gebhart/patrepeval huggingface dataset:
Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs (2011)

Corneas treated with ketorolac 0.45% healed as rapidly as those treated with MEM, likely secondary to addition of CMC and removal of BAK. In the ex vivo corneal organ culture model, ketorolac 0.45% had statistically less impact on corneal re-epithelialization than prior ketorolac formulations (0.4% and 0.5%), bromfenac 0.09%, and nepafenac 0.01%.
Comparative genome assembly (2004)

One of the most complex and computationally intensive tasks of genome sequence analysis is genome assembly. Even today, few centres have the resources, in both software and hardware, to assemble a genome from the thousands or millions of individual sequences generated in a whole-genome shotgun sequencing project. With the rapid growth in the number of sequenced genomes has come an increase in the number of organisms for which two or more closely related species have been sequenced. This has created the possibility of building a comparative genome assembly algorithm, which can assemble a newly sequenced genome by mapping it onto a reference genome. We describe here a novel algorithm for comparative genome assembly that can accurately assemble a typical bacterial genome in less than four minutes on a standard desktop computer. The software is available as part of the open-source AMOS project.
Imaging layers for the directed assembly of block copolymer films: Dependence of the physical and chemical properties of patterned polymer brushes on brush molecular weight (2007)

The directed assembly of polystyrene-block-poly(methyl methacrylate) films using chemically nanopatterned polymer brush surfaces with various molecular weights was investigated. The brushes (3–10nm in thickness) were made from polystyrene that was end grafted to silicon wafers and patterned to have 40–60nm period stripes consisting of unmodified polymer and polymer that was subjected to brief oxygen plasma. The best assembly of block copolymer films was achieved using brushes with molecular weights of 3kg∕mol or less. The brushes were analyzed by goniometry, infrared reflection-absorption spectroscopy, x-ray photoelectron spectroscopy, and ellipsometry. The brush thickness increased nonlinearly with molecular weight and the high molecular weight brushes reconstructed under solvent and thermal annealing. The lower molecular weight brushes form the best imaging layers due to their optimum thickness that provides uniform surface coverage and prevents reconstruction of the film surface. The thin brushes ensure contact between the block copolymer and the hydrophilic groups in the modified regions of the brush during annealing, maximizing the effective interfacial energy contrast and the driving force for perfect directed assembly.
Ligand binding and antigenic properties of a human neonatal Fc receptor with mutation of two unpaired cysteine residues (2008)

The neonatal Fc receptor (FcRn) is a major histocompatibility complex class I-related molecule that regulates the half-life of IgG and albumin. In addition, FcRn directs the transport of IgG across both mucosal epithelium and placenta and also enhances phagocytosis in neutrophils. This new knowledge gives incentives for the design of IgG and albumin-based diagnostics and therapeutics. To study FcRn in vitro and to select and characterize FcRn binders, large quantities of soluble human FcRn are needed. In this report, we explored the impact of two free cysteine residues (C48 and C251) of the FcRn heavy chain on the overall structure and function of soluble human FcRn and described an improved bacterial production strategy based on removal of these residues, yielding approximately 70 mg.L(-1) of fermentation of refolded soluble human FcRn. The structural and functional integrity was proved by CD, surface plasmon resonance and MALDI-TOF peptide mapping analyses. The strategy may generally be translated to the large-scale production of other major histocompatibility complex class I-related molecules with nonfunctional unpaired cysteine residues. Furthermore, the anti-FcRn response in goats immunized with the FcRn heavy chain alone was analyzed following affinity purification on heavy chain-coupled Sepharose. Importantly, purified antibodies blocked the binding of both ligands to soluble human FcRn and were thus directed to both binding sites. This implies that the FcRn heavy chain, without prior assembly with human beta2-microglobulin, contains the relevant epitopes found in soluble human FcRn, and is therefore sufficient to obtain binders to either ligand-binding site. This finding will greatly facilitate the selection and characterization of such binders.
Preparation of Spherical LiCoO<sub>2</sub> Powders by the Ultrasonic Spray Decomposition and Its Application to Cathode Active Material in Lithium Secondary Battery (1993)

Spherical LiCoO2 fine powders were prepared by the ultrasonic spray decomposition. The effect of synthesis factors on particle morphology, particle size and its distribution, and crystallinity was investigated. LiCoO2 was obtained by the spray decomposition at 500°C. Asprepared powders were porous and nonagglomerated particles with sub-micrometer sizes having narrow size distribution. The particle size and crystallinity were dependent on the synthesis conditions. However, the particle size distribution was not affected by the synthesis conditions. LiCoO2 powders were used as cathode active material for lithium secondary battery and its charge/discharge property was investigated. The charge/discharge voltage of lithium secondary battery was 3.9V.
Genetic suppressor elements: new tools for molecular oncology--thirteenth Cornelius P. Rhoads Memorial Award Lecture. (1995)

Genetic suppressor elements (GSEs) are short biologically active gene fragments that encode dominantly acting peptides or inhibitory antisense RNAs. GSEs can be isolated from a single gene or from a multigene complex by constructing a library of short random fragments of the target gene(s) in an expression vector, followed by expression selection for the desired phenotype in a suitable cellular system. GSE selection from a single gene allows one to develop efficient and specific inhibitors of the gene function and to identify functional protein domains. GSE selection from a multigene complex, such as a normalized (uniform abundance) cDNA population from mammalian cells, makes it possible to identify genes that are involved in selectable cellular phenotypes. The potential of GSE selection for uncovering novel gene functions was first demonstrated using bacteriophage lambda as a model system. GSE selection in retroviral expression vectors has been applied in mammalian cells to identify genes responsible for sensitivity to etoposide and other chemotherapeutic drugs. GSE selection is also useful for cloning and analysis of tumor suppressor genes and can be applied to identifying tumor-specific targets for future anticancer drugs. Investigators should find this experimental strategy applicable to many different areas of medical and biological research.
Outcome of Transplantation of Autologous Retinal Pigment Epithelium in Age-Related Macular Degeneration: A Prospective Trial (2004)

Patients undergoing fCNV removal with autologous transplantation of RPE reached significantly better reading acuity and higher mfERG-response density than control subjects. The results provide evidence that autologous transplantation of RPE is a beneficial supplement to membrane excision alone in patients with fCNV in AMD and may be regarded as a reasonable treatment option.
Gamma‐linolenic acid treatment of rheumatoid arthritis. A randomized, placebo‐controlled trial (1996)

GLA at doses used in this study is a well-tolerated and effective treatment for active RA. GLA is available as a component of several plant seed oils and is usually taken in far lower doses than were used in this trial. It is not approved in the United States for the treatment of any condition, and should not be viewed as therapy for any disease. Further controlled studies of its in RA are warranted.
WEAVE: WEb Applications Validation Environment (2009)

Ensuring software quality in the presence of multiple software development methodologies such as agile and waterfall models is a challenging task. Web applications are released to customers in “Beta” mode due to tremendous pressure on “time-to-market”. In order to check end-to-end functional behavior of web applications, conventional testing tools have not matched short release cycles and have not kept up with agile software methodologies. In this paper we present a tool framework called WEb Applications Validation Environment (WEAVE) for checking functional behavior such as business logic and security of web applications. We have used WEAVE for finding defects in large Javacentric commercial-strength Web applications. As part of WEAVE, we have developed (1) a semi-automatic method for environment generation to constrain the behavior of the application for scalability, (2) an intuitive interface for engineers to construct requirements that are compiled into temporal logic to address the issue of usability, and (3) symbolic execution tailored to finding business logic and security defects. We describe how we have architected WEAVE as a web service for company's internal software teams to improve software quality without an upfront investment in licenses and computing infrastructure.
Molecular Insights into Burkholderia pseudomallei and Burkholderia mallei Pathogenesis (2010)

Burkholderia pseudomallei and Burkholderia mallei are closely related gram-negative bacteria that can cause serious diseases in humans and animals. This review summarizes the current and rapidly expanding knowledge on the specific virulence factors employed by these pathogens and their roles in the pathogenesis of melioidosis and glanders. In particular, the contributions of recently identified virulence factors are described in the context of the intracellular lifestyle of these pathogens. Throughout this review, unique and shared virulence features of B. pseudomallei and B. mallei are discussed.
Clinical use of the total dose intravenous infusion of iron dextran. (1988)

Eighty-seven patients with anemia and absent bone marrow hemosiderin were given treatment with total dose intravenous infusions of iron dextran. The effect of rate of infusion and premedication with diphenhydramine, aspirin, and methylprednisolone on acute and delayed reactions was assessed. All patients were monitored for 72 hours after infusion. Two patients reacted to the test dose. One responded with generalized body pain that lasted approximately 5 minutes. In one an anaphylactoid reaction developed, which was promptly terminated by intravenous methylprednisolone, subcutaneous epinephrine, and intravenous diphenhydramine. Transient delayed adverse reactions easily controlled by nonsteroidal anti-inflammatory drugs occurred in 37 patients. The most common delayed reaction was a syndrome characterized by arthralgia, myalgia, and fever. Seven subjects had a chronic disease in addition to anemia with absent bone marrow iron. In all seven normal hemoglobin and hematocrit values were attained after treatment. The results of our experience with total dose intravenous iron dextran therapy suggest that it be the preferred method of replenishment in clinical situations where parenteral administration of iron is indicated. An unexpected benefit was the efficaciousness of this method of administration in patients with iron deficiency and coexisting chronic disease. A protocol for its administration is proposed.
A comparison of the Thrombelastograph and the ROTEM (2007)

Elastic modulus-based assessment of hemostasis in clinical and research settings has been conducted for nearly 60 years. Two systems utilizing this technology include the Thrombelastograph (Haemoscope Corporation, Niles, Illinois, USA) and the ROTEM (Pentapharm GmbH, Munich, Germany). The study goal was to compare the Thrombelastograph and the ROTEM to determine whether differences in data could be detected. Plasma (n = 8 per condition) was not activated (native); was celite-activated, hypocoagulable by dilution with hydroxyethyl starch; was celite-activated, normal; and was celite-activated, hypercoagulable by addition of fibrinogen. Equivalent ratios of plasma mixture to CaCl2 were maintained between the Thrombelastograph and ROTEM systems. Data collected included the reaction time, angle, maximum amplitude and maximum elastic modulus. The ROTEM system generated significantly (P<0.05) smaller reaction time (mean +/- SD, 459 +/- 39 versus 788 +/- 94 s) and greater angle (60.1 +/- 5.3 versus 46.4 +/- 4.6 degrees ), maximum amplitude (27.6 +/- 1.6 versus 24.4 +/- 1.4 mm) and maximum elastic modulus (1911 +/- 152 versus 1616 +/- 121 dynes/cm2) values with native plasma compared with the Thrombelastograph. Celite-activation tended to attenuate differences between the two systems. In conclusion, a comparison of the Thrombelastograph and the ROTEM with similar samples demonstrated clinically significant differences in the data generated without exogenous activation. Given these data and the differences in proprietary activator, divergent results are expected, perhaps affecting clinical decision-making.
Characterization of an Adenovirus Gene Transfer Vector Containing an E4 Deletion (1995)

We describe the construction and characterization of an adenovirus type 2 vector, Ad2E4ORF6, which has been modified in the E4 region to contain only open reading frame 6. When assayed in cultured cells, Ad2E4ORF6 virus replication is slightly delayed but viral DNA synthesis, host-cell protein synthesis shut-off, and virus yield are indistinguishable from wild type. Late protein synthesis is normal with the exception of fiber synthesis, which is reduced approximately 10-fold. Despite the reduced fiber synthesis, Ad2E4ORF6 viral particles appear to contain a full complement of fiber protein. Virus replication in cotton rats indicates that Ad2E4ORF6 is replication defective in vivo. This may have safety implications for the development adenovirus vectors in that virus arising by recombination in the E1 region of an Ad2E4ORF6-based vector would be defective for growth in vivo. The deletion of E4 open reading frames that are not required for virus growth in vitro increases the cloning capacity of adenovirus vectors by 1.9 kb and may be generally useful for the construction of adenovirus vectors containing large cDNA inserts and/or regulatory elements. We describe the inclusion of the A2E4ORF6 modification in a recombinant adenovirus vector, Ad2/CFTR-2, for gene transfer of the human cystic fibrosis transmembrane regulator (CFTR). Adenoviruses are increasingly being utilized as vectors for efficient gene transfer. Simple E1 replacement vectors that retain E3 have a cloning capacity of approximately 5 kb. To accommodate large cDNA inserts or expression cassettes, we chose to increase vector cloning capacity by deleting open reading frames of E4 that are nonessential for virus growth in cultured cells. A new adenovirus vector, Ad2E4ORF6, has been modified in the E4 region to contain only open reading frame 6. Although this vector is replication competent in vitro, it is replication defective in vivo. Incorporation of this partial E4 deletion into a new vector for cystic fibrosis gene therapy, Ad2/CFTR-2, has alleviated the poor growth characteristics observed with a previously described vector, Ad2/CFTR-1.
Spinal cord stimulation attenuates augmented dorsal horn release of excitatory amino acids in mononeuropathy via a GABAergic mechanism (1997)

Neuropathic pain may be effectively relieved by electric stimulation of the spinal cord (SCS). However, the underlying mechanisms for the ensuing pain relief are poorly understood. In a rat model of neuropathy displaying hypersensitivity to innocuous tactile stimuli, (allodynia), we have earlier demonstrated that SCS may normalise withdrawal response thresholds. In the present study, using microdialysis, it is shown that SCS induces a decreased release of the dorsal horn excitatory amino acids (EAA), glutamate and aspartate, concomitant with an increase of the GABA release. Local perfusion with a GABA(B)-receptor antagonist in the dorsal horn transiently abolishes the SCS-induced suppression of the EAA release. Thus, the effect of SCS on neuropathic pain and allodynia may be due to an activation of local GABAergic mechanisms inhibiting the EAA release which is chronically elevated in such conditions.
Oxidase activity of a flavin‐dependent thymidylate synthase (2009)

Flavin-dependent thymidylate synthases (FDTS) catalyze the production of dTMP from dUMP and N(5),N(10)-methylene-5,6,7,8-tetrahydrofolate (CH(2)H(4)folate). In contrast to human and other classical thymidylate synthases, the activity of FDTS depends on a FAD coenzyme, and its catalytic mechanism is very different. Several human pathogens rely on this recently discovered enzyme, making it an attractive target for novel antibiotics. Like many other flavoenzymes, FDTS can function as an oxidase, which catalyzes the reduction of O(2) to H(2)O(2), using reduced NADPH or other reducing agents. In this study, we exploit the oxidase activity of FDTS from Thermatoga maritima to probe the binding and release features of the substrates and products during its synthase activity. Results from steady-state and single-turnover experiments suggest a sequential kinetic mechanism of substrate binding during FDTS oxidase activity. CH(2)H(4)folate competitively inhibits the oxidase activity, which indicates that CH(2)H(4)folate and O(2) compete for the same reduced and dUMP-activated enzymatic complex (FDTS-FADH(2)-NADP(+)-dUMP). These studies imply that the binding of CH(2)H(4)folate precedes NADP(+) release during FDTS activity. The inhibition constant of CH(2)H(4)folate towards the oxidase activity was determined to be rather small (2 microm), which indicates a tight binding of CH(2)H(4)folate to the FDTS-FADH(2)-NADP(+)-dUMP complex.
Accelerated image reconstruction using ordered subsets of projection data (1994)

The authors define ordered subset processing for standard algorithms (such as expectation maximization, EM) for image restoration from projections. Ordered subsets methods group projection data into an ordered sequence of subsets (or blocks). An iteration of ordered subsets EM is defined as a single pass through all the subsets, in each subset using the current estimate to initialize application of EM with that data subset. This approach is similar in concept to block-Kaczmarz methods introduced by Eggermont et al. (1981) for iterative reconstruction. Simultaneous iterative reconstruction (SIRT) and multiplicative algebraic reconstruction (MART) techniques are well known special cases. Ordered subsets EM (OS-EM) provides a restoration imposing a natural positivity condition and with close links to the EM algorithm. OS-EM is applicable in both single photon (SPECT) and positron emission tomography (PET). In simulation studies in SPECT, the OS-EM algorithm provides an order-of-magnitude acceleration over EM, with restoration quality maintained.
Bioisosterism:  A Rational Approach in Drug Design (1996)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBioisosterism: A Rational Approach in Drug DesignGeorge A. Patani and Edmond J. LaVoieView Author Information Department of Pharmaceutical Chemistry, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08855-0789 Cite this: Chem. Rev. 1996, 96, 8, 3147–3176Publication Date (Web):December 19, 1996Publication History Received15 May 1996Revised25 July 1996Published online19 December 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/cr950066qhttps://doi.org/10.1021/cr950066qresearch-articleACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views22046Altmetric-Citations1027LEARN 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 SUBJECTS:Bioactivity,Hydroxyls,Inhibition,Peptides and proteins,Receptors Get e-Alerts
Replication and segregation of plasmids containing cis-acting regulatory sites of silent mating-type genes in Saccharomyces cerevisiae are controlled by the SIR genes. (1987)

In Saccharomyces cerevisiae, two cis-acting regulatory sites called E and I flank the silent mating-type gene, HMRa, and mediate SIR-dependent transcriptional repression of the a1-a2 promoters. It has been shown previously that the E and I sites have plasmid replicator (ARS) activity. We show in this report that the ARS activity of the E and I sites is governed by the SIR genotype of the cell. In wild-type cells, a plasmid carrying the E site from HMRa (HMR E) in the vector YIp5 exhibited very high mitotic stability at a copy number of approximately 25 per cell. However, in sir2, sir3, or sir4 mutants, plasmids with HMR E had the low mitotic stability characteristic of plasmids containing ARS1, a SIR-independent replicator. Elevated mitotic stability of plasmids that carry HMR E is due to a segregation mechanism provided by SIR and HMR E. In sir2 and sir4 mutants, the plasmid copy number was significantly lowered, suggesting that these gene products also participate in the replication of plasmids carrying HMR E. The phenotype of point mutations introduced at an 11-base-pair ARS consensus sequence present at HMR E indicated that this sequence is functional but not absolutely required for autonomous replication of the plasmid and that it is not required for SIR-dependent mitotic stabilization. A plasmid carrying both a centromere and HMR E exhibited reduced mitotic stability in wild-type cells. This destabilization appeared to be due to antagonism between the segregation functions provided by the centromere and by HMR E.