gebhart/patrepeval huggingface dataset:
Rho GTPases and signaling networks (1997)

The Rho GTPases form a subgroup of the Ras superfamily of 20- to 30-kD GTP-binding proteins that have been shown to regulate a wide spectrum of cellular functions. These proteins are ubiquitously expressed across the species, from yeast to man. The mammalian Rho-like GTPases comprise at least 10 distinct proteins: RhoA, B, C, D, and E; Rac1 and 2; RacE; Cdc42Hs, and TC10. A comparison of the amino acid sequences of the Rho proteins from various species has revealed that they are conserved in primary structure and are 50%–55% homologous to each other. Like all members of the Ras superfamily, the Rho GTPases function as molecular switches, cycling between an inactive GDP-bound state and an active GTP-bound state. Until recently, members of the Rho subfamily were believed to be involved primarily in the regulation of cytoskeletal organization in response to extracellular growth factors. However, research from a number of laboratories over the past few years has revealed that the Rho GTPases play crucial roles in diverse cellular events such as membrane trafficking, transcriptional regulation, cell growth control, and development. Consequently, a major challenge has been to unravel the underlying molecular mechanisms by which the Rho GTPases mediate these various activities. Many targets of the Rho GTPases have now been identified and further characterization of some of them has provided major insights toward our understanding of Rho GTPase function at the molecular level. This review aims to summarize the general established principles about the Rho GTPases and some of the more recent exciting findings, hinting at novel, unanticipated functions of the Rho GTPases.
Prevention of Acute Liver Failure in Rats with Reversibly Immortalized Human Hepatocytes (2000)

Because of a critical shortage in suitable organs, many patients with terminal liver disease die each year before liver transplantation can be performed. Transplantation of isolated hepatocytes has been proposed for the temporary metabolic support of patients awaiting liver transplantation or spontaneous reversion of their liver disease. A major limitation of this form of therapy is the present inability to isolate an adequate number of transplantable hepatocytes. A highly differentiated cell line, NKNT-3, was generated by retroviral transfer in normal primary adult human hepatocytes of an immortalizing gene that can be subsequently and completely excised by Cre/Lox site-specific recombination. When transplanted into the spleen of rats under transient immunosuppression, reversibly immortalized NKNT-3 cells provided life-saving metabolic support during acute liver failure induced by 90% hepatectomy.
Pantothenic acid in ruminant nutrition: a review (2010)

Pantothenic acid (PA) is essential in metabolism due to its incorporation into coenzyme A and acyl-carrier-protein. In addition to fodder, ruminants have another PA source, as the micro-organisms in the rumen can synthesize PA. However, it has not been evaluated whether synthesis can meet the PA requirements of dairy cows. Furthermore, synthesis appears to be influenced by forage to concentrate ratio in the diet. It is not yet clear, if oral PA supplementations can increase the duodenal PA flow in dairy cows, but it has been reported that about 80% of supplemented PA disappears between the mouth and duodenum. However, supplementation of PA can increase blood PA levels. To give a general view of the actual state of research, the present review discusses the current knowledge, identifies gaps in knowledge and presents areas for future research.
Bone Marrow Deficiency of MCPIP1 Results in Severe Multi-Organ Inflammation but Diminishes Atherogenesis in Hyperlipidemic Mice (2013)

Hematopoietic deficiency of MCPIP1 resulted in severe systemic and multi-organ inflammation but paradoxically diminished atherogenesis in mice. The reduced atheroegensis may be explained by the decreased plasma cholesterol levels, the anti-atherogenic leukocyte profile, as well as enhanced cholesterol efflux capability. This study suggests that, while atherosclerosis is a chronic inflammatory disease, the mechanisms underlying atherogenesis-associated inflammation in arterial wall versus the inflammation in solid organs may be substantially different.
Animal model of systemic sclerosis (2010)

Scleroderma is a fibrotic condition characterized by immunological abnormalities, vascular injury and increased accumulation of extracellular matrix proteins in the skin. Although the etiology of scleroderma has not yet been fully elucidated, a growing body of evidence suggests that extracellular matrix overproduction by activated fibroblasts results from a complex interaction among endothelial cells, lymphocytes, macrophages and fibroblasts, through a number of mediators, such as cytokines, chemokines and growth factors. For a better understanding of the pathophysiology of scleroderma, animal models are important tools. These models reproduce several histological as well as biochemical aspects of human scleroderma, and we can learn a lot through animal studies. On the other hand, it must be emphasized that studying animal models cannot answer all the problems of human scleroderma. In this review, I introduce current insights into the pathogenesis and also recent updates of therapeutic approaches using several animal models of SSc, and discuss their contribution to our understanding of the pathogenesis of, and treatments for, human scleroderma.
Innate and Adaptive Mucosal Immunity in Protection against HIV Infection (2006)

The appalling toll on the populations of developing countries as a result of the HIV epidemic shows no signs of abatement. While costly drug therapies are effective in developed nations, the sheer scale of the epidemic elsewhere makes the need for a vaccine an ever more urgent goal. The prevalent DNA prime-viral boost strategy aims to elicit cytotoxic lymphocytes (CTL) against HIV, but this approach is undermined by the rapid mutation of HIV, which thereby escapes CTL control. Alloimmunity has been found to be protective in vertical transmission from infected mothers to their babies, in alloimmunization of women with their partners' mononuclear cells, and in monkeys immunized with SIV grown in human T-cells. Vaginal mucosal immunization, as a result of unprotected sex with a regular partner, induced in vitro protection against HIV infection, and this was confirmed in macaques. The second type of natural protection is found in persons with the homozygous 32 CCR5 mutation, a 32-base-pair deletion of the CCR5 gene, which results in a lack of cell-surface expression of CCR5, which is associated with an increase in CC chemokines and the development of CCR5 antibodies. These two 'experiments of nature' have been used to develop vaccine strategies--first, in vaginal immunization of macaques with CCR5 peptides, in addition to HIV envelope (env) and SIV core (gag) antigens, all of which were linked to the 70-kD heat-shock protein (HSP70); and second, in mucosal allo-immunization of macaques, which also gave rise to in vitro protection from infection. Immunization with this vaccine elicited serum and vaginal IgG and IgA antibodies, IFNgamma- and IL-12-producing cells, and increased concentrations of CCL-3 and CCL-4. Vaginal challenge with a simian immunodeficiency virus engineered to carry a human envelope protein (SHIV 89.6) showed significant clearance of SHIV in the immunized macaques. This platform strategy will now be developed to activate the co-stimulatory pathways with the aim of enhancing the primary allogeneic and CCR5-directed responses which are involved in natural protection against HIV infection.
Transapical mitral valve implantation: the Lutter valve. (2013)

The development of transcatheter techniques for treatment of severe mitral valve regurgitation in the beating heart is focus of recent research. An off-pump treatment technique poses great benefits, particularly for multimorbid patients, often being non-compliant to the gold standard treatment, being open heart surgery with use of a cardiopulmonary bypass. Thereto, two approaches are being followed: transcatheter valve repair and transcatheterimplantation of a valved stent into the native mitral valve annulus. A valved stent has to provide safe and secure fixation within the high pressure system of the left heart. One of the main challenges in the development of such a valved stent is the complex anatomy of the mitral valve, with no clearly defined structures for device anchorage. Our group has developed a self-expanding nitinolvalved stent for transapical implantation in the beating heart. During the development process of thevalved stent, different design iterations were conducted to decrease the risk of paravalvular leakages, to enhance the reproducibility and to improve the overall stent performance. This article reviews the major milestones passedin the development process of our mitral valved stent and advances achieved withinthe last years. Multiple design iterations lead to a prototype providing secure stent deployment, hig h reproducibility, low paravalvular leakages and only mild stent deformation in the beating heart. In future, further long-term in vivo trials have to be conducted before attempting the step towards clinical application of this novel device.
Single-polarisation fibre amplifier (1992)

A novel single-polarisation fibre amplifier design is presented. The use of a Faraday mirror in a double-pass design yields optical gain with high efficiency, without spatial hole burning and independent of gain-fibre birefringence. An amplifier, tunable polarised laser, and a high-power polarised super-fluorescent source are demonstrated.
Sub-nm resolution cavity enhanced microspectrometer (2009)

A novel on-chip spectrometer device using combined functionalities of a micro-ring resonator and a planar diffraction grating is proposed. We investigate the performance of this architecture by implementing it in a silicon-on-insulator platform. We experimentally demonstrate such a device with 100 channels, 0.1 nm channel spacing and a channel crosstalk less than -10 dB. The entire device occupies an area of less than 2 mm(2). Based on our initial results we envision that this device enables the possibility of the realization of low-cost and high-resolution ultra-compact spectroscopy.
Randomized Controlled Trial of Percutaneous Intradiscal Radiofrequency Thermocoagulation for Chronic Discogenic Back Pain (2001)

Percutaneous intradiscal radiofrequency thermocoagulation (90 seconds, 70 C) is not effective in reducing chronic discogenic low back pain.
Ultrafast Laser Induced Structural Modification of Fused Silica—Part II: Spatially Resolved and Decomposed Raman Spectral Analysis (2010)

Nonlinear absorption of femtosecond laser pulses enables the induction of structural changes in the interior of bulk transparent materials without affecting their surface. In the present study, femtosecond laser pulses were tightly focused within the interior of bulk fused silica specimen. Localized plasma was formed, initiating rearrangement of the random network structure. Cross sections of the induced features were examined via decomposition of spatially resolved Raman spectra and a new method for the quantitative characterization of the structure of amorphous fused silica was developed. The proposed method identifies the volume fraction distribution of ring structures within the continuous random network of the probed volume of the target material and changes of the distribution with laser process conditions. Effects of the different process conditions and the material response to different mechanisms of feature generation were discussed as well.
Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes. (1995)

A family of interferon (IFN) regulatory factors (IRFs) have been shown to play a role in transcription of IFN genes as well as IFN-stimulated genes. We report the identification of a member of the IRF family which we have named IRF-3. The IRF-3 gene is present in a single copy in human genomic DNA. It is expressed constitutively in a variety of tissues and no increase in the relative steady-state levels of IRF-3 mRNA was observed in virus-infected or IFN-treated cells. The IRF-3 gene encodes a 50-kDa protein that binds specifically to the IFN-stimulated response element (ISRE) but not to the IRF-1 binding site PRD-I. Overexpression of IRF-3 stimulates expression of the IFN-stimulated gene 15 (ISG15) promoter, an ISRE-containing promoter. The murine IFNA4 promoter, which can be induced by IRF-1 or viral infection, is not induced by IRF-3. Expression of IRF-3 as a Gal4 fusion protein does not activate expression of a chloramphenicol acetyltransferase reporter gene containing repeats of the Gal4 binding sites, indicating that this protein does not contain the transcription transactivation domain. The high amino acid homology between IRF-3 and ISG factor 3 gamma polypeptide (ISGF3 gamma) and their similar binding properties indicate that, like ISGF3 gamma, IRF-3 may activate transcription by complex formation with other transcriptional factors, possibly members of the Stat family. Identification of this ISRE-binding protein may help us to understand the specificity in the various Stat pathways.
Effective Immunotherapy of Cancer in MUC1-Transgenic Mice Using Clonal Cytotoxic T Lymphocytes Directed Against an Immunodominant MUC1 Epitope (2002)

The tumor-associated autoantigen MUCI is intensively studied as a potential target for antigen-specific immunotherapy of cancer. Previous reports concerning experiments in preclinical murine tumor models have provided evidence supporting the feasibility of this approach. However, such studies have not been performed with clonal cytotoxic T lymphocyte populations displaying a highly defined MUC1 specificity. The authors demonstrate that the immunodominant MUC1-specific cytotoxic T lymphocyte response in C57BL/6 mice is directed against an H-2Kb-restricted epitope, MUC1(19-27), which is derived from the N-terminal signal sequence of the MUC1 protein. Processing of this epitope was independent of transporter of antigen presentation and proteasome function. Importantly, successful immunotherapy of MUC1-overexpressing tumors in MUC1-transgenic mice was not accompanied by damage to normal somatic MUC1-positive tissues, even when this involved the infusion of large numbers of clonal cytotoxic T lymphocyte that recognized the immunodominant MUC1 epitope. Although the risk for autoimmune pathology is limited, data indicate that immune tolerance in MUC1-positive subjects restricts the breadth of the MUC1-specific cytotoxic T lymphocyte repertoire that is available for recruitment to immunotherapeutic antitumor responses.
Phenotypic stability of bovine articular chondrocytes after long-term culture in alginate beads (1994)

Articular chondrocytes embedded in alginate gel produce de novo a matrix rich in collagens and proteoglycans. A major advantage of this culture system is that the cells can be recovered by chelating the calcium, which otherwise maintains the alginate in its gel state. Chondrocytes thus released are surrounded by tightly bound cell-associated matrix, which seems to correspond to the pericellular and territorial matrices identified in cartilage by electron microscopy. The cells and their associated matrix can be easily separated by mild centrifugation from more soluble matrix components derived principally from the 'interterritorial' matrix. This new cell culture system thus makes it possible to study the assembly and turnover of molecules present in two distinct matrix pools. Importantly, a significant proportion of the aggrecan molecules in each of these two pools can be extracted using a non-denaturing solvent, thereby making possible studies of the metabolism and turnover of native proteoglycan aggregates. We show in this report that chondrocytes isolated from the full depth of adult bovine articular cartilage and maintained for 8 months in alginate gel are still metabolically active and continue to synthesize cartilage-specific type II collagen and aggrecan. The cells did not synthesize large amounts of type I collagen or of the small nonaggregating proteoglycans as usually occurs when chondrocytes lose their phenotypic stability. After this extended period of time in culture, the cells were present as two populations exhibiting differences in size, shape and amount of extracellular matrix surrounding them. The first population was found only near the surface of the bead: these cells were flattened and surrounded by a matrix sparse in proteoglycans and collagen fibrils. The second population was found throughout the remaining depth of the bead: the cells were more round and almost always surrounded by a basket-like meshwork consisting of densely packed fibrils running tangential to the surface.
The primary structure of human cartilage link protein (1990)

Journal Article The primary structure of human cartilage link protein Get access Jayesh Dudhia, Jayesh Dudhia Kennedy Institute of Rheumatology, Division of BiochemistryBute Gardens, Hammersmith, London W6 7DW, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Timothy E. Hardingham Timothy E. Hardingham Kennedy Institute of Rheumatology, Division of BiochemistryBute Gardens, Hammersmith, London W6 7DW, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 5, 11 March 1990, Page 1292, https://doi.org/10.1093/nar/18.5.1292 Published: 11 March 1990 Article history Received: 29 January 1990 Published: 11 March 1990
Selective localization and rotational immobilization of univalent cations on quadruplex DNA (1993)

The quadruplex structure of the oligomer d(T2G4T) is more stable in the presence of K+ than in the presence of Na+. This enhanced stability correlates with the preferential binding of K+ to a small number of specific sites on the quadruplex. In contrast, Na+ and K+ compete on an equal footing for atmospheric binding. Both 39K+ and 23Na+ are, when specifically bound, significantly inhibited in their rotational mobility, so that the quadrupolar relaxation reflects the molecular tumbling of the oligomer, which occurs on the time scale of nanoseconds. This rotational immobilization is in distinct contrast to the high rotational mobility of atmospherically bound cations. On the other hand, all NMR-visible 39K+ in solution is in rapid exchange among all environments (free, specifically bound, and atmospherically bound) implying that the lifetime of specifically coordinated 39K+ must be significantly shorter than a millisecond. A similar conclusion holds for 23Na+. The oligomer d(T2G4T) forms two distinct Hoogsteen base-paired structures in NaCl solution, separated by a large kinetic barrier. Neither of these structures is as stable with respect to base pair opening as is the quadruplex structure formed in KCl solution. Only one of these two structures is associated with rotational immobilization of bound 23Na+.
Advances in functional protein microarray technology (2005)

Numerous innovations in high-throughput protein production and microarray surface technologies have enabled the development of addressable formats for proteins ordered at high spatial density. Protein array implementations have largely focused on antibody arrays for high-throughput protein profiling. However, it is also possible to construct arrays of full-length, functional proteins from a library of expression clones. The advent of protein-based microarrays allows the global observation of biochemical activities on an unprecedented scale, where hundreds or thousands of proteins can be simultaneously screened for protein-protein, protein-nucleic acid, and small molecule interactions. This technology holds great potential for basic molecular biology research, disease marker identification, toxicological response profiling and pharmaceutical target screening.
High and low affinity receptors for interleukin 2: implications of pronase, phorbol ester, and cell membrane studies upon the basis for differential ligand affinities. (1986)

Cellular binding sites for IL 2 exist in two forms which differ with respect to their apparent affinity for the factor. The present studies were designed to evaluate various models for the difference. Receptor-mediated internalization and covalent receptor-ligand coupling were discounted as explanations on the basis of ligand binding and elution studies on permeabilized cells and cell membranes. Phosphorylation of the receptor during activation of protein kinase C failed to modulate the ratio of high and low affinity sites, demonstrating that it also did not provide a potential mechanism. Selective destruction of low affinity receptors with pronase, on the other hand, indicated that the two forms of binding sites differed significantly in their cell surface structure. Either the two types of receptor consist of distinct molecules or the conformation of the high affinity binding sites renders them more resistant to proteolysis. Antibody inhibition studies revealed that the high affinity receptors remaining after protease treatment and their low affinity counterparts both utilized the same ligand-binding component. Thus, this result ruled out the possibility of two totally distinct receptor structures. Together, the findings support the hypothesis that other membrane components modify the conformation of the ligand-binding polypeptide to confer a high affinity protease-resistant configuration.
Paramagnetic NMR Contrast Agents (1984)

Paramagnetic ions could be theoretically used as NMR contrast agents because of their effect upon T1. However, the toxicity of these ions prevents their application. By the formation of appropriate chemical complexes with these ions, the toxicity of these agents can be substantially reduced while maintaining the paramagnetic effect. Two potential NMR contrast agents, one for oral use and one for intravenous administration, were developed and evaluated both in vitro and in vivo. The effect upon T1 in vitro of these paramagnetic compounds was determined using a JEOL FX-90Q NMR spectrometer. These agents were evaluated in vivo in dogs with a Technicare 0.3 tesla superconducting magnet system and in rabbits with the Aberdeen 0.04 tesla resistive NMR imager. Using calculated T1 NMR images, a nontoxic dose of gadolinium oxalate provided visualization of the gastrointestinal tract. Intravenous administration of chromium EDTA provided enhancement of the kidneys, ureters, and bladder, thereby potentially allowing for the evaluation of renal function with magnetic resonance imaging. Stable paramagnetic complexes can serve as effective, nontoxic, oral and intravenous NMR contrast agents.
Microarrays of Tagged Combinatorial Triazine Libraries in the Discovery of Small-Molecule Ligands of Human IgG (2004)

A novel and highly diverse tagged triazine library incorporating a triethylene glycol-based linker was synthesized using an orthogonal combinatorial approach on the solid phase and covalently immobilized on a glass substrate as a small molecule microarray (SMM). The SMM was screened with a fluorophore-conjugated human IgG, and 4 novel binders from a library of 2688 compounds were identified from the fully spatially addressable array without the need for compound decoding. Using surface plasmon resonance (SPR) analysis, binding seen on the array was confirmed, and a binding constant as low as Kd = 2.02 x10(-6) M was measured.