gebhart/patrepeval huggingface dataset:
Chemistry of dioxiranes. 12. Dioxiranes (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry of dioxiranes. 12. DioxiranesRobert W. MurrayCite this: Chem. Rev. 1989, 89, 5, 1187–1201Publication Date (Print):July 1, 1989Publication History Published online1 May 2002Published inissue 1 July 1989https://pubs.acs.org/doi/10.1021/cr00095a013https://doi.org/10.1021/cr00095a013research-articleACS PublicationsRequest reuse permissionsArticle Views3842Altmetric-Citations611LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Antitumor immune effector mechanisms recruited by phage display-derived fully human IgG1 and IgA1 monoclonal antibodies. (1999)

We have constructed a recombinant, fully human IgA1 monoclonal antibody, UBS-54/IgA1, against the tumor-associated Ep-CAM molecule and compared its tumor-killing capacity with its IgG1 counterpart in in vitro assays. The data show that phage display-derived fully human IgA1 antibodies efficiently recruit immune effector cells that express the Fc receptor for IgA, FcalphaRI (CD89). UBS-54/IgA1-mediated killing of tumor cells by isolated polymorphonuclear cells (PMNs) and in whole blood was found to proceed without the necessity to preactivate effector cells with cytokines. In addition, the IgA1 anti-Ep-CAM human monoclonal antibody (huMab) triggered phagocytosis of tumor cells by monocyte-derived macrophages. Strikingly, simultaneous addition of IgA1 and IgG1 anti-Ep-CAM antibodies did not result in enhancement of tumor cell killing unless the effector cells were stimulated with granulocyte colony-stimulating factor. The lack of an additive effect could be attributed to an inhibitory effect of IgG on IgA-mediated tumor cell killing through binding of IgG1 to the inhibitory FcgammaRIIb receptor expressed by PMNs. These results show that IgA1 antitumor huMabs are capable of recruiting the large population of peripheral blood PMNs for tumor cell killing. This population is not effectively recruited by IgG type antibodies, currently the antibodies most frequently used for clinical application. In addition, the data suggest that a combination of IgG1 and IgA1 antitumor huMabs may collaborate in tumor cell killing in patients treated with granulocyte colony-stimulating factor.
Transmembrane channel-formation by five complement proteins. (1985)

Five serum proteins act in concert to form the membrane attack complex (MAC) of complement. The precursor proteins, C5, C6, C7, C8 and C9, are hydrophilic glycoproteins with molecular weights ranging from 70,000 to 180,000. When C5 is cleaved by the serine protease C5 convertase, nascent C5b is produced which forms together with C6 a soluble and stable bimolecular complex (C5b,6). Upon binding of C5b,6 to C7 a trimolecular complex (C5b-7) is formed, which expresses a metastable membrane binding site. Membrane-bound C5b-7 constitutes the receptor for C8 and the tetramolecular C5b-8 complex binds and polymerizes C9. During the assembly process the proteins undergo hydrophilic-amphiphilic transition and the end product consists of C5b-8 (Mr approx. 550,000) and of tubular poly C9 (Mr approx. 1,100,000). The functional channel size varies but its maximal diameter is approximately 10 nm. C9 polymerization appears to involve initial reversible associations of several C9 molecules, which leads to temperature dependent, constrained unfolding. Unfolded C9 monomers then associate laterally with each other and polymerization terminates with closure of the circular structure, which consists of 12-18 C9 monomers. Amino acid composition and sequence indicate that the N-terminal half of the single chain C9 molecule is hydrophilic and the C-terminal half rather hydrophobic. Phospholipid binding and insertion into membranes are functions of the C-terminal portion of the molecule.
GlcNAc 2-Epimerase Can Serve a Catabolic Role in Sialic Acid Metabolism (2003)

Sialic acid is a major determinant of carbohydrate-receptor interactions in many systems pertinent to human health and disease. N-Acetylmannosamine (ManNAc) is the first committed intermediate in the sialic acid biosynthetic pathway; thus, the mechanisms that control intracellular ManNAc levels are important regulators of sialic acid production. UDP-GlcNAc 2-epimerase and GlcNAc 2-epimerase are two enzymes capable of generating ManNAc from UDP-GlcNAc and GlcNAc, respectively. Whereas the former enzyme has been shown to direct metabolic flux toward sialic acid in vivo, the function of the latter enzyme is unclear. Here we study the effects of GlcNAc 2-epimerase expression on sialic acid production in cells. A key tool we developed for this study is a cell-permeable, small molecule inhibitor of GlcNAc 2-epimerase designed based on mechanistic principles. Our results indicate that, unlike UDP-GlcNAc 2-epimerase, which promotes biosynthesis of sialic acid, GlcNAc 2-epimerase can serve a catabolic role, diverting metabolic flux away from the sialic acid pathway.
Cloning, expression, and characterization of an (R)-specific alcohol dehydrogenase fromLactobacillus kefir (2006)

Lactobacillus kefir DSM 20587 produces an (R)-specific NADP-dependent alcohol dehydrogenase (ADH) with a broad substrate specificity. The gene of this ADH was isolated and the complete nucleotide sequence determined. The adh gene comprises 759 bp and encodes a protein of 252 amino acids with a calculated molecular weight of 26 781 Da. The deduced amino acid sequence indicated a high degree of similarity to short-chain dehydrogenases. After cloning and expression in Escherichia coli the enzyme was purified and characterized. For the reduction of acetophenone the specific activity of the homogeneous recombinant ADH was 558 U mg−1. The enzyme shows its maximum activity at 50°C while the pH optimum was at pH 7.0. In order to demonstrate its preparative application, purified ADH was used for the stereoselective reduction of several aliphatic and aromatic ketones as well as β-keto esters. Glucose dehydrogenase was added for the regeneration of NADPH. All prochiral ketones were stereoselectively reduced to the corresponding alcohols with >99% ee and in the case of diketones >99% de.
Molecular cloning, partial purification, and characterization of a haemin‐binding lipoprotein from Haemophilus influenzae type b (1991)

A library of genomic DNA fragments from Haemophilus influenzae type b (Hib) DL42 was constructed in plasmid pBR322, transformed into Escherichia coli strain RR1, and screened for recombinant clones with haemin-binding activity by plating onto haemin-containing agar. Expression of haemin-binding activity by clones correlated with the expression of a protein with an apparent molecular weight of 51,000 (51K) that was also recognized by anti-Hib strain DL42 serum in immunoblots. One recombinant clone, designated pHM2, with the smallest DNA insert (3.62 kb) was characterized further. Ethanol inhibition of expression of pHM2 in minicells revealed that the 51K protein was the result of a processing event involving a larger precursor. E. coli RR1(pHM2) adsorbed haemin in liquid suspensions as well as from solid media. Subcloning of a 2.6 kb fragment of pHM2 into a shuttle vector permitted the construction of a recombinant Hib clone, DL42(pHM1002), which overexpressed the 51K haemin-binding protein. This 51K protein appears to be peripherally associated with the inner, and possibly outer, membranes of Hib. Affinity chromatography on haemin-agarose was utilized to purify the haemin-binding protein from both E. coli RR1(pHM2) and Hib DL42(pHM1002) to near homogeneity. The use of the antibiotic globomycin in a minicell expression system and radioimmunoprecipitation analysis of Hib proteins intrinsically radiolabelled with [3H]-palmitate indicated that the 51K haemin-binding protein is a lipoprotein.
Discrete Cosine Transform: Algorithms, Advantages, Applications (1990)

This is the first comprehensive treatment of the theoretical aspects of the discrete cosine transform (DCT), which is being recommended by various standards organizations, such as the CCITT, ISO etc., as the primary compression tool in digital image coding. The main purpose of the book is to provide a complete source for the user of this signal processing tool, where both the basics and the applications are detailed. An extensive bibliography covers both the theory and applications of the DCT. The novice will find the book useful in its self-contained treatment of the theory of the DCT, the de
Ethanol attenuates ischemic and hypoxic injury in rat brain and cultured neurons (2003)

Reactive oxygen species play a critical role in ischemic injury and oxidative stress induces apoptosis and triggers inflammation in neural cells. The effect of ethanol on ischemic brain injury was examined. Ethanol attenuated ischemia/reperfusion-induced brain infarction and elevation of inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha) expression, metalloproteinase-9, and neutrophil-associated myeloperoxidase activities. In cultured neurons, ethanol suppressed combined oxygen and glucose deprivation (COGD)/reoxygenation-induced oxidative stress and neuronal apoptosis. Furthermore, ethanol suppressed COGD/reoxygenation-induced activation of NF-kappaB, a free-radical-sensitive regulator, leading to the attenuation of TNF-alpha expression in glial cultures. We propose that scavenging of free radicals and attenuation of free-radical-induced alterations might account for ethanol's beneficial action against ischemic brain injury.
Density Estimation and Incremental Learning of Latent Vector for Generative Autoencoders (2019)

In this paper, we treat the image generation task using the autoencoder, a representative latent model. Unlike many studies regularizing the latent variable's distribution by assuming a manually specified prior, we approach the image generation task using an autoencoder by directly estimating the latent distribution. To do this, we introduce 'latent density estimator' which captures latent distribution explicitly and propose its structure. In addition, we propose an incremental learning strategy of latent variables so that the autoencoder learns important features of data by using the structural characteristics of under-complete autoencoder without an explicit regularization term in the objective function. Through experiments, we show the effectiveness of the proposed latent density estimator and the incremental learning strategy of latent variables. We also show that our generative model generates images with improved visual quality compared to previous generative models based on autoencoders.
Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro (2006)

Hepatitis C virus (HCV) is a major cause of chronic liver disease, frequently progressing to cirrhosis and increased risk of hepatocellular carcinoma. Current therapies are inadequate and progress in the field has been hampered by the lack of efficient HCV culture systems. By using a recently described HCV genotype 2a infectious clone that replicates and produces infectious virus in cell culture (HCVcc), we report here that HCVcc strain FL-J6/JFH can establish long-term infections in chimpanzees and in mice containing human liver grafts. Importantly, virus recovered from these animals was highly infectious in cell culture, demonstrating efficient ex vivo culture of HCV. The improved infectivity of animal-derived HCV correlated with virions of a lower average buoyant density than HCVcc, suggesting that physical association with low-density factors influences viral infectivity. These results greatly extend the utility of the HCVcc genetic system to allow the complete in vitro and in vivo dissection of the HCV life cycle.
Biomarkers for diagnosing and monitoring autoimmune diseases (2005)

The goal of studies of autoimmune disease biomarkers is to identity markers that fluctuate with disease development and severity, but then normalize following successful therapy. The perfect marker could thus serve as a diagnostic tool, as well as a monitoring device for therapeutic drug efficacy. Current biomarker discovery efforts are focused on three groups of proteins reflective of the autoimmune disease process: (1) degradation products arising from destruction of affected tissues, (2) enzymes that play a role in tissue degradation and (3) cytokines and other proteins associated with immune activation. Potential biomarkers for two autoimmune diseases, rheumatoid arthritis and multiple sclerosis, have been described in recent publications. For rheumatoid arthritis, these markers (by group) include (1) aggrecan fragments, C-propeptide of type II collagen and cartilage oligomeric matrix protein, (2) matrix metalloprotease (MMP)-1, MMP-3 and MMP-1/inhibitor complexes and (3) thioredoxin, IL-16 and tumour necrosis factor (TNF)-alpha. For multiple sclerosis, they include (1) neurofilament light protein and glial fibrillary acidic protein, (2) MMP-2 and MMP-9 and (3) TNF-alpha and soluble vascular adhesion molecule-1. The utility of most of these markers is limited by their restriction to relatively inaccessible anatomic sites (synovial or cerebrospinal fluid). Thus, from a practical standpoint, the most useful autoimmune biomarkers will be those measurable in serum or plasma.
Bending loss of propagation modes in arbitrary-index profile optical fibers (1978)

A bending loss formula for optical fibers with an axially symmetric arbitrary-index profile is derived by approximating the refractive-index profile with a staircase function. The permissible bending radius R* defined for a given value of bending loss is derived. It is deduced that R* is nearly proportional to wavelength lambda when the normalized frequency nu and the refractive-index difference Delta are fixed. The ratio of R* at two different values of nu depends only on the ratio of nu. The influence of an index dip and profile smoothing on R* is numerically evaluated.
Sigma-1 Receptors Bind Cholesterol and Remodel Lipid Rafts in Breast Cancer Cell Lines (2007)

Lipid rafts are membrane platforms that spatially organize molecules for specific signaling pathways that regulate various cellular functions. Cholesterol is critical for liquid-ordered raft formation by serving as a spacer between the hydrocarbon chains of sphingolipids, and alterations in the cholesterol contents of the plasma membrane causes disruption of rafts. The role that sigma receptors play in cancer is not clear, although it is frequently up-regulated in human cancer cells and tissues and sigma receptors inhibit proliferation in carcinoma and melanoma cell lines, induce apoptosis in colon and mammary carcinoma cell lines, and reduce cellular adhesion in mammary carcinoma cell lines. In this study, we provide molecular and functional evidence for the involvement of the enigmatic sigma 1 receptors in lipid raft modeling by sigma 1 receptor-mediated cholesterol alteration of lipid rafts in breast cancer cell lines. Cholesterol binds to cholesterol recognition domains in the COOH terminus of the sigma 1 receptor. This binding is blocked by sigma receptor drugs because the cholesterol-binding domains form part of the sigma receptor drug-binding site, mutations of which abolish cholesterol binding. Furthermore, we outline a hypothetical functional model to explain the myriad of biological processes, including cancer, in which these mysterious receptors are involved. The findings of this study provide a biological basis for the potential therapeutic applications of lipid raft cholesterol regulation in cancer therapy using sigma receptor drugs.
Flow-mediated endothelial mechanotransduction (1995)

Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed.
Glucose-independent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition (2012)

Linagliptin demonstrated pleiotropic vasodilatory, antioxidant, and anti-inflammatory properties independent of its glucose-lowering properties. These pleiotropic properties are generally not shared by other DPP-4 inhibitors and might translate into cardiovascular benefits in diabetic patients.
Adenosine A2A agonist CGS 21680 decreases the affinity of dopamine D2 receptors for dopamine in human striatum (2001)

Adenosine A2A receptors (A2AR) and dopamine D2 receptors (D2R) are highly concentrated in the striatum, where they are co-localized and exert reciprocal antagonistic interactions. It has been suggested that the A2R/D2R interactions might provide a therapeutic approach for basal ganglia disorders, such as Parkinson's disease, and schizophrenia. In the present work evidence is presented for the existence of an A2AR/D2R interaction in human brain by using quantitative autoradi- ography. The areas analyzed were the dorsal caudate nucleus and putamen. Parallel studies were performed in rat striatal sections. The A2AR agonist CGS 21680 was found to significantly increase IC50 values of competitive inhibition curves of the D2R/D3R antagonist [125I]iodosulpiride vs dopamine both in rat striatal and human striatal brain sections.
Gray matter atrophy is related to long‐term disability in multiple sclerosis (2008)

In MS patients with a relatively long and homogeneous disease duration, GM atrophy is more marked than WM atrophy, and reflects disease subtype and disability to a greater extent than WM atrophy or lesions.
A Simplified and Efficient Route to 2‘-O, 4‘-C-Methylene-Linked Bicyclic Ribonucleosides (Locked Nucleic Acid) (2001)

A novel efficient method for the synthesis of locked nucleic acid (LNA) monomers is described. The LNA 5',3'-diols containing thymine, 4-N-acetyl- and 4-N-benzoylcytosine, 6-N-benzoyladenine, and 2-N-isobutyrylguanine as nucleobases were prepared via convergent syntheses. The method is based on the use of the common sugar intermediate 1,2-di-O-acetyl-3-O-benzyl-4-C-methanesulfonoxymethyl-5-O-methanesulfonyl-D-erythro-pentofuranose (8) that easily can be prepared from D-glucose in multigram scale. Four different nucleobases were stereoselectively coupled to 8 using a modified Vorbrüggen procedure to give the corresponding 4'-C-branched nucleoside derivatives. Subsequent ring closing furnished the protected LNA nucleosides. The 5'-O-mesyl groups were efficiently displaced by nucleophilic substitution using sodium benzoate. Saponification of the 5'-benzoates followed by catalytic removal of the 3'-O-benzyl groups afforded the free LNA diols. The exocyclic amino groups of adenosine and cytidine were selectively acylated to give 4-N-acetyl- or 4-N-benzoyl-LNA-C and 6-N-benzoyl-LNA-A. The isobutyryl group of guanine was retained during the preparation of 2-N-isobutyryl-LNA-G. The LNA-T diol and base-protected LNA diols can be directly converted into LNA-phosphoramidites for automated chemical synthesis of LNA containing oligonucleotides.
RNA binding site of R17 coat protein (1987)

The specific interaction between R17 coat protein and its target of translational repression at the initiation site of the R17 replicase gene was studied by synthesizing variants of the RNA binding site and measuring their affinity to the coat protein by using a nitrocellulose filter binding assay. Substitution of two of the seven single-stranded residues by other nucleotides greatly reduced the Ka, indicating that they are essential for the RNA-protein interaction. In contrast, three other single-stranded residues can be substituted without altering the Ka. When several of the base-paired residues in the binding site are altered in such a way that pairing is maintained, little change in Ka is observed. However, when the base pairs are disrupted, coat protein does not bind. These data suggest that while the hairpin loop structure is essential for protein binding, the base-paired residues do not contact the protein directly. On the basis of these and previous data, a model for the structural requirements of the R17 coat protein binding site is proposed. The model was successfully tested by demonstrating that oligomers with sequences quite different from the replicase initiator were able to bind coat protein.
PEGylation of lnterleukin-6 Effectively Increases Its Thrombopoietic Potency (1997)

The in vivo thrombopoietic activity of polyethylene glycol-modified interleukin-6 (MPEG-IL-6), in which 54% of the 14 lysine amino groups of IL-6 were coupled with PEG, was compared to that of native IL-6. Native IL-6 and MPEG-IL-6, which showed about 51% of the specific bioactivity of native IL-6, were administered subcutaneously to mice every 2 days for 7 days. Native IL-6 increased not only the peripheral platelet count, but also the plasma-IgG1 level in a dose-dependent manner. MPEG-IL-6 showed about 500 times higher thrombopoietic potency than native IL-6. Further, in comparison to native IL-6, MPEG-IL-6 did not enhance IgG1 production as much as it enhanced platelet production. MPEG-IL-6 significantly stimulated platelet recovery in mice treated with 5-fluorouracil, whereas the administration of native IL-6 had a negligible effect. The plasma half-life of MPEG-IL-6 was about 100-fold longer than that of native IL-6. The decrease in the plasma clearance of MPEG-IL-6 was thought to be due, in part, to the shielding of the proteolytic sites in the IL-6 molecule by the PEG chain. The uptake of IL-6 by the reticuloendothelial system, such as the liver and spleen, was markedly limited by PEGylation. The PEGylation of IL-6 markedly enhanced the blood-residency of IL-6, resulting in effective augmentation of its thrombopoietic activity and a marked decrease in its side-effects. These findings suggest that MPEG-IL-6 may be a potential candidate for thrombopoietic agent.