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Special Theme 01 - 필라델피아 소방서의 화재안전교육 소개
Sawyer, Derrick 한국화재보험협회 2011 防災와 保險 Vol.143 No.-
Derrick Sawyer는 26년간 소방관으로 재직하면서 대민화재안전교육 업무를 총괄하고 있다. NFPA의 대도시 화재안전 TF에 참여하는 등 활발한 활동을 하고 있다.
Stereochemistry of metal tetramethylcyclam complexes directed by an unexpected anion effect
Derrick, Jeffrey S.,Kim, Yujeong,Tak, Hyeonwoo,Park, Kiyoung,Cho, Jaeheung,Kim, Sun Hee,Lim, Mi Hee Royal Society of Chemistry 2017 Dalton Transactions Vol. No.
<▼1><P>An unexpected anion effect leads to the direct and selective preparation of the <I>trans</I>-III-[Cu(TMC)]<SUP>2+</SUP> complex that is fully characterized by X-ray crystallography, UV-visible spectroscopy, advanced EPR spectroscopy, and computational studies.</P></▼1><▼2><P>Metal(TMC) complexes (TMC = tetramethylcyclam) exclusively form <I>trans</I>-I diastereoisomers; thus, little is known about the <I>trans</I>-III isomers. Herein, we report a new method to prepare the <I>trans</I>-III-[Cu(TMC)]<SUP>2+</SUP> complex <I>via</I> an anion effect. Our crystallographic, spectroscopic, and computational analyses validated that [Cu(TMC)](NO3)2 produced the <I>trans</I>-III complex, different from the <I>trans</I>-I structure of [Cu(TMC)](ClO4)2.</P></▼2>
Derrick, Jeffrey S.,Kerr, Richard A.,Korshavn, Kyle J.,McLane, Michael J.,Kang, Juhye,Nam, Eunju,Ramamoorthy, Ayyalusamy,Ruotolo, Brandon T.,Lim, Mi Hee American Chemical Society 2016 Inorganic Chemistry Vol.55 No.10
<P>The complex and multifaceted pathology of Alzheimer's disease (AD) continues to present a formidable challenge to the establishment of long-term treatment strategies. Multifunctional compounds able to modulate the reactivities of various pathological features, such as amyloid-beta (A beta) aggregation, metal ion dyshomeostasis, and oxidative stress, have emerged as useful tactic. Recently, an incorporation approach to the rational design of multipurpose small molecules has been validated through the production of a multifunctional ligand (ML) as a potential chemical tool for AD. In order to further the development of more diverse and improved multifunctional reagents, essential pharmacophores must be identified. Herein, we report a series of aminoquinoline derivatives (AQ1-4, AQP1-4, and AQDA1-3) based on ML's framework, prepared to gain a structure reactivity understanding of ML's multifunctionality in addition to tuning its metal binding affinity. Our structure reactivity investigations have implicated the dimethylamino group as a key component for supplying the antiamyloidogenic characteristics of ML in both the absence and presence of metal ions. Two-dimensional NMR studies indicate that structural variations of ML could tune its interaction sites along the A beta sequence. In addition, mass spectrometric analyses suggest that the ability of our aminoquinoline derivatives to regulate metal-induced A beta aggregation may be influenced by their metal binding properties. Moreover, structural modifications to ML were also observed to noticeably change its metal binding affinities and metal-to-ligand stoichiometries that were shown to be linked to their antiamyloidogenic and antioxidant activities. Overall, our studies provide new insights into rational design strategies for multifunctional ligands directed at regulating metal ions, A beta, and oxidative stress in AD and could advance the development of improved next-generation multifunctional reagents.</P>
Mechanistic Insights into Tunable Metal-Mediated Hydrolysis of Amyloid-β Peptides
Derrick, Jeffrey S.,Lee, Jiwan,Lee, Shin Jung C.,Kim, Yujeong,Nam, Eunju,Tak, Hyeonwoo,Kang, Juhye,Lee, Misun,Kim, Sun Hee,Park, Kiyoung,Cho, Jaeheung,Lim, Mi Hee American Chemical Society 2017 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.139 No.6
<P>An amyloidogenic peptide, amyloid-beta (A beta), has been implicated as a contributor to the neurotoxicity of Alzheimer's disease (AD) that continues to present a major socioeconomic burden for our society. Recently, the use of metal complexes capable of cleaving peptides has arisen as an efficient tactic for amyloid management; unfortunately, little has been reported to pursue this strategy. Herein, we report a novel approach to validate the hydrolytic cleavage of divalent metal complexes toward two major isoforms of A beta (A beta(40) and A beta(42)) and tune their proteolytic activity based on the choice of metal centers (M = Co, Ni, Cu, and Zn) which could be correlated to their anti-amyloidogenic properties. Such metal-dependent tunability was facilitated employing a tetra-N-methylated cyclam (TMC) ligand that imparts unique geometric and stereochemical control, which has not been available in previous systems. Co(II)(TMC) was identified to noticeably cleave A beta peptides and control their aggregation, reporting the first Co(II) complex for such reactivities to the best of our knowledge. Through detailed mechanistic investigations by biochemical, spectroscopic, mass spectrometric, and computational studies, the critical importance of the coordination environment and acidity of the aqua-bound complexes in promoting amide hydrolysis was verified. The biological applicability, of Co(II)(TMC) was also illustrated via its potential blood-brain barrier permeability, relatively low cytotoxicity, regulatory capability against toxicity induced by both A beta(40) and A beta(42) in living cells, proteolytic activity with A beta peptides under biologically relevant conditions, and inertness toward cleavage of structured proteins. Overall,, our approaches and findings on reactivities of divalent metal complexes toward Afi, along with the mechanistic insights, demonstrate the feasibility of utilizing such metal complexes for amyloid control.</P>
Derrick J. Sanderson,Matthew Gevelinger,Elaine Jaworski,Paula J. Doyle 대한비뇨의학회 2020 Investigative and Clinical Urology Vol.61 No.2
Purpose: The aim of this study is to evaluate changes in sleep disturbance following treatment of overactive bladder with sacral neuromodulation. Materials and Methods: This is a sub-analysis of data collected from an institutional review board approved retrospective cohort study evaluating women with Patient-Reported Outcomes Measurement Information System–Sleep Disturbance (PROMIS-SD) before and after sacral neuromodulation for overactive bladder between March 2016 and October 2017. Data collected included demographics, clinical characteristics, and additional PROMIS item banks. Within-group analysis was performed with paired t-tests. Groups based up on PROMIS-SD improvement (change <0) were then compared using Fisher's exact test, t-test, or Mann–Whitney U-test as appropriate. Results: Those with improved sleep disturbance (n=7) noted a significant mean improvement of −3.99 (95% confidence interval, −6.32, −1.65; p<0.01). Both pre- and post-procedure PROMIS-Physical Function (38.86±2.35 vs. 34.13±5.58, p=0.07 and 37.14±5.10 vs. 35.44±4.74, p=0.53), Pain Interference (60.04±6.34 vs. 65.50±6.20, p=0.13 and 57.89±5.08 vs. 64.73±7.35, p=0.07), Depression (44.2±4.73 vs. 61.29±9.53, p=0.17 and 54.29±6.25 vs. 57.96±11.42, p=0.47) t-scores were similar between sleep response groups. Conclusions: Those with improved sleep disturbance reported significant changes after sacral neuromodulation for overactive bladder. However, no significant differences were identified between those with and without improvement. Further investigation of changes in sleep disturbance and factors affecting change are needed within this population.