gebhart/patrepeval huggingface dataset:
Adeno-Associated Virus Type 2 Capsids with Externalized VP1/VP2 Trafficking Domains Are Generated prior to Passage through the Cytoplasm and Are Maintained until Uncoating Occurs in the Nucleus (2006)

Common features of parvovirus capsids are open pores at the fivefold symmetry axes that traverse the virion shell. Upon limited heat treatment in vitro, the pores can function as portals to externalize VP1/VP2 protein N-terminal sequences which harbor infection-relevant functional domains, such as a phospholipase A(2) catalytic domain. Here we show that adeno-associated virus type 2 (AAV2) also exposes its VP1/VP2 N termini in vivo during infection, presumably in the endosomal compartment. This conformational change is influenced by treatment with lysosomotropic reagents. While incubation of cells with bafilomycin A1 reduced exposure of VP1/VP2 N termini, incubation with chloroquine stimulated externalization transiently. N-terminally located basic amino acid clusters with nuclear localization activity also become exposed in this process and are accessible on the virus capsid when it enters the cytoplasm. This is an obligatory step in AAV2 infection. However, a direct role of these sequences in nuclear translocation of viral capsids could not be determined by microinjection of wild-type or mutant viruses. This suggests that further modifications of the capsid have to take place in a precytoplasmic entry step that prepares the virus for nuclear entry. Microinjection of several capsid-specific antibodies into the cell nucleus blocked AAV2 infection completely, supporting the conclusion that AAV2 capsids bring the infectious genome into the nucleus.
Research progress of neuroglobin (2008)

在组织氧利用的研究方面,作为意识中枢的脑组织历来是人们关注的重点.虽然人脑仅占体重的2%,但由于脑中具有十分复杂的神经网络以及复杂的神经功能活动,所以即使在安静状态脑组织的耗氧量就可占到全身耗氧量的20%以上。
SH-PTP2/Syp SH2 domain binding specificity is defined by direct interactions with platelet-derived growth factor beta-receptor, epidermal growth factor receptor, and insulin receptor substrate-1-derived phosphopeptides. (1994)

Signaling by tyrosine kinases involves direct associations between proteins with Src homology 2 (SH2) domains and sites of tyrosine phosphorylation. Specificity in signaling pathways results in part from inherent selectivity in interactions between particular SH2 domains and phosphopeptide sequences. The cytoplasmic phosphotyrosine phosphatase SH-PTP2 (Syp, PTP 1D, PTP-2C) contains two SH2 domains (N and C) which mediate its association with and activation by the platelet-derived growth factor (PDGF) and epidermal growth factor receptors and IRS-1. We have developed a competitive phosphopeptide binding assay to analyze specificity of the SH-PTP2 N-SH2 domain for phosphorylation sites of these phosphoproteins. The sequence surrounding Tyr1009 bound with greatest affinity (ID50 = 14 microM) of eight PDGF receptor-derived phosphopeptides tested. No peptides corresponding to known epidermal growth factor receptor phosphorylation sites bound with high affinity. However, an alternative sequence surrounding Tyr954 bound tightly (ID50 = 21 microM). Of the 13 IRS-1-related peptides analyzed, sequences surrounding Tyr546, Tyr895, and Tyr1172 bound with highest affinity (ID50 = 11, 4, and 1 microM, respectively). Alternative phosphopeptides generally bound with much weaker affinity (ID50 > 150 microM). These findings are consistent with recent mutational analyses of the PDGF receptor and predict site-specific interactions between SH-PTP2 and each of these phosphoproteins. Comparisons between peptide sequences suggest that the N-terminal SH2 domain of SH-PTP2 binds with highest affinity to phosphotyrosine (pY) followed by a beta-branched residue (Val, Ile, Thr) at pY+1 and a hydrophobic residue (Val, Leu, Ile) at pY+3 positions. Peptide truncation studies also indicate that residues outside of the pY-1 to pY+4 motif are required for high affinity interactions.
A surface-modified functional liposome capable of binding to cell membranes (1999)

A liposome including the lipopeptide RGD-C4A2, whose surface is modified by a GRGDS-repeating peptide ligand, is found to bind to NIH3T3 cells via the interaction between the peptide ligand and the membrane receptor.
Input shapers for improving the throughput of torque-limited systems (1994)

A technique is presented for designing command profiles for flexible systems whose operational performance is restricted by a limit on actuator effort. To ensure maximum throughput, the command signal is restricted to a series of positive and negative pulses, whose amplitude is equal to the maximum actuator effort (torque limit). The command profiles are further required to move the system to a desired setpoint with very little residual vibration, even in the presence of modeling errors. The process for extending the method to eliminate multiple modes of vibration is also presented. The control technique is verified with both computer simulation and hardware experiments.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Immunosuppressive acidic protein in patients with gynecologic cancer (1984)

Immunosuppressive acidic protein (IAP) was determined in sera of patients with gynecologic tumors using the single radial immunodiffusion method. The normal limit of IAP of 490 micrograms/ml was derived from the mean value + 2 SD of IAP in 150 healthy females. Among 141 patients with gynecologic cancers, serum IAP was elevated in 87 patients (62%). Among 190 patients with benign tumors (98 uterine myoma, 92 benign ovarian tumors) serum IAP was elevated in 14 patients (7%). Elevated levels of IAP were recognized in 43% of 77 patients with cervical cancer, in 55% of 11 endometrial cancer patients, and in 91% of 53 ovarian cancer patients. The frequency of elevated levels showed a tendency to increase with advancing stage of disease. In ovarian cancer elevation of IAP was observed even in early stages. All of 13 patients with recurrent cervical cancer had elevated IAP while only 6 of 35 (17%) previously treated patients without evidence of recurrence had elevated IAP. Immunosuppressive acidic protein determinations may be useful in monitoring the recurrence of cervical cancer. The measurement of serum IAP as a marker for gynecologic cancer is recommended as an addition to diagnostic procedures.
Formation of Native-like Mammalian Sperm Cell Chromatin with Folded Bull Protamine (2004)

The DNA of most vertebrate sperm cells is packaged by protamines. The primary structure of mammalian protamine I can be divided into three domains, a central DNA binding domain that is arginine-rich and amino- and carboxyl-terminal domains that are rich in cysteine residues. In native bull sperm chromatin, intramolecular disulfide bonds hold the terminal domains of bull protamine folded back onto the central DNA binding domain, whereas intermolecular disulfide bonds between DNA-bound protamines help stabilize the chromatin of mature mammalian sperm cells. Folded bull protamine was used to condense DNA in vitro under various solution conditions. Using transmission electron microscopy and light scattering, we show that bull protamine forms particles with DNA that are morphologically similar to the subunits of native bull sperm chromatin. In addition, the stability provided by intermolecular disulfide bonds formed between bull protamine molecules within in vitro DNA condensates is comparable with that observed for native bull sperm chromatin. The importance of the bull protamine terminal domains in controlling the bull sperm chromatin morphology is indicated by our observation that DNA condensates formed under identical conditions with a fish protamine, which lacks cysteine-rich terminal domains, do not produce as uniform structures as bull protamine. A model is also presented for the bull protamine.DNA complex in native sperm cell chromatin that provides an explanation for the positions of the cysteine residues in bull protamine that form intermolecular disulfide bonds.
Oligonucleotides as therapeutic agents (1997)

Oligonucleotide analogues - an overview phosphorothioate oligodeoxynucleotides - large scale synthesis and analysis, impurity characterization and the effects of phosphorous stereochemistry discovering antisense reagents by hybridization of RNA to oligonucleotide arrays pharmacokinetics of oligonucleotides in cell culture pharmacokinetics of antisense oligonucleotides cellular pharmacology of antisense oligodeoxynucleotides sequence-specific control of gene expression by antigene and clamp oligonucleotides differential oligonucleotide activity in cell culture versus mouse models structure-activity relationships in cell culture progress in antisense therapeutics treating human myelogenous leukaemia with oligonucleotides targeted to the C-Myb gene - two years clinical experience therapeutic applications of catalytic antisense RNA's exogenous application of ribozymes for the inhibition of gene expression SELEX derived drugs in vivo production of oligonucleotide applications for antisense DNA.
Folic Acid Targeting of Protein Conjugates into Ascites Tumour Cells from Ovarian Cancer Patients (2000)

Despite a wealth of in vitro data describing the use of folic acid for drug and DNA delivery into ovarian cancer cell lines, there have been no reports describing the targeting of such compounds to freshly isolated tumour cells. We have carried out a study to determine the usefulness of folic acid as a targeting ligand for ovarian cancer by measuring the uptake of folic acid-BSA-FITC in tumour cells isolated from the ascitic fluid of ovarian cancer patients. In 7 out of 7 patients we have found folic acid mediated uptake of the fluorescently labelled albumin, with the accumulation (average cell fluorescence) and differential uptake (ratio between receptor mediated and fluid phase uptake) varying between patients. Accumulation of folic acid-albumin FITC occurs in ascites tumour cells expressing the epithelial cell marker EMA, with a significant proportion of EMA negative cells also accumulating the conjugate. There is no correlation between cell cycle and uptake of folic acid-BSA-FITC. These results suggest that folic acid-targeting of therapeutics is a promising approach for the treatment of ovarian cancer.
Mycoplasma cynos, a New Canine Mycoplasma Species (1973)

Eleven glucose-fermenting Mycoplasma strains were isolated from the respiratory and genital tracts of dogs. Biological and serological studies demonstrated that the group was different from the established canine Mycoplasma species and glucose-fermenting species of noncanine origin. It is concluded that this group of mycoplasmas should be classified as a new species, and the name Mycoplasma cynos is proposed. The type strain of M. cynos is H 831 (ATCC 27544; NCTC 10142).
Embryonic stem cell-mediated transfer and correct regulation of the chicken δ-crystallin gene in developing mouse embryos (1988)

To study regulation of delta-crystallin expression during ontogeny, we transferred the gene from chicken into developing mouse embryos by first transforming an embryonic stem (ES) cell line of mouse and then producing chimaeric embryos by combining them with normal mouse embryos. Using this technique, genes were transferred into a variety of developing mouse tissues with high efficiency. Two delta-crystallin gene constructs were used: the wild-type gene with 2200 bp of the 5' flanking sequence, shown to be lens-specific in an assay using cultured mouse cells, and a mutant gene with 51 bp of the 5' flanking sequence, lacking the sequence required for expression in lens cells. Five independent lines carrying the former and two lines carrying the latter were employed in producing chimaeras. In the chimaeric embryos having the wild-type gene, delta-crystallin was expressed in the lens and in specific regions of the primitive central nervous system (CNS) as is seen in embryonic expression in the chicken. In adult mouse chimaeras also, expression was restricted to the lens and the CNS, in the pyramidal neurones of the piriform cortex and the hippocampus. delta-crystallin expression in these tissues is due to proper transcriptional regulation, since no expression was observed when chimaeras were produced with the ES lines carrying the mutant gene. The experimental results reported here demonstrate the advantage of ES-cell-mediated gene transfer in the study of embryonic gene regulation, because a number of gene constructs and chromosomal sites can be analysed shortly after embryo manipulation without requiring gene transmission to the next generation.
Beyond the Black Hole (1989)

The paper will explore issues arising from technological changes and work re‐structuring within a high volume manufacturing organisation based at Kirkby, Merseyside. It is hoped that the paper will contribute to the post‐Braverman debate. Braverman's thesis is well‐known, as are the criticisms of it. Our reasons for going ‘beyond Braverman’ are two‐fold.
Current Tendencies in French and German Thought (1995)

NYONE WHO ATTEMPTS T O WRITE A BIOGRAPHY OF A philosopher is faced with a fundamental methodological question. What is the proper relationship between the work of a philosopher .and the events in his or her life? The literary definition of biography a chronicle of a life does not seem to be appropriate when dealing with human beings whose primary significance is in the realm of ideas and concepts, and not in the events of their personal lives. Ideas cannot simply be reduced or explained away by a reference to a historical sequence of events; they possess, as Plato argued over two thousand years ago, an existence of their own, apart from the thinkers who have conceived of them. Yet no one can deny the importance, for example, of the influence exerted on Hegel's thought by his Lutheran background and his initiation into the university culture of his native Germany. Similar remarks could be made
Site-selective cleavage of structured RNA by a staphylococcal nuclease-DNA hybrid. (1989)

A hybrid enzyme consisting of an oligodeoxyribonucleotide fused to a unique site on staphylococcal nuclease site-selectively cleaves a number of natural RNAs including Escherichia coli M1 RNA (377 bases), 16S rRNA (1542 bases), and yeast tRNA(Phe). The oligonucleotide directs the nuclease activity of the enzyme to the nucleotides directly adjacent to the complementary target sequence on the substrate RNA. In the case of M1 RNA, hydrolysis occurs primarily at one phosphodiester bond, converting 50% of the starting material to product. Furthermore, the reaction products can be enzymatically manipulated: tRNA(Phe) was cleaved in the anticodon region and was religated to form the full-length tRNA in high yield. Because the specificity of these hybrid enzymes can be easily altered, they should prove to be useful tools for probing RNA structure and function.
Inhibitors of carbohydrate processing: A new class of anticancer agents. (1995)

There is a need for anticancer agents with novel mechanisms of action. Recently identified molecular targets for new anticancer agents include inducers of cell differentiation, cell cycle arrest, and apoptosis, as well as signaling pathways for growth factors and cytokines. Another unexplored opportunity is presented by the ubiquitous intracellular glycoprotein glycosylation pathway. This complex process, concerned with the addition of sugars onto newly synthesized proteins, occurs in the lumen of the rough endoplasmic reticulum and in the Golgi. There are estimates of over 200 glycosyltransferase enzymes in this pathway, which results in considerable structural diversity of carbohydrates found on secreted and transmembrane glycoproteins. The specificity of glycosyltransferases for acceptors and sugar-nucleotide donors dictates linkage positions between sugars, anomeric configuration of linkages, and monosaccharide composition. Specific carbohydrate structures participate in cell-cell and cell-substratum interactions affecting processes such as lymphocyte trafficking, immune cell stimulation, embryogenesis, and cancer metastasis. Of the carbohydrate-processing inhibitors presently available, the alkaloid swainsonine, a Golgi alpha-mannosidase II inhibitor, is the first to have been selected for clinical testing based on its anticancer activity, p.o. availability, and low toxicity in mice. Herein, we review the rationale for targeting Golgi carbohydrate processing pathways in the treatment of cancer, and summarize the preclinical and clinical results with swainsonine. Prospects for the development of second generation inhibitors with improved specificity for Golgi-processing enzymes are discussed. Potential clinical applications of this new class of anticancer agents are emphasized.
Nonaqueous Liquid Electrolytes for Lithium-Based Rechargeable Batteries (2004)

ADVERTISEMENT RETURN TO ISSUEPREVarticleNEXTNonaqueous Liquid Electrolytes for Lithium-Based Rechargeable BatteriesKang XuKang XuElectrochemistry Branch, Sensor and Electron Devices Directorate, U.S. Army Research Laboratory, Adelphi, Maryland 20783-1197 More by Kang XuCite this: Chem. Rev. 2004, 104, 10, 4303–4418Publication Date (Web):September 16, 2004Publication History Received3 November 2003Published online16 September 2004Published inissue 1 October 2004https://pubs.acs.org/doi/10.1021/cr030203ghttps://doi.org/10.1021/cr030203gresearch-articleACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views89913Altmetric-Citations5770LEARN 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:Electrodes,Electrolytes,Ions,Lithium,Solvents Get e-Alerts
Recombinant Adeno-Associated Virus Vector-Based Gene Transfer for Defects in Oxidative Metabolism (2000)

Defects in oxidative metabolism may be caused by mutations either in nuclear genes or in mitochondrial DNA (mtDNA). We tested the hypothesis that recombinant adeno-associated virus (rAAV) could be used to complement mtDNA mutations. AAV vector constructs were designed to express the reporter gene encoding green fluorescent protein (GFP), fused to a targeting presequence that directed GFP to be translocated into mitochondria. These vectors mediated expression of mitochondrial-localized GFP, as indicated by fluorescence microscopy and electron microscopy, in respiring human embryonic kidney 293 cells and nonrespiring mtDNA-deficient (rho 0) cells. However, when sequences encoding hydrophobic segments of proteins normally encoded by mtDNA were inserted between the presequence and GFP, mitochondrial import failed to occur. In similar experiments, a fusion was created between pyruvate dehydrogenase (PDH) E1 alpha subunit, a nuclear-encoded mitochondrial gene with its own targeting presequence, and GFP. With this construct, expression of GFP was observed in mitochondria in vitro and in vivo. We conclude that the hydrophobicity of mtDNA-encoded proteins limits their ability to be transported from the cytoplasm. However, rAAV-based gene therapy may hold promise for gene therapy of PDH deficiency, the most common biochemically proven cause of congenital lactic acidosis.
Recent Developments in Lanthanide Catalysts for 1,3-Diene Polymerization (1999)

Lanthanide catalysts are typical for the cis polymerization of 1,3-dienes. The ternary system AlEt2Cl - Nd(OCOR)3 - Al(iBu)3 (R = alkyl group) is now used for the commercial production of cis polybutadiene. The effect of catalyst component addition order on activity and heterogeneity has been examined. In the ternary systems, only part of the lanthanide (Ln) is active in the catalysis. Much more active systems are obtained using allyl derivatives of Nd, Pr, Gd, in combination with methylaluminoxane (MAO). Evidence is reported suggesting that Ln catalysts have an ionic structure. Ln catalysts are also active for the polymerization of substituted butadienes and give cis-isotactic polymers from terminally substituted monomers.
Increasing and detecting memory address congruence (2003)

A static memory reference exhibits a unique property when its dynamic memory addresses are congruent with respect to some non-trivial modulus. Extraction of this congruence information at compile-time enables new classes of program optimization. In this paper, we present methods for forcing congruence among the dynamic addresses of a memory reference. We also introduce a compiler algorithm for detecting this property. Our transformations do not require interprocedural analysis and introduce almost no overhead. As a result, they can be incorporated into real compilation systems. On average, our transformations are able to achieve a five-fold increase in the number of congruent memory operations. We are then able to detect 95% of these references. This success is invaluable in providing performance gains in a variety of areas. When congruence information is incorporated into a vectorizing compiler we can increase the performance of a G4 AltiVec processor up to a factor of two. Using the same methods, we are able to reduce energy consumption in a data cache by as much as 35%.
Advances in analytical methodology for bioinorganic speciation analysis: metallomics, metalloproteomics and heteroatom-tagged proteomics and metabolomics (2005)

The recent developments in analytical techniques capable of providing information on the identity and quantity of heteroatom-containing biomolecules are critically discussed. Particular attention is paid to the emerging areas of bioinorganic analysis including: (i) a comprehensive analysis of the entirety of metal and metalloid species within a cell or tissue type (metallomics), (ii) the study of the part of the metallome involving the protein ligands (metalloproteomics), and (iii) the use of a heteroelement, naturally present in a protein or introduced in a tag added by means of derivatisation, for the spotting and quantification of proteins (heteroatom-tagged proteomics). Inductively coupled plasma mass spectrometry (ICP MS), used as detector in chromatography and electrophoresis, and supported by electrospray and MALDI MS, appears as the linchpin analytical technique for these emerging areas. This review focuses on the recent advances in ICP MS in biological speciation analysis including sensitive detection of non-metals, especially of sulfur and phosphorus, couplings to capillary and nanoflow HPLC and capillary electrophoresis, laser ablation ICP MS detection of proteins in gel electrophoresis, and isotope dilution quantification of biomolecules. The paper can be considered as a followup of a previous review by the author on a similar topic (: J. Szpunar, Analyst, 2000, 125, 963).