gebhart/patrepeval huggingface dataset:
Molecular Field Analysis and 3D-Quantitative Structure−Activity Relationship Study (MFA 3D-QSAR) Unveil Novel Features of Bile Acid Recognition at TGR5 (2008)

Bile acids regulate nongenomic actions through the activation of TGR5, a membrane receptor that is G protein-coupled to the induction of adenylate cyclase. In this work, a training set of 43 bile acid derivatives is used to develop a molecular interaction field analysis (MFA) and a 3D-quantitative structure-activity relationship study (3D-QSAR) of TGR5 agonists. The predictive ability of the resulting model is evaluated using an external set of compounds with known TGR5 activity, and six bile acid derivatives whose unknown TGR5 activity is herein assessed with in vitro luciferase assay of cAMP formation. The results show a good predictive model and indicate a statistically relevant degree of correlation between the TGR5 activity and the molecular interaction fields produced by discrete positions of the bile acid scaffold. This information is instrumental to extend on a quantitative basis the current structure-activity relationships of bile acids as TGR5 modulators and will be fruitful to design new potent and selective agonists of the receptor.
Effects of the Amino Acid Linkers on the Melanoma-Targeting and Pharmacokinetic Properties of 111In-Labeled Lactam Bridge–Cyclized α-MSH Peptides (2011)

The amino acid linkers exhibited profound effects on the melanoma-targeting and pharmacokinetic properties of the (111)In-labeled lactam bridge-cyclized α-melanocyte-stimulating hormone peptides. Introduction of the -GG- linker maintained high melanoma uptake while reducing kidney and liver uptake of (111)In-DOTA-GGNle-CycMSH(hex), highlighting its potential as an effective imaging probe for melanoma detection, as well as a therapeutic peptide for melanoma treatment when labeled with a therapeutic radionuclide.
Comparison of HER2 gene amplification assessed by fluorescence in situ hybridization and HER2 protein expression assessed by immunohistochemistry in gastric cancer (2006)

A monoclonal antibody to HER2 protein is widely used in the treatment of patients with HER2-overexpressing breast cancer and has also been found to exhibit antitumor activity in human gastric cancer cells that overexpress HER2. The purpose of this study was to evaluate the frequency of HER2 overexpression and concordance between the results for protein expression and gene amplification in both surgical and biopsy specimens of gastric cancer as assessed with two commercial kits, one for immunohistochemistry (IHC) and the other for fluorescence in situ hybridization (FISH). The specimens consisted of formalin-fixed, paraffin-embedded sections of biopsy specimens and surgically resected tumors from 200 cases of invasive gastric cancer that had been treated surgically at the National Cancer Center Hospital East. The lesions were analyzed with the IHC kit, and expression was graded by the United States Food and Drug Administration (FDA)-approved grading system. Gene amplification was evaluated by FISH. IHC revealed HER2 overexpression in 46 of the 200 (23%) cases. The FISH assay was technically successful in 199 cases (99.5%), and gene amplification was observed in 54 cases (27.1%). The concordance rate between the results obtained by IHC and FISH was 86.9%. The concordance rate between the findings in the surgically resected tumors and the 200 pre-treatment biopsy specimens was 88.7%. HER2 expression can be assessed in gastric cancer with a commercial kit as previously reported in breast cancer. Even small biopsy specimens were found to be suitable for evaluating gastric cancer for HER2 overexpression.
RAFT polymerization of styrenic‐based phosphonium monomers and a new family of well‐defined statistical and block polyampholytes (2007)

Abstract We describe herein the first example of the controlled reversible addition‐fragmentation chain transfer (RAFT) radical homo‐ and copolymerization of phosphonium‐based styrenic monomers mediated with a trithiocarbonate‐based RAFT chain transfer agent (CTA) directly in aqueous media. In the case of homopolymer syntheses the polymerizations proceed in a controlled fashion yielding materials with predetermined molecular characteristics as evidenced from the narrow molecular mass distributions (MMD) and the excellent agreement between the theoretical and experimentally determined molecular masses (MM). We also demonstrate the controlled nature of the homopolymerization of 4‐vinylbenzoic acid with the same CTA in DMSO. We subsequently prepared both statistical and block copolymers from the phosphonium/4‐vinylbenzoic acid monomers to yield the first examples of polyampholytes in which the cationic functional group is a quaternary phosphonium species. We show that the kinetic characteristics of the statistical copolymerizations are different from the homopolymerizations and proceed, generally, at a significantly faster rate although there appears to be a composition dependence on the rate. Given the inherent problems in characterizing such polyampholytic copolymers via aqueous size exclusion chromatography we have qualitatively proved their successful formation via FTIR spectroscopy. Finally, in a preliminary experiment we qualitatively demonstrate the ability of such pH‐responsive block copolymers to undergo supramolecular self‐assembly. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2468–2483, 2007
Phosphoramidites of Chiral (Rp)‐and (Sp)‐Configurated d(T[P‐18O]‐A): Synthesis, Configurational Assignment, and Use as Dimer Blocks in Oligonucleotide Synthesis (1985)

Abstract The N , N ‐diisopropylphosphoramidites 10a and 10b of appropriately protected chiral diastereoisomers of d(T[ P ‐ 18 O]‐A) ( 8a and 8b , resp.), chiral by virtue of the isotope 18 O at the P‐atom, have been synthesized. The 18 O‐isotope was incorporated by oxidation of the phosphite triester 3 with H 2 [ 18 O]/I 2 . Separation of the diastereoisomers was accomplished by flash chromatography of the O ‐3′‐deprotected phosphate triesters 5a/b . The absolute configuration at the chiral P‐atom was deduced from the methylation products of the fully deprotected diastereoisomers 8a and 8b . Phosphinylation of 5a and 5b yielded the configurationally pure phosphoramidites 10a and 10b , respectively, which were then employed in solid‐phase synthesis to yield the self‐complementary oligomers d(G‐A‐G‐T‐( R p )‐[P‐ 18 O]‐A‐C‐T‐C) ( 13 ) and d(G‐A‐G‐T‐( S P )‐[ P ‐ 18 O]‐A‐C‐T‐C) ( 14 ), respectively.
Comparative Review of Endoscopic Devices Articulations Technologies Developed for Minimally Invasive Medical Procedures (2011)

This study introduces a comparative performance analysis of the technological solutions that have been used to build distal active articulations for minimally invasive medical procedures. The aim is to provide a practical and concise database and classification tool for anyone that wants to learn more about the technologies involved in minimally invasive medical devices, or for any designer interested in further improving these devices. A review of the different articulations developed in this field is therefore performed and organized by both actuation technology and structural architecture. Details are presented concerning the mechanical structures as well as the actuation and the mechanical transmission technologies available. The solutions are evaluated keeping as a reference some chosen required performances and characteristics for minimally invasive surgical procedures. Finally, a quantified comparison chart of these devices is given regarding selected criteria of interest for minimally invasive surgical application.
Host resistance to Toxoplasma gondii: model for studying the selective induction of cell-mediated immunity by intracellular parasites. (1993)

Cell-mediated immunity (CMI) provides a major host defense against infectious disease and malignancy. Nevertheless, the mechanisms underlying the induction of CMI remain poorly understood and this lack of knowledge remains an important impasse in the design of rationally based vaccines and immunotherapies. Toxoplasma gondii is an intracellular pathogen that, as part of its normal life cycle, induces a potent CMI response leading to host resistance. Studies on the interaction of this parasite with the immune system therefore provide a unique approach for identifying events that selectively lead to the triggering of host-protective CMI. In addition, this knowledge may provide new strategies for immunotherapy of opportunistic infections in immunodeficient hosts.
HDAC4 and PCAF Bind to Cardiac Sarcomeres and Play a Role in Regulating Myofilament Contractile Activity (2008)

Reversible acetylation of lysine residues within a protein is considered a biologically relevant modification that rivals phosphorylation ( Kouzarides, T. (2000) EMBO J. 19, 1176-1179 ). The enzymes responsible for such protein modification are called histone acetyltransferases (HATs) and deacetylases (HDACs). A role of protein phosphorylation in regulating muscle contraction is well established ( Solaro, R. J., Moir, A. J., and Perry, S. V. (1976) Nature 262, 615-617 ). Here we show that reversible protein acetylation carried out by HATs and HDACs also plays a role in regulating the myofilament contractile activity. We found that a Class II HDAC, HDAC4, and an HAT, PCAF, associate with cardiac myofilaments. Primary cultures of cardiomyocytes as well as mouse heart sections examined by immunohistochemical and electron microscopic analyses revealed that both HDAC4 and PCAF associate with the Z-disc and I- and A-bands of cardiac sarcomeres. Increased acetylation of sarcomeric proteins by HDAC inhibition (using class I and II HDAC inhibitors or anti-HDAC4 antibody) enhanced the myofilament calcium sensitivity. We identified the Z-disc-associated protein, MLP, a sensor of cardiac mechanical stretch, as an acetylated target of PCAF and HDAC4. We also show that trichostatin-A, a class I and II HDAC inhibitor, increases myofilament calcium sensitivity of wild-type, but not of MLP knock-out mice, thus demonstrating a role of MLP in acetylation-dependent increased contractile activity of myofilaments. These studies provide the first evidence that HATs and HDACs play a role in regulation of muscle contraction.
Alternative binding proteins: Biological activity and therapeutic potential of cystine‐knot miniproteins (2008)

Cystine-knot miniproteins are members of a large family of small proteins that are defined by a common structural scaffold which is stabilized by three intramolecular disulfide bonds. Cystine-knot miniproteins display a broad spectrum of therapeutically useful natural biological activities and several family members are marketed as therapeutics or are in clinical development. Because of their extraordinary intrinsic chemical and proteolytic stability they provide promising scaffolds for the introduction of therapeutically relevant functionalities. Several successful engineering efforts have been reported to generate miniproteins with novel activities by rational design via functional loop grafting or by directed evolution via screening of scaffold-constrained random libraries. Owing to their small size they are amenable to recombinant as well as to chemical routes of synthesis, which opens up new avenues in optimizing biological activity, specificity and bioavailability by site-specific modification, introduction of non-natural amino acids or chemical conjugation.
Immunology and Inflammation: Basic Mechanisms and Clinical Consequences (1994)

Part I: Basic Mechanisms of Immunity.Effector Cells and Tissues of the Immune System.Antigens, Immunogens, Epitopes.Antigen-Antibody Interactions.Inflammation.Complement System.Coagulation, Fibrinolytic, and Kinin Systems.Lipid Mediators of Inflammation.Polymorphonuclear Cells.Macrophage/Monocyte.Eosinophils/Basophils/Mast Cells.Major Histocompatibility Complex.Generation of Diversity.Ontogeny and Differentiation.Cell Mediated Cytotoxicity.Hypersensitivity.Regulation of the Immune Response I.Regulation of the Immune Response II.Regulatory Molecules of the Immune System.Mucosa Associated Lymphoid Tissues.Mechanisms of Lymphocyte Re-Circulation and Homing and Alternations of Endothelium.Part II: Clinical Immunology.Immunity to Micro-organisms.Immunodeficiency Syndromes.Psycho-Neuro-Immunology.Nutrition, Aging, and the Immune System.Tumor Immunology.Transplantation Immunology.Pregnancy and the Feto-Maternal Relationship.The Immune System of Normal Children.Allergy.Immunohematology.Autoimmunity I and II.Immunotoxicology.Immunopharmacology.Vaccination and Vaccine Design.Immune Mechanisms in Disease.
A new DNA-dependent ATPase which stimulates yeast DNA polymerase I and has DNA-unwinding activity. (1986)

Two forms of DNA-dependent ATPase activity were previously purified from the yeast Saccharomyces cerevisiae and characterized (Plevani, P., Badaracco, G., and Chang, L. M. S. (1980) J. Biol. Chem. 255, 4957-4963). Here, an additional DNA-dependent ATPase (ATPase III) has been purified from S. cerevisiae to near homogeneity. This ATPase differs from those described previously in its chromatographic properties, molecular weight, reaction properties and immunological relatedness. Its molecular weight is about 63,000 in the presence of sodium dodecyl sulfate. It hydrolyzes ATP to ADP and orthophosphate in the presence of DNA as an effector. In addition, yeast DNA polymerase I, which is a true DNA replicase of yeast, is stimulated severalfold by this ATPase. Neither yeast DNA polymerase II nor prokaryotic DNA polymerases are stimulated. This stimulation is intrinsic to the ATPase activity, since both activities copurified in the last four steps of purification, showed the same heat stability and showed dependence on and hydrolysis of ATP. The ATPase III preparation also contains a DNA-unwinding (DNA helicase) activity, which unwinds double-stranded DNA in the presence of ATP. In the S. cerevisiae radiation-sensitive mutant rad3, no significant ATPase III activity could be detected, suggesting that the RAD3 gene, which codes for a different polypeptide, regulates the expression of ATPase III activity.
Molecular characterization of the plasmid‐encoded eps gene cluster essential for exopolysaccharide biosynthesis in Lactococcus lactis (1997)

Lactococcus lactis strain NIZO B40 produces an extracellular phosphopolysaccharide containing galactose, glucose, and rhamnose. A 40 kb plasmid encoding exopolysaccharide production was isolated through conjugal transfer of total plasmid DNA from strain NIZO B40 to the plasmid-free L. lactis model strain MG1614 and subsequent plasmid curing. A 12 kb region containing 14 genes with the order epsRXABCDEFGHIJKL was identified downstream of an iso-IS982 element. The predicted gene products of epsABCDEFGHIJK show sequence homologies with gene products involved in exopolysaccharide, capsular polysaccharide, lipopolysaccharide, or teichoic acid biosynthesis of other bacteria. Transcriptional analysis of the eps gene cluster revealed that the gene cluster is transcribed as a single 12 kb mRNA. The transcription start site of the promoter was mapped upstream of the first gene epsR. The involvement of epsD in exopolysaccharide (EPS) biosynthesis was demonstrated through a single gene disruption rendering an exopolysaccharide-deficient phenotype. Heterologous expression of epsD in Escherichia coli showed that its gene product is a glucosyltransferase linking the first sugar of the repeating unit to the lipid carrier.
A Comparison between Crop Domestication, Classical Plant Breeding, and Genetic Engineering (2002)

ABSTRACT Several claims have been made about genetic engineering (GE) in comparison with crop domestication and classical plant breeding, including the similarity of genetic changes between those taking place during domestication and by GE, the increased speed and accuracy of GE over classical plant breeding, and the higher level of knowledge about the actual genes being transferred by GE compared with classical breeding. In reviewing evidence pertaining to these claims, I suggest that (i) it is unlikely that changes introduced by GE will make crops weedier, although exceptions have been noted, (ii) changes brought about by GE currently often involve gain‐of‐function mutations, whereas changes selected during domestication generally involve loss‐of‐function mutations, (iii) adoption of GE cultivars has been much faster than any previous introduction and spread of agriculture that occurred earlier but has occurred at about the same rate as the spread of cultivars obtained by plant breeding, (iv) introduction of agriculture reduced the health of agriculturists compared with that of hunter–gatherers, suggesting that introduction of innovations do not automatically improve well being, (v) although GE is not a substitute for plant breeding, it can significantly contribute to plant breeding by generating additional genetic diversity, (vi) uncertainties associated with the site of insertion of transgenes in the genome and the expression of transgenes following insertion, makes GE less rapid and precise than originally claimed, and (vii) a potential advantage of GE over classical breeding is the knowledge of the actual gene(s) being inserted, although few cases of unwanted gene introductions through classical plant breeding have been documented. Further advances in GE will increase the precision of the technique, its relevance to consumers, and its environmental friendliness. What is most needed are even‐handed, case‐by‐case assessments of the benefits and potential pitfalls of GE in comparison with other crop improvement techniques. Classical plant breeding may, in the end, also be regulated in the same way as GE.
Multiframe demosaicing and super-resolution of color images (2005)

In the last two decades, two related categories of problems have been studied independently in image restoration literature: super-resolution and demosaicing. A closer look at these problems reveals the relation between them, and, as conventional color digital cameras suffer from both low-spatial resolution and color-filtering, it is reasonable to address them in a unified context. In this paper, we propose a fast and robust hybrid method of super-resolution and demosaicing, based on a maximum a posteron estimation technique by minimizing a multiterm cost function. The L1 norm is used for measuring the difference between the projected estimate of the high-resolution image and each low-resolution image, removing outliers in the data and errors due to possibly inaccurate motion estimation. Bilateral regularization is used for spatially regularizing the luminance component, resulting in sharp edges and forcing interpolation along the edges and not across them. Simultaneously, Tikhonov regularization is used to smooth the chrominance components. Finally, an additional regularization term is used to force similar edge location and orientation in different color channels. We show that the minimization of the total cost function is relatively easy and fast. Experimental results on synthetic and real data sets confirm the effectiveness of our method.
Discovery of the Pyrrolo[2,1-f][1,2,4]triazine Nucleus as a New Kinase Inhibitor Template (2004)

The pyrrolo[2,1-f][1,2,4]triazine nucleus was identified as a novel kinase inhibitor template which effectively mimics the well-known quinazoline kinase inhibitor scaffold. Attachment of a 4-((3-chloro-4-fluorophenyl)amino) substituent to the template provided potent biochemical inhibitors of the tyrosine kinase activity of EGFR, as well as inhibition of cellular proliferation of the human colon tumor cell line DiFi. Attachment of a 4-((3-hydroxy-4-methylphenyl)amino) substituent provided potent inhibitors of VEGFR-2 which also showed effects on the VEGF-dependent proliferation of human umbilical vein endothelial cells. Biological activity was maintained with substitution at positions 5 or 6, but not 7, suggesting that the former positions are promising sites for introducing side chains which modulate physicochemical properties. Preliminary inhibition studies with varying ATP concentrations suggest that, like the quinazoline-based kinase inhibitors, the pyrrolotriazine-based inhibitors bind in the ATP pocket.
Multiple sodium channels and their roles in electrogenesis within dorsal root ganglion neurons (2006)

Dorsal root ganglion neurons express an array of sodium channel isoforms allowing precise control of excitability. An increasing body of literature indicates that regulation of firing behaviour in these cells is linked to their patterns of expression of specific sodium channel isoforms, which have been discovered to possess distinct biophysical characteristics. The pattern of expression of sodium channels differs in different subclasses of DRG neurons and is not fixed but, on the contrary, changes in response to a variety of disease insults. Moreover, modulation of channels by their environment has been found to play an important role in the response of these neurons to stimuli. In this review we illustrate how excitability can be finely tuned to provide contrasting firing templates in different subclasses of DRG neurons by selective deployment of various sodium channel isoforms, by plasticity of expression of these proteins, and by interactions of these sodium channel isoforms with each other and with other modulatory molecules.
PROLONGATION OF SKIN ALLOGRAFT SURVIVAL IN RATS BY A NOVEL IMMUNOSUPPRESSIVE AGENT, FK 506 (1988)

FK506, an immunosuppresant, was isolated from Streptomyces tsukubaensis. Intramuscular administration of FK506 (0.32 mg/kg or more) 5 days a week for two weeks after grafting prolonged the acceptance time of F344 skin allograft to WKA rats. Similar results were obtained with cyclosporine at 32 mg/kg or more, but other immunosuppressives (i.e., prednisolone, azathioprine, and bredinin) gave only a marginal prolongation. The prolonging effect of FK506 was obtained in various donor-recipient combinations across a major or minor histocompatibility barrier. The agent also prolonged the acceptance time of mouse skin xenografts to rats. Furthermore, maintenance doses of 3.2 or 0.32 mg/kg twice a week after an initial 14-day treatment with the agent at 3.2 mg/kg gave graft survival as long as the treatment was continued for more than 120 days. Our findings show that FK506 has a potent immunosuppressive effect in rats and suggest that the agent merits further investigation.