gebhart/patrepeval huggingface dataset:
Amniotic Membrane Transplantation for Persistent Epithelial Defects With Ulceration (1997)

Amniotic membrane transplantation may be considered an alternative method for treating persistent epithelial defects and sterile ulceration that are refractory to conventional treatment and before considering treatment by conjunctival flaps or tarsorrhaphy.
β PDGFR‐IgG chimera demonstrates that human β PDGFR Ig‐like domains 1 to 3 are sufficient for high affinity PDGF BB binding (1995)

To localize human beta PDGFR binding determinants, we constructed a fusion protein comprising beta PDGFR Ig-like domains 1 to 3 and an IgG1 Fc domain (beta PDGFR-HFc). beta PDGFR-HFc was expressed as a 200 kDa dimeric molecule and contained Fc epitopes as demonstrated by anti-mouse Fc antibody recognition. Scatchard analysis revealed that PDGF BB possessed a dissociation constant of 1.5 nM for beta PDGFR-HFc. Thus, beta PDGFR Ig-like domains 1 to 3 are sufficient for high affinity PDGF BB binding. We exploited this fusion protein technology to identify and characterize beta PDGFR antagonists using a sensitive beta PDGFR immunosorbent assay. In this assay, beta PDGFR-HFc half-maximally bound to PDGF BB with an affinity of around 150 pM. Suramin, as well as bacterially expressed and refolded human alpha PDGFR domains 1-3, inhibited beta PDGFR-HFc binding to PDGF BB half-maximally at 25 microM and 10 nM respectively. Therefore, alpha PDGFR D1-3, like beta PDGFR D1-3, are sufficient for high affinity PDGF BB binding. Furthermore, the beta PDGFR-HFc immunosorbent assay will be useful to identify beta PDGFR antagonists as well as to study alpha and beta PDGFR substitution mutants which further map receptor binding determinants.
Estrogen Receptor-β Potency-Selective Ligands:  Structure−Activity Relationship Studies of Diarylpropionitriles and Their Acetylene and Polar Analogues (2001)

Through an effort to develop novel ligands that have subtype selectivity for the estrogen receptors alpha (ERalpha) and beta (ERbeta), we have found that 2,3-bis(4-hydroxyphenyl)propionitrile (DPN) acts as an agonist on both ER subtypes, but has a 70-fold higher relative binding affinity and 170-fold higher relative potency in transcription assays with ERbeta than with ERalpha. To investigate the ERbeta affinity- and potency-selective character of this DPN further, we prepared a series of DPN analogues in which both the ligand core and the aromatic rings were modified by the repositioning of phenolic hydroxy groups and by the addition of alkyl substituents and nitrile groups. We also prepared other series of DPN analogues in which the nitrile functionality was replaced with acetylene groups or polar functions, to mimic the linear geometry or polarity of the nitrile, respectively. To varying degrees, all of the analogues show preferential binding affinity for ERbeta (i.e., they are ERbeta affinity-selective), and many, but not all of them, are also more potent in activating transcription through ERbeta than through ERalpha (i.e., they are ERbeta potency-selective). meso-2,3-Bis(4-hydroxyphenyl)succinonitrile and dl-2,3-bis(4-hydroxyphenyl)succinonitrile are among the highest ERbeta affinity-selective ligands, and they have an ERbeta potency selectivity that is equivalent to that of DPN. The acetylene analogues have higher binding affinities but somewhat lower selectivities than their nitrile counterparts. The polar analogues have lower affinities, and only the fluorinated polar analogues have substantial affinity selectivities. This study suggests that, in this series of ligands, the nitrile functionality is critical to ERbeta selectivity because it provides the optimal combination of linear geometry and polarity. Furthermore, the addition of a second nitrile group beta to the nitrile in DPN or the addition of a methyl substitutent at an ortho position on the beta-aromatic ring increases the affinity and selectivity of these compounds for ERbeta. These ERbeta-selective compounds may prove to be valuable tools in understanding the differences in structure and biological function of ERalpha and ERbeta.
Apolipoprotein E-dependent cholesterol efflux from macrophages: kinetic study and divergent mechanisms for endogenous versus exogenous apolipoprotein E (1999)

In these studies, we have utilized a J774 macrophage model in order to compare phospholipid and cholesterol efflux kinetics in macrophage cells that do not express endogenous apoE to cells transfected to express physiologic levels of human apoE. This model was also used to compare the effect of exogenously added versus endogenously expressed apoE on cholesterol efflux kinetics from macrophages. ApoE expression increased free cholesterol and phospholipid efflux into the medium, but did not change the free cholesterol/phospholipid molar ratio of secreted lipids. Kinetic examination showed that free cholesterol and phospholipid appeared simultaneously in the medium, and that cholesterol loading widened the difference in the rate of cholesterol efflux between apoE-expressing and non-expressing macrophages. Addition of exogenous lipid-free apoE added to non-expressing cells, at a >2-fold higher medium concentration than that produced by endogenous expression, produced less cholesterol efflux than that observed from apoE-expressing cells. The addition of phosphatidylcholine liposomes substantially increased cholesterol efflux from apoE-expressing and non-expressing J774 cells. Addition of these liposomes eliminated the enhanced cholesterol efflux produced by addition of exogenous apoE. On the other hand, even in the presence of phosphatidylcholine liposomes, cholesterol efflux rates remained significantly higher from apoE-expressing macrophages than non-expressing cells. Similar results were obtained when efflux was studied in the presence of cyclodextrin. These results suggest that endogenous expression of apoE by macrophages alters cell cholesterol balance via mechanisms distinct from those utilized by the extracellular addition of apoE, and may involve intracellular or pericellular mechanisms.
Reaching for objects in VR displays (1994)

This article reports the results from three experimental studies of reaching behavior in a head-coupled stereo display system with a hand-tracking subsystem for object selection. It is found that lag in the head-tracking system is relatively unimportant in predicting performance, whereas lag in the hand-tracking system is critical. The effect of hand lag can be modeled by means of a variation on Fitts' Law with the measured system lag introduced as a multiplicative variable to the Fitts' Law index of difficulty. This means that relatively small lags can cause considerable degradation in performance if the targets are small. Another finding is that errors are higher for movement in and out of the screen, as compared to movements in the plane of the screen, and there is a small (10%) time penalty for movement in the Z direction in all three experiments. Low frame rates cause a degradation in performance; however, this can be attributed to the lag which is caused by low frame rates, particularly if double buffering is used combined with early sampling of the hand-tracking device.
Biodistribution of 18F- and 125I-labeled anti-Tac disulfide-stabilized Fv fragments in nude mice with interleukin 2 alpha receptor-positive tumor xenografts. (1995)

We evaluated the biodistribution, pharmacokinetics, and generation of catabolites of an 18F- and 125I-labeled anti-Tac disulfide-stabilized Fv fragment (dsFv) in tumor-bearing nude mice. This dsFv is genetically engineered from a murine monoclonal antibody that recognizes the alpha subunit of the interleukin 2 (IL-2 alpha) receptor. Labeling was performed with 18F using N-succinimidyl 4-([18F]fluoromethyl)benzoate or with 125I using the Iodo-Gen method. The immunoreactivities of the radiolabeled anti-Tac dsFv were > 82%. The biodistribution was evaluated (at 15, 45, and 90 min and 6 h) in athymic nude mice (approximately five/group) bearing s.c. tumor xenografts. Cell line A431 served as the IL-2 receptor-negative control tumor, whereas the ATAC4 cell line served as our IL-2 receptor-positive tumor. Animals received injections of 18F-labeled anti-Tac dsFv (0.7-1.4 megabecquerels/1.5-3 micrograms) and 125I-labeled anti-Tac dsFv (0.1-0.4 megabecquerels/0.9-1 microgram). Blood clearance for both preparations was rapid, with < 10% retained in the blood by 15 min. Maximum accumulation in ATAC4 tumors occurred between 45 and 90 min and peaked at a mean of 4.2% injected dose/g (18F) and 5.6% of injected dose/g (125I). At 6 h, the ATAC4 tumors contained 11 times more 18F and 3 times more 125I than did the A431 tumors. The ATAC4 tumor:blood ratios for the 18F and 125I were > 12:1 and > 1.4:1 at 6 h, respectively, whereas the ratios for the antigen-negative A431 tumor were less than 1. The kidneys were the major route of elimination. Catabolites appeared quickly and were identified as [125I]iodide and predominantly N-epsilon-[18F]4-fluoromethylbenzoyl(alpha-N-acetyl) lysine. This is the first study to evaluate the biodistribution of an 18F-labeled Fv fragment in vitro and in vivo. In vivo, the dsFv was taken up rapidly by the kidneys, producing lysine-containing catabolites for 18F-labeled dsFv and [125I]iodide for 125I-labeled dsFv.
Review article: the prevalence and clinical relevance of cytochrome P450 polymorphisms (2007)

In the future genotyping should be considered to identify patients who might be at risk of severe toxic responses, in order to guide appropriate individual dosage. Medical therapy should be a close cooperation between clinicians, pharmacologists and laboratory specialists, leading to reduced therapeutic errors, ADRs and health care costs.
Recent trends in library design: 'rational design' revisited. (2008)

Diversity has historically played a critical role in the design of combinatorial libraries, screening sets and corporate collections for lead discovery. Large library design dominated the field of lead discovery in the 1990s, with design methods ranging from arbitrary and property-based reagent selection to product-based approaches. Over time, however, there has been a downward trend in library size as the genomics revolution and the increasing availability of target protein structures from X-ray crystallography and homology modeling have increased the volume of information concerning desired targets. Concurrently, computing grids and CPU clusters have facilitated the development of structure-based tools that are able to screen hundreds of thousands of molecules. Smaller, 'smarter' combinatorial and focused parallel libraries have replaced the unfocused large libraries in the drug design paradigm of the 21st century. While diversity continues to play a role in lead discovery, the focus of current library design methods has shifted to scaffold design and bio-isostere searching, with a greatly needed emphasis on synthetic feasibility.
In vivo quantum dot labeling of mammalian stem and progenitor cells (2007)

Fluorescent semiconductor nanocrystal quantum dots (QDs) are a class of multifunctional inorganic fluorophores that hold great promise for clinical applications and biomedical research. Because no methods currently exist for directed QD-labeling of mammalian cells in the nervous system in vivo, we developed novel in utero electroporation and ultrasound-guided in vivo delivery techniques to efficiently and directly label neural stem and progenitor cells (NSPCs) of the developing mammalian central nervous system with QDs. Our initial safety and proof of concept studies of one and two-cell QD-labeled mouse embryos reveal that QDs are compatible with early mammalian embryonic development. Our in vivo experiments further show that in utero labeled NSPCs continue to develop in an apparent normal manner. These studies reveal that QDs can be effectively used to label mammalian NSPCs in vivo and will be useful for studies of in vivo fate mapping, cellular migration, and NSPC differentiation during mammalian development.
CMOS Circuit Design, Layout, and Simulation (1997)

The Third Edition of CMOS Circuit Design, Layout, and Simulation continues to cover the practical design of both analog and digital integrated circuits, offering a vital, contemporary view of a wide range of analog/digital circuit blocks including: phase-locked-loops, delta-sigma sensing circuits, voltage/current references, op-amps, the design of data converters, and much more. Regardless of one's integrated circuit (IC) design skill level, this book allows readers to experience both the theory behind, and the hands-on implementation of, complementary metal oxide semiconductor (CMOS) IC design via detailed derivations, discussions, and hundreds of design, layout, and simulation examples.
Robust learning algorithmfor blind separation of signals (1994)

The authors present a novel, efficient, self-normalising, unsupervised adaptive learning algorithm for the on-line (real-time) separation of statistically independent unknown source signals from a linear mixture of them. In contrast to the known algorithms the new algorithm allows the separation (or extraction) of extremely badly scaled signals (i.e. some or even all of the source and/or sensor signals can be very weak). Moreover, the mixing matrix can be very ill-conditioned.
Dissection of the methyl-CpG binding domain from the chromosomal protein MeCP2 (1993)

MeCP2 is a chromosomal protein which binds to DNA that is methylated at CpG. In situ immunofluorescence in mouse cells has shown that the protein is most concentrated in pericentromeric heterochromatin, suggesting that MeCP2 may play a role in the formation of inert chromatin. Here we have isolated a minimal methyl-CpG binding domain (MBD) from MeCP2. MBD is 85 amino acids in length, and binds exclusively to DNA that contains one or more symmetrically methylated CpGs. MBD has negligable non-specific affinity for DNA, confirming that non-specific and methyl-CpG specific binding domains of MeCP2 are distinct. In vitro footprinting indicates that MBD binding can protect a 12 nucleotide region surrounding a methyl-CpG pair, with an approximate dissociation constant of 10(-9) M.
Domains of tau Protein and Interactions with Microtubules (1994)

The role of the neuronal microtubule-associated protein tau has been studied by generating a series of tau constructs differing in one or several of its subdomains: length and composition of the repeat domains, extensions of the repeats in the N- or C-terminal direction, constructs without repeats, assembly vs projection domain, and number of N-terminal inserts. The interaction of the mutant tau proteins with microtubules was judged by several independent methods. (i) Direct binding assays between tau and taxol-stabilized microtubules yield dissociation constants and stoichiometries. (ii) Light scattering and X-ray scattering of assembling microtubule solutions reflect the capacity of tau to promote microtubule nucleation, elongation, and bundling in bulk solution. (iii) Dark field microscopy of assembling microtubules allows one to assess the efficiency of nucleation and bundling separately. The repeat region alone, the N-terminal domains alone, or the C-terminal tail alone binds only weakly to microtubules. However, binding is strongly enhanced by combinations such as the repeat region plus one or both of the flanking regions which could be viewed as "jaws" for tau on the microtubule surface (the proline-rich domain P upstream of the repeats and the "fifth" repeat R' downstream). Such combinations make tau's binding productive in terms of microtubule assembly and stabilization, while the combination of the flanking regions without repeats binds only unproductively. Efficient nucleation parallels strong binding in most cases, i.e., when a construct binds tightly to microtubules, it also nucleates them efficiently and vice versa. In addition, the proline-rich domain P in combination with the repeats R or the flanking domain R' causes pronounced bundling. This effect disappears when the N-terminal domains (acidic or basic) are added on, suggesting that the tau isoforms are not "bundling proteins" in the proper sense. In spite of the wide range of binding strength and nucleation efficiency, the stoichiometries of binding are rather reproducible (around 0.5 tau/tubulin dimer); this is in remarkable contrast to the effect of certain types of phosphorylation which can strongly reduce the stoichiometry.
Plant Biotechnology and Molecular Markers (2005)

In Vitro Androgenesis: Events Preceding Its Cytological Manifestation.- Doubled Haploids: A Powerful Biotechnological Tool for Genetic Enhancement in Oilseed Brassicas.- Double Fertilisation in vitro and Transgene Technology.- Polymorphism of Sexual and Somatic Embryos as Manifestation of Their Developmental Parallelism under Natural Conditions and in Tissue Culture.- Molecular Biology and Genetic Engineering of Polyamines in Plants.- Biotechnological Approaches Towards Improvement of Medicinal Plants.- Production of Phytochemicals in Plant Cell Bioreactors.- Development of Biotechnology for Commiphora wightii: A Potent Source of Natural Hypolipidemic and Hypocholesterolemic Drug.- Biotechnology in Quality Improvement of Oilseed Brassicas.- Role of Biotechnology for Incorporating White Rust Resistance in Brassica Species.- Current Trends in Forest Tree Biotechnology.- Cloning Forestry Species.- Micropropagation of Woody Plants.- Biotechnology in Mulberry (Morus spp.) Crop Improvement: Research Directions and Priorities.- Development of High Efficiency Micropropagation Protocol of an Adult Tree-Wrightia tomentosa.- In Vitro Regeneration and Improvement in Tropical Fruit Trees: An Assessment.- Tissue Culture of Cashewnut.- Changing Scenarios in Indian Horticulture.- Cryopreservation: A Potential Tool for Long-term Conservation of Medicinal Plants.- Molecular Mapping and Marker Assisted Selection of Traits for Crop Improvement.- Studies on Male Meiosis in Cultivated and Wild Vigna Species.- Transgenic Crops for Abiotic Stress Tolerance.- Cell Differentiation in Shoot Meristem: A Molecular Perspective.
Structure of products prepared by freeze-drying solutions containing organic solvents. (1985)

An increasing number of parenteral products are being prepared by freeze-drying techniques. In this method, a sterile aqueous solution of the drug is frozen in a sterile container and the ice and bound water are removed aseptically by sublimation and vacuum drying, respectively. The method reduces the particulate contamination and improves the product quality. The purity of the product may be increased and the dissolution rate on reconstitution is enhanced. Solutions of pharmaceutical powders, prepared for freeze-drying often contain various concentrations of organic solvent. The solvents may be added to reduce the degradation rate of the active material in water during processing or may be present as a residual impurity in the pharmaceutical powder or bulk intermediate used to prepare the freeze-drying solution. The presence of organic solvents affects the freezing characteristics of products cooled by conventional techniques. The solvents may freeze or remain present as an unfrozen liquid residue distributed throughout the ice matrix as an interconnecting capillary network. The solvents retain varying quantities of associated water and various concentrations of dissolved drug. The volumes vary and are related to the hydrophilic properties of the solvent. The presence of solvents affects the rate of drying and influences the choice of plant design, the production capacity, and the product quality. Products which are frozen, dry rapidly by direct sublimation drying. In semi-frozen systems, the products dry more slowly by the simultaneous sublimation of ice and the evaporation of the liquid solvents. In this paper, the freeze-drying properties of a number of drug solutions containing various organic solvents have been studied. Several drugs have been processed from aqueous solution containing up to 20% of ethanol, n. propanol, n. and tert. butanol, ethylacetate, dimethyl carbonate, acetonitrite, dichloromethane, methylethyl ketone, and methylisobutyl ketone. The studies have been conducted in a small research dryer and in both pilot plant and large scale industrial freeze dryers. In this paper, the principles of the methods are reviewed and the physical chemistry of the operation is discussed. The mechanisms of freeze-drying are elucidated and the characteristics of the finished products are compared.
A New Glycopeptide Antibiotic, OA-7653, Produced byStreptomyces hygroscopicussubsp.hiwasaensis (1983)

A new glycopeptide antibiotic, OA-7653, was isolated and purified from the culture broth of an actinomycete, designated as Streptomyces hygroscopicus subsp. hiwasaensis subsp. nov. OA-7653 appears to be most analogous to vancomycin in that it is a water-soluble compound with an ultraviolet absorption maximum at around 280 nm, containing only glucose as a neutral carbohydrate component and active against Gram-positive bacteria. The antibiotic exhibited moderate antimicrobial activities against Gram-positive bacteria including Mycobacterium and showed very low toxicity. It inhibited specifically the synthesis of cell wall peptidoglycan in bacteria.
2‐Thioindoles as Precursors to Spiro‐Fused Indolines: Synthesis of (±)‐Dehaloperophoramidine (2006)

Closing the ring: The cyclization of a 2-thioindole with an electrophilic substituent serves as the key transformation in a synthetic strategy for the generation of indole alkaloids of the perophoramidine and communesin class. DBU=1,8-diazabicyclo[5.4.0]undec-7-ene, Ms=methanesulfonyl chloride. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z601278_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.
Genetically engineered broad-spectrum disease resistance in tomato (1998)

Resistance in tomato to the bacterial pathogen Pseudomonas syringae pathovar tomato requires Pto and Prf. Mutations that eliminate Prf show a loss of both Pto resistance and sensitivity to the organophosphate insecticide fenthion, suggesting that Prf controls both phenotypes. Herein, we report that the overexpression of Prf leads to enhanced resistance to a number of normally virulent bacterial and viral pathogens and leads to increased sensitivity to fenthion. These plants express levels of salicylic acid comparable to plants induced for systemic acquired resistance (SAR) and constitutively express pathogenesis related genes. These results suggest that the overexpression of Prf activates the Pto and Fen pathways in a pathogen-independent manner and leads to the activation of SAR. Transgene-induced SAR has implications for the generation of broad spectrum disease resistance in agricultural crop plants.