gebhart/patrepeval huggingface dataset:
Inducible expression of glial fibrillary acidic protein in HT-1080 human fibrosarcoma cells. (1996)

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein expressed almost exclusively by glial cells of the central nervous system. We have previously transfected GFAP-negative human astrocytoma cells with the gene for GFAP and have demonstrated that GFAP transfection decreases astrocytoma proliferation and alters astrocytoma morphology. To determine if the same cellular responses could be elicited upon GFAP transfection of nonglial tumor cells, in the present study we have transfected a GFAP-negative human malignant fibrosarcoma cell line (HT-1080) with a cDNA containing the entire coding sequence of the human GFAP gene under the control of an inducible metallothionein promoter. Stably transfected HT-1080 clones were identified that are GFAP-positive by PCR and immunocytochemistry. GFAP-positive HT-1080 fibrosarcoma cells also demonstrate a decrease in tumor cell proliferation, altered morphological features characterized by cell elongation and cytoplasmic process formation, and reduction of invasive potential when compared to controls. These findings suggest that the inducible expression of the cytoskeletal protein GFAP can also be associated with dramatic cellular effects in nonglial non-central nervous system tumor cells.
Effects of DsbA on the Disulfide Folding of Bovine Pancreatic Trypsin Inhibitor and .alpha.-Lactalbumin (1994)

DsbA is a protein found in the periplasm of Escherichia coli that is required for the formation of disulfide bonds in secreted proteins. It contains only two cysteine residues, which can form reversibly a very unstable disulfide bond that has been proposed to be the oxidant that introduces disulfide bonds into secreted proteins. The present study investigates the effect of DsbA on the well-characterized disulfide-coupled refolding processes of BPTI and of alpha-lactalbumin. Disulfide-bonded DsbA in stoichiometric amounts proved to be a very potent donor of disulfide bonds to reduced BPTI but showed little catalytic activity at neutral pH in the presence of a glutathione redox buffer. In contrast to the related eukaryotic enzyme protein disulfide isomerase, DsbA did not substantially catalyze the usual intramolecular disulfide bond rearrangements of quasi-native folding intermediates of BPTI. Neither did DsbA catalyze the intramolecular rearrangements observed in the three disulfide-bonded "molten globule" form of alpha-lactalbumin at neutral pH. Thiol-disulfide exchange is normally very slow at acidic pH but occurs rapidly with DsbA; consequently, DsbA catalyzed the disulfide folding of BPTI under acidic conditions. It was then possible to detect some increase in the rates of disulfide rearrangements, but only with stoichiometric amounts of DsbA and on the hour time scale. These results suggest that the primary role of DsbA in the bacterial periplasm is to introduce disulfide bonds into newly secreted proteins.
Spatial characterization of interictal high frequency oscillations in epileptic neocortex (2009)

Interictal high frequency oscillations (HFOs), in particular those with frequency components in excess of 200 Hz, have been proposed as important biomarkers of epileptic cortex as well as the genesis of seizures. We investigated the spatial extent, classification and distribution of HFOs using a dense 4 x 4 mm(2) two dimensional microelectrode array implanted in the neocortex of four patients undergoing epilepsy surgery. The majority (97%) of oscillations detected included fast ripples and were concentrated in relatively few recording sites. While most HFOs were limited to single channels, approximately 10% occurred on a larger spatial scale with simultaneous but morphologically distinct detections in multiple channels. Eighty per cent of these large-scale events were associated with interictal epileptiform discharges. We propose that large-scale HFOs, rather than the more frequent highly focal events, are the substrates of the HFOs detected by clinical depth electrodes. This feature was prominent in three patients but rarely seen in only one patient recorded outside epileptogenic cortex. Additionally, we found that HFOs were commonly associated with widespread interictal epileptiform discharges but not with locally generated 'microdischarges'. Our observations raise the possibility that, rather than being initiators of epileptiform activity, fast ripples may be markers of a secondary local response.
Allergen-Specific MHC Class II Tetramer+ Cells Are Detectable in Allergic, but Not in Nonallergic, Individuals (2006)

Allergen-specific cells are present in very low frequency in peripheral blood of humans, and differ in function in allergic and nonallergic individuals. We report in this study that soluble class II MHC tetramers can be used to directly identify and study such allergen epitope-specific CD4+ T cells in humans. We identified the major antigenic epitope of rye grass allergen Lol p 1 in HLA-DRB1*0401 individuals using HLA-DR*0401 transgenic mice and peripheral blood cells from HLA-DR*0401 individuals. Using DRB1*0401 tetramers loaded with this major epitope of Lol p 1, we detected allergen-specific CD4+ T cells in the peripheral blood of DRB1*0401 rye grass allergic individuals after ex vivo expansion with allergen. These tetramer-positive cells produced IL-4, but little IFN-gamma. In contrast, we were unable to detect rye grass tetramer-positive cells in cultures from HLA-DR*0401 nonallergic individuals, even after expansion with IL-2. Thus, our results suggest that rye grass allergen-specific T cells in DR*0401 nonallergic subjects are present at very low levels (e.g., because of deletion or suppression), differ in a fundamental way in their requirement for ex vivo expansion (e.g., they may be anergic), or use TCRs distinct from those of allergic individuals. Thus, analysis using DRB1*0401 tetramers loaded with a major epitope of Lol p 1 indicates that allergen-specific CD4+ T cells in nonallergic individuals are distinct from those in allergic subjects.
Expression of the (Recombinant) Endogenous Immunoglobulin Heavy-Chain Locus Requires the Intronic Matrix Attachment Regions (1997)

The elements which regulate gene expression have traditionally been identified by their effects on reporter genes which have been transfected into cell lines or animals. It is generally assumed that these elements have a comparable role in expression of the corresponding endogenous locus. Nevertheless, several studies of immunoglobulin heavy-chain (IgH) gene expression have reported that the requirements for expressing IgH-derived transgenes differ from the requirements for expression of the endogenous IgH locus. Thus, although expression of transgenes requires multiple elements from the J(H)-C mu intron--the E mu core enhancer, the matrix attachment regions (MARs) which flank E mu, and several switch-associated elements--B-cell lines in which expression of the endogenous heavy-chain gene is maintained at the normal level in the absence of these intronic elements have occasionally been reported. Gene targeting offers an alternative method for assessing regulatory elements, one in which the role of defined segments of endogenous genes can be evaluated in situ. We have applied this approach to the IgH locus of a hybridoma cell line, generating recombinants which bear predetermined modifications in the functional, endogenous mu heavy-chain gene. Our analysis indicates the following. (i) Ninety-eight percent of the expression of the recombinant endogenous mu gene depends on elements in the MAR-E mu-MAR segment. (ii) Expression of the recombinant mu gene depends strongly on the MARs of the J(H)-C mu intron but not on the adjoining E mu core enhancer and switch regions; because our recombinant cell lines bear only a single copy of the mu gene, our results indicate that mu expression is activated by MAR elements lying within that same mu transcription unit. (iii) The MAR segment includes at least one activating element in addition to those defined previously by the binding of presumptive activating proteins in the nuclear matrix. (iv) Close association of the MARs with the E mu enhancer is not required for MAR-stimulated expression. (v) The other MARs in the IgH locus do not in their normal context provide the requisite MAR function.
Developmental Change of the Nestin-Immunoreactive Midline Raphe Glial Structure in Human Brainstem and Spinal Cord (1997)

To elucidate the development of the midline raphe glial structure (MRGS) in human brainstem and spinal cord, immunohistochemistry was carried out in 10 developmentally normal brains (age range, 11 weeks postconception to 6 months) using antibodies to nestin and glial fibrillary acidic protein (GFAP). Nestin expression was most extensive in the youngest fetus (11 weeks postconceptional age, PCA), which showed strong immunoreactivity in radial glial fibers in the midline raphe and paramedian areas of brainstem and spinal cord. Nestin-immunoreactive radial glial fibers in the midline raphe gradually decreased in length and intensity, losing contact with the pial surface 20-24 weeks PCA. Radial glial cells in midbrain transformed into subependymal cells at 30 weeks PCA. Some fragments of radial fibers in brainstem and spinal cord could still be detected up to 30 weeks PCA. Weak GFAP immunoreactivity in the midline raphe was found in radial fibers in the dorsal midline of the midbrain and cervical spinal cord at 30 and 38 weeks PCA. This change of nestin positivity was thought to be due to the process remodeling the MRGS, not to the intracellular distribution and any identifiable clinical factors in the stillbirths. This irregularity in the appearance of the MRGS supports its proposed role as a guide for cell migration, a potential source of new astrocytes, and a barrier to aberrant decussation of growing axons.
Characterization of Alkanes and Paraffin Waxes for Application as Phase Change Energy Storage Medium (1994)

Abstract Latent thermal energy storage is one of the favorable kinds of thermal energy storage methods considered for renewable energy source utilization, as in solar photothermal systems. Heat is stored mostly by means of the latent heat of phase change of the medium. The temperature of the medium remains more or less constant during the phase transition. A large number of materials have been identified for low, intermediate, and high operating temperatures for application as latent thermal energy storage media. In the present paper a method for characterization of alkanes (C1,-C100) and paraffin waxes for application as the low-temperature (298-323 K) phase change energy storage medium is introduced. A computational technique is introduced by which the alkanes and paraffin waxes could be evaluated, and possibly upgraded, as the phase change energy storage media. It is demonstrated that the family of n-alkanes has a large spectrum of latent heats, melting points, densities, and specific heats so that the heat storage designer has a good choice of n-alkanes as storage materials for any particular low-temperature thermal energy storage application. As an example of the proposed method, a particular paraffin wax for which appropriate experimental data are available is analyzed and the results of the analysis are presented.
Faecal Short-Chain Fatty Acids in Patients with Antibiotic-Associated Diarrhoea, before and after Faecal Enema Treatment (1998)

Intestinal microflora showed great disturbances, and the amounts of SCFAs were reduced, although the diarrhoea was not related to total amount SCFAs. Administration of a faecal enema resulted in the clinical recovery of most patients with severe diarrhoea within 4 days.
Selectin-Carbohydrate Interactions and the Initiation of the Inflammatory Response (1995)

The orderly migration of various white blood cell types to inflammatory sites is a highly regulated process that involves a diversity of adhesion and signaling molecules. This cellular influx is initiated by relatively low affinity interactions that allow for leukocytes to roll along the vascular surface. This rolling phenomenon is mediated by adhesive interactions between lectin containing adhesion molecules, termed selectins, on both the vascular endothelium and leukocytes, and carbohydrate ligands immobilized on mucin-like scaffolds. This adhesion allows for a rapid recognition of various cell types under the conditions of vascular flow, with the result that inflammatory cells are specifically decelerated adjacent to sites of inflammation. This review focuses on the various biochemical aspects of the interactions between the selectins and their cognate carbohydrate ligands, with an emphasis on the importance of these adhesive events to the inflammatory response.
Ability of specific monoclonal antibodies and conventional antisera conjugated to hematoporphyrin to label and kill selected cell lines subsequent to light activation. (1985)

A variety of cell lines have been prepared by fusion of the murine WEH1 3B cell line with peripheral blood leukocytes from a patient with chronic granulocytic leukemia. Fusion products were selected for their ability to produce a leukemia-associated antigen (CAMAL) previously described. One such line which originally produced CAMAL subsequently lost this ability and was used as a negative control. A number of antibodies were conjugated to hematoporphyrin (HP) and tested for their ability to bind to cell lines as detected by either fluorescence or by their ability to kill cells after light activation. The antibodies used were: rabbit anti-Hu (a conventional rabbit antiserum raised to membrane preparations from normal human peripheral blood leukocytes which served as a positive control); CAMAL-1 (a monoclonal gamma 1 antibody with specificity for the CAMAL antigen); and L1210 (an irrelevant monoclonal gamma 1 antibody). HP was conjugated to the antibodies by a carbodiimide procedure. When labeled cells were examined by fluorescence microscopy, it was apparent that both the rabbit antibody and CAMAL-1:HP showed positive labeling. The ability of the antibody:HP conjugates to kill labeled cells following light activation was tested. It was shown that rabbit anti-Hu:HP and CAMAL-1:HP conjugates were capable of killing significant numbers of cells when HP concentrations were as low as 1.2 ng/10(6) cells, whereas similarly treated cells exposed to either L1210:HP or HP alone did not exhibit significant killing until concentrations reached 240 and 120 ng/10(6) cells, respectively. Further experiments in which other cell lines were tested, all at HP concentrations of 12 ng/10(6) cells, demonstrated that those lines producing CAMAL were killed, whereas negative lines were not.
Transfer and Expression of the Interferon Gamma Gene in Human Endothelial Cells Inhibits Vascular Smooth Muscle Cell Growth in Vitro (1997)

Intimal hyperplasia in blood vessels is primarily caused by the migration and proliferation of vascular smooth muscle cells. Excessive intimal thickening characterizes atherosclerosis as well as bypass graft and angioplasty failures. Endothelial cell-smooth muscle cell interactions and local cytokine production are important regulators of smooth muscle cell growth. Interferon gamma (γ-IFN), a product of T lymphocytes found in atherosclerotic lesions, inhibits smooth muscle cell proliferation in vitro. To determine if local delivery of γ-IFN may be useful in the treatment or prevention of vascular proliferative diseases, we transferred the human γ-IFN gene into endothelial cells isolated from human arteries and microvessels using a retroviral vector. Biologically active γ-IFN was produced and secreted by γ-IFN transduced endothelial cells, but not by control, nontransduced cells, or cells identically transduced with E. coli beta galactosidase (β-gal). To more closely approximate the microenvironment of blood vessels, subconfluent smooth muscle cells were plated in coculture with control, nontransduced endothelial cells, γ-IFN transduced endothelial cells, or β-gal transduced endothelial cells. Smooth muscle cell growth was inhibited 30-70% by coculture with γ-IFN transduced endothelial cells compared to coculture with β-gal transduced or control endothelial cells (p &lt; 0.05). Our results suggest endothelial cells modified to produce γ-IFN may be a useful therapy in proliferative vascular diseases. Copyright © 1997 Elsevier Science Inc.
Macrochelation, Cyclometallation and G-Quartet Formation: N3- and C8-Bound PdII Complexes of Adenine and Guanine (2001)

The reactions of Pd(II) ions with a series of chelate-tethered derivatives of adenine and guanine have been studied and reveal a difference in the reactivity of the purine bases. Reactions of [PdCl2(MeCN)2] and A-alkyl-enH x Cl (alkyl = propyl or ethyl, A adenine, en = ethylenediamine) yield the monocationic species [PdCl(A-N3-Et-en)]+ (1) and [PdCl(A-N3-Pr-en)]+ (2). Both involve co-ordination at the minor groove site N3 of the nucleobase as confirmed by single-crystal X-ray analysis. Reactions with the analogous G-alkyl-enH x Cl derivatives (G=guanine, alkyl = ethyl or propyl) were more complex with a mixture of species being observed. For G-Et-en HCI a product was isolated which was identified as [PdCl(G-C8-Et-en)]+ (3). This compound contains a biomolecular metal-carbon bond involving C8 of the purine base. Crystallography of a product obtained from reaction of G-Pr-enH x Cl and [Pd(MeCN)4][NO3]2 reveals an octacationic tetrameric complex (4), in which each ligand acts to bridge two metal ions through a combination of a tridentate binding mode involving the diamine and N3 and monodentate coordination at N7.
Inducible membrane-bound L-lactate dehydrogenase from Escherichia coli. Purification and properties. (1977)

ble cytochromes (2, 3).The sequence of electron flow has been studied biochemically and genetically (see Ref. 4 for review), although it is not yet completely established.A few dehydro-
Immune resistance orchestrated by the tumor microenvironment (2006)

It is now little disputed that most if not all cancer cells express antigens that can be recognized by specific CD8(+) T lymphocytes. However, a central question in the field of anti-tumor immunity is why such antigen-expressing tumors are not spontaneously eliminated by the immune system. While in some cases, this lack of rejection may be due to immunologic ignorance, induction of anti-tumor T-cell responses in many patients has been detected in the peripheral blood, either spontaneously or in response to vaccination, without accompanying tumor rejection. These observations argue for the importance of barriers downstream from initial T-cell priming that need to be addressed to translate immune responses into clinical tumor regression. Recent data suggest that the proper trafficking of effector T cells into the tumor microenvironment may not always occur. T cells that do effectively home to tumor metastases are often found to be dysfunctional, pointing toward immunosuppressive mechanisms in the tumor microenvironment. T-cell anergy due to insufficient B7 costimulation, extrinsic suppression by regulatory cell populations, inhibition by ligands such as programmed death ligand-1, metabolic dysregulation by enzymes such as indoleamine-2,3-dioxygenase, and the action of soluble inhibitory factors such as transforming growth factor-beta have all been clearly implicated in generating this suppressive microenvironment. Identification of these downstream processes points to new therapeutic targets that should be manipulated to facilitate the effector phase of anti-tumor immune responses in concert with vaccination or T-cell adoptive transfer.
Prime-boost strategies for malaria vaccine development (2003)

Malaria is an intracellular pathogen, for which an effective vaccine is likely to require induction of cell-mediated immunity. Immunisation approaches that stimulate strong and persistent levels of effector T-cells are being sought by many researchers. DNA vaccines, recombinant protein and viral vectors were amongst the vaccine delivery systems that appeared promising for the generation of cellular immunity, and in some initial studies in small animals this goal was achieved. However, clinical trials of these candidate vaccines when used alone or in repeated homologous boosting regimes have been disappointing, with short-lived low levels of induced specific T-cell responses. Recent years have seen the development of immunisation strategies using a combination of different antigen delivery systems encoding the same epitopes or antigen, delivered at an interval of a few weeks apart. This sequential immunisation approach with different vectors is known as heterologous prime-boosting and is capable of inducing greatly enhanced and persistent levels of CD8+ T-cells and Th1-type CD4+ T-cells compared to homologous boosting. This review will summarise the key pre-clinical studies of prime-boost strategy and outline recent progress in clinical trials of this approach. Possible mechanisms of action and potential improvements to existing delivery systems will be discussed. The prime-boost approach represents an encouraging step towards establishing an effective preventative vaccine to one of the world's greatest killers.
Catalytic reactions in ionic liquids. (2001)

The chemical industry is under considerable pressure to replace many of the volatile organic compounds (VOCs) that are currently used as solvents in organic synthesis. The toxic and/or hazardous properties of many solvents, notably chlorinated hydrocarbons, combined with serious environmental issues, such as atmospheric emissions and contamination of aqueous effluents is making their use prohibitive. This is an important driving force in the quest for novel reaction media. Curzons and coworkers, for example, recently noted that rigorous management of solvent use is likely to result in the greatest improvement towards greener processes for the manufacture of pharmaceutical intermediates. The current emphasis on novel reaction media is also motivated by the need for efficient methods for recycling homogeneous catalysts. The key to waste minimisation in chemicals manufacture is the widespread substitution of classical 'stoichiometric' syntheses by atom efficient, catalytic alternatives. In the context of homogeneous catalysis, efficient recycling of the catalyst is a conditio sine qua non for economically and environmentally attractive processes. Motivated by one or both of the above issues much attention has been devoted to homogeneous catalysis in aqueous biphasic and fluorous biphasic systems as well as in supercritical carbon dioxide. Similarly, the use of ionic liquids as novel reaction media may offer a convenient solution to both the solvent emission and the catalyst recycling problem.
Modeling and Mitigation of Narrowband Interference for Transmitted-Reference UWB Systems (2007)

Transmitted-reference ultra-wideband (TR-UWB) systems, in conjunction with autocorrelation-receivers (AcR), can collect all energy of the multipath channel response at low complexity. Unfortunately the AcR front-end also collects the energy of narrowband interference (NBI) signals, which severely degrades its performance. We present an elaborate statistical analysis of the NBI for a multichannel AcR front-end. Our results show specific correlation properties, which can be exploited to mitigate the NBI by post-processing the AcR output samples. This explains how linear signal processing algorithms can be used to efficiently suppress the cross-terms arising in the nonlinear AcR between all input signals: the UWB, NBI, and noise signals. Linear least squares (LS) and minimum mean squared error (MMSE) receivers are investigated. To support our analysis, computer simulations are conducted using an IEEE802.11a WLAN signal as NBI.