gebhart/patrepeval huggingface dataset:
QSAR Analysis of 5‐Substituted‐2‐Benzoyl‐aminobenzoic acids as PPAR Modulator (2004)

A quantitative structure activity relationship (QSAR) study on a series of analogs of 5‐aryl thiazolidine‐2, 4‐diones with activity on PPAR‐α and PPAR‐ γ was made using combination of various thermodynamic, electronic and spatial descriptors. Several statistical regression expressions were obtained using multiple linear regression analysis. The best QSAR model was further validated by leave one out cross validation method. The studied revealed that for dual PPAR‐α/ γ activity dipole‐dipole energy and PMI‐Z play significant role and contributed positively for PPAR‐ γ and PPAR‐α activity respectively. Thus, QSAR brings important structural insight to aid the design of dual PPAR‐α / γ receptor agonist.
Lifespan of γ/δ T Cells (1998)

Information on the turnover and lifespan of murine gamma/delta cells was obtained by administering the DNA precursor, bromodeoxyuridine (BrdU), in the drinking water and staining lymphoid cells for BrdU incorporation. For TCR-gamma/delta (Vgamma2) transgenic mice, nearly all gamma/delta thymocytes became BrdU+ within 2 d and were released rapidly into the peripheral lymphoid tissues. These recent thymic emigrants (RTEs) underwent phenotypic maturation in the periphery for several days, but most of these cells died within 4 wk. In adult thymectomized (ATx) transgenic mice, only a small proportion of gamma/delta cells survived as long-lived cells; most of these cells had a slow turnover and retained a naive phenotype. As in transgenic mice, the majority of RTEs generated in normal mice (C57BL/6) appeared to have a restricted lifespan as naive cells. However, in marked contrast to TCR transgenic mice, most of the gamma/delta cells surviving in ATx normal mice had a rapid turnover and displayed an activated/memory phenotype, implying a chronic response to environmental antigens. Hence, in normal mice many gamma/delta RTEs did not die but switched to memory cells.
Transient and Stable Transgene Expression in Human Embryonic Stem Cells (2007)

Plasmid vectors remain a valuable yet capricious tool for the genetic manipulation of human embryonic stem (hES) cells. We have compared the efficacy of four promoters to mediate transient and stable transfection in hES and human embryonal carcinoma cell lines with the reporter enhanced green fluorescent protein (eGFP). In transient assays, the two mammalian promoters, UbiquitinC and Rosa26 (pUbiC and pR26), the human cytomegalovirus major immediate early promoter (HCMV-MIE; pCMV), and the HCMV-MIE/chicken beta-actin/rabbit beta-globin hybrid promoter (pCAGG) gave variable results that depended upon the cell line transfected but in an unpredictable way: each promoter supported strong transient expression in at least one cell line. The results for stable transfection were generally at variance with the transient assays. In each case, transgene silencing was quite marked, most notably with the pCMV, with which no eGFP-positive clones were obtained. An exception was the pCAG vector, in which the CAGG composite promoter is linked to the polyoma virus mutant enhancer PyF101; stable eGFP-positive transfectants were obtained, and these clones retained eGFP expression for over 120 passages, even in the absence of selection. However, if the PyF101 elements were removed, the resulting transfectants were also subjected to progressive gene silencing. Thus, the choice of promoter is critical for determining the desired effect of transgene expression in hES cells. Our data also demonstrate that pUbiC, pR26, pCAGG, and pCAG are more superior to the pCMV for generation of stable transfectants in hES cells. Disclosure of potential conflicts of interest is found at the end of this article.
Azithromycin in Patients With Cystic Fibrosis Chronically Infected With Pseudomonas aeruginosa (2003)

Azithromycin treatment was associated with improvement in clinically relevant end points and should be considered for patients with CF who are 6 years or older and chronically infected with P aeruginosa.
Expression of normal and cystic fibrosis phenotypes by continuous airway epithelial cell lines (1990)

Continuous epithelial cell lines from individuals with cystic fibrosis (CF) and normal controls are required to understand the genetic and cellular defects in CF. We used retroviruses to transduce SV40 large T antigen into nasal epithelial cells. Transformed continuous cell lines were isolated that expressed epithelial markers, cytokeratin, and tight junctions. Northern blot analysis shows that all of the cell lines express the putative CF gene mRNA. Studies of transepithelial electrolyte transport show that CF and normal cell lines develop a transepithelial electrical resistance. Normal but not CF cell lines secreted Cl- in response to agonists that increase cellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) (isoproterenol, forskolin, and a membrane-permeant analogue of cAMP) or in response to a tumor-promoting phorbol ester that activates protein kinase C. In contrast, the Ca2(+)-elevating agonist bradykinin and the Ca2+ ionophore A23187 stimulated secretion in both normal and CF cell lines. The continuous cell lines we have produced maintain their proper phenotypes and will serve as useful tools in understanding the pathophysiology of CF.
Hepatocyte Nuclear Factor-4α Involved in Type 1 Maturity-Onset Diabetes of the Young Is a Novel Target of AMP-Activated Protein Kinase (2001)

Mutations in the HNF4α gene are responsible for type 1 maturity-onset diabetes of the young (MODY1), which is characterized by a defect in insulin secretion. Hepatocyte nuclear factor (HNF)-4α is a transcription factor that plays a critical role in the transcriptional regulation of genes involved in glucose metabolism in both hepatocytes and pancreatic β-cells. Recent evidence has implicated AMP-activated protein kinase (AMPK) in the modulation of both insulin secretion by pancreatic β-cells and the control of glucose-dependent gene expression in both hepatocytes and β-cells. Therefore, the question could be raised as to whether AMPK plays a role in these processes by modulating HNF-4α function. In this study, we show that activation of AMPK by 5-amino-4-imidazolecarboxamide riboside (AICAR) in hepatocytes greatly diminished HNF-4α protein levels and consequently downregulates the expression of HNF-4α target genes. Quantitative evaluation of HNF-4α target gene expression revealed diminished mRNA levels for HNF-1α, GLUT2, l-type pyruvate kinase, aldolase B, apolipoprotein (apo)-B, and apoCIII. Our data clearly demonstrate that the MODY1/HNF-4α transcription factor is a novel target of AMPK in hepatocytes. Accordingly, it can be suggested that in pancreatic β-cells, AMPK also acts by decreasing HNF-4α protein level, and therefore insulin secretion. Hence, the possible role of AMPK in the physiopathology of type 2 diabetes should be considered.
Of JAKs, STATs, blind watchmakers, jeeps and trains (2003)

Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling is essential but not sufficient for full responses to the interferons (IFNs), most cytokines and some growth factors. The IFN-gamma and interleukin-6 (IL-6) response pathways have been used as model systems to investigate both the signals involved and their organisation. Activated STAT1 diffuses freely in the cytoplasmic and nuclear compartments of the cell providing a 'random walk' element in the IFN-gamma response. Completely foreign chimeric receptors and, remarkably, in the absence of STAT3, the endogenous IL-6 receptor can efficiently mediate an IFN-gamma-like response. Accordingly all of the signals required for an IFN-gamma response can be generated through physiological levels of a foreign ligand. JAK/STAT signalling, therefore, appears 'soft-wired', modular and highly flexible with substantial overlap between different response pathways. The data are consistent with a generic or 'core' set of signals from JAK/receptor complexes with 'add-on' modulation through specific receptor motifs. The cellular background likely profoundly affects the nature of the response.
Nonopsonic activation of neutrophils by Helicobacter pylori is inhibited by rebamipide. (1998)

Some clinical isolates of nonopsonized H. pylori have the ability to activate neutrophils to an oxidative burst (neutrophil activating capacity, NAC), and such strains were significantly more often isolated from patients with peptic ulcer disease and active chronic gastritis. The purpose of the present work was to investigate the effect of rebamipide (Mucosta) on the release of reactive oxygen metabolites from neutrophils activated by various strains of H. pylori with or without NAC, nonopsonized or opsonized, using as controls fMLP and PMA, known activators of neutrophils, and to study the kinetics of these events by luminol-enhanced chemiluminescence and by flow cytometry. The results showed that the oxidative burst induced in neutrophils by fMLP and by nonopsonized or opsonized H. pylori with NAC was inhibited by rebamipide in a dose-dependent manner both in the early and late phases of activation. In contrast, the oxidative burst induced by opsonized H. pylori without NAC was not inhibited by rebamipide, which might indicate that it does not have the ability to block CR1 or CR3 receptors involved in opsonic phagocytosis but still has the ability to block the receptor(s) for NAC. The oxidative burst induced by PMA, which primarily activates protein kinase C, was not inhibited in the early phase but diminished 40-45% in the late phase with the 2 mM concentration of rebamipide, probably due to scavenging of reactive oxygen species. In conclusion, rebamipide has the ability to diminish the oxidative burst of neutrophils activated by nonopsonized or opsonized H. pylori organisms with neutrophil activating capacity, most likely through the blocking of fMLP-related receptors, inhibition of the production of reactive oxygen species, and the scavenging of such metabolites. Rebamipide may therefore be useful to prevent gastroduodenal lesions associated with gastric mucosal inflammation in H. pylori infection.
Equine granulocytic ehrlichiosis in Connecticut caused by an agent resembling the human granulocytotropic ehrlichia (1996)

The first recognized cases of equine granulocytic ehrlichiosis in New England are described. The DNA sequence of the 16S rRNA gene of the causative ehrlichia was found to be identical to that of the human granulocytotropic ehrlichia, the agent of human granulocytic ehrlichiosis.
Granulocyte Transfusion Therapy of Experimental Pseudomonas Pneumonia (1974)

Pseudomonas pneumonia was produced in dogs with radiation-induced leukopenia. Treatment of this infection with either gentamicin alone or gentamicin plus daily granulocyte transfusion was compared in a randomized controlled trail. The dogs receiving granulocytes plus gentamicin survived significantly longer than those treated with gentamicin alone (P < 0.05). The Pseudomonas immunotype which was inoculated into the dogs were recovered at autopsy from none of the granulocyte-transfused dogs, whereas seven or eight of the dogs treated with gentamicin alone had the inoculated Pseudomonas immunotype in the area of induced pneumonia at autopsy. As measured by the limulus test, the granulocyte-transfused dogs also did not have endotoxemia as frequently as the dogs given only gentamicin (P < 0.05). This controlled study establishes that transfused granulocytes can favorably alter the course of experimental Pseudomonas pneumonia and suggests that granulocyte transfusion may be a useful therapy in serious bacterial infections of leukopenic subjects.
Challenges in the Treatment of Chronic Wounds (2015)

<b>Significance:</b> Chronic wounds include, but are not limited, to diabetic foot ulcers, venous leg ulcers, and pressure ulcers. They are a challenge to wound care professionals and consume a great deal of healthcare resources around the globe. This review discusses the pathophysiology of complex chronic wounds and the means and modalities currently available to achieve healing in such patients. <b>Recent Advances:</b> Although often difficult to treat, an understanding of the underlying pathophysiology and specific attention toward managing these perturbations can often lead to successful healing. <b>Critical Issues:</b> Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. However, selection of an appropriate therapy is often not evidence based. <b>Future Directions:</b> Basic tenets of care need to be routinely followed, and a systematic evaluation of patients and their wounds will also facilitate appropriate care. Underlying pathologies, which result in the failure of these wounds to heal, differ among various types of chronic wounds. A better understanding of the differences between various types of chronic wounds at the molecular and cellular levels should improve our treatment approaches, leading to better healing rates, and facilitate the development of new more effective therapies. More evidence for the efficacy of current and future advanced wound therapies is required for their appropriate use.
Trehalose–protein interaction in aqueous solution (2004)

A variety of sugars are known to enhance the stability of biomaterials. Trehalose, a nonreducing disaccharide composed of two alpha, alpha(1 --> 1)-linked D-glucopyranose units, appears to be one of the most effective protectants. Both in vivo and in vitro, trehalose protects biostructures such as proteins and membranes from damage due to dehydration, heat, or cold. However, despite the significant amount of experimental data on this disaccharide, no clear picture of the molecular mechanism responsible for its stabilizing properties has emerged yet. Three major hypotheses (water-trehalose hydrogen-bond replacement, coating by a trapped water layer, and mechanical inhibition of the conformational fluctuations) have been proposed to explain the stabilizing effect of trehalose on proteins. To investigate the nature of protein-trehalose-water interactions in solution at the molecular level, two molecular dynamics simulations of the protein lysozyme in solution at room temperature have been carried out, one in the presence (about 0.5 M) and one in the absence of trehalose. The results show that the trehalose molecules cluster and move toward the protein, but neither completely expel water from the protein surface nor form hydrogen bonds with the protein. Furthermore, the coating by trehalose does not significantly reduce the conformational fluctuations of the protein compared to the trehalose-free system. Based on these observations, a model is proposed for the interaction of trehalose molecules with a protein in moderately concentrated solutions, at room temperature and on the nanosecond timescale.
A hexapeptide VTKFYF from C-terminal part of interleukin-1 receptor antagonist, an inhibitor of IL-1-IL-1 receptor interaction. (1998)

In order to find the low-molecular-weight interleukin-1 (IL-1) inhibitors we synthesized a series of peptides, derived from three regions of interleukin-1 receptor antagonist (IL-1ra): N-terminal (residues 5-9), central (90-98) and C-terminal (143-148). The decision was based on the thorough analysis of structural and functional properties of IL-1 proteins and the resemblance of some fragments of IL-1ra to well-known immunomodulators, like thymopentin and tuftsin. The competition between our peptides and IL-1 was measured as the inhibition of IL-1 induced IL-2 production in LBRM/CTLL cell line system. The activity of tuftsin (TKPR), a peptide immunomodulator derived from IgG molecule, was also examined. All peptides presented some activity, although the most interesting results (when the range of activity and dose-dependence were taken into account) were obtained for tuftsin and peptide VTKFYF from the C-terminal part of IL-1ra, which is in agreement with the latest reports on the structure of IL-1ra-receptor complex.
Process can efficiently treat gases associated with CO/sub 2/ miscible flood (1983)

Using membranes along with distillation techniques for separating CO/sub 2/ from hydrocarbon streams can improve the turndown capability of a gas-processing plant while offering a means of phasing in the capital requirements of the project. For example, an ideal application for membranes is one in which the ethane fraction from the distillation column is allowed to carry the CO/sub 2/ with it for downstream separation by membranes. This concept is the heart of Fluor's new patented process in which the ethane-CO/sub 2/ mixture is the clean, methane-free overhead product of a distillation column. In a single pass, the membrane system can separate a 70% CO/sub 2/ and 30% ethane stream into a CO/sub 2/ stream with less than 5% hydrocarbons and an ethane product with about 15% CO/sub 2/. Cost comparisons show that the savings in both operating and capital costs using the Fluor process to break the CO/sub 2//C/sub 2/ azeotrope are high enough to pay for H/sub 2/S removal at the front end and still realize a net saving of 20% in utilities and 25% in capital over conventional extractive distillations.
Effects of chronic indomethacin therapy on the development and progression of spontaneous mammary tumors in C3H/HEJ mice (1997)

The present study was designed to test the hypothesis that endogenous prostaglandin E (PGE) promotes the development, growth and metastasis of spontaneous mammary tumors in C3H/HeJ female retired breeder mice. The effect of chronic oral indomethacin (indo) therapy starting at 6 months of age was tested on these parameters as well as on animal survival, in comparison with control mice placed on 0.2% ethanol in drinking water for up to 25 months of age. Indo treatment delayed the initial (up to 27 weeks) development of primary tumors by 11-12 weeks; however, the subsequent rate of tumor appearance was unaffected (totaling 82% in indo-treated vs. 90% in controls by 25 months of age). Spontaneous regression of primary tumors (26% in controls) increased 2-fold (53%) with indo therapy. While the apparent reduction in the growth rate of primary tumors and the overall prolongation of animal survival were not significant, the lifespan of mice bearing multiple tumors was significantly prolonged by therapy. There was also a 2-fold reduction in the incidence of lung metastases in mice bearing detectable primary tumors, and this was more pronounced during the earlier phase of tumor development. Positive immunostaining for cyclooxygenase-2 enzyme (indicative of the cellular source of PGE) was exhibited by tumor cells, stromal cells and macrophages within the primary tumors. Tumors in indo-treated mice exhibited histological evidence of increased differentiation (acinar architecture), significant tumor cell death, mononuclear cell infiltration and reduction in vascularity, indicating that the beneficial effects of indo were due to multiple mechanisms, including improved immune response and reduced angiogenesis.
An Open Space of College Campus according to the Changes of the Times : A Visual Analysis of Cases (2002)

This paper is to evaluate an open space on university campuses enclosed within buildings, with respect to building elevation a wall of an open space including outer wall materials and window forms and an open space itself. It uses case study methods to periodically know specific details about open spaces and surrounding buildings elevation. It was found, at first, that it was emphasized vertical elements on window frames as well as building elements in an era of the 1910's to the 1930's. It, however, was changed into emphasizing on horizontal features in the era of the 1960's to the 1970's. Meanwhile the period from the 1940's to the 1950's was a turning point. The horizontal style was continued until the 1980s and the style was changed into various style mixed with various types. Secondly, an open space was recognized as a valuable design criteria for a construction of buildings in the 1930s to the 1970s. It was, however, a forgotten criteria during the late 1970's and the 1980's because of short age of the construction budget of the government. In the 1990's, the importance of open space design reappeared on the design of a block plan. Thirdly, a design style of an open space was authoritarianism using symmetrical and magnificent style in the 1910's to the 1930's. The time of 1945 to the 1950's was a turning point from authoritarianism to an idea of efficiency. In the 1960's and the 1970s, an idea of efficiency emphasizing their functions was prevalent to the design of buildings and open spaces and this trend was continued until the 1980's. A romanticism was realized on the design of an open space and surrounded building's.
Binding of the Inward Rectifier K+ Channel Kir 2.3 to PSD-95 Is Regulated by Protein Kinase A Phosphorylation (1996)

Dynamic regulation of ion channel interactions with the cytoskeleton mediates aspects of synaptic plasticity, yet mechanisms for this process are largely unknown. Here, we report that two inwardly rectifying K+ channels, Kir 2.1 and 2.3, bind to PSD-95, a cytoskeletal protein of postsynaptic densities that clusters NMDA receptors and voltage-dependent K+ channels. Kir 2.3 colocalizes with PSD-95 in neuronal populations in forebrain, and a PSD-95/Kir 2.3 complex occurs in hippocampus. Within the C-terminal tail of Kir 2.3, a serine residue critical for interaction with PSD-95, is also a substrate for phosphorylation by protein kinase A (PKA). Stimulation of PKA in intact cells causes rapid dissociation of the channel from PSD-95. This work identifies a physiological mechanism for regulating ion channel interactions with the postsynaptic density.
A new, structurally nonredundant, diverse data set of protein–protein interfaces and its implications (2004)

Here, we present a diverse, structurally nonredundant data set of two-chain protein-protein interfaces derived from the PDB. Using a sequence order-independent structural comparison algorithm and hierarchical clustering, 3799 interface clusters are obtained. These yield 103 clusters with at least five nonhomologous members. We divide the clusters into three types. In Type I clusters, the global structures of the chains from which the interfaces are derived are also similar. This cluster type is expected because, in general, related proteins associate in similar ways. In Type II, the interfaces are similar; however, remarkably, the overall structures and functions of the chains are different. The functional spectrum is broad, from enzymes/inhibitors to immunoglobulins and toxins. The fact that structurally different monomers associate in similar ways, suggests "good" binding architectures. This observation extends a paradigm in protein science: It has been well known that proteins with similar structures may have different functions. Here, we show that it extends to interfaces. In Type III clusters, only one side of the interface is similar across the cluster. This structurally nonredundant data set provides rich data for studies of protein-protein interactions and recognition, cellular networks and drug design. In particular, it may be useful in addressing the difficult question of what are the favorable ways for proteins to interact. (The data set is available at http://protein3d.ncifcrf.gov/~keskino/ and http://home.ku.edu.tr/~okeskin/INTERFACE/INTERFACES.html.)