gebhart/patrepeval huggingface dataset:
Engineered Biosynthesis of Structurally Diverse Tetraketides by a Trimodular Polyketide Synthase (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTEngineered Biosynthesis of Structurally Diverse Tetraketides by a Trimodular Polyketide SynthaseCamilla M. Kao, Guanglin Luo, Leonard Katz, David E. Cane, and Chaitan KhoslaView Author Information Departments of Chemical Engineering Chemistry, and Biochemistry Stanford University, Stanford, California 94305-5025 Department of Chemistry, Brown University, Box H Providence, Rhode Island 02912 Antiinfective Discovery Research Abbott Laboratories, Abbott Park, Illinois 60064 Cite this: J. Am. Chem. Soc. 1996, 118, 38, 9184–9185Publication Date (Web):September 25, 1996Publication History Received24 May 1996Published online25 September 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja9617552https://doi.org/10.1021/ja9617552rapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views449Altmetric-Citations82LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Alkyls,Biosynthesis,Lactones,Metabolism,Reaction products Get e-Alerts
Aligned Copper Nanorod Arrays for Surface-enhanced Raman Scattering (2007)

Highly ordered copper nanorod arrays have been synthesized using potentiostatic electrodeposition within the confined nanochannels of a porous anodic alumina membrane (PAAM). These arrays were evaluated as potential surface- enhanced Raman scattering (SERS) active substrates using Rhodamine 6G as a reported molecule. SERS activity was shown to depend upon the length of the nanorods exposed to the surface which is controlled by the etching time. The Cu nanorods with average lengths of 200 nm exposed to surface exhibited the maximum SERS enhancement. Theoretical analyses indicate that this large SERS enhancement may be partially explained by the shape, density, and lateral arrangement of the Cu nanorod arrays.
Expression, secretion and folding of human growth hormone in Escherichia coli (1986)

An efficient secretion vector containing a gene coding for an E. coli signal peptide fused to human growth hormone (hGH) was cloned into E. coli. The recombinant fusion protein was expressed and correctly processed hGH was secreted into the periplasmic space at a yield of 10-15 micrograms hGH/A600. Purification of hGH from the periplasmic fraction by anion exchange and size exclusion gave hGH of greater than 90% purity. Characterization by SDS-PAGE, amino terminal analysis, trypsin mapping, and circular dichroism demonstrated that the fusion protein was correctly processed to authentic hGH and that the E. coli periplasm provided an appropriate environment for proper folding of hGH and disulfide bond formation.
One-Pot Synthesis of 5′-Diaryl Esters and Diamidates of Phosphate, Phosphorothioate, and Phosphoroselenoate Derivatives of AZT and d4T (2009)

Abstract Modified nucleosides such as 3′-azido-2′,3′-dideoxythymide (AZT) and 2′,3′-dideoxy-2′,3′-didehydrothymide (d4T) are of importance as antiviral agents and in other medicinal applications. Consequently, there is interest in new analogs of these compounds and in new methods for preparing them. In this article, a simple but efficient, one-pot synthesis of 5′-diaryl esters and diamidates of phosphate, phosphorothioate, and phosphoroselenoate derivatives of AZT and d4T is described. The reaction of AZT/d4T with phosphorus trichloride, followed with phenols, aniline, or amino acid methyl esters in the presence of a base, led to the corresponding tricoordinated phosphite compounds of AZT/d4T, which were then oxidized with 3-chloroperoxybenzoic acid (m-CPBA), sulfur, or selenium powder to finally afford the corresponding target compounds in good yield. Keywords: AZT/d4T pro-drugdiamidate of phosphate5′-diaryl estersphosphoroselenoate derivativesphosphorothioate ACKNOWLEDGMENT The authors thank the National Natural Science Foundation of China (No. 20572061) and the Major Program of National Natural Science Foundation of China (No. 20732004) for financial support. Notes a Isolated yield of the three steps.
Structures of the Cuprous-Thiolate Clusters of the Mac1 and Ace1 Transcriptional Activators (2002)

X-ray absorption spectroscopy on the minimal copper-regulatory domains of the two copper-regulated transcription factors (Ace1 and Mac1) in Saccharomyces cerevisiae revealed the presence of a remarkably similar polycopper cluster in both proteins. The Cu-regulatory switch motif of Mac1 consisting of the C-terminal first Cys-rich motif, designated the C1 domain, binds four Cu(I) ions as does the Cu-regulatory domain of Ace1. The four Cu(I) ions are bound to each molecule in trigonal geometry. An extended X-ray absorption fine structure (EXAFS) arising from outer-shell Cu...Cu interactions at 2.7 and 2.9 A was apparent in each Cu(I) complex indicative of a polycopper cluster. The intensity of the 2.9 A Cu...Cu backscatter peak, apparently diminished by partial cancellation, dominates the EXAFS. The results suggest that CuAce1 and CuMac1(C1) contain somewhat distorted forms of a known [Cu(4)-S(6)] cage in which a core of Cu atoms forming an approximate tetrahedron is bound by bridging thiolates above each of the six edges. The tetracopper clusters bound by Ace1 and Mac1 differ in that the Ace1 cluster is coordinated entirely by cysteinyl thiolate, whereas the cysteine-deficient Mac1 cluster appears to consist of a Cu(4)(S-Cys)(5)(N-His) cluster with a bridging histidyl-derived nitrogen.
Huge Proteins in The Human Proteome and Their Participation in Hereditary Diseases (2006)

Protein lengths vary considerably from a few to thousands of amino acids and length variations are documented to have multiple effects. A computational approach to investigate the functional impact of protein length variation in genetic disorders is presented. The genes for huge proteins are found to have more introns. Our analysis also shows greater involvement of huge proteins in hereditary diseases.
Brain transglutaminase: in vitro crosslinking of human neurofilament proteins into insoluble polymers. (1982)

The accumulation in aged human neurons of insoluble, high molecular weight filamentous polymers apparently linked by nondisulfide covalent bonds led us to examine human brain for the presence of transglutaminase (EC 2.3.2.13) and endogenous protein substrates for this crosslinking enzyme. We demonstrate the presence in brain of a transamidating enzyme that can covalently crosslink brain proteins into insoluble polymers in vitro by forming gamma-glutamyl-epsilon-lysine intermolecular bridges. Brain transglutaminase is Ca2+ dependent, has an electrophoretic mobility similar to that of erythrocyte transglutaminase, and is active in human postmortem brain from aged normal individuals and patients with Alzheimer disease (senile dementia). Brain neurofilament fractions incubated in the presence of transglutaminase, Ca2+, and the fluorescent amine dansylcadaverine form a fluorescent, nondisulfide-bonded insoluble polymer; this process is associated with a decrease in the amount of soluble neurofilament polypeptides in the preparation. Electron microscopy of the polymeric material reveals an extensive network of connecting filaments, which can be immunostained with various neurofilament antisera. Cystamine, an inhibitor of transglutaminase, prevents the neurofilament crosslinking. Glial filaments and myelin basic protein can also serve as substrates of brain transglutaminase in vitro. Although Alzheimer disease-type paired helical filaments are not formed under the specific in vitro conditions employed, the data suggest one possible mechanism for the covalent crosslinking of filaments into insoluble polymers during human neuronal aging.
In vivo administration of a lentiviral vaccine targets DCs and induces efficient CD8+ T cell responses (2003)

The present study evaluates the potential of third-generation lentivirus vectors with respect to their use as in vivo–administered T cell vaccines. We demonstrate that lentivector injection into the footpad of mice transduces DCs that appear in the draining lymph node and in the spleen. In addition, a lentivector vaccine bearing a T cell antigen induced very strong systemic antigen-specific cytotoxic T lymphocyte (CTL) responses in mice. Comparative vaccination performed in two different antigen models demonstrated that in vivo administration of lentivector was superior to transfer of transduced DCs or peptide/adjuvant vaccination in terms of both amplitude and longevity of the CTL response. Our data suggest that a decisive factor for efficient T cell priming by lentivector might be the targeting of DCs in situ and their subsequent migration to secondary lymphoid organs. The combination of performance, ease of application, and absence of pre-existing immunity in humans make lentivector-based vaccines an attractive candidate for cancer immunotherapy.
Systemic bioavailability of fluticasone propionate administered as nasal drops and aqueous nasal spray formulations (2001)

Both formulations exhibited low systemic bioavailability, even at 12 times the normal daily dose. The bioavailability from the nasal drops was approximately eight times lower than from the nasal spray.
Large Genomic Fragment Deletions and Insertions in Mouse Using CRISPR/Cas9 (2015)

ZFN, TALENs and CRISPR/Cas9 system have been used to generate point mutations and large fragment deletions and insertions in genomic modifications. CRISPR/Cas9 system is the most flexible and fast developing technology that has been extensively used to make mutations in all kinds of organisms. However, the most mutations reported up to date are small insertions and deletions. In this report, CRISPR/Cas9 system was used to make large DNA fragment deletions and insertions, including entire Dip2a gene deletion, about 65kb in size, and β-galactosidase (lacZ) reporter gene insertion of larger than 5kb in mouse. About 11.8% (11/93) are positive for 65kb deletion from transfected and diluted ES clones. High targeting efficiencies in ES cells were also achieved with G418 selection, 46.2% (12/26) and 73.1% (19/26) for left and right arms respectively. Targeted large fragment deletion efficiency is about 21.4% of live pups or 6.0% of injected embryos. Targeted insertion of lacZ reporter with NEO cassette showed 27.1% (13/48) of targeting rate by ES cell transfection and 11.1% (2/18) by direct zygote injection. The procedures have bypassed in vitro transcription by directly co-injection of zygotes or co-transfection of embryonic stem cells with circular plasmid DNA. The methods are technically easy, time saving, and cost effective in generating mouse models and will certainly facilitate gene function studies.
Inhibition of human colon cancer cell growth by selective inhibition of cyclooxygenase-2. (1997)

A considerable amount of evidence collected from several different experimental systems indicates that cyclooxygenase-2 (COX-2) may play a role in colorectal tumorigenesis. Large epidemiologic studies have shown a 40-50% reduction in mortality from colorectal cancer in persons taking aspirin or other nonsteroidal antiinflammatory drugs on a regular basis. One property shared by all of these drugs is their ability to inhibit COX, a key enzyme in the conversion of arachidonic acid to prostaglandins. Two isoforms of COX have been characterized, COX-1 and COX-2. COX-2 is expressed at high levels in intestinal tumors in humans and rodents. In this study, we selected two transformed human colon cancer cell lines for studies on the role of COX-2 in intestinal tumorigenesis. We evaluated HCA-7 cells which express high levels of COX-2 protein constitutively and HCT-116 cells which lack COX-2 protein. Treatment of nude mice implanted with HCA-7 cells with a selective COX-2 inhibitor (SC-58125), reduced tumor formation by 85-90%. SC-58125 also inhibited colony formation of cultured HCA-7 cells. Conversely, SC-58125 had no effect on HCT-116 implants in nude mice or colony formation in culture. Here we provide evidence that there may be a direct link between inhibition of intestinal cancer growth and selective inhibition of the COX-2 pathway.
Three-dimensional topography simulation model: etching and lithography (1990)

An etching model in which topography is derived by solving a modified diffusion equation is introduced. This model is simple and makes it possible to simulate three-dimensional (3-D) topography accurately and quickly. Based on this model, a 3-D topography simulator which can be applied in the development of photolithography and isotropic/anisotropic etching has been developed. With this simulator, it is possible to simulate the series processes and multilayer etching, such as contact hole and trench etching. By simulating photolithography, diffraction and standing-wave effects can be found clearly in the 3-D topography of the developed photoresist. In the case of an etching process which is restricted by diffusion, the dependence of the etch front topography on the window width of the mask is examined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Report of the committee on structural chromosome changes in neoplasia (1989)

An enormous amount of data on neoplasia-associated chromosome aberrations has accumulated over the past two years. More than 4,000 tumors with a chromosome anomaly identified by banding have been published since HGM9, and the total number of cases contained in the registry on which the Catalog of Chromosome Aberrations in Cancer (Mitelman, 1988) is based is now well above 12,000. The information presently available is, however, still in many respects incomplete. First, the data is heavily biased in favor of hematologic disorders. Solid tumors comprise only 20% of the total data base, which is totally disproportionate to the relative contribution of these disorders to human cancer morbidity and mortality. For example, malignant epithelial tumors (carcinomas), which cause almost 80% of all cancer deaths in man, comprise only 7% of the total. Second, our knowledge about early stage tumors is very limited. For example, the great majority of the solid tumors that have been studied cytogenetically have been metastatic lesions or effusions (advanced tumors usually have a large number of complex structural and numerical chromosome aberrations). Obviously, many more such neoplasms will have to be studied before the primary (pathogenetically essential) changes can be distinguished from the confusing variety of secondary abnormalities that may dominate the karyotype. It should be noted that secondary changes may also be nonrandom, and may be important for tumor progression. Therefore, no attempt has been made in this report to distinguish between primary and secondary changes. All nonrandomly occurring abnormalities that met the criteria for inclusion are listed in Table 1 irrespective of their presumed pathogenetic significance. Results of molecular genetic studies (e.g. the demonstration of loss of heterozygosity or gene amplification) were not considered, although they may be included in the HGM10.5 report. A total of 149 nonrandom chromosome changes were identified (Table 1) in 43 different types of neoplastic disorders, including hematologic diseases and malignant lymphomas, as well as tumors of epithelial, mesenchymal, neurogenic, germ cell, and melanocytic origin. The aberrations comprise a variety of structural chromosome rearrangements (translocations, inversions, insertions, deletions, duplications and isochromosomes), and all chromosomes, except the Y chromosome are involved. The great majority (121 of the 149 identified aberrations) represent well-defined, specific structural changes. More than half of them are consistently associated with a particular morphologic disease characteristic. Twenty-eight of the aberrations, although nonrandom, are not characterized as well. Most are deletions or translocations that only affect a certain chromosome region, often spanning several bands.(ABSTRACT TRUNCATED AT 400 WORDS)
IL-18 Induces Monocyte Chemotactic Protein-1 Production in Macrophages through the Phosphatidylinositol 3-Kinase/Akt and MEK/ERK1/2 Pathways (2005)

Macrophages are activated during an inflammatory response and produce multiple inflammatory cytokines. IL-18 is one of the most important innate cytokines produced from macrophages in the early stages of the inflammatory immune response. Monocyte chemoattractant protein (MCP-1) is expressed in many inflammatory diseases such as multiple sclerosis and rheumatoid arthritis, and its expression is correlated with the severity of the disease. Both IL-18 and MCP-1 have been shown to be involved in inflammatory immune responses. However, it has been unclear whether IL-18 is involved in the induction of MCP-1. This investigation was initiated to determine whether IL-18 can induce MCP-1 production, and if so, by which signal transduction pathways. We found that IL-18 induced the production of MCP-1 in macrophages, which was IL-12-independent and was not mediated by autocrine cytokines such as IFN-gamma or TNF-alpha. We then examined signal transduction pathways involved in IL-18-induced MCP-1 production. We found that IL-18 did not activate the IkappaB kinase/NF-kappaB pathway, evidenced by no degradation of IkappaBalpha and no translocation of NF-kappaB p65 to the nucleus in IL-18-stimulated macrophages. Instead, IL-18 activated the PI3K/Akt and MEK/ERK1/2 pathways. Inhibition of either of these pathways attenuated MCP-1 production in macrophages, and inhibition of both signaling pathways resulted in the complete inhibition of MCP-1 production. On the basis of these observations, we conclude that IL-18 induces MCP-1 production through the PI3K/Akt and MEK/ERK1/2 pathways in macrophages.
Novel Genes Associated with Malignant Melanoma but not Benign Melanocytic Lesions (2005)

Our study systematically identified novel melanoma-specific genes and showed the feasibility of using a combination of PLAB and L1CAM in a reverse transcription-PCR assay to differentiate clinically relevant samples containing benign or malignant melanocytes.
A survey of tools for the analysis of quantitative PCR (qPCR) data (2014)

Real-time quantitative polymerase-chain-reaction (qPCR) is a standard technique in most laboratories used for various applications in basic research. Analysis of qPCR data is a crucial part of the entire experiment, which has led to the development of a plethora of methods. The released tools either cover specific parts of the workflow or provide complete analysis solutions. Here, we surveyed 27 open-access software packages and tools for the analysis of qPCR data. The survey includes 8 Microsoft Windows, 5 web-based, 9 R-based and 5 tools from other platforms. Reviewed packages and tools support the analysis of different qPCR applications, such as RNA quantification, DNA methylation, genotyping, identification of copy number variations, and digital PCR. We report an overview of the functionality, features and specific requirements of the individual software tools, such as data exchange formats, availability of a graphical user interface, included procedures for graphical data presentation, and offered statistical methods. In addition, we provide an overview about quantification strategies, and report various applications of qPCR. Our comprehensive survey showed that most tools use their own file format and only a fraction of the currently existing tools support the standardized data exchange format RDML. To allow a more streamlined and comparable analysis of qPCR data, more vendors and tools need to adapt the standardized format to encourage the exchange of data between instrument software, analysis tools, and researchers.
Peri-oestrous hormone profiles, embryonic survival and variation in embryonic development in gilts and primiparous sows (1994)

The primary objective of this study was to determine whether embryo survival in gilts and primiparous sows is related to variations in the peri-oestrous profiles of oestradiol, progesterone and LH. A secondary objective of the present work was to compare embryo development and certain endocrine characteristics in gilts and primiparous sows. Sows (n = 6) and gilts (n = 6) were catheterized in the jugular vein on the day after weaning or on day 14 of the oestrous cycle, respectively. Additional females (one gilt and seven sows) were examined only for characteristics of embryonic development. Embryos were recovered on day 11.5-11.75 of gestation, and size and volume of individual embryos were recorded. Minimal differences were observed between sows and gilts for endocrine and embryo data. Embryo recovery was 71.38 +/- 4.77% based on the number of corpora lutea. However, endocrine differences were noted for pigs with high embryo survival (> 71% recovery) compared with those with low survival. Peak oestradiol concentration occurred closer (P < 0.05) to the onset of oestrus in pigs with high embryo survival than in pigs with low embryo survival (3.3 +/- 4.6 h after oestrus versus 13.0 +/- 5.5 h before oestrus) and peak LH concentration occurred later (P < 0.05) after the onset of oestrus for pigs with high embryo survival. Peak oestradiol concentration tended (P = 0.07) to be higher in pigs with low embryo survival (35.21 +/- 2.56 pg ml-1) compared with pigs with high embryo survival (28.17 +/- 2.14 pg ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Assessment of the speed of flea kill of lotilaner (Credelio™) throughout the month following oral administration to dogs (2017)

Lotilaner's rapid flea knockdown immediately following treatment and sustained SOK through 35 days post-treatment offers a new solution for helping to eliminate the health risks that accompany flea infestations on dogs. The consistency of the rapid, sustained flea SOK demonstrated in these studies generates confidence that monthly use of lotilaner in dogs can be valuable in disrupting the flea life cycle in a contaminated environment, and that newly acquired fleas will die quickly, thereby reducing the discomfort of flea bites. The sustained lotilaner SOK also provides confidence that there will be no "end-of-dose" resurgence in flea burdens with the potential accompanying consequence of flares in flea-bite hypersensitivity.