gebhart/patrepeval huggingface dataset:
Adaptation of a retrovirus as a eucaryotic vector transmitting the herpes simplex virus thymidine kinase gene. (1982)

We investigated the feasibility of using retroviruses as vectors for transferring DNA sequences into animal cells. The thymidine kinase (tk) gene of herpes simplex virus was chosen as a convenient model. The internal BamHI fragments of a DNA clone of Moloney leukemia virus (MLV) were replaced with a purified BamHI DNA segment containing the tk gene. Chimeric genomes were created carrying the tk insert in both orientations relative to the MLV sequence. Each was transfected into TK- cells along with MLV helper virus, and TK+ colonies were obtained by selection in the presence of hypoxanthine, aminopterin, and thymidine (HAT). Virus collected from TK+-transformed, MLV producer cells passed the TK+ phenotype to TK- cells. Nonproducer cells were isolated, and TK+ transducing virus was subsequently rescued from them. The chimeric virus showed single-hit kinetics in infections. Virion and cellular RNA and cellular DNA from infected cells were all shown to contain sequences which hybridized to both MLV- and tk-specific probes. The sizes of these sequences were consistent with those predicted for the chimeric virus. In all respects studied, the chimeric MLV-tk virus behaved like known replication-defective retroviruses. These experiments suggest great general applicability of retroviruses as eucaryotic vectors.
Allograft Prosthetic Composite Arthroplasty for Osteosarcoma and Other Aggressive Bone Tumors (1991)

Allograft prosthetic composite arthroplasty is a reconstruction alternative after limb salvage for aggressive bone tumors. It combines an off-the-shelf implant with a fresh-frozen allograft and has several potential advantages over conventional techniques. Good clinical results can be achieved with acceptable morbidity. The procedure can be performed successfully even in patients receiving chemotherapy. Nonunion was the most common complication encountered but was amenable to autogenous iliac bone graft. The procedure can be customized to meet the needs of the patient, making custom implant manufacturing delay and expense unnecessary.
Formation of Protoanemonin from 2-Chloro-cis,cis-Muconate by the Combined Action of Muconate Cycloisomerase and Muconolactone Isomerase (2002)

Muconate cycloisomerases are known to catalyze the reversible conversion of 2-chloro-cis,cis-muconate by 1,4- and 3,6-cycloisomerization into (4S)-(+)-2-chloro- and (4R/5S)-(+)-5-chloromuconolactone. 2-Chloromuconolactone is transformed by muconolactone isomerase with concomitant dechlorination and decarboxylation into the antibiotic protoanemonin. The low k(cat) for this compound compared to that for 5-chloromuconolactone suggests that protoanemonin formation is of minor importance. However, since 2-chloromuconolactone is the initially predominant product of 2-chloromuconate cycloisomerization, significant amounts of protoanemonin were formed in reaction mixtures containing large amounts of muconolactone isomerase and small amounts of muconate cycloisomerase. Such enzyme ratios resemble those observed in cell extracts of benzoate-grown cells of Ralstonia eutropha JMP134. In contrast, cis-dienelactone was the predominant product formed by enzyme preparations, in which muconolactone isomerase was in vitro rate limiting. In reaction mixtures containing chloromuconate cycloisomerase and muconolactone isomerase, only minute amounts of protoanemonin were detected, indicating that only small amounts of 2-chloromuconolactone were formed by cycloisomerization and that chloromuconate cycloisomerase actually preferentially catalyzes a 3,6-cycloisomerization.
A Facile Synthesis of Azido-Terminated Heterobifunctional Poly(ethylene glycol)s for “Click” Conjugation (2007)

New azido-terminated heterobifunctional poly(ethylene glycol) (PEG) derivatives having primary amine and carboxyl end groups, (Azide-PEG-NH 2 and Azide-PEG-COOH, respectively) were synthesized with high efficiency. An alpha-allyl-omega-hydroxyl PEG was prepared as the first step to Azide-PEG-X (X = NH 2 and COOH) through the ring-opening polymerization of ethylene oxide (EO) with allyl alcohol as an initiator, followed by two-step modification of the hydroxyl end to an azido group. To introduce primary amino or carboxyl functional groups, amination and carboxylation reactions of the allyl terminal ends was then conducted by a radical addition of thiol compounds. Molecular functionalities of both ends of the PEG derivatives thus prepared were characterized by (1)H, (13)C NMR, and MALDI-TOF MS spectra, validating that the reaction proceeded quantitatively. The terminal azido functionality is available to conjugate various ligands with an alkyne group through the 1,3-dipolar cycloaddition reaction condition ("click chemistry").
Site-Specific PEGylation of Engineered Cysteine Analogues of Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (2005)

Granulocyte macrophage colony-stimulating factor (GM-CSF) stimulates proliferation of hematopoietic cells of the macrophage and granulocyte lineages and is used clinically to treat neutropenia and other myeloid disorders. Because of its short circulating half-life, GM-CSF is administered to patients by daily injection. We describe here the engineering of highly potent, long-acting human GM-CSF proteins through site-specific modification of GM-CSF cysteine analogues with a cysteine-reactive poly(ethylene glycol) (PEG) reagent. Thirteen cysteine analogues of GM-CSF were constructed, primarily in nonhelical regions of the protein believed to lie away from the major receptor binding sites. The GM-CSF cysteine analogues were properly processed but insoluble following secretion into the Escherichia coli periplasm. The proteins were refolded and purified by column chromatography. Ten of the cysteine analogues could be modified with a 5-kDa maleimide PEG, and seven of the mono-PEGylated proteins were purified by ion-exchange column chromatography. Biological activities of the 13 cysteine analogues and 7 PEGylated cysteine analogues were comparable to that of wild-type GM-CSF in an in vitro cell proliferation assay using human TF-1 cells. One cysteine analogue was modified with larger 10-, 20-, and 40-kDa PEGs, with only minimal loss of in vitro bioactivity. Pharmacokinetic experiments in rats demonstrated that the PEGylated proteins had up to 47-fold longer circulating half-lives than wild-type GM-CSF. These data demonstrate the utility of site-specific PEGylation for creating highly potent, long-acting GM-CSF analogues and provide further evidence that the nonhelical regions of human GM-CSF examined are largely nonessential for biological activity of the protein.
Xist RNA exhibits a banded localization on the inactive X chromosome and is excluded from autosomal material in cis (1999)

The propagation of X chromosome inactivation is thought to be mediated by the cis- limited spreading of the non-protein coding Xist transcript. In this report we have investigated the localization of Xist RNA on rodent metaphase chromosomes. We show that Xist RNA exhibits a banded pattern on the inactive X and is excluded from regions of constitutive heterochromatin. The banding pattern suggests a preferential association with gene-rich, G-light regions. Analysis of X:autosome rearrangements revealed that restricted propagation of X inactivation into cis -linked autosomal material is reflected by a corresponding limited spread of Xist RNA. We discuss these results in the context of models for the function of Xist RNA in the propagation of X inactivation.
A Straight Path to Circular Proteins (2009)

Folding and stability are parameters that control protein behavior. The possibility of conferring additional stability on proteins has implications for their use in vivo and for their structural analysis in the laboratory. Cyclic polypeptides ranging in size from 14 to 78 amino acids occur naturally and often show enhanced resistance toward denaturation and proteolysis when compared with their linear counterparts. Native chemical ligation and intein-based methods allow production of circular derivatives of larger proteins, resulting in improved stability and refolding properties. Here we show that circular proteins can be made reversibly with excellent efficiency by means of a sortase-catalyzed cyclization reaction, requiring only minimal modification of the protein to be circularized.
Isolation and Characterization of a Starchless Mutant of Arabidopsis thaliana (L.) Heynh Lacking ADPglucose Pyrophosphorylase Activity (1988)

A mutant of Arabidopsis thaliana lacking ADPglucose pyrophosphorylase activity (EC 2.7.7.27) was isolated (from a mutagenized population of plants) by screening for the absence of leaf starch. The mutant grows as vigorously as the wild type in continuous light but more slowly than the wild type in a 12 hours light/12 hours dark photoperiod. Genetic analysis showed that the deficiency of both starch and ADPglucose pyrophosphorylase activity were attributable to a single, nuclear, recessive mutation at a locus designated adg1. The absence of starch in the mutant demonstrates that starch synthesis in the chloroplast is entirely dependent on a pathway involving ADPglucose pyrophosphorylase. Analysis of leaf extracts by two-dimensional polyacrylamide gel electrophoresis followed by Western blotting experiments using antibodies specific for spinach ADPglucose pyrophosphorylase showed that two proteins, present in the wild type, were absent from the mutant. The heterozygous F(1) progeny of a cross between the mutant and wild type had a specific activity of ADPglucose pyrophosphorylase indistinguishable from the wild type. These observations suggest that the mutation in the adg1 gene in TL25 might affect a regulatory locus.
Rituximab Anti-CD20 Monoclonal Antibody Therapy in Non-Hodgkin’s Lymphoma: Safety and Efficacy of Re-Treatment (2000)

In this re-treatment population, safety and efficacy were not apparently different from those after initial rituximab exposure.
Evolution of the Human Immunodeficiency Virus Type 1 Envelope during Infection Reveals Molecular Corollaries of Specificity for Coreceptor Utilization and AIDS Pathogenesis (2000)

The evolution of human immunodeficiency virus type 1 infection is associated with a shift in the target cell population, driven by variability in coreceptor utilization resulting from diversity in env. To elucidate the potential consequences of these changes for Env-mediated fusion over the course of AIDS, we examined the biological properties of serial viral isolates and determined coreceptor utilization by the products of env cloned from two individuals, followed from the detection of seroconversion throughout the course of their infection. One had a typical course, and the other had an accelerated progression. Early isolates were non-syncytium inducing, and the corresponding Env exclusively utilized CCR5, whereas Env from late phases of infection showed restricted utilization of CXCR4 in both patients. Env from subject SC24, who had a standard progression, demonstrated multitropism, manifested by utilization of CCR3, CXCR4, and CCR5 in the intervening period. In contrast, Env from patient SC51, who experienced early conversion to the syncytium-inducing phenotype, developed dualtropic coreceptor utilization of CCR5 and CXCR4. Genetic analysis of env from each isolate revealed that those with an X4 phenotype formed a distinct subcluster within each subject. Analysis of chimeras constructed from R5 and multispecific env from patient SC24 demonstrated that while the V3 domain played a dominant role in determining coreceptor utilization, sequences in the V4-V5 region also contributed to the latter phenotype. Immunoprecipitation experiments confirmed that the hybrid Env proteins were expressed at similar levels. These experiments demonstrate that progression from the R5 to X4 phenotype may occur through a multi- or dual-tropic intermediate and that multiple domains contribute to this process.
Future neuroprotective strategies in the post-thrombolysis era -Neurovascular unit protection and vascular endothelial protection- (2011)

From an appearance of recombinant tissue plasminogen activator (rt-PA) in the clinical therapy on 2005 in Japan, the therapeutic strategy of ischemic stroke therapy is now changing dramatically. Many experimental data from animal stroke and clinical trials of neuroprotective agents failed to clinical useful therapeutic strategy. A free radical scavenger, edaravone is the first clinical drug for neuroprotection in the world which has been used in almost all ischemic stroke patients in Japan from 2001. Now, it is especially useful in thrombolytic therapy with rtPA, whereas we still need the newly more effective neuroprotective drugs which can be applied to many ischemic stroke patients. Therefore, we review and describe the future neuroprotective strategies in the post-thrombolysis era.
The Animal Pathogen-Like Type III Secretion System Is Required for the Intracellular Survival of Burkholderia mallei within J774.2 Macrophages (2006)

Burkholderia mallei is a highly infectious gram-negative pathogen and is the causative agent of human and animal glanders. By generating polar mutations (disruption of bsaQ and bsaZ) in the B. mallei ATCC 23344 animal pathogen-like type III secretion system (TTS), we demonstrate that this bacterial protein delivery system is required for intracellular growth of B. mallei in J774.2 cells, formation of macrophage membrane protrusions, actin polymerization, and phagosomal escape. These findings suggest that TTS plays a role in the intracellular trafficking of B. mallei and may facilitate cell-to-cell spread via actin-based motility.
A MOUSE β-GLOBIN MUTANT THAT IS AN EXACT MODEL OF HEMOGLOBIN RAINIER IN MAN (1985)

A mutation induced by ethylnitrosourea in a spermatogonial stem cell of a 101/H mouse has resulted in a structurally altered beta-diffuse major globin in one of his offspring. The mutant hemoglobin is associated with polycythemia, rubor, increased oxygen affinity and decreased hem-hem interaction. The mutant haplotype has been designated Hbbd4, polycythemia. Amino acid analysis of the mutant globin has shown that a single substitution beta 145 Tyr----Cys has occurred, and it is proposed that ethylnitrosourea induced an A----G transition in the tyrosine codon (TAC----TGC). This murine polycythemia is homologous with hemoglobin Rainier in man, in which the amino acid substitution is also beta 145 Tyr----Cys and which is associated with similar physiological consequences.
Production of MDC/CCL22 by human intestinal epithelial cells (2001)

The intestinal mucosa contains a subset of lymphocytes that produce Th2 cytokines, yet the signals responsible for the recruitment of these cells are poorly understood. Macrophage-derived chemokine (MDC/CCL22) is a recently described CC chemokine known to chemoattract the Th2 cytokine producing cells that express the receptor CCR4. The studies herein demonstrate the constitutive production of MDC/CCL22 in vivo by human colon epithelium and by epithelium of human intestinal xenografts. MDC/CCL22 mRNA expression and protein secretion was upregulated in colon epithelial cell lines in response to proinflammatory cytokines or infection with enteroinvasive bacteria. Inhibition of nuclear factor (NF)-kappaB activation abolished MDC/CCL22 expression in response to proinflammatory stimuli, demonstrating that MDC/CCL22 is a NF-kappaB target gene. In addition, tumor necrosis factor-alpha-induced MDC/CCL22 secretion was differentially modulated by Th1 and Th2 cytokines. Supernatants from the basal, but not apical, side of polarized epithelial cells induced a MDC/CCL22-dependent chemotaxis of CCR4-positive T cells. These studies demonstrate the constitutive and regulated production by intestinal epithelial cells of a chemokine known to function in the trafficking of T cells that produce anti-inflammatory cytokines.
A Role for Nitric Oxide in Muscle Repair: Nitric Oxide–mediated Activation of Muscle Satellite Cells (2000)

Muscle satellite cells are quiescent precursors interposed between myofibers and a sheath of external lamina. Although their activation and recruitment to cycle enable muscle repair and adaptation, the activation signal is not known. Evidence is presented that nitric oxide (NO) mediates satellite cell activation, including morphological hypertrophy and decreased adhesion in the fiber-lamina complex. Activation in vivo occurred within 1 min after injury. Cell isolation and histology showed that pharmacological inhibition of nitric oxide synthase (NOS) activity prevented the immediate injury-induced myogenic cell release and delayed the hypertrophy of satellite cells in that muscle. Transient activation of satellite cells in contralateral muscles 10 min later suggested that a circulating factor may interact with NO-mediated signaling. Interestingly, satellite cell activation in muscles of mdx dystrophic mice and NOS-I knockout mice quantitatively resembled NOS-inhibited release of normal cells, in agreement with reports of displaced and reduced NOS expression in dystrophin-deficient mdx muscle and the complete loss of NOS-I expression in knockout mice. Brief NOS inhibition in normal and mdx mice during injury produced subtle alterations in subsequent repair, including apoptosis in myotube nuclei and myotube formation inside laminar sheaths. Longer NOS inhibition delayed and restricted the extent of repair and resulted in fiber branching. A model proposes the hypothesis that NO release mediates satellite cell activation, possibly via shear-induced rapid increases in NOS activity that produce "NO transients."
Lymphocytes induce monocyte chemoattractant protein-1 production by renal cells after Fc gamma receptor cross-linking: role of IL-1beta. (2001)

Leukocyte recruitment to the kidney in immune complex disease like systemic lupus erythematosus (SLE) is mediated in part by local expression of chemokines such as monocyte chemoattractant protein-1 (MCP-1). Recent studies from this laboratory demonstrated that cross-linking Fc gammaR on lymphocytes causes release of a soluble factor that induces monocyte chemokine production. To explain the induction of renal chemokine expression in immune complex disease, we postulated that this lymphocyte factor stimulates renal parenchymal cell MCP-1 expression. To test this hypothesis, human peripheral blood lymphocytes were incubated on immobilized IgG, a model for immune complex Fc gammaR cross-linking. Supernatants from these lymphocyte cultures significantly increased MCP-1 production by human mesangial, glomerular capillary endothelial, and proximal tubular epithelial cells. Mesangial cells incubated on immobilized IgG or with soluble, preformed immune complexes did not secrete MCP-1 above control levels. Lymphocyte supernatant-induced MCP-1 production appeared to be dependent on the presence of interleukin (IL)-1beta in the supernatant. Removing IL-1beta from the supernatants, antagonizing its activity, or preventing conversion to mature IL-1beta abrogated renal cell MCP-1 expression by the lymphocyte supernatants. These data demonstrate that in response to cross-linking Fc gammaR, lymphocytes induce renal cell MCP-1 expression by secreting IL-1beta. Renal chemokine expression in immune complex disease may thus be triggered as lymphocytes traffic through the kidney and encounter deposited immune complexes.
Photoactive Poly(ethylene glycol) Organosilane Films for Site-Specific Protein Immobilization (2001)

We describe the synthesis, characterization, and use of a new photoactive organosilane developed for the photoimmobilization of proteins. Thin films of 2-nitro-5-[11-(trimethoxysilyl)undecyl]oxybenzyl methoxy poly(ethylene glycol) propanoate are characterized using atomic force microscopy, spectroscopic ellipsometry, and attenuated total reflection-Fourier transform infrared spectroscopy. When this organosilane is used to modify silicon substrates, the solvent used during deposition affects the surface concentration and morphology of the resultant film. Although films deposited from either aqueous buffer or anhydrous toluene can be used to attach proteins to surfaces, films deposited from aqueous buffer display 4−6 times less nonspecific protein adsorption that those deposited from toluene. Modification of surfaces with this type of photoactive and protein “rejecting” film should aid in the development of high-resolution protein microarrays.
Plasmonic Nanoantennas: Fundamentals and Their Use in Controlling the Radiative Properties of Nanoemitters (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTPlasmonic Nanoantennas: Fundamentals and Their Use in Controlling the Radiative Properties of NanoemittersVincenzo Giannini*, Antonio I. Fernández-Domínguez, Susannah C. Heck, and Stefan A. MaierView Author Information Department of Physics, Imperial College London, London SW7 2AZ, United Kingdom*E-mail: [email protected]Cite this: Chem. Rev. 2011, 111, 6, 3888–3912Publication Date (Web):March 24, 2011Publication History Received17 August 2010Published online24 March 2011Published inissue 8 June 2011https://pubs.acs.org/doi/10.1021/cr1002672https://doi.org/10.1021/cr1002672review-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views26647Altmetric-Citations1184LEARN 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-Alertsclose SUBJECTS:Light,Metals,Nanodevices,Plasmonics,Quantum mechanics Get e-Alerts
Growth of GaN on a nanoscale periodic faceted Si substrate by metal organic vapor phase epitaxy (2005)

Growth of GaN on a nanoscale periodic faceted Si substrate by metal organic vapor phase epitaxy is reported. The surface of the Si(001) substrate is patterned with a one-dimensional, 355-nm period array of grooves. Each groove consisted of two facing Si{111} stripe facets separated by upper and lower Si(001) surfaces. GaN deposition on this groove array shows a strong selectivity with epitaxial growth of the hexagonal phase on the Si {111} facets being dominant. The initial stage of GaN growth appears to be amorphous. This is followed by GaN containing a high-density of stacking faults to accommodate the large lattice mismatch strain but the defect density decreases as growth proceeds. Lateral overgrowth from the Si{111} facets toward neighboring Si(001) facets leads to coalescence between GaN from opposing Si{111} facets. These GaN regions have misaligned c-axes and the crystal structure becomes unstable as they merge, resulting in a phase transition from hexagonal to cubic at the coalescence region. Experimental results of GaN grown on a nanoscale faceted Si surface including: nucleation, crystal structure, and lateral growth depending on Si orientation are presented.