gebhart/patrepeval huggingface dataset:
Polyamide supports for polypeptide synthesis (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolyamide supports for polypeptide synthesisE. Atherton, D. L. J. Clive, and R. C. SheppardCite this: J. Am. Chem. Soc. 1975, 97, 22, 6584–6585Publication Date (Print):October 1, 1975Publication History Published online1 May 2002Published inissue 1 October 1975https://pubs.acs.org/doi/10.1021/ja00855a053https://doi.org/10.1021/ja00855a053research-articleACS PublicationsRequest reuse permissionsArticle Views904Altmetric-Citations193LEARN 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 Get e-Alerts
Bisdeoxycoelenterazine Derivatives for Improvement of Bioluminescence Resonance Energy Transfer Assays (2007)

We report here syntheses of bisdeoxycoelenterazine derivatives that show significantly improved kinetics of the bioluminescent reaction. All derivatives contain a protecting group at the carbonyl group of the imidazopyrazinone moiety that ensures slower light signal decay. The longer lasting light signal offers the possibility of real-time imaging of protein−protein interactions.
Reprogrammed Mouse Fibroblasts Differentiate into Cells of the Cardiovascular and Hematopoietic Lineages (2008)

Forced expression of the four transcription factors Oct4, Sox2, c-Myc, and Klf4 is sufficient to confer a pluripotent state upon the murine fibroblast genome, generating induced pluripotent stem (iPS) cells. Although the differentiation potential of these cells is thought to be equivalent to that of embryonic stem (ES) cells, it has not been rigorously determined. In this study, we sought to identify the capacity of iPS cells to differentiate into Flk1-positive progenitors and their mesodermal progeny, including cells of the cardiovascular and hematopoietic lineages. Immunostaining of tissues from iPS cell-derived chimeric mice demonstrated that iPS cells could contribute in vivo to cardiomyocytes, smooth muscle cells, endothelial cells, and hematopoietic cells. To compare the in vitro differentiation potential of murine ES and iPS cells, we either induced embryoid body (EB) formation of each cell type or cultured the cells on collagen type IV (ColIV), an extracellular matrix protein that had been reported to direct murine ES cell differentiation to mesodermal lineages. EB formation and exposure to ColIV both induced iPS cell differentiation into cells that expressed cardiovascular and hematopoietic markers. To determine whether ColIV-differentiated iPS cells contained a progenitor cell with cardiovascular and hematopoietic differentiation potential, Flk1-positive cells were isolated by magnetic cell sorting and exposed to specific differentiation conditions, which induced differentiation into functional cardiomyocytes, smooth muscle cells, endothelial cells, and hematopoietic cells. Our data demonstrate that murine iPS cells, like ES cells, can differentiate into cells of the cardiovascular and hematopoietic lineages and therefore may represent a valuable cell source for applications in regenerative medicine. Disclosure of potential conflicts of interest is found at the end of this article.
Selected classes of minimised hammerhead ribozyme have very high cleavage rates at low Mg2+ concentration (1999)

In vitro selection was used to enrich for highly efficient RNA phosphodiesterases within a size-constrained (18 nt) ribonucleotide domain. The starting population (g0) was directed in trans against an RNA oligonucleotide substrate immobilised to an avidin-magnetic phase. Four rounds of selection were conducted using 20 mM Mg2+to fractionate the population on the basis of divalent metal ion-dependent phosphodiesterase activity. The resulting generation 4 (g4) RNA was then directed through a further two rounds of selection using low concentrations of Mg2+. Generation 6 (g6) was composed of sets of active, trans cleaving minimised ribozymes, containing recognised hammerhead motifs in the conserved nucleotides, but with highly variable linker domains (loop II-L.1-L.4). Cleavage rate constants in the g6 population ranged from 0.004 to 1.3 min-1at 1 mM Mg2+(pH 8.0, 37 degrees C). Selection was further used to define conserved positions between G(10.1) and C(11.1) required for high cleavage activity at low Mg2+concentration. At 10 mM MgCl2the kinetic phenotype of these molecules was comparable to a hammerhead ribozyme with 4 bp in helix II. At low Mg2+concentration, the disparity in cleavage rate constants increases in favour of the minimised ribozymes. Favourable kinetic traits appeared to be a general property for specific selected linker sequences, as the high rates of catalysis were transferable to a different substrate system.
Successful autografting following myeloablative conditioning therapy with blood stem cells mobilized by chemotherapy plus rhG-CSF. (1993)

High-dose conditioning therapy followed by autografting with blood stem cells rather than bone marrow has become an increasingly used transplantation modality for patients with chemosensitive malignancies. We treated 10 patients with malignant lymphoma in sensitive relapse with recombinant human granulocyte colony-stimulating factor (rhG-CSF) following salvage therapy. rhG-CSF was given subcutaneously (5 micrograms/kg/day) starting 24 hours after chemotherapy and stem cell collection was performed by repeated leukaphereses during leukocyte recovery. The yield of myeloid progenitors varied between 0.79 and 38.36 x 10(4) CFU-GM/kg body weight (median 4.1 x 10(4). A strong correlation was found between the number of granulocyte-macrophage colony-forming cells (CFU-GM) plus blast-forming erythroid cells (BFU-E) and CD34-positive (CD34+) cells (R = 0.80; p < 0.001). The majority of CD34+ cells (> 95%) strongly coexpressed human lymphocyte antigen-DR (HLA-DR) and CD38, whereas CD33 varied between 20% and 94%. Costaining of CD34+ cells for CD19 above the control level could not be detected, suggesting that early B lymphoid progenitors are not expanded or released into the circulation by rhG-CSF. Following total body irradiation (TBI)/cyclophosphamide or the CBV regimen (cyclophosphamide, BCNU, VP-16), all patients achieved complete engraftment with a median of 14 days for 1.0 x 10(9)/L white blood cells (WBC), 15 days for 0.5 x 10(9)/L polymorphonuclear cells (PMN) and 22 days for 20 x 10(9)/L platelets. The quantity of CFU-GM/kg transplanted was predictive for neutrophil and platelet recovery. The strongest correlation, however, was found between the number of CD34+ cells/kg autografted and platelet recovery (R = -0.86; p < 0.001). The patients transplanted with more than 5 x 10(6)/kg CD34+ cells reached an unsubstituted platelet count > 20 x 10(9)/L within 8 to 12 days. Our data demonstrate that rapid and complete engraftment can be achieved following myeloablative conditioning therapy with rhG-CSF-exposed blood stem cells without the need for additional bone marrow support or growth factor administration posttransplantation.
Application of Ring-Closing Metathesis to the Synthesis of Rigidified Amino Acids and Peptides (1996)

Ruthenium complexes 1a and 1b have been applied to the ring-closing metathesis (RCM) reactions of a number of dienic substrates. The substrate scope includes rings of 6 to 20 members. In addressing macrocyclic peptides, a class of tetrapeptide disulfides inspired the synthesis of the carbon−carbon bond analogs. Replacement of cysteine residues with allylglycines resulted in the acyclic precursors which were subjected to RCM to afford the corresponding macrocycles. In addition, several macrocycles were prepared which were not based upon disulfide-bridge-containing species found in nature. The method was found to function on dienic peptides which were either dissolved in organic solvents or bound to solid supports.
Advances in glaucoma therapeutics (2002)

Glaucoma is a major cause of irreversible blindness in the world. The prevalence of glaucomatous loss in vision will continue to grow as our populations age. Ocular hypertension is a major risk factor for the development of glaucoma and current glaucoma therapy is directed at lowering intraocular pressure. Several new ocular hypotensive agents have been introduced in the past several years providing a variety of treatment options. In addition, various classes of neuroprotective agents demonstrating activity in a wide variety of animal models have been proposed as potential new glaucoma therapeutics. Although these approaches will slow the progression of vision loss, they do not directly intervene in the disease process(es). Advances have been made attempting to understand the pathogenic pathways involved in glaucomatous damage to the eye and in methods to clinically measure glaucoma damage. An increased understanding of the pathophysiology of glaucoma will lead to the development of new therapeutic agents that intervene and perhaps even reverse glaucomatous damage to the eye. There also is a need to develop new methods to clinically measure glaucoma damage because, currently, considerable damage occurs before glaucoma is diagnosed and glaucoma remains underdiagnosed in the general population.
Locating essential Escherichia coli genes by using mini-Tn10 transposons: the pdxJ operon (1992)

The mini-Tn10 transposon (delta 16 delta 17Tn10) confers tetracycline resistance. When inserted between a gene and its promoter, it blocks transcription and prevents expression of that gene. Tetracycline in the medium induces divergent transcription of the tetA and tetR genes within the transposon, and this transcription extends beyond the transposon in both directions into the bacterial genes. If the mini-Tn10 inserts between an essential bacterial gene and its promoter, the insertion mutation can cause conditional growth which is dependent on the presence of tetracycline. Two essential genes in adjacent operons of Escherichia coli have been detected by screening for tetracycline dependence among tetracycline-resistant insertion mutants. These essential genes are the era gene in the rnc operon and the dpj gene in the adjacent pdxJ operon. The pdxJ operon has not been described previously. It consists of two genes, pdxJ and dpj. Whereas the dpj gene is essential for E. coli growth in all media tested, pdxJ is not essential. The pdxJ gene encodes a protein required in the biosynthesis of pyridoxine (vitamin B6).
The theoretical basis for the determination of optical pathlengths in tissue: temporal and frequency analysis (1992)

A concise theoretical treatment is developed for the calculation of mean time, differential pathlength, phase shift, modulation depth and integrated intensity of measurements of light intensity as a function of time on the surface of tissue, resulting from either the input of picosecond light pulses, or radio frequency-modulated light. The treatment uses the Green's function of the diffusion approximation to the radiative transfer equation, and develops this and its Fourier transform in a variety of geometries. Detailed comparisons are made of several of these parameters in several geometries, and their relation to experimentally measured clinical data. The limitations of the use of phase measurements is discussed.
Novel feto‐specific mRNA species suitable for identification of fetal cells from the maternal circulation (2001)

Feto-specific markers are necessary for genetic diagnostics on fetal cells isolated from maternal blood. Differential display reverse transcription-polymerase chain reaction (DDRT-PCR) was used to identify mRNA species preferentially expressed in trophoblast-enriched primary cell cultures compared to female peripheral mononuclear blood cells (FPMBCs). We obtained 15 different cDNA clones expressed predominantly in placenta cells using a commercial kit with oligo-(dT) anchor primers and arbitrary upstream primers for differential display analysis of total RNA. Reverse Northern dot-blot analysis and semi-quantitative RT-PCR confirmed the different expression levels. Seven mRNA species were exclusively expressed in the placenta: the mRNAs of epsilon-globin, a renowned marker of fetal erythroblasts, early placenta insulin-like peptide (EPIL), Yes-associated protein (YAP65) and osteopontin were expressed at high levels, whereas the mRNAs of PP14, JM27 protein, and an unidentified expressed sequence tag (EST) were moderately expressed. A further eight mRNAs with low expression in FPMBCs and higher expression in first trimester placenta were identified. Some mRNAs were expressed in a trophoblast cell line, e.g. YAP65, whereas others were not, e.g. EPIL. The new mRNA markers may be used to construct DNA/RNA probes to identify fetal cells in maternal circulation by hybridization techniques, or to identify proteins selectively expressed in fetal cells and amenable to immunocytochemical detection.
Thermosensitive mutants of Escherichia coli K-12 altered in the catalytic Subunit and in a Regulatory factor of the glutamy-transfer ribonucleic acid synthetase (1975)

The glutamyl-transfer ribonucleic acid synthetase (GluRS) of a partial revertants (ts plus or minus) of the thermosensitive (ts) mutant strain JP1449 (LOcus gltx) and of a ts mutant strain EM111-ts1 with a lesion in or near the locus gltx have been studied to find the relation between these two genetic loci known to influence the GluRS activity in vitro and the presence of a catalytic subunit and of a regulatory subunit in the GluRS purified from Escherichia coli K-12. The ts character of strain JP1449-18ts plus or minus is co-transduced with the marker dsdA at the same frequency as is the ts character of strain JP1449. Its purified GluRS is very thermolabile and its Km for glutamate is higher than that of a wild-type GluRS. These results indicate that the locus gltX is in the structural gene for the catalytic subunit of this enzyme. The location of the mutation causing the partial ts reversion in strain JP1449-18ts plus or minus is discussed. The GluRS purified from the ts mutant strain EM111-ts1 has the same stability as the wild-type enzyme, but its Km forglutamate increases with the temperature, suggesting that the locus gltE codes for a regulatory factor, possibly for the polypeptide chain that is co-purified with the catalytic subunit.
Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo. (2001)

Hypoxia and acidosis are hallmarks of tumors as well as critical determinants of response to treatments. They can upregulate vascular endothelial growth factor (VEGF) in vitro. However, the relationship between tissue oxygen partial pressure (pO(2))/pH and VEGF transcription in vivo is not known. Thus, we developed a novel in vivo microscopy technique to simultaneously measure VEGF promoter activity, pO(2), and pH. To monitor VEGF expression in vivo, we engineered human glioma cells that express green fluorescent protein (GFP) under the control of the VEGF promoter. These cells were implanted into the cranial windows in severe combined immunodeficient mice, and VEGF promoter activity was assessed by GFP imaging. Tissue pO(2) and pH were determined by phosphorescence quenching microscopy and ratio imaging microscopy, respectively. These techniques have allowed us to show, for the first time, that VEGF transcription in brain tumors is independently regulated by the tissue pO(2) and pH. One week after tumor implantation, significant angiogenesis was observed, with increased GFP fluorescence throughout the tumor. Under hypoxic or neutral pH conditions, VEGF-promoter activity increased, with a decrease in pO(2) and independent of pH. Under low pH or oxygenated conditions, VEGF-promoter activity increased, with a decrease in pH and independent of pO(2). In agreement with the in vivo findings, both hypoxia and acidic pH induced VEGF expression in these cells in vitro and showed no additive effect for combined hypoxia and low pH. These results suggest that VEGF transcription in brain tumors is regulated by both tissue pO(2) and pH via distinct pathways.
Idiotype vaccines against human T cell acute lymphoblastic leukemia. I. Generation and characterization of biologically active monoclonal anti-idiotopes. (1987)

A murine monoclonal anti-tumor antibody termed SN2 (Ab1), isotype IgG1-kappa, that defines a unique human T cell leukemia-associated cell-surface glycoprotein, gp37 (m.w. 37,000), was used to generate monoclonal anti-idiotype antibodies (Ab2) in syngeneic BALB/c mice. The Ab2 were screened on the basis of their binding to the F(ab')2 fragments of SN2 and not to the F(ab')2 of pooled normal BALB/c mice sera IgG1 or to an unrelated BALB/c monoclonal antibody of the same isotype. Fifteen Ab2, obtained from two fusions, were specific for the SN2 idiotope and not against isotype or allotype determinants. To find out whether these Ab2 are directed against the paratope of SN2, the binding of radiolabeled SN2 to leukemic MOLT-4 and JM cells which contain gp37 as a surface constituent was studied in the presence of these anti-idiotopes. Clone 4EA2 inhibited the binding 100% at a concentration of 50 ng and 4DC6 inhibited 90% at a concentration of 250 ng. A third clone 4DD6 gave about 50% inhibition. Similar was the inhibition of SN2 binding to insolubilized MOLT-4 antigen or cell membrane preparation. The binding of SN2 (Ab1) to 4EA2 and 4DC6 was also inhibited by semipurified preparation of gp37 antigen. These results demonstrate that at least two of the anti-idiotope antibodies are binding either at or near the binding site idiotope of SN2. Next, the purified Ab2 was used to immunize syngeneic mice to induce antibody binding to MOLT-4 cells or gp37. Sera from mice immunized with 4EA2 and 4DC6 coupled to keyhole limpet hemocyanin contained antibodies which bind to semipurified gp37 antigen and MOLT-4 cells. Immune sera inhibited the binding of iodinated Ab2 and Ab1 indicating that an anti-anti-idiotopic antibody (Ab3) in mice shares idiotopes with Ab1 (SN2). Also, the binding of iodinated Ab2 to Ab1 was inhibited by rabbit antisera specific for gp37. Collectively, these data suggest that anti-idiotype antibodies 4EA2 and 4DC6 may be useful in the generation of idiotype vaccines against human T cell leukemia.
Antigens of the basement membrane and the peritumoral stroma in human colonic adenocarcinomas: An immunofluorescence study (1982)

Twenty colonic adenocarcinomas were studied by immunofluorescence with antisera against components of the basement membrane: type IV collagen, laminin and heparan sulfate-rich proteoglycan, as well as antisera against antigens of the connective tissue: type-III collagen, fibronectin and hyaluronectin. Marked alterations of the basement membranes were consistently observed on staining with each one of the first three antisera. In contrast, staining of the normal components of connective tissue was in most cases as intense as in normal colonic mucosa. Hyaluronectin, a marker of peritumoral stroma, was found to be present in 12 out 15 tumors studied.
Identification and characterization of a Saccharomyces cerevisiae gene (PAR1) conferring resistance to iron chelators (1991)

o-Phenanthroline (1,10-phenanthroline) is a chemical known to chelate iron and other transition metal ions. This compound was added to solid yeast media to reduce the concentration of biologically available iron. Other essential divalent cations, like Zn2+ or Cu2+, which could also be bound, were supplemented. Growth of wild-type yeast strains was totally inhibited at specific concentrations of the chelator. However, several cells containing plasmids of a multicopy vector genomic library of S. cerevisiae could be selected by growth on these media. All of the resistant clones carried a single additional gene, PAR1 on their multicopy plasmids. Plasmid-directed overexpression of PAR1 increased the resistance of transformants to o-phenanthroline and additionally conferred resistance to 1-nitroso-2-naphthol, an iron(III)-binding molecule with different coordinating ligands. By supplementing the o-phenanthroline-containing media with several different metal ions, it could be proved that the selection plates really caused a specific iron limitation. These observations clearly demonstrated that the overexpressed PAR1 gene enables the cell to compete with iron-chelating organic molecules. PAR1 null mutants, constructed by insertion of the LEU2 gene into the open reading frame, showed a remarkable phenotype: they did not grow on slightly alkaline buffered media (pH greater than 7) and became hypersensitive to oxidative stress by hydrogen peroxide. Of several heavy metal ions, such as Fe3+, Fe2+, Co2+, Ni2+, Cu2+ and Zn2+, tested for supplementation of the alkaline growth deficiency, only iron, either added in the ferrous or ferric form, was able to restore cellular growth. It can be concluded from the DNA sequence that PAR1 encodes a highly acidic protein of 650 residues with mostly hydrophilic character. Some interesting repetitive amino acid motifs, such as (Asp-Asn)4 or Cys-Ser-Glu, may act as metal-binding sites. The possible role of PAR1 is discussed.
Endoscopic Injection of Glutaraldehyde Cross-Linked Bovine Dermal Collagen for Correction of Vesicoureteral Reflux (1991)

From November 1986 through May 1989, a Food and Drug Administration approved investigational study was done to assess the safety and efficacy of glutaraldehyde cross-linked bovine dermal collagen in the endoscopic treatment of vesicoureteral reflux. Over-all, 57 patients (92 ureters) were treated. The majority of ureters (68.5%) had grade II to III/V vesicoureteral reflux (international classification). One treatment was given in 61.4% of the patients, while 33.3% required 2 and 5.3% required 3 treatments. Nonduplicated/primarily refluxing ureters comprised 68.5% of the total, while 13% were duplex/primarily refluxing and 18.5% were surgical failures. The procedures were performed on an outpatient basis in all but 3 patients. Patients were evaluated by voiding cystourethrogram and renal/bladder sonography before and after treatment at 1 month and 1 year. Cure at 1 month after the last treatment was achieved in 75% of the ureters. Among the ureters cured at 1 month the cure persisted in 79% at 1 year after treatment. Cure at 1 year was achieved in 65% of all ureters evaluated, regardless of the status at 1 month. Procedure-related morbidity was minimal and there were no adverse reactions to the implant substance. Thus, glutaraldehyde cross-linked bovine dermal collagen appears to be safe and effective in the endoscopic treatment of vesicoureteral reflux.