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Natural Killer Cells Degenerate Intact Sensory Afferents following Nerve Injury
Davies, Alexander J.,Kim, Hyoung Woo,Gonzalez-Cano, Rafael,Choi, Jahyang,Back, Seung Keun,Roh, Seung Eon,Johnson, Errin,Gabriac, Melanie,Kim, Mi-Sun,Lee, Jaehee,Lee, Jeong Eun,Kim, Yun Sook,Bae, Yong Cell Press 2019 Cell Vol. No.
<P><B>Summary</B></P> <P>Sensory axons degenerate following separation from their cell body, but partial injury to peripheral nerves may leave the integrity of damaged axons preserved. We show that an endogenous ligand for the natural killer (NK) cell receptor NKG2D, Retinoic Acid Early 1 (RAE1), is re-expressed in adult dorsal root ganglion neurons following peripheral nerve injury, triggering selective degeneration of injured axons. Infiltration of cytotoxic NK cells into the sciatic nerve by extravasation occurs within 3 days following crush injury. Using a combination of genetic cell ablation and cytokine-antibody complex stimulation, we show that NK cell function correlates with loss of sensation due to degeneration of injured afferents and reduced incidence of post-injury hypersensitivity. This neuro-immune mechanism of selective NK cell-mediated degeneration of damaged but intact sensory axons complements Wallerian degeneration and suggests the therapeutic potential of modulating NK cell function to resolve painful neuropathy through the clearance of partially damaged nerves.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cytotoxic NK cells infiltrate the damaged peripheral nerve within days of injury </LI> <LI> Injured sensory axons express NKG2D ligand RAE1 to signal degeneration by NK cells </LI> <LI> Clearance of damaged axons reduces development of chronic pain after nerve injury </LI> <LI> NK cells complement Wallerian degeneration to aid functional regeneration of PNS </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
The Theology of Henry G. Appenzeller.
Davies, Daniel M. 성화대학교 1993 成和論叢 Vol.- No.1
Henry G. Appenzeller (1858-1902), raised by pious German Reformed parents and in the German Reformed Church of Pennsylvania, had a rebirth experience in 1876. He joined the Methodist Church in Lancaster, Pennsylvania in 1880 while attending the German Reformed Franklin and Marshall College. By 1882, when he entered Drew Theological Seminary in New Jersey to become a Methodist minister, Appenzeller had been immersed in the Heidelberg Catechism, Mercersburg Theology, and Methodist preaching. At Drew theological Seminary, Appenzeller received theological training from the "Great Five" (Strong, Miley, Buttz, Upham, and Crooks) and imbibed the pietistic spiritual atmosphere of the seminary. He continued his theological education in Korea through the study course required of all ordained Methodist ministers. Both as a student at Drew Theological Seminary and as a missionary in Korea, Appenzeller embraced a evangelical theology that reflected the Heidelberg Catechism, Mercersburg theology, and the teachings of the Great Five. He held conversion and sanctification as his paramount concerns, placing Jesus Christ and redemption through the Cross at the center of his theology. He concerned himself only with those theological categories, both at Drew Theological Seminary and in Korea, that he found pertinent to conversion and sanctification. In Korea, Appenzeller's theology developed through the influence of escapism and liberal theological ideas. Appenzeller's theology set the direction for theology in Korea that has continued until today. It is impossible to understand the evangelical, conservative character of present day Protestant theology in Korea without taking into account the impact of Appenzeller's theology.
HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures
Davies, Helen,Glodzik, Dominik,Morganella, Sandro,Yates, Lucy R,Staaf, Johan,Zou, Xueqing,Ramakrishna, Manasa,Martin, Sancha,Boyault, Sandrine,Sieuwerts, Anieta M,Simpson, Peter T,King, Tari A,Raine, Nature Publishing Group, a division of Macmillan P 2017 Nature medicine Vol.23 No.4
<P>Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (similar to 1-5%) who could have selective therapeutic sensitivity to PARP inhibition.</P>
Nonlinear System Modeling and Identification
Davies,Patricia 대한기계학회 1993 Korea - U. S. Vibration Engineering Seminar Vol.1 No.1
Digital models have been used extensively to model the relationship between the sampled input and sampled output of vibrating linear systems. By using established mapping techniques, the parameters of these digital models can be translated into estimates of physical parameters, such as natural frequencies, damping ratios and modal amplitudes. The use of digital models to model the relationship between the sampled input and sampled output of nonlinear systems is not so widespread. Mapping between the digital model parameters and the physical parameters that describe the system behavior is not straightforward. The paper will contain an overview of system identification techniques for nonlinear systems. The use of some of the techniques to identify the behavior of thin plates with coincident natural frequencies will be discussed.