Improving physical realism, stereochemistry, and side‐chain accuracy in homology modeling: Four approaches that performed well in CASP8

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>

Hautmann and Studer orthotopic neobladders : the Michigan experience 미시간 대학병원 경험

Lee, Kyung Seop,Montie, James E.,Dunn, Rodney L.,Lee, Cheryl T. 東國大學校醫學硏究所 2002 東國醫學 Vol.9 No.2

연구목적 : 요로전환술의 치료에 있어서 Hautmann과 Studer 정위방광대치술은 획기적인 방법이다. 이에 저자들은 Hautmann과 Studer 정위방광대치술을 시행했던 환자들을 대상으로 임상적 결과를 후향적으로 분석하였다. 대상 및 방법 : 1995년 3월 1일부터 2000년 9월 30일까지 미시간 대학 병원 비뇨기과에서 방광종양으로 방광절제술 후 Hautmann과 Studer 정위방광대치술을 시행받았던 130명(Hautmann 37명, Studer 93명)을 대상으로 하였다. 이 환자들을 대상으로 두 술식에 대한 환자의 나이, 성, 수술 소요 시간, 입원 기간, 수술 중 출혈 양, 병리학적 병기와 합병증율, 요자제율 및 재수술률을 비교분석해 보았다. 통계적 분석은 Fishers exact test, T-test와 Wilcoxon rank-sum 분석을 이용하였다. 결과 : Hautmann과 Studer 정위방광대치술에 걸린 수술 시간은 각각 5.9, 5.3시간이었다(p=0.003). 입원 기간은 7일과 8.3일로 Hautmann 정위방광대치술이 짧았다(p=0.02). 그 외 나이, 성, 수술 중 출혈 양, 병리학적 병기와 합병증률 및 재수술률은 차이를 보이지 않았다. 요 자제율은 Hautmann과 Studer 정위방광대치술 각각에서 낮 시간은 67%로 같았으며 밤 시간에는 47%와 40%로 비슷하였다. 결론 : Hautmann과 Studer 정위방광대치술 두 술식 모두 안전하고 쉽게 시행할 수 있는 좋은 방법이며 요 자제율 면에서 Hautmann 정위방광대치술이 좀 더 나은 것 같으나 통계적으로 유의하지는 않았다. 또한 Hautmann 정위방광대치술이 수술 시간이 좀 덜 걸리는 것은 요관문합에서의 차이로 생각되며 입원 기간 역시 좀 더 빨리 퇴원을 종용한 결과로 생각된다. Objectives: The development of Studer and Hautmann orthotopic neobladders has revolutionized the management of urinary diversion. Several series have promoted one technique over the other This study examines the clinical outcome of a contemporary cohort of bladder cancer patients who underwent either Hautmann or Studer orthotopic reconstruction. Materials and Methods: Retrospective analysis was performed on 130 patients (93 Studer and 37 Hautmann) who underwent cystectomy and orthotopic diversion between 1st march. 1995 and 30th September 2000. Clinical parameters evaluated were age, gender, procedure time, length of hospital stay, blood loss, pathologic stage, and rate of complication, continence, and reoperation. Diversion type was compared with clinical parameters using the Fishers exact Test, t-test, and Wilcoxon rank-sum analysis. Results: Studer and Hautmann techniques had mean procedure times of 5.9 and 5.3 hours, respectively (p=0.003); Hautmann patients also had a shorter mean length of hospital stay (LOS) (7.0 vs 8.3 days, respectively; p=0.02). When comparing both populations, there was no difference in age, gender, estimated blood loss (EBL), pathologic stage, or rate of complication or reoperation. Total continence was similar in the Hautmann and Studer cohorts, whether during daytime (67% vs 67%) or nighttime (47% vs 40%) hours, respectively. Conclusions: The data suggests that both orthotopic techniques can be performed in men and women in a safe and timely fashion. Continence rates appear better with the Hautmann technique, though the limited cohort size did not offer sufficient power to detect a statistical difference. The shortened procedure time in Hautmann patients likely relates to variations in th ureteral anastomosis. Decreased LOS may reflect recent trends of early patient discharge.

A Near-Infrared Fluorescence-Based Optical Thermosensor

Lee, Seung-Young,Lee, Seulki,Youn, In-Chan,Yi, Dong Kee,Lim, Yong Taik,Chung, Bong Hyun,Leary, James F.,Kwon, Ick Chan,Kim, Kwangmeyung,Choi, Kuiwon WILEY-VCH Verlag 2009 Chemistry Vol.15 No.25

<P>A polymeric thermosensor composed of the thermo-responsive block copolymer Pluronic F127 (PF127) and the near-infrared (NIR) dye Cy5.5 can simply monitor, image, and analyze temperature changes. The thermoprobe exhibited linear NIR fluorescent emission changes (see figure) over a broad temperature range (0–80 °C). <img src='wiley_img/09476539-2009-15-25-CHEM200900683-content.gif' alt='wiley_img/09476539-2009-15-25-CHEM200900683-content'> </P> <B>Graphic Abstract</B> <P>A polymeric thermosensor composed of the thermo-responsive block copolymer Pluronic F127 (PF127) and the near-infrared (NIR) dye Cy5.5 can simply monitor, image, and analyze temperature changes. The thermoprobe exhibited linear NIR fluorescent emission changes (see figure) over a broad temperature range (0–80 °C). <img src='wiley_img/09476539-2009-15-25-CHEM200900683-content.gif' alt='wiley_img/09476539-2009-15-25-CHEM200900683-content'> </P>

Application of Image Analysis for Precise, Noninvasive Measurement of Plant Culture Growth

James, Eddie,Yoo, In Sang,Lee, James M. 한국화학공학회 2004 Korean Journal of Chemical Engineering Vol.21 No.1

Accurately measuring the growth of solid cultures is important for evaluating regrowth following low temperature storage, cell screening on selective media, or the suitability of different media formulation. However, current procedures are inadequate to provide precise, quantitative data non-invasively. This paper describes the development of an image analysis technique to provide quantitative growth data for callus cultures. Various properties obtained from image analysis, such as area, perimeter, diameter, and integrated density valued, were correlated with the observed mass of plant callus. Based on this data, a predictive linear model was developed. The image analysis method was used to estimate cell mass as a function of various media components and growth conditions. This work demonstrates that image analysis is a flexible and useful tool for monitoring cultures.

Genetic framework for flowering-time regulation by ambient temperature-responsive miRNAs in <i>Arabidopsis</i>

Lee, Hanna,Yoo, Seong Jeon,Lee, Jeong Hwan,Kim, Wanhui,Yoo, Seung Kwan,Fitzgerald, Heather,Carrington, James C.,Ahn, Ji Hoon Oxford University Press 2010 Nucleic acids research Vol.38 No.9

<P>Flowering is the primary trait affected by ambient temperature changes. Plant microRNAs (miRNAs) are small non-coding RNAs playing an important regulatory role in plant development. In this study, to elucidate the mechanism of flowering-time regulation by small RNAs, we identified six ambient temperature-responsive miRNAs (miR156, miR163, miR169, miR172, miR398 and miR399) in <I>Arabidopsis</I> via miRNA microarray and northern hybridization analyses. We also determined the expression profile of 120 unique miRNA loci in response to ambient temperature changes by miRNA northern hybridization analysis. The expression of the ambient temperature-responsive miRNAs and their target genes was largely anticorrelated at two different temperatures (16 and 23°C). Interestingly, a lesion in <I>short vegetative phase</I> (<I>SVP</I>), a key regulator within the thermosensory pathway, caused alteration in the expression of miR172 and a subset of its target genes, providing a link between a thermosensory pathway gene and miR172. The miR172-overexpressing plants showed a temperature-independent early flowering phenotype, suggesting that modulation of miR172 expression leads to temperature insensitivity. Taken together, our results suggest a genetic framework for flowering-time regulation by ambient temperature-responsive miRNAs under non-stress temperature conditions.</P>

Novel biphenyl-oxidizing bacteria and dioxygenase genes from a korean tidal mudflat.

Lee, Tae Kwon,Lee, Jaejin,Sul, Woo Jun,Iwai, Shoko,Chai, Benli,Tiedje, James M,Park, Joonhong American Society for Microbiology 2011 Applied and environmental microbiology Vol.77 No.11

<P>Gene-targeted FLX titanium pyrosequencing integrated with stable isotope probing (SIP) using [(13)C]biphenyl substrate revealed that tidal mudflat sediments harbor novel aromatic ring hydroxylating dioxygenases (ARHD). More than 80% of the detected ARHD genes comprise four clades (0.5 distance) with 49 to 70% amino acid identity to sequences in public databases. The 16S rRNA sequences enriched in the (13)C fraction were from the Betaproteobacteria, bacilli (primarily Paenibacillus-like), and unclassified phyla.</P>

High-Strength Chemical-Vapor–Deposited Graphene and Grain Boundaries

Lee, Gwan-Hyoung,Cooper, Ryan C.,An, Sung Joo,Lee, Sunwoo,van der Zande, Arend,Petrone, Nicholas,Hammerberg, Alexandra G.,Lee, Changgu,Crawford, Bryan,Oliver, Warren,Kysar, Jeffrey W.,Hone, James American Association for the Advancement of Scienc 2013 Science Vol.340 No.6136

<P><B>Graphene Staying Strong</B></P><P>Although exfoliated graphene can be extremely strong, it is produced on too small a scale for materials application. Graphene can be produced on a more practical scale by chemical vapor deposition, but the presence of grain boundaries between crystallites apparently weakens the material. <B>Lee <I>et al.</I></B> (p. 1073) show that postprocessing steps during the removal of the graphene sheets can oxidize the grain boundaries and weaken them. If these steps are avoided, the material is comparable in strength to exfoliated graphene.</P>

Influence of Drying Temperature and Duration on the Quantification of Particulate Organic Matter

Lee, Jin-Ho,Doolittle, James J.,Lee, Do-Kyoung,Malo, Douglas D. The Korean Society of Environmental Agriculture 2006 한국환경농학회지 Vol.25 No.4

Various drying conditions, temperatures (40 to $80^{\circ}C$) and durations (overnight to 72 hrs), for the particulate organic matter (POM) fraction after wet-sieving size fractionation have been applied for determination of POM contents in the weight loss-on-ignition method. In this study, we investigated the optimum drying condition for POM fraction in quantification of POM and/or mineral-associated organic matter (MOM; usually indirectly estimated). The influence of the drying conditions on quantifying POM was dependent upon soil properties, especially the amount of soil organic components. In relatively high organic soils (total carbon > 40 g/kg in this study), the POM values were significantly higher (overestimated) with drying at $55^{\circ}C$ than those values at $105^{\circ}C$, which were, for example, 173.2 and 137.3 mg/kg, respectively, in a soil studied. However, drying at $55^{\circ}C$ for longer than 48 hrs of periods produced consistent POM values even though the values were much higher than those at $105^{\circ}C$. Thus, indirect estimates of MOM (MOM = SOM-POM) also tended to be significantly impacted by the dry conditions. Therefore, we suggest POM fractions should be dried at $105^{\circ}C$ for 24 hrs as determining POM and MOM contents. If the POM traction is needed to be dried at a lower temperature (e.g. $55^{\circ}C$) with a specific reason, at least 48 hrs of drying period is necessary to obtain consistent POM values, and a moisture correction factor should be determined to adjust the values back to a $105^{\circ}C$ weight basis.

Berberine, a Natural Plant Product, Activates AMP-Activated Protein Kinase With Beneficial Metabolic Effects in Diabetic and Insulin-Resistant States

Lee, Y. S.,Kim, W. S.,Kim, K. H.,Yoon, M. J.,Cho, H. J.,Shen, Y.,Ye, J.-M.,Lee, C. H.,Oh, W. K.,Kim, C. T.,Hohnen-Behrens, C.,Gosby, A.,Kraegen, E. W.,James, D. E.,Kim, J. B. American Diabetes Association 2006 Diabetes Vol.55 No.8

<P>Berberine has been shown to have antidiabetic properties, although its mode of action is not known. Here, we have investigated the metabolic effects of berberine in two animal models of insulin resistance and in insulin-responsive cell lines. Berberine reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in db/db mice. Similarly, berberine reduced body weight and plasma triglycerides and improved insulin action in high-fat-fed Wistar rats. Berberine downregulated the expression of genes involved in lipogenesis and upregulated those involved in energy expenditure in adipose tissue and muscle. Berberine treatment resulted in increased AMP-activated protein kinase (AMPK) activity in 3T3-L1 adipocytes and L6 myotubes, increased GLUT4 translocation in L6 cells in a phosphatidylinositol 3' kinase-independent manner, and reduced lipid accumulation in 3T3-L1 adipocytes. These findings suggest that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity.</P>

Surface-fluorinated proton-exchange membrane with high electrochemical durability for direct methanol fuel cells.

Lee, Chang Hyun,Lee, So Young,Lee, Young Moo,Lee, Sang Yun,Rhim, Ji Won,Lane, Ozma,McGrath, James E American Chemical Society 2009 ACS APPLIED MATERIALS & INTERFACES Vol.1 No.5

<P>Random disulfonated poly(arylene ether sulfone)-silica nanocomposite (FSPAES-SiO(2)) membranes were physicochemically tuned via surface fluorination. Surface fluorination for 30 min converted about 20% of the C-H bonds on the membrane surface into C-F bonds showing hydrophobicity and electronegativity at the same time. The membranes with hydrophobic surface properties showed high dimensional stability and low methanol permeability when hydrated for direct methanol fuel cell applications. In particular, the surface enrichment of fluorine atoms led to anisotropic swelling behavior, associated with a stable electrode interface formation. Interestingly, in spite of the use of a random copolymer as a polymer matrix, the low surface free energy of the C-F bonds induced a well-defined continuous ionic channel structure, similar to those of multiblock copolymers. In addition to the morphological transition, fluorine atoms with high electron-withdrawing capability promoted the dissociation of sulfonic acid (-SO(3)H) groups. Consequently, FSPAES-SiO(2) membranes exhibited improved proton conductivity. Thus, FSPAES-SiO(2) membranes exhibited significantly improved single-cell performances (about 200%) at a constant voltage of 0.4 V in comparison with those of Nafion 117 and nonfluorinated membranes. Surprisingly, their good electrochemical performances were maintained with very low nonrecovery loss over the time period of 1400 h and interfacial resistances 380% times lower than those of conventional membrane-electrode assemblies comprising the control hydrocarbon membrane and a Nafion binder for the electrodes.</P>