gebhart/patrepeval huggingface dataset:
Topical Ocular Drug Delivery: Recent Developments and Future Challenges (1986)

Existing ocular drug delivery systems are fairly primitive and inefficient, but the stage is set for the rational design of newer and significantly improved systems. The focus of this review is on recent developments in topical ocular drug delivery systems relative to their success in overcoming the constraints imposed by the eye and to the improvements that have yet to be made. In addition, this review attempts to place in perspective the importance of pharmacokinetic modeling, ocular drug pharmacokinetic and bioavailability studies, and choice of animal models in the design and evaluation of these delivery systems. Five future challenges are perceived to confront the field. These are: (a) The extent to which the protective mechanisms of the eye can be safely altered to facilitate drug absorption, (b) Delivery of drugs to the posterior portion of the eye from topical dosing, (c) Topical delivery of macromolecular drugs including those derived from biotechnology, (d) Improved technology which will permit non-invasive monitoring of ocular drug movement, and (e) Predictive animal models in all phases of ocular drug evaluation.
Molecular modeling and preclinical evaluation of the humanized NR-LU-13 antibody. (1999)

A mouse-human chimeric monoclonal antibody (chNR-LU-13), specific for the EGP40 pancarcinoma antigen, was humanized through three-dimensional molecular modeling. Humanization of the chNR-LU-13 antibody is expected to enhance its use for patients undergoing immunotherapy. On the basis of the observed amino acid sequence identity, chNR-LU-13 complementary determining regions (CDRs) of the V(L) and V(H) regions were grafted onto the human anti-DNA-associated idiotype immunoglobulin clone, R3.5H5G'CL. Ten amino acids residues within the humanized framework were back-mutated to their corresponding chNR-LU-13 sequence, because they were predicted to disrupt the canonical classification of the CDRs or were within 5 A of a CDR. Synthesis of the V(L) and V(H) regions was accomplished by recursive PCR, and the dual-chain expression vector p451.C4 was positioned under control of the CMV(P+E). We observed by competitive ELISA that the recombinant humanized NR-LU-13 (huNR-LU-13) IgG1 antibody exhibited an indistinguishable immunoreactivity profile when compared with the murine monoclonal antibody (muNR-LU-10). The huNR-LU-13 antibody was effective in mediating both antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity when assayed against either the breast carcinoma cell line, MCF-7, or the colon adenocarcinoma cell line, SW1222. Biodistribution studies using i.v. coinjected 131I-muNR-LU-10 and 125I-huNR-LU-13 confirmed that the huNR-LU-13 specifically targets to the tumor in athymic BALB/c mice bearing the SW1222 human tumor xenograft. Humanization of the chNR-LU-13 antibody is expected to eliminate an undesired human antimouse antibody response, allowing for repeated i.v. administration into humans.
Viscoelastic properties of young and old human dermis: A proposed molecular mechanism for elastic energy storage in collagen and elastin (2002)

Abstract We have studied the strain‐rate dependency of the viscoelastic mechanical properties of human dermis from young (23‐year‐old) and old (87‐year‐old) donors using incremental stress–strain measurements. The elastic spring constant for elastic fibers was found to be strain‐rate and age dependent, whereas that for collagen was only age dependent. Fibril lengths were observed to decrease with increased strain rates and age for both elastic and collagen fibers; however, the large decrease in collagen fibril viscosity was hypothesized to be a result of thixotropy that results when neighboring collagen fibrils slide by each other. It is concluded that the elastic spring constant measured for elastic fibers may be higher than previously reported and is consistent with stretching of α‐helical segments of elastin into a more extended conformation during the initial part of the elastic stress–strain curve. The decrease in the elastic spring constant with increased age observed is consistent with disruption of the elastic fibers and loss of α‐helical structure. The pH dependency of the elastic modulus reported previously for collagen suggests that charge–charge interactions within and between collagen molecules are involved in energy storage during stretching. Elastic energy storage is consistent with the stretching of charged pairs located in flexible regions of the collagen molecule. Shear thinning, or thixotropy of skin, is hypothesized to reflect breakage of bonds that occur between collagen fibrils. It is hypothesized that both collagen and elastin are complex macromolecules that are hybrids of flexible and rigid regions. The flexible regions reversibly store elastic energy during stretching by breakage of secondary bonds. After stretching, the flexible regions become extended and transfer stress to the rigid regions of these molecules. This prevents premature mechanical failure of collagen and elastic fibers in the dermis. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1978–1985, 2002
Necrotizing enterocolitis prophylaxis: oral antibiotics and lyophilized enterobacteria vs oral immunoglobulins (1994)

We conducted a prospective randomized trial to compare the efficacy of oral gentamicin versus oral IgA-IgG for the prophylaxis of necrotizing enterocolitis (NEC); 200 newborns considered at high risk for NEC were assigned to group A (oral IgA-IgG, n = 100) or group B (oral Gentamicin, n = 100). NEC was diagnosed in 13 cases in group A and in 1 case in group B between the 3rd and 16th days of life. Surgical treatment was necessary in 3 cases (2 in group A). All infants survived. We conclude that oral gentamicin is more effective than oral IgA-IgG in the prevention of NEC in infants at high risk.
Facile aerial oxidation of a porphyrin. Part 3. Some metal complexes of meso-tetrakis-(3,5-di-t-butyl-4-hydroxyphenyl)porphyrin (1988)

Metal complexes of the title porphyrin were prepared and their behaviour in basified dichloromethane solution examined using u.v.–visible and e.s.r. spectroscopy. The free base, ZnII, FeIII, and CoII complexes undergo drastic colour changes with rapid and irreversible aerial oxidation. Acidification does not regenerate the porphyrin spectrum, but shaking with aqueous metabisulphite or dithionite does. The VIVO, MnIII, CuII, SnIV, PdII, and PtII complexes also change colour but their metalloporphyrin u.v.–visible spectra largely return on acidification. Some deterioration over time in the returned B band intensity is noted, which is greatest for the NiII complex and is most likely due to autoxidation. E.s.r. spectra, arising from oxidation or autoxidation of the complexes to radical species, were observed for the MnIII, NiII, ZnII, and SnIV complexes, the latter in neutral dichloromethane. This gave a triplet e.s.r. spectrum that decayed with second-order kinetics. Addition of base to the SnIV complex quenched the e.s.r. spectrum. An explanation is offered in which the metal modulates electron transfer onto the macrocycle, from the phenoxy meso-substituents, via back-bonding and changes in porphyrin conformation.
Epitope-Dependent Blocking of the Angiotensin-Converting Enzyme Dimerization by Monoclonal Antibodies to the N-Terminal Domain of ACE:  Possible Link of ACE Dimerization and Shedding from the Cell Surface (2003)

In a biomembrane modeling system, reverse micelles, somatic ACE forms dimers via carbohydrate-mediated interaction, providing evidence for the existence of a carbohydrate-recognizing domain on the ACE molecule. We localized this putative region on the N-domain of ACE using monoclonal antibodies (mAbs) to seven different epitopes of ACE. Two mAbs, 9B9 and 3G8, directed to distinct, but overlapping, epitopes of the N-domain of ACE shielded the CRD. Only "simple" ACE-antibody complexes were found in the system. Five mAbs allowed the formation of "double" antibody-ACE-ACE-antibody complexes via carbohydrate-mediated interactions. The results were confirmed using the ACE N- and C-domains. Testicular ACE was unable to form carbohydrate-mediated ACE dimers in the reverse micelles, while the N-domain of ACE, obtained by limited proteolysis of the parent full-length ACE, retained the ability to form dimers. Furthermore, mAb 3G8, which blocked ACE dimerization in micelles, significantly inhibited ACE shedding from the surface of ACE-expressing cells. Galactose prevented ACE dimerization in reverse micelles and also affected antibody-induced ACE shedding in an epitope-dependent manner. Restricted glycosylation of somatic ACE, obtained by the treatment of CHO-ACE cells with the glucosidase inhibitor N-butyldeoxynojirimycin, significantly increased the rate of basal ACE shedding and altered antibody-induced ACE shedding. A chemical cross-linking approach was used to show that ACE is present (at least in part) as noncovalently linked dimers on the surface of CHO-ACE cells. These results suggest a possible link between putative ACE dimerization on the cell surface and the proteolytic cleavage (shedding) of ACE.
Acquisition of Sensitivity of Stress-activated Protein Kinases to the p38 Inhibitor, SB 203580, by Alteration of One or More Amino Acids within the ATP Binding Pocket (1998)

Pyridinyl imidazole inhibitors of p38 mitogen-activated protein kinase compete with ATP for binding. Mutation of 23 residues in the ATP pocket indicated that several residues which affected binding of pyridinyl imidazole photoaffinity cross-linker 125I-SB 206718 did not affect kinase activity, and vice versa, suggesting that pyridinyl imidazoles bind p38 differently than ATP. Two close homologues of p38, SAPK3 and SAPK4, are not inhibited by SB 203580 and differ from p38 by three amino acids near the hinge of the ATP pocket. Substitution of the three amino acids in p38 by those in SAPK3/4 (Thr-106, His-107, and Leu-108 to Met, Pro, and Phe) resulted in decreased 125I-SB 206718 cross-linking and loss of inhibition by SB 203580. Substitution of just Thr-106 by Met resulted in incomplete loss of inhibition. Conversely, substitution of the three amino acids of p38 into SAPK3, SAPK4, or the more distantly related JNK1 resulted in inhibition by SB 203580, whereas mutation of just Met-106 to Thr resulted in weaker inhibition. These results indicate that these three amino acids can confer specificity and sensitivity to SB 203580 for at least two different classes of MAPKs.
Organocatalyzed Enantioselective Fluorocyclizations (2011)

Enantioenriched fluorinated heterocycles can be prepared through fluorocyclizations of prochiral indoles (see scheme; Ts=tosyl, Bn=benzyl, Boc=tert-butoxycarbonyl). More than twenty examples for this cascade fluorination-cyclization, which is catalyzed by cinchona alkaloids and employs N-fluorobenzenesulfonimide as the electrophilic fluorine source have been explored, and an unprecedented catalytic asymmetric difluorocyclization has also been identified.
Ia-independent binding of peptide antigen to the T cell receptor. (1990)

We have investigated the potential for direct interaction between a peptide Ag, human fibrinopeptide B (hFPB), and the TCR on an hFPB-specific murine T hybridoma. Fluoresceinated hFPB binds specifically to hFPB-responsive T cells, but not to unrelated T hybrids. Among variant subclones of the original hybridoma, ability to bind hFPB correlates with hFPB-specific response and expression of the CD3/TCR complex, indicating that hFPB is binding to the TCR. This TCR-hFPB interaction has an affinity of approximately 6.6 microM, reflecting slow association and rapid dissociation of the Ag from its receptor. These findings confirm the potential for direct Ag-TCR interaction and indicate an Ag recognition mechanism that is not initiated by Ag-MHC interaction.
The Synthesis of Hydrastic Acid (1951)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Synthesis of Hydrastic AcidWilkins Reeve and Herbert MyersCite this: J. Am. Chem. Soc. 1951, 73, 3, 1371–1372Publication Date (Print):March 1, 1951Publication History Published online1 May 2002Published inissue 1 March 1951https://pubs.acs.org/doi/10.1021/ja01147a526https://doi.org/10.1021/ja01147a526research-articleACS PublicationsRequest reuse permissionsArticle Views152Altmetric-Citations6LEARN 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
Classification of Myoviridae bacteriophages using protein sequence similarity (2009)

The hierarchical clustering of these groupings provide biologically significant subdivisions, which are consistent with our previous analysis of the Podoviridae.
Mutations in the WSAWSE and cytosolic domains of the erythropoietin receptor affect signal transduction and ligand binding and internalization. (1992)

The terminal development of erythroid progenitor cells is promoted in part through the interaction of erythropoietin (EPO) with its cell surface receptor. This receptor and a growing family of related cytokine receptors share homologous extracellular features, including a well-conserved WSXWS motif. To explore the functional significance of this motif in the murine EPO receptor, five WSAWSE mutants were prepared and their signal-transducing, ligand binding, and endocytotic properties were compared. EPO receptors mutated at tryptophan residues (W-232, W-235----G; W-235----G; W-235----F) failed to mediate EPO-induced growth or pp100 phosphorylation, while S-236----T and E-237----K mutants exhibited partial to full activity (50 to 100% of wild-type growth and induced phosphorylation). Ligand affinity was reduced for mutant receptors (two- to fivefold), yet expression at the cell surface for all receptors was nearly equivalent. Also, the ability of mutated receptors to internalize ligand was either markedly reduced or abolished (W-235----F), indicating a role for the WSAWSE region in hormone internalization. Interestingly, receptor forms lacking 97% of the cytosolic domain (no signal-transducing capacity; binding affinity reduced two- to threefold) internalized EPO efficiently. This and all WSAWSE receptor forms studied also mediated specific cross-linking of 125I-EPO to three accessory membrane proteins (M(r)s, 120,000, 105,000, and 93,000). These findings suggest that the WSAWSE domain of the EPO receptor is important for EPO-induced signal transduction and ligand internalization. In contrast, although the cytosolic domain is required for growth signaling, it appears nonessential for efficient endocytosis.
Functional mosaic organization of mouse olfactory receptor neurons (2000)

In contrast to rapid progress in the molecular biology of olfaction, there are few physiological data to characterize the odor response properties of different populations of olfactory receptor neurons (ORNs) and their spatial distributions across the epithelium, which is essential for understanding the coding mechanisms underlying odor discrimination and recognition. We have tested the hypothesis that the ORNs are arranged in a functional mosaic, using an intact epithelial preparation from the mouse, in which odor responses of many ORNs in situ can be monitored simultaneously with calcium imaging techniques. ORNs responding to a given odor were widely distributed across epithelium and intermingled with ORNs responding to other odors. Tight clusters of ORNs responding to the same odor were observed. For a given odor, more ORNs were recruited when the concentration was increased. ORNs were able to distinguish between pairs of enantiomers by showing distinct but somewhat overlapping patterns. The results provide evidence regarding the response spectra of ORNs in situ, supporting the combinatorial coding of odor quality and intensity by different ORN subsets.
Homeostasis as Regulated by Activated Macrophage. II. LPS of Plant Origin Other than Wheat Flour and Their Concomitant Bacteria. (1992)

In order to seek a macrophage-activating substance, lipopolysaccharide (LPS) of plant origin other than that of wheat flour was surveyed. A large amount of LPS (10-100 micrograms/g) was detected in Laminaria japonica (kelp), Curcuma longa (turmeric), Undaria pinnatifida and other substances. Since concomitant bacteria possibly existing in root of farm products can be considered to contribute to LPS of plant origin, a count was taken of bacterial cells both dead and alive. This count revealed that some LPS were derived from concomitant bacteria which had probably come from root. Few concomitant bacterial cells were found in seaweed, while stem-root contained enough bacterial cells. Three predominant bacteria have been isolated and identified; Pantoea agglomerans, Enterobacter cloacae, and Serratia ficaria. These LPSs were purified and their chemical compositions were examined. They are similar to that of Escherichia coli except that their molecular sizes are smaller. Since LPS is non-toxic when taken orally or percutaneously, these LPSs may also be advantageous in the cure of intractable diseases.
Quantum Transport in a Multiwalled Carbon Nanotube (1996)

We report on electrical resistance measurements of an individual carbon nanotube down to a temperature $T\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}20\mathrm{mK}$. The conductance exhibits a $\mathrm{ln}T$ dependence and saturates at low temperature. A magnetic field applied perpendicular to the tube axis increases the conductance and produces aperiodic fluctuations. The data find a global and coherent interpretation in terms of two-dimensional weak localization and universal conductance fluctuations in mesoscopic conductors. The dimensionality of the electronic system is discussed in terms of the peculiar structure of carbon nanotubes.
Gaussian Pulse Based Tone Reservation for Reducing PAPR of OFDM Signals (2007)

One of the major drawbacks of OFDM is high peak-to-average power ratio (PAPR) which can result in poor power efficiency and serious distortion in the transmitter amplifier. Tone reservation (TR) is a technique designed to combat this problem by reserving a number of carriers (tones) in the frequency domain to generate a cancellation signal in the time domain to remove high peaks. However TR can have a high associated computational cost due to the difficulties in finding an effective cancellation signal in the time domain by using only a few tones in the frequency domain. In this paper, we propose a novel approach to overcoming this problem by creating a Gaussian pulse as the cancellation signal from only a small number of reserved tones. This facilitates a simple and effective algorithm for reducing peak values while minimizing the occurrence of secondary peaks, the latter being a key factor in contributing to the high computational complexity of tone reservation algorithms.
Collective generation of milliemulsions by step-emulsification (2017)

Milliemulsions are produced by microcapillary films based on step-emulsification and the flow behaviors depend on the geometry and capillary number.
Thrombus imaging with an I-123-labeled F(ab')2 fragment of an anti-human fibrin monoclonal antibody in a rabbit model. (1989)

The murine monoclonal antibody MA-15C5 binds to cross-linked fibrin but not to fibrinogen. Fab or F(ab')2 fragments of MA-15C5, labeled with iodine-123, were injected intravenously into nine rabbits with a nonocclusive 0.2-mL human plasma clot in the jugular vein and into eight control rabbits. Scintigrams obtained at hourly intervals after injection of the F(ab')2 fragment revealed a significantly higher accumulation of tracer in the clot region than in the contralateral region. The relative excess of tracer in the jugular vein region was significantly greater in the study animals than in the control animals throughout the study period. Blind reading of serial scans revealed no visible tracer accumulation in seven of eight control rabbits, whereas the scans of seven of nine study rabbits showed clearly visible accumulation (sensitivity = 77%, specificity = 87%). The Fab fragment of MA-15C5 had a lower affinity and bound less avidly to the blood clot in vivo. These results suggest that the F(ab')2 fragment has better imaging properties than the Fab fragment and that it may be useful for imaging blood clots in man.
A protein tyrosine phosphatase expressed within dopaminoceptive neurons of the basal ganglia and related structures (1993)

Immunocytochemical and biochemical studies were conducted to characterize a brain-specific protein tyrosine phosphatase, designated STEP for striatal enriched phosphatase. STEP immunoreactivity was most intense in select regions of the CNS receiving a dopaminergic input, and was localized to cell bodies, dendrites, and axonal processes. Western blot analyses of rat brain homogenates revealed a triplet of polypeptides with relative mobilities (M(r)) of 46 kDa, 37 kDa, and 33 kDa enriched within the striatum. Phase separation of protein homogenates by Triton X-114 extraction indicated that this triplet was enriched in soluble but not membrane fractions. Affinity-purified STEP fusion protein exhibited phosphatase activity while a mutated form of the STEP fusion protein (Cys300Ser) showed no demonstrable phosphatase activity.
DNA polymerase III accessory proteins. III. holC and holD encoding chi and psi (1993)

Genes encoding the chi and psi accessory proteins of the DNA polymerase III holoenzyme replicase of Escherichia coli have been identified, sequenced, and used to express and purify both chi and psi in quantity. The holC gene encoding chi is located between the xerB and valS genes at 96.5 min on the chromosome; it encodes a 147-amino acid protein of 16.6 kDa. holD encoding psi lies upstream of rimI at 99.3 min and encodes a 137-amino acid protein of 15.2 kDa. The genes have been cloned into expression vectors, and both chi and psi have been purified in quantity. The accompanying report characterizes the function and physical interactions of chi and psi with other holenzyme subunits (Xiao, H., Dong, Z., and O'Donnell, M. (1993) J. Biol. Chem. 268, 11779-11784).
Multimedia systems design (1995)

Informative as well as tutorial, this book explores the design of advanced multimedia systems in depth - the characteristics, design challenges, emerging technologies, methodologies, and implementation techniques. Using coded modules to illustrate design aspects, it covers the underlying data management system, specialized hardware and software, and an advanced user interface - and presents a number of new concepts and methodologies.