gebhart/patrepeval huggingface dataset:
An Antibody Fusion Protein for Cancer Immunotherapy Mimicking IL-15 trans -Presentation at the Tumor Site (2012)

Cytokines driving the immune response are powerful tools for cancer immunotherapy, but their application is generally limited by severe systemic toxicity. Targeted approaches by means of antibody-cytokine fusion proteins might enable focus on the cytokine activity to the tumor site, thereby reducing unwanted side effects. Here, we investigated the possibility to improve the efficiency of interleukin (IL)-15 presentation in a targeted approach by the incorporation of an IL-15Rα chain fragment, mimicking physiologic trans-presentation. Therefore, an antibody cytokine fusion protein (scFv_RD_IL-15) composed of an antibody moiety targeting the tumor stromal fibroblast activation protein (FAP), an extended IL-15Rαsushi domain (RD) and IL-15 was generated, exhibiting antibody-mediated specific binding and cytokine activity in soluble and targeted form. Comparative analysis with a corresponding antibody fusion protein devoid of RD (scFv_IL-15) showed for scFv_RD_IL-15 in solution enhanced stimulatory activity on Mo7e (IL-15Rβγ) cells and reduced proliferation response on CTLL-2 (IL-15Rαβγ) cells, while in FAP-targeted, that is, membrane-bound form, comparable proliferation of CTLL-2 (IL-15Rαβγ) cells was obtained. In addition, scFv_RD_IL-15 achieved in its soluble and target-bound form stronger proliferation and cytotoxicity on unstimulated and activated T cells, respectively. Furthermore, in vivo analysis in a lung metastasis tumor mouse model revealed a superior antitumor effect for scFv_RD_IL-15 in comparison with that obtained by an untargeted or RD missing version of IL-15 fusion protein. Thus, tumor-directed trans-presentation of IL-15 in association with RD in form of an antibody fusion protein seems to be a promising approach to further improve the antitumor effect of IL-15.
Was Induction of HIV-1 Through TLR9? (2003)

Equils et al. ([1][1]) reported implication of simultaneous activation of Toll-like receptors (TLRs) on HIV replication. When spleen cells from HIV-1 transgenic mice were exposed to agonists of TLR2, TLR4, and TLR9, p24 production was induced. The agonist of TLR9 used in this study was bacterial CpG
Solution and Solid-Support Synthesis of a Potential Leishmaniasis Carbohydrate Vaccine (2001)

The synthesis of a potential carbohydrate vaccine for the parasitic disease leishmaniasis is described. New solution- and solid-phase synthetic strategies were explored for the assembly of a unique tetrasaccharide antigen found on the Leishmania lipophosphoglycan. An initial solution-phase synthesis relied on thioglycosides as building blocks and the establishment of the central disaccharide from lactal via an oxidation-reduction sequence. A second approach was completed both in solution and on solid support. The solid-phase synthesis relied on assembly from monosaccharide units and was used to evaluate different glycosylating agents in the efficient installation of the galactose beta-(1-->4) mannoside. Glycosyl phosphates proved most successful in this endeavor. This first solid-phase synthesis of the Leishmania cap provided rapid access to the tetrasaccharide in 18% overall yield while requiring only a single purification step. The synthetic cap tetrasaccharide was conjugated to the immunostimulator Pam3Cys to create fully synthetic carbohydrate vaccine 1 and to the carrier protein KLH to form semisynthetic vaccine 2. Currently, both constructs have entered initial immunological experiments in mice targeted at the development of a vaccine against the parasitic disease leishmaniasis.
Cholesterol efflux from cells to immunopurified subfractions of human high density lipoprotein: LP-AI and LP-AI/AII. (1991)

Using immunoaffinity chromatography, we separated human high density lipoprotein (HDL) into two subfractions: LP-AI, in which all particles contain apolipoprotein A-I (apoA-I) but no apoA-II, and LP-AI/AII, in which all particles contain both apoA-I and apoA-II. To compare LP-AI and LP-AI/AII as acceptors of cell cholesterol, the isolated subfractions were diluted to 50 micrograms phospholipid/ml, and then incubated with monolayer cultures of cells in which whole-cell and lysosomal cholesterol has been labeled with 14C and 3H, respectively. We used three cell types (Fu5AH rat hepatoma cells, normal human skin fibroblasts, and rabbit aortic smooth muscle cells). When these cells were prepared to contain normal physiological quantities of cholesterol (20-35 micrograms/mg protein), LP-AI and LP-AI/AII were nearly equally efficient in promoting efflux of both whole-cell and lysosomal cholesterol. For whole-cell cholesterol, the rate constants for efflux to LP-AI and LP-AI/AII were: 0.050/h and 0.053/h, respectively, with Fu5AH cells; 0.0063/h and 0.0074/h with GM3468 human skin fibroblasts; and 0.0076/h and 0.0079/h with rabbit aortic smooth muscle cells. When cholesterol in hepatoma cells or fibroblasts was elevated two- to threefold above normal, there was still not difference in efflux of whole-cell cholesterol to LP-AI and LP-AI/AII. In longterm incubations, the net depletion of cholesterol mass from cholesterol-enriched cells was either identical with the two HDL subfractions, or somewhat greater with LP-AI/AII.(ABSTRACT TRUNCATED AT 250 WORDS)
Characterization of a Neuraminidase-Deficient Influenza A Virus as a Potential Gene Delivery Vector and a Live Vaccine (2004)

We recently identified a packaging signal in the neuraminidase (NA) viral RNA (vRNA) segment of an influenza A virus, allowing us to produce a mutant virus [GFP(NA)-Flu] that lacks most of the NA open reading frame but contains instead the gene encoding green fluorescent protein (GFP). To exploit the expanding knowledge of vRNA packaging signals to establish influenza virus vectors for the expression of foreign genes, we studied the replicative properties of this virus in cell culture and mice. Compared to wild-type virus, GFP(NA)-Flu was highly attenuated in normal cultured cells but was able to grow to a titer of >10(6) PFU/ml in a mutant cell line expressing reduced levels of sialic acid on the cell surface. GFP expression from this virus was stable even after five passages in the latter cells. In intranasally infected mice, GFP was detected in the epithelial cells of nasal mucosa, bronchioles, and alveoli for up to 4 days postinfection. We attribute the attenuated growth of GFP(NA)-Flu to virion aggregation at the surface of bronchiolar epithelia. In studies to test the potential of this mutant as a live attenuated influenza vaccine, all mice vaccinated with >/==" BORDER="0">10(5) PFU of GFP(NA)-Flu survived when challenged with lethal doses of the parent virus. These results suggest that influenza virus could be a useful vector for expressing foreign genes and that a sialidase-deficient virus may offer an alternative to the live influenza vaccines recently approved for human use.
Rational design of high-responsivity detectors of terahertz radiation based on distributed self-mixing in silicon field-effect transistors (2009)

In search of novel detectors of electromagnetic radiation at terahertz frequencies, field-effect transistors (FETs) have recently gained much attention. The current literature studies them with respect to the excitation of plasma waves in the two-dimensional channel. Circuit aspects have been taken into account only to a limited degree. In this paper, we focus on embedding silicon FETs in a proper circuitry to optimize their responsivity to terahertz radiation. This includes impedance-matched antenna coupling and amplification of the rectified signal. Special attention is given to the investigation of high-frequency short-circuiting of the gate and drain contacts by a capacitive shunt, a common approach of high-frequency electronics to induce resistive mixing in transistors. We theoretically study the effect of shunting in the framework of the Dyakonov–Shur plasma-wave theory, with the following key results. In the quasistatic limit, the capacitive shunt induces the longitudinal high-frequency field needed in the FET’s channel for resistive mixing. In the non-quasi-static case, the shunt’s role is taken over by plasma waves. Rectification can then be described as distributed self-mixing in the transistor’s channel. Based on such considerations as well as other circuit-related aspects, we arrive at a rational design for FET-based detectors of terahertz radiation, and implement the first monolithically integrated 0.65 THz focal-plane array including antennas and amplifiers on a single silicon die. The measured performance data compare well with the theoretical predictions.
Thyroperoxidase, but not the Thyrotropin Receptor, Contains Sequential Epitopes Recognized by Autoantibodies in Recombinant Peptides Expressed in the pUEX Vector (1991)

The sequential epitopes on the human thyroperoxidase (TPO) recognized by antibodies in the sera of patients with autoimmune thyroid disease were investigated using a recombinant DNA technique. Previous studies led to the isolation of two overlapping cDNA clones that encode polypeptides of TPO (85 residues, C2; 100 residues, C21) recognized by sera from several patients with autoimmune disease that contained antimicrosomal autoantibodies. In this report the vector pUEX1 was used to clone and express small random fragments of TPO cDNA in Escherichia coli as a beta-galactosidase fusion protein. Colonies were screened with a serum from a patient with Hashimoto's thyroiditis, and immunoreactive peptides were identified by sequencing the corresponding DNA inserts. Two linear epitopes of human TPO (amino acids 590-622 and 710-722) were recognized by the autoantibodies. This confirmed our previous results and provide a more precise localization of the antigenic determinants involved. The same approach has been applied in an attempt to identify the binding site(s) for autoantibodies on the human TSH receptor. In contrast to the data obtained with TPO, sera from patients with blocking (from idiopathic myxoedema) or stimulating (from Graves' disease) activity did not recognize the linear TSH receptor peptide fragments generated in our libraries.
T cell adhesion. (1990)

Antigen recognition by the T cell receptor cannot ensure by its own T cell activation. Other membranes molecules are required in order to achieve transient but strong adhesion of the T cell to the antigen presenting cell. Two main molecular adhesion pathways have been characterized involving the CD2 molecule binding the LFA-3 molecule and the LFA-1 molecule binding the ICAM-1 or ICAM-2 molecule. These results have been provided by the use of the three approaches, i-e inhibition of T cell activation and adhesion by monoclonal antibodies, the study of the adhesion of lymphocytes that do not express one or several adhesion molecules and finally the demonstration that the transfection of gene(s) coding for adhesion molecules into fibroblasts cotransfected with HLA molecules make the latter cells able to present antigen(s). The importance of the concept of antigen-independent T cell adhesion has been further underlined by in vivo use of monoclonal antibodies specific for adhesion molecule(s): LFA-1. Such antibody can efficiently block rejection of HLA non identical bone marrow in children. This opens further prospect of immunosuppression through blocking of T cell adhesion.
Chemokine SDF-1 enhances circulating CD34+ cell proliferation in synergy with cytokines: possible role in progenitor survival (2000)

The chemokine stromal cell-derived factor-1 (SDF-1), and its receptor, CXCR-4, have been implicated in the homing and mobilization of human CD34(+) cells. We show here that SDF-1 may also be involved in hematopoiesis, promoting the proliferation of human CD34(+) cells purified from normal adult peripheral blood (PB). CXCR-4 was expressed on PB CD34(+) cells. The amount of CXCR-4 on PB CD34(+) cells was 10 times higher when CD34(+) cells were purified following overnight incubation. CXCR-4 overexpression was correlated with a primitive PB CD34(+) cell subset defined by a CD34(high) CD38(low)CD71(low)c-Kit(low)Thy-1(+) antigenic profile. The functional significance of CXCR-4 expression was ascertained by assessing the promoting effect of SDF-1alpha on cell cycle, proliferation, and colony formation. SDF-1 alone increased the percentage of CD34(+) cells in the S+G(2)/M phases and sustained their survival. In synergy with cytokines, SDF-1 increased PB CD34(+) and CD34(high)CD38(low) cell expansion and colony formation. SDF-1 also stimulated the growth of colonies derived from primitive progenitors released from quiescence by anti-TGF-beta treatment. Thus, our results shed new light on the potential role of this chemokine in the stem cell engraftment process, which involves migration, adhesion, and proliferation. Furthermore, both adhesion-induced CXCR-4 overexpression and SDF-1 stimulating activity may be of clinical relevance for improving cell therapy settings in stem cell transplantation.
Inhibition of polo-like kinase 1 leads to the suppression of osteosarcoma cell growth in vitro and in vivo (2011)

Osteosarcoma is the most common type of primary bone cancer in children and adolescents. Treatment options for osteosarcoma may include surgery, chemotherapy, and radiotherapy. Unfortunately, many patients eventually relapse, resulting in an unsatisfactory outcome. The serine/threonine-specific polo-like kinase 1 (PLK1) is a kinase that plays an important role in mitosis and the maintenance of genomic stability. PLK1 has been found to be highly expressed in the malignant cells of osteosarcoma. Here, we describe the in-vitro and in-vivo effects of BI 2536, a small-molecule inhibitor of PLK1, which through inhibiting PLK1 enzymatic activity, causes mitotic arrest and eventually induces cancer cell apoptosis. In this study, we show that the PLK1 inhibitor, BI 2536, inhibits proliferation and induces apoptosis in two-dimensional and three-dimensional cultures of osteosarcoma cell lines, KHOS and U-2OS. A proliferation assay performed both in two-dimensional and three-dimensional culture showed that the growth of both cell lines was inhibited by BI 2536. Cell cycle analysis showed that the cells treated with BI 2536 were mainly arrested in the G2/M phase. Immunofluorescence and western blotting analysis confirmed that the administration of BI 2536 led to significant decrease of PLK1 and Mcl-1 protein expression levels in dose-dependent and time-dependent manners. Furthermore, BI 2536-induced apoptosis in the osteosarcoma cell lines was shown by poly (ADP-ribose) polymerase cleavage and caspase assay. Finally, in mouse osteosarcoma xenografts, BI 2536-treated mice had significantly smaller tumors compared with the control mice. These findings offer evidence of the potential role for targeting PLK1 in osteosarcoma therapy.
Networked MIMO with Clustered Linear Precoding (2008)

A clustered base transceiver station (BTS) coordination strategy is proposed for a large cellular MIMO network, which includes full intra-cluster coordination to enhance the sum rate and limited inter-cluster coordination to reduce interference for the cluster edge users. Multi-cell block diagonalization is used to coordinate the transmissions across multiple BTSs in the same cluster. To satisfy per-BTS power constraints, three combined precoder and power allocation algorithms are proposed with different performance and complexity tradeoffs. For inter-cluster coordination, the coordination area is chosen to balance fairness for edge users and the achievable sum rate. It is shown that a small cluster size (about 7 cells) is sufficient to obtain most of the sum rate benefits from clustered coordination while greatly relieving channel feedback requirement. Simulations show that the proposed coordination strategy efficiently reduces interference and provides a considerable sum rate gain for cellular MIMO networks.
Construction of phi29 DNA-Packaging RNA Monomers, Dimers, and Trimers with Variable Sizes and Shapes as Potential Parts for Nanodevices (2003)

Recently, DNA and RNA have been under extensive scrutiny with regard to their feasibility as parts in nanotechnology. The DNA-packaging motor of bacterial virus phi29 contains six copies of pRNA molecules, which together form a hexameric ring as a crucial part of the motor. This ring is formed via hand-in-hand interaction by Watson-Crick base pairing of four nucleotides from the left and right loops. Here we report that this pRNA tends to form a circular ring by hand-in-hand contact even when in dimer or trimer form, thus implying that the pRNA structure is flexible. Stable dimers and trimers have been formed from the monomer unit in a protein-free environment with nearly 100% efficiency. The dimers and trimers could be isolated by density gradient sedimentation or purified from native gel. Dimers and trimers were resistant to pH levels as low as 4 and as high as 10, to temperatures as low as -70 degrees C and as high as 80 degrees C, and to high salt concentrations such as 2 M NaCl and 2 M MgCl2. Further study showed that pRNA dimers or trimers with variable lengths could be constructed. Seventy-five bases were found to be the central component in this formation. The elongation of RNA at the 3' end up to 120 bases did not hinder their formation. Other conditions, including the salt requirement for the formation of monomers, dimers, and trimers, have been investigated. RNA monomers, dimers, and trimers with variable lengths are potential parts for nanodevices.
Hematopoietic stem-cell defects underlying abnormal macrophage development and maturation in NOD/Lt mice: defective regulation of cytokine receptors and protein kinase C. (1993)

The immunopathogenesis of autoimmune insulin-dependent diabetes in NOD mice entails defects in the development of macrophages (M phi s) from hematopoietic precursors. The present study analyzes the cellular and molecular basis underlying our previous finding that the Mø growth factor colony-stimulating factor 1 (CSF-1) promotes a reduced level of promonocyte proliferation and M phi development from NOD bone marrow. CSF-1 stimulation of NOD marrow induced Møs to differentiate to the point that they secreted levels of tumor necrosis factor alpha equivalent to that of controls. However, CSF-1 failed to prime NOD M phi s to completely differentiate in response to gamma-interferon, as shown by their decreased lipopolysaccharide-stimulated interleukin 1 secretion. These defects, in turn, were associated with an inability of CSF-1 to up-regulate c-fms (CSF-1 receptor) and Ifgr (gamma-interferon receptor) expression. Even though the combination of CSF-1 and gamma-interferon up-regulated c-fms and Ifgr transcript levels in NOD M phi s to levels induced in control M phi s by CSF-1 alone, the protein kinase C activities coupled to these receptors remained 4-fold lower in NOD M phi s than in M phi s derived from the marrow of diabetes-resistant NON and SWR control mice. Despite expressing the diabetogenic H-2g7 haplotype, M phi s derived from cytokine-stimulated marrow of the NON.H-2g7 congenic stock were functionally more mature than similarly derived M phi s from NOD mice. Whereas diabetes resistance was abrogated in 67% of irradiated (NOD x NON)F1 females reconstituted with NOD marrow, no recipients became diabetic after reconstitution with a 1:1 mixture of marrow from NOD and the congenic stock. Thus, failure to develop functionally mature monocytes may be of pathogenic significance in NOD mice.
Trigonal-bipyramidal and square-pyramidal tungstacyclobutane intermediates are both present in systems in which olefins are metathesized by complexes of the type W(CHR')(N-2,6-C6H3-iso-Pr2)(OR)2 (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTrigonal-bipyramidal and square-pyramidal tungstacyclobutane intermediates are both present in systems in which olefins are metathesized by complexes of the type W(CHR')(N-2,6-C6H3-iso-Pr2)(OR)2Jerald Feldman, William M. Davis, and Richard R. SchrockCite this: Organometallics 1989, 8, 9, 2266–2268Publication Date (Print):September 1, 1989Publication History Published online1 May 2002Published inissue 1 September 1989https://pubs.acs.org/doi/10.1021/om00111a026https://doi.org/10.1021/om00111a026research-articleACS PublicationsRequest reuse permissionsArticle Views260Altmetric-Citations57LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Beyond Intercalation‐Based Li‐Ion Batteries: The State of the Art and Challenges of Electrode Materials Reacting Through Conversion Reactions (2010)

Despite the imminent commercial introduction of Li-ion batteries in electric drive vehicles and their proposed use as enablers of smart grids based on renewable energy technologies, an intensive quest for new electrode materials that bring about improvements in energy density, cycle life, cost, and safety is still underway. This Progress Report highlights the recent developments and the future prospects of the use of phases that react through conversion reactions as both positive and negative electrode materials in Li-ion batteries. By moving beyond classical intercalation reactions, a variety of low cost compounds with gravimetric specific capacities that are two-to-five times larger than those attained with currently used materials, such as graphite and LiCoO(2), can be achieved. Nonetheless, several factors currently handicap the applicability of electrode materials entailing conversion reactions. These factors, together with the scientific breakthroughs that are necessary to fully assess the practicality of this concept, are reviewed in this report.
Thermal modelling of a kilovoltage X-ray source for portal imaging (2002)

The authors have developed a finite element model that exactly matches the dimensions of the megavoltage target assembly of a Varian 2100C/D linear accelerator. The geometry of the model has then been modified to include a kilovoltage target with a 300 target angle. Using this modified model, along with accurate knowledge of the heat transfer mechanisms in the target assembly (e.g., forced convection heat transfer, fully developed boiling, and critical heat flux), the authors have predicted the thermal behaviour of the model. The results show that for a 1.0 mm thick tungsten target more than 2000 W can be applied when using a small area heat source and more than 3000 W can be applied when using a large area heat source. The authors' studies suggest - from a thermal perspective - that it should be possible to incorporate a kilovoltage X-ray source inside the head of a medical linear accelerator.