gebhart/patrepeval huggingface dataset:
Molecular targets in immune-mediated diseases: the case of tumour necrosis factor and rheumatoid arthritis (2003)

Rheumatoid arthritis is a common autoimmune condition in which, for unknown reasons, synovial joints become the target of a sustained immune response. For many years, rheumatoid arthritis was in the ‘too hard basket’ in terms of understanding disease mechanisms and providing rational therapy. This has changed dramatically over the last 10 years and rheumatoid arthritis is now at the forefront of biotechnology. In this review, we outline one of the most exciting recent developments, namely antagonists of the cytokine TNF. The preclinical evaluation of TNF in animal models of rheumatoid arthritis, and subsequent clinical trials of TNF inhibitors in patients, provides insight into the ‘bench to bedside’ paradigm. We therefore briefly review rheumatoid arthritis, animal models of rheumatoid arthritis, the biology of TNF, the pivotal clinical trials of TNF antagonists and the emerging data on side-effects. Tumour necrosis factor inhibitors in rheumatoid arthritis represent the first attempt to achieve sustained blockade of a single cytokine in a human disease. Whilst this approach has been even more successful than might have been predicted, we suggest it is only the beginning of what has become a new therapeutic era.
Man's best friend: what can pet dogs teach us about non‐Hodgkin's lymphoma? (2014)

Animal models are essential for understanding lymphoma biology and testing new treatments prior to human studies. Spontaneously arising lymphomas in pet dogs represent an underutilized resource that could be used to complement current mouse lymphoma models, which do not adequately represent all aspects of the human disease. Canine lymphoma resembles human lymphoma in many important ways, including characteristic translocations and molecular abnormalities and similar therapeutic responses to chemotherapy, radiation, and newer targeted therapies (e.g. ibrutinib). Given the large number of pet dogs and high incidence of lymphoma, particularly in susceptible breeds, dogs represent a largely untapped resource for advancing the understanding and treatment of human lymphoma. This review highlights similarities in molecular biology, diagnosis, treatment, and outcomes between human and canine lymphoma. It also describes resources that are currently available to study canine lymphoma, advantages to be gained by exploiting the genetic breed structure in dogs, and current and future challenges and opportunities to take full advantage of this resource for lymphoma studies.
Reengineering immunoglobulin domain interactions by introduction of charged residues (1998)

The formation of the antibody variable domain binding unit (Fv) is the net result of three competing assembly reactions. The affinities of concurrent homologous interactions of heavy and light chain variable domains limits the heterologous interaction leading to productive formation of the Fv. To address the possible role of light chain dimerization in this phenomenon, the Gln38 residue at the dimer interface of an immunoglobulin light chain variable domain (VL) was replaced by charged amino acids. The effects of these mutations on VL homodimer formation were monitored by small-zone size exclusion HPLC and the affinities of interaction were determined by computer simulation. Reduced VL homodimerization was observed in three of the four mutants, Q38R, Q38D and Q38K. The association constants for the Q38R and Q38D homodimers were 1.2 x 10(4) and 3.2 x 10(3) M(-1), respectively. This corresponded to a 20-75-fold reduction in the homodimer association constant relative to the wild-type VL, which had an association constant of 2.4 x 10(5) M(-1). Surprisingly, the fourth charge mutant, Q38E, had a higher association constant than the wild-type VL. The potential for charged residues to facilitate heterodimeric assembly of immunoglobulin domains was also tested. Heterodimerization was observed between the Q38D and Q38R V(L)s, but with an association constant of 4.7 x 10(4) M(-1), approximately fivefold lower than that obtained for homodimerization of the native V(L). In addition, replacement of the neutral, solvent-accessible Gln38 residue with either Asp or Arg was found to be significantly destabilizing. These results suggest that charged residues could be introduced at immunoglobulin domain interfaces to guide heterodimer formation and to minimize unfavorable competing homologous associations. Nonetheless, these apparently simple modifications may also result in unintended consequences that are likely to depend upon structural features of particular variable domains.
Development and Characterization of a Novel Fusion Protein Composed of a Human IgG1 Heavy Chain Constant Region and a Single-Chain Fragment Variable Antibody against Venezuelan Equine Encephalitis Virus (2003)

Murine monoclonal antibody 1A4A1 has been shown to recognize a conserved neutralizing epitope of envelope glycoprotein E2 of Venezuelan equine encephalitis virus. It is a potential candidate for development of a second generation antibody for both immunodiagnosis and immunotherapy. In order to minimize the immunogenicity of murine antibodies and to confer human immune effector functions on murine antibodies, a recombinant gene fusion was constructed. It encoded a human IgG1 heavy chain constant region and a single-chain fragment variable antibody of 1A4A1. After expression in bacteria as inclusion bodies, the recombinant antibody was purified and refolded in vitro. The recombinant soluble antibody was demonstrated to retain high antigen-binding affinity to Venezuelan equine encephalitis virus and to possess some human IgG crystallizable fragment domain functions, such as recognition by protein G and human complement C1q binding. On non-reducing and reducing gel electrophoresis analysis of proteolytic fragments of the recombinant antibody, disulfide bond formation was found in the hinge region of the antibody. From these data, it was concluded that the recombinant antibody was capable of antigen recognition, and retained several functional activities. This work forms the basis for characterization of the recombinant antibody as to efficacy in vivo.
Calculating the surgically induced refractive change following ocular surgery (1992)

Calculating the surgically induced refractive change following ocular surgery is important for evaluating the results of keratore-fractive procedures, smaller incisions and various wound closures for cataract surgery, and the effect of suturing techniques and suture removal following corneal transplant surgery. We present a ten-step method of calculating the spherical- and cylindrical-induced refractive change in a manner suitable for a programmable calculator or personal computer. Several applications are given including (1) adding the overrefraction to the spectacle correction, (2) determining the surgically induced refractive change from the preoperative and postoperative refractions, (3) determining the surgically induced refractive change from the K-readings, (4) rotating axes, (5) determining the power at meridians oblique to the principal meridians of a spherocylinder, (6) determining the coupling ratio, and (7) averaging axes. Standard methods for calculating and reporting aggregate results are also given.
Mild Heat Shock Induces Proliferation, Alkaline Phosphatase Activity, and Mineralization in Human Bone Marrow Stromal Cells and Mg-63 Cells In Vitro (2001)

Bone formation has been shown to be stimulated by local diathermy in vivo; however, the mechanisms involved in this heat-induced osteogenesis are unclear. In this study, we investigated the direct effect of temperature on human bone marrow-derived stromal cells (BMSCs) and the human osteoblast-like, osteosarcoma-derived MG-63 cells in culture conditions. Both cell types were shown to tolerate the transient exposure to mild heat shock conditions (1 h at 39-41 degrees C), and long-term (96 h) exposure at 39 degrees C stimulated DNA synthesis in BMSC but caused growth arrest in MG-63 cells. Furthermore, 1-h exposure to higher temperatures (42.5-45 degrees C) or continuous 96-h exposure to 40 degrees C or 41 degrees C inhibited the proliferation of both BMSCs and MG63 cells. The level of alkaline phosphatase (ALP) in these cells linearly correlated with the increase in temperature, and the ALP expression, either at the basal level or in response to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], was enhanced after a single 1-h exposure to 42.5 degrees C. In addition, continuous incubation at 39 degrees C or repeated transient exposure to 39/41 degrees C greatly enhanced the ability of BMSCs to form mineralizing nodules. The heat shock protein HSP70, which was expressed constitutively by BMSCs, was found to be up-regulated by hyperthermia (39 degrees C) and down-regulated at 33 degrees C. The expression of HSP70 could be induced in MG-63 cells by both low- and high-temperature conditions. These data suggest that treatment with a mild heat shock induces the proliferation and differentiation of osteoprogenitor cells, and the direct effects of temperature on bone-forming cells might be one of the mechanisms involved in heat-induced bone formation in vivo.
Investigation of Atypical Bacteria and Virus Antigens in Respiratory Tract Infections by Use of an Immunofluorescence Method (2004)

In this study an immunofluorescence (IF) method was used to investigate the antigens of viruses and atypical bacteria in respiratory tract infections (RTI) in pediatric and adult age groups. In this prospective study of 2 years (1998-2000), IF was used to investigate the antigens of 7 viral and 3 atypical bacteria to be used for the etiological diagnosis of RTI. Sputum (33.6%) and nasopharyngeal aspirate specimens were obtained from pediatric patients (Group I, 76 cases) and adults (Group II, 135 cases) with RTI symptoms. Antigen detection rates were found to be 44.7% in Group I and 67.4% in Group II (P < 0.05). The following rates for specific antigens in Groups I and II, respectively, were as follows: Chlamydia pneumoniae, 17.1 and 13.3% (P > 0.05); Mycoplasma pneumoniae, 0 and 9.6% (P < 0.05); influenza A virus, 3.9 and 16.3% (P < 0.05); adenovirus, 3.9 and 14.8% (P < 0.05); parainfluenza virus type 1, 5.3 and 7.4% (P > 0.05); respiratory syncytial virus, 9.2 and 1.5% (P < 0.05); parainfluenza virus type 2, 3.9 and 3%(P > 0.05); and influenza B virus, 1.3 and 1.5% (P > 0.05). Mixed agents were found at a rate of 2.6 and 3.7% (P > 0.05) in Groups I and II, respectively. Parainfluenza virus type 3 and Legionella pneumophila antigens were not found. Since detecting etiological agents provides an important guide for determining the most appropriate antibiotic therapy, this IF method could be applied in clinical practice for arriving at a correct diagnosis and administration of effective treatment.
Treatment of alopecia areata: “What is new on the horizon?” (2011)

New drug treatment opportunities based on the results of a genome-wide association study, which implicate T cell and natural killer (NK)-cell activation pathways, are leading to new approaches in future clinical trials of alopecia areata. Special attention is being given to the UL 16-binding protein (ULBP3) gene cluster on chromosome 6q25, as these genes make the NKG2D-activating ligand or signal that can trigger the NKG2D receptor, initiating an autoimmune response. A greater expression of ULBP3 has also been found in hair follicles in scalp biopsy specimens from patients with active disease. It is now postulated that the characteristic T cell "swarm of bees" infiltrate seen in alopecia areata is the result of T cells being attracted to the hair follicle by NKG2D-activating ligands. Future treatment approaches for alopecia areata include use of drugs that: (i) block the NKGD-activating ligand and NKG2D receptor interaction, (ii) halt activated T cells, or (iii) modification of the inflammatory cytokine network. Many drugs currently being used or being evaluated for other autoimmune diseases that work through these mechanisms might prove to be very effective in alopecia areata.
Filling Narrow Trenches by Iodine-Catalyzed CVD of Copper and Manganese on Manganese Nitride Barrier/Adhesion Layers (2011)

We present a process for the void-free filling of sub-100 nm trenches with copper or copper-manganese alloy by chemical vapor deposition (CVD). Conformally deposited manganese nitride serves as an underlayer that initially chemisorbs iodine. CVD of copper or copper-manganese alloy releases the adsorbed iodine atoms from the surface of the manganese nitride, allowing iodine to act as a surfactant catalyst floating on the surface of the growing copper layer. The iodine increases the growth rate of the copper and manganese by an order of magnitude. As the iodine concentrates near the narrowing bottoms of features, void-free, bottom-up filling of CVD of pure copper or copper-manganese alloy is achieved in trenches narrower than 30 nm with aspect ratios up to at least 5:1. The manganese nitride films also show barrier properties against copper diffusion and enhance adhesion between copper and dielectric insulators. During post-deposition annealing, manganese in the alloy diffuses out from copper through the grain boundaries and forms a self-aligned layer that further improves adhesion and barrier properties at the copper/insulator interface. This process provides nanoscale interconnects for microelectronic devices with higher speeds and longer lifetimes.
Expression of lymphocyte-endothelial receptor-ligand pairs, α4β7/MAdCAM-1 and OX40/OX40 ligand in the colon and jejunum of patients with inflammatory bowel disease (1999)

The expression of MAdCAM-1 and OX40 ligand on gut endothelial and OX40+ cells is increased in sites of mucosal inflammation in patients with inflammatory bowel disease. No evidence was found for increased lamina propria T cells or increased vascular adhesion molecule expression in the proximal intestine of patients with distal inflammatory bowel disease.
Hypoxia-induced Angiogenesis during Carcinogenesis (2003)

The formation of new blood vessels, angiogenesis, is an essential process during development and disease. Angiogenesis is well known as a crucial step in tumor growth and progression. Angiogenesis is induced by hypoxic conditions and regulated by the hypoxia-inducible factor 1 (HIF-1). The expression of HIF-1 correlates with hypoxia-induced angiogenesis as a result of the induction of the major HIF-1 target gene, vascular endothelial cell growth factor (VEGF). In this review, a brief overview of the mechanism of angiogenesis is discussed, focusing on the regulatory processes of the HIF-1 transcription factor. HIF-1 consists of a constitutively expressed HIF-1 beta (HIF-1beta) subunit and an oxygen-regulated HIF-1 alpha (HIF-1a) subunit. The stability and activity of HIF-1alpha are regulated by the interaction with various proteins, such as pVHL, p53, and p300/CBP as well as by post-translational modifications, hydroxylation, acetylation, and phosphorylation. It was recently reported that HIF-1alpha binds a co-activator of the AP-1 transcription factor, Jab-1, which inhibits the p53-dependent degradation of HIF-1 and enhances the transcriptional activity of HIF-1 and the subsequent VEGF expression under hypoxic conditions. ARD1 acetylates HIF-1alpha and stimulates pVHL-mediated ubiquitination of HIF-1alpha. With a growing knowledge of the molecular mechanisms in this field, novel strategies to prevent tumor angiogenesis can be developed, and from these, new anticancer therapies may arise.
Treatment with geraniol ameliorates methionine‐choline‐deficient diet‐induced non‐alcoholic steatohepatitis in rats (2015)

Treatment with geraniol attenuated MCD-induced NASH in rats.
Marsupial teams of robots: deployment of miniature robots for swarm exploration under communication constraints (2014)

SUMMARY Mobile Ad hoc Networks have attracted much attention in the last years, since they allow the coordination and cooperation between agents belonging to a multi-robot system. However, initially deploying autonomously a wireless sensor robot network in a real environment has not taken the proper attention. Moreover, maintaining the connectivity between agents in real and complex environments is an arduous task since the strength of the connection between two nodes (i.e., robots) can change rapidly in time or even disappear. This paper compares two autonomous and realistic marsupial strategies for initial deployment in unknown scenarios, in the context of swarm exploration: Random and Extended Spiral of Theodorus . These are based on a hierarchical approach, in which exploring agents, named scouts , are autonomously deployed through explicit cooperation with supporting agents, denoted as rangers . Experimental results with a team of heterogeneous robots are conducted using both real and virtual robots. Results show the effectiveness of the methods, using a performance metric based on dispersion. Conclusions drawn in this work pave the way for a whole series of possible new approaches.
Functional magnetic resonance imaging in oncology for diagnosis and therapy monitoring. (2003)

Functional magnetic resonance imaging is rapidly evolving as a capable noninvasive assessment tool for oncology to improve diagnosis and to monitor therapy. Current clinical techniques are based on microcirculation imaging using extracellular low molecular weight contrast agents such as gadopentetate dimeglumine and analogues. The temporal evolution of the enhancement visualizes the angiogenic properties of lesions with regard to vascular density and permeability, heterogeneity, and changes during therapy.
Interleukin-17 and CD40-Ligand Synergistically Enhance Cytokine and Chemokine Production by Renal Epithelial Cells (2000)

Renal allograft rejection is characterized by an influx of inflammatory cells. Interaction between infiltrating T cells and resident parenchymal cells might play an important role in the ongoing inflammatory response. The present study demonstrates that CD40L, a product of activated T cells, is locally expressed in kidneys undergoing rejection. Furthermore, during rejection, CD40 expression not only is present on most graft infiltrating cells but also is increased on resident tubular epithelial cells (TEC). To obtain more detailed insight in the consequences of T cell/TEC interaction, we analyzed the production of chemokines, including interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and regulated upon activation, normal T cell expressed and secreted (RANTES), and the production of IL-6 by cultured human primary TEC in response to activation with CD40L in vitro. In addition, we studied the interaction with IL-17, a T-cell-specific cytokine previously demonstrated to be present during renal allograft rejection. The results, obtained by enzyme-linked immunosorbent assay, indicate that simultaneous activation of TEC with IL-17 and CD40L synergistically enhances production of IL-6 (2.1-fold higher than sum of single stimulations) and the chemokines IL-8 (15-fold) and RANTES (5.8-fold) as demonstrated by statistical analysis (P: < 0.05), whereas effects on MCP-1 (1.4-fold) are additive. Part of the synergy can be explained by increased CD40 expression on TEC upon IL-17 stimulation. The synergy is not unique for TEC, because similar responses were found with human synoviocytes and a foreskin fibroblast cell line (FS4). Stimulation of TEC with CD40L results in activation of NF-kappaB and induction of cytokine production by IL-17 and CD40L is prevented by addition of the NF-kappaB inhibitor pyrrolidine dithiocarbamate. These data suggest an important role for T cells in renal allograft rejection by acting on parenchymal cells via both soluble mediators and direct cellular contact.
Agonist-independent Activation of Src Tyrosine Kinase by a Cholecystokinin-2 (CCK2) Receptor Splice Variant (2004)

Src activity is elevated in a majority of colonic and pancreatic cancers and is associated with late stage aggressive cancers. However, the mechanisms leading to its increased activity remain largely undefined. Agonist binding to the cholecystokinin-2 (CCK2)/gastrin receptor (CCK2R), a G-protein-coupled receptor, increases Src activity in a variety of normal and neoplastic cell lines. Recently, we and others (Hellmich, M. R., Rui, X. L., Hellmich, H. L., Fleming, R. Y., Evers, B. M., and Townsend, C. M., Jr. (2000) J. Biol. Chem. 275, 32122-32128; Ding, W. Q., Kuntz, S. M., and Miller, L. J. (2002) Cancer Res. 62, 947-952; Smith, J. P., Verderame, M. F., McLaughlin, P., Martenis, M., Ballard, E., and Zagon, I. S. (2002) Int. J. Mol. Med. 10, 689-694) have identified a splice variant of CCK2R, called CCK2i4svR, that is expressed in human colorectal and pancreatic cancers but not by cells of the adjacent nonmalignant tissue. Compared with CCK2R, CCK2i4svR contains an additional 69 amino acids within its third intracellular loop (3il) domain. Because CCK2i4svR is the only splice variant expressed in some human colon and pancreatic cancers, we questioned whether CCK2i4svR could regulate Src activity. Stably transfected HEK293 cells were used because, unlike many cancer-derived cells, they have a low level of basal Src activity. We report that, in contrast to CCK2R, CCK2i4svR activates Src kinase in the absence of agonist stimulation. In vitro kinase assay of immunoprecipitated receptor protein showed a 6-8-fold increase in Src kinase activity associated with CCK2i4svR compared with CCK2R. Expression of the 3il domain of the CCK2i4svR alone was sufficient to partially activate Src kinase. Together, these data support the hypothesis that the increased Src activity observed in some pancreatic and colorectal cancers is due, in part, to the co-expression of CCK2i4svR.
Muscle polyribosomes and the coprecipitation of polyribosomes with myosin (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMuscle polyribosomes and the coprecipitation of polyribosomes with myosinStuart M. Heywood, Robert M. Dowben, and Alexander. RichCite this: Biochemistry 1968, 7, 9, 3289–3296Publication Date (Print):September 1, 1968Publication History Published online1 May 2002Published inissue 1 September 1968https://pubs.acs.org/doi/10.1021/bi00849a036https://doi.org/10.1021/bi00849a036research-articleACS PublicationsRequest reuse permissionsArticle Views45Altmetric-Citations50LEARN 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
Platelet 5-Hydroxytryptamine and Vascular Adrenergic Nerves (1988)

Platelets contain and release large amounts of 5-hydroxytryptamine that can influence the function of vascular adrenergic nerves. The immediate effect on neuronal function of low concentrations of the amine is to inhibit norepinephrine release. 5-Hydroxytryptamine may also be accumulated by the same uptake mechanism that reaccumulates norepinephrine into the adrenergic nerve endings. In diseased blood vessels where platelet aggregation occurs, 5-hydroxytryptamine may therby assume an alternative transmitter role, altering the function of the sympathetic nerves.