gebhart/patrepeval huggingface dataset:
Successful Production of Pseudotyped rAAV Vectors Using a Modified Baculovirus Expression System (2005)

Scalable production of rAAV vectors remains a major obstacle to the clinical application of this prototypical gene therapy vector. A recently developed baculovirus-based production protocol (M. Urabe et al., 2002, Hum. Gene Ther. 13, 1935-1943) found limited applications due to the system's design. Here we report a detailed analysis of the stability of the original baculovirus system components BacRep, BacVP, and transgene cassette-containing BacGFP. All of the baculovirus helpers analyzed were prone to passage-dependent loss-of-function deletions resulting in considerable decreases in rAAV titers. To alleviate the instability and to extend the baculovirus platform to other rAAV serotypes, we have modified both Rep- and Cap-encoding components of the original system. The modifications include a parvoviral phospholipase A2 domain swap allowing production of infectious rAAV8 vectors in vivo. Alternatively, an infectious rAAV8 (or rAAV5) vector incorporating the AAV2 VP1 capsid protein in a mosaic vector particle with AAV8 capsid proteins was produced using a novel baculovirus vector. In this vector, the level of AAV2 VP1 expression is controlled with a "riboswitch," a self-cleaving ribozyme controlled by toyocamycin in the "ON" mode. The redesigned baculovirus system improves our capacity for rAAV manufacturing by making this production platform more applicable to other existing serotypes.
The role of nuclear factor-κB essential modulator (NEMO) in B cell development and survival (2003)

The transcription factor nuclear factor-kappaB (NF-kappaB) is essential for immune and inflammatory responses. NF-kappaB essential modulator (NEMO) is a scaffolding component of the IkappaB kinase complex required for NF-kappaB activation in vitro. Because NF-kappaB activation is involved in B cell development and function, we set out to determine whether NEMO is required for these processes. NEMO(-/-) mice die very early during embryogenesis, and fetal livers from NEMO(-/-) embryos can not reconstitute either B or T lymphopoiesis in irradiated host mice. We therefore used NEMO(-/-) embryonic stem cells and the OP9 in vitro differentiation system to demonstrate that NEMO is not required for B cell development but plays an important role in B cell survival.
Protein L. A bacterial Ig-binding protein that activates human basophils and mast cells. (1990)

Peptostreptococcus magnus strain 312 (10(6) to 10(8)/ml), which synthesizes a protein capable of binding to kappa L chains of human Ig (protein L), stimulated the release of histamine from human basophils in vitro. P. magnus strain 644, which does not synthesize protein L, did not induce histamine secretion. Soluble protein L (3 x 10(-2) to 3 micrograms/ml) induced histamine release from human basophils. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE): it was Ca2(+)- and temperature-dependent, optimal release occurring at 37 degrees C in the presence of 1.0 mM extracellular Ca2+. There was an excellent correlation (r = 0.82; p less than 0.001) between the maximal percent histamine release induced by protein L and that induced by anti-IgE, as well as between protein L and protein A from Staphylococcus aureus (r = 0.52; p less than 0.01). Preincubation of basophils with either protein L or anti-IgE resulted in complete cross-desensitization to a subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (lambda-chains) blocked anti-IgE-induced histamine release but failed to block the histamine releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (kappa-chains) blocked both anti-IgE- and protein L-induced releases, whereas human polyclonal IgG selectively blocked protein L-induced secretion. Protein L acted as a complete secretagogue, i.e., it activated basophils to release sulfidopeptide leukotriene C4 as well as histamine. Protein L (10(-1) to 3 micrograms/ml) also induced the release of preformed (histamine) and de novo synthesized mediators (leukotriene C4 and/or PGD2) from mast cells isolated from lung parenchyma and skin tissues. Intradermal injections of protein L (0.01 to 10 micrograms/ml) in nonallergic subjects caused a dose-dependent wheal-and-flare reaction. Protein L activates human basophils and mast cells in vitro and in vivo presumably by interacting with kappa L chains of the IgE isotype.
Novel CD43 specific phage antibodies react with early stage colorectal tumours (2004)

Two panning strategies have been used to isolate phage antibody clones that recognise an intracellular epitope of CD43. Firstly, a naive scFv library was panned against a 15-mer CD43 synthetic peptide (RGGKRNGVVDAWAGP), and secondly the naive library was panned against native CD43, isolated from whole cell lysate of Colo205 cells, followed by selection with the synthetic CD43 peptide. Four phage antibodies (HapE8, F2, G9 and G11) were isolated and used in a preliminary immunohistochemistry study of CD43 expression on frozen colorectal adenoma and carcinoma tissue. The three antibodies HapE8, F2 and G11 showed a similar reactivity pattern, staining all adenomas and Dukes' A carcinomas, but only 2/4 Dukes' B and 1/9 Dukes' C. Antibody HapG9 similarly bound to 5/5 adenomas, but only 1/5 Dukes' A carcinoma and no tumours of a more advanced stage. No reactivity with normal colonic epithelium was observed but cross-reactivity with stromal lymphocytes was seen. These new anti-CD43 antibodies are likely to prove useful as screening tools in the detection of colorectal adenomas.
Vanadia/silica xerogels and nanocomposites (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTVanadia/silica xerogels and nanocompositesA. E. Stiegman, Hellmut Eckert, Gary Plett, Soon Sam Kim, Mark Anderson, and Andre YavrouianCite this: Chem. Mater. 1993, 5, 11, 1591–1594Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/cm00035a001https://doi.org/10.1021/cm00035a001research-articleACS PublicationsRequest reuse permissionsArticle Views220Altmetric-Citations59LEARN 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 Get e-Alerts
Peroxisome Proliferator-Activated Receptor γ Agonist Down-Regulates IL-17 Expression in a Murine Model of Allergic Airway Inflammation (2009)

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a critical role in the control of airway inflammation. Recently, IL-17 has been found to be implicated in many immune and inflammatory responses, including airway inflammation. However, no data are available concerning the effect of PPARgamma on IL-17 production in airway inflammatory diseases. In this study, we used a mouse model of asthma to evaluate the effect of two PPARgamma agonists, rosiglitazone or pioglitazone, on IL-17 expression in allergic airway disease. After OVA inhalation, mice developed the typical pathophysiological features of asthma, and the expression of IL-17 protein and mRNA in the lungs was increased. Administration of rosiglitazone or pioglitazone reduced the pathophysiological features of asthma and decreased the increased IL-17 protein and mRNA expression after OVA inhalation. In addition, the attenuating effect of PPARgamma agonist on allergic airway inflammation and bronchial hyperresponsiveness is abrogated by coadministration of rIL-17. This study also showed that the inhibition of IL-17 activity with anti-IL-17 Ab remarkably reduced the increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, and the increased levels of IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid and OVA-specific IgE in serum. In addition, we found that administration of rosiglitazone or pioglitazone decreased the increased NF-kappaB activity and that a NF-kappaB inhibitor, BAY 11-7085, substantially reduced the increased IL-17 protein levels in the lung tissues after OVA inhalation. These findings suggest that the therapeutic effect of PPARgamma in asthma is partly mediated by regulation of IL-17 expression via NF-kappaB pathway.
Human carbonic anhydrase I cDNA (1987)

Journal Article Human carbonic anhydrase I cDNA Get access Jonathan H. Barlow, Jonathan H. Barlow Department of Biochemistry and MRC Human Biochemical Genetics Unit,University College,London WC1E 6BT,UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Nicholas Lowe, Nicholas Lowe Department of Biochemistry and MRC Human Biochemical Genetics Unit,University College,London WC1E 6BT,UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Yvonne H. Edwards, Yvonne H. Edwards Department of Biochemistry and MRC Human Biochemical Genetics Unit,University College,London WC1E 6BT,UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter H. W. Butterworth Peter H. W. Butterworth Department of Biochemistry and MRC Human Biochemical Genetics Unit,University College,London WC1E 6BT,UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 15, Issue 5, 11 March 1987, Page 2386, https://doi.org/10.1093/nar/15.5.2386 Published: 15 March 1987 Article history Received: 09 February 1986 Published: 15 March 1987
Grip Strength and the Risk of Incident Alzheimer’s Disease (2007)

Decline in strength is common in older persons but little data are available about its association with Alzheimer's disease (AD). We studied the association of level of and rate of change in strength in 877 older persons without dementia at baseline and risk of AD. In a proportional hazards model adjusted for age, sex and education, each 1-lb decrease in grip strength at baseline was associated with about a 1.5% increase in the risk of AD (HR, 0.986; 95% CI, 0.973-0.998). These results persisted even after excluding persons who developed AD in the first 5 years of follow-up. In a subsequent model examining the association of the annual rate of change in grip strength with incident AD, each 1-lb annual decline in grip strength was associated with about a 9% increase in the risk of AD (HR, 0.915; 95% CI, 0.884-0.948). Results were similar after controlling for level and rate of change in body mass index, parkinsonian signs, physical and cognitive activity, depressive symptoms, vascular diseases and risk factors, social networks and early-life socioeconomic status. Declining strength in old age is associated with an increased risk of AD.
Computed Tomographic Analysis of the Anatomy of the Left Atrium and the Esophagus (2004)

The esophagus and posterior LA wall are in close contact over a large area that may often lie within the atrial fibrillation ablation zone, and there is marked variation in the anatomic relationship of the esophagus and the posterior LA. Both the esophageal and atrial walls are quite thin. However, a layer of adipose tissue may serve to insulate the esophagus from thermal injury, explaining why atrioesophageal fistulas are rare.
Leukemia Inhibitory Factor, a Potent Cardiac Hypertrophic Cytokine, Activates the JAK/STAT Pathway in Rat Cardiomyocytes (1997)

Leukemia inhibitory factor (LIF) is a member of the interleukin-6 family of cytokines, which induces a wide range of responses in a variety of cells. The aim of this study was to investigate whether LIF induces cardiomyocyte hypertrophy and transmits signals through the JAK/STAT (indicating just another kinase/signal transducer and activator of transcription) pathway in primary cultured neonatal rat cardiomyocytes. LIF increased protein content and [3H]phenylalanine uptake in cardiomyocytes in a dose-dependent manner. LIF (10(3) U/mL) induced rapid tyrosine phosphorylation of gp130, JAK1, JAK2, STAT1, and STAT3 but not Tyk2 or STAT2. LIF also induced autokinase activity of JAK1 in a time-dependent manner. Gel shift assays for interferon gamma activation site/interferon-stimulated responsive element and sis-inducible element (SIE) revealed that LIF induced dimerization of STAT1 and STAT3 and formation of sis-inducing factor complexes, which subsequently interacted with SIE in the promoter. Preincubation with anti-STAT1 and anti-STAT3 antibodies inhibited the binding of SIF complexes. In conclusion, LIF induces cardiac hypertrophy and directly stimulates the JAK/STAT pathway in cardiomyocytes.
ChemInform Abstract: VINYL CATIONS. 32. SOLVOLYSIS REACTIONS OF CYCLONONYNYL AND CYCLOOCTYNYL DERIVATIVES (1980)

Abstract Der Ester (Ia) liefert bei seiner Solvolyse mit 50proz. wäßrigem Ethanol unter Umlagerung das Keton (III) als cis‐trans‐Isomerengemisch (Verhältnis 85:15), wobei intermediär unter Beteiligung der Dreifachbindung das Vinylkation (II) gebildet wird, sowie den Alkohol (Ib) (Ausb. 8%).
Purification and characterization of a new alcohol dehydrogenase from human stomach. (1991)

Starch gel electrophoresis of homogenates from human stomach mucosa resolves three alcohol dehydrogenase (ADH) forms: the anodic chi-ADH (class III), the cathodic gamma-ADH (class I), and a new form of slow cathodic mobility that has not been previously characterized. In this work, we describe the purification in three chromatographic steps and the physical and kinetic characterization of this new human alcohol dehydrogenase, which we have named sigma-ADH. The enzyme exhibits the general physicochemical features (Mr, zinc content, subunit Mr, cofactor preference) of all mammalian alcohol dehydrogenases. The kinetic studies show a high Km value (41 mM) and a high kcat value (280 min-1) for ethanol at pH 7.5. The Km decreases as the alcohol increases its chain length. The aldehydes are better substrates than the corresponding alcohols, with m-nitrobenzaldehyde being the best substrate examined. sigma-ADH is strongly inhibited by 4-methylpyrazole, but with a Ki (10 microM) still higher than that for a class I isoenzyme. These properties suggest that sigma-ADH is a class II isoenzyme, different from pi-ADH and similar to that previously described by us in rat stomach. At the high ethanol concentrations in stomach after drinking, sigma-ADH is probably the ADH form with the largest contribution to human gastric ethanol metabolism.
Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen (2009)

Gene therapy of human cancer using genetically engineered lymphocytes is dependent on the identification of highly reactive T-cell receptors (TCRs) with antitumor activity. We immunized transgenic mice and also conducted high-throughput screening of human lymphocytes to generate TCRs highly reactive to melanoma/melanocyte antigens. Genes encoding these TCRs were engineered into retroviral vectors and used to transduce autologous peripheral lymphocytes administered to 36 patients with metastatic melanoma. Transduced patient lymphocytes were CD45RA(-) and CD45RO(+) after ex vivo expansion. After infusion, the persisting cells displayed a CD45RA(+) and CD45RO(-) phenotype. Gene-engineered cells persisted at high levels in the blood of all patients 1 month after treatment, responding patients with higher ex vivo antitumor reactivity than nonresponders. Objective cancer regressions were seen in 30% and 19% of patients who received the human or mouse TCR, respectively. However, patients exhibited destruction of normal melanocytes in the skin, eye, and ear, and sometimes required local steroid administration to treat uveitis and hearing loss. Thus, T cells expressing highly reactive TCRs mediate cancer regression in humans and target rare cognate-antigen-containing cells throughout the body, a finding with important implications for the gene therapy of cancer. This trial was registered at www.ClinicalTrials.gov as NCI-07-C-0174 and NCI-07-C-0175.
Synthesis and evaluation of optically pure [3H]‐(+)‐pentazocine, a highly potent and selective radioligand for σ receptors (1989)

Tritium‐labeled (+)‐pentazocine ([ 3 H]‐1b) of specific activity 26.6 Ci/mmol was synthesized in 3 steps starting with (+)‐normetazocine (2) of defined optical purity. [ 3 H]‐1b has been characterized as a highly selective ligand for labeling of σ receptors. Competition data revealed that [ 3 H]‐1b could be displaced from guinea pig brain membrane preparations with a number of commonly used σ receptor ligands. [ 3 H]‐1b exhibited saturable, enantioselective binding with a K d of 5.13±0.97 nM and a B max of 1146±122 fmol/mg protein. Phencyclidine (PCP) displaced [ 3 H]‐1b with low affinity while MK‐801 was inactive, thus indicating insignificant activity at the PCP‐binding site; apomorphine failed to displace [ 3 H]‐1b indicating lack of dopamine receptor cross‐reactivity. Since the affinity of [ 3 H]‐1b is about 6 times that of the two commonly employed σ ligands ((+)‐3‐[ 3 H]PPP and [ 3 H]DTG) and since it is more selective for σ receptors than the benzomorphan [ 3 H]SKF‐10,047, it represents the first example of a highly selective benzomorphan based σ receptor ligand. [ 3 H]‐1b should prove useful for further study of the structure and function of σ receptors.
Susceptibility to Type 1 Diabetes Is Associated With ApoCIII Gene Haplotypes (2006)

Type 1 diabetes is a disease of beta-cell destruction leading to insulin deficiency. Genes for type 1 diabetes have been identified; however, much of the genetic risk remains unexplained. Genetic variation within the apolipoprotein CIII (apoCIII) gene alters apoCIII levels, which are increased in type 1 diabetes and induce beta-cell apoptosis. We therefore hypothesize haplotypes within the apoCIII gene are associated with type 1 diabetes. DNA from 584 type 1 diabetic patients and 591 control subjects were genotyped for six single nucleotide polymorphisms (SNPs) in the apoCIII gene (C-641A, C-482T, T-455C, C1100T, C3175G, and T3206G). Two alleles of a haplotype block (promoter SNPs + C3175G) were associated with type 1 diabetes. The A-T-C-C allele frequency was higher in type 1 diabetes (0.19 vs. 0.16, P = 0.05), and the C-C-T-C allele was reduced in type 1 diabetes (0.60 vs. 0.65, P = 0.04). The odds ratio (OR) for A-T-C-C allele increased with 0, 1, and 2 copies (OR of 1.00, 1.24, and 1.60, respectively; P = 0.05) and decreased for the C-C-T-C allele (1.00, 0.97, and 0.73, respectively; P = 0.03). This haplotype block contains an insulin response element. Screening for this haplotype may identify at-risk individuals, and this pathway may offer a target for prevention of type 1 diabetes.
Caenorhabditis elegans in Parkinson's Disease Drug Discovery: Addressing an Unmet Medical Need (2008)

It has been over forty years since dopamine neuron degeneration in the substantia nigra and Lewy body formation within surviving cells were described as the pathological hallmarks of Parkinson's disease (PD). Although research in the intervening decades particularly in the last twenty-five years has yielded a variety of robust animal models and invaluable mechanistic insights into PD-associated neuronal dysfunction and cell death, therapeutic agents have not been forthcoming to alter the course of PD. Recently, the screening of experimental therapeutics for PD has been pursued through the use of genetically tractable models, such as the nematode Caenorhabditis elegans. This simple worm remarkably recapitulates the basic cellular and molecular pathways associated with PD, is amenable to facile genetic methods, and through the use of high-throughput screening technologies, provides powerful new opportunities for the in vivo identification of therapeutic targets. In this review we briefly describe the utility that the C. elegans model system may have for PD drug discovery.
The responsiveness of embryonic stem cells to alpha and beta interferons provides the basis of an inducible expression system for analysis of developmental control genes. (1993)

Embryonic stem (ES) cells, derived from the inner cell mass of the preimplantation mouse embryo, are used increasingly as an experimental tool for the investigation of early mammalian development. The differentiation of these cells in vitro can be used as an assay for factors that regulate early developmental decisions in the embryo, while the effects of altered gene expression during early embryogenesis can be analyzed in chimeric mice generated from modified ES cells. The experimental versatility of ES cells would be significantly increased by the development of systems which allow precise control of heterologous gene expression. In this paper, we report that ES cells are responsive to alpha and beta interferons (IFNs). This property has been exploited for the development of inducible ES cell expression vectors, using the promoter of the human IFN-inducible gene, 6-16. The properties of these vectors have been analyzed in both transiently and stably transfected ES cells. Expression was minimal or absent in unstimulated ES cells, could be stimulated up to 100-fold by treatment of the cells with IFN, and increased in linear fashion with increasing levels of IFN. High levels of induced expression were maintained for extended periods of time in the continuous presence of the inducing signal or following a 12-h pulse with IFN. Treatment of ES cells with IFN did not affect their growth or differentiation in vitro or compromise their developmental potential. This combination of features makes the 6-16-based expression vectors suitable for the functional analysis of developmental control control genes in ES cells.
<title>Techniques for pixel-level analog-to-digital conversion</title> (1998)

Two techniques for performing pixel level analog to digital conversion (ADC) are reviewed. The first is an over-sampling technique which uses a one bit first order (Sigma) (Delta) modulator for each 2 X 2 block of pixels to directly convert photocharge to bits. Each modulator is implemented using 17 transistors. The second technique is a Nyquist rate multi-channel-bit-serial (MCBS) ADC. The technique use successive comparisons to convert the pixel voltage to bits. Results obtained from implementations of these ADC techniques are presented. The techniques are compared based on size, charge handling capacity, FPN, noise sensitivity, data throughput, quantization, memory/processing, and power dissipation requirements for both visible an dIR imagers. From the comparison it appears that the (Sigma) (Delta) ADC is better suited to IR imagers, while the MCBS ADC is better suited to imagers in the visible range.