gebhart/patrepeval huggingface dataset:
Replacement of isoleucine-397 by threonine in the clotting proteinase factor IXa (Los Angeles and Long Beach variants) affects macromolecular catalysis but not l-tosylarginine methyl ester hydrolysis. Lack of correlation between the ox brain prothrombin time and the mutation site in the variant proteins (1990)

Previously, from the plasma of unrelated haemophilia-B patients, we isolated two non-functional Factor IX variants, namely Los Angeles (IXLA) and Long Beach (IXLB). Both variants could be cleaved to yield Factor IXa-like molecules, but were defective in catalysing the cleavage of Factor X (macromolecular substrate) and in binding to antithrombin III (macromolecular inhibitor). In the present study we have identified the mutation of IXLA by amplifying the exons (including flanking regions) as well as the 5' end of the gene by polymerase-chain-reaction (PCR) method and sequencing the amplified DNA by the dideoxy chain-termination method. Comparison of the normal IX and IXLA sequences revealed only one base substitution (T----C) in exon VIII of IXLA, with a predicted replacement of Ile-397 to Thr in the mature protein. This mutation is the same as found recently for IXLB. The observation that IXLB and IXLA have the same mutation is an unexpected finding, since, on the basis of their ox brain prothrombin time (PT, a test that measures the ability of the variant Factor IX molecules to inhibit the activation of Factor X by Factor VIIa-tissue factor complex), these variants have been classified into two different groups and were thought to be genetically different. Our observation thus suggests that the ox brain PT does not reflect the locus of mutation in the coding region of the variant molecules. However, our analysis suggests that the ox brain PT is related to Factor IX antigen concentration in the patient's plasma. Importantly, although the mutation in IXLA or IXLB protein is in the catalytic domain, purified IXaLA and IXaLB hydrolyse L-tosylarginine methyl ester at rates very similar to that of normal IXa. These data, in conjunction with our recent data on Factor IXBm Lake Elsinore (Ala-390----Val mutant), strengthen a conclusion that the peptide region containing residues 390-397 of normal Factor IXa plays an essential role in macromolecular substrate catalysis and inhibitor binding. However, the two mutations noted thus far in this region do not distort S1 binding site in the Factor IXa enzyme.
Netrin Binds Discrete Subdomains of DCC and UNC5 and Mediates Interactions between DCC and Heparin (2003)

Netrins are secreted proteins that elicit both attractive and repulsive responses in migrating cells in the central and peripheral nervous systems. Netrins interact with members of two distinct families of transmembrane receptors, represented by DCC (deleted in colorectal cancer) and UNC5. A human netrin fragment (soluble netrin; sNetrin) was purified from an engineered Chinese hamster ovary cell line and used in a pull-down assay to map the interactions between netrin and its receptors. We find that sNetrin binds exclusively to the fifth fibronectin type III repeat of DCC and to each immunoglobulin repeat of UNC5. Both DCC and UNC5 bind to sNetrin with 1:1 stoichiometry in solution, and the minimal receptor fragments behave similarly to larger fragments in cross-linking experiments with purified sNetrin. We find no evidence for formation of a ternary complex between sNetrin and soluble forms of DCC and UNC5. We also find no evidence for an interaction between DCC and heparin and instead demonstrate that a loop on the fifth fibronectin type III repeat of DCC previously implicated in mediating interactions with heparin is important for sNetrin binding. Since netrin binds heparin, our results suggest that interactions between DCC and heparin are probably mediated by netrin.
dialogue (2012)

March 01 2012 dialogue Christopher Spring Christopher Spring Curator, Sainsbury African Galleries, Department of Africa, Oceania and the Americas, The British Museum Search for other works by this author on: This Site Google Scholar Author and Article Information Christopher Spring Curator, Sainsbury African Galleries, Department of Africa, Oceania and the Americas, The British Museum Online Issn: 1937-2108 Print Issn: 0001-9933 © 2012 by the Regents of the University of California.2012 African Arts (2012) 45 (1): 14. https://doi.org/10.1162/afar.2012.45.1.14 Cite Icon Cite Permissions Share Icon Share Facebook Twitter LinkedIn MailTo Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Search Site Citation Christopher Spring; dialogue. African Arts 2012; 45 (1): 14. doi: https://doi.org/10.1162/afar.2012.45.1.14 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsAfrican Arts Search Advanced Search This content is only available as a PDF. © 2012 by the Regents of the University of California.2012 Article PDF first page preview Close Modal You do not currently have access to this content.
Practical Aspects of Quantitative and High-Fidelity STEM Data Recording (2020)

Expressing annular dark-field scanning transmission electron microscopy (ADF-STEM) images on a quantitative absolute scale presents the experimentalist with a powerful opportunity for comparison with image simulations. Image simulations are natively expressed in the range from 0 to 100% of “fractional beam”. However, to obtain experimental data in these units detailed and careful calibrations are necessary. Some calibrations, such as magnification, are obvious; but other parameters, especially those relating to inhomogeneous ADF detector sensitivity or scanning distortion, require more careful consideration. This chapter will discuss the approaches for experiment design and execution in the recording of high-fidelity quantitative ADF data. The dominant sources of error in both signal intensity and spatial precision will be explored from the most severe down to the more esoteric. While the focus will be on ADF imaging, many of the factors are also common to other imaging signals or even spectroscopy. The most common type of scintillator-photomultiplier ADF detectors will be discussed, along with their strengths and (several) weaknesses. With this, techniques to minimize the introduction of errors from these will be presented along with strategies for dealing with any residual errors. The emerging practice of reliable multi-frame imaging will be introduced, along with the benefits and new experimental opportunities it presents in electron dose or dose-rate management. Various tools will be discussed as well as their use in multi-frame image, or multi-pass spectrum-image, alignment.
Spheromaks: A Practical Application of Magnetohydrodynamic Dynamos and Plasma Self-Organization (2001)

Basic concepts magnetic helicity relaxation of an isolated configuration to the Taylor State relaxation in driven configurations the MHD energy principle, helicity, and Taylor States survey of spheromak formation schemes classification of regimes - an imperfect analogy to thermodynamics analysis of isolated cylindrical spheromaks the role of the wall analysis of driven spheromaks - strong coupling helicity flow and dynamos confinement and transport in spheromaks some important practical issues basic diagnostics for spheromaks applications of spheromaks solar and space phenomena related to speromaks.
An Inquiry Into the Benefits of Multigauge Parallel Computation. (1985)

Abstract : A multigauge parallel computer is a machine whose processor elements can be partitioned into distinct processors with narrower data paths, ILLIAC IV was multigauge machine. This paper addresses the question of whether multigauge computation is useful. First, the concept is defined. Next it is argued that multigauge machines offer truly new computational facilities, rather than being other architectures in disguise. Finally , a class of algorithms is identified that can exploit multigauge architectures and an example is presented to illustrate multigauge machine performance improvements. Keywords: Parallel programming, Multigauge parallel computer, Gauge shifting, Multitier algorithms.
Assignment of a Locus for Familial Melanoma, MLM, to Chromosome 9p13-p22 (1992)

Linkage analysis of ten Utah kindreds and one Texas kindred with multiple cases of cutaneous malignant melanoma (CMM) provided evidence that a locus for familial melanoma susceptibility is in the chromosomal region 9p13-p22. The genetic markers analyzed reside in a candidate region on chromosome 9p21, previously implicated by the presence of homozygous deletions in melanoma tumors and by the presence of a germline deletion in an individual with eight independent melanomas. Multipoint linkage analysis was performed between the familial melanoma susceptibility locus (MLM) and two short tandem repeat markers, D9S126 and the interferon-alpha (IFNA) gene, which reside in the region of somatic loss in melanoma tumors. An analysis incorporating a partially penetrant dominant melanoma susceptibility locus places MLM near IFNA and D9S126 with a maximum location score of 12.71. Therefore, the region frequently deleted in melanoma tumors on 9p21 presumably contains a locus that plays a critical role in predisposition to familial melanoma.
In vivo rearrangement of foreign DNA by Fusarium oxysporum produces linear self-replicating plasmids (1990)

Particular combinations of fungal strains and transformation vectors allow for fungal rearrangement of normally integrative plasmids, resulting in the creation of linear self-replicating plasmids in Fusarium oxysporum. The rearrangement results in the addition of fungal DNA, including telomere consensus sequences, to plasmid termini. The mechanism by which this rearrangement occurs is unclear, but it has similarities to extrachromosomal gene amplification. A DNA fragment which allows for linear autonomous replication upon reintroduction to the fungus was subcloned and sequenced. This DNA sequence contains the repeated telomeric sequence TTAGGG flanked by a region of twofold symmetry consisting primarily of pUC12 DNA. Isolation and identification of this sequence is the first step toward development of vectors that function as artificial chromosomes in filamentous fungi. This sequence was shown to promote autonomous replication and enhance transformation in several strains of F. oxysporum, Nectria haematococca, and Cryphonectria parasitica.
Selective and ATP-Dependent Translocation of Peptides by the MHC-Encoded Transporter (1993)

Major histocompatibility complex (MHC) class I molecules present peptides derived from nuclear and cytosolic proteins to CD8+ T cells. These peptides are translocated into the lumen of the endoplasmic reticulum (ER) to associate with class I molecules. Two MHC-encoded putative transporter proteins, TAP1 and TAP2, are required for efficient assembly of class I molecules and presentation of endogenous peptides. Expression of TAP1 and TAP2 in a mutant cell line resulted in the delivery of an 11-amino acid oligomer model peptide to the ER. Peptide translocation depended on the sequence of the peptide, was adenosine triphosphate (ATP)-dependent, required ATP hydrolysis, and was inhibited in a concentration-dependent manner.
Stacking Resistance Alleles from Wild and Domestic Soybean Sources Improves Soybean Cyst Nematode Resistance (2011)

ABSTRACT The soybean cyst nematode (SCN; Heterodera glycines Ichinohe) is the most economically important soybean [ Glycine max (L.) Merr.] pathogen in the United States. Field SCN populations are adapting to the narrowly based SCN resistance currently deployed in soybean cultivars. The objective of our research was to measure the effects of combinations of SCN resistance genes or quantitative trait loci (QTL) from the wild soybean ( Glycine soja Siebold &amp; Zucc.) PI 468916 and the domesticated soybean accessions PI 88788 and PI 437654. Two populations were developed to test the combinations of QTL and genes. Both populations segregated for the G. soja resistance QTL cqSCN‐006 and cqSCN‐007. Population 1 also segregated for resistance from PI 88788 and Population 2 segregated for resistance from PI 437654. The populations were tested for resistance to three SCN isolates in a greenhouse and with single nucleotide polymorphism (SNP) and simple sequence repeat (SSR) markers. In both populations, the two G. soja resistance alleles significantly increased SCN resistance compared with the alternative alleles. The SCN resistance alleles rhg1 and Rhg4 from PI 437654 and rhg1‐b from PI 88788 also significantly increased resistance compared with the alternative alleles. The two G. soja QTL alleles significantly enhanced the resistance derived from PI 88788. These results show that SCN resistance can be increased through stacking genes and QTL from multiple resistance sources.
Dipeptidyl Peptidase IV Inhibition for the Treatment of Type 2 Diabetes (2005)

Dipeptidyl peptidase (DPP)-IV inhibitors are a new approach to the treatment of type 2 diabetes. DPP-IV is a member of a family of serine peptidases that includes quiescent cell proline dipeptidase (QPP), DPP8, and DPP9; DPP-IV is a key regulator of incretin hormones, but the functions of other family members are unknown. To determine the importance of selective DPP-IV inhibition for the treatment of diabetes, we tested selective inhibitors of DPP-IV, DPP8/DPP9, or QPP in 2-week rat toxicity studies and in acute dog tolerability studies. In rats, the DPP8/9 inhibitor produced alopecia, thrombocytopenia, reticulocytopenia, enlarged spleen, multiorgan histopathological changes, and mortality. In dogs, the DPP8/9 inhibitor produced gastrointestinal toxicity. The QPP inhibitor produced reticulocytopenia in rats only, and no toxicities were noted in either species for the selective DPP-IV inhibitor. The DPP8/9 inhibitor was also shown to attenuate T-cell activation in human in vitro models; a selective DPP-IV inhibitor was inactive in these assays. Moreover, we found DPP-IV inhibitors that were previously reported to be active in models of immune function to be more potent inhibitors of DPP8/9. These results suggest that assessment of selectivity of potential clinical candidates may be important to an optimal safety profile for this new class of antihyperglycemic agents.
Antibody-ribosome-mRNA (ARM) complexes as efficient selection particles for in vitro display and evolution of antibody combining sites (1997)

We describe a rapid, eukaryotic, in vitro method for selection and evolution of antibody combining sites using antibody-ribosome-mRNA (ARM) complexes as selection particles. ARMs carrying single-chain (VH/K) binding fragments specific for progesterone were selected using antigen-coupled magnetic beads; selection simultaneously captured the genetic information as mRNA, making it possible to generate and amplify cDNA by single-step RT-PCR on the ribosome-bound mRNA for further manipulation. Using mutant libraries, antigen-binding ARMs were enriched by a factor of 10(4)-10(5)-fold in a single cycle, with further enrichment in repeated cycles. While demonstrated here for antibodies, the method has the potential to be applied equally for selection of receptors or peptides from libraries.
Generation of Tyrosine Hydroxylase Positive Neurons from Human Embryonic Stem Cells after Coculture with Cellular Substrates and Exposure to GDNF (2004)

Tyrosine hydroxylase (TH)-positive neurons were generated from human embryonic stem (hES) cells by coculturing on astrocytes or PA6 stromal cells. After 3 to 4 weeks in culture, TH-positive cells with neuronal morphology developed. Coculture with astrocytes from the embryonic striatum produced a larger number of TH-positive cells than did coculture with astrocytes from embryonic mesencephalon (329 +/- 149 versus 33 +/- 16 TH-positive cells per well, p < .05). In other experiments using PA6 cells as a substrate, glial-derived neurotrophic factor (GDNF) was added to the media of differentiating hES cells, and this led to a doubling of the number of TH-positive cells (PA6: 443 +/- 105 TH-positive cells per well versus PA6 + GDNF: 934 +/- 136, p < .05). We conclude that substrates of striatal astrocytes and PA6 cells can promote differentiation of human embryonic stem cells to a TH-positive phenotype and that GDNF can increase the number of cells expressing that phenotype.
Hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry for the quantification of uridine diphosphate-glucose, uridine diphosphate-glucuronic acid, deoxynivalenol and its glucoside: In-house validation and application to wheat (2015)

Nucleotide sugars, the activated forms of monosaccharides, are important metabolites involved in a multitude of cellular processes including glycosylation of xenobiotics. Especially in plants, UDP-glucose is one of the most prominent members among these nucleotide-sugars, as it is involved in the formation of glucose conjugates of xenobiotics, including mycotoxins, but also holds a central role in the interconversion of energized sugars such as the formation of UDP-glucuronic acid required for cell wall biosynthesis. Here, we present the first HILIC-LC-ESI-TQ-MS/MS method for the quantification of UDP-glucose and UDP-glucuronic acid together with the Fusarium toxin deoxynivalenol (DON) and its major plant detoxification product DON-3-O-glucoside (DON-3-Glc) utilizing a polymer-based column. For sample preparation a time-effective and straightforward 'dilute and shoot' protocol was applied. The chromatographic run time was minimized to 9min including proper column re-equilibration. In-house validation of the method verified its linear range, intra- (1-7%) and interday (8-20%) precision, instrumental LODs between 0.6 and 10ngmL(-1), selectivity and moderate matrix effects with mean recoveries of 85-103%. To prove the methods applicability, we analyzed two sets of wheat extracts obtained from different cultivars grown under standardized greenhouse conditions. The results clearly demonstrated the suitability of the developed method to quantify UDP-glucose, DON and its masked form D3G in diluted wheat extracts. We observed differing concentration levels of UDP-glucose in the two wheat cultivars showing different resistance to the severe plant disease Fusarium head blight. We propose that the higher ability to detoxify DON into DON-3-Glc might be a consequence of the higher cellular UDP-glucose pool in the resistant cultivar.
Performance Criteria for Spread Spectrum Communications (1977)

The criteria for antijam (AJ) and anti-intercept (AI) systems are described, in terms of the appropriate action taken by the jammer or interceptor. Avoiding pseudonoise (PN) sequences which can be partially or totally predicted is a foremost criteria, especially for AJ, and use of nonlinear feedforward logic (NFFL) with long-period linear maximal sequences appears attractive. A frequency-hopping (FH) system must anticipate a multitone jamming signal, and an error-control code is necessary. A novel method for generating a multitone signal using repeating maximal sequences is described. PN systems must anticipate a tone jammer, and now an errorcontrol code may be needed to assure that sporadic PN sequence correlation with the tone does not reduce the processing gain. Any AI system must anticipate that the interceptor may, if advantageous, integrate his decision energy over many communicator symbols (up to the message length). Now spreading both in frequency and in time may be valuable. Finally, the use of an automatic adaptive data rate is suggested to realize flexibly either AJ or AI objectives.
Characterization and applications of Nanobodies against human procalcitonin selected from a novel naïve Nanobody phage display library (2015)

We have constructed a large and diverse naïve phage display Nb library, which potentially functioning as a good resource for selecting antigen-binders with high quality. Moreover, functional Nbs against PCT were successfully characterized and applied, providing great values on medical application.
Diels−Alder Click Cross-Linked Hyaluronic Acid Hydrogels for Tissue Engineering (2011)

Hyaluronic acid (HA) is a naturally occurring polymer that holds considerable promise for tissue engineering applications. Current cross-linking chemistries often require a coupling agent, catalyst, or photoinitiator, which may be cytotoxic, or involve a multistep synthesis of functionalized-HA, increasing the complexity of the system. With the goal of designing a simpler one-step, aqueous-based cross-linking system, we synthesized HA hydrogels via Diels-Alder "click" chemistry. Furan-modified HA derivatives were synthesized and cross-linked via dimaleimide poly(ethylene glycol). By controlling the furan to maleimide molar ratio, both the mechanical and degradation properties of the resulting Diels-Alder cross-linked hydrogels can be tuned. Rheological and degradation studies demonstrate that the Diels-Alder click reaction is a suitable cross-linking method for HA. These HA cross-linked hydrogels were shown to be cytocompatible and may represent a promising material for soft tissue engineering.
Selective Stimulation of Renal Nerves in the Anesthetized Dog (1973)

The combined effects of low-frequency stimulation of the renal sympathetic nerves and reductions in renal arterial blood pressure on various hemodynamic parameters of the in situ kidney and on renal venous renin levels were determined in 17 dogs. Autoregulation of flow (measured using noncannulating electromagnetic probes) and glomerular filtration (measured using continuous extraction of 131 I-iothalamate) was followed before, during, and after nerve stimulation. Stimulation of isolated renal nerves (0.5 msec, 10-15 v, 0.1-3.0/sec) produced distinct changes in the release of renin with only minimal changes in the autoregulatory curves for glomerular filtration rate and renal plasma flow. Reducing arterial blood pressure from 150 to 50 mm Hg caused an increase in the release of renin from 4 to 35 ng/ml hour -1 . Stimulation of the renal nerves increased renin production at both pressures (from 4 to 10 ng/ml hour -1 at 150 mm Hg and from 35 to 50 ng/ml hour -1 at 50 mm Hg). In fact, renal nerve stimulation elicited increases in renin release at all pressures examined. In contrast, sodium excretion following nerve stimulation was depressed at comparable sodium loads in spite of minimal changes in renal hemodynamics. It appears that the effect of the renal sympathetic nerves on renin release is evident at all pressures; however, the sympathetic nerves are proportionately more important at pressures above 100 mm Hg and the renal artery pressure plays a greater role at pressures below 115-100 mm Hg.