (2013)

By using an oxidizing directing group, a mild, efficient Rh(III) catalyzed C–H olefination reaction between N-phenoxyacetamides and alkenes was developed. This reaction provided a straightforward way for the synthesis of ortho-alkenyl phenols, and the directing group is traceless in the product.
In vitro induction of apoptosis of neoplastic cells in low-grade non-Hodgkin's lymphomas using combinations of established cytotoxic drugs with bendamustine. (2001)

In conclusion, our results suggest that schedules using combinations of bendamustine and anthracyclines should not be recommended for the treatment of low-grade NHL, whereas bendamustine combined with 2-CdA could be considered for the development of future treatment strategies.
P1‐307: Upregulation of T‐helper subtype 17 lymphocytes in cultured peripheral blood mononuclear cells of patients with Alzheimer's disease (2010)

Much evidence is available that inflammation contributes to the development of neurodegenerative disorders such as Alzheimer`s disease (AD). Modulation of proinflammatory cytokine levels such as IL-1, IL-6 and TGF-beta are thought to be mediators of neuroinflammation and are involved in neuronal damage. Il-6 and TGF-beta are on the other hand the main cytokines for Th17 cell differentiation, a subgroup of T helper lymphocytes, involved in several autoimmune and inflammatory diseases. Th17 T cells have recently been discovered to show a marked response when stimulated with Abeta-peptide (25-35) under hypoxic conditions. In this pilot-investigation we tested the following hypothesis: Is there in vitro evidence that AD patients have an elevated peripheral Th17 T cell response compared to healthy controls (HC). Methods: Peripheral blood mononuclear cells (PBMCs) of two patients with AD (according to NINCDS-ADRDA criteria with MMSE 20 and 22) and three HC were activated with anti-CD3 and anti-CD28 and cultured for 4 days. The CD4+ Th17 T cell number was determined by flow cytometry after intracellular staining with Interleukin-17(IL-17). Th1 were characterized by double staining of anti-CD4 and intracellular staining with anti-Interferon-gamma. Results: In AD-patients compared to HC we could detect a significant elevated Th17 T cell response (10,7 +1,27% vs. 1,26 +0,65% of CD4+ T cells). Interestingly there was no difference in the amount of Th1 positive T cells, (AD 6,07 +1,94% vs. 6,7% +1,94%). Conclusion: This pilot-study provides the first report that a peripheral Th17 T cell reponse is elevated in AD. This finding highlights the importance of inflammation in AD, and indicates a possible involvement of Th17 Tlymphocytes to reflect the aspect of neuroinflammation in the pathogenesis of AD.
Concentrations of three hapten‐binding immunoglobulins in pooled normal human serum (1976)

The amount of natural anti-DNP-cap, anti-NIP-cap or anti-ABA-TYR in human IgM was measured by using immunoabsorbents and hapten elution. We found that 1.0% of pooled human IgM is specific for DNP-cap, 0.2% for NIP-cap and 0.02% for ABA-TYR. Haptens NIP and DNP were found to be cross-reactive when tested with natural antibodies even though they were not cross-reactive when tested with immune antibodies.
On the origins of the tetraploidBromusspecies (sectionBromus, Poaceae): insights from internal transcribed spacer sequences of nuclear ribosomal DNA (1997)

The internal transcribed spacer (ITS) region of nuclear ribosomal DNA from 22 diploid and tetraploid annual Bromus species of section Bromus (Poaceae) and three species belonging to other Bromus sections, Bromus catharticus (section Ceratochloa), Bromus anomalus (section Pnigma), and Bromus sterilis (section Genea), were investigated by PCR amplification and direct sequencing. The length of the ITS-1 region varied from 215 to 218 bp, and that of the ITS-2 region from 215 to 216 bp, in the species analyzed. ITS-1 was more variable and provided more informative sites (49) than ITS-2 (32). No variation was encountered within species. In pairwise comparison among species of section Bromus, sequence divergence ranged from 0.0 to 8.0% for the combined ITS-1 and ITS-2 regions. Parsimony analysis using Avena longiglumis and Hordeum vulgare as outgroups resulted in well-resolved phylogenetic trees and showed that section Bromus is monophyletic according to the species analyzed outside of the section. The analysis clarified the phylogenetic relationships among monogenomic (diploid) species. Introduction of the allotetraploid species did not change the general topology of the trees obtained using only the diploid species. Although some tetraploid-diploid species relationships will have to be clarified with faster evolving markers, the ITS sequences are shown to be useful for assessing evolutionary relationships among closely related Bromus species, as well as for clarifying taxonomic problems in previously controversial cases (e.g., Bromus alopecuros and Bromus caroli-henrici). New hypotheses are proposed concerning the origin of several allotetraploid species. For example, it is shown that the tetraploid Bromus hordeaceus diverged earlier than all other species of section Bromus, excluding the diploid B. caroli-henrici, which is found to be basal in this group. The tetraploid Bromus arenarius, which was considered a hybrid between sections Bromus and Genea, and the tetraploid Bromus adoensis are sister taxa within section Bromus; they belong in a weakly differentiated clade with the diploids Bromus brachystachys, Bromus japonicus, Bromus squarrosus, Bromus arvensis, and Bromus intermedius.
Poly-3-hydroxyoctanoate P(3HO), a Medium Chain Length Polyhydroxyalkanoate Homopolymer from Pseudomonas mendocina (2011)

Pseudomonas mendocina was found to produce a unique homopolymer of poly(3-hydroxyoctanoate), P(3HO), rather than a copolymer, when grown on sodium octanoate as the sole carbon source. Although this polymer has been produced by other organisms, interestingly this is the first time an absolute homopolymer has been produced by a wild type organism. In addition, a detailed study on the effects of different extraction methods on the yield, molecular weight, thermal properties, and lipopolysaccharide content of P(3HO) has been carried out. The organism was able to accumulate P(3HO) up to 31.38% of its dry cell weight within 48 h in mineral salt medium. Characterization of the monomer was carried out using FTIR, GC-MS, (13)C, (1)H, and HSQC NMR spectroscopy. The polymer had a crystallinity of 37.5%, Young's modulus value of 11.6 MPa and contact angle of 77.3°. Microstructural studies of solvent cast polymer films revealed a smooth surface topography with a root-mean-square roughness value of 0.238 μm.
AHP기법 및 FGI를 통한 분임토의의 활성화의 문제점과 개선 방안에 관한 연구 (2013)

분임토의 교육은 공무원교육원 등 각급 교육기관에서 대부분 실시하고 있다. 특히 공무원교육훈련 프로그램에서 대부분 분임토의 교육시간이 배정되어 있어 공무원들이 분임토의 교육을 받을 기회는 많다. 그러나 아직까지 분임토의가 교육훈련중 하나로 형식적으로 실시되고 있고 실제 업무추진과정에 잘 활용하지 못하는 등 분임토의의 개념과 기능에 걸맞게 이용되지 못하고 있는...
Gluconate formation and polyol metabolism in Aspergillus niger (1993)

t\uo8?oi t (U& 1 Vele artikelen zijn verschenen over de rol die polyolen spelen bij osmoregulatie in schimmels.Daarin wordt ten onrechte geen aandacht besteed aan de plaats van accumulatie van polyolen in de eel.2 Bij de door Henrissat voorgestelde classificatie van glycosyl hydrolases, gebaseerd op overeenkomsten in aminozuurvolgordes, hadden de voor de verschillende families karakteristieke kenmerken van aminozuursamenstelling aangegeven moeten worden.
Insertion of a N-Heterocyclic Carbene (NHC) into a Platinum−Olefin Bond (2007)

The insertion of a N-heterocyclic carbene (NHC) into a coordinated olefin moiety is observed for a Pt-based system. Important intermediates along the reaction pathway have been isolated and fully characterized. Computational work supports a proposed mechanistic pathway involving external attack at the olefin by a NHC ligand rather than an intramolecular migratory insertion route.
125I-labeled anti-epidermal growth factor receptor-vIII single-chain Fv exhibits specific and high-level targeting of glioma xenografts. (1999)

A single-chain antibody fragment, MR1(scFv), with specific binding to epidermal growth factor receptor-vIII (EGFRvIII), was produced, radiolabeled, and evaluated for biodistribution in human glioma-bearing athymic mice. The mutant receptor EGFRvIII has a deletion in its extracellular domain that results in the formation of a new, tumor-specific antigen found in glioblastomas, breast carcinomas, and other tumors. The scFv molecule, designed as V(H)-(Gly4-Ser)3-V(L), was expressed in Escherichia coli in inclusion body form; recovered scFv fragments were properly refolded in redox-shuffling buffer. Size-exclusion chromatography of purified scFv demonstrated a protein monomer of Mr 26,000. Labeling was performed using N-succinimidyl 5-[125I]iodo-3-pyridinecarboxylate (SIPC) or Iodogen to specific activities of 0.5-2.0 mCi/mg, with yields of 35-50% and 45-70%, respectively. The immunoreactive fraction (IRF) of the labeled MR1(scFv) was 65-80% when SIPC was used and 50-55% when Iodogen was used. The affinity (K(A)) of MRI(scFv) for EGFRvIII was 4.3 x 10(7) +/- 0.1 x 10(7) M(-1) by BIAcore analysis, and it was 1.0 x 10(8) +/- 0.1 x 10(8) M(-1) and by Scatchard analysis versus EGFRvIII-expressing cells. After incubation at 37 degrees C for 24 h, the binding affinity was maintained, and the IRF was maintained at 60-70%. The specificity of MR1(scFv) for EGFRvIII was demonstrated in vitro by incubation of radiolabeled MR1(scFv) with the EGFRvIII-expressing U87MG.deltaEGFR cell line in the presence or absence of competing unlabeled MR1(scFv) or anti-EGFRvIII MAbs L8A4 and H10. In biodistribution studies using athymic mice bearing s.c. U87MG.deltaEGFR tumor xenografts, animals received intratumoral or i.v. infusions of paired-label [125I]SIPC-MR1(scFv) and [131I]SIPC-anti-Tac(scFv) as a control. When given by the intratumoral route, MR1(scFv) retained high tumor uptakes of 85% injected dose per gram of tissue at 1 h and 16% injected dose per gram of tissue at 24 h following administration. Specific: control scFv tumor uptake ratios of more than 20:1 at 24 h demonstrated specific localization of MR1(scFv). The excellent tumor retention of MR1(scFv), combined with its rapid clearance from normal tissues, resulted in high tumor:normal organ ratios.
A probabilistic framework for semantic video indexing, filtering, and retrieval (2001)

Semantic filtering and retrieval of multimedia content is crucial for efficient use of the multimedia data repositories. Video query by semantic keywords is one of the most difficult problems in multimedia data retrieval. The difficulty lies in the mapping between low-level video representation and high-level semantics. We therefore formulate the multimedia content access problem as a multimedia pattern recognition problem. We propose a probabilistic framework for semantic video indexing, which call support filtering and retrieval and facilitate efficient content-based access. To map low-level features to high-level semantics we propose probabilistic multimedia objects (multijects). Examples of multijects in movies include explosion, mountain, beach, outdoor, music etc. Semantic concepts in videos interact and to model this interaction explicitly, we propose a network of multijects (multinet). Using probabilistic models for six site multijects, rocks, sky, snow, water-body forestry/greenery and outdoor and using a Bayesian belief network as the multinet we demonstrate the application of this framework to semantic indexing. We demonstrate how detection performance can be significantly improved using the multinet to take interconceptual relationships into account. We also show how the multinet can fuse heterogeneous features to support detection based on inference and reasoning.
A CONSERVED SIGNALING PATHWAY: The Drosophila Toll-Dorsal Pathway (1996)

The Toll-Dorsal pathway in Drosophila and the interleukin-1 receptor (IL-1R)-NF-kappa B pathway in mammals are homologous signal transduction pathways that mediate several different biological responses. In Drosophila, genetic analysis of dorsal-ventral patterning of the embryo has defined the series of genes that mediate the Toll-Dorsal pathway. Binding of extracellular ligand activates the transmembrane receptor Toll, which requires the novel protein Tube to activate the cytoplasmic serine/threonine kinase Pelle. Pelle activity controls the degradation of the Cactus protein, which is present in a cytoplasmic complex with the Dorsal protein. Once Cactus is degraded in response to signal, Dorsal is free to move into the nucleus where it regulates transcription of specific target genes. The Toll, tube, pelle, cactus, and dorsal genes also appear to be involved in Drosophila immune response. Because the IL-1R-NF-kappa B pathway plays a role in vertebrate innate immunity and because plant homologues of the Toll-Dorsal pathway are important in plant disease resistance, it is likely that this pathway arose before the divergence of plants and animals as a defense against pathogens.