gebhart/patrepeval huggingface dataset:
Rapid retroviral delivery of tetracycline-inducible genes in a single autoregulatory cassette. (1996)

We describe a single autoregulatory cassette that allows reversible induction of transgene expression in response to tetracycline (tet). This cassette contains all of the necessary components previously described by others on two separate plasmids that are introduced sequentially over a period of months [Gossen, M. & Bujard, H. (1992) Proc. Natl. Acad. Sci. USA 89, 5547-5551]. The cassette is introduced using a retrovirus, allowing transfer into cell types that are difficult to transfect. Thus, populations of thousands of cells, rather than a few clones, can be isolated and characterized within weeks. To avoid potential interference of the strong retroviral long terminal repeat enhancer and promoter elements with the function of the tet-regulated cytomegalovirus minimal promoter, the vector is self-inactivating, eliminating transcription from the long terminal repeat after infection of target cells. Tandem tet operator sequences and the cytomegalovirus minimal promoter drive expression of a bicistronic mRNA, leading to transcription of the gene of interest (lacZ) and the internal ribosome entry site controlled transactivator (Tet repressor-VP16 fusion protein). In the absence of tet, there is a progressive increase in transactivator by means of an autoregulatory loop, whereas in the presence of tet, gene expression is prevented. Northern blot, biochemical, and single cell analyses have all shown that the construct yields low basal levels of gene expression and induction of one to two orders of magnitude. Thus, the current cassette of the retroviral construct (SIN-RetroTet vector) allows rapid delivery of inducible genes and should have broad applications to cultured cells, transgenic animals, and gene therapy.
Discriminant Analysis and Statistical Pattern Recognition. (1994)

Provides a systematic account of the subject area, concentrating on the most recent advances in the field. While the focus is on practical considerations, both theoretical and practical issues are explored. Among the advances covered are: regularized discriminant analysis and bootstrap-based assessment of the performance of a sample-based discriminant rule and extensions of discriminant analysis motivated by problems in statistical image analysis. Includes over 1,200 references in the bibliography.
Synthesen heterocyclischer Aldehyde : Pyrimidinaldehyd-(4) (Synthesen in der heterocyclischen Reihe ; 4) (1964)

Unter Verwendung von bifunktionellen Verbindungen mit einer Aldehydacetalgruppe werden mit geeigneten Ringschlußkomponenten heterocyclische Aldehydacetale bzw. Aldehyde erhalten. Aus [β-Dimethylamino-vinyl]-glyoxaldiäthylacetal und Formamidinacetat erhält man Pyrimidinaldehyd-(4)-diäthylacetal und daraus als ersten Pyrimidinaldehyd den freien Pyrimidinaldehyd-(4). Dessen Eigenschaften sowie Umsetzungen werden beschrieben.
Robust properties of membrane-embedded connector channel of bacterial virus phi29 DNA packagingmotor (2010)

Biological systems contain highly-ordered macromolecular structures with diverse functions, inspiring their utilization in nanotechnology. A motor allows linear dsDNA viruses to package their genome into a preformed procapsid. The central component of the motor is the portal connector that acts as a pathway for the translocation of dsDNA. The elegant design of the connector and its channel motivates its application as an artificial nanopore (Nature Nanotechnology, 4, 765-772). Herein, we demonstrate the robust characteristics of the connector of the bacteriophage phi29 DNA packaging motor by single pore electrophysiological assays. The conductance of each pore is almost identical and is perfectly linear with respect to the applied voltage. Numerous transient current blockade events induced by dsDNA are consistent with the dimensions of the channel and dsDNA. Furthermore, the connector channel is stable under a wide range of experimental conditions including high salt and pH 2-12. The robust properties of the connector nanopore made it possible to develop a simple reproducible approach for connector quantification. The precise number of connectors in each sheet of the membrane was simply derived from the slopes of the plot of voltage against current. Such quantifications led to a reliable real time counting of DNA passing through the channel. The fingerprint of DNA translocation in this system has provided a new tool for future biophysical and physicochemical characterizations of DNA transportation, motion, and packaging.
Transcatheter occlusion of the patent ductus arteriosus with Cook detachable coils. (1996)

Transcatheter occlusion using detachable (Cook) spring coils is a safe and effective alternative to presently available devices. The delivery system allows full retrieval of the coil until a satisfactory position is obtained.
Isolation and characterization of the sulfated gangliotriaosylceramide from rat kidney. (1982)

A sulfoglycosphingolipid containing N-acetylgalactosamine has been isolated from the lipid extract of rat kidney. The isolation procedure involved extraction of lipids with chloroform/methanol, alkaline methanolysis, and column chromatographies with DEAE-Sephadex and Silica beads. The components were N-acetylgalactosamine, galactose, glucose, sphingoid bases, fatty acids, and sulfate in equimolar amounts. The yield of this sulfoglycolipid was about 24 nmol/g of tissue, which was about 13% of that of galactosylceramide 3-sulfate from rat kidney. By infrared spectroscopy, proton magnetic resonance spectroscopy, periodate oxidation, solvolysis, chromium trioxide oxidation, and methylation analysis of the native and partially degraded compound, the structure of this glycolipid is proposed to be GalNAc beta 1--4(HSO3-3)Gal beta 1--4Glc beta 1--1Cer.
Lectins for electromagnetic purification of islets from humans and large mammals. (1990)

One prerequisite for unimpaired islet graft function is the separation from the presumably cytotoxic and highly immunogenic exocrine tissue (Ulricks and MuUer-Ruchholtz: cf. page 123 in this book; Gray 1989). Three different principles of islet purification are used: (A) Hand-picking is a method eSUlblished for purification of islets from the rodent pancreas (Finke, Lacy and Ono 1979). But for the high number of islets needed for human islet transplantation this method is too time-consuming and far too laborious. (B) Density gradient centrifugation is dependent on the different densities of exocrine and endocrine tissue. Large scale purification by this method presently achieves purity degrees of approx. 40%-70% (Lake, Bassett, Larkins, Revell, Walczak. Chamberlain. Rumford. London. Veitch. Bell and lames 1989; Ricordi. Lacy and Scharp 1989; Warnock, Ellis. Cattral. Untch. Kneteman and Rajotte 1989). This is partly explained by the difficulties to control the collagenase digestion process. (C) The principle of electromagnetic cell separation (EMS; Kandzia. Scholz. Anderson and Muller-Ruchholtz 1984; Muller-Ruchholtz. Kandzia and Leyhausen 1987) was further developed for large scale islet purification (Muller-Ruchholtz. Leyhausen. Petersen. Schubert and Ulricks 1987). Magnetic microspheres (MMS) were coupled to lectins with binding specificity for exocrine tissue. UEA-I was found to be a highly selective lectin for rat (Muller-Ruchholtz et al. 1987) and WFA for human (Winoto-Morbach. Ulricks. Leyhausen and Muller-Ruchholtz 1989; Winoto-Morbach. Leyhausen. Schunke. Ulrichs and Muller-Ruchholtz 1989) exocrine tissue. Lectincoupled MMS can trap the latter in an electromagnetic field, thus providing effluent islets of a high degree of purity. Functional integrity of EMS-separated rat islets was tested in vivo (Muller-Ruchholtz et al. 1987) and in vitro (Winoto-Morbach et al. 1989). Because of the difficulties to obtain sufficient human material we propose other species (cattle, pig and dog) to perform extensive preclinical studies and to collect data in view of the possibility of future islet xenotransplantation (Reemtsma 1989). This has the advantage of unlimited access to material for large scale islet separation. But for each new species used as islet donor, a particular lectin has to be found to make this approach effective for either experimental or clinical purposes. Therefore our interest was focussed on lectins with adequate specificity for pancreatic exocrine tissue of cattle, pig and dog. The characteristics of suitable lectins are the following: (a) high degree of binding specificity for the adequate mammalian tissue, (b) non toxicity to endocrine cells, and (c) maintenance of binding specificity for exocrine cells after coupling to microspheres.
Large medical gantries (2002)

A combination of a Medical Gantry and Patient Positioning System is required to direct a particle therapy beam to a supine patient from a variety of angles. The requirements of beam direction and size for precision beam treatment result in stringent criteria for the magnetics and mechanical structure of the gantry. In this paper the requirements of large gantries for ion therapy will be discussed. A variety of ion beam gantries for beam energies up to and beyond 250 MeV have been designed, constructed and are being planned. The mechanical alignment requirements will be discussed and compared with actual performance where available. The beam optics requirements will also be discussed and compared amongst different gantry designs.
Mucoadhesive Fenretinide Patches for Site-Specific Chemoprevention of Oral Cancer: Enhancement of Oral Mucosal Permeation of Fenretinide by Coincorporation of Propylene Glycol and Menthol (2012)

The objective of this study was to enhance oral mucosal permeation of fenretinide by coincorporation of propylene glycol (PG) and menthol in fenretinide/Eudragit RL PO mucoadhesive patches. Fenretinide is an extremely hydrophobic chemopreventive compound with poor tissue permeability. Coincorporation of 5-10 wt % PG (mean J(s) = 16-23 μg cm⁻² h⁻¹; 158-171 μg of fenretinide/g of tissue) or 1-10 wt % PG + 5 wt % menthol (mean J(s) = 18-40 μg cm⁻² h⁻¹; 172-241 μg of fenretinide/g of tissue) in fenretinide/Eudragit RL PO patches led to significant ex vivo fenretinide permeation enhancement (p < 0.001). Addition of PG above 2.5 wt % in the patch resulted in significant cellular swelling in the buccal mucosal tissues. These alterations were ameliorated by combining both enhancers and reducing PG level. After buccal administration of patches in rabbits, in vivo permeation of fenretinide across the oral mucosa was greater (∼43 μg fenretinide/g tissue) from patches that contained optimized permeation enhancer content (2.5 wt % PG + 5 wt % menthol) relative to permeation obtained from enhancer-free patch (∼17 μg fenretinide/g tissue) (p < 0.001). In vitro and in vivo release of fenretinide from patch was not significantly increased by coincorporation of permeation enhancers, indicating that mass transfer across the tissue, and not the patch, largely determined the permeation rate control in vivo. As a result of its improved permeation and its lack of deleterious local effects, the mucoadhesive fenretinide patch coincorporated with 2.5 wt % PG + 5 wt % menthol represents an important step in the further preclinical evaluation of oral site-specific chemoprevention strategies with fenretinide.
[The role of G protein, protein kinase C and Na(+)-H+ exchanger in endothelin-1-induced cardiomyocyte hypertrophic responses]. (1998)

Endothelin-1 (ET-1) has been shown to be a potent growth factor and to induce cardiac hypertrophy. In the present study, we examined the role of G protein, protein kinase C (PKC) and Na(+)-H+ exchanger in ET-1-induced cardiac hypertrophy in cultured neonatal rat cardiac myocytes. ET-1 (10(-10)-10(-7) mol/L) induced promotion of 3H-leucine incorporation, increase in cell protein content and cell surface area in a dose-dependent manner with EC50 value of 5.2 x 10(-10), 5.2 x 10(-10) and 7.3 x 10(-10) mol/L respectively. All of these ET-1-induced cardiomyocyte hypertrophic responses were completely blocked by pretreatment with staurosporine (2 nmol/L), a protein kinase C inhibitor, and stimulated by 4-phorbol, 12-myristate, 13-acetate (PMA) (10(-8)-10(-6) mol/L), a protein kinase C activator, in a dose-dependent manner. Pretreatment of amiloride (10(-4) mol/L), a Na(+)-H+ exchange inhibitor completely inhibited the ET-1-induced, but not PMA-induced cardiomyocyte hypertrophic responses. The ET-1-induced increase in cardiomyocyte protein synthesis and cell surface area was significantly inhibited by pretreatment with pertussis toxin (150 ng/ml). These results suggest that ET-1-induced cardiomyocyte hypertrophy was linked with pertussis toxin sensitive G protein, and PKC and Na(+)-H+ exchange may be an important intracellular signaling transduction pathway during ET-1-induced cardiac hypertrophy in cultured neonatal rat cardiac myocytes.
Antibody-Drug Conjugates for the Treatment of Non–Hodgkin's Lymphoma: Target and Linker-Drug Selection (2009)

Antibody-drug conjugates (ADC), potent cytotoxic drugs covalently linked to antibodies via chemical linkers, provide a means to increase the effectiveness of chemotherapy by targeting the drug to neoplastic cells while reducing side effects. Here, we systematically examine the potential targets and linker-drug combinations that could provide an optimal ADC for the treatment for non-Hodgkin's lymphoma. We identified seven antigens (CD19, CD20, CD21, CD22, CD72, CD79b, and CD180) for potential treatment of non-Hodgkin's lymphoma with ADCs. ADCs with cleavable linkers mediated in vivo efficacy via all these targets; ADCs with uncleavable linkers were only effective when targeted to CD22 and CD79b. In target-independent safety studies in rats, the uncleavable linker ADCs showed reduced toxicity, presumably due to the reduced release of free drug or other toxic metabolites into the circulation. Thus, our data suggest that ADCs with cleavable linkers work on a broad range of targets, and for specific targets, ADCs with uncleavable linkers provide a promising opportunity to improve the therapeutic window for ADCs in humans.
Endoproteolytic processing of a farnesylated peptide in vitro. (1992)

Numerous eukaryotic proteins containing a carboxyl-terminal CAAX motif (C, cysteine; A, aliphatic amino acid; X, any amino acid) require a three-step posttranslational processing for localization and function. The a mating factor of Saccharomyces cerevisiae is one such protein, requiring cysteine farnesylation, proteolysis of the terminal three amino acids, and carboxyl methylation for biological activity. We have used farnesylated a-factor peptides to examine the proteolytic step in the maturation of CAAX-containing proteins. Three distinct carboxyl-terminal protease activities were found in yeast cell extracts that could remove the terminal three residues of a-factor. Two of the proteolytic activities were in cytosolic fractions. One of these activities was a PEP4-dependent carboxypeptidase that was sensitive to phenylmethylsulfonyl fluoride. The other cytosolic activity was PEP4-independent, sensitive to 1,10-phenanthroline, and effectively inhibited by an unfarnesylated a-factor peptide. In contrast, a protease activity in membrane fractions was unaffected by phenylmethylsulfonyl fluoride, 1,10-phenanthroline, or unfarnesylated a-factor peptide. Incubation of membrane preparations from either yeast or rat liver with a radiolabeled farnesylated a-factor peptide released the terminal three amino acids intact as a tripeptide, indicating that this reaction occurred by an endoproteolytic mechanism and that the enzyme most likely possesses a broad substrate specificity. The yeast endoprotease was not significantly affected by a panel of protease inhibitors, suggesting that the enzyme is novel. Zinc ion was shown to inhibit the endoprotease (Ki less than 100 microM). The specific activities of the a-factor carboxyl-terminal membrane endoprotease and methyltransferase clearly indicated that the proteolytic reaction was not rate-limiting in these processing reactions in vitro.
Radiation Response of Mammalian Cells Grown in Culture: I. Repair of X-Ray Damage in Surviving Chinese Hamster Cells (1960)

M. M. Elkind, Harriet Sutton, Radiation Response of Mammalian Cells Grown in Culture: I. Repair of X-Ray Damage in Surviving Chinese Hamster Cells, Radiation Research, Vol. 13, No. 4 (Oct., 1960), pp. 556-593
Hybridisation based DNA screening on peptide nucleic acid (PNA) oligomer arrays (1997)

Arrays of up to some 1000 PNA oligomers of individual sequence were synthesised on polymer membranes using a robotic device originally designed for peptide synthesis. At approximately 96%, the stepwise synthesis efficiency was comparable to standard PNA synthesis procedures. Optionally, the individual, fully deprotected PNA oligomers could be removed from the support for further use, because an enzymatically cleavable but otherwise stable linker was used. Since PNA arrays could form powerful tools for hybridisation based DNA screening assays due to some favourable features of the PNA molecules, the hybridisation behaviour of DNA probes to PNA arrays was investigated for a precise understanding of PNA-DNA interactions on solid support. Hybridisation followed the Watson-Crick base pairing rules with higher duplex stabilities than on corresponding DNA oligonucleotide sensors. Both the affinity and specificity of DNA hybridisation to the PNA oligomers depended on the hybridisation conditions more than expected. Successful discrimination between hybridisation to full complementary PNA sequences and truncated or mismatched versions was possible at salt concentrations down to 10 mM Na+and below, although an increasing tendency to unspecific DNA binding and few strong mismatch hybridisation events were observed.
An Infra-Red Wireless Speaker System Utilizing a Super Wideband FM Carrier (1975)

In a Quadraphonic Hi-Fi system it would be highly desirable that the two rear speakers be wireless. The two rear speakers would be completely independent from the main unit and would be composed of a receiving system, power amplifier and speaker. A short range communication system is needed that has full Hi-Fi performance; a bandwidth of 50 to 15 KC signal-to-noise ratio greater than 60 dB and total harmonic distortion of less than 1%. Also, the cost of the system should be as low as possible. There should be no interference between the two rear speakers or with a neighboring system in a nearby room. It would be desirable that the volume level and balance of the whole system could be accomplished at the main unit. This would necessitate that each of the rear speakers also have a remote volume control function. This may be accomplished in two manners. A special control signal may be sent to each of the rear speakers where it will be decoded and set the volume level of that speaker; or, the signal-to-noise ratio of the system can be raised sufficiently high so that the power amplifier can be operated at full volume and during a quiet passage no background noise be heard in a quiet room. A signal-to-noise ratio of approximately 85 dB would be needed.
Gram-Scale Synthesis of (+)-Discodermolide (2000)

ADVERTISEMENT RETURN TO ISSUEPREVAdditions & Corr...Additions & CorrectionsNEXTORIGINAL ARTICLEThis notice is a correctionGram-Scale Synthesis of (+)-DiscodermolideAmos B. Smith, Michael D. Kaufman, Thomas J. Beachamp, Matthew J. LaMarche, and Hirokazu ArimotoCite this: Org. Lett. 2000, 2, 13, 1983Publication Date (Web):June 22, 2000Publication History Published online22 June 2000Published inissue 1 June 2000https://pubs.acs.org/doi/10.1021/ol006090uhttps://doi.org/10.1021/ol006090ucorrectionACS PublicationsCopyright © 2000 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views621Altmetric-Citations10LEARN 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 PDF (37 KB) Get e-Alertsclose Get e-Alerts
<b>Protein expression profile related to cisplatin resistance in bladder cancer cell lines detected by two-dimensional gel electrophor</b><b>esis </b> (2015)

We used a proteomic approach to compare the differentially regulated protein expression profiles of cisplatin-naïve and cisplatin-resistant bladder cancer cell lines to screen candidate molecules related to cisplatin resistance. The cisplatin-resistant cell line T24 was established by the stepwise exposure of T24 cells to up to 40 μM of cisplatin. We performed a comprehensive study of protein expression in bladder cancer cell lines that included cisplatin-naïve (T24) and cisplatin-resistant cells (T24CDDPR) by means of agarose two-dimensional gel electrophoresis followed by analysis of liquid chromatography tandem mass spectroscopy. We identified 25 obviously different spots for T24 and T24 CDDPR. Seven spots had increased expression and 18 spots had decreased expression in T24CDDPR compared to those in T24. Cytoskeletal proteins and enzyme modulators were prominent among differential proteins. Of the 25 proteins, we selected HNRNPA3, PCK2, PPL, PGK1, TKT, SERPINB2, GOT2, and EIF3A for further validation by Western blot. HNRNPA3, PGK1, TKT, and SERPINB2 had more than 1.5-times incremental expression in T24CDDPR compared to that in T24. PCK2 and PPL expressions were decreased less than 20% in T24CDDPR compared to that in T24. The results of 25 new proteins in this study could be valuable and could lead to the development of a new molecular marker.
Optimization of mRNA untranslated regions for improved expression of therapeutic mRNA (2018)

mRNA based therapies hold great promise for the treatment of genetic diseases. However, this therapeutic approach suffers from multiple challenges including the short half-life of exogenously administered mRNA and subsequent protein production. Modulation of untranslated regions (UTR) represents one approach to enhance both mRNA stability and translation efficiency. The current studies describe and validate screening methods using a diverse set of 5'UTR and 3'UTR combinations for improved expression of the Arginase 1 (ARG1) protein, a potential therapeutic mRNA target. Data revealed a number of critical aspects which need to be considered when developing a screening approach for engineering mRNA improvements. First, plasmid-based screening methods do not correlate with protein expression driven by exogenously expressed mRNA. Second, improved ARG1 protein production was driven by increased translation and not improved mRNA stability. Finally, the 5' UTR appears to be the key driver in protein expression for exogenously delivered mRNA. From the testing of the combinatorial library, the 5'UTR for complement factor 3 (C3) and cytochrome p4502E1 (CYP2E1) showed the largest and most consistent increase in protein expression relative to a reference UTR. Collectively, these data provide important information for the development and optimization of therapeutic mRNAs.
Beyond mapping: estimating complexity of multichannel EEG recordings (1996)

A new measure of complexity of multichannel EEG recordings is proposed. The quantity assesses the diversity of activities of different brain generators contributing to the global dynamics of electric field of brain.