682 research outputs found
Calibration of a fission gas monitor
Calibration of argon gas neutron activation sampling devic
High-Level Expression of Various Apolipoprotein (a) Isoforms by "Transferrinfection". The Role of Kringle IV Sequences in the Extracellular Association with Low-Density Lipoprotein
Characterization of the assembly of lipoprotein(a) [Lp(a)] is of fundamental importance to understanding the biosynthesis and metabolism of this atherogenic lipoprotein. Since no established cell lines exist that express Lp(a) or apolipoprotein(a) [apo(a)], a "transferrinfection" system for apo(a) was developed utilizing adenovirus receptor- and transferrin receptor-mediated DNA uptake into cells. Using this method, different apo(a) cDNA constructions of variable length, due to the presence of 3, 5, 7, 9, 15, or 18 internal kringle IV sequences, were expressed in cos-7 cells or CHO cells. All constructions contained kringle IV-36, which includes the only unpaired cysteine residue (Cys-4057) in apo(a). r-Apo(a) was synthesized as a precursor and secreted as mature apolipoprotein into the medium. When medium containing r-apo(a) with 9, 15, or 18 kringle IV repeats was mixed with normal human plasma LDL, stable complexes formed that had a bouyant density typical of Lp(a). Association was substantially decreased if Cys-4057 on r-apo(a) was replaced by Arg by site-directed mutagenesis or if Cys-4057 was chemically modified. Lack of association was also observed with r-apo(a) containing only 3, 5, or 7 kringle IV repeats without "unique kringle IV sequences", although Cys-4057 was present in all of these constructions. Synthesis and secretion of r-apo(a) was not dependent on its sialic acid content. r-Apo(a) was expressed even more efficiently in sialylation-defective CHO cells than in wild-type CHO cells. In transfected CHO cells defective in the addition of N-acetylglucosamine, apo(a) secretion was found to be decreased by 50%. Extracellular association with LDL was not affected by the carbohydrate moiety of r-apo(a), indicating a protein-protein interaction between r-apo(a) and apoB. These results show that, besides kringle IV-36, other kringle IV sequences are necessary for the extracellular association of r-apo(a) with LDL. Changes in the carbohydrate moiety of apo(a), however, do not affect complex formation
Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans
Rabies kills many people throughout the developing world every year. The murine monoclonal antibody (mAb) 62-71-3 was recently identified for its potential application in rabies postexposure prophylaxis (PEP). The purpose here was to establish a plant-based production system for a chimeric mouse-human version of mAb 62-71-3, to characterize the recombinant antibody and investigate at a molecular level its interaction with rabies virus glycoprotein. Chimeric 62-71-3 was successfully expressed in Nicotiana benthamiana. Glycosylation was analyzed by mass spectroscopy; functionality was confirmed by antigen ELISA, as well as rabies and pseudotype virus neutralization. Epitope characterization was performed using pseudotype virus expressing mutagenized rabies glycoproteins. Purified mAb demonstrated potent viral neutralization at 500 IU/mg. A critical role for antigenic site I of the glycoprotein, as well as for two specific amino acid residues (K226 and G229) within site I, was identified with regard to mAb 62-71-3 neutralization. Pseudotype viruses expressing glycoprotein from lyssaviruses known not to be neutralized by this antibody were the controls. The results provide the molecular rationale for developing 62-71-3 mAb for rabies PEP; they also establish the basis for developing an inexpensive plant-based antibody product to benefit low-income families in developing countries.—Both, L., van Dolleweerd, C., Wright, E., Banyard, A. C., Bulmer-Thomas, B., Selden, D., Altmann, F., Fooks, A. R., Ma, J. K.-C. Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans
Education policy as an act of white supremacy: whiteness, critical race theory and education reform
The paper presents an empirical analysis of education policy in England that is informed by recent developments in US critical theory. In particular, I draw on ‘whiteness studies’ and the application of Critical Race Theory (CRT). These perspectives offer a new and radical way of conceptualising the role of racism in education. Although the US literature has paid little or no regard to issues outside North America, I argue that a similar understanding of racism (as a multifaceted, deeply embedded, often taken-for-granted aspect of power relations) lies at the heart of recent attempts to understand institutional racism in the UK. Having set out the conceptual terrain in the first half of the paper, I then apply this approach to recent changes in the English education system to reveal the central role accorded the defence (and extension) of race inequity. Finally, the paper touches on the question of racism and intentionality: although race inequity may not be a planned and deliberate goal of education policy neither is it accidental. The patterning of racial advantage and inequity is structured in domination and its continuation represents a form of tacit intentionality on the part of white powerholders and policy makers. It is in this sense that education policy is an act of white supremacy. Following others in the CRT tradition, therefore, the paper’s analysis concludes that the most dangerous form of ‘white supremacy’ is not the obvious and extreme fascistic posturing of small neonazi groups, but rather the taken-for-granted routine privileging of white interests that goes unremarked in the political mainstream
Do Human Resource Departments Act as Strategic Partners? Strategic Human Capital Management Adoption by County Governments
Drawing on qualitative data from forty counties in New York and North Carolina, this article examines the adoption of strategic human capital management (SHCM) principles and practices at the county level and presents a typology of five levels of SHCM adoption. The level of SHCM implementation in a county depends on: the view of the HR function by executive county leadership, the capacity of the county to engage in strategic planning and management, and the capacity of the HR director to think strategically about the role of HR in the government. The article concludes with recommendations for practice, which focus on educating a diverse set of actors about SHCM, building executive level support, developing HR skill and competencies, and applying basic change management practices
A Mathematical Model of Liver Cell Aggregation In Vitro
The behavior of mammalian cells within three-dimensional structures is an area of intense biological research and underpins the efforts of tissue engineers to regenerate human tissues for clinical applications. In the particular case of hepatocytes (liver cells), the formation of spheroidal multicellular aggregates has been shown to improve cell viability and functionality compared to traditional monolayer culture techniques. We propose a simple mathematical model for the early stages of this aggregation process, when cell clusters form on the surface of the extracellular matrix (ECM) layer on which they are seeded. We focus on interactions between the cells and the viscoelastic ECM substrate. Governing equations for the cells, culture medium, and ECM are derived using the principles of mass and momentum balance. The model is then reduced to a system of four partial differential equations, which are investigated analytically and numerically. The model predicts that provided cells are seeded at a suitable density, aggregates with clearly defined boundaries and a spatially uniform cell density on the interior will form. While the mechanical properties of the ECM do not appear to have a significant effect, strong cell-ECM interactions can inhibit, or possibly prevent, the formation of aggregates. The paper concludes with a discussion of our key findings and suggestions for future work
Effects of systematic asymmetric discounting on physician-patient interactions: a theoretical framework to explain poor compliance with lifestyle counseling
BACKGROUND: This study advances the use of a utility model to model physician-patient interactions from the perspectives of physicians and patients. PRESENTATION OF THE HYPOTHESIS: In cases involving acute care, patient counseling involves a relatively straightforward transfer of information from the physician to a patient. The patient has less information than the physician on the impact the condition and its treatment have on utility. In decisions involving lifestyle changes, the patient may have more information than the physician on his/her utility of consumption; moreover, differences in discounting future health may contribute significantly to differences between patients' preferences and physicians' recommendations. TESTING THE HYPOTHESIS: The expectation of differences in internal discount rate between patients and their physicians is discussed. IMPLICATIONS OF THE HYPOTHESIS: This utility model provides a conceptual basis for the finding that educational approaches alone may not effect changes in patient behavior and suggests other economic variables that could be targeted in the attempt to produce healthier behavior
Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%.
Cystic fibrosis (CF)--an autosomal recessive disorder caused by mutations in CF transmembrane conductance regulator (CFTR) and characterized by abnormal chloride conduction across epithelial membranes, leading to chronic lung and exocrine pancreatic disease--is less common in African-Americans than in Caucasians. No large-scale studies of mutation identification and screening in African-American CF patients have been reported, to date. In this study, the entire coding and flanking intronic sequence of the CFTR gene was analyzed by denaturing gradient-gel electrophoresis and sequencing in an index group of 82 African-American CF chromosomes to identify mutations. One novel mutation, 3120+1G-->A, occurred with a frequency of 12.3% and was also detected in a native African patient. To establish frequencies, an additional group of 66 African-American CF chromosomes were screened for mutations identified in two or more African-American patients. Screening for 16 "common Caucasian" mutations identified 52% of CF alleles in African-Americans, while screening for 8 "common African" mutations accounted for an additional 23%. The combined detection rate of 75% was comparable to the sensitivity of mutation analysis in Caucasian CF patients. These results indicate that African-Americans have their own set of "common" CF mutations that originate from the native African population. Inclusion of these "common" mutations substantially improves CF mutation detection rates in African-Americans
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