gebhart/patrepeval huggingface dataset:
Characterization of T7-specific Ribonucleic Acid Polymerase (1974)

Abstract The major in vitro RNA transcripts synthesized by T7 RNA polymerase with T7 and T3 DNA templates have been resolved by electrophoresis on polyacrylamide gels. Six discrete size classes of T7 RNAs are found, designated I to VI. The apparent molecular weights, estimated from their electrophoretic mobilities, span a broad range, from 2 x 105 to 5 x 106. At least two minor RNA species, with molecular weights greater than 5 x 106, are also detected. The six major T7 RNA species are synthesized in approximately equimolar amounts, with the exception of species III, which is made in about twice this amount. It is likely that species III is a mixture of two RNAs (IIIa and IIIb) transcribed from separate regions of the T7 genome. Hence, the six major T7 RNA species are tentatively identified with seven late transcription units on the phage chromosome, which are read with equal efficiences. The six (or seven) transcription products are initiated independently with guanosine triphosphate at the 5' terminus, and are elongated at a rate of 230 nucleotides per s under standard in vitro conditions. When T7 RNA polymerase is used to transcribe T3 DNA, a single RNA transcript is found, with a molecular weight similar to that of T7 RNA species III. This suggests an explanation for the reduced rate of T3 RNA synthesis by T7 RNA polymerase in vitro, and implies that T3 promoter sites read by the T3 RNA polymerase are heterogeneous in nature.
Resistance of peripheral autonomic neurons to in vivo productive infection by herpes simplex virus mutants deficient in thymidine kinase activity (1981)

We used a model involving acute and latent herpes simplex virus (HSV) infections of mouse superior cervical ganglia to assess in vivo neuronal infections with two thymidine kinase-deficient (TK-) mutants of HSV type 1. Despite replication of the TK- HSV strains at the site of inoculation in the eyes, little if any viral replication occurred in the superior cervical ganglia, as assessed by the viral titers of ganglion homogenates, viral antigens in tissue sections, and histopathological evidence of cytopathology or inflammation. Cyclophosphamide-induced immunosuppression and treatment with 6-hydroxydopamine, which enhanced productive infections of superior cervical ganglia with TK+ HSV did not induce TK- HSV ganglionic infections. Latent TK- HSV infections were not detected by cocultivation of ganglion explants. Efforts to infect ganglia in culture after they were removed from animals indicated that superior cervical ganglia, and particularly their neuronal elements, resisted productive TK- HSV infection. These results supported the hypothesis that viral thymidine kinase facilitates acute and reactivated productive HSV infections of neurons.
Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens. (1990)

The human tumor-associated antigen CO-029 is a monoclonal antibody-defined cell surface glycoprotein of 27-34 kDa. By using the high-efficiency COS cell expression system, a full-length cDNA clone for CO-029 was isolated. When transiently expressed in COS cells, the cDNA clone directed the synthesis of an antigen reactive to monoclonal antibody CO-029 in mixed hemadsorption and immunoblot assays. Sequence analysis revealed that CO-029 belongs to a family of cell surface antigens that includes the melanoma-associated antigen ME491, the leukocyte cell surface antigen CD37, and the Sm23 antigen of the parasitic helminth Schistosoma mansoni. CO-029 and ME491 antigen expression and the effect of their corresponding monoclonal antibodies on cell growth were compared in human tumor cell lines of various histologic origins.
A Comparison of Commercial and Military Computer Security Policies (1987)

Most discussions of computer security focus on control of disclosure. In Particular, the U.S. Department of Defense has developed a set of criteria for computer mechanisms to provide control of classified information. However, for that core of data processing concerned with business operation and control of assets, the primary security concern is data integrity. This paper presents a policy for data integrity based on commercial data processing practices, and compares the mechanisms needed for this policy with the mechanisms needed to enforce the lattice model for information security. We argue that a lattice model is not sufficient to characterize integrity policies, and that distinct mechanisms are needed to Control disclosure and to provide integrity.
Increasing the Efficiency of Ideal Solar Cells by Photon Induced Transitions at Intermediate Levels (1997)

Recent attempts have been made to increase the efficiency of solar cells by introducing an impurity level in the semiconductor band gap. We present an analysis of such a structure under ideal conditions. We prove that its efficiency can exceed not only the Shockley and Queisser efficiency for ideal solar cells but also that for ideal two-terminal tandem cells which use two semiconductors, as well as that predicted for ideal cells with quantum efficiency above one but less than two.
RF-MEMS switches for reconfigurable integrated circuits (1998)

This paper deals with a relatively new area of radio-frequency (RF) technology based on microelectro-mechanical systems (MEMS). RF MEMS provides a class of new devices and components which display superior high-frequency performance relative to conventional (usually semiconductor) devices, and which enable new system capabilities. In addition, MEMS devices are designed and fabricated by techniques similar to those of very large-scale integration, and can be manufactured by traditional batch-processing methods. In this paper, the only device addressed is the electrostatic microswitch - perhaps the paradigm RF-MEMS device. Through its superior performance characteristics, the microswitch is being developed in a number of existing circuits and systems, including radio front-ends, capacitor banks, and time-delay networks. The superior performance combined with ultra-low-power dissipation and large-scale integration should enable new system functionality as well. Two possibilities addressed here are quasi-optical beam steering and electrically reconfigurable antennas.
L-Arginine improves vascular function by overcoming deleterious effects of ADMA, a novel cardiovascular risk factor. (2005)

There is abundant evidence that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide (NO), an endogenous messenger molecule formed in healthy vascular endothelium from the amino acid precursor L-arginine. Endothelial dysfunction is caused by various cardiovascular risk factors, metabolic diseases, and systemic or local inflammation. One mechanism that explains the occurrence of endothelial dysfunction is the presence of elevated blood levels of asymmetric dimethylarginine (ADMA)--an L-arginine analogue that inhibits NO formation and thereby can impair vascular function. Supplementation with L-arginine has been shown to restore vascular function and to improve the clinical symptoms of various diseases associated with vascular dysfunction.
Metazidohemerythrin models featuring a bis-benzimidazole tripod ligand. Structure and spectroscopy of .mu.-oxobis(.mu.-benzoato)bis(bis(2-benzimidazolylmethyl)amine)diiron(III) (1988)

We gratefully acknowledge the support of the National Institute of Diabetes and Digestive and Kidney Diseases through Grant 5ROI DK37702-02. P.G.-R. gratefully acknowledges the award of a fellowship from the Comite Conjunto Hispano-Norteamericano para la Cooperacion Cultural y Educativa.
Cloning and Expression of DNA Coding for the Major House Dust Mite Allergen <i>Der p</i> 1 in <i>Escherichia coli</i> (1988)

A cDNA clone coding for the major house dust mite allergen Der p 1 was isolated from a lambda gt 11 library. Its sequence correlates with known amino acid sequences of Der p 1 and it produces a fusion protein which reacts with rabbit anti-Der p 1 antiserum.
Solid‐Phase, Parallel Syntheses by Ugi Multicomponent Condensation (1996)

The number and availability of starting compounds determine the structure diversity possible in a multicomponent reaction. For example, in a set of parallel reactions an amino-functionalized resin (P) was treated with 8 aldehydes, 12 carboxylic acids, and 1 isocyanide to provide 88 of the desired α-acyl amino amides [Eq. (a)]. Additional isocyanides not available commercially can be prepared from α-lithiated benzylisonitrile and used without purification. R1, R2 = alkyl, aryl.
Lipid Rafts and Pseudotyping (2001)

Specific interactions between envelope and core proteins govern the membrane assembly of most enveloped viruses. Despite this, mixed infections lead to pseudotyping, the association of the viral cores of one virus with the envelopes of another. How does this occur? We show here that the detergent-insoluble lipid rafts of the plasma membrane function as a natural meeting point for the transmembrane and core components of a phylogenetically diverse collection of enveloped viruses. As a result, viral particles preferentially incorporate both the envelope components of other viruses as well as the extra- and intracellular constituents of host cell lipid rafts, including gangliosides, glycosyl phosphatidylinositol-anchored surface proteins, and intracellular signal transduction molecules. Pharmacological disruption of lipid rafts interferes with virus production.
Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer (2012)

Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use. Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00730639.).
Abstract A047: Targeting androgen receptor decreases proliferation of triple-negative breast cancer (2013)

Abstract Recent studies demonstrate that the androgen receptor (AR) is expressed in up to a third of triple negative breast cancer (TNBC) and define a subtype of TNBC with a “luminal AR” gene signature. We hypothesized that AR+TNBC are dependent on AR for growth and that inhibiting AR activity by preventing nuclear localization and DNA binding will decrease proliferation and tumor burden in preclinical models of breast cancer. Indeed, knock down of AR expression using a lentiviral shRNA significantly reduced proliferation in cell line models of TNBC compared to cells transduced with a non-targeting control (2-fold reduction, p&amp;lt;0.001). Propidium iodide cell cycle analysis demonstrated that TNBC cells with reduced AR expression had a 22% increase in the percentage of cells in S-phase (p&amp;lt;0.001). In TNBC cells that exhibit androgen-stimulated growth, reduced AR expression inhibited response to ligand. Enzalutamide, an AR inhibitor, inhibited ligand mediated nuclear translocation of AR as assessed by nuclear cytosolic fractionation and significantly decreased baseline proliferation of TNBC in vitro (p&amp;lt;0.001). In MDA453 xenografts, enzalutamide significantly decreased tumor volume and weight by up to 85% and increased apoptosis as measured by cleaved caspase-3 by 60% compared to mice that received DHT alone. In addition, a 50% reduction in nuclear AR was observed in the tumors of mice treated with enzalutamide. Thus AR may play an important role in a subset of TNBC and presents an opportunity for targeted therapy. Citation Format: Valerie Barton, Nicholas D'Amato, Jennifer Richer. Targeting androgen receptor decreases proliferation of triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A047.
A Distinct Expression of Various Gene Subsets in CD34+ Cells Obtained From Patients with Early and Advanced Myelodysplastic Syndrome. (2009)

Abstract Abstract 3795 Poster Board III-731 Gene expression profiles of CD34+ cells were compared between a cohort of 51 patients with MDS or AML from MDS and 7 healthy controls. The patients were classified according to the WHO criteria as follows: 5q- syndrome (n=7), RA (n=3), RARS (n=2), RCMD (n=10), RAEB-1 (n=7), RAEB-2 (n=15), and AML with MLD (multilineage dysplasia) (n=7). HumanRef-8 v2 Expression Bead Chips (Illumina) were used to generate expression profiles of the samples for &gt;22,000 transcripts. The raw data were normalized data with the R software, lumi package. Normalized data were filtered by detection p-value &lt;0.01, resulting in total number of 9811genes. To identify differentially expressed genes we performed two parallel statistical hypothesis testings: Analysis of Variance (ANOVA) together with Tukey test and empirical bayesian thresholding correction for multiple testing problem; and Significance Analysis of Microarrays (SAM). The results were confirmed by real-time quantitative PCR for six genes (TaqMan Gene Expression Assays). Hierarchical clustering of significantly differentially expressed genes clearly separated patients and controls, 5q-syndrome and RAEB-1 as a separate entities confirming usefulness of WHO classification subgroups. The most up-regulated genes in all patients included HBG2, HBG1, CYBRD1, HSPA1B, ANGPT1, and MYC. We assume that expression changes in globin genes, both fetal and adult globins (HBG2, HBG1 and HBA1, HBB) may play role not only in dysregulation of erythropoiesis but also in the disease progression or leukemic transformation of MDS. Among the most down-regulated genes, 13 genes related to B-lymphopoiesis (e.g. POU2AF1, VPREB1, VPREB3, CD79A, EBF1, LEF1, BCL3, IRF8 &amp; IRF4) were detected, suggesting the abnormal development of B-cell progenitors in all MDS patients. Some of these genes (e.g. VPREB3, LEF1) showed decreasing trend in expression level from early to advanced MDS with the lowest expression in AML with MLD. Patients with advanced MDS had significantly decreased expression of genes involved in in the mitotic cell cycle, DNA replication, and chromosome segregation compared to early MDS where these gene subsets were up-regulated. The DAVID database also identified de-regulation in the cell cycle pathway through its 7 genes (CDC25C, CDC7, CDC20, ORC1L, CCNB2, BUB1, &amp; CCNA2). On the other hand, advanced MDS patients showed significant up-regulation of proto-oncogenes (BMI1, MERTK) and genes related to angiogenesis (ANGPT1), anti-apoptosis (VNN1). The results confirm on molecular basis that increased cell proliferation and resistance to apoptosis together with a loss of cell cycle control, damaged DNA repair and altered immune response may play an important role in the expansion of malignant clone in MDS patients. The study was supported by Grant NR-9235 obtained from the Ministry of Health, Czech Republic. Disclosures: No relevant conflicts of interest to declare.
Inhibitor of poly(ADP-ribose)transferase potentiates the recombinogenic but not the mutagenic action of alkylating agents in somatic cells in vivo in Drosophila melanogaster (1990)

The effect on somatic mutations and recombination by 3-aminobenzamide (3-ABA), an inhibitor of poly(ADP-ribose) transferase, was studied in the somatic wing spot test in Drosophila melanogaster, 3-ABA did not exert any effect by itself, but caused a strong increase of wing spots in combination with methyl methanesulphonate (MMS) and ethylnitrosourea (ENU). MMS and ENU differ in their mutagenic effects, ENU causing a much higher frequency of point mutations than MMS. The enhancement by 3-ABA of chemically induced wing spots was totally eliminated by the introduction of a heterozygous inversion. It can be concluded that 3-ABA interacted with the chemical mutagens for the induction of somatic recombination, but had no effect on point mutations or intragenic events.
Tissue Expression, Protease Specificity, and Kunitz Domain Functions of Hepatocyte Growth Factor Activator Inhibitor-1B (HAI-1B), a New Splice Variant of HAI-1 (2003)

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is an integral membrane protein expressed on epithelial cells and contains two extracellular Kunitz domains (N-terminal KD1 and C-terminal KD2) known to inhibit trypsin-like serine proteases. In tumorigenesis and tissue regeneration, HAI-1 regulates the hepatocyte growth factor (HGF)/c-Met pathway by inhibiting the activity of HGF activator (HGFA) and matriptase, two serine proteases that convert pro-HGF into its biologically active form. By screening a placental cDNA library, we discovered a new splice variant of HAI-1 designated HAI-1B that contains an extra 16 amino acids adjacent to the C terminus of KD1. To investigate possible consequences on Kunitz domain function, a soluble form of HAI-1B (sHAI-1B) comprising the entire extracellular domain was produced. First, we found that sHAI-1B displayed remarkable enzyme specificity by potently inhibiting only HGFA (IC50 = 30.5 nm), matriptase (IC50 = 16.5 nm), and trypsin (IC50 = 2.4 nm) among 16 serine proteases examined, including plasminogen activators (urokinase- and tissue-type plasminogen activators), coagulation enzymes thrombin, factors VIIa, Xa, XIa, and XIIa, and activated protein C. Relatively weak inhibition was found for plasmin (IC50 = 399 nm) and plasma kallikrein (IC50 = 686 nm). Second, the functions of the KD1 and KD2 domains in sHAI-1B were investigated using P1 residue-directed mutagenesis to show that inhibition of HGFA, matriptase, trypsin, and plasmin was due to KD1 and not KD2. Furthermore, analysis by reverse transcription-PCR demonstrated that HAI-1B and HAI-1 were co-expressed in normal tissues and various epithelial-derived cancer cell lines. Both isoforms were up-regulated in eight examined ovarian carcinoma specimens, three of which had higher levels of HAI-1B RNA than of HAI-1 RNA. Therefore, previously demonstrated roles of HAI-1 in various physiological and pathological processes likely involve both HAI-1B and HAI-1.
Padlock Probes: Circularizing Oligonucleotides for Localized DNA Detection (1994)

Nucleotide sequence information derived from DNA segments of the human and other genomes is accumulating rapidly. However, it frequently proves difficult to use such short DNA segments to identify clones in genomic libraries or fragments in blots of the whole genome or for in situ analysis of chromosomes. Oligonucleotide probes, consisting of two target-complementary segments, connected by a linker sequence, were designed. Upon recognition of the specific nucleic acid molecule the ends of the probes were joined through the action of a ligase, creating circular DNA molecules catenated to the target sequence. These probes thus provide highly specific detection with minimal background.
Extraction of erythropoietin from isolated renal glomeruli of hypoxic rats (1983)

We investigated whether erythropoietin (Ep) can be extracted from renal glomeruli of hypoxic rats. Hypoxia was induced in a hypobaric chamber at 0.42 atmospheres for usually 6 h. Glomeruli were isolated with a sieving technique from kidneys that were flushed free of blood. Ep activities in glomeruli homogenates were determined in the fetal mouse liver cell assay and in the hypoxia exposed mouse assay. We found in vitro erythropoietic activity of glomerular extracts, which increased about 25-fold during hypoxia. Incubation of the extracts with anti-Ep serum abolished the activity. Its binding characteristics on Wheat germ lectin. Ricinus communis lectin and DEAE-cellulose suggested that glomeruli contained Ep precursor(s) that lacked terminal sugar residues. Such an incomplete carbohydrate portion seems also compatible with the finding that glomerular extracts did not stimulate erythropoiesis in hypoxia exposed mice.
Rolling in the clover: trefoil factor family (TFF)‐domain peptides, cell migration and cancer (1997)

Trefoil factor family (TFF)-domain peptides 1-3 are mucin-associated molecules, largely found in epithelia of gastrointestinal tissues. Structurally similar, resistant to enzymatic degradation, they are up-regulated around areas of epithelial damage such as ulcers. Transgenic expression or exogenous peptide ameliorates or prevents gastric mucosal damage due to indomethacin and some are rapidly up-regulated after cryogenic burns. A role in promoting cell migration is strongly suggested. Knockout mice lacking TFF1 or TFF3 show significant pathology, with the former developing gastric tumours. A recent Conference Philippe Laudat agreed upon a new nomenclature for these peptides.
Drug Delivery to Posterior Intraocular Tissues: Third Annual ARVO/Pfizer Ophthalmics Research Institute Conference (2008)

The third Annual ARVO/Pfizer Ophthalmic Research Institute Conference was held Friday and Saturday, May 4 and 5, 2007 at the Fort Lauderdale Grande Hotel and Yacht Club, Fort Lauderdale, Florida. The conference, funded by the ARVO Foundation for Eye Research through a grant from Pfizer Ophthalmics, provided an opportunity to gather experts from within and outside ophthalmology to develop strategies to address drug delivery to posterior intraocular tissues—a topic of great interest, as the major route of drug delivery is via intravitreous injection.

A working group of 33 participants, focused interdisciplinary contributors, 19 observers from ARVO/Pfizer, and clinical and basic ophthalmic researchers convened to identify (1) unmet patient needs regarding current drug delivery, novel treatment of retinal diseases, the potential for novel drug design opportunities, drug delivery methods for targeted localized and sustained release, and delivery of macromolecules (siRNA, DNA); and (2) to evaluate the usefulness of nanoparticles, microbeads, and implants for drug delivery, as well as physical means of drug delivery (ionophoresis, electroporation, and microneedles).


Session I: Unmet Needs and New Drug Opportunities in Treating Disorders of the Posterior Segment


Session II: Animal Models of Posterior Ocular Diseases


Session III: New Drug Design and Delivery Systems: What Do Experts See Beyond the Horizon?


Session IV: Ocular Drug Delivery Using Nanoparticles, Microbeads, and Microneedles


Session V: Transscleral, Intravitreous, and Suprachoroidal Drug Delivery


Session VI: Ocular Tissue Dissection, Modeling, and Ocular Tissue Assays


Session VII: Iontophoresis, Electroporation, Electrophoresis, and Photo-acoustic Delivery



Each session began with a 10-minute introduction followed by a 30-minute lecture by a distinguished expert. Allan S. Hoffman, ScD, Professor of Bioengineering at the University of Washington, Seattle, presented “Design of Polymer Carriers for Intracellular Delivery of Biomolecular Drugs” and Mansoor Amiji, RPh, PhD, Professor and Associate Chairman of Pharmaceutical Science at Northeastern University (Boston, MA), presented “Nanotechnology for Advanced Drug Delivery.”

During the remainder of each session, participants, and attendees discussed pertinent questions, voiced opinions, and identified unanswered questions. These discussions confirmed current and future needs for ocular drug delivery to the posterior segment.