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Krieger, Elmar,Joo, Keehyoung,Lee, Jinwoo,Lee, Jooyoung,Raman, Srivatsan,Thompson, James,Tyka, Mike,Baker, David,Karplus, Kevin Wiley Subscription Services, Inc., A Wiley Company 2009 Proteins Vol.77 No.suppl9
<P>A correct alignment is an essential requirement in homology modeling. Yet in order to bridge the structural gap between template and target, which may not only involve loop rearrangements, but also shifts of secondary structure elements and repacking of core residues, high-resolution refinement methods with full atomic details are needed. Here, we describe four approaches that address this 'last mile of the protein folding problem' and have performed well during CASP8, yielding physically realistic models: YASARA, which runs molecular dynamics simulations of models in explicit solvent, using a new partly knowledge-based all atom force field derived from Amber, whose parameters have been optimized to minimize the damage done to protein crystal structures. The LEE-SERVER, which makes extensive use of conformational space annealing to create alignments, to help Modeller build physically realistic models while satisfying input restraints from templates and CHARMM stereochemistry, and to remodel the side-chains. ROSETTA, whose high resolution refinement protocol combines a physically realistic all atom force field with Monte Carlo minimization to allow the large conformational space to be sampled quickly. And finally UNDERTAKER, which creates a pool of candidate models from various templates and then optimizes them with an adaptive genetic algorithm, using a primarily empirical cost function that does not include bond angle, bond length, or other physics-like terms.</P>
Amelioration of sepsis by TIE2 activation–induced vascular protection
Han, Sangyeul,Lee, Seung-Jun,Kim, Kyung Eun,Lee, Hyo Seon,Oh, Nuri,Park, Inwon,Ko, Eun,Oh, Seung Ja,Lee, Yoon-Sook,Kim, David,Lee, Seungjoo,Lee, Dae Hyun,Lee, Kwang-Hoon,Chae, Su Young,Lee, Jung-Hoon American Association for the Advancement of Scienc 2016 Science translational medicine Vol.8 No.335
<P>Protection of endothelial integrity has been recognized as a frontline approach to alleviating sepsis progression, yet no effective agent for preserving endothelial integrity is available. Using an unusual anti-angiopoietin 2 (ANG2) antibody, ABTAA (ANG2-binding and TIE2-activating antibody), we show that activation of the endothelial receptor TIE2 protects the vasculature from septic damage and provides survival benefit in three sepsis mouse models. Upon binding to ANG2, ABTAA triggers clustering of ANG2, assembling an ABTAA/ANG2 complex that can subsequently bind and activate TIE2. Compared with a conventional ANG2-blocking antibody, ABTAA was highly effective in augmenting survival from sepsis by strengthening the endothelial glycocalyx, reducing cytokine storms, vascular leakage, and rarefaction, and mitigating organ damage. Together, our data advance the role of TIE2 activation in ameliorating sepsis progression and open a potential therapeutic avenue for sepsis to address the lack of sepsisspecific treatment.</P>
Robotic Prostatectomy: What We Have Learned and Where We Are Going
David I. Lee 연세대학교의과대학 2009 Yonsei medical journal Vol.50 No.2
Radical prostatectomy became a mainstay of treatment for prostate cancer in the United States after the pioneering work of Walsh in defining the nerve sparing technique. Efforts to reproduce this operation in a minimally invasive fashion resulted in slow progress that recently have flourished with the application of the daVinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) by Menon and colleagues. This article summarizes the origins of robotic prostatectomy, some of the current data regarding this operation and potential future directions. Radical prostatectomy became a mainstay of treatment for prostate cancer in the United States after the pioneering work of Walsh in defining the nerve sparing technique. Efforts to reproduce this operation in a minimally invasive fashion resulted in slow progress that recently have flourished with the application of the daVinci Surgical System (Intuitive Surgical, Sunnyvale, CA, USA) by Menon and colleagues. This article summarizes the origins of robotic prostatectomy, some of the current data regarding this operation and potential future directions.
Lee, Yu-Mi,Bae, Sang-Geun,Lee, Seon-Hwa,Jacobs Jr, David R.,Lee, Duk-Hee The Korean Academy of Medical Sciences 2013 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.28 No.8
<P>There are substantial variations of relative risks (RR) in smoking-related mortality by country and time. We hypothesized the RRs in smoking-related mortality might differ depending on serum concentrations of persistent organic pollutants (POPs). We evaluated the associations of cigarette smoking with total mortality in 610 elderly (aged ≥ 70 yr) (702 elderly for organochlorine pesticides [OCPs]) after stratification by serum concentration of POPs, in the National Health and Nutrition Examination Survey (NHANES) 1999-2004 followed through 2006. Summary measures of POPs subclasses showed significant or marginally significant interaction with cigarette smoking on the risk of total mortality. <I>P</I> values for interaction were 0.069 for polychlorinated dibenzo-p-dioxins (PCDDs), 0.008 for polychlorinated biphenyls (PCBs), and 0.024 for OCPs. The effect of smoking on total mortality showed different patterns according to the serum concentration of some POPs. Former or current smokers had 1.4 to 2.9 times higher mortality rates compared with never smokers among participants with higher serum concentrations of POPs (2nd or 3rd tertiles). However, when the level of PCBs or OCPs were low (1st tertile), there were little positive associations between smoking and mortality. Our study suggests that the background exposure to several POPs may be related to variability in smoking-related total mortality.</P>
Lee, Woomin,Kihm, Kenneth David,Kim, Hong Goo,Shin, Seungha,Lee, Changhyuk,Park, Jae Sung,Cheon, Sosan,Kwon, Oh Myoung,Lim, Gyumin,Lee, Woorim American Chemical Society 2017 Nano letters Vol.17 No.4
<P>Manipulation of the chemical vapor deposition graphene synthesis conditions, such as operating P, T, heating/cooling time intervals, and precursor gas concentration ratios (CH4/H-2), allowed for synthesis of polycrystalline single layered graphene with controlled grain sizes. The graphene samples were then suspended on 8 mu m diameter patterned holes on a silicon-nitride (Si3N4) substrate, and the in-plane thermal conductivities k(T) for 320 K < T < 510 K were measured to be 2660-1230, 1890-1020, and 680-340 W/m center dot K for average grain sizes of 4.1, 2.2, and 0.5 mu m, respectively, using an opto-thermal Raman technique. Fitting of these data by a simple linear chain model of polycrystalline thermal transport determined k = 5500-1980 W/m center dot K for single-crystal graphene for the same temperature range above; thus, significant reduction of k was achieved when the grain size was decreased from infinite down to 0.5 mu m. Furthermore, detailed elaborations were performed to assess the measurement reliability of k by addressing the hole-edge boundary condition, and the airconvection/radiation losses from the graphene surface.</P>
Nrf2 Expression and Apoptosis in Quercetin-treated Malignant Mesothelioma Cells
Lee, Yoon-Jin,Lee, David M.,Lee, Sang-Han Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.5
NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor, has recently received a great deal of attention as an important molecule that enhances antioxidative defenses and induces resistance to chemotherapy or radiotherapy. In this study, we investigated the apoptosis-inducing and Nrf2- upregulating effects of quercetin on malignant mesothelioma (MM) MSTO-211H and H2452 cells. Quercetin treatment inhibited cell growth and led to upregulation of Nrf2 at both the mRNA and protein levels without altering the ubiquitination and extending the half-life of the Nrf2 protein. Following treatment with quercetin, analyses of the nuclear level of Nrf2, Nrf2 antioxidant response element-binding assay, Nrf2 promoter-luc assay, and RT-PCR toward the Nrf2-regulated gene, heme oxygenase-1, demonstrated that the induced Nrf2 is transcriptionally active. Knockdown of Nrf2 expression with siRNA enhanced cytotoxicity due to the induction of apoptosis, as evidenced by an increase in the level of proapoptotic Bax, a decrease in the level of antiapoptotic Bcl-2 with enhanced cleavage of caspase-3 and PARP proteins, the appearance of a sub-$G_0/G_1$ peak in the flow cytometric assay, and increased percentage of apoptotic propensities in the annexin V binding assay. Effective reversal of apoptosis was observed following pretreatment with the pan-caspase inhibitor Z-VAD. Moreover, Nrf2 knockdown exhibited increased sensitivity to the anticancer drug, cisplatin, presumably by potentiating the oxidative stress induced by cisplatin. Collectively, our data demonstrate the importance of Nrf2 in cytoprotection, survival, and drug resistance with implications for the potential significance of targeting Nrf2 as a promising strategy for overcoming resistance to chemotherapeutics in MM.
Lee, Byeong-Cheol,Jeong, Gwanghui,Park, Myeong-Gu,Han, Inwoo,Mkrtichian, David E.,Hatzes, Artie P.,Gu, Shenghong,Bai, Jinming,Lee, Sang-Min,Oh, Hyeong-Il,Kim, Kang-Min American Astronomical Society 2017 The Astrophysical journal Vol.844 No.1
<P>We present the detection of long-period RV variations in HD. 36384, HD. 52030, and HD. 208742 by using the high-resolution, fiber-fed Bohyunsan Observatory Echelle Spectrograph (BOES) for the precise radial velocity (RV) survey of about 200 northern circumpolar stars. Analyses of RV data, chromospheric activity indicators, and bisector variations spanning about five years suggest that the RV variations are compatible with planet or brown dwarf companions in Keplerian motion. However, HD. 36384 shows photometric variations with a period very close to that of RV variations as well as amplitude variations in the weighted wavelet Z-transform (WWZ) analysis, which argues that the RV variations in HD. 36384 are from the stellar pulsations. Assuming that the companion hypothesis is correct, HD. 52030 hosts a companion with minimum mass 13.3 M-Jup orbiting in 484 days at a distance of 1.2 au. HD. 208742 hosts a companion of 14.0 M-Jup at 1.5 au with a period of 602 days. All stars are located at the asymptotic giant branch (AGB) stage on the H-R diagram after undergoing. the helium flash and leaving. the giant clump. With stellar radii of 53.0 R-circle dot and 57.2 R-circle dot for HD. 52030 and HD. 208742, respectively, these stars may be the largest yet, in terms of stellar radius, found to host substellar companions. However, given possible RV amplitude variations and the fact that these are highly evolved stars, the planet hypothesis is not yet certain.</P>