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- 저자 : Youngblood, Marston Jr. (검색결과 5 건)
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Youngblood, Ben,Oestreich, Kenneth ,J.,Ha, Sang-Jun,Duraiswamy, Jaikumar,Akondy, Rama ,S.,West, Erin ,E.,Wei, Zhengyu,Lu, Peiyuan,Austin, James ,W.,Riley, James ,L.,Boss, Jeremy&nb Elsevier 2011 Immunity Vol.35 No.3
<P><B>Summary</B></P><P>Functionally exhausted T cells have high expression of the PD-1 inhibitory receptor, and therapies that block PD-1 signaling show promise for resolving chronic viral infections and cancer. By using human and murine systems of acute and chronic viral infections, we analyzed epigenetic regulation of PD-1 expression during CD8<SUP>+</SUP> T cell differentiation. During acute infection, naive to effector CD8<SUP>+</SUP> T cell differentiation was accompanied by a transient loss of DNA methylation of the <I>Pdcd1</I> locus that was directly coupled to the duration and strength of T cell receptor signaling. Further differentiation into functional memory cells coincided with <I>Pdcd1</I> remethylation, providing an adapted program for regulation of PD-1 expression. In contrast, the <I>Pdcd1</I> regulatory region was completely demethylated in exhausted CD8<SUP>+</SUP> T cells and remained unmethylated even when virus titers decreased. This lack of DNA remethylation leaves the <I>Pdcd1</I> locus poised for rapid expression, potentially providing a signal for premature termination of antiviral functions.</P> <P><B>Highlights</B></P><P>► <I>Pdcd1</I> locus demethylation is coupled to naive to effector CD8<SUP>+</SUP> T cell differentiation ► After <I>Pdcd1</I> remethylation, select CpGs remain unmethylated in memory CD8<SUP>+</SUP> T cells ► Exhausted virus-specific CD8<SUP>+</SUP> T cells retain an unmethylated <I>Pdcd1</I> regulatory region ► Human CD8<SUP>+</SUP> T cells specific to chronic viruses retain an unmethylated <I>PDCD1</I> locus</P>
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ISSUES IN FORMULATING PERFORMANCE-BASED APPROACHES TO REGULATORY OVERSIGHT OF NUCLEAR POWER PLANTS
YOUNGBLOOD R. W.,KIM I. S. Korean Nuclear Society 2005 Nuclear Engineering and Technology Vol.37 No.3
In recent decades, significant effort has led to risk-informed improvements to regulation. Performance-based approaches also promise significant gains in efficiency (level of safety versus effort). However, significant work remains to be done before performance-based approaches realize their full potential in regulation of nuclear power plants. This paper reviews key concepts related to performance-based regulation, discusses some applications of performance-based approaches, and identifies issues that still need to be addressed. Realistic, experience-based models of licensee performance are still lacking; this makes it difficult to assess the prospective effectiveness of any given regulatory approach, in light of the performance issues that it will actually face. Also, while 'compliance' is an intuitively straightforward concept to apply within a prescriptive implementation, its analog in a performance-based approach remains unclear. An overarching theme of the paper is that formal methods of decision analysis are very helpful in developing appropriate regulatory approaches, especially performance-based ones; this theme is illustrated at several points.
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Sequential patient recruitment monitoring in multi-center clinical trials
Kim, Dong-Yun,Han, Sung-Min,Youngblood, Marston Jr. The Korean Statistical Society 2018 Communications for statistical applications and me Vol.25 No.5
We propose Sequential Patient Recruitment Monitoring (SPRM), a new monitoring procedure for patient recruitment in a clinical trial. Based on the sequential probability ratio test using improved stopping boundaries by Woodroofe, the method allows for continuous monitoring of the rate of enrollment. It gives an early warning when the recruitment is unlikely to achieve the target enrollment. The packet data approach combined with the Central Limit Theorem makes the method robust to the distribution of the recruitment entry pattern. A straightforward application of the counting process framework can be used to estimate the probability to achieve the target enrollment under the assumption that the current trend continues. The required extension of the recruitment period can also be derived for a given confidence level. SPRM is a new, continuous patient recruitment monitoring tool that provides an opportunity for corrective action in a timely manner. It is suitable for the modern, centralized data management environment and requires minimal effort to maintain. We illustrate this method using real data from two well-known, multicenter, phase III clinical trials.
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최진희,이상미,강호정,이재열,김정안,유현오,T. R. Stratton,Bruce M. Applegate,Jeffrey P. Youngblood,김형중,류경남 한국고분자학회 2010 Macromolecular Research Vol.18 No.5
A simple and useful method to synthesize water-soluble chitosan is proposed. Water-soluble chitosan-gpoly(ethylene oxide) could be synthesized readily by modification of authentic chitosan with a 150,000 g/mol molecular weight using ω-anhydride-functionalized poly(ethylene oxide)s (PEOs) with or without small molecular anhydride compounds, such as phthalic anhydride or acetic anhydride through a ‘grafting onto’ method. The PEOgrafting method in the presence of acetic anhydride leading to partial acetylation appears to be more effective in synthesizing relatively high water-soluble chitosan. The bactericidal properties of PEO-modified chitosan and small molecular anhydride over a moderate concentration range (over 500 μg/mL) suggest that they might be used in the biomedical field. The PEO-grafted chitosans were used successfully as polymeric stabilizers to prepare nano-sized iron oxide particles as a magnetic resonance imaging contrast agent for tumor cells. The size of the iron oxide nanoparticles stabilized by modified chitosans was controlled in the range of 5 to 30 nm with superparamagnetic properties in aqueous media. All the materials were characterized by 1H NMR, UV/Visible spectroscopy, TEM,magnetization, and XRD pattern analyses.
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