gebhart/patrepeval huggingface dataset:
Switching On and Off Transgene Expression within Lactotrophic Cells in the Anterior Pituitary Gland in Vivo (2001)

To further develop our understanding of anterior pituitary (AP) function and to aid the development of gene therapy strategies for the treatment of pituitary diseases, adenovirus (Ad)-mediated gene transfer to the AP gland will be a useful tool. Although successful widespread gene transfer within the AP has been achieved using first generation Ads the ability to control transgene expression would be very beneficial when studying AP regulatory functions and delivering a potentially therapeutic gene into the AP gland. A dual adenoviral vector system encoding for cell type-specific and regulatable transcription units was developed to achieve transcriptionally targeted transgenesis within specific cell populations in the adult AP gland. To achieve regulatable transgene expression within predetermined AP cells, the tetracycline-responsive transcriptional elements have been engineered to be under the control of human, lactotroph-specific PRL (hPRL) promoter elements within a dual adenoviral vector system. The inducibility, cell type specificity, and levels of transgene expression were characterized in vitro and in vivo and compared with the strong ubiquitous β-actin/human cytomegalovirus (CAG) promoter. Inducible expression of the marker geneβ -galactosidase under the control of the hPRL promoter was restricted to lactotrophic tumor cell lines and lactotrophic cells within primary AP cultures. Lactotroph cell type specificity and inducible transgene expression were also observed within the AP gland in vivo, and this could be switched on or off. Administration of doxycycline abrogated transgene expression both in vitro and in vivo. Our results also provide evidence that an excess of trans-activator is needed to achieve maximal transgene expression. Our data indicate that combined transcriptional and inducible transgenesis can be achieved using adenoviral vectors that allow spatial and temporal restriction of transgene expression within the adult AP gland in vivo.
Oligomeric tau-targeted immunotherapy in Tg4510 mice (2017)

These data suggest that there is some exposure of the Tg4510 mouse brain to TOMA, but it was inadequate to affect the phenotype in these mice at the doses used. These data are consistent with other observations that the rapidly depositing Tg4510 mouse is a challenging model in which to demonstrate efficacy of tau-lowering treatments compared to some other preclinical models of tau deposition/overexpression.
Precoating of alloplastic materials with living human fibroblasts (2005)

Background: The use of alloplastic materials such as polypropylene and polyester has reduced the recurrence of abdominal wall hernias. Concomitantly, new problems have arisen such as inflammatory response against the implanted material and the development of enteric fistulas in case of direct contact of the bowel to polypropylene and polyester. A precoating of the PP with collagen and other absorbable materials seems to reduce the incidence of adhesions and fistulas. The aim of this study was to show the technical feasibility of a precoating of polypropylene with living human fibroblasts and to investigate the growth properties of the cells under these conditions in vitro. Methods: The textile structure of three different alloplastic materials is described (SurgiPro � , TycoHealthcare; Parietene3 PP1510 � , Dallhausen; VIPRO II � , Ethicon Endosurgery). Enhanced Green Fluorescence Protein (EGFP) transduced human foreskin fibroblasts (KiF5) were seeded onto these different alloplastic materials. Proliferation was analyzed by FACS analysis of Ki67 expression. The coating process of the whole mesh area was observed over time with UV-light microscopy, immunostaining, and scanning electron microscopy (SEM). The expression of collagen type I and III was investigated by immunostaining. Results: The three alloplastic materials used were knitted fabrics with different textile structures. KiF5 colonized the entire alloplastic material within 4–6 weeks. Cells were proliferating, as detected by Ki67 expression. SEM showed surface ruffles and long cellular extensions, indicating an active cell metabolism. Light microscopy and SEM suggested that the cells modify the apolar surface by deposition of extracellular matrix components before colonization. Conclusion: Our study shows the feasibility of precoating of polypropylene meshes with living human fibroblasts and opens the possibility for clinical use in the future.
Evidence for two structural genes for alkaline phosphatase in Bacillus subtilis (1990)

Two secreted alkaline phosphatase proteins were purified from cultures of Bacillus subtilis JH646MS. The two proteins showed slight differences in subunit molecular weight, substrate specificity, and charge characteristics. A total of 62% of the first 22 amino-terminal amino acids were identical. Both sequences showed conservation of structural features identified in Escherichia coli and human alkaline phosphatases. One alkaline phosphatase was a monomer and the other was a dimer. Southern analysis of genomic DNA with degenerative oligomers based on the amino acid sequences suggest that there are two structural genes for alkaline phosphatase in the genome of B. subtilis.
Simulation of intrinsic bipolar transistor mechanisms for future capacitor-less eDRAM on bulk substrate (2010)

Embedded DRAM technology is undergoing a radical evolution. With size reduction, capacity shrink seems to be a complex obstacle to overcome. Alternative memory cells have been proposed to respond to this problem; capacitorless eDRAM is one of most promising solution. In this paper, after reviewing the current status on eDRAM market and recent evolution of eDRAM trends we study the feasibility of an innovative capacitorless eDRAM based on intrinsic bipolar transistor on bulk substrate.
The Nematode Caenorhabditis elegans (1988)

In 1965 Sydney Brenner chose free-living nematode Caenorhabditis elegans as a promising model system for a concerted genetic, ultrastructural, and behavioral attack on development and function of a simple nervous system. Since then, with help of a growing number of investigators, knowledge about biology of the worm has accumulated at a steadily accelerating pace to extent that C. elegans is now probably most completely understood metazoan in terms of anatomy, genetics, development, and behavior. The past few years have seen completion of two major long-term projects that provide new insights into C. elegans development and lay important groundwork for future investigation: completion of cell lineages of both sexes, from zygote to adult, and description of complete anatomy at level of electron microscope resolution, providing a complete wiring diagram of cell contacts in animal. Recent years have also brought first successes in molecularly cloning genes of developmental interest defined only by mutation, using transposon tagging as a generally applicable method for identification of desired DNA sequences. Reintroduction of cloned DNA sequences into genome has recently been accomplished. A physical map of genome has been assembled with a combination of cosmid and YAC genes. This Book of Worm serves as a reference source for C. elegans investigators as well as an introductory monograph for other biologists.
A Gene Cluster for the Mevalonate Pathway from Streptomyces sp. Strain CL190 (2000)

A biosynthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1. 1.1.34), the rate-limiting enzyme of the mevalonate pathway for isopentenyl diphosphate biosynthesis, had previously been purified from Streptomyces sp. strain CL190 and its corresponding gene (hmgr) had been cloned (S. Takahashi, T. Kuzuyama, and H. Seto, J. Bacteriol. 181:1256-1263, 1999). Sequence analysis of the flanking regions of the hmgr gene revealed five new open reading frames, orfA to -E, which showed similarity to those encoding eucaryotic and archaebacterial enzymes for the mevalonate pathway. Feeding experiments with [1-(13)C]acetate demonstrated that Escherichia coli JM109 harboring the hmgr gene and these open reading frames used the mevalonate pathway under induction with isopropyl beta-D-thiogalactopyranoside. This transformant could grow in the presence of fosmidomycin, a potent and specific inhibitor of the nonmevalonate pathway, indicating that the mevalonate pathway, intrinsically absent in E. coli, is operating in the E. coli transformant. The hmgr gene and orfABCDE are thus unambiguously shown to be responsible for the mevalonate pathway and to form a gene cluster in the genome of Streptomyces sp. strain CL190.
Comparison of TP53 mutations identified by oligonucleotide microarray and conventional DNA sequence analysis. (2000)

As the rate of gene discovery accelerates, more efficient methods are needed to analyze genes in human tissues. To assess the efficiency, sensitivity, and specificity of different methods, alterations of TP53 were independently evaluated in 108 ovarian tumors by conventional DNA sequence analysis and oligonucleotide microarray (p53 GeneChip). All mutations identified by oligonucleotide microarray and all disagreements with conventional gel-based DNA sequence analysis were confirmed by re-analysis with manual and automated dideoxy DNA sequencing. A total of 77 ovarian cancers were identified as having TP53 mutations by one of the two approaches, 71 by microarray and 63 by gel-based DNA sequence analysis. The same mutation was identified in 57 ovarian cancers, and the same wild type TP53 sequence was observed in 31 ovarian cancers by both methods, for a concordance rate of 81%. Among the mutation analyses discordant by these methods for TP53 sequence were 14 cases identified as mutated by microarray but not by conventional DNA sequence analysis and 6 cases identified as mutated by conventional DNA sequence analysis but not by microarray. Overall, the oligonucleotide microarray demonstrated a 94% accuracy rate, a 92% sensitivity, and an 100% specificity. Conventional DNA sequence analysis demonstrated an 87% accuracy rate, 82% sensitivity, and a 100% specificity. Patients with TP53 mutations had significantly shorter overall survival than those with no mutation (P = 0.02). Women with mutations in loop2, loop3, or the loop-sheet-helix domain had shorter survival than women with other mutations or women with no mutations (P = 0.01). Although further refinement would be helpful to improve the detection of certain types of TPS3 alterations, oligonucleotide microarrays were shown to be a powerful and effective tool for TP53 mutation detection.
[Preparation, characterization and antiviral activity of phenolic polymers. 2. Antiviral activity of phenolic polymers (proceedings)]. (1979)

President Roosevelt discusses the presidential campaign and the platforms of the other candidates in a letter to Dr. Hart.
Innervation of the renal cortex. (1978)

Morphologic studies of renal innervation have utilized the methods of histochemistry and electron microscopy. Much information has been derived from examination of the renal cortex in monkey and rat. Fluorescence histochemistry shows a rich adrenergic innervation. Acetylcholinesterase can be demonstrated histochemically in the renal nerves by light and electron microscopy. Studies in the rat using 6-hydroxydopamine, a drug that selectively destroys adrenergic nerves, indicate that the glomerular arterioles and surrounding tubules are innervated by adrenergic nerves containing acetylcholinesterase. Distinct neurovascular and neurotubular junctions are observed the electron microscope. They are anatomically consistent with being the sites of synaptic transmission. Ultrastructural analysis of serial sections reveals that single individual axons contact multiple vascular cells and renal tubules. We now have a considerable body of information concerning the morphology of renal innervation are are beginning to appreciate the role of the renal nerves in kidney function.
Lipopolysaccharide-Based Enzyme-Linked Immunosorbent Assay for Experimental Use in Detection of Antibodies toLawsonia intracellularisin Pigs (2005)

An enzyme-linked immunosorbent assay (ELISA) for Lawsonia intracellularis was developed and compared with a whole-cell antigen-based immunofluorescence antibody test (IFAT). The antigen-containing lipopolysaccharide (LPS) was derived from Percoll gradient purified cultures of L. intracellularis by using a modification of the Westphal hot phenol procedure. The antigen was bound directly to polystyrene 96-well microtiter plates, and the assay was performed in an indirect ELISA format. Specificity and sensitivity values based on 80 known positive and 80 known negative serum samples from controlled experimental trials were 93.7% and 88.7%, respectively. Serological results from a controlled L. intracellularis challenge exposure study confirmed the high specificity and sensitivity of this assay (100% and 99.5%, respectively). Comparisons between the LPS ELISA and the IFAT in detecting anti-Lawsonia antibodies in this controlled study revealed significantly more LPS ELISA-positive pigs than IFAT-positive pigs on days 21, 28, 35, and 42 (P = 0.003, 0.030, 0.002, and 0.006, respectively). This indirect ELISA (LPS ELISA) test is an improved method of detecting antibodies in pigs soon after exposure to L. intracellularis, regardless of isolate type (vaccine or wild type) in experimental studies. The LPS ELISA may be used as a tool to support future research trials on vaccine efficacy and to further understand the immune response induced by L. intracellularis.
Intracameral tissue plasminogen activator to prevent severe fibrinous effusion after congenital cataract surgery (2005)

It seems that prophylactic intracameral r-TPA is effective in prevention of fibrinous effusion at least in the first 2 weeks after cataract extraction in the paediatric age group and decreases the incidence of pigmented IOL precipitates.
Synthesis and antifungal activity of a series of difluorotritylimidazoles. (1992)

1-[(2-Fluorophenyl)(4-fluorophenyl)phenylmethyl]-1H-imidazole (flutrimazole, UR-4056, CAS 119006-77-8) (15) was selected among a series of mono-, di- and tri-fluorotrityl-imidazole antifungal agents as the most potent fluorine containing analogue of clotrimazole
Probing Protein/Protein Interactions with Mass Spectrometry and Isotopic Labeling:  Analysis of the p21/Cdk2 Complex (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTProbing Protein/Protein Interactions with Mass Spectrometry and Isotopic Labeling: Analysis of the p21/Cdk2 ComplexRichard W. Kriwacki, Jiang Wu, Gary Siuzdak, and Peter E. WrightView Author Information Departments of Molecular Biology and Chemistry The Scripps Research Institute, La Jolla, California 92037 Cite this: J. Am. Chem. Soc. 1996, 118, 22, 5320–5321Publication Date (Web):June 5, 1996Publication History Received7 March 1996Published online5 June 1996Published inissue 5 June 1996https://doi.org/10.1021/ja960752mCopyright © 1996 American Chemical SocietyRequest reuse permissions Article Views367Altmetric-Citations54LEARN 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 InReddit Read OnlinePDF (84 KB) Get e-AlertscloseSUBJECTS:Crystal cleavage,Interfaces,Mass spectrometry,Monomers,Peptides and proteins Get e-Alerts
Abstract SY03-02: Preclinical assessment of JTX-2011, an agonist antibody targeting ICOS, supports evaluation in ICONIC clinical trial (2017)

Abstract ICOS (the inducible T-cell co-stimulator) is a co-stimulatory molecule expressed on the surface of T cells and a member of the CD28 family, which includes clinically validated targets of cancer immunotherapies, such as PD-1 and CTLA-4. Clinical data identified ICOS as a potentially key molecule in providing optimal antitumor benefit following anti-CTLA-4 therapy. We have developed a species cross-reactive humanized IgG1 agonist antibody, JTX-2011, that binds ICOS and is designed to induce an antitumor immune response. Our preclinical data suggest that JTX-2011 functions through a dual mechanism of action, by stimulating T effector cells (Teff) and depleting intratumoral T regulatory cells (Tregs). The ICOS antibody is efficacious as a single agent in mouse syngeneic tumor models and demonstrates enhanced activity when administered in combination with anti-PD-1. Single-agent activity in the preclinical models appears to correlate with ICOS expression, with greater efficacy observed in tumor models that exhibit a higher percentage of ICOS-expressing immune cell infiltrate. An integrated expression analysis of human tumors identified non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) as indications with higher percentages of ICOS-expressing cell infiltrate. Preclinical studies performed in rodent and monkeys evaluated safety, pharmacokinetics, and pharmacodynamics of JTX-2011 to inform the first in-human study. The ICONIC phase I/II clinical trial is currently ongoing for evaluation of JTX-2011 alone or in combination with the anti-PD-1 antibody Nivolumab in patients with advanced solid tumors and incorporates a patient enrichment strategy design based on the preclinical and translational findings. Citation Format: Jennifer S. Michaelson, Christopher Harvey, Kutlu Elpek, Ellen Duong, Lindsey Shallberg, Matthew Wallace, Robert Mabry, Jenny Shu, Amit Deshpande, Tong Zi, Stephen Sazinsky, Joshua Apgar, Barbara Mounho-Zamora, Michael Briskin, Elizabeth Trehu, Jason Reeves, Heather Hirsch, Sriram Sathyanarayanan, Deborah Law. Preclinical assessment of JTX-2011, an agonist antibody targeting ICOS, supports evaluation in ICONIC clinical trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY03-02. doi:10.1158/1538-7445.AM2017-SY03-02
17 Hydroxyprogesterone for the Prevention of Preterm Delivery (2005)

The recent publication of 2 large randomized trials of 17 alpha hydroxyprogesterone caproate (17P) and progesterone suppositories, respectively, for the prevention of premature labor have renewed interest in the use of progesterone to prevent preterm birth. The results of these trials have reinforced the positive results of earlier smaller trials of 17P to prevent preterm delivery. A large body of evidence attests to the lack of teratogenic effects of 17P in pregnancy. Although progesterone is known to have many actions beneficial to the maintenance of pregnancy, the exact mode of action of 17P therapy in preventing preterm labor and delivery is not known. Current evidence supports the use of 17P treatment, begun early in the second trimester of gestation and continued weekly until 36 weeks, for women with a history of a previous spontaneous preterm delivery. At present no evidence exists for the use of 17P to prevent preterm delivery in women with multiple gestation, a short uterine cervix, or other high-risk conditions. The use of 17P or other progestins should not be encouraged for these indications outside of randomized trials. At present no evidence exists for the efficacy of any oral progesterone compound in preventing preterm labor. Four trials reporting the use of a progestational drug in patients with symptoms of preterm labor found no efficacy in prolonging pregnancy, and the use of 17P or other progestational drugs as tocolytic therapy should not be encouraged.
Surface Plasmon Resonance Imaging Measurements of DNA and RNA Hybridization Adsorption onto DNA Microarrays (2000)

Surface plasmon resonance (SPR) imaging is a surface-sensitive spectroscopic technique for measuring interactions between unlabeled biological molecules with arrays of surface-bound species. In this paper, SPR imaging is used to quantitatively detect the hybridization adsorption of short (18-base) unlabeled DNA oligonucleotides at low concentration, as well as, for the first time, the hybridization adsorption of unlabeled RNA oligonucleotides and larger 16S ribosomal RNA (rRNA) isolated from the microbe Escherichia coli onto a DNA array. For the hybridization adsorption of both DNA and RNA oligonucleotides, a detection limit of 10 nM is reported; for large (1,500-base) 16S rRNA molecules, concentrations as low as 2 nM are detected. The covalent attachment of thiol-DNA probes to the gold surface leads to high surface probe density (10(12) molecules/cm2) and excellent probe stability that enables more than 25 cycles of hybridization and denaturing without loss in signal or specificity. Fresnel calculations are used to show that changes in percent reflectivity as measured by SPR imaging are linear with respect to surface coverage of adsorbed DNA oligonucleotides. Data from SPR imaging is used to construct a quantitative adsorption isotherm of the hybridization adsorption on a surface. DNA and RNA 18-mer oligonucleotide hybridization adsorption is found to follow a Langmuir isotherm with an adsorption coefficient of 1.8 x 10(7) M(-1).
Identification of posttranscriptionally active inhibitory sequences in human immunodeficiency virus type 1 RNA: novel level of gene regulation (1991)

cis-acting inhibitory region (IR) sequences were identified within the gag/pol gene of the human immunodeficiency virus type 1 (HIV-1) by using a novel feedback-stimulated, rev-independent tat reporter gene to screen HIV-1 sequences in transient expression assays. Two regions, a 1,295-nucleotide segment in the gag gene (IR-1) and a 1,932-nucleotide segment of the pol gene (IR-2), each inhibited reporter gene expression 10- to 20-fold. IR-1 and IR-2 both contained subsequences which inhibited reporter gene expression. Introduction of IR sequences into a heterologous reporter plasmid, pCMV-CAT, resulted in decreased chloramphenicol acetyltransferase expression, suggesting that the inhibitory effect was not restricted to a reporter gene under the control of the HIV-1 promoter. The presence of HIV IR sequences in cis did not alter relative levels of reporter gene RNA; however, fractionation studies revealed IR-containing RNA accumulated in the nucleus. These findings demonstrate that IR sequences within the gag/pol region affect gene expression by altering the cellular distribution of viral RNA.
Economic Valuation and Environmental Values (1998)

The origins of both economic and philosophical value theory are examined and shown to be closely related. The status of neo-classical value theory is that it is internally flawed in any attempt to describe the real world. Cost-benefit analysis as it applies to the valuation of environmental agents relies upon the claim that this neo-classical theory has a particular status in optimal welfare maximisation and, therefore, suffers the same problems of internal consistency. Economic valuation of the environment is not a scientific process derived from external law but a social process relying upon social agreement. Alternatives to economic valuation are considered and may possess a more plausible social base. However, all environmental valuation is at odds with beliefs based upon the existence of objective and intrinsic values.