gebhart/patrepeval huggingface dataset:
Stem cell properties of human periodontal ligament cells (2006)

The findings of this study indicated that PDL cells possess crucial stem cell properties, such as self-renewal and multipotency, and express the mesenchymal stem cell markers CD105, CD166, and STRO-1 on their cell surface, although there were some variations. Thus, PDL cells can be used for periodontal regenerative procedures.
Chondrocyte Apoptosis: Implications for Osteochondral Allograft Transplantation (2008)

Osteochondral allograft transplantation is a useful technique to manage larger articular cartilage injuries. One factor that may compromise the effectiveness of this procedure is chondrocyte cell death that occurs during the storage, preparation, and implantation of the osteochondral grafts. Loss of viable chondrocytes may negatively affect osteochondral edge integration and long-term function. A better understanding of the mechanisms responsible for chondrocyte loss could lead to interventions designed to decrease cell death and improve results. Recent studies indicate that apoptosis, or programmed cell death, is responsible for much of the chondrocyte death associated with osteochondral allograft transplantation. Theoretically, some of these cells can be rescued by blocking important apoptotic mediators. We review the role of apoptosis in cartilage degeneration, focusing on apoptosis associated with osteochondral transplantation. We also review the pathways thought to be responsible for regulating chondrocyte apoptosis, as well as experiments testing inhibitors of the apoptotic pathway. These data suggest that key contributors to the apoptotic process can be manipulated to enhance chondrocyte survival. This knowledge may lead to better surgical outcomes for osteochondral transplantation.
Purification and Properties of NADH-Dependent 5,10-Methylenetetrahydrofolate Reductase (MetF) from Escherichia coli (1999)

A K-12 strain of Escherichia coli that overproduces methylenetetrahydrofolate reductase (MetF) has been constructed, and the enzyme has been purified to apparent homogeneity. A plasmid specifying MetF with six histidine residues added to the C terminus has been used to purify histidine-tagged MetF to homogeneity in a single step by affinity chromatography on nickel-agarose, yielding a preparation with specific activity comparable to that of the unmodified enzyme. The native protein comprises four identical 33-kDa subunits, each of which contains a molecule of noncovalently bound flavin adenine dinucleotide (FAD). No additional cofactors or metals have been detected. The purified enzyme catalyzes the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, using NADH as the reductant. Kinetic parameters have been determined at 15 degreesC and pH 7.2 in a stopped-flow spectrophotometer; the Km for NADH is 13 microM, the Km for CH2-H4folate is 0.8 microM, and the turnover number under Vmax conditions estimated for the reaction is 1,800 mol of NADH oxidized min-1 (mol of enzyme-bound FAD)-1. NADPH also serves as a reductant, but exhibits a much higher Km. MetF also catalyzes the oxidation of methyltetrahydrofolate to methylenetetrahydrofolate in the presence of menadione, which serves as an electron acceptor. The properties of MetF from E. coli differ from those of the ferredoxin-dependent methylenetetrahydrofolate reductase isolated from the homoacetogen Clostridium formicoaceticum and more closely resemble those of the NADH-dependent enzyme from Peptostreptococcus productus and the NADPH-dependent enzymes from eukaryotes.
Tripeptides as Efficient Asymmetric Catalysts for 1,4‐Addition Reactions of Aldehydes to Nitroolefins–A Rational Approach (2008)

Bridging the gap: Conformational analysis of a peptidic catalyst for aldol reactions led to the development of H-D-Pro-Pro-Asp-NH2 as a highly efficient catalyst for conjugate addition reactions between aldehydes and nitroolefins (see scheme). Only 1 mol % of catalyst suffices to obtain γ-nitroaldehydes in excellent yields and stereoselectivities. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z704972_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Superoxide radical inhibits catalase. (1982)

Catalase was inhibited by a flux of O2- generated in situ by the aerobic xanthine oxidase reaction. Two distinct types of inhibition could be distinguished. One of these was rapidly established and could be as rapidly reversed by the addition of superoxide dismutase. The second developed slowly and was reversed by ethanol, but not by superoxide dismutase. The rapid inhibition was probably due to conversion of catalase to the ferrooxy state (compound III), while the slow inhibition was due to conversion to the ferryl state (compound II). Since neither compound III nor compound II occurs in the catalatic reaction pathway, they are inactive. This inhibition of catalase by O2- provides the basis for a synergism between superoxide dismutase and catalase. Such synergisms have been observed in vitro and may be significant in vivo.
The Effects of Platelet-Derived Growth Factor Antagonism in Experimental Glomerulonephritis Are Independent of the Transforming Growth Factor–β System (2002)

Platelet-derived growth factor B-chain (PDGF-B)- and transforming growth factor beta (TGF-beta)-mediated accumulation of extracellular matrix proteins contributes to many progressive renal diseases. In vivo, specific antagonism of either PDGF-B or TGF-beta in experimental mesangioproliferative glomerulonephritis resulted in an almost complete inhibition of matrix protein accumulation, which suggests an interaction between signaling pathways of these two growth factors. Because nothing is known on the nature of this possible interaction, PDGF-B was antagonized in the rat anti-Thy 1.1 model of glomerulonephritis by use of specific aptamers and its effects on the TGF-beta system were investigated. Antagonism of PDGF-B led to a significant reduction of glomerular matrix accumulation compared with scrambled aptamer-treated nephritic controls. PDGF-B antagonism had no effect on the overexpression of glomerular TGF-beta mRNA, TGF-beta protein, or the expression of TGF-beta receptor type I and II mRNA. By immunohistology, it was possible to detect overexpression of the cytoplasmic TGF-beta signaling molecules Smad2 (agonistic) and Smad7 (antagonistic) in glomeruli of nephritic control rats which peaked on day 7 after disease induction, i.e., the peak of mesangial cell proliferation in this model. However, immunohistology and Western blot analysis again revealed no difference in the glomerular expression of both Smad proteins between PDGF-B antagonized and nonantagonized nephritic animals. In addition, no difference in the glomerular expression of phosphorylated Smad2 (P-Smad2) was detected between the differently treated nephritic groups. These observations suggest that the effects of PDGF-B antagonism are independent of TGF-beta in mesangioproliferative glomerulonephritides.
CIGS absorbers and processes (2010)

Abstract The current status and future perspectives of Cu(In 1−x Ga x )Se 2 (CIGS) solar cells and modules will be discussed in this paper. The conversion efficiencies of the state of the art laboratory‐scale CIGS solar cells exceeded 20%, which are comparable to those of crystalline Si solar cells. The requirements on the properties of CIGS absorbers to achieve such high efficiencies will be described. The CIGS modules are already commercially available based on two major CIGS deposition techniques such as co‐evaporation and selenization. The current status, problems, and prospects of co‐evaporation and selenization will also be discussed. High‐efficiency flexible CIGS solar cells with efficiencies similar to those fabricated on soda–lime glass (SLG) substrates have been achieved by developing a novel Na incorporation technique. Critical issues to demonstrate high‐efficiency flexible solar cells will also be discussed. Copyright © 2010 John Wiley &amp; Sons, Ltd.
Membrane recruitment of Rac1 triggers phagocytosis (2000)

Rac1 is a &Rgr;-family GTP-binding protein that controls lamellipodia formation and membrane ruffling in fibroblasts. Recently, Rac1 and Cdc42, another member of the &Rgr;-family, have been shown to regulate Fc receptor-mediated phagocytosis in macrophages by controlling different steps of membrane and actin dynamics leading to particle engulfment. Here, we investigated the function of Rac1 using a membrane recruitment system that mimics phagocytosis. Recruitment of an activated Rac1 protein to the cytoplasmic domain of an engineered membrane receptor by using rapamycin as a bridge induces ingestion of latex beads bound to the receptor. Rac1-mediated bead uptake depends on actin polymerisation since actin filaments accumulate at the bead/membrane binding sites and internalisation is inhibited by cytochalasin D. Internalisation is also abolished upon substitution of Phe37 to Leu in the Rac1 effector region. Our results indicate that by promoting actin polymerisation at particle attachment sites, Rac1 by acting through specific downstream effectors induces plasma membrane remodeling that allows particle internalisation in a membrane-enclosed phagosome.
A new indirect encoding method with variable length gene code to optimize neural network structures (2003)

A new encoding method for optimizing neural network structures is proposed. It is based on an indirect encoding method with variable length gene code. The search ability for finding an optimal solution is higher than the direct encoding methods because redundant information in gene code is reduced and the search space is also reduced. The proposed method easily operates adding and deleting hidden units. The performance of the proposed method is evaluated through computer simulations.
Total Synthesis of Cryptophycin-24 (Arenastatin A) Amenable to Structural Modifications in the C16 Side Chain (2000)

Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E, 7E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-8-phenyl-2, 7-octadienoate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl of the cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-alpha-pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl (5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-2, 7-octadienoate, in five steps. This compound was readily converted to the 8-phenyl compound via Heck coupling. The silanyloxy esters were efficiently deprotected and coupled to the C2-C10 amino acid fragment to provide desepoxyarenastatin A and its dephenyl analogue. The terminal olefin of the latter was further elaborated via Heck coupling. Epoxidation provided cryptophycin-24 (arenastatin A).
DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4–ROC1 ubiquitin ligases (2006)

Cullins assemble the largest family of ubiquitin ligases by binding with ROC1 and various substrate receptors. CUL4 function is linked with many cellular processes, but its substrate-recruiting mechanism remains elusive. We identified a protein motif, the DWD box (DDB1-binding WD40 protein), and demonstrated the binding of 15 DWD proteins with DDB1-CUL4A. We provide evidence supporting the critical function of the DWD box and DDB1's role as the linker mediating DWD protein association with CUL4A. A database search predicts that about one-third of WD40 proteins, 90 in humans, contain the DWD box, suggesting a potentially large number of DWD-DDB1-CUL4-ROC1 E3 ligases.
Development of Near-Infrared Fluorophore (NIRF)-Labeled Activity-Based Probes for in Vivo Imaging of Legumain (2009)

Asparaginyl endopeptidase, or legumain, is a lysosomal cysteine protease that was originally identified in plants and later found to be involved in antigen presentation in higher eukaryotes. Legumain is also up-regulated in a number of human cancers, and recent studies suggest that it may play important functional roles in the process of tumorigenesis. However, detailed functional studies in relevant animal models of human disease have been hindered by the lack of suitably selective small molecule inhibitors and imaging reagents. Here we present the design, optimization, and in vivo application of fluorescently labeled activity-based probes (ABPs) for legumain. We demonstrate that optimized aza-peptidyl Asn epoxides are highly selective and potent inhibitors that can be readily converted into near-infrared fluorophore-labeled ABPs for whole body, noninvasive imaging applications. We show that these probes specifically label legumain in various normal tissues as well as in solid tumors when applied in vivo. Interestingly, addition of cell-penetrating peptides to the probes enhanced cellular uptake but resulted in increased cross-reactivity toward other lysosomal proteases as the result of their accumulation in lysosomes. Overall, we find that aza-peptidyl Asn ABPs are valuable new tools for the future study of legumain function in more complex models of human disease.
Integrated functional genomics approach for the design of patient-individual antitumor vaccines. (2002)

Our aim is to identify as many candidates as possible for tumor-associated T-cell epitopes in individual patients. First, we performed expression profiling of tumor and normal tissue to identify genes exclusively expressed or overexpressed in the tumor sample. Then, using mass spectrometry, we characterized up to 77 different MHC ligands from the same tumor sample. Several of the MHC ligands were derived from overexpressed gene products, one was derived from a proto-oncogene, and another was derived from a frameshift mutation. At least one was identified as an actual T-cell epitope. Thus, we could show that by combining these two analytic tools, it is possible to propose several candidates for peptide-based immunotherapy. We envision the use of this novel integrated functional genomics approach for the design of antitumor vaccines tailored to suit the needs of each patient.
Immediate effects of UV radiation on the skin: modification by an antioxidant complex containing carotenoids (2003)

After the oral intake of an antioxidant complex, many parameters of the epidermal defense against UV-induced damages are significantly improved. The oral intake of AOC could provide a safe, daylong and efficient complement to photo-protective measures provided by topical and physical agents and may contribute to reduce the DNA damages leading to skin aging and skin cancers.
Novel Nucleotide Human Immunodeficiency Virus Reverse Transcriptase Inhibitor GS-9148 with a Low Nephrotoxic Potential: Characterization of Renal Transport and Accumulation (2008)

Accumulation of antiviral nucleotides in renal proximal tubules is controlled by their basolateral uptake via the human renal organic anion transporters type 1 (hOAT1) and 3 (hOAT3) and apical efflux via the multidrug resistance protein 4 (MRP4). GS-9148 is a novel ribose-modified nucleotide human immunodeficiency virus (HIV) reverse transcriptase inhibitor, and its oral prodrug GS-9131 is currently being evaluated in the clinic as an anti-HIV agent. To assess the potential of GS-9148 for nephrotoxicity, its mechanism of renal transport, cytotoxicity, and renal accumulation were explored in vitro and in vivo. In comparison with the acyclic nucleotides cidofovir, adefovir, and tenofovir, GS-9148 showed 60- to 100-fold lower efficiency of transport (V(max)/K(m)) by hOAT1 and was 20- to 300-fold less cytotoxic in cells overexpressing hOAT1, indicating its lower hOAT1-mediated intracellular accumulation and reduced intrinsic cytotoxicity. GS-9148 was also relatively inefficiently transported by hOAT3. Similar to acyclic nucleotides, GS-9148 was a substrate for MRP4 as evidenced by its reduced intracellular retention in cells overexpressing the efflux pump. Consistent with these molecular observations, GS-9148 was inefficiently taken up by fresh human renal cortex tissue in vitro and showed a limited accumulation in kidneys in vivo following oral administration of [(14)C]GS-9131 to dogs. Compared to acyclic nucleotide analogs, GS-9148 was also found to have lower net active tubular secretion in dogs. Collectively, these results suggest that GS-9148 exhibits a low potential for renal accumulation and nephrotoxicity.
Molecular Pathways: Targeting MALT1 Paracaspase Activity in Lymphoma (2013)

MALT1 mediates the activation of NF-κB in response to antigen receptor signaling. MALT1, in association with BCL10 and CARD11, functions as a scaffolding protein to activate the inhibitor of IκB kinase (IKK) complex. In addition, MALT1 is a paracaspase that targets key proteins in a feedback loop mediating termination of the NF-κB response, thus promoting activation of NF-κB signaling. Activated B-cell subtype of diffuse large B-cell lymphomas (ABC-DLBCL), which tend to be more resistant to chemotherapy, are often biologically dependent on MALT1 activity. Newly developed MALT1 small-molecule inhibitors suppress the growth of ABC-DLBCLs in vitro and in vivo. This review highlights the recent advances in the normal and disease-related functions of MALT1. Furthermore, recent progress targeting MALT1 proteolytic activity raises the possibility of deploying MALT1 inhibitors for the treatment of B-cell lymphomas and perhaps autoimmune diseases that involve increased B- or T-cell receptor signaling.
Production of Hydrogen Peroxide by Polyphenols and Polyphenol-rich Beverages underQuasi-physiological Conditions (2003)

To investigate the ability of the production of H(2)O(2) by polyphenols, we incubated various phenolic compounds and natural polyphenols under a quasi-physiological pH and temperature (pH 7.4, 37 degrees C), and then measured the formation of H(2)O(2) by the ferrous ion oxidation-xylenol orange assay. Pyrocatechol, hydroquinone, pyrogallol, 1,2,4-benzenetriol, and polyphenols such as catechins yielded a significant amount of H(2)O(2). We also examined the effects of a metal chelator, pH, and O(2) on the H(2)O(2)-generating property, and the generation of H(2)O(2) by the polyphenol-rich beverages, green tea, black tea, and coffee, was determined. The features of the H(2)O(2)-generating property of green tea, black tea, and coffee were in good agreement with that of phenolic compounds, suggesting that polyphenols are responsible for the generation of H(2)O(2) in beverages. From the results, the possible significances of the H(2)O(2)-generating property of polyphenols for biological systems are discussed.
Practical Applications of Phosphors (2006)

Drawn from the second edition of the best-selling Phosphor Handbook, Practical Applications of Phosphors outlines methods for the production of various phosphors and discusses a broad spectrum of applications. Beginning with methods for synthesis and related technologies, the book sets the stage by classifying and then explaining practical phosphors according to usage. It describes the operating principle and structure of phosphor devices and the phosphor characteristics required for a given device, then covers the manufacturing processes and characteristics of phosphors. The book discusses research and development currently under way on phosphors with potential for practical usage and touches briefly on phosphors that have played a historical role, but are no longer of practical use. It provides a comprehensive treatment of applications including lamps and cathode-ray tubes, x-ray and ionizing radiation, and for vacuum fluorescent and field emission displays and covers inorganic and organic electroluminescence materials. The book also covers phosphors for plasma displays, organic fluorescent pigments, and phosphors used in a variety of other practical applications. Emphasizing the practical and cutting-edge nature of the material included, the editors round out their coverage with a discussion of solid-state and organic laser materials.
Enhanced suppression of human myeloid leukemic cell lines by combinations of IL‐6, LIF, GM‐CSF and G‐CSF (1990)

The interactions of purified recombinant human leukemia inhibitory factor (LIF), interleukin-6 (IL-6), granulocyte colony stimulating factor (G-CSF), and granulocyte-macrophage CSF (GM-CSF) on the clonogenicity of HL60 cells and U937 cells were studied in vitro. IL-6 alone strongly suppressed colony formation by U937 cells with induction of differentiation and loss of clonogenicity. GM-CSF interacted synergistically with IL-6 to further reduce colony number and suppress the growth of clonogenic cells formed by HL60 and U937 cells. LIF synergized with IL-6 to reduce colony number and enhance the suppression of the clonogenic U937 cells. The results suggest that these 4 glycoproteins, acting alone or in combination, may be able to suppress human leukemia cells of appropriate type and be of value in the clinical management of myeloid leukemia.
Dopamine D4 Gene 7-Repeat Allele and Attention Deficit Hyperactivity Disorder (1999)

Prior reports of an association between ADHD and DRD4 generalize to families recruited through clinically referred ADHD adults. However, because there are some conflicting studies, further work is needed to clarify the role of DRD4 in the etiology of the disorder.
Advertising and Competition in the Ethical Pharmaceutical Industry: The Case of Antihypertensive Drugs (1999)

This paper uses data on the majority of name‐brand antihypertensive drugs marketed in the United States during 1988–93 to test the hypothesis that advertising decreases the price elasticity of demand in the pharmaceutical industry. This is the first study to directly estimate the effects of drug product promotion on the price elasticity of demand in this industry. We find strong evidence of an advertising effect. In particular, detailing efforts (the salient means for product promotion in this industry) systematically lower price sensitivity. Given the inverse relationship between elasticity of demand and price, it is likely that consumers pay higher prices as a result of the advertising that occurs in this industry. Our findings are thus consistent with Hurwitz and Caves, who find evidence that advertising inhibits entry into this market but in contrast to earlier research that found no anticompetitive effect.